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Michael Weekes

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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.

Guangming Wang

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Tam Hunt

and 1 more

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.

Susanne Schilling*^

and 9 more

Jessica mead

and 6 more

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.  

Mark Ferris

and 14 more

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.

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Most recent documents

Wenhao Li

and 7 more

Less is known about the interaction of viruses with their prokaryotic host in the gut of wild animal. Here we used fecal DNA metagenomic data (n = 24) from black-necked cranes during the wintering period for virus characterization. The results were found to be consistent with the trend of bacterial community changes, and the black-necked crane gut viruses community structure was conservative during the wintering period. A total of 280 vOTUs (6 complete, 3 HQ, 2 MQ and 269 LQ) were obtained and life history predictions identified 207 virulent viruses. 269 LQ vOTUs contained at least 10 viral genes, hence several of these viruses may be too distinct from viral species in the CheckV database to properly estimate their completeness. Meanwhile, gene-sharing network analysis revealed that the gut viruses of black-necked crane formed 32 unique viral clusters (VCs). Virus taxonomic assignment has revealed that Azeredovirinae is the most abundant family during the wintering period of black-necked cranes. Furthermore. Black-necked crane gut viruses have a complex relationship with their prokaryotic hosts, and virus-encoded auxiliary metabolic genes (AMGs) enhance the potential of infecting bacteria for chitin degradation, methionine and tetrahydrofolate (THF) metabolism. These results imply the presence of a large number of novel viruses in the intestinal tract of black-necked cranes, which may further affect birds by regulating prokaryotic bacterial metabolism including lyse prokaryotic host cells and encodes AMGs related to the degradation of complex carbohydrates and amino acid metabolism.

Haohao Yan

and 14 more

Puccinia striiformis f. sp. tritici (Pst), the causative agent of wheat stripe rust, poses a significant threat to wheat production due to its rapid long-distance migration and epidemic properties. Understanding the genetic structure and dynamics of the Pst population is crucial for early prediction and establishment of effective control strategies. The types of molecular marker analyses used in previous population genetic studies are often costly, time-consuming, and labor-intensive. We developed a genotyping by target sequencing (GBTS) chip for Pst designed with candidate secretion proteins and highly polymorphic single nucleotide polymorphism (SNP) sites identified from genome resequencing. The chip can be used directly with diseased leaves, saving time and avoiding cross-contamination between samples. The feasibility and efficiency of the chip was tested using 225 infected leaf samples collected from the northwest oversummering region of China. This test yielded 1,293,150 high-quality SNPs with a maximum gap of 99,512 bp. Strict quality controls produced 19,139 SNPs, comprising the final Pst 20K GBTS chip. Population genetic analysis revealed frequent gene flow and similar genetic diversity of Pst between epidemic regions, consistent with wind field analysis, trajectory tracking, and field monitoring. The results demonstrated that the GBTS chip is more efficient, convenient, and lower in cost than previous methods. This study provides new insights into stripe rust population dynamics. Furthermore, the newly established chip offers a valuable method for enriching epidemiological recognition, guiding future research into inter-regional or continental transmission of an important plant pathogen.

Po-Yu Chen

and 3 more

Introduction:Invasive cribriform carcinoma of the breast, initially described by Page et al in 1983 due to its predominant cribriform growth pattern in the invasive component and relatively favourable prognosis, is a rare type of breast carcinoma, accounting for 0.3 to 3.5% of primary breast carcinomas [1, 2]. ICC patients typically have a small tumour size, few axillary lymph node invasion, low distant metastasis rate, tumour with a high frequency of well differentiation, high ER and PR positive rates with rarely-observed human epidermal growth factor receptor 2 (HER2) amplification and a low proliferation index [3, 4, 5]. To date, studies of skin manifestations of invasive cribriform breast of the breast are notably scarce. We herein report a patient of ICC with a presentation as an erythematous papule on the nipple that no one has reported before.Case history / examination:A 71-year-old Asian woman visited our Department of Dermatology with a chief complaint of a reddish protruding skin lesion on the tip of her right nipple that had appeared for 6 months. Upon physical examination, the skin lesion was a solitary, well-demarcated papule, 0.2 by 0.2 cm in size, appearing centrally erythematous with violaceous in the periphery, fairly dome-shaped and firm [Figure 1a-c]. Besides, the papule was completely asymptomatic. The patient did not report any other abnormal symptoms. Her medical history was also unremarkable.Differential diagnosis and investigations:With these clues, a benign skin lesion had been impressed. Therefore, a local excision was performed to obtain a specimen of 0.7 by 0.5 by 0.3 cm in size. Biopsy results turned out to be pure invasive cribriform carcinoma of the breast (pure ICC), characterized by the invasive cribriform pattern comprising >90% of the lesion, in addition to mammary Paget’s disease (MPD) in the epidermis [Figure 2a-c]. Immunohistochemical tests showed positive expressions of both oestrogen and progesterone receptors [ER >95%, PgR >95%]. The reaction to HER2 (human epidermal growth factor receptor type 2) protein was negative [HER 2 (-)] [Figure 3a-c]. The Ki-67 labelling index was 5 %.Treatment, outcome and follow-up:In the diagnosis of pure ICC with MPD, she was referred to the Breast Surgery Department for further survey and treatment. Results on both CEA and CA15-3 levels were normal. Bilateral breast mammography (CC and MLO view) revealed segmental fine pleomorphic microcalcifications in the lower-inner quadrant of her right breast. These findings raise high suspicion for malignancy and are consistent with a classification of 4C in the BIRADS-US system. Breast ultrasound revealed two oval hypoechoic lesions with tiny calcifications which were 7.8 mm and 24.5 mm in size at the right breast near the areola. Whole body bone scan found no evidence of bone metastasis. With a previous biopsy pathology report revealing ICC and MPD, a full discussion was carried out with the patient. Finally, a simple mastectomy and sentinel lymph node biopsy were performed on her right breast.With the right side simple mastectomy, pathology of the surgical specimen showed residual multifocal ductal carcinomas in situ. Both frozen sections of sentinel lymph nodes revealed no evidence of metastasis. The pathological TNM stage was pT1aN0 according to AJCC eighth edition. Further treatment plans for this patient included a five-year Tamoxifen therapy and regular follow-up at the Breast Surgery Department.Discussion:Based on the clinical features of the papule on her nipple, our initial impressions were benign skin lesions such as pyogenic granuloma, nipple adenoma, Spitz nevus and intradermal nevus. However, the pathologic diagnosis was pure ICC with MPD in the epidermis. Although ICC usually presents as an asymptomatic mass or may even be clinically occult[1, 3], the chance of ICC presenting as skin lesions cannot be ignored. The case reported by Katarzyna et al, in which ICC mimicked a breast abscess [6], along with our case of ICC presenting as a nipple papule, collectively demonstrates ICC’s potential to primarily manifest through skin lesions. To the best of our knowledge, ICC is a tumour having a more favourable prognosis than invasive breast carcinoma with less cribriform pattern and low grade invasive ductal carcinoma [11]. Despite favourable prognosis of ICC, there are still chances of aggressive behaviour or development into an advanced stage if left untreated long enough. Mishra et al reported a case of ICC with extensive perineural infiltration and lymphovascular invasion in a 58-year-old female; and Zhang et al also reported a case of pure ICC with bone metastasis when left untreated for 13 years[7, 8]. Therefore, such manifestation of a papule on the nipple, as in our case, may result in delayed diagnosis and treatment to ICC. It is crucial for dermatologists to have early awareness about skin manifestation of ICC and to avoid misdiagnosis.Mammary Paget’s disease (MPD), first described by Sir Paget in 1874 as eczematous nipple and areola skin lesions, is a rare form of breast carcinoma comprising 1 to 3% of all breast cancers. Nearly all cases of MPD are affiliated with underlying breast carcinomas, typically located near the areola, and >90% are either ductal carcinomas in situ (DCIS) or invasive ductal carcinomas (IDC). Pathophysiologically, there are two main hypotheses proposed for the origin of MPD: the epidermotropic theory and the malignant transformation theory. The epidermotropic theory states that Paget cells originate from underlying breast carcinoma, and they migrate via the lactiferous ducts to the epidermis of the nipple. On the other hand, the malignant transformation theory states that Paget cells are malignant transformation of pluripotent keratinocyte stem cells or cells of apocrine gland ducts[9]. Although remains controversial, it is currently widely accepted that MPD is associated with underlying breast carcinoma, forming the concept based on the epidermotropic theory. In our case, ICC and MPD were diagnosed within the papular lesion on the nipple. This case stands out from >90% of cases in which mammary Paget’s disease was diagnosed exclusively with underlying DCIS or IDC. Furthermore, to the best of knowledge, only one publication focusing on radiologic characteristics of 52 MPD cases mentioned a case of invasive lobular and invasive cribriform carcinoma being diagnosed with mammary Paget’s disease presenting as a mass on mammography[10], but details or images were not provided. As to our case, it is worth knowing that the patient was diagnosed with multifocal DCIS at 1 cm near the right areola in the surgical specimen from simple mastectomy. In our opinion, it was the invasive cribriform carcinoma of the breast but not DCIS resulting in the mammary Paget’s disease in the epidermis of the papule [Figure 2c] as consistent with the epidermotropic theory. Although DCIS has been diagnosed near the areola, we believe that the chance of mammary Paget’s disease originating from the DCIS was slim. That is because malignant Paget cells were not seen at other parts of the nipple nor at the areola, but merely in the epidermis of the papule on the nipple. Furthermore, based on pathologic images, the gross pictures and the clinical manifestations of ICC and MPD, we believe that the invasive cribriform carcinoma of breast had caused the dome-shaped violaceous papule on the nipple, and mammary Paget’s disease contributed to the central erythematous part of the papular lesion [Figure 1a]. Undoubtedly, more studies are needed to bring attention to the skin manifestation of invasive cribriform carcinoma of the breast. As far as we know, no publication has ever reported on ICC with skin manifestation as a papule on the nipple. Also, no case has been reported with detailed images and descriptions regarding a pure ICC being diagnosed with MPD. In this case report, we aim to bring awareness to skin manifestation of ICC.References:1. Cong Y, Qiao G, Zou H, Lin J, Wang X, Li X, et al. Invasive cribriform carcinoma of the breast: A report of nine cases and a review of the literature. Oncol Lett. 2015;9: 1753-1758.2. Page DL, Dixon JM, Anderson TJ, Lee D, Stewart HJ. Invasive cribriform carcinoma of the breast. Histopathology. 1983;7: 525-36.3. Zhang W, Zhang T, Lin Z, Zhang X, Liu F, Wang Y, et al. Invasive cribriform carcinoma in a Chinese population: comparison with low-grade invasive ductal carcinoma-not otherwise specified. Int J Clin Exp Pathol. 2013;6: 445-57.4. Mo CH, Ackbarkhan Z, Gu YY, Chen G, Pang YY, Dang YW, et al. Invasive cribriform carcinoma of the breast: a clinicopathological analysis of 12 cases with review of literature. Int J Clin Exp Pathol. 2017;10: 9917-9924.5. Liu J, Zheng X, Han Z, Lin S, Han H, Xu C. Clinical characteristics and overall survival prognostic nomogram for invasive cribriform carcinoma of breast: a SEER population-based analysis. BMC Cancer. 2021;21: 168.6. Dobruch-Sobczak K, Roszkowska-Purska K, Chrapowicki E. Cribriform carcinoma mimicking breast abscess - case report. Diagnostic and therapeutic management. J Ultrason. 2013;13: 222-9.7. Zhang W, Lin Z, Zhang T, Liu F, Niu Y. A pure invasive cribriform carcinoma of the breast with bone metastasis if untreated for thirteen years: a case report and literature review. World J Surg Oncol. 2012;10: 251.8. Mishra S, Yadav K, Singh Anshul, Misra Vatsala, Chaudhary Kuldeep. Unusual case of Invasive Cribriform Carcinoma of Breast (ICC). JCR [serial online] 20219. Lopes Filho LL, Lopes IM, Lopes LR, Enokihara MM, Michalany AO, Matsunaga N. Mammary and extramammary Paget’s disease. An Bras Dermatol. 2015;90: 225-31.10. Günhan-Bilgen I, Oktay A. Paget’s disease of the breast: clinical, mammographic, sonographic and pathologic findings in 52 cases. Eur J Radiol. 2006;60: 256-63.

Fangfang Lu

and 6 more

Background Inflammation significantly impacts the pathogenesis of age-related macular degeneration (AMD), the primary cause of vision loss in the elderly. With the aging global population and increasing incidence of AMD, understanding the inflammation-related mechanisms and identifying potential therapeutic targets have become paramount. This study aims to offer a bibliometric analysis of global research contributions focused on inflammation in AMD, shedding light on research trends, collaborations, and future directions. Methods We retrieved publications related to inflammation in AMD from 2003 to 2023 from the Web of Science Core Collection database. A total of 2044 articles were analyzed using VOSviewer, CiteSpace, and R-bibliometrix to examine publication trends, influential countries, institutions, authors, and journals, as well as emerging research topics. Results Our analysis revealed a steady global increase in annual publications. The United States and China emerged as leading contributors, demonstrating substantial collaboration and investment in AMD research. Among institutions, the National Eye Institute in the United States and the University of Eastern Finland stood out for their prolific contributions. Key researchers such as K. Kaarniranta have been central to advancing the field, offering potential collaboration opportunities. Investigative Ophthalmology & Visual Science and Experimental Eye Research were identified as the top journals publishing significant work on inflammation in AMD. Keywords such as “oxidative stress,” “complement” “autophagy,” “macrophage,” and “microglia” were frequently mentioned, highlighting these as current research hotspots. Conclusion This analysis underscores the importance of inflammation in AMD and maps the evolution of research, suggesting future directions that may offer new therapeutic strategies.

Raseel Alroba

and 4 more

Purpose: This study aims to investigate the potential causal relationship between the use of indapamide and rhabdomyolysis. Previous research and pharmacovigilance monitoring activities have suggested a potential association between indapamide use and rhabdomyolysis. However, limited information is available on this association. Methods: A case-control study conducted using EHR data, between July 1,2016, and December 31,2022. Patients who have rhabdomyolysis event (cases) were matched to four controls bases on age, gender and date. We examined the odds for indapamide exposure through three risk periods: current use, recent use, and former. The study outcome was ascertained through the presence of CK level over 1,000 U/L (i.e. rhabdomyolysis event). Subsequently, a multivariable conditional logistic regression analysis was utilized to assess the causal impact of indapamide exposure on the likelihood of developing rhabdomyolysis, while accounting for potential confounding variables. Results: The study population consisted of 2,965 cases and 11,860 controls. The results of the conditional logistic regression analysis indicated a lack of association between exposure to indapamide for the current users the OR was 0.7 (95% CI: 0.49 - 0.92) and the AOR was 0.6 (95% CI: 0.39 - 1.05). The recent users showed OR of 0.9 (95% CI: 0.56 - 1.50) and AOR of 0.2 (95% CI: 0.14 - 0.47). Lastly, the former users demonstrated an OR of 0.8 (95% CI: 0.47 - 1.26), and AOR of 0.1 (95% CI: 0.07 - 0.23). Conclusions: In this study, we did not find association between indapamide use and rhabdomyolysis regardless timing of exposure.

Jie Liu

and 5 more

Objective: To investigate whether hormone treatments following hysteroscopic resection of endometrial polyps can further effectively alleviate clinical symptoms and enhance reproductive outcomes and to analyze the factors that influence successful conception in such cases. Design: A large-scale, single-center, retrospective cohort study was conducted in the Day Surgery Department of a tertiary teaching hospital. Setting: The study included pre-menopausal women aged 18-55 with endometrial polyps who underwent hysteroscopic polypectomy. Following the procedure, patients were prescribed oral progesterone/dydrogesterone, combined oral contraceptives, a levonorgestrel-releasing intrauterine system, or received no postoperative medication. Population: A total of 1021 patients were enrolled in the study. Methods: Data were collected and analyzed using SPSS Statistics 26.0 software. Main Outcome Measures: Data including postoperative menstrual status and reproductive outcomes. Results: Among 1021 patients, 222 individuals received either progesterone or dydrogesterone following hysteroscopy, 173 received combined oral contraceptives, 84 were fitted with a levonorgestrel-releasing intrauterine system, and 542 did not receive any postoperative medication. Most patients in the progesterone group (94.6%) and the combined oral contraceptives group (83.8%) received short-term drug treatment within 3 months after the hysteroscopic polypectomy. Prior to treatment, 696 patients (68.2%) had experienced abnormal uterine bleeding. The percentage of patients with resolved abnormal uterine bleeding symptoms post-operation was 78.2% in the progesterone group, 70.2% in the combined oral contraceptives group, 22.2% in the levonorgestrel-releasing intrauterine system group, and 73.4% in the no-medication group. There was no significant difference among the progesterone group, combined oral contraceptives group and no-medication group (p>0.05). Despite having the lowest rate of relief for abnormal uterine bleeding (p=0.000), levonorgestrel-releasing intrauterine system exhibited the highest rate of normal endometrial ultrasound images during follow-up (p=0.001). Out of the 300 participants aiming to conceive, a successful pregnancy was achieved by 78.3%. The success rates of pregnancy were higher in both the progesterone group (82.9%) and the combined oral contraceptives group (85.0%) compared to the no-medication group (74.7%). However, statistical analysis revealed no significant difference (p=0.179) among the groups. Increasing age (OR 1.153, 95% CI 1.078-1.234, p=0.000), persistent abnormal uterine bleeding (OR 5.742, 95% CI 2.269-14.531, p=0.000), and reduced menstrual volume after treatment (OR 3.810, 95% CI 1.398-10.383, p=0.009) identified as unfavorable factors for successful pregnancy. Conclusions: Adding short-term combined oral contraceptive or progesterone after hysteroscopy does not significantly increase the long-term remission of abnormal uterine bleeding symptoms or the pregnancy rates compared to hysteroscopy alone. The LNG-IUS seems to be most beneficial in preventing the postoperative recurrence of EPs. Funding: None. Keywords: Endometrial polyps, Hysteroscopic polypectomy, Abnormal uterine bleeding, Pregnancy, Hormone medication

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Urbanization modifies ecosystem conditions and evolutionary processes. This includes air pollution, mostly as tropospheric ozone (O3), which contributes to the decline of urban and peri-urban forests. A notable case are fir(Abies religiosa) forests in the peripheral mountains southwest of Mexico City, which have been severely affected by O3 pollution since the 1970s. Interestingly, some young individuals exhibiting minimal O3—related damage have been observed within a zone of significant O3 exposure. Using this setting as a natural experiment, we compared asymptomatic and symptomatic individuals of similar age (≤15 years old; n = 10) using histological, metabolomic and transcriptomic approaches. Plants were sampled during days of high (170 ppb) and moderate (87 ppb) O3 concentration. Given that there have been reforestation efforts in the region, with plants from different source populations, we first confirmed that all analysed individuals clustered within the local genetic group when compared to a species-wide panel (Admixture analysis with ~1.5K SNPs). We observed thicker epidermis and more collapsed cells in the palisade parenchyma of needles from symptomatic individuals than from their asymptomatic counterparts, with differences increasing with needle age. Furthermore, symptomatic individuals exhibited lower concentrations of various terpenes (ß-pinene, ß-caryophylene oxide, α-caryophylene and ß-α-cubebene) than asymptomatic trees, as evidenced through GC-MS. Finally, transcriptomic analyses revealed differential expression for thirteen genes related to carbohydrate metabolism, plant defense, and gene regulation. Our results indicate a rapid and contrasting phenotypic response among trees, likely influenced by standing genetic variation and/or plastic mechanisms. They open the door to future evolutionary studies for understanding how O3 tolerance develops in urban environments, and how this knowledge could contribute to forest restoration.

Mohammad Rowshan

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Channel coding plays a pivotal role in ensuring reliable communication over wireless channels. With the growing need for ultra-reliable communication in emerging wireless use cases, the significance of channel coding has amplified. Furthermore, minimizing decoding latency is crucial for critical-mission applications, while optimizing energy efficiency is paramount for mobile and the Internet of Things (IoT) communications. As the fifth generation (5G) of mobile communications is currently in operation and 5G-advanced is on the horizon, the objective of this paper is to assess prominent channel coding schemes in the context of recent advancements and the anticipated requirements for the sixth generation (6G). In this paper, after considering the potential impact of channel coding on key performance indicators (KPIs) of wireless networks, we review the evolution of mobile communication standards and the organizations involved in the standardization, from the first generation (1G) to the current 5G, highlighting the technologies integral to achieving targeted KPIs such as reliability, data rate, latency, energy efficiency, spectral efficiency, connection density, and traffic capacity. Following this, we delve into the anticipated requirements for potential use cases in 6G. The subsequent sections of the paper focus on a comprehensive review of three primary coding schemes utilized in past generations and their recent advancements: lowdensity parity-check (LDPC) codes, turbo codes (including convolutional codes), and polar codes (alongside Reed-Muller codes). Additionally, we examine alternative coding schemes like Fountain codes (also known as rate-less codes), sparse regression codes, among others. Our evaluation includes a comparative analysis of error correction performance and the performance of hardware implementation for these coding schemes, providing insights into their potential and suitability for the upcoming 6G era. Lastly, we will briefly explore considerations such as higher-order modulations and waveform design, examining their contributions to enhancing key performance indicators in conjunction with channel coding schemes.
The involvement of users in the product development process can significantly enhance product quality. The relationship between user experience and knowledge in product design contributes to product efficiency during the development phase. Users often struggle to align their perceptions, leading to extended product usage times and an inability to react to potential performance variations. Product manufacturers also face challenges in identifying suitable features that can positively impact product success and marketability. User experience in product interactions, encompassing both aesthetic and functional aspects, plays a pivotal role in influencing user evaluations and distinguishing characteristics crucial for achieving product success. Determining user knowledge’s influence on product success characteristics can provide valuable insights for the new product development process. This study conducted a survey to gather user experiences and knowledge, aiming to enhance the understanding of how users perceive products. This understanding is crucial for identifying product success characteristics, encompassing aspects such as specifications, sustainability, and recognition, which are instrumental in achieving overall product success. The results of the survey indicate that user knowledge, emotional experiences, and product attribute knowledge can assist product designers and manufacturers in identifying key characteristics for success during the early stages of the new product development process.

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