Background: Human Immunodeficiency Virus (HIV), Human T Lymphotropic Virus (HTLV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection may lead to disease progression or worsen its clinical presentation. Viral coinfections screening during blood donation is critical. Methods: To identify risk factors for coinfection among blood donors, we assessed the blood donations at the Fundação de Hematologia e Hemoterapia da Bahia, from 2008 – 2017. We compared single infection versus coinfection, defined as individuals with two or more blood-borne viruses. A multivariable logistic regression model was performed to evaluate independent associations between characteristics of donors with single infection and multiple infection using “non-infection” category as reference. Results: Among 777,446 collected blood donations, 27,458 (3.5%) were reactive, most (n=26,677, 97.6%) for a single infection and 681 (2.4%) for coinfection. The most frequent coinfections were HBV-HIV (30.6%), HBV-HCV (30.4%), and HBV-HTLV (24.4%). Male sex, lower education, being single, and being a first-time donor were independently associated with both single and coinfection. Nevertheless, the adjusted odds for risk factors of coinfection were notably higher than for single infection. Conclusions: Single and coinfection shared identical risks, but they were significantly higher for coinfection. Preventive strategies addressing the identified risks can decrease transmission of blood-borne viruses via blood transfusion.

Purpose We describe a novel model for collaboration between academia and the pharmaceutical industry, focused on post-marketing pharmacovigilance. Methods Otsuka Pharmaceutical, a global Japan-based pharmaceutical company, and Columbia University, a major university, have established a collaboration dedicated to working together in pharmacoepidemiology and post-marketing pharmacovigilance. An oversight committee, made up of individuals from each institution, meets on a regular basis to set policy and provide oversight. Results The primary aim of this novel academia-industry collaboration is to provide expert research guidance for the industry pharmacovigilance group on questions involving pharmacoepidemiology. University epidemiologists may also be consulted by other divisions of industry, such as the clinical trials group. The first aim of the collaboration is to provide epidemiologic input to industry by determining the incidence, prevalence, and outcomes of diseases; drafting the epidemiology components of risk management plans for drugs; and planning retrospective database analyses. A second major aim is to provide educational services to industry by conducting workshops on basic epidemiology and biostatistics; leading a monthly lecture/journal club series; hosting seminars on medical topics; and providing a writing workshop to assist in preparing abstracts and papers for presentation and publication. University epidemiologists provide oversight/evaluation through quarterly presentations and updates to the industry partner’s external advisory committee as well as to University leadership. Conclusions This unique academia-pharmaceutical industry collaboration enhances understanding of the medical and epidemiologic challenges faced within a pharmacovigilance department of a global pharmaceutical company. We offer it as a model for others performing mandatory regulatory post-marketing pharmacovigilance activities.

Large Language Models (LLMs) are continuously being applied in a more diverse set of con‐ texts. At their current state, however, even state‐of‐the‐art LLMs such as Generative Pre‐Trained Transformer 4 (GTP‐4) have challenges when extracting information from real‐world technical docu‐ mentation without a heavy preprocessing. One such area with real‐world technical documentation is telecommunications engineering, which could greatly benefit from domain‐specific LLMs. The unique format and overall structure of telecommunications internal specifications differs greatly from standard English and thus it is evident that the application of out‐of‐the‐box Natural Language Processing (NLP) tools is not a viable option. This article provides a brief outline of the limitations of out‐of‐the‐box NLP tools for processing technical information generated by telecommunications experts and expand the concept of Technical Language Processing (TLP) to the telecommunica‐ tions domain. Additionally, we emphasize the importance of use case definition by introducing the required information mapping from the perspective of a Q&A application that uses internal speci‐ fications as the source of knowledge. Finally, we recommend actions to mitigate the effect of the internal specifications format on information extraction, effectively achieving LLM‐friendly inter‐ nal specifications.

Rare cases of neonatal thrombosis - case seriesRamesh Khadayat1, Prerana Kansakar1, Sailesh Shrestha1, Shreya Thapa1, Tilak Gautam1, Ramesh Basnet1, Sagar Rana Magar11. Patan Hospital, Patan Academy of Health Science, Lalitpur, Nepal*Corresponding author:-Ramesh KhadayatPatan Hospital, Patan Academy of Health Science, Lalitpur, NepalEmail:- [email protected]

1 Medical Intern, Faculty of Medicine, School of Medicine, Shahrood Branch, Islamic Azad University, Shahrood, Semnan, Iran a Emial Address: [email protected] Student Research Committee, Shahrood Branch, Islamic Azad University, Shahrood, Iran b Email Address: [email protected] Student Research Committee, Shahrood Branch, Islamic Azad University, Shahrood, Iran c Email Address: [email protected]: Hessamedin Babaei Email: [email protected] Clinical MassageAcute appendicitis remains one of the most frequent cause of emergent abdominal operations, diagnosed by combination of history, examination, and investigations to build a full clinical picture. The 63-year-old female presented in this case has had right lower quadrant abdominal pain for 10 days before the presentation. Her history, examination, and laboratory results didn’t support a diagnosis of acute appendicitis. Ultrasonography identified acute perforated appendicitis with minimal fluid collection, which led to her hospital admission. Subsequent laboratory investigations became consistent over time and patient prepared for the appendectomy. This case focuses on a rare presentation of a common disease. It seeks to point out the significance of using para-clinical tests judiciously in conjunction with clinical findings.Keywords: Appendicitis,INTRODUCTIONAcute appendicitis remains one of the most frequent cause of emergent abdominal operations with a lifetime risk of 8.6% in males and 6.7% in females1,2. Although in most cases this is an easily reached diagnosis, presentation is not always typical and there are certain other conditions which may mimic appendicitis. In fact the classical presentations only occur in 50% of cases2. Anatomical variations of the appendix and timing of presentation can make the clinical picture more cumbersome3. While there may be instances where operating on a patient without prior imaging examination is deemed appropriate, this should be regarded as an exception rather than a rule. The liberal utilization of imaging techniques to enhance preoperative diagnostic accuracy and minimize the incidence of negative appendectomy is an ongoing trend that is expected to persist4,5. The goal of treatment is preventing the condition to reach its potentially serious complications, including perforated and gangrenous appendicitis, abscess formation, intestinal obstruction, septic seeding of mesenteric vessels6.

Objective: This case report aims to illustrate the management of single tooth replacement in the esthetic region using immediate implant placement, highlighting the importance of interdisciplinary treatment planning and adherence to esthetic principles. Clinical Considerations: A 37-year-old female presented with a fractured upper front tooth, necessitating immediate attention to restore esthetic

Central hemangioma of mandible: Rare case

Background and Purpose: Pharmacokinetics have traditionally been assessed using concentration measurements from methods with low temporal resolution, such as blood draws, leading to profiles being estimated from sparse or blended data. Recent advances in in vivo sensors, however, now enable the collection of hundreds of observations over a few-hours for each individual drug administration. Previous analyses of such data for the antibiotic tobramycin have identified significant (several-fold), hours-scale changes in the efficiency with which this renally cleared drug is eliminated. Here we apply similar analyses to study the pharmacokinetics of another renally cleared drug, the antibiotic vancomycin. Experimental Approach: We estimate vancomycin pharmacokinetic profiles using previously collected time-dense plasma concentration measurements within six anesthetized rats. Specifically, we fit standard one- and two-compartment models, as well as time-varying one-compartment models (in which the proportionality relating concentration to elimination rate is time-varying), to these data to investigate if the time-varying models are statistically preferred for describing individual-level vancomycin pharmacokinetics, over standard one- and two-compartment models. Key Results: One-compartment models incorporating time-varying elimination proportionalities are statistically preferred over standard one- and two- compartment models for 5 of our 6 vancomycin time courses. When the initial impact of the distribution phase is removed from these data, a reciprocally time-varying one-compartment model is preferred over the standard-one compartment model in 4 of 5 considered datasets. Conclusion and Implications: These results provide further animal-model evidence that the pharmacokinetics of renally cleared drugs can vary significantly over timescales as short as a few hours.

Grapevine Trunk Diseases (GTDs) are among the most destructive diseases in viticulture due to global climate change. Some causal agents like Neofusicoccum parvum can be latent endophytic and become pathogenic under abiotic stress. Microtubules (MTs) have been found to play a role in mediating the pathogen-related signaling in grapevine. In this study, a novel transcription factor VrWRKY22 was identified and cloned from the native American grapevine Vitis rupestris. Leaves of the table grape variety ‘Kyoho’ ( V. vinifera × V. labrusca L.) overexpressing VrWRKY22 showed less necroses after N. parvum Bt‐67 inoculation and activated signaling pathways. VrWRKY22 was phosphorylated by VrMPK3 and then bound to the TTGACC motif in the promoter of VrKIN10C, which was confirmed by Y2H and Y1H assays. Since VrKIN10C is one of the important kinesin-like proteins associated with microtubules, a grapevine MT marker line overexpressing VrWRKY22 was generated to test the responses of grapevine cells to N. parvum Bt‐67. An increased number of prompt movement proteins can be traced within the peri-nuclear MTs and along the cortical MTs. The skewness and thickness of both central and cortical MTs were significantly increased. Moreover, a prominent (resulting from both the number and the rate) accumulation of speckles appeared in the nucleus and cortical MTs. A significant reduction in cell mortality and a stronger antioxidant capacity were detected. This study demonstrates that VrWRKY22 plays positive roles during N. parvum Bt‐67 invasion by rapidly increasing the concentration and dynamics of MTs in the peri-nuclear and cortical regions via VrKIN10, and will facilitate the interpretation of the results of further GTD mitigation studies.

Extracting water from discrete xylem and soil samples and continuous (long-term) monitoring of water vapor across the soil-plant-atmosphere continuum remains challenging and under a large debate. Here, we present a detailed one-year study in the Fort Worth Botanic Garden (north-central Texas) to evaluate the analytical robustness of the centrifugation extraction method and understand water sourcing from three common urban tree species (Elderberry, Sambucus canadensis; Cherry Laurel, Prunus caroliniana; and Boxelder Maple, Acer negundo). Xylem (N=110) isotope ratios (δ 18O and δ 2H) are compared to local precipitation (N=498), throughfall (N=33), and soil water (N=105) at different depths (0-38 cm). Complementary soil water samples were obtained from cup suction lysimeters (N=42) (0-38 cm). Soil and xylem water extraction volumes ranged from 100 µL to 7.5 mL in plant samples and from 100 µL to 10.5 mL in soil samples. Extraction success rates were 68.8% and 75.2% for xylem and soil samples, respectively. The minimum sample total water content for effective extractions was determined as 10.6% (soil) and 17.8% (xylem). Xylem mean narrowband and broadband (proxy for organic contamination) were 0.23±0.40 (-) and 1.00±0.01 (-), respectively. These values agree with mean narrowband and broadband metrics from throughfall and soils, which highlight the non-invasive nature of centrifugated extractions. Annual mean soil δ 18O compositions (-3.6±1.7‰) corresponded with the throughfall input (-3.6±2.4‰). Xylem δ 18O compositions exhibited a strong temporal enrichment trend at the end of the winter, summer, and fall seasons. Mean spring xylem δ 18O (-2.85‰) was less variable and close to soil mean compositions (-2.82‰). For this season, Bayesian mixing analysis showed source water contributions from distinct soil depths: 0 cm to 12.7 cm for Boxelder Maple, 12.7 cm to 25.4 cm for Cherry Laurel, and 12.7 cm to 38.1 cm for Elderberry. Our results offer a standardized and effective protocol for centrifugation extractions and reveal plant water uptake preferences in a highly altered urban green space during an unprecedented warm year.

Background: Respiratory syncytial virus (RSV) is an important cause of bronchiolitis and pneumonia in children globally. This study aimed to incorporate new data to update estimates of RSV burden in children through 5 years of age in Western Pacific and Southeast Asia Regions. Methods: A systematic review and meta-analysis was conducted to examine the proportion of RSV among cases of respiratory tract infection (RTI) in children in Western Pacific and Southeast Asia Regions using random effects models. Studies were eligible if they met the following inclusion criteria: (1) observational studies such as cohort and cross-sectional studies; (2) studies on humans; (3) studies on patients with respiratory tract infection (RTI) or influenza-like illness (ILI); (4) studies reporting incidence or proportion of RSV infection among respiratory related illness; and (5) studies on children aged 5 years or less. Findings: A total of 4,403 studies were identified from an initial search. After screening titles, abstracts, and full-text review, a total of 173 studies that met predefined eligibility criteria were included in the analysis. The overall proportion of RSV infections among all ARTIs was 18.7% (95% CI: 16.0-21.5%), while the proportion of RSV infections among LRTIs was 28.7% (95% CI: 2.6-30.3) in children in Western Pacific and Southeast Asia Regions between 1970 and 2021. The proportion trend increased from 10.6% (95% CI: 2.90-22.2%) in the 1970s to 26.8% (95% CI: 22.0-31.9%) in the 1980s and 33.3% (95% CI :14.7-55.3%) in the 1990s. It then decreased to 25.0% (95% CI 22.8-27.3%) in the 2000s and 19.7% (95% CI 17.3-22.2%) in the 2010s. By country, Myanmar (50.0%; 95% CI, 47.5-52.4%) and New Zealand (45.3%; 95% CI, 37.2-56.4%) had the highest proportion during the overall time period, followed by Bhutan (45.2%; 95% CI, 36.4-54.3%), Lao PDR (41.0%; 95% CI, 36.2-46.0%), and Vietnam (36.0%; 95% CI, 19.3-53.6%). Interpretation: Substantial RSV-associated disease burden occurs in children in Western Pacific and Southeast Asia Regions. Our findings provide new and important evidence of the need for RSV prevention in Western Pacific and Southeast Asia countries. They could inform future preventive policy.

Abstract Aim Goldenseal (Hydrastis canadensis L.) is a perennial herbaceous plant native to eastern North America. Commercial harvesting for the medicinal plant trade and habitat loss have led to international conservation concerns. This study aimed to gain an understanding of habitat predilections for the purpose of guiding in situ conservation efforts. Location This study was conducted in Pennsylvania, within natural range of the species in the northeastern U.S. The state’s variation in geology and biogeographic location an opportunity to examine the influences of edaphic, topographic, and climatic factors on goldenseal habitat suitability here. Methods GIS-based Maximum Entropy (Maxent) modeling using known occurrence points (n=51) was combined with field plot data (n=28) to identify potential factors governing goldenseal’s distribution in PA and identify vegetative indicators of supportive habitat. Results Bedrock type and winter temperature were the best predictors of habitat suitability. Suitable bedrock types were base-rich; a trait confirmed in the field by soil test results showing high calcium and pH levels. However, the influence of bedrock is complicated by overlapping land use legacy. Suitability increased with average winter temperature, peaking at 1.0°C toward upper end of winter temperatures in PA. Community analysis identified 159 woody and herbaceous associates, including indicators of the following supportive rich mesic forest types: “Tuliptree-Beech-Maple,” “Red Oak-Mixed hardwood,” and “Central Appalachian Rich Cove”. Main Conclusions Model and field results can be used in tandem to assess site suitability, which was found to be greatest within forestlands with slightly acidic to neutral loamy soils underlain by base-rich bedrock types on moist, lower slope positions. Vegetative “indicator” species of these rich-mesic forests including Liriodendron tulipifera, Acer saccharum, Lindera benzoin, Arisaema triphyllum, and Botrypus virginianus appeared to be useful field indicators of supportive habitat for in situ conservation efforts.

Background Necroptosis could be a trigger and amplifier of anti-tumor immunity in cancer therapy. LncRNAs are vital in controlling immune system gene expression. We designed to establish a NRlncRNA signature for evaluation and prognosis prediction in HNSCC, ultimately providing a new perspective for clinical application. Materials and methods We acquired RNA-seq and clinical data for HNSCC and 67 NRGs. Subsequently, diverse analytical methods were utilized to discern predictive NRlncRNAs, calculate the risk score, and construct a meticulous risk evaluation model. Furthermore, the predictive capability of the risk model was confirmed through survival analysis, ROC curves, PCA, DCA, C-index, and nomograms. We endeavored to discern disparities among distinct cohorts concerning clinical characteristics, the infiltration of immune cells, the sensitivity to pharmaceutical agents, as well as molecules associated with immune response. Results A risk signature for 12 NRlncRNAs was developed, and the signature had high sensitivity and specificity in predicting survival rates. The established model exhibited a strong association with both survival outcomes and clinical features. Notably, the low-risk group demonstrated a substantially elevated survival probability and displayed a significant positive correlation with diverse immune cell infiltrations. Lastly, we selected different clinical drug regimens based on the different risk groups. Conclusion A prognostic model of NRlncRNAs has been developed for HNSCC that enables the estimation of the TME and the response to cancer immunotherapy. The model also has the potential to predict the prognosis, which may pave the way for novel clinical applications.

Non-steroidal anti-inflammatory drugs (NSAIDs), especially acetyl salicylic acid (ASA), associate with reduced breast cancer (BCa) mortality. COX-2 overexpression is tied to worse BCa prognosis, but COX-2 inhibitors (coxibs) have not been shown to have survival advantage. However, the evidence is conflicting and limited. We examined the association between BCa mortality and NSAID use in a Finnish population-based cohort. The study cohort, 73,170 females diagnosed with BCa during 1995-2013 was identified from The Finnish Cancer Registry. NSAID purchases during 1995-2015, the time and causes of death, mammographic screening participation and tumor hormone receptor status were obtained from national registries. Separate exposure variables were created for purchases of all NSAIDs combined, ASA and coxibs . Multivariable-adjusted Cox proportional hazard regression was used to compare BCa-specific and overall survival by the use of NSAIDs, ASA and coxibs compared to non-users. Pre-diagnostic use of any NSAIDs (HR 0.78, 95% CI 0.75-0.81) and coxibs (HR 0.76, 95% CI 0.71-0.81), but not ASA were associated with lowered BCa mortality. Conversely post-diagnostic use of any NSAIDs was associated with increased BCa mortality (HR 1.27, 95% CI 1.22-1.33), while ASA use (HR 0.84, 95% CI 0.73-0.97) showed dose-dependent risk reduction. Post-diagnostic use of ASA associated with reduced BCa-specific mortality, distinguishing ASA from other NSAIDs. Clinical trials should be performed to confirm this association and to determine ideal post-diagnostic ASA dose, frequency, and duration for improving BCa-specific survival. The significance of pre-diagnostic NSAID use as a prognostic factor in BCa warrants further investigation.

Fragmentation of landscapes is a common impairment of habitats highlighting the need to increase connectivity to support wildlife populations. This study focuses on the Eastern green lizard (Lacerta viridis) and investigates the effectiveness of a species-specific corridor network in a vineyard landscape. Using a non-invasive photographic capture-recapture approach, individual movements were tracked to assess sex-specific patterns and distances covered in adult lizards. The study also provided insight into population parameters such as sex ratio and spatial distribution of the resident green lizard population. Results showed a surplus of male individuals and clustered distributions along the habitats. Both, male and female green lizards use the habitat network, with males covering larger distances. The connectivity structures facilitated the movement of males between habitat sections with some individuals covering distances exceeding 250 m. Hereby, male movement distances correlated with female abundance, which emphasizes the importance of connectivity structures in maintaining population stability. Two parameters correlated to female abundance showed significance in the models. First, the fewer females were detected in a male’s core area, the higher the probability that it migrated a long distance. Secondly, a positive correlation existed between males’ covered distance and female abundance in its entire activity range. Overall, this research highlights the importance of habitat connectivity measures for natural population dynamics through supporting male lizards to migrate in search of females.

Biogeographical partitioning of ecological communities has been renewed in recent decades to illustrate broad distributional patterns. In the oceans, observational datasets have grown substantially and open new access to test bioregional patterns beyond the classical fixed thresholds of endemism to differentiate regions. This work combines a recently collated dataset of 29 different scientific bottom trawl surveys spanning 21 years with network-based clustering to illustrate biogeographical partitions of vast tracts of the northern hemisphere’s continental shelf seas. Our work contributes to testing bioregionalization patterns in demersal fishes using observational data, totaling >2.5 million species records and >2000 species, with bipartite network clustering weighted by species occurrence frequencies. We propose eight major bioregions across shelf seas which fall along the longest geographical axis in each shelf region and against continua of species richness gradients, endemicity, and phylogenetic turnover rates. These patterns capture known biogeographical boundaries (e.g., North Sea–Baltic Sea, Cape Hatteras) alongside potential transition areas deduced from uncertainty estimates based on shared network nodes between bioregions. The most species-rich areas include the Southeast US Shelf, Temperate Pacific, Northeast Atlantic Shelf, and the Outer European Shelf— corresponding to relatively high endemicity. However, the relatively species-poor partitions including the Baltic Sea and the North & Celtic Seas display comparatively low endemicity (<8%), illustrating apparent statistical differences in partitions captured by bipartite networks and occurrence frequencies that would otherwise be missed using a fixed endemic criterion. Our proposed bioregionalization can be compared against the growing availability of species occurrence data, dispersal limitations, or other quantitative observations of ecological communities.

Algorithm for the management of Primary Diffuse Chronic RhinosinusitisW.J. Fokkens1, , E. de Corso2 , P.W.Hellings3,4, R. J. Harvey5,6, C. Hopkins7, S. Reitsma11 Amsterdam UMC, University of Amsterdam, Department of Otorhinolarynogology, Amsterdam2. Unit of Otorhinolaryngology and Head-Neck Surgery, ”A. Gemelli” University Hospital Foundation IRCCS, 00168 Rome, Italy.3. University of Leuven, Department of Otorhinolaryngology, Leuven,4.The European Forum for Research and Education in Allergy and Airway Diseases Scientific Expert Team Members, Brussels, Belgium.5. Rhinology and Skull Base Research Group, St Vincent’s Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.6. Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.7. King’s College London, London, UK.

Valproate-containing medicines (VPA) are first-line treatment for epilepsy; however, they pose teratogenic risks, restricting their use in women of childbearing age. We aimed to estimate the secular trends in use of VPA and alternative treatments in young women, and to characterise dose/strength, treatment duration and indication in new VPA users We conducted a population-based cohort study using primary care records from the Netherlands, Spain and the UK, primary and outpatient specialist care records from Germany and Belgium (and hospital records from Finland, all mapped to the OMOP Common data model. All women present in the databases aged ≥12 years and ≤55 years on 1st of January of each year in the period 2010-2022 (or latest available), with at least 365 days of prior observation were included. Incidence and prevalence of VPA use in young women decreased between 2010 and 2021, while prevalence of the alternative treatments pregabalin and gabapentin increased, especially in CPRD (it rises from 0.5% to 1.5%). Median age of new VPA users ranged between 40-43 years. Anxiety and depressive disorder were frequent comorbidities, and use of hormonal contraceptives low. Average treatment duration varied substantially across databases . Incidence and prevalence of use of VPA among young women declined since 2015. Conversely, alternative antiepileptics have increased in uptake, particularly gabapentinoids. The use of standardized federated analytics allowed for a rapid assessment of VPA utilisation, supporting the regulatory agencies in their decision making and improving patient safety across Europe.