Search Results (4,266)

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer (NMSC) and represents the leading cause of NMSC-related deaths. Despite its growing global burden, comprehensive epidemiological and clinicopathological data from Easter Europe remains limited. This study aimed to evaluate the epidemiological, clinical, histopathological, and surgical characteristics of cSCC diagnosed before, during and after the COVID-19 pandemic. Methods: We conducted a retrospective, descriptive observational study including 332 lesions diagnosed between January 2017 and December 2025 at the Clinical Pathology Department of the Mureș Clinical County Hospital. Demographic, epidemiological, topographic, histopathologic, surgical, and volumetric parameters were analyzed. Tumours were stratified into low-, high-, and very-high-risk categories according to the National Comprehensive Cancer Network (NCCN) criteria. Results: The cohort demonstrated a significant male predominance (n = 193 vs. n = 139; p = 0.0355), with females presenting a higher median age (77 vs. 75; p = 0.0489). Lesions were predominantly located in the head and neck region (n = 216; p < 0.0001), which was significantly associated with very-high-risk tumours (p = 0.0051). Low-risk tumours accounted for 62.35% of cases, while high-risk and very-high-risk lesions comprised 19.88% and 17.77%, respectively (p < 0.0001). Ulcerations were strongly associated with very-high-risk tumours (p < 0.0001). Poor differentiation was more frequent outside the head and neck region (p < 0.0001) and varied significantly across the pandemic periods (p = 0.0349). Tumoral and excision volumes were higher in very-high-risk (p = 0.0070; p = 0.0004) and ulcerated tumours (p < 0.001), with a peak in volume during the COVID-19 period (p < 0.0001). A decrease through the years of diagnosis was observed in tumoral volumes (r = −0.2295; p < 0.0001) and patients showed a weak positive correlation with diagnosis year (r = +0.13; p = 0.019). Conclusions: The study provides an epidemiological and clinicopathological characterization of cSCC within one of the largest Romanian cohorts to date. Tumour aggressiveness was primarily driven by histopathological and topographical features rather than demographic factors. While the COVID-19 pandemic did not induce persistent changes in tumour risk profiles or surgical outcomes, it influenced diagnosis timing and tumour burden. These findings highlight the importance of incorporating temporal and emerging systemic factors, such as pandemics, and infectious events, into future epidemiological models to improve preparedness, early detection, future treatment schemes, and risk stratification in cSCC. Full article

Genome-wide association studies have identified numerous genetic variants statistically significantly associated with body mass index (BMI). However, the functional mechanisms underlying most associations between single nucleotide polymorphisms (SNPs) in non-coding regions and BMI remain poorly understood. Here, we implemented an integrative 7-criterion quantitative scoring system (gene localization, histone modifications, transcription factor binding sites (TFBS), SNP clouds, tissue expression patterns, evolutionary conservation, and COVID-19 associations) to prioritize putative functional loci among 94 BMI-associated SNPs. Six SNPs resided within long non-coding RNA (lncRNA) genes: rs2245368 (exonic, DTX2P1-UPK3BP1-PMS2P11), rs2033529 (exonic, LINC00951), rs2836754 (intronic, ETS2-AS1), rs2815752 (intronic, LINC02796), rs17203016 (intronic, MYOSLID-AS1), and rs7239883 (intronic, LINC00907). We prioritized them because they are located within lncRNA gene bodies and therefore showed stronger functional support compared to other variants which only had non-coding regulatory elements in their vicinity. Notably, rs1928295 exhibited strong GATA2 binding evidence, while rs13201877 had extensive transcription factor occupancy (64 factors). Multiple variants demonstrated putative regulatory potential through epigenomic evidence, including DNase I hypersensitivity and cell-type-specific chromatin accessibility. We show that most BMI risk alleles are not human-specific and are conserved across primates. Our findings suggest putative candidate non-coding regulatory elements in BMI and provide prioritized obesity-associated non-coding variants for functional validations. Full article

Pedestrian safety represents a critical priority for the development of sustainable urban mobility systems. This study proposes an innovative methodological framework integrating supervised and unsupervised learning techniques with econometric modeling to identify and interpret risk scenarios. Using the Italian national dataset from 2010 to 2023, an XGBoost model has been initially trained and tested. Then, SHapley Additive exPlanations (SHAPs) have been applied to highlight contributing factors. Using the resulting SHAP values, a K-Means clustering algorithm was finally employed to segment crashes into homogeneous clusters. For each cluster, a Generalized Linear Mixed Model incorporating geographic random intercepts and temporal random slopes was calibrated. Through this hybrid-stratified approach, three risk scenarios have been identified, primarily driven by demographic vulnerability. For elderly pedestrians, the involvement of heavy vehicles nearly doubles the odds of a fatal outcome. Crash dynamics varied significantly: heavy vehicles and speeding nearly double the fatality risk for elderly pedestrians; nighttime represents a severe hazard for adults (OR = 3.87) and youths (OR = 7.99), with the latter also highly penalized by unsafe road behaviors (OR = 3.12). From a spatio-temporal perspective, random effects revealed that the Islands (Sicily and Sardinia) are the most critical macro-areas (+55.2% baseline risk for adults) and the North-West the safest. Furthermore, the COVID-19 pandemic mitigated fatal risk for young pedestrians nationwide, had a neutral impact on the elderly, and for adults was protective in Southern regions but corresponded to higher odds of mortality in the North, reflecting altered traffic dynamics. Full article

Background and Objectives: In-hospital cardiac arrest (IHCA) in critically ill patients with COVID-19 is among the most severe clinical outcomes, associated with high mortality and a significant risk to healthcare workers during cardiopulmonary resuscitation (CPR). The aim of this study was to evaluate the incidence, characteristics, associated factors, and outcomes of IHCA among COVID-19 patients treated in the intensive care unit (ICU), with particular emphasis on resuscitation outcomes and survival. Materials and Methods: A retrospective cohort study was conducted including critically ill patients with confirmed SARS-CoV-2 infection treated in the ICU of the Clinical-Hospital Center (KBC) in Kosovska Mitrovica between March 2020 and December 2022. Patients were categorized into two groups: (1) CA group—patients who experienced CA in the ICU, and (2) non-CA group—patients who did not experience CA during ICU treatment. Results: A total of 222 patients were analyzed, of whom 114 (51.4%) experienced IHCA. Patients with IHCA were significantly older, more frequently obese, and had a higher burden of comorbidities. They also exhibited more pronounced hematological and inflammatory abnormalities, including lower erythrocyte and hemoglobin levels, thrombocytopenia, and elevated leukocyte counts, fibrinogen, C-reactive protein, and procalcitonin levels. In addition, higher lactate and D-dimer concentrations were observed, along with a more frequent occurrence of hyperkalemia and hypernatremia. The predominant cause of IHCA was respiratory failure, most commonly associated with severe hypoxemia (59.6%), while non-shockable initial rhythms (asystole and pulseless electrical activity (PEA)) were most common (76.3%). Among patients with IHCA, return of spontaneous circulation (ROSC) was achieved in 11 patients (9.6%), and 3 patients (2.6%) survived to hospital discharge. Conclusions: Despite rapid response and CPR in the ICU setting, outcomes remained poor. More favorable outcomes were observed mainly in cases with potentially reversible etiologies (such as myocardial infarction and pulmonary embolism (PE)), in contrast to hypoxia-mediated CA. Full article

Understanding the clinical and hospital trajectory of fatal COVID-19 cases is essential to clarify disease progression and support healthcare planning. This study analyzed the temporal trajectory of patients with confirmed COVID-19 who died in Campo Grande, Brazil, during 2021–2022. A retrospective observational study was conducted using secondary data from 3572 fatal cases. Time intervals between symptom onset, hospitalization, intensive care unit (ICU) admission, and death were calculated. Survival analyses were performed using Kaplan–Meier curves and Cox proportional hazards regression. Most patients were aged 61–80 years (48%), male (55%), and had at least one reported risk factor (86%). The most frequent comorbidities were cardiopathy (56%), diabetes mellitus (35%), and obesity (20%). The mean time from symptom onset to hospitalization was 7.70 days, while the mean time from symptom onset to death was 22.87 days. Survival analyses showed significant differences according to age, neurologic disease, pneumopathy, and obesity. In the multivariable Cox model, age remained independently associated with shorter survival time. Fatal COVID-19 cases were characterized by a relatively short interval from symptom onset to hospitalization and a prolonged in-hospital course until death. By characterizing the timing of clinical deterioration, ICU admission, and death, these findings may inform regional assessments of critical care demand, expected ICU bed occupancy, and capacity planning during periods of increased healthcare demand. Full article

Background: Increased placental thickness has been associated with adverse perinatal outcomes and fetal functional and structural abnormalities. However, whether marked third-trimester placental thickening is associated with a distinct maternal clinical profile compared with pregnancies with normal placental thickness remains insufficiently characterized. This study aimed to compare maternal characteristics, comorbidities, medication exposure, infection history, and fetal findings between pregnancies with marked placental thickening, defined as placental thickness ≥70 mm, and gestational-age-matched control pregnancies with a placental thickness <70 mm and no documented maternal or fetal abnormalities. Methods: This retrospective matched case–control study included singleton pregnancies referred for fetal echocardiography to a tertiary referral center in Łódź, Poland, between 1 January 2022 and 14 March 2025. Placental thickness was measured sonographically in a perpendicular plane from the chorionic plate to the basal plate, excluding the umbilical cord insertion site. Only anterior and/or fundal placentas assessed at ≥28 weeks of gestation were included. Among pregnancies with recorded third-trimester placental thickness measurements, 99 cases with placental thickness ≥70 mm were identified as the thick-placenta group. A control group of 99 pregnancies with placental thickness <70 mm was selected and matched for gestational age. Control pregnancies had no documented maternal disease, no fetal structural or functional abnormalities, and no exposure to the medications analyzed in this study. Maternal demographic characteristics, body mass index, comorbidities, infection history, obstetric history, and medication use were compared between groups. Continuous variables were compared using Welch’s t-test and the Mann–Whitney U test, and categorical variables were compared using Fisher’s exact test. Results: The study included 99 pregnancies with marked placental thickening and 99 control pregnancies with normal placental thickness. Gestational age at examination was comparable between groups, with a mean of 35.5 weeks in controls and 35.0 weeks in the thick-placenta group (p = 0.662, Welch’s t-test). Median gestational age was also not significantly different between groups (35.4 vs. 36.43 weeks; p = 0.340, Mann–Whitney U test). Mean placental thickness was significantly greater in the thick-placenta group than in controls (81.4 mm vs. 46.9 mm; p < 0.0001). Maternal age and anthropometric characteristics were comparable between groups, whereas BMI > 25 kg/m² was more common in the thick-placenta group. In contrast to the clinically healthy control group, maternal infection was documented in 100.0% of thick-placenta cases, hormonal treatment in 97.0%, history of COVID-19 in 52.5%, hypothyroidism in 44.4%, prior miscarriage in 37.4%, aspirin or anticoagulant use in 32.3%, gestational diabetes mellitus in 25.3%, and pregnancy-induced hypertension in 7.1%. All evaluated maternal clinical factors were significantly more common in the thick-placenta group than in controls. Fetal cardiac or extracardiac dysfunction was present in 68.7% of thick-placenta pregnancies. Conclusions: In this gestational-age-matched case–control study, pregnancies with marked third-trimester placental thickening showed a distinct maternal profile compared with healthy controls with normal placental thickness. Despite comparable gestational age, maternal age, and maternal anthropometric characteristics, the thick-placenta group demonstrated a significantly higher infectious, hormonal, metabolic, and endocrine burden. These findings indicate that, in this selected tertiary referral cohort, placental thickness ≥70 mm was associated with a higher burden of maternal clinical abnormalities and fetal functional findings. Rather than representing an independent marker of placental maladaptation or maternal-fetal risk, marked placental thickening should be interpreted as a clinically relevant ultrasound finding that may prompt careful review of maternal history and targeted fetal assessment. Prospective studies are needed to determine which maternal factors are independently associated with placental thickening and to clarify their relationship with fetal function and perinatal outcomes. Full article

Background: Early discrimination between viral, bacterial, and mixed respiratory tract infections remains challenging in clinical practice. Conventional microbiological methods may be limited by turnaround time and specimen-related factors, whereas routine inflammatory markers lack sufficient specificity for etiological classification. We investigated whether flow cytometry-derived immune markers combined with C-reactive protein (CRP) could improve early infection stratification. Methods: In this prospective single-center study, adult patients with acute respiratory tract infection and healthy controls were enrolled between 29 July 2025 and 31 January 2026. Peripheral blood CD169 positivity on monocytes (CD169%), neutrophil CD64 index (nCD64 index), monocyte HLA-DR positivity (HLA-DR%), and CRP were measured and compared across viral infection (influenza A, influenza B, or COVID-19), bacterial infection, mixed infection, and healthy control groups. Logistic regression models were developed for three diagnostic tasks: viral versus bacterial infection, mixed versus bacterial infection, and mixed versus viral infection. Model performance was evaluated using receiver operating characteristic (ROC) analysis, DeLong testing, calibration, decision curve analysis (DCA), and bootstrap internal validation. Nomograms were constructed from the final models. Results: A total of 216 infected patients were included: 112 with viral infection, 67 with bacterial infection, and 37 with mixed infection; 50 healthy individuals served as controls. CD169% was increased in viral and mixed infection, whereas the nCD64 index was increased in bacterial and mixed infection. HLA-DR% was lower in bacterial infection. For differentiating viral from bacterial infection, the optimized three-marker model combining CD169%, nCD64 index, and CRP achieved an area under the ROC curve (AUC) of 0.8947 (95% CI: 0.8463–0.9432), with a sensitivity of 81.25% and a specificity of 80.70%. In mixed infection, CD169% was the main discriminator versus bacterial infection, while the nCD64 index and CRP were more informative versus viral infection. The combined model yielded an AUC of 0.7618 (95% CI: 0.6485–0.8751) for mixed versus bacterial infection and 0.8406 (95% CI: 0.7594–0.9218) for mixed versus viral infection. Longitudinal analyses showed that CD169% declined during recovery from viral infection, whereas the nCD64 index and CRP decreased after treatment in bacterial infection; all three markers declined in mixed infection. Conclusions: CD169%, the nCD64 index, and CRP reflect complementary dimensions of the host response to acute infection. Their combined assessment showed good performance for differentiating viral from bacterial infection and provided clinically relevant information in mixed infection. This host-response-based nomogram may serve as a practical adjunct for early etiological stratification and mixed-infection risk assessment. Full article

Background: Vaccine acceptance is a fundamental prerequisite for uptake, which may vary over time in response to contextual and vaccine-specific factors and major global disruption. This systematic review and meta-analysis evaluated global trends and determinants of vaccine acceptance between 2009 and 2024. Methods: A comprehensive literature search was conducted using pre-defined keywords and controlled vocabulary related to vaccination, vaccine acceptance or hesitancy, with a broad search strategy designed to capture global evidence across multiple vaccine categories and geographic settings. Studies restricted to high-risk groups or other specific sub-populations (e.g., healthcare workers) were excluded. Studies reporting vaccine acceptance outcomes were systematically identified and pooled estimates were calculated across vaccine categories, WHO regions, income groups, and pandemic periods. Temporal trends and interaction effects were assessed to evaluate changes in vaccine acceptance among different vaccines and before, during, and after the COVID-19 pandemic. Results: A total of 264 publications, including 650,772 participants from 97 countries, were included. Overall, pooled vaccine acceptance was 70.63% and remained relatively stable throughout the study period. Most studies originated from high-income countries, whereas low-income countries and the African region were underrepresented. Childhood vaccines demonstrated the highest pooled acceptance (80.26%), followed by HPV vaccines (66.48%), while influenza vaccines showed the lowest acceptance (52.00%). Childhood vaccine acceptance increased over time and during the COVID-19 period, whereas significant negative interaction trends were observed for HPV and influenza vaccines. Higher vaccine acceptance was observed in African and South-East Asian regions compared with Western Pacific and European regions. Acceptance also varied across income groups, with greater hesitancy generally observed in higher-income settings. Conclusions: Vaccine acceptance among the general population remained relatively stable globally between 2009 and 2024 but varied substantially by vaccine categories, geographic regions, and economic settings. These findings highlight the context-specific nature of vaccine acceptance and the need for harmonized measurement tools and stronger evidence from underrepresented regions to support equitable immunization strategies. Full article

Background: The post-acute consequences of prolonged Coronavirus Disease 2019 (COVID-19) infection are a major public health problem characterized by long-lasting, multisystem manifestations. There is limited evidence from Saudi Arabia, particularly from nationally representative studies using standard case definitions. Objective: This study aimed to estimate the prevalence of Long COVID, characterize its symptoms, identify risk factors, and assess disease burden and healthcare utilization among Saudi adults. Methods: Between June 2023 and December 2024, we conducted a national cross-sectional mixed-methods study among 1790 adults with PCR-confirmed COVID-19 infection in all 13 regions of Saudi Arabia. Long COVID was defined using the WHO consensus case definition (symptoms persisting ≥ 3 months post-infection not attributable to alternative diagnoses). Results: The prevalence of Long COVID was 32.0% (95% CI 29.8–34.3). The most common symptoms were fatigue (68%), dyspnea (45%), and cognitive impairment (39%). Independent predictors included female sex (adjusted odds ratio [aOR] 1.8, 95% CI 1.4–2.3), moderate-to-severe acute infection (aOR 2.5, 95% CI 2.0–3.1), incomplete vaccination (aOR 1.6, 95% CI 1.2–2.1), metabolic disorders (aOR 1.6, 95% CI 1.2–2.1), and obesity (aOR 1.5, 95% CI 1.2–1.9). Among Long COVID patients, 41% required specialty care and 12% reported work disability. Conclusions: Long COVID affects approximately one-third of COVID-19 survivors in Saudi Arabia, imposing a significant healthcare and socioeconomic burden. These findings highlight the need for swift action and policy implementation within the health care system to mitigate long-term consequences. Full article

Introduction: Interleukin-6 is one of the key mediators of the inflammatory response and has repeatedly been associated with severe COVID-19 and an increased risk of death. However, its clinical significance depends on the timing of measurement, the characteristics of the study population, and the organizational context of care. Data on the significance of IL-6 in temporary hospital settings remain limited. Objective: The objective of this study was to assess the association between the highest available interleukin-6 (IL-6) concentration recorded during hospitalization and in-hospital mortality among patients hospitalized for COVID-19 at the Temporary Hospital in Gdansk. Additional objectives were to assess the ability of IL-6 to discriminate in-hospital mortality, determine an exploratory cutoff point for the study cohort, and assess selected clinical factors associated with elevated IL-6 concentrations. Materials and Methods: A retrospective, single-center cohort study was conducted involving 1214 patients hospitalized for COVID-19 during two periods of operation of the Temporary Hospital in Gdansk. IL-6 measurements were performed selectively, at the discretion of the attending physician; therefore, IL-6 analyses were conducted in a subcohort of 171 patients with an available result. The highest available IL-6 concentration recorded during each patient’s hospitalization was used in the analysis. Patients with and without an IL-6 measurement were compared. The association between IL-6 and in-hospital mortality was assessed using ROC analysis and a multivariable logistic regression model in which IL-6 was analyzed as a continuous variable after log₂ transformation. Results: A total of 230 in-hospital deaths were recorded in the entire cohort. IL-6 was measured in 171 patients. Patients with an IL-6 measurement differed from the remaining hospitalized patients in terms of age, sex, year of hospitalization, mortality, length of hospital stay, and the prevalence of respiratory disease, indicating the clinically selective nature of this subcohort. ROC analysis for IL-6 levels yielded an AUC of 0.73, and the cutoff point determined using the Youden method was 94.3 pg/mL. In the multivariable logistic regression model, log₂-transformed IL-6 remained associated with in-hospital mortality after adjustment for age, year of hospitalization, and respiratory disease. A two-fold increase in IL-6 concentration was associated with an approximately 27.5% increase in the odds of death. Conclusions: The highest available IL-6 concentration recorded during hospitalization was associated with in-hospital mortality in the analyzed subcohort of patients hospitalized for COVID-19. The findings support the relevance of IL-6 as a marker of an intensified inflammatory response during hospitalization, but should not be interpreted as validation of IL-6 as a standalone prognostic tool measured at hospital admission. Full article

Background: Post-acute sequelae of COVID-19 (PASC), commonly known as long COVID, affects an estimated 10–30% of SARS-CoV-2 non-hospitalised and 50–70% of hospitalised survivors. This condition remains clinically heterogeneous, and the specific mechanisms driving the transition from acute infection to chronic sequelae remain poorly understood. We assessed independent risk factors, tracked the evolution of clinical features, defined distinct symptom-based phenotypes, and assessed the impact of different pandemic waves on the likelihood of developing long COVID in hospitalised survivors. Methods: We conducted a single-centre, retrospective cohort study at a university hospital in London. The population comprised 627 adults hospitalised with acute COVID-19 between February 2020 and December 2022. Baseline characteristics and outcomes were compared between long COVID and resolved cases using appropriate statistical tests for continuous and categorical variables. Multivariable logistic regression identified risk factors. McNemar’s test quantified the phenotypic shift from admission to follow-up. Latent Class Analysis (LCA) identified clinical subtypes based on symptom clusters. Results: Of 627 patients, 252 (40.2%) met long COVID criteria. Comorbidity burden was the strongest predictor; patients with a single condition had a 4-fold increase in odds (aOR 4.62, 95% CI 2.36–9.04). The ORs were also significantly elevated among patients with 2 (aOR 3.26), 3 (aOR 2.68), or 4 or more (aOR 3.24) comorbidities. Older age (aOR 1.04), acute disease severity (measured by length of hospital stay) (aOR 1.27 per log-day) and elevated admission fibrinogen (aOR 1.21 per g/L) were significant predictors. Temporal analysis revealed a precipitous decline in risk from Wild-type/Alpha (>50%) to Delta/Omicron (<21%). We observed a distinct phenotypic shift: while acute respiratory inflammation resolved, systemic fatigue increased fourfold (7.0% to 32.4%), and memory difficulties emerged in the post-acute phase. LCA identified two phenotypes: fatigue-dominant and multisystem phenotypes. Conclusions: Long COVID is a multifactorial syndrome driven by host susceptibility, acute severity, and persistent coagulopathy. Clinical management should move beyond a monolithic approach and favour phenotype-specific strategies. Full article

Background/Objectives: Congenital gastrointestinal malformations (CGIMs) remain a significant cause of pediatric mortality, particularly during the neonatal period in resource-limited settings. Mortality varies widely, across conditions and healthcare systems, yet data from Eastern European centers remain limited. We aimed to determine mortality during index admission and identify baseline factors associated with death among children with CGIMs treated at our tertiary surgical center, including the COVID-19 pandemic years. Methods: We conducted a single-center retrospective study (January 2020–December 2024) of all consecutive children admitted with congenital gastrointestinal malformations. The primary outcome was death during index admission. Secondary mortality outcomes included death within 30 days of admission and 30-day postoperative mortality. Comparisons were performed between survivors and non-survivors. Data were extracted from medical records and potential risk factors of mortality were evaluated using univariable analyses and multivariable logistic regression. Statistical analysis was performed using SPSS version 31 (IBM) and a p-value of <0.05 was considered statistically significant. Results: Overall, index-admission mortality was 11.7% (27/231), with 55.6% of deaths occurring within 30 days from admission and 85.2% occurring postoperatively. Mortality was highest among patients with cloacal malformations, duodenal atresia/stenosis, and esophageal atresia ± tracheoesophageal fistula. Deaths occurring during the neonatal period accounted for 85% of all deaths. Compared with survivors, non-survivors had significantly lower birth weight, gestational age, and Apgar scores, increased ASA score, and higher rates of prematurity, syndromic conditions, associated anomalies, and sepsis. In multivariable analysis, prematurity remained independently associated with index-admission mortality (adjusted OR 3.20, 95% CI 1.23–8.31; p = 0.017). In an exploratory multivariable analysis including in-hospital complications, sepsis was strongly associated with mortality (adjusted OR 8.63, 95% CI 3.16–23.55, p < 0.001). Conclusions: Mortality during index admission remained substantial among children with congenital gastrointestinal malformations. Prematurity was the only baseline characteristic independently associated with mortality. In an exploratory analysis, sepsis identified from retrospective clinical documentation was associated with mortality. Improved care for preterm infants and prevention of severe infection may improve outcomes. Larger multicenter studies are needed to validate these findings and refine risk stratification strategies for high-risk patients. Full article

A bidirectional relationship has been observed between COVID-19 and respiratory disorders, where respiratory comorbidities increase severity, and COVID-19 induces respiratory sequelae. The underlying biological and genetic mechanisms remain unclear. While previous studies have identified overlapping genetic loci, few have systematically disentangled the genetic factors shared between these conditions versus those specific to COVID-19, particularly at a multi-omics level. We developed and applied a unified analytical framework to compare three COVID-19 phenotypes with eight respiratory disorders (including asthma, COPD, IPF, and pneumonia). Utilizing the cofdr method for shared genetic signal analysis and DDx/mtCOJO for differentiation, we integrated genome-wide association statistics with multi-omics data (transcriptome, splicing, and proteome). This approach allowed for the simultaneous identification of shared genetic signals (concordant or discordant) and disease-specific variants across expression (TWAS), alternative splicing (spTWAS), and protein abundance (PWAS). We delineated a comprehensive atlas of 214 differential and numerous shared loci across 24 pairwise comparisons. The shared genetic architecture was characterized by pleiotropic effects in genes such as ATP11A (exhibiting opposing effects in COVID-19 vs. IPF) and GSDMB (shared with COPD). Crucially, differentiation analysis revealed that severe COVID-19 is genetically distinct from other respiratory infections (e.g., pneumonia and influenza) through dysregulated Type I/III interferon signaling and specific defects in alveolar epithelial and macrophage function, as well as GM-CSF/surfactant metabolism pathways. These findings provide human genetic evidence consistent with the therapeutic rationale underlying GM-CSF modulators and interferon-lambda for COVID-19, both of which have entered clinical trials. Furthermore, multi-trait conditional analysis prioritized FYCO1 and HCN3 as potential COVID-19-specific risk genes. Splicing analysis underscored the critical role of alternative splicing in both shared and differential architectures, highlighting IFNAR2 isoform regulation as a key discriminator between COVID-19 and other respiratory traits. This study provides the first genome-wide, multi-omics map revealing the shared and differential genetic landscapes of COVID-19 and other respiratory phenotypes. By uncovering specific molecular mechanisms that distinguish COVID-19 pathology, specifically involving surfactant homeostasis and interferon pathways, our findings offer novel insights for targeted drug repurposing and precision risk stratification. Full article

Modern Bayesian hierarchical methodologies allow us to leverage spatio-temporal dependencies between observations, enhancing both health effect estimation and map visualization in efficient and flexible ways. However, the necessary levels of statistical software are often unavailable or difficult to access. We have recently examined Bayesian spatio-temporal models to estimate the association between COVID-19 death counts and various social and environmental risk factors, including ambient air pollution exposure. Typically, it is very common that in an infection disease mapping problem with count data, we have excessive zeros, and it is usually for over-dispersed count outcome variables. Furthermore, the theory suggests that the excess zeros are generated by a separate process from the count values and that the excess zeros need to be modeled independently. Our proposed models are specially designed to handle the zero-inflation and over-dispersion in count data through Zero-Inflated Negative Binomial regression with random effects that vary across time and space within a Markov Chain Monte Carlo framework. Drawing on our knowledge and experience, we aim to provide a simple, unified, and publicly available software that can be applied in various disease mapping studies under the contemporary Bayesian framework. Full article

Elder abuse is internationally recognized as a growing problem of the 21st century that requires urgent intervention and action. This review aimed to synthesize evidence on the prevalence and risk factors of elder abuse between 2010 and 2022. A total of 2875 articles were identified through database searches, of which 28 met the inclusion criteria and were included in the final analysis (24 cross-sectional studies, 3 prospective studies, and 1 descriptive study). Reported prevalence rates of elder abuse ranged from 2.2% to 81.2% overall, while studies conducted during the COVID-19 pandemic reported rates ranging from 1.6% to 44.7%. Psychological abuse was the most frequently reported form of violence. The most commonly identified risk factors included low income, low educational level, gender, disability, depression, and—during the COVID-19 pandemic—social isolation. Across most studies, individuals with lower education and women were statistically more likely to experience abuse. The findings indicate substantial variability in the prevalence of elder abuse both before and during the pandemic, with consistently high rates observed. These results highlight the urgent need for improved screening, education, and targeted interventions by healthcare and social service professionals. Full article