The advent of social media has catalyzed a paradigm shift in the way information is disseminated and consumed, giving rise to novel phenomena such as viral trends and information diffusion. This review article provides an in-depth scholarly examination of network science as applied to social media analysis, focusing on the mathematical formulations, algorithmic techniques, and interdisciplinary methodolo-gies that underpin the field. By exploring graph theory, community detection, scale-free networks, centrality measures, machine learning applications, and cultural influences, this study offers a comprehensive and nuanced understanding of network structures and dynamics. As a top-tier contribution to the field of computer science, this review serves as a nexus for the interdisciplinary study of network science, providing valuable insights and directions for future research in the analysis of information diffusion and viral trends within social media platforms.

A document by Charles Kusniec. Click on the document to view its contents.

Considering three viral transmission routes— fomites, droplets, and aerosols— two routes have been the focus of debate about the relative role of droplets and aerosols in SARS-CoV-2 infection. We seek to quantify infection risk in an enclosed space via short-range and long-range airborne transmission to inform public health decision making. Data from five published studies were analyzed to predict relative exposure at distances of 1 m and farther, mediated by droplet size divided into two bins: ≧ 8 μm (medium and large droplets that we call “droplets”) and < 8 μm (small droplets that we call “aerosols”). The results at 1 m from an infectious individual were treated as a boundary condition to model infection risk at shorter and longer distance. At all distances, infection risk was treated as the sum of exposure to aerosols and droplets. It was assumed that number of virions is proportional to particle volume. The largest infection risk occurred close to the infectious individual, and out to approximately 1m, droplets and aerosols both contributed. Farther away, the largest risk was due to aerosols. For one model, droplet exposure disappeared at 1.8 m. Policy concerning physical distancing for meaningful infection reduction relies on exposure as a function of distance, yet within this construct particle size determines respiratory deposition. This two-fold distance effect can be used to evaluate measures such as plexiglass barriers, masking, and ventilation.

Meta-ecosystems are the largest and probably most complex structures investigated in ecol-ogy. Because of their complexity they are often separated into their respective ecosystems and then studied in isolation. This is often done without analysing whether an understanding of the individual ecosystems can lead to a proper understanding of the meta-ecosystem, like-ly because we lack clear guidelines when such a separation is sufficient. We here propose four conceptual models for which a separation appropriately approximates the full dynamics. For each of these models we provide empirical evidence from riparian meta-ecosystems to showcase that the terrestrial or aquatic ecosystem should likely not be studied in isolation. Finally, we provide a new theoretical framework to assess how strongly two ecosystems are linked and discuss how this framework might be applied in future empirical research.

Increasing human pressures threaten fish diversity, with potentially severe but unknown consequences to the functioning of riverine food webs. Using a 17-years dataset from multi-trophic fish communities, we investigated the long-term effects of human pressure (represented by human footprint) on the species richness and energy flux across fish food webs, a measure of ecosystem functioning. Combining metabolic scaling theory and ecological network principles, we calculate the annual energy flux through varying trophic compartments (i.e., top-carnivore, mesocarnivore, detritivore, and omnivore). Species richness across all trophic compartments was positively associated with energy flux. However, species richness decreased over time, alongside with the energy flux at the whole-network level, which reduced by 75%. Human pressure negatively affected both species richness and energy flux, and the negative impacts of human pressure have intensified over time. These results illustrate how human pressure can reduce diversity and erode the energy flux through food webs, with long-term negative implications for the functioning of natural ecosystems

Objective To describe the maternal and neonatal outcomes of pregnant women with fasting blood glucose <4.7 mmol/L for whom the diagnosis and treatment pathways differed due to COVID-19. Design, setting and population. An Australian population-based data linkage study involving 3891 women. Methods: Pregnant women with fasting blood glucose <4.7 mmol/L between 24-32 weeks of gestation were categorized into three groups: women diagnosed with gestational diabetes by postprandial hyperglycaemia (PPGDM; n= 226); normal glucose tolerance group (NGT; n= 3125) and women not tested for postprandial hyperglycaemia, mostly during COVID-19 (LFBG; n= 540). The maternal and neonatal outcomes between groups were compared using generalized linear models. Main outcome measures: Risk of Large for gestational age baby. Results: Mean difference in birth weight (-115 grams, 95%CI -175.5— -32.6) and z-scores (-0.11, 95%CI -0.26— 0.02) were lower in the PPGDM group compared to the LFBG group. However, there were no differences between PPGDM and LFBG groups in the risk of large for gestational age (LGA) infants (RR: 1.09, 95%CI 0.66— 1.78). The maternal and neonatal outcomes in the LFBG group were comparable to the NGT group. Conclusion: The risk of LGA was similar across all groups regardless of post prandial glycemia and its treatment. Overall, women with a fasting blood glucose <4.7 mmol/L can be considered as a low-risk group for adverse perinatal outcomes.

Objective: Venous thromboembolism (VTE) occurs in 0.4-0.7% of benign hysterectomies. Pelvic vascular compression secondary to fibroids may represent a mechanism for elevated VTE risk. We aimed to evaluate the incidence and timing of VTE among individuals undergoing hysterectomy for fibroids and other benign indications. Design: Retrospective cohort. Setting: Vizient clinical database. Population: Adult patients without thrombophilias or malignancies who underwent hysterectomy January 2015-December 2021. Methods: Demographics, comorbidities, surgical characteristics, and VTE rates were compared by surgical indication. Main Outcome Measures: VTE consisted of pulmonary embolism or deep venous thrombosis diagnosed during three periods: 1) preoperative (one year before surgery until day before surgery), 2) early postoperative (surgery date through six weeks after surgery), and 3) late postoperative (six weeks to one year after surgery). Results: 467,027 patients were identified (263,844 with fibroids and 203,183 without) and 1.1% experienced VTE. On multivariable regressions adjusting for demographic confounders and route of surgery, the presence of fibroids was associated with higher odds of preoperative (aOR 1.12, 95% CI 1.03-1.22, p=0.011) and lower odds of late postoperative VTE (aOR 0.81, 95% CI 0.73-0.91, p<0.001). For individuals with fibroids, uterine weight ≥250 grams and undergoing hysterectomy via laparotomy were associated with preoperative (aOR 1.29, 95% CI 1.09-1.52, p=0.003 and aOR 2.32, 95% CI 2.10-2.56, p<0.001) and early postoperative VTE (aOR 1.32, 95% CI 1.08-1.62, p=0.006 and aOR 1.72, 95% CI 1.50-1.96, p<0.001), respectively. Conclusion: Patients with fibroids were at higher odds of having VTE in the year before hysterectomy. For those with fibroids, elevated uterine weight and open hysterectomy were associated with greater risk of preoperative and early postoperative VTEs. Funding: There was no funding source for this study.

Purpose The global older population is growing rapidly, and the rise in polypharmacy has increased potentially inappropriate medication (PIM) encounters. PIMs pose health risks, but detecting them automatically in large medical databases is complex. This review aims to uncover PIM prevalence in people aged over 65 using health databases and emphasize the risk of underestimating PIM prevalence due to underutilization of detection tools. Methods This study conducted a broad search on the Medline database to identify articles about the prevalence of PIMs in older adults using various databases. Articles published between January 2010 and June 2023 were included, and specific criteria were applied for study selection. Two literature reviews conducted before our study period were integrated in order to obtain a perspective from the 1990s to the present day. The selected papers were analysed for variables including database type, screening method, adaptations, and PIM prevalence. The study categorized databases and screening methods for clarity, examined adaptations, and assessed concordance among different screening methods. Results This study encompassed 48 manuscripts, covering 58 sample evaluations. The mean prevalence of PIMs within the general population aged over 65 was 29.3% (95%CI: 18.7%- 37.5%). Significant heterogeneity emerged in both the utilized databases and the detection methods. Adaptation of original methods was observed in 86.2% (50/58) of cases. Half of the methods used for assessing PIMs belonged to the “List of drugs” category. About a third of the studies employed less than half of the original criteria after adaptation. Only three studies used over 75% of the original criteria and more than 50 criteria. Conclusion This extensive review highlights PIM prevalence among the older adults, emphasizing method intricacies and the potential for underestimation due to data limitations and algorithm adjustments. The findings call for enhanced methodologies, transparent algorithms, and a deeper understanding of intricate rules’ impact on public health implications

Background: Valsartan is commonly used for cardiac conditions. In 2018, the Food and Drug Administration recalled generic valsartan due to the detection of impurities. Our objective was to determine if heart failure patients receiving valsartan at the recall date had a greater likelihood of unfavorable outcomes than patients using comparable antihypertensives. Methods: We conducted a cohort study of Optum’s de-identified Clinformatics® Datamart (July 2017-January 2019). Heart failure patients with commercial or Medicare Advantage insurance who received valsartan were compared to persons who received non-recalled angiotensin receptor blockers (ARBs) and angiotensin converting enzyme-inhibitors (ACE-Is) for 1 year prior and including the recall date. Outcomes included a composite for all-cause hospitalization, emergency department (ED), and urgent care (UC) use and a measure of cardiac events which included hospitalizations for acute myocardial infarction and hospitalizations/ED/UC visits for stroke/transient ischemic attack, heart failure or hypertension at 6-months post-recall. Cox proportional hazard models with propensity score weighting compared the risk of outcomes between groups. Results: Of the 87,130 patients, 15% were valsartan users and 85% were users of non-recalled ARBs/ACE-Is. Valsartan use was not associated with an increased risk of all-cause hospitalization/ED/UC use six-months post-recall (HR 1.00; 95%CI 0.96–1.03), compared with individuals taking non-recalled ARBs/ACE-Is. Similarly, cardiac events 6-months post-recall did not differ between individuals on valsartan and non-recalled ARBs/ACE-Is (HR 1.04; 95%CI 0.97–1.12). Conclusions: The valsartan recall did not affect short-term outcomes of heart failure patients. However, the recall potentially disrupted the medication regimens of patients, possibly straining the healthcare system.

Antibody mimetics is a novel antibody engineering approach after the development of polyclonal, monoclonal antibodies, and genetically engineered antibody fragments. Inspired by the structure and function of natural antibodies, antibody mimetics offer many advantages over conventional antibodies and can be constructed by protein-directed evolution, peptide design and synthesis, or fusion of complementarity-determining regions through intervening framework regions. A series of parent protein/peptide structures and technical roadmaps have been established to induce better recognising properties, superior affinity, stability, penetrability, and cost-effectiveness of the designed mimetics. This article aims to summarise the evolution of antibody mimetics engineering, illustrate the highlights and hotpots in this research field using scientometric analysis, and give an anticipatory analysis on this increasing research topic.

Power system management and operation rely heavily on short-term power load forecasting. Accurate forecasting results can help reduce power waste and economic losses. The existing power forecasting methods only forecast the future load based on historical data, which factors have the greatest influence on the power load is not considered enough, and there are no effective methods for simultaneously mining time characteristics and correlation characteristics of multidimensional time series. Therefore, we propose a new hybrid approach, which combines LSTM with attention mechanism and GA (genetic algorithm). In LSTM, GA optimizes the number of layers, dense layers, hidden layer neurons, and dense layer neurons, so as to determine the optimal parameters. On the basis of the load data set containing five characteristics of dry bulb temperature, dew point temperature, wet bulb temperature, humidity and electricity price, the method proposed in this paper will be verified. By comparing with RNN, LSTM, GRU, LSTM-Attention and GRU-Attention. According to the experimental results, the application of the proposed method noticeably minimizes the prediction error and elevates the goodness of fit of the model.

Background: The conjunctiva of the eye is a mucosal surface that is colonized by various bacteria. Following surgeries, trauma, or other underlying conditions the normal flora of these bacteria may cause some eye infections such as conjunctival, corneal infections, or endophthalmitis. Objectives: This study aimed to investigate the bacterial population and antibiotic resistance of the conjunctiva in healthy horses. Study design: Random sampling of ocular samples from 20 horse during the winter (2019). Methods: Swab samples were collected from the eyes of 20 healthy horses of different breeds, ages, and sexes in Tehran province, Iran. The swabs were cultured on blood agar and MacConkey agar and incubated at 37°C for 24-48 hours. The isolated bacteria were characterized using cellular morphology, gram-staining, and biochemical tests. Sensitivity and resistance to 10 different antibiotics were measured using an antibiogram test. Results: Results showed that the bacterial population consisted of various species, with Bacillus cereus being the most frequent. There were no significant differences in the frequency of isolated bacteria between sexes and age groups. There were no significant differences in the sensitivity of bacterial flora of the eyes to Colistin, ceftiofur, florfenicol, amoxicillin, and ampicillin between neither different age groups nor different sexes of the horses (P>0.05). However, sensitivity to enrofloxacin and ciprofloxacin was significantly correlated with the age groups of the horses (P>0.05). Significant difference in sensitivity to trimethoprim-sulfamethoxazole between various sexes of horses was observed. Main limitations: The non-uniformity of the follow-up examination reliance owners or caregiver of the horse for follow-up information and Lack of adequate financial resources to study more horses. Conclusions: The study suggests that the frequency of bacterial flora in horses’ eyes is influenced by housing and management conditions rather than age and sex. Keywords: Microbial flora, Conjunctiva, Eyes, Horse, Mucosal surface.

Brief Introduction: This article summarizes a case of successful radiofrequency ablation of atrial tachycardia in a patient with dextrocardia in combination with intracardiac echocardiography, and summarizes the relevant experience.

Background and purpose: Bilirubin toxicity in newborn infants leading to kernicterus disturbs immune and neuronal functions through proinflammatory cytokines and a hyperglutamatergic state. Tryptophan metabolism along the kynurenine pathway may underpin both features. Phototherapy of neonatal hyperbilirubinemia (NNH) converts bilirubin to harmless products, mainly lumirubin. Lumirubin possesses protective properties, though its precise mechanism(s) of action is less understood. The tryptophan metabolite and photooxidation product 6-formylindolo[3,2-b]carbazole (FICZ) may also be formed during NNH phototherapy. Experimental approach: We have explored the basis of potential mechanisms of lumirubin and FICZ actions by their molecular docking to the following receptors: the aryl hydrocarbon (AhR), NMDA, kainate and GABA receptors. We compared their docking to the AhR with those of bilirubin and biliverdin and the potent AhR agonists FICZ, indirubin and 2,3,7,8-Tetrachlorodibenzo-p-dioxin and their docking to the other receptors with those of kynurenic (KA) and quinolinic (QA) acids. Key results: lumirubin and FICZ dock very strongly to the AhR, whereas biliverdin and bilirubin do not. Both lumirubin and FICZ also dock strongly to the NMDA and GABA receptors, as do KA and QA. Conclusions and implications: AhR activation by lumirubin may form the basis of NNH phototherapy. FICZ is also likely to play a role in NNH phototherapy. Interaction of lumirubin and FICZ with glutamate and GABA receptors may underpin antagonism of the excitotoxicity of kernicterus. Development of lumirubin- and FICZ-based pharmaceuticals may advance NNH therapy. Interaction of KA and QA with GABA receptors requires investigation at the pharmacological and behavioural levels.

Candida onychomycosis is a common fungal infection affecting the nails, primarily caused by Candida species. Regarding the increasing trend of Candida onychomycosis and antifungal-resistant phenomenon in recent years, this study aims to evaluate the epidemiological characteristics of Candida onychomycosis, the distribution of emerging species, and the antifungal susceptibility profiles of isolates. Onychomycosis caused by yeast species was confirmed through direct examination and culture of nail scraping among all individuals suspected to have onychomycosis and referred to a medical mycology laboratory between June 2019 and March 2022. Species of yeast isolates were identified using the multiplex PCR and RFLP-PCR methods. The antifungal susceptibility of isolates to common antifungal agents and imidazole drugs was evaluated according to the M-27 A3 CLSI protocol. Among 101 yeast strains isolated from onychomycosis, Candida parapsilosis complex (50.49 %) was the most common species, followed by C. albicans (20.79 %) and C. tropicalis (10.89 %). Rare species of yeasts such as C. guilliermondii and Saccharomyces cerevisiae were also identified by molecular methods. Results obtained from antifungal susceptibility testing showed significant differences in MIC values of isoconazole, fenticonazole, and sertaconazole among different species. Overall, 3% fluconazole-resistant rate was found among Candida species. Moreover, there was a statistically significant difference in MICs of fenticonazole and clotrimazole between the two most prevalent causative species, C. parapsilosis complex and C. albicans. Correct identification of the causative agents of onychomycosis and performing susceptibility testing could be helpful in choosing the most appropriate antifungal therapy.

The study aimed to quantify the carbon (C) contents and stocks and evaluate the structural stability and the total emission of mineralizable carbon (C-CO 2) in different areas with sandy-textured soil. Three managed areas were evaluated: conventional tillage system (CTS) considered as a reference, no-tillage (NT), permanent pasture (PP), and an area in the process of environmental recovery that comprises the Binational Biological Refuge of Maracaju (BBRM). Samples of deformed and undisturbed soils were collected from all areas in years 0-0.05; 0.05-0.10; 0.10-0.20; Soil layers of 0.20-0.40 m. From the samples, carbon stocks were analyzed, soil aggregation in CO 2 emission. There was a positive variation of ∆Stock-C for all areas compared to the reference area. The best structural parameters were observed in the PP and BBRM areas. The highest peaks of C-CO 2 emission occurred in the CTS area, especially on the 29 th and 49 th day. The CTS area evidenced that inadequate management decreased soil quality. The areas with conservation practices contributed to the quality of the edaphic environment for the attributes evaluated. The BBRM area demonstrated a great capacity to increase carbon stocks, also contributing to the improvement of the physical quality of the soil.

Accurate and efficient genotyping of microsatellite loci is essential for their application in population genetics and various demographic analysis. Protocols for next generation sequencing of microsatellite loci generate high-throughput and cross-compatible allele scoring characteristics: common issues associated with size separation on conventional capillary-based protocols. As a result, we have developed a novel, ultra-fast, all-in-one software Seq2Sat in C++ to support accurate automated microsatellite genotyping. It directly takes raw reads of microsatellite amplicons and subsequently performs read quality control before inferring genotypes based on depth of read, sequence composition and length. It does not produce any intermediate files, making I/O very efficient. Additionally, we developed a module in Seq2Sat for sex identification based on sex locus amplicons. We further developed a user-friendly website-based platform SatAnalyzer to conduct reads-to-report analyses by calling Seq2Sat to generate genotype tables and interactive genotype graphs for manual editing. SatAnalyzer also allows visualization of read quality and distribution across loci and samples to troubleshoot multiplex optimization and high-quality library preparation. To evaluate its performance, we benchmarked SatAnalyzer against conventional capillary gel electrophoresis and an existing microsatellite genotyping software MEGASAT. Results show that SatAnalyzer can achieve > 0.993 genotyping accuracy and Seq2Sat is ~ 5 times faster than MEGASAT despite many more informative tables and figures generated. Seq2Sat and SatAnalyzer are freely available at github (https://github.com/ecogenomicscanada/Seq2Sat) and dockerhub (https://hub.docker.com/r/rocpengliu/satanalyzer).

Cancer in adolescents and young adults (AYAs) is associated with an increased risk for suicidal ideation (SI). There are no reported pediatric oncology cases describing management of SI during end of life. We present a case of a 14-year-old male with relapsed, high-risk B-cell acute lymphoblastic leukemia (B-ALL) who received a haploidentical stem cell transplant (HSCT) and was acutely suicidal at the end of life. We discuss how to navigate acute suicidality in this patient population, the impact of discordant goals of care amongst family members, and potential preventative strategies for similar cases.

Objective: To develop a novel non-invasive model for CSPH, and investigate whether carvedilol could reduce the risk of decompensation in patients with high-risk CSPH stratified by the novel model. Methods: International multicenter observational study with a median follow-up time of 38 months. Three cohorts were included in study from 6 countries. In this study, a total of 1,304 patients were fulfilled diagnosis of liver cirrhosis. Patients were treated with carvedilol in longitudinal carvedilol-treating cohort. The primary outcome was the development of the first hepatic decompensation . Results: Six studies from the meta-analysis were involved (n=819), and LSM and platelet count (PLT) were identified as independent risk factors of CSPH, with pooled risk ratios of 1.10 (95% confidence interval [CI] 1.06-1.15) and 0.99 (95% CI 0.98-0.99). A novel model was established. In HVPG cohort (n=151), the areas under the receiver operating characteristic curve (AUC) of the novel model, ANTICIPATE model, and Baveno VII criteria for CSPH were 0.91 (95% CI 0.86-0.95), 0.80 (95% CI 0.73-0.87), and 0.83 (95% CI 0.77-0.89). The novel model narrows down the grey zone to 22.5%, significantly lower than 50.3%, using Baveno VII criteria (p<0.001). In follow-up cohort (n=1,102), the cumulative incidences (1.7% vs 2.5% vs 15.8%) of decompensation events were significantly different by using the novel model cutoff values of >0, 0 to -0.68 (medium-risk), and <-0.68 (p<0.001). In the carvedilol-treating cohort, the patients with high-risk CSPH stratified by the novel model (treating cohort, n=51) had significantly lower rates of decompensation than those of NSBBs untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=102 after PSM, all p<0.05). Conclusion: A novel model provides stratification for CSPH and decompensation in patients with liver cirrhosis. Treatment with carvedilol significantly reduces the risk of decompensation among high-risk CSPH patients stratified by the novel model.

Objectives: Community-acquired pneumonia (CAP) was a common respiratory tract infection in children, which can be caused by various pathogens, including bacteria, mycoplasma (MP), respiratory syncytial virus (RSV), and recently SARS-CoV-2 are the most widespread. We attempt to distinguish common and pathogen-specific host response characteristics by comparing the CAP of different pathogens. Methods: We included 200 CAP hospitalized cohort caused by SARS-CoV-2 (COVID-19, n=50), mycoplasma (CAP-MP, n=50), RSV (CAP-RSV, n=50) and other bacteria (CAP-Bacteria, n=50), of whom were balanced the potentially confounding factors (such as age and gender) based on Propensity Score Matching algorithm(PSM). We compared hematologic and biochemical indicators for different CAPs, samples were taken within 48 hours of admission. Results: Main clinical features of COVID-19 were fever, faster heart rate and lower antibiotic use. Notably, markers of immuno-inflammatory, including white blood cell, lymphocyte and procalcitonin (PCT) were not different among the CAP groups. Biomarkers reflecting nutrient metabolism showed total protein (TP) and albumin (ALB) levels in the COVID-19 group were lower than those in the CAP-MP group, the creatinine and urea levels of the COVID-19 patients were higher than that of CAP-MP group. The serum sodium and calcium levels in the COVID-19 group were the lowest and significantly lower than that in the CAP-MP group, while serum phosphorus levels were opposite. Moreover, we observed that the creatine kinase (CK) and creatine kinase-MB (CK-MB) levels in the COVID-19 were higher than those in the CAP-MP groups. Conclusions: Our study revealed common and unique pathophysiological features of different pathogens‐associated CAP, which may facilitate the pathogen-specific precision diagnosis and treatment.

Background Though humans are fallible, Physicians as humans, unfortunately, commit unintentional errors while providing healthcare services. Medical errors are dangerous injuries caused to patients, by physicians, nurses, or the medical team leading to harmful effects to the patient that can be fatal. Clinicians can prevent medical errors in healthcare with the use of diligence. In addition to the harm caused to the patient, medical errors are expensive. Methods We searched the PUBMED using the keywords ‘medical errors’, errors in medicine, and its cost to human lives as well as its effect on healthcare providers and reporting systems. Results Medication errors and Diagnosis errors comprise a majority of medical errors. However, a lack of data, an overlap in the definition of medical error, and the absence of standardized nomenclature have led to difficulty in the evaluation and analysis of data related to medical error. The remedial measures vary from one setting to another, however efficient reporting and clinical audits can help prevent medical errors. Conclusion Medical error is an effect arising out of patient care that can be harmful and fatal to the patients. This results in the failure of an action plan to be implemented for treating a disease. Both patients and healthcare providers are affected. Effective dialogue between the two,, clinical audits ,a support system for healthcare providers and open disclosure policy by the service provider are some effective measures to consider. KEYWORDS: Medical error, Impact on healthcare provide, Solutions on preventing error, Role of reporting and clinical audit

Objectives: Part I analyzes the clinical characteristics of JO-RRP and AO-RRP. Part II explores the influencing factors of surgical intervals. Methods: Part I: Clinical features were analyzed in 168 RRP patients (59 JO-RRP and 109 AO-RRP) diagnosed and treated in our hospital. Part II: The correlation of interoperative time with onset age, gender, Derkay anatomical score or surgical methods were analyzed in JO-RRP patients. Results: The interoperative time between operations in the JO-RRP group was 116.3±75.9 days, and in the AO-RRP group was 169.1±141.7 days (p<0.05). In the JO-RRP group, the CO2 laser treatment interval (186.2±140.1 days) was significantly longer than that of the microdebrider group (124.7±114.5 days) (p=0.011). Conclusions: 1. JO-RRP patients had higher Derkay score, higher surgical frequency and shorter surgical interval. 2. The surgical intervals lengthened with age and shortened with higher Derkay scores. CO2 laser surgery has the longest interoperative time.

Prolonged oseltamivir treatment for severe influenza pneumonia: Requirement of combination therapies. Teluguakula Narasaraju1,2 PhD, Pandareesh M2 PhD, Shivaramu MG3 MD1 Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA2 Center for Research and Innovation, Adichunchanagiri University, BG Nagara, Karnataka, India3 Department of Forensic Medicine, Adichunchanagiri Institute of Medical Sciences, BG Nagara, Karnataka, IndiaCorresponding author: Teluguakula Narasaraju ntelugua@uthsc.eduA recent article by Gerard Moreno et al. compared the efficacy of a standard oseltamivir (5 doses) versus a prolonged oseltamivir treatment (10 doses) in critically ill influenza patients admitted into intensive care units (ICUs).1 Oseltamivir was administered at 75 mg/dose twice daily, and patients were monitored for death or discharge from the hospital as primary outcomes. Overall, this retrospective multicenter cohort study provides valuable insights and important scientific rationale that patients with severe lower respiratory tract influenza infections require extended antiviral therapy to contain the virus shedding in the deeper lungs. However, this study raises several concerns about the limitations of prolonged oseltamivir therapy in ICU patients.First, although this retrospective study demonstrates the beneficial effects of prolonged oseltamivir treatment, due to the high diversity in influenza virus strains, their persistent mutative ability, and being a most common community-acquired viral pathogen, extreme caution must be taken to avoid unwanted use of extended oseltamivir and prevent the origin of resistant viral strains. Genetic fluctuations of the surface genes of the influenza virus are potent contributors for the origin of resistance via  antigenic drift or spontaneous mutations2 and lacking this information is one of the major limitations of this study. Second, prolonged oseltamivir treatment in immunocompromised patients functions as a double-edged sword. It has been reported that immunocompromised patients on chemotherapy, solid organ transplantation, or under corticosteroid therapies take more extended periods for virus clearance.3-4 Although prolonged oseltamivir treatment will likely yield potent antiviral effect, extended oseltamivir therapy induce spontaneous origin of the oseltamivir-resistant mutant (H275Y) strain in immunocompromised patients.5 The origin of H275Y mutants was observed within a week when influenza-infected immunocompromised ferrets were treated with oseltamivir.5 The origin of quick resistance to oseltamivir is truly alarming, as oseltamivir will be the top choice of antiviral drug used in case of a pandemic outbreak, and there is a high chance for quick origin of the resistant viral strains due to extensive use of this drug. Further, it is not clear whether the proposed prolonged oseltamivir treatment strategy can be applied to other approved antiviral drugs, such as zanamivir, peramivir, or baloxavir in ICU-admitted patients.Third, it is critical to explore other choices of treatments to overcome the problem of the origin of resistant viral strains. One such alternative is using a combination of two or more antiviral agents.6-7 Several clinical trials have tested a combination of antiviral agents that target either the same viral protein (ex. neuraminidase, which helps in progeny virus release) or different viral proteins that interfere with different stages of virus infection (viral attachment, replication, or progeny virus release). A combination of antiviral drugs, including oseltamivir plus baloxavir marboxil (inhibitor of cap-dependent endonuclease activity), has shown synergistic effects compared to oseltamivir alone treated patients, but no significant improvements in the clinical outcomes were observed.8 Similarly, a triple combination antiviral therapy that includes oseltamivir, Amantadine (M2 ion channel inhibitor), and ribavirin (inhibitor of the viral polymerase) yielded promising results as oseltamivir and amantadine also exhibited antiviral activity against resistant viral strain in the combination therapy.9 However, although the triple combination drugs are well tolerated in the mechanically ventilated critically ill pandemic H1N1 influenza-infected patients, the clinical signatures were comparable with oseltamivir alone treated patients.10While treating critically ill influenza patients, it is critical to monitor two additional parameters including superinfections11 and host-induced immunopathology12 that could significantly exacerbate pulmonary pathology, thus worsening clinical outcome.From the history of influenza pandemics since 1918, it is known that secondary bacterial superinfections mainly contributed to devastating mortalities during influenza outbreaks.11 The failure in the clinical outcome, despite using antivirals and antibiotics in severe influenza, could be due to a lack of proper diagnosis of resistant viruses and bacterial pathogens involved in superinfections. Hence, efforts must be made to strengthen the screening and diagnostic capacities for early detection and rapid onset of antiviral treatment, together with continuous monitoring of secondary bacterial infections for selective antibiotic treatment, especially in patients admitted into ICUs.

BACKGROUNDAndrogenetic alopecia, often referred to as male pattern baldness, stands as the most prevalent form of alopecia. It is primarily characterized by a progressive reduction in hair diameter, length, and pigmentation.1 This process is driven by the influence of androgens, specifically dihydrotestosterone (DHT), in individuals genetically predisposed to this condition. The manifestation of androgenetic alopecia typically centers on the frontal and vertex regions of the scalp, while interestingly, the occipital area is usually spared from its effects.2 This localized pattern of hair loss can create distinctive patterns, such as receding hairlines and balding crowns, that are recognizable hallmarks of this condition. Beyond its mere physical impact, androgenetic alopecia exerts a profound influence on the psychological and emotional well-being of those affected. Hair is not merely a biological feature; it often carries a significant part of an individual’s identity and self-esteem.3 Consequently, the hair loss experienced in androgenetic alopecia can result in feelings of diminished self-confidence and self-image.CASE REPORTWe report the case of a 35-year-old man without comorbidities. The patient comes to the attention of the dermatologist complaining a progressive hair loss over the past 2 years. The patient reports that, at first, the hair loss was evidenced by the presence of hair on the pillow when he woke up and later, he noticed increased hair loss while showering. He initially attributed the fall to a period of work stress and did not give importance to it. However, progressive thinning in the fronto-parietal and vertex region led him to pay more attention to the problem, until he decided to book a dermatological examination with the intention of undergoing a hair transplant. At the dermatological examination, the patient presented a clinical picture compatible with androgenetic alopecia with involvement of the frontal and vertex region assessable as grade V, according to the Hamilton-Norwood scale4 (Figure 1A). Pull Test was positive and trichoscopy showed miniaturization of hair in androgen-dependent areas and hair reduction per pilo-sebaceous unit. The patient reported that hair loss had a strong impact on quality of life and personal, work, and relationship habits. In relation to the strong functional and esthetic impact of the problem, before deciding to undergo hair transplantation, the dermatologist proposed a conservative therapy: topical minoxidil 5% two times daily, oral finasteride 1 mg daily and topical application of a gel containing three oligopeptides mimicking growth factors, caffeine and taurine, and an iron chelating complex, one time per week. The patient underwent monthly follow-ups, and at 6 months after the start of the therapy, the results were striking: increased thickness of the shaft at the fronto-parietal and vertex levels and increased hair density per pilo-sebaceous unit were observed (Figure 1D). The patient was satisfied by the treatment and decided to postpone the transplantation.DISCUSSIONMale androgenetic alopecia is the most common cause of hair loss and has a strong impact on the quality of life of patients suffering from it. Currently, there are several treatments approved by the US FDA that have proven efficacy such as oral finasteride and topical minoxidil. On the other hand, some pioneering studies have demonstrated the efficacy of drugs such as dutasteride, topical finasteride, and/or oral minoxidil. Good emerging alternatives also include nondrug therapies such as platelet-rich plasma or laser therapy with wavelengths between 630 and 660 nm. In addition, studies on topical androgen receptor antagonists and topical cetirizine have provided promising results5. Recently, very promising data have been reported regarding the topical use of growth factor mimetic oligopeptides6, caffeine7, and taurine8 in individuals with androgenetic alopecia and/or telogen effluvium. Specifically, weekly use of a gel containing three growth factor mimicking oligopeptides, caffeine and taurine, and an iron chelating complex (GFmgel) has been shown to be particularly effective in subjects with androgenetic alopecia when used in combination with anti-hair loss medications such as topical minoxidil and oral finasteride9. In the case described, the patient applied a gel containing three growth factors mimicking oligopeptides, caffeine and taurine, and an iron chelating complex (GFmgel) in combination with dual therapy with minoxidil and finasteride. The patient, who initially expressed the will to undergo hair transplantation, was incredibly satisfied with the result achieved with conservative therapy six months later. Although our patient showed an excellent outcome, further real-world studies are needed to confirm the effectiveness of the combination of drug therapy and topical gel containing oligopeptides mimicking growth factors for the treatment of androgenetic alopecia.Figure 1Clinical presentation at baseline visit (Figure 1A); after 2 months (Figure 1B), after 4 months (Figure 1C) and after 6 months of therapy (Figure 1D).References:Piraccini BM, Alessandrini A. Androgenetic alopecia. G Ital Dermatol Venereol. 2014 Feb;149(1):15-24.Lolli F, Pallotti F, Rossi A et al. Androgenetic alopecia: a review. Endocrine. 2017 Jul;57(1):9-17. doi: 10.1007/s12020-017-1280-y. Epub 2017 Mar 28. PMID: 28349362.Huang CH, Fu Y, Chi CC. Health-Related Quality of Life, Depression, and Self-esteem in Patients With Androgenetic Alopecia: A Systematic Review and Meta-analysis. JAMA Dermatol. 2021 Aug 1;157(8):963-970.Rossi A, Ferranti M, Magri F et al. Clinical and Trichoscopic Graded Live Visual Scale for Androgenetic Alopecia. Dermatol Pract Concept. 2022 Apr 1;12(2):e2022078.Saceda-Corralo D, Domínguez-Santas M, Vañó-Galván S et al. What’s New in Therapy for Male Androgenetic Alopecia? Am J Clin Dermatol. 2023 Jan;24(1):15-24.Shome D, Kapoor R, Surana M et al. Neo® hair growth factor formulation for the treatment of hair loss in Covid-19-induced persistent Telogen Effluvium-A prospective, clinical, single-blind study. J Cosmet Dermatol. 2022 Jan;21(1):16-23. doi: 10.1111/jocd.14626. Epub 2021 Dec 7.Völker JM, Koch N, Becker M et al. Caffeine and Its Pharmacological Benefits in the Management of Androgenetic Alopecia: A Review. Skin Pharmacol Physiol. 2020;33(3):93-109.Kim H, Chang H, Lee DH. Simulative evaluation of taurine against alopecia caused by stress in Caenorhabditis elegans. Adv Exp Med Biol. 2013; 776:267-76.Lazzari, Tiziana & Milani, Massimo. (2019). Efficacy of Autologous Platelet-Rich Plasma alone or in Combination with a Lotion Containing Growth-Factor like Polypeptides and Taurine in the Treatment of Androgenic Alopecia: A Randomized, Prospective, AssessorBlinded Trial. Journal of Clinical & Experimental Dermatology Research.