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Nick K. Jones1,2*, Lucy Rivett1,2*, Chris Workman3, Mark Ferris3, Ashley Shaw1, Cambridge COVID-19 Collaboration1,4, Paul J. Lehner1,4, Rob Howes5, Giles Wright3, Nicholas J. Matheson1,4,6¶, Michael P. Weekes1,7¶1 Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK2 Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, UK3 Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, UK4 Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK5 Cambridge COVID-19 Testing Centre and AstraZeneca, Anne Mclaren Building, Cambridge, UK6 NHS Blood and Transplant, Cambridge, UK7 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK*Joint first authorship¶Joint last authorshipCorrespondence: [email protected] UK has initiated mass COVID-19 immunisation, with healthcare workers (HCWs) given early priority because of the potential for workplace exposure and risk of onward transmission to patients. The UK’s Joint Committee on Vaccination and Immunisation has recommended maximising the number of people vaccinated with first doses at the expense of early booster vaccinations, based on single dose efficacy against symptomatic COVID-19 disease.1-3At the time of writing, three COVID-19 vaccines have been granted emergency use authorisation in the UK, including the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). A vital outstanding question is whether this vaccine prevents or promotes asymptomatic SARS-CoV-2 infection, rather than symptomatic COVID-19 disease, because sub-clinical infection following vaccination could continue to drive transmission. This is especially important because many UK HCWs have received this vaccine, and nosocomial COVID-19 infection has been a persistent problem.Through the implementation of a 24 h-turnaround PCR-based comprehensive HCW screening programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT), we previously demonstrated the frequent presence of pauci- and asymptomatic infection amongst HCWs during the UK’s first wave of the COVID-19 pandemic.4 Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and cycle threshold (Ct) values in the asymptomatic arm of our programme, which now offers weekly screening to all staff.Vaccination of HCWs at CUHNFT began on 8th December 2020, with mass vaccination from 8th January 2021. Here, we analyse data from the two weeks spanning 18thto 31st January 2021, during which: (a) the prevalence of COVID-19 amongst HCWs remained approximately constant; and (b) we screened comparable numbers of vaccinated and unvaccinated HCWs. Over this period, 4,408 (week 1) and 4,411 (week 2) PCR tests were performed from individuals reporting well to work. We stratified HCWs <12 days or > 12 days post-vaccination because this was the point at which protection against symptomatic infection began to appear in phase III clinical trial.226/3,252 (0·80%) tests from unvaccinated HCWs were positive (Ct<36), compared to 13/3,535 (0·37%) from HCWs <12 days post-vaccination and 4/1,989 (0·20%) tests from HCWs ≥12 days post-vaccination (p=0·023 and p=0·004, respectively; Fisher’s exact test, Figure). This suggests a four-fold decrease in the risk of asymptomatic SARS-CoV-2 infection amongst HCWs ≥12 days post-vaccination, compared to unvaccinated HCWs, with an intermediate effect amongst HCWs <12 days post-vaccination.A marked reduction in infections was also seen when analyses were repeated with: (a) inclusion of HCWs testing positive through both the symptomatic and asymptomatic arms of the programme (56/3,282 (1·71%) unvaccinated vs 8/1,997 (0·40%) ≥12 days post-vaccination, 4·3-fold reduction, p=0·00001); (b) inclusion of PCR tests which were positive at the limit of detection (Ct>36, 42/3,268 (1·29%) vs 15/2,000 (0·75%), 1·7-fold reduction, p=0·075); and (c) extension of the period of analysis to include six weeks from December 28th to February 7th 2021 (113/14,083 (0·80%) vs 5/4,872 (0·10%), 7·8-fold reduction, p=1x10-9). In addition, the median Ct value of positive tests showed a non-significant trend towards increase between unvaccinated HCWs and HCWs > 12 days post-vaccination (23·3 to 30·3, Figure), suggesting that samples from vaccinated individuals had lower viral loads.We therefore provide real-world evidence for a high level of protection against asymptomatic SARS-CoV-2 infection after a single dose of BNT162b2 vaccine, at a time of predominant transmission of the UK COVID-19 variant of concern 202012/01 (lineage B.1.1.7), and amongst a population with a relatively low frequency of prior infection (7.2% antibody positive).5This work was funded by a Wellcome Senior Clinical Research Fellowship to MPW (108070/Z/15/Z), a Wellcome Principal Research Fellowship to PJL (210688/Z/18/Z), and an MRC Clinician Scientist Fellowship (MR/P008801/1) and NHSBT workpackage (WPA15-02) to NJM. Funding was also received from Addenbrooke’s Charitable Trust and the Cambridge Biomedical Research Centre. We also acknowledge contributions from all staff at CUHNFT Occupational Health and Wellbeing and the Cambridge COVID-19 Testing Centre.

Scene flow tracks the three-dimensional (3D) motion of each point in adjacent point clouds. It provides fundamental 3D motion perception for autonomous driving and server robot. Although the Red Green Blue Depth (RGBD) camera or Light Detection and Ranging (LiDAR) capture discrete 3D points in space, the objects and motions usually are continuous in the macro world. That is, the objects keep themselves consistent as they flow from the current frame to the next frame. Based on this insight, the Generative Adversarial Networks (GAN) is utilized to self-learn 3D scene flow with no need for ground truth. The fake point cloud of the second frame is synthesized from the predicted scene flow and the point cloud of the first frame. The adversarial training of the generator and discriminator is realized through synthesizing indistinguishable fake point cloud and discriminating the real point cloud and the synthesized fake point cloud. The experiments on Karlsruhe Institute of Technology and Toyota Technological Institute (KITTI) scene flow dataset show that our method realizes promising results without ground truth. Just as human, the proposed method can identify the similar local structures of two adjacent frames even without knowing the ground truth scene flow. Then, the local correspondence can be correctly estimated, and further the scene flow is correctly estimated.   Corresponding author(s) Email: [email protected]

Leukocyte differential test is a widely performed clinical procedure for screening infectious diseases. Existing hematology analyzers require labor-intensive work and a panel of expensive reagents. Here we report an artificial-intelligence enabled reagent-free imaging hematology analyzer (AIRFIHA) modality that can accurately classify subpopulations of leukocytes with minimal sample preparation. AIRFIHA is realized through training a two-step residual neural network using label-free images of isolated leukocytes acquired from a custom-built quantitative phase microscope. By leveraging the rich information contained in quantitative phase images, we not only achieved high accuracy in differentiating B and T lymphocytes, but also classified CD4 and CD8 cells, therefore outperforming the classification accuracy of most current hematology analyzers. We validated the performance of AIRFIHA in a randomly selected test set and cross-validated it across all blood donors. Owing to its easy operation, low cost, and accurate discerning capability of complex leukocyte subpopulations, we envision AIRFIHA is clinically translatable and can also be deployed in resource-limited settings, e.g., during pandemic situations for the rapid screening of infectious diseases.  Corresponding author(s) Email:    [email protected],  [email protected]

Tam Hunt [1], Jonathan SchoolerUniversity of California Santa Barbara Synchronization, harmonization, vibrations, or simply resonance in its most general sense seems to have an integral relationship with consciousness itself. One of the possible “neural correlates of consciousness” in mammalian brains is a combination of gamma, beta and theta synchrony. More broadly, we see similar kinds of resonance patterns in living and non-living structures of many types. What clues can resonance provide about the nature of consciousness more generally? This paper provides an overview of resonating structures in the fields of neuroscience, biology and physics and attempts to coalesce these data into a solution to what we see as the “easy part” of the Hard Problem, which is generally known as the “combination problem” or the “binding problem.” The combination problem asks: how do micro-conscious entities combine into a higher-level macro-consciousness? The proposed solution in the context of mammalian consciousness suggests that a shared resonance is what allows different parts of the brain to achieve a phase transition in the speed and bandwidth of information flows between the constituent parts. This phase transition allows for richer varieties of consciousness to arise, with the character and content of that consciousness in each moment determined by the particular set of constituent neurons. We also offer more general insights into the ontology of consciousness and suggest that consciousness manifests as a relatively smooth continuum of increasing richness in all physical processes, distinguishing our view from emergentist materialism. We refer to this approach as a (general) resonance theory of consciousness and offer some responses to Chalmers’ questions about the different kinds of “combination problem.”  At the heart of the universe is a steady, insistent beat: the sound of cycles in sync…. [T]hese feats of synchrony occur spontaneously, almost as if nature has an eerie yearning for order. Steven Strogatz, Sync: How Order Emerges From Chaos in the Universe, Nature and Daily Life (2003) If you want to find the secrets of the universe, think in terms of energy, frequency and vibration.Nikola Tesla (1942) I.               Introduction Is there an “easy part” and a “hard part” to the Hard Problem of consciousness? In this paper, we suggest that there is. The harder part is arriving at a philosophical position with respect to the relationship of matter and mind. This paper is about the “easy part” of the Hard Problem but we address the “hard part” briefly in this introduction.  We have both arrived, after much deliberation, at the position of panpsychism or panexperientialism (all matter has at least some associated mind/experience and vice versa). This is the view that all things and processes have both mental and physical aspects. Matter and mind are two sides of the same coin.  Panpsychism is one of many possible approaches that addresses the “hard part” of the Hard Problem. We adopt this position for all the reasons various authors have listed (Chalmers 1996, Griffin 1997, Hunt 2011, Goff 2017). This first step is particularly powerful if we adopt the Whiteheadian version of panpsychism (Whitehead 1929).  Reaching a position on this fundamental question of how mind relates to matter must be based on a “weight of plausibility” approach, rather than on definitive evidence, because establishing definitive evidence with respect to the presence of mind/experience is difficult. We must generally rely on examining various “behavioral correlates of consciousness” in judging whether entities other than ourselves are conscious – even with respect to other humans—since the only consciousness we can know with certainty is our own. Positing that matter and mind are two sides of the same coin explains the problem of consciousness insofar as it avoids the problems of emergence because under this approach consciousness doesn’t emerge. Consciousness is, rather, always present, at some level, even in the simplest of processes, but it “complexifies” as matter complexifies, and vice versa. Consciousness starts very simple and becomes more complex and rich under the right conditions, which in our proposed framework rely on resonance mechanisms. Matter and mind are two sides of the coin. Neither is primary; they are coequal.  We acknowledge the challenges of adopting this perspective, but encourage readers to consider the many compelling reasons to consider it that are reviewed elsewhere (Chalmers 1996, Griffin 1998, Hunt 2011, Goff 2017, Schooler, Schooler, & Hunt, 2011; Schooler, 2015).  Taking a position on the overarching ontology is the first step in addressing the Hard Problem. But this leads to the related questions: at what level of organization does consciousness reside in any particular process? Is a rock conscious? A chair? An ant? A bacterium? Or are only the smaller constituents, such as atoms or molecules, of these entities conscious? And if there is some degree of consciousness even in atoms and molecules, as panpsychism suggests (albeit of a very rudimentary nature, an important point to remember), how do these micro-conscious entities combine into the higher-level and obvious consciousness we witness in entities like humans and other mammals?  This set of questions is known as the “combination problem,” another now-classic problem in the philosophy of mind, and is what we describe here as the “easy part” of the Hard Problem. Our characterization of this part of the problem as “easy”[2] is, of course, more than a little tongue in cheek. The authors have discussed frequently with each other what part of the Hard Problem should be labeled the easier part and which the harder part. Regardless of the labels we choose, however, this paper focuses on our suggested solution to the combination problem.  Various solutions to the combination problem have been proposed but none have gained widespread acceptance. This paper further elaborates a proposed solution to the combination problem that we first described in Hunt 2011 and Schooler, Hunt, and Schooler 2011. The proposed solution rests on the idea of resonance, a shared vibratory frequency, which can also be called synchrony or field coherence. We will generally use resonance and “sync,” short for synchrony, interchangeably in this paper. We describe the approach as a general resonance theory of consciousness or just “general resonance theory” (GRT). GRT is a field theory of consciousness wherein the various specific fields associated with matter and energy are the seat of conscious awareness.  A summary of our approach appears in Appendix 1.  All things in our universe are constantly in motion, in process. Even objects that appear to be stationary are in fact vibrating, oscillating, resonating, at specific frequencies. So all things are actually processes. Resonance is a specific type of motion, characterized by synchronized oscillation between two states.  An interesting phenomenon occurs when different vibrating processes come into proximity: they will often start vibrating together at the same frequency. They “sync up,” sometimes in ways that can seem mysterious, and allow for richer and faster information and energy flows (Figure 1 offers a schematic). Examining this phenomenon leads to potentially deep insights about the nature of consciousness in both the human/mammalian context but also at a deeper ontological level.

Cannabis sativa is an extraordinarily versatile species. Hemp and its cousin marijuana, both C. sativa, have been used for millennia as a source of fibre, oil and for medicinal, spiritual and recreational purposes. Because the consumption of Cannabis can have psychoactive effects, the plant has been widely banned throughout the last century. In the past decade, evidence of its medicinal properties did lead to the relaxation of legislation in many countries around the world. Consequently, the genetics and development of Cannabis as well as Cannabis-derived products are the subject of renewed attention.Here, we review the biology of C. sativa, including recent insights from taxonomy, morphology and genomics, with an emphasis on the genetics of cannabinoid synthesis. Because the female Cannabis flower is of special interest as the site of cannabinoid synthesis, we explore flower development, flowering time well as the species’ unique sex determination system in detail. Furthermore, we outline the tremendous medicinal, engineering, and environmental opportunities that Cannabis bears. Together, the picture emerges that our understanding of Cannabis biology currently progresses at an unusual speed. A future challenge will be to preserve the multi-purpose nature of Cannabis, and to harness its medicinal properties and sustainability advantages simultaneously.

Quantum chemistry must evolve if it wants to fully leverage the benefits of the internet age, where the world wide web offers a vast tapestry of tools that enable users to communicate and interact with complex data at the speed and convenience of a button press. The Open Chemistry project has developed an open source framework that offers an end-to-end solution for producing, sharing, and visualizing quantum chemical data interactively on the web using an array of modern tools and approaches. These tools build on some of the best open source community projects such as Jupyter for interactive online notebooks, coupled with 3D accelerated visualization, state-of-the-art computational chemistry codes including NWChem and Psi4 and emerging machine learning and data mining tools such as ChemML and ANI. They offer flexible formats to import and export data, along with approaches to compare computational and experimental data.

This paper responds to one by Graham Martin and colleagues, who offered a critique of my previous publications on masks for the lay public in the Covid-19 pandemic. I address their charges that my co-authors and I had misapplied the precautionary principle; drawn conclusions that were not supported by empirical research; and failed to take account of potential harms. But before that, I remind Martin et al that the evidence on mask wearing goes beyond the contested trials and observational studies they place centre stage. I set out some key findings from basic science, epidemiology, mathematical modelling, case studies and natural experiments, and use this rich and diverse body of evidence as the backdrop for my rebuttal of their narrowly-framed objections. I challenge my critics’ apparent assumption that a particular kind of systematic review should be valorised over narrative and real-world evidence, since stories are crucial to both our scientific understanding and our moral imagination. I conclude by thanking my academic adversaries for the intellectual sparring match, but exhort them to remember our professional accountability to a society in crisis. It is time to lay straw men to rest and engage, scientifically and morally, with the dreadful tragedy that is unfolding across the world.

This Supporting information includes interactive plots, videos, and data captured while performing evaluation and validation experiments for our paper. 

The construct of wellbeing has been criticised as a neoliberal construction of western individualism that ignores wider systemic issues including increasing burden of chronic disease, widening inequality, concerns over environmental degradation and anthropogenic climate change. While these criticisms overlook recent developments, there remains a need for biopsychosocial models that extend theoretical grounding beyond individual wellbeing, incorporating overlapping contextual issues relating to community and environment. Our first GENIAL model \cite{Kemp_2017} provided a more expansive view of pathways to longevity in the context of individual health and wellbeing, emphasising bidirectional links to positive social ties and the impact of sociocultural factors. In this paper, we build on these ideas and propose GENIAL 2.0, focusing on intersecting individual-community-environmental contributions to health and wellbeing, and laying an evidence-based, theoretical framework on which future research and innovative therapeutic innovations could be based. We suggest that our transdisciplinary model of wellbeing - focusing on individual, community and environmental contributions to personal wellbeing - will help to move the research field forward. In reconceptualising wellbeing, GENIAL 2.0 bridges the gap between psychological science and population health health systems, and presents opportunities for enhancing the health and wellbeing of people living with chronic conditions. Implications for future generations including the very survival of our species are discussed.  

Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield across global regions is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control and pollination services in adjacent crops using a global dataset of 529 sites. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimize floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future.

Researchers' ability to accurately screen fossil and subfossil specimens for preservation of DNA and protein sequences remains limited. Thermal exposure and geologic age are usable proxies for sequence preservation on a broad scale but are of nominal use for specimens of similar depositional environments. Cell and tissue biomolecular histology is thus proposed as a novel proxy for determining sequence preservation potential of ancient specimens with improved accuracy. Biomolecular histology as a proxy is hypothesized to elucidate why fossils/subfossils of some depositional environments preserve sequences while others do not and to facilitate selection of ancient specimens for use in molecular studies.

IntroductionConsistent with World Health Organization (WHO) advice [1], UK Infection Protection Control guidance recommends that healthcare workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment (RPE), unless aerosol generating procedures (AGPs) are being undertaken or are likely, when a filtering face piece 3 (FFP3) respirator should be used [2]. In a recent update, an FFP3 respirator is recommended if “an unacceptable risk of transmission remains following rigorous application of the hierarchy of control” [3]. Conversely, guidance from the Centers for Disease Control and Prevention (CDC) recommends that HCWs caring for patients with COVID-19 should use an N95 or higher level respirator [4]. WHO guidance suggests that a respirator, such as FFP3, may be used for HCWs in the absence of AGPs if availability or cost is not an issue [1].A recent systematic review undertaken for PHE concluded that: “patients with SARS-CoV-2 infection who are breathing, talking or coughing generate both respiratory droplets and aerosols, but FRSM (and where required, eye protection) are considered to provide adequate staff protection” [5]. Nevertheless, FFP3 respirators are more effective in preventing aerosol transmission than FRSMs, and observational data suggests that they may improve protection for HCWs [6]. It has therefore been suggested that respirators should be considered as a means of affording the best available protection [7], and some organisations have decided to provide FFP3 (or equivalent) respirators to HCWs caring for COVID-19 patients, despite a lack of mandate from local or national guidelines [8].Data from the HCW testing programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT) during the first wave of the UK severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic indicated a higher incidence of infection amongst HCWs caring for patients with COVID-19, compared with those who did not [9]. Subsequent studies have confirmed this observation [10, 11]. This disparity persisted at CUHNFT in December 2020, despite control measures consistent with PHE guidance and audits indicating good compliance. The CUHNFT infection control committee therefore implemented a change of RPE for staff on “red” (COVID-19) wards from FRSMs to FFP3 respirators. In this study, we analyse the incidence of SARS-CoV-2 infection in HCWs before and after this transition.

Lithium salt as a common drug in the clinical treatment of bipolar disorder, its application range is very wide. Lithium ions have many physiological functions, such as improving hematopoietic function, regulating the nervous system, improving heart function, antiviral, immune regulation, and neuroprotective effects. Lithium also has numerous pharmacological effects. For example, it can be used as an emotional stabilizer and has anti-inflammatory effects in dermatology. It also has protective effects against various neurological diseases, leukopenia, hepatitis, pancreatic islet cells, etc. After oral absorption of lithium salt, it can regulate gastrointestinal epithelial ion transport, affect intestinal absorption and secretion, and repair mucosal damage to promote wound healing. In this review, we review in detail the current status of lithium on gastrointestinal physiology and pathology. Based on the multiple regulatory effects of lithium salts on the gastrointestinal tract, we expect to find new drug targets to better treat gastrointestinal diseases.

Room-temperature sodium-sulfur (RT-Na/S) batteries display attractive potential in large-scale energy-storage, but their practical application was still restricted by the serious dissolution of polysulfides. Herein, supported by the constructing of interface engineering, the metal sulfide-carbon nanocomposite can be prepared with considerable electrochemical properties. Utilizing the double-helix structure of carrageenan-metal hydrogels as precursors, in-situ metal sulfide (MxSy) nanostructure/3D carbon aerogels (3D CAs) can be successfully constructed. Importantly, with the assistance of the vulcanization process, 3D carbon architecture was maintained in the composites and act as a skeleton to optimize their structural stability. As the anode of RT-Na/S batteries, ZnS/S@C and NiS2/S@C delivered an excellent cycling stability and rate performance (179.8mAhg−1 at 20Ag−1 after 10000 cycling for ZnS/S@C, 220.3 mAhg−1 at 10Ag−1 after 3000 cycling for NiS2/S@C). The detailed investigation of mechanism revealed that the powerful adsorption for Na2S4 was originated from 3D metal sulfide-carbon structure. The well-designed architecture of sulfide-carbon composites servers as an electrocatalyst to alleviate the shuttle effect of polysulfides, resulting in the long-term electrochemical stability. Given this, the work is expected to provide promising insights for designing advanced anode materials for RT-Na/S batteries.

The Green Revolution, which entails the use of pesticides, fertilisers, and other agrochemicals, has greatly increased worldwide food production in the last sixty years. Nevertheless, this heightened efficiency has resulted in adverse consequences, including environmental deterioration such as water and land pollution. Land degradation, resulting from both natural phenomena and human actions, has a significant impact on a considerable area of the Earth’s land and affects billions of individuals globally. The annual economic cost of land degradation exceeds $300 billion, resulting from a variety of causes such as insufficient land management and the pressures of population increase. Anthropogenic factors such as deforestation, intensified agriculture, and population growth worsen soil degradation, jeopardising essential ecosystem services and endangering food security. Simultaneously, the increasing release of greenhouse gases and the resulting climate change pose a significant threat to the long-term viability of agriculture. It is imperative to take immediate action to reduce their impact. Given the importance of soil health in sustainable agriculture and climate mitigation, conservation agriculture (CA) is seen as a possible option. Conservation agriculture approaches promote soil health, lower cultivation expenses, and decrease land degradation by minimising soil disturbance, boosting soil organic matter, and stimulating biological activity. Land Degradation Neutrality (LDN) initiatives, which are essential for achieving Sustainable Development Goal 15, provide a structure for achieving a balance between land restoration and degradation. These initiatives highlight the significance of implementing sustainable land management methods. This review compiles up-to-date research on conservation measures that promote Land Degradation Neutrality (LDN) and examines their implications for ecosystem services and policy interventions. The assessment emphasises the importance of sustainable land management and stresses the necessity of collective actions to tackle land degradation concerns and ensure agricultural sustainability in response to increasing environmental risks.

CASE REPORTTITLE: Persistent Hypotension in a Patient on Trifluoperazine Undergoing Staging laparotomy under Combined General and Epidural Anaesthesia: A case report.1. Nirupa Ramakumar, Assistant professor, Department of Anaesthesiology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India, 2480162. Arnpriya Pal, Junior resident, Department of Anaesthesiology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India, 2480163. Ruhi Vaid , Senior resident, Department of Anaesthesiology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India , 248016Correspondence to:Nirupa Ramakumar,Assistant Professor,Department of Anaesthesiology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India,248016Email- [email protected] hypotension after combined epidural and general anaesthesia in a patient on trifluoperazine is rare. It is acceptable to continue these drugs; however, the anesthesiologist must be aware of the risk of interaction with other drugs and subsequent hemodynamic pertubations. Early use of nor-adrenaline should be considered to counter refractory hypotension.INTRODUCTIONDoctors prescribe long-term anxiolytic therapy, including benzodiazepines, anti-depressants, and anti-psychotics, to many patients with anxiety disorders. Meta-analyses reveal that India’s prevalence of anxiety neurosis, which ranges between 0.9% and 28.3%, is comparable to global reports. 1 A few case reports report perioperative hypotension in patients on long-term tricyclic depressants (TCAs). 2-4 It is imperative for anesthesiologists to possess knowledge regarding the potential interactions between psychotropic medications and anaesthetic agents. We present a case of persistent hypotension occurring after low thoracic epidural blockade in a patient who was on long-term trifluoperazine (an anti-psychotic drug) for anxiety disorder. This case highlights the importance of vigilant perioperative management of patients on longstanding antipsychotics.CASE PRESENTATIONCase history and examinationA 40-year-old woman (150 cm, 52 kg,BMI 23 kg/m2) was planned for an elective staging laparotomy. The team detected an adnexal mass in the patient. She had a medical history of anxiety disorder for one year and was under regular benzodiazepine (chlordiazepoxide 10mg OD) and anti-psychotic drug (trifluoperazine 1 mg HS) treatment; hypertension was under control with amlodipine 5mg H and atenolol 25mg HS for one year. Her past surgical history included a caesarean section. The patient was independent in routine household chores and had a metabolic equivalent of task >= 4. Her general physical and systemic examinations were normal. Routine preoperative investigations, including a complete hemogram, liver function tests, renal function tests, chest x-rays, and thyroid function tests, were normal. Her electrocardiogram was suggestive of sinus tachycardia. We asked the patient to continue taking her anxiolytics and anti-hypertensive drugs.TreatmentGeneral anaesthesia with epidural anaesthesia was planned to provide good postoperative analgesia considering the nature of surgery. We placed an epidural catheter at the T9-T10 interspace and tested it using 3 ml of 2% lignocaine and adrenaline. A positive meniscus sign was utilised to ensure the correct placement of the catheter. The patient’s pre-induction blood pressure was 130/80 mmHg, and her heart rate was 100 bpm. After a few minutes, the patient complained of feeling dizzy. We made her lie down and took her blood pressure, which was 102/56 mm Hg. We used propofol 100 mg and fentanyl 100 ug for induction. Tracheal intubation was facilitated with atracurium 25 mg, and maintenance of anaesthesia was done using 1% sevoflurane and an O2:air (50:50) mixture. 15 minutes after induction of anaesthesia, bupivacaine (5%) in 6 ml was given through the epidural catheter. The blood pressure reduced to 70/40 mmHg, and the heart rate ranged between 80 and 90 bpm. We administered rapid colloid and crystalloid boluses, along with boluses of mephentramine, but the mean arterial pressure was still lower than 65 mmHg. The surgery then started. We gave hydrocortisone 100 mg intravenously to treat possible adrenal insufficiency or anaphylaxis, but the blood pressure remained low. Blood pressure normalised with 50–100 ug bolus doses of phenylephrine. We administered 3 mg of morphine mixed in 7 ml of normal saline via epidural for analgesia.The ECG showed no abnormalities. We performed an ultrasound to examine the inferior vena caval distensibility index to assess hydration status prior to extubation and found it to be normal. A focused cardiac ultrasound revealed a normal ejection fraction and no other abnormalities. After the patient resumed spontaneous breathing and generated adequate tidal volume, we extubated her.Outcome and follow-upPost-extubation, the patient again had persistent hypotension with a mean arterial pressure (MAP) below 65 mmHg. We started a nor-adrenaline infusion at a rate of 0.03 mcg/kg/min, tapered it to maintain a MAP >65 mmHg, and gradually stopped it after 24 hours. We restarted her anxiolytics and discharged her on post-operative period 5.DISCUSSIONWe encountered a case of persistent hypotension following an epidural injection of lignocaine and adrenaline in a patient who had been on a year-long anxiolytic therapy that continued until the day of surgery. She did not respond to fluid bolusus and mephentramine but did respond to a high dose of phenylephrine and a nor-adrenaline infusion. We considered multiple potential factors contributing to her persistently low blood pressure. Long-lasting subarachnoid blockage leading to severe hypotension didn’t seem likely because aspiration tests done through the epidural catheter came back negative. This meant that the catheter’s accidental displacement wasn’t likely to be the cause. The patient did not exhibit bradycardia at the onset of hypotension, despite the possibility of high thoracic blockade. We were unlikely to attribute the patient’s refractory hypotension to an inadequate cortisol response to stress. Additionally, administering hydrocortisone did not effectively treat her hypotension. Furthermore, there were no indications of drug-related anaphylaxis. The onset of hypotension was influenced by preoperative hypovolemia and acute sympathectomy caused by epidural anaesthesia. However, we hypothesise that the main cause of refractory hypotension was the lack of cardiovascular response to sympathomimetics, likely due to the prolonged use of trifluoperazine (an anti-psychotic drug) until the day before surgery.We classify trifluoperazine as a first-generation antipsychotic drug with typical properties. Some first-generation antipsychotic (AP) drugs work by blocking dopamine receptors, which stops dopaminergic neurotransmission. This can cause a number of adverse effects, with extrapyramidal symptoms being the most common. The inhibition of muscarinic receptors and histamine receptors results in the occurrence of cholinergic side effects and sedation. Moreover, the antagonism of α-1 adrenergic receptors plays a crucial role in the occurrence of orthostatic hypotension and reflex tachycardia. First-generation AP use has been associated with several ECG changes, mainly QT abnormalities.5 The hypotension that occurred did not show improvement with the standard doses of sympathomimetics and fluid replacement. The ECG showed no abnormalities, indicating that AP’s cardiotoxicity was unlikely to have played a role in her hypotension. The normal echocardiographic observations further substantiate the previously stated conclusion.Ramirez reported a case of refractory hypotension in a patient on a high dose of quetiapine undergoing endovascular abdominal aortic aneurysm repair. The blood pressure normalised after starting the nor-adrenaline infusion as it has higher alpha-1 action with less affinity for beta-2 receptors. 6 Tanzer et al. included a study in their systematic review where clozapine caused low blood pressure that was unfixable with intravenous fluids or vasopressors. This happened during surgery. 7Antipsychotic drugs’s resistance to sympathomimetic drugs can be due to strong inhibition of α1-adrenergic activity, which in turn leads to vasodilation and a reflexive sympathetic response. It is likely that the added vasodilation occurred in our patient as a consequence of the combined impact of general and epidural anaesthesia. Furthermore, the concurrent injection of adrenaline has documented an inverse response to profound hypotension.8AP-induced β-blockade, especially in cases of overdose, can lead to uncontrolled β2-agonism when adrenaline is given, which causes a lot of vasodilation and low blood pressure that can’t be fixed with IV fluids and vasopressors.The Society for Perioperative Assessment and Quality Improvement came out with a consensus statement to provide recommendations regarding the use of psychotropic medications to improve perioperative care. They came to the conclusion that, while these drugs are better to be continued to avoid the risk of relapse of the patient’s condition, modifications are required on a case-by-case basis for particular drugs.9 Its crucial to avoid antipsychotic medication in situations of worsening pre-existing low or unstable blood pressures. The study’s findings suggest that sulpiride, amisulpiride, ariprazole, and olazepine have the least significant effects on blood pressure.10CONCLUSIONOur case highlights that the anaesthesia provider must be cautious when administering epidural anaesthesia to patients on long-term, first-generation anti-psychotic drugs. Lignocaine and adrenaline given through the epidural can cause paradoxical hypotension in these patients. All patients with anxiety disorders may experience increased anxiety before any surgical procedure. It is acceptable to continue these drugs; however, the anesthesiologist must be aware of the risk of interaction with other drugs and subsequent hemodynamic pertubations. It is therefore essential to take a detailed medical history. One must weigh the risk-to-benefit ratio of stopping or continuing these drugs. Stopping APs for one day before surgery is unlikely to change the anxiety status, bereft of unwanted cardiovascular effects. Early usage of nor-adrenaline should be considered to counter refractory hypotension.AUTHOR CONTRIBUTION1. Nirupa Ramakumar: This author helped in design of the work, substantial contributions to the conceptions, the acquisition of data, drafting the work and revising it critically for important intellectual content. All the authors approved the final version to be published and are accountable for all aspects of the work in ensuring that questions related to accuracy and integrity of any part of the work are appropriately investigated and resolved.2. Arnpriya Pal: This author helped in drafting of work, analysis, interpretation of data for the work and revising it critically for intellectual content.3.Ruhi Vaid: This author helped in drafting of work, analysis, interpretation of data for the work and revising it critically for intellectual content.ACKNOWLEDGMENTSI would like to thank Mr Mandal, anaesthesua technician in charge for assisting us in management of our patient.CONFLICT OF INTERESTNoneCONSENT STATEMENTWritten informed consent was obtained from the patient for publication of this case report.REFERENCESKhambaty M, Parikh RM. Cultural aspects of anxiety disorders in India. Dialogues Clin Neurosci. 2017;19(2):117-126.Chang HC, Guo SL, Feng YP, Wong CS, Liao JH. Severe Refractory Intraoperative Hypotension in a Patient with Major Depression under Long-Term Antidepressant Treatment: A Case of Left Nephrectomy Surgery. Journal of Medical Sciences. 2018;38(4):192. doi:10.4103/jmedsci.jmedsci_23_18Takakura K, Nagaya M, Mori M, Koga H, Yoshitake S, Noguchi T. Refractory hypotension during combined general and epidural anaesthesia in a patient on tricyclic antidepressants. Anaesth Intensive Care . 2006;34(1):111-114. doi:10.1177/0310057X0603400108Malan TP, Nolan PE, Lichtenthal PR, et al. Severe, Refractory Hypotension during Anesthesia in a Patient on Chronic Clomipramine Therapy. Anesthesiology . 2001;95(1):264-266. doi:10.1097/00000542-200107000-00040Meltzer HY. Update on Typical and Atypical Antipsychotic Drugs. Annual Review of Medicine. 2013;64(Volume 64, 2013):393-406. doi:10.1146/annurev-med-050911-161504Espinós Ramírez C, Artigas Soler A, Gil Esteller P, García Medina N, Tangarife Benjumea J, Martínez García M. Refractory hypotension secondary to chronic treatment with high doses of quetiapine. Revista Española de Anestesiología y Reanimación (English Edition). 2023;70(5):305-307. doi:10.1016/j.redare.2023.05.001Tanzer TD, Brouard T, Pra SD, et al. Treatment strategies for clozapine-induced hypotension: a systematic review. Therapeutic Advances in Psychopharmacology. 2022;12:20451253221092931. doi:10.1177/2045125322109293.Alagappan A, Baruah R, Cockburn A, Sandilands EA. Paradoxical refractory hypotension following adrenaline administration in a patient taking clozapine. BMJ Case Rep. 2021;14(11):e243363. doi:10.1136/bcr-2021-243363.Oprea AD, Keshock MC, O’Glasser AY, et al. Preoperative Management of Medications for Psychiatric Diseases: Society for Perioperative Assessment and Quality Improvement Consensus Statement. Mayo Clinic Proceedings. 2022;97(2):397-416. doi:10.1016/j.mayocp.2021.11.011Proudman RGW, Pupo AS, Baker JG. The affinity and selectivity of α-adrenoceptor antagonists, antidepressants, and antipsychotics for the human α1A, α1B, and α1D-adrenoceptors. Pharmacology Research & Perspectives. 2020;8(4):e00602. doi:10.1002/prp2.602

Title PageTitle: Endobronchial metastasis of fibrosarcoma successfully managed via rigid bronchoscopy: A Case Report

A document by Mehdi Jafarpour. Click on the document to view its contents.

Photoperiod is a pivotal factor in affecting spermatogenesis in seasonal-breeding animals. Transposable elements, a class of DNA sequences that can replicate and translocate in the genome, have regulatory functions during spermatogenesis. However, whether it also functions in photoperiodic spermatogenesis in seasonal breeding animals is unknown. To explore this, we first annotated 5,501,822 transposons in the whole genome of Brandt’s voles (Lasiopodomys brandtii), and revealed that LINEs were the most abundant, comprising 16.61% of the genome. Following closely, SINEs accounted for 10.13%, LTRs for 7.54%, and DNA transposons for 0.70%. Insertion bias analysis revealed that 74.75% of transposons were outside coding genes. Subsequently, we exposed male Brandt’s voles to long-photoperiod (LP, 16 hours/day) and short-photoperiod (SP, 8 hours/day) from their embryonic stages, and obtained testes transcriptome at 4 and 10 weeks after birth. Differential expression and Pearson analysis indicated strongly positive correlations between the expression of differentially expressed retrotransposons and the adjacent genes. KO, KEGG and GSEA results showed that flagellar genes were key target genes regulated by retrotransposons. RT-qPCR results validated the accuracy of the transcriptome using randomly selected six genes (Dnah1, Axdnd1, Ccdc13, Dnah17, Dnah2, Dnali1) and five transposons (LTR/ERVL-MaLR_113132, LINE/L1_1811211, LINE/L1_69082, LINE/L1_662502, SINE/Alu_1213291). RT-PCR results showed that SINE/Alu_1213291 regulates the transcriptional expression of the Dnali1 gene. This study suggests that transposon play a crucial role in the photoperiodic spermatogenesis in Brandt’s voles, especially in the flagella assembly at the late spermiogenesis. Our findings first reveal the regulatory function of transposons in photoperiodic spermatogenesis, providing insights into the role of photoperiod in seasonal reproduction in wild animals.

Aim: To investigate if interventions to discontinue or down-titrate heart failure (HF)-pharmacotherapy are feasible and associated with risks in older people. Methods: A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Electronic databases were searched from inception to March 8th 2023. Randomised controlled trials (RCTs) and observational studies included people with HF, aged >50 years and who discontinued or down-titrated HF-pharmacotherapy. Outcomes were feasibility (whether discontinuation or down-titration of HF-pharmacotherapy was sustained at follow-up) and associated risks (mortality, hospitalisation, adverse drug withdrawal effects [ADWE]). Random-effects meta-analysis was performed when heterogeneity was not substantial (Higgins I2<70%). Sub-analysis by frailty status was conducted. Results: Six RCTs (536-participants) and 27 observational studies (810,499-participants) across six therapeutic classes were included, for 3-260 weeks follow-up. RCTs were conducted in patients presenting with stable HF. Down-titrating a renin-angiotensin system inhibitor (RASI) in patients with chronic kidney disease was 76% likely than continuation (Risk Ratio [RR] 1.76, 95%CI 1.14-2.73), with no difference in mortality (RR 0.64, 95%CI 0.30-1.64). Discontinuation of beta-blockers were feasible compared to continuation in preserved ejection fraction (RR 1.00, 95%CI 0.68-1.47). Participants were 25% likely to re-initiate discontinued diuretics (RR 0.75, 95%CI 0.66-0.86). Digoxin discontinuation was associated with 5.5-fold risk of hospitalisation compared to continuation. Worsening HF was the commonest ADWE. One observational study measured frailty but did not report outcomes by frailty status. Conclusions: The appropriateness and associated risks of down-titrating or discontinuing HF-pharmacotherapy in people aged >75 years is uncertain. Evaluation of outcomes by frailty status necessitates investigation.

Massive malignant phyllodes tumor accompanied by anemia and ulceration in the breast: A case reportAttention:Written informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy.[Abstract] Large malignant breast phyllodes tumors are uncommon in clinical settings. Here, we report such a case to provide a reference for clinical work. A 48-year-old woman discovered a lump in her right breast, which eventually grew to 25 cm by 10 cm and began to rapidly bleed and ulcerate within 3 months. The patient had visible signs of anemia and significant emaciation as a result of the tumor’s wasting effect and the protracted course of the disease. The patient underwent modified radical mastectomy on the right breast. The pathology results obtained after surgery revealed a malignant phyllodes tumor. No adjuvant therapy, such as chemotherapy or radiation, was administered. The patient had no symptoms of tumor recurrence and complications from the surgery after a follow-up of 9 months.[Keywords] Breast cancer; Malignant phyllodes tumor; Diagnosis; Complications; Pathology1.IntroductionPhyllodes tumors of the breast (PTB), formerly known as ”cystosarcoma phyllodes,” are relatively rare in clinical practice, and they account for 0.3%–1% of breast tumors[1]. According to the histological features, the World Health Organization currently divides PTB into three categories, namely benign, borderline (also known as low-grade malignant PTB), and malignant (also known as high-grade malignant PTB)[2]. PTB rarely affects men, and typically affects women between 40 and 50 years of age[3]. In most cases, the clinical signs are unilateral, typically exhibited as a painless mass, and there may be a history of quick growth.The high-risk factors and pathogenesis of PTB are currently unclear. There are hypotheses suggesting that PTB originates from fibroadenomas, but there is still a significant debate[4]. High estrogen status may also be an independent pathogenic factor for PTB[5]. This tumor is a fibroepithelial tumor that contains both stromal and epithelial components. Reduction of the epithelial component is associated with greater malignancy. The characteristics of phyllodes tumors are composed of proliferative stroma accompanied by elongated fissure-like gaps, with the surface of the gaps covered by epithelium. Chromosomal changes are associated with the malignant phenotype of PTB. In borderline and malignant PTB, chromosome 1q amplification is common, and as the degree of amplification increases, malignant behavior increases[6, 7].Phyllodial breast tumors are generally rare, however, their incidence rates have increased in recent years. The clinical manifestations of phyllodial tumors lack specific characteristics but include insidious onset, slow progression, a long medical history, and the main manifestation being rapid growth of painless masses in the affected breast. These characteristics make it difficult to determine the nature of phyllodial tumors without surgery. In the present study, we report a case of a giant malignant phyllodial tumor and emphasize the importance of ”detect, diagnose, and treat early” to avoid serious complications.Case presentation 2.1 Background of the caseA 48-year-old woman with a right breast tumor was admitted to the hospital on February 2, 2023. Six years ago, the patient discovered the tumor in her right breast by chance. The tumor was left untreated and showed no signs of redness, swelling, pain, or ulceration. Three months ago, following a COVID-19 infection, the right breast’s lump rapidly grew, accompanied by bleeding and ulceration but without purulent secretion.2.2 Physical examination and laboratory testsPhysical examination of the patient revealed pale nail beds on both hands, pale eyes, and an anemic face. The skin in the right breast’s lateral quadrant was pigmented, with surface ulceration and bleeding, and the right breast was noticeably bigger than the left one. The left breast showed no signs of skin redness, swelling, nipple depression, dimples, or orange peel sign. The right breast was noticeably enlarged, and the tumor measuring roughly 25 cm by 10 cm protruded from the skin (Figures 1 and 2). The left breast did not have any discernible bulk. There were no swollen lymph nodes palpable in the bilateral supraclavicular area or left armpit, but there was a lymph node measuring roughly 2 cm by 1 cm in the right armpit. Ultrasound examination revealed a mixed echogenic mass of approximately 20 cm by 5.2 cm in the right breast. Blood flow signals were present within the bulk, and the boundary was clearly defined despite the uneven shape. In addition, ultrasound indicated hyperplastic alterations in the left breast. The left axillary region did not appear to have any noticeable anomalous lymph nodes. The right armpit revealed many lymph nodes, and the largest one was 1.6 cm by 0.6 cm in size and had a thicker cortex compared with the normal cortex. Ultrasonography of the right breast tumor indicated that the lesion was BI-RADS4 class 4b (Figure 3). Positron emission tomography–computed tomography (PET-CT) was also performed, and the right breast mass could not be ruled out as a phyllodes tumor with malignant transformation due to (1) its heterogeneous metabolism and mixed density; (2) elevated metabolism of lymph nodes situated in the right axilla and behind the pectoralis major and minor muscles, possibly suggesting the presence of metastasis; (3) slight inflammation in the upper and lower lobes of both lungs; an inflammatory small nodule in the upper lobe of the right lung; localized emphysema in the upper lobe of the right lung; and anemia. Puncture pathology of the right breast fibroepithelial tumor did not show any conclusive indications of malignancy. Because fibroepithelial tumors are heterogeneous and biopsy tissue is limited, it is important to integrate clinical information and, if necessary, perform full lesion resection. Owing to the tumor’s massive size and ulceration, the patient’s blood routine test revealed mild anemia (hemoglobin, 75 g/L) and infection (white blood cell count, 13.68×109/L). Hemoglobin level reached 99 g/L following a 400 mL leukocyte-free suspended red blood cell transfusion and using cephalosporin drugs to treat inflammation.2.3 TreatmentPreoperative diagnosis was a right breast phyllodes tumor (high likelihood of malignancy), and right axillary lymph node metastasis was highly probable. A modified radical mastectomy of the right breast was carried out (Figure 4). About 40 mL of blood was lost during the successful procedure.General morphology of surgical specimens: There was a large lobulated mass in the breast tissue (22 cm × 21 cm × 7.5 cm), with a solid and tough cut surface. The total volume of the breast and axilla measured 24 cm × 23 cm × 8 cm; the area of the spindle skin measured 24 cm × 17 cm; and the diameter of the nipple was 1.8 cm. The breast did not contain any normal glands. The tumor was located 0.1 cm from the superficial fascia. Locally, the tumor affected the skin. A single adipose tissue mass of 8 cm × 7 cm × 2 cm was discovered, and 25 lymph nodes with a diameter of 0.3–2 cm were palpable inside the mass. Microscopic examination (Figure 5) showed a 22 cm × 21 cm × 7.5 cm malignant phyllodes tumor in the right breast. Low-grade fibrosarcoma, characterized by localized ossification, intrusion into the duct to generate papilloma-like morphology, and myofibroblastic differentiation, constituted the sarcoma component. The tumor lacked a distinct capsule, most of which exhibit expansion and progressive growth, local skin invasion, and formation of skin ulcers. The tumor cells showed a wide range of morphologies, including myxoid, sparse, dense, and collagenized cells, and presented mild to severe atypia. Mitotic figures were found in 1–7/10 HPFs. No tumor metastases were found in the axillary lymph nodes, and there was no tumor infiltration of the papillary or superficial fascia (0/25). The postoperative pathological(Figure 6) diagnosis was a malignant breast phyllodes tumor. Immunohistochemistry: -3: CK5/6(−), CKpan(−), SATB2(+), ER(−); -8: Ki-67 (+20%), β-catenin (membrane +), CKpan (−), CD34 (+), CD31 (blood vessels +); -11: Ki-67 (+10% to 20%), Desmin (−), Calponin (foci+), S-100 (−), β-catenin (membrane +).2.4 Outcome and follow-upAfter surgery, the patient made a full recovery. Half a month after the operation, hemoglobin level improved (92 g/L), and no adjuvant therapy, such as chemotherapy or radiation, was administered. At a follow-up 9 months after surgery, the patient has not experienced any associated problems or indications of tumor recurrence thus far.

A document by SUBHOJIT CHAKRABORTY. Click on the document to view its contents.

In this paper, we study scalable δ–level coherent state synchronization for multi-agent systems (MAS) where the agents are subject to bounded disturbances/noises. We propose a scale-free framework designed solely based on the knowledge of agent models and agnostic to the communication graphs and size of the network. We define the level of coherency for each agent as the norm of the weighted sum of the disagreement dynamics with its neighbors. The objective is to restrict the level of coherency of the network to δ without a-priori information about the disturbance.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) significantly impacts global health, with a prevalence affecting roughly 25% of adults worldwide. GLP-1 receptor agonists (GLP-1RAs) offer potential therapeutic benefits beyond glycemic control, including improvement in hepatic steatosis, inflammation, and fibrosis. Objectives: This study aims to systematically review and meta-analyze randomized clinical trials to evaluate the efficacy and safety of GLP-1RAs in MASLD patients, focusing on hepatic outcomes, cardiovascular outcomes, anthropometric measurements, and mortality. Methods: Following PRISMA guidelines, a comprehensive database search was conducted to include RCTs assessing GLP-1RAs’ effects on MASLD. Quality assessment was conducted using the Revised Cochrane Risk of Bias tool. Our meta-analysis utilized a random-effects model, calculating standardized mean differences for continuous outcomes to determine the agents’ efficacy and safety. Additionally, funnel plots were generated to assess publication bias, ensuring the integrity of our meta-analytical findings. Results: The review included 27 trials, revealing GLP-1RAs significantly improved hepatic function markers (ALT, AST, GGT, and liver fat content) and cardiovascular risk factors (fasting blood sugar, HbA1c levels, lipid profiles). Additionally, GLP-1RAs were associated with significant reductions in body weight, BMI, subcutaneous fat, and waist circumference. Conclusion: GLP-1RAs demonstrate a promising therapeutic role in managing MASLD, offering benefits that extend to improving liver function, mitigating cardiovascular risk, and promoting weight loss. Further research is needed to confirm these findings and optimize GLP-1RAs’ usage in MASLD treatment.