Since the 2013 Nobel Prize in Physiology or Medicine was awarded, extracellular vesicles(EVs) have made the transition from the laboratory to clinical practice. Platelets, as emerging multifunctional immune cells, have garnered significant attention due to the natural biocompatibility and low immunogenicity of platelet-derived extracellular vesicles (pEVs). However, research in this field currently lacks comprehensive review and analysis. This study utilized the Web of Science database, along with tools such as VOSviewer and CiteSpace, and employed bibliometric analysis and Latent Dirichlet Allocation (LDA) to systematically examine international collaboration, thematic evolution, and research hotspots in this field. In addition, clinical trials related to pEVs were extracted from the PubMed database to assess translational progress. Since 2021, the volume of publications in the field of pEVs has remained stable at a high level. The International Journal of Molecular Sciences was the most productive journal. The United States and China were the leading contributing countries, with the United States occupying a central position in global collaboration networks. Harvard Medical School and Eric Boilard were among the most influential institution and author, respectively. Research hotspots have shifted from basic platelet biology and cardiovascular studies toward regenerative medicine and oncology. Clinical trials remain limited and primarily focus on pathophysiological mechanisms, biomarker applications, and therapeutic exploration. This study provides a comprehensive visualization of the global research landscape and developmental trends in pEVs from 2015 to 2026. Although basic research has expanded rapidly, clinical translation remains limited, indicating a clear gap between laboratory findings and clinical application. Emerging trends highlight increasing attention toward regenerative medicine, oncology, and advanced therapeutic strategies, providing directions for future research.
Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on lacto-N-triose II (LNTri II) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) LNTri II, but it also contains d-glucose, d-galactose, d-lactose and lacto-N-triitol. The NF is produced by fermentation with a genetically modified strain (Kluyveromyces lactis DSM 709-2-02) of K. lactis DSM 70799. The information on the identity, production process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant formula (IF), follow-on formula (FOF), food supplements (FS) and food for special medical purposes (FSMP). The target population is the general population. In line with other HiMOs, the safety assessment of this NF is mainly based on the comparison between the intake of breastfed infants and the estimated intake of the NF. The anticipated daily intake from its use in IF is similar to the estimated natural mean highest daily intake in breastfed infants. The anticipated daily intake from the NF as a food ingredient at the maximum proposed use levels exceeds the intake level of breastfed infants on a body weight basis in infants and children. Of note, higher exposure can be obtained from LNTri II as it is a by-product in the already authorised HiMOs (e.g. Lacto-N-tetraose). In addition, the natural intake estimate does not consider the formation of LNTri II at gastrointestinal level by gut microbiota fermentation or acid hydrolysis. The Panel considers that the consumption of the NF at the proposed uses and use levels does not raise safety concerns and concludes that the NF is safe under the proposed conditions of use.
Evidence on the association between dental caries and chronic obstructive pulmonary disease (COPD) risk in older adults is limited. This cross-sectional study aimed to explore the associations of coronal and root caries with self-reported COPD prevalence in this population. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2015-2020. Coronal caries was measured by the decayed, missing and filled teeth (DMFT) index. Root caries was recorded as presence or absence. Weighted multivariable logistic regression models were applied to assess the associations of coronal caries and root caries with COPD. A total of 3,972 eligible participants were included, with a weighted self-reported COPD prevalence of 13.68%. Per 1-unit increase in DMFT was associated with higher odds of COPD (OR = 1.04, 95%CI: 1.02-1.06, p < 0.001). Participants with root caries had elevated odds (OR = 1.47, 95%CI: 1.02-2.11, p = 0.048). Coronal and root caries are independently associated with higher odds of self-reported COPD in U.S. older adults. However, given the cross-sectional design, causal inference cannot be established, and further prospective research is needed. Each 1-unit in crease in the DMFT index was associated with 4% higher odds of self-reported COPD (OR = 1.04, 95% CI: 1.02–1.06).Root caries was associated with 47% higher odds of self-reported COPD (OR = 1.47, 95% CI: 1.02–2.11).The associations between dental caries and COPD remain consistent in most subgroups.
An important component of medical care in line with demand is the prevention of overuse. Both internationally and in Germany, there are numerous examples of low-value care, i.e., measures that contribute neither to the health of the individual nor to the health status of entire patient or population groups in a meaningful way. These measures waste large shares of resources in healthcare and have harmful effects from a medical perspective for individuals as well as for the community. The driving forces behind overuse are diverse and lie both in systemic factors and in the personal behavior of doctors and patients. Since 2012, internationally with "Choosing Wisely," and since 2015, in Germany with "Klug entscheiden," initiatives have been in place aiming to effect behavioral change at a personal level. The tools are thematically well-focused recommendations that identify individual measures as low-value care, aiming to position doctors and patients at a critical distance from their application. The present article deals with the driving forces for medical overuse, describes the "Choosing Wisely" and "Klug entscheiden" campaigns, and attempts to estimate their potential effectiveness. Eine wichtige Komponente von Bedarfsgerechtigkeit in der Medizin ist die Vermeidung von Überversorgung. International wie auch in Deutschland gibt es zahlreiche Beispiele von „low-value care“, d. h. Maßnahmen, die weder zur Gesundheit des Einzelnen noch zum Gesundheitszustand ganzer Patienten- oder Bevölkerungsgruppen einen wertvollen Beitrag leisten. Diese Maßnahmen vergeuden große Anteile der Ressourcen im Gesundheitswesen und haben aus medizinischer Sicht schädliche Folgen für Einzelne wie für die Gemeinschaft. Die treibenden Kräfte für Überversorgung sind vielfältig und liegen sowohl in Systemfaktoren als auch im persönlichen Verhalten von Ärzt:innen und Patient:innen. Seit 2012 gibt es international mit Choosing Wisely und seit 2015 in Deutschland mit Klug entscheiden Initiativen, die auf der persönlichen Ebene Verhaltensänderungen bewirken sollen. Werkzeug sind thematisch eng fokussierte Empfehlungen, die einzelne Maßnahmen als „low-value care“ kennzeichnen und Ärzt:innen und Patient:innen auf kritische Distanz zu ihrer Anwendung bringen sollen. Der vorliegende Beitrag beschäftigt sich mit den treibenden Kräften für Überversorgung, schildert die Kampagnen Choosing Wisely und Klug entscheiden und versucht eine Einordnung ihres Wirksamkeitspotenzials.
Next-generation Sequencing (NGS) is critical for providing treatment recommendations across multiple stages of non-small cell lung cancer (NSCLC). However, a substantial proportion of patients do not undergo testing. This study evaluated the completion rates and timeliness of NGS in patients with stage II to IV NSCLC at a single academic institution with a reflex NGS testing protocol. Patients with stage II to IV nonsquamous NSCLC (ns-NSCLC) diagnosed between 2015 and 2022 were identified retrospectively. A reflex, tissue-based testing protocol was initiated in 2015 using in-house NGS. Pyrosequencing was performed if NGS failed. 501 patients were included: 75 (15.0%) with stage II, 82 (16.4%) with stage III, and 344 (68.6%) with stage IV ns-NSCLC. Tissue NGS was completed in 380 (75.8%) patients and 465 (92.8%) completed some tissue-based genomic testing when including pyrosequencing. Median time from biopsy to NGS was 17.0 days (range, 6-61 days). 61.0% of patients had NGS results prior to a first treatment of any type and 88.4% had tissue NGS results prior to systemic therapy. Among stage IV patients with completed NGS, median overall survival was 2.27 years for patients with NGS results prior to first treatment compared to 1.08 years for patients without NGS results prior to treatment initiation (P = .04). Implementation of an in-house, reflex NGS testing protocol enabled rapid genomic profiling in a high proportion of patients with stage II to IV ns-NSCLC. NGS completion prior to receiving first-line therapy was associated with improved survival compared to completion after first line treatment in stage IV patients.
To evaluate whether remote fetal heart rate monitoring (FHRM) is associated with neonatal and obstetric outcomes comparable to conventional in-person fetal heart rate monitoring in randomized controlled trials. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database inception through November 25, 2025. Reference lists of relevant reviews and included studies were screened to identify additional eligible trials. Randomized controlled trials enrolling pregnant individuals undergoing antenatal surveillance or intrapartum monitoring were eligible. Studies comparing remote or home-based FHRM with conventional in-person monitoring were included if they reported obstetric or perinatal outcomes. Eight randomized controlled trials enrolling 1,813 pregnancies were included. One trial was judged low risk of bias, three had some concerns, and four were judged high risk. Six trials (n=1,648) reported 5-minute Apgar scores below 7; the pooled risk ratio was 1.01 with a 95% CI of 0.73 to 1.39; I²=0% τ²=0.00, moderate-certainty evidence. Cesarean delivery was reported by all 8 trials (n=1,813); the pooled risk ratio was 1.09, with a 95% CI of 0.94 to 1.26; I²=0 percent; moderate-certainty evidence. Prespecified subgroup analyses by monitoring timing (antepartum versus intrapartum; Qᵇ=1.26, p=0.26) and publication era (≥2015 versus <2015; Qᵇ=1.52, p=0.22) did not modify the effect estimates. Remote and home-based FHRM was associated with 5-minute Apgar <7 and cesarean delivery rates comparable with conventional in-person monitoring in available randomized evidence. The negligible heterogeneity across older telemetry systems and contemporary digital platforms support consistency of these findings; however several trials had high risk of bias and neonatal outcomes beyond Apgar score were inconsistently reported. Adoption should therefore be guided not only by short-term perinatal safety, but also by access, patient satisfaction, hospital utilization, clinician workload, data reliability, cost, and timely response infrastructure.
Blake's pouch cyst (BPC) is traditionally attributed to failure of perforation of the posterior membranous area, resulting in persistent membranous obstruction at the fourth ventricular outlet. However, direct evidence of this membrane in postnatal cases remains limited and controversial. This research aimed to investigate the presence of membranous obstruction at the foramen of Magendie in pediatric patients with BPC and hydrocephalus using multimodal imaging and direct surgical inspection. We retrospectively analyzed 20 pediatric patients with BPC who underwent surgery for associated hydrocephalus at our institution from October 2015 to February 2026. Patients underwent detailed imaging including T2 constructive interference in steady state sequence and cine phase-contrast MRI sequences to study cerebrospinal fluid flow. Direct surgical inspection was performed in 4 patients who underwent flexible endoscopy or open surgery. Filiform structures in the posterior fossa were visualized on T2 constructive interference in steady state MRI in 100% (14/14) of the evaluated cases. Cerebrospinal fluid flow studies in all 16 tested patients demonstrated patent flow through the foramen of Magendie with no evidence of complete membranous obstruction. Direct visualization revealed no complete obstruction but filiform remnants in the posterior fossa in 4 patients. Primary treatment with endoscopic third ventriculostomy was attempted in 10 patients, and posterior fossa exploration was attempted in 1 patient, but all the patients required ventriculoperitoneal shunt placement (except for 1 patient who was lost to follow-up). Our findings challenge the concept of persistent complete membranous obstruction at the foramen of Magendie in postnatal pediatric patients with BPC and hydrocephalus. On the basis of these observations, we propose a delayed perforation theory. In our cohort, endoscopic third ventriculostomy showed limited efficacy in treating hydrocephalus associated with BPC. Careful evaluation of the posterior fossa anatomy is therefore essential when planning treatment.
The double burden of malnutrition (DBM), the co-occurrence of micronutrient deficiencies and overweight/obesity, is a rising challenge in transitioning economies. However, longitudinal evidence on its structural evolution and demographic shifts remains limited. To analyze the long-term trajectories and socio-metabolic determinants of DBM among adults in Southwest China using three decades of cohort data. A total of 10,703 person-wave observations from 3,117 adults (aged ≥18) across 11 rounds of the China Health and Nutrition Survey (the Guizhou cohort, 1991-2023) were analyzed. Nutrient intake was derived from three-day 24-h recalls and household salt/oil weighing. Joinpoint regression characterized temporal trends, and Generalized Estimating Equations (GEE) identified population-averaged associations between DBM and socio-metabolic factors. DBM prevalence surged from 12.8% (95% CI: 10.8-14.9%) in 1991 to 53.4% (95% CI: 49.8-56.9%) in 2023, with an overall AAPC of 4.97% (95% CI: 4.21-5.74%). Growth significantly decelerated after the 2015 inflection point, shifting from an APC of 5.37% (95% CI: 4.50-6.24%) to 3.79% (95% CI: 1.11-6.55%; p = 0.013). Notably, distinct growth rates across subgroups led to a reversal of prevalence patterns by 2023, at which point DBM prevalence in rural areas (53.8%) and among males (57.6%) exceeded that of their urban and female counterparts. GEE models further indicated that while urban residency, female gender, and higher education were historically associated with higher DBM risk, the absence of hypertension (OR: 0.79; 95% CI: 0.71-0.87) and higher riboflavin intake (OR: 0.74; 95% CI: 0.62-0.89) were significantly associated with a lower risk. The DBM landscape in this regional cohort has undergone a fundamental shift, with the burden shifting toward rural residents and males. Targeted public health strategies should prioritize these emerging high-risk groups, emphasizing dietary improvements such as riboflavin optimization to mitigate the dual burden of adiposity and micronutrient inadequacy.
Stent-assisted coil embolization (SAC) has expanded the treatment options for ruptured wide-neck aneurysms; however, SAC during the acute phase of subarachnoid hemorrhage (SAH) remains controversial owing to concerns regarding thromboembolic and hemorrhagic complications. This study aimed to evaluate the feasibility and safety of SAC for ruptured wide-neck aneurysms in the acute phase of SAH at a single center in Japan. Patients with ruptured wide-neck aneurysms who underwent endovascular treatment within 48 h after SAH onset between January 2015 and December 2024 were retrospectively evaluated. Wide-neck aneurysms were defined as those with a neck width of ≥4 mm or a dome-to-neck ratio of <2. Patients were divided into 2 groups: the SAC group and the non-SAC group. The primary outcome was perioperative complications. Secondary outcomes included angiographic outcomes, clinical outcomes at discharge and 1-year follow-up, and retreatment rates. A total of 140 patients were included (SAC group, n = 24; non-SAC group, n = 116). Aneurysms in the SAC group demonstrated more complex morphology, particularly lower aneurysm height and smaller dome-to-neck ratios. The rates of perioperative hemorrhagic complications (12.5% vs. 9.4%) and symptomatic thromboembolic complications (8.3% vs. 8.6%) were comparable between the SAC and non-SAC groups. The immediate angiographic outcomes did not differ significantly between the 2 groups. Clinical outcomes at discharge and at 1-year follow-up did not differ significantly. SAC for ruptured wide-neck aneurysms in the acute phase of SAH appears to be feasible with no significant differences in perioperative complication rates or clinical outcomes compared with non-SAC treatment. With appropriate patient selection and careful antiplatelet management, SAC may be a reasonable treatment option.
To evaluate the safety and efficacy of high-dose-rate (HDR) prostate brachytherapy (BT) in patients with local relapse after initial treatment with radical prostatectomy and salvage external beam radiation therapy (EBRT). Patients with local recurrence of prostate adenocarcinoma were retrospectively identified at a single-institution between 2015 and 2024. Recurrence was confirmed by imaging (MRI or choline PET) after prostatectomy and EBRT. Patients had no evidence of distant disease. A total HDR-BT dose of 17 Gy to 20 Gy was administered in two fractions. Seventeen patients received salvage HDR-BT. The median follow-up time was 74 months (range, 6-100). Twelve patients (70.6%) received salvage-intent EBRT after surgery, while five (29.4%) had adjuvant EBRT. Three patients received androgen deprivation therapy (ADT) concurrently with EBRT in a mean ADT duration of 72 months (range, 6-126). The median time to PSA nadir after EBRT was 14 months. The median interval between EBRT and HDR-BT was 4 years (range, 1-14). After a median follow-up of six years from HDR-BT, 9 (52.9%) patients remained free of local recurrence, and 11 (64.7%) were recurrence-free in the treated region. In terms of toxicity, one patient experienced chronic grade 4 genitourinary toxicity requiring cystectomy, but no acute or late gastrointestinal toxicity was observed. At last follow-up, 15 patients (88.2%) were alive. In this long-term single-institution series, salvage HDR-BT demonstrates durable local control with acceptable toxicity in patients with local recurrence after prostatectomy and EBRT.
Recurrence rates in patients with resected pancreatic ductal adenocarcinoma (PDAC) remain high, posing a significant clinical challenge. Pre-operative neutrophil-to-lymphocyte ratio (NLR) has shown promise as a prognostic marker in various cancers. NLR's role in PDAC recurrence has not been widely explored. This study aims to investigate the effect of pre-operative NLR on post-operative PDAC recurrence. A retrospective analysis was performed on patients who underwent surgery with curative intent for PDAC between 2015 and 2024. Patients were divided into two groups (high and low) using an NLR threshold of 3. Primary outcome was disease recurrence. The predictive value of NLR was compared using receiver operating characteristic curves and univariable and multivariable Cox regression models. 125 Patients were included; high NLR group n = 53 and low NLR group n = 72. Both groups were well balanced across all baseline characteristics. NLR is a strong predictor of recurrence compared to platelet-to-lymphocyte ratio (PLR) (AUC: NLR 0.716 vs. PLR 0.593, p = 0.022). The high NLR group had a significantly greater recurrence rate compared to the low NLR group (62.3% vs. 31.9%, p = 0.002) and a significantly greater local recurrence rate (43.4% vs. 19.4%, p = 0.004). A high NLR remains a significant negative prognosticator for recurrence in univariable (hazard ratio [HR] 2.540, p < 0.001) and multivariable analysis (HR 2.817, p < 0.001). A high pre-operative NLR (> 3) was associated with significantly greater risk of recurrence, especially local recurrence. NLR may be used within risk stratification models to identify patients at risk of PDAC recurrence.
An increasing discrepancy between the measured reference air kerma rate (RAKR) of high-dose-rate (HDR) iridium-192 (192Ir) sources and that reported by the manufacturer on the source certificate was observed at a hospital in Australia. This study aimed to determine whether the drift recorded in a single clinic was a local anomaly or more widespread. A survey was distributed to physicists at brachytherapy clinics across Australia, New Zealand, the United Kingdom (UK), France, and Ireland, gathering details on HDR 192Ir source model and origin, well chamber model, well chamber calibration provider, and each department's history on the discrepancy between locally measured and manufacturer's source certificate RAKR. Data from each clinic was assigned to a separate series, with an additional series if a clinic changed well chamber calibration provider. Linear regression analysis was performed on data from each series. One thousand one hundred fifty observations from 32 clinics were analyzed, with RAKR measurement histories ranging from 2 to 20 years (mean, 9 years). The manufacturer of all sources included in this analysis was Curium. A trend of increasing local measurement value compared with the manufacturer certificate value was observed for all series, with 20 or more observations. Sites with well chambers calibrated at NPL or UWADCL showed an increase in discrepancy between measured and source certificate RAKR, approximately 0.2% per year on average, from 2015 to present. There is an increasing discrepancy between locally measured 192Ir HDR source strength compared with the manufacturer's certificate. The manufacturer's measurement procedure does not meet the same standard set for the user. Unless the agreement between the Curium and user measurements can improve, brachytherapy societies may need to re-examine the requirement for direct comparison between local and manufacturer's measurements.
Intraoperative margin assessment techniques have been developed to reduce positive margin rates after breast-conserving surgery (BCS). These techniques show limited diagnostic accuracy, particularly after neoadjuvant systemic therapy (NST). The study aim was to evaluate the diagnostic accuracy of intraoperative macroscopic pathological margin evaluation (IMPME). This was a retrospective study including patients with invasive breast cancer (BC) who underwent BCS between 2015 and 2017. A tumor-margin distance ≤1 mm was considered positive at IMPME. Diagnostic accuracy, sensitivity (Se), specificity (Sp) and negative predictive value (NPV) of IMPME were calculated according to the timing of surgery. The gold standard was margin status at final pathology. A total of 698 BC tumors, were included, 561 in the upfront BCS group (UBCS) and 137 in the delayed (after NST) BCS group (DBCS). According to IMPME, 25.1% and 27.7% of BC tumors had positive margins in the UBCS and DBCS groups, respectively. Final pathological examination showed positive margins for 5.9% in the UBCS group and 8.8% in the DBCS group. Diagnostic accuracy, Se, Sp, and NPV were, respectively, 82.5%, 83.1%, 82.5%, and 97.4%, for the UBCS group and 81.7%, 76%, 84%, and 93.9%, respectively, for the DBCS group. IMPME-guided re-excision reduced secondary surgeries rates by 74% in the UBCS group, and by 50% in the DBCS group. IMPME can enhance correlations between the margin status of the main breast surgical specimen and final pathology. With its high NPV rates, IMPME can predict negative final margins and avoid additional intraoperative re-excisions.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare autoimmune disease in which renal involvement is a major determinant of morbidity and mortality. Epidemiologic data suggest lower reported prevalence of AAV among Black populations, but whether differences exist in disease presentation and renal severity at diagnosis remains poorly characterized. We conducted a retrospective cohort study using a large, multi-institutional electronic health record network. Adults diagnosed with AAV between 2015 and 2025 were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes. Demographic characteristics, renal manifestations at presentation, dialysis dependence, and ANCA serologic testing were extracted. Primary analyses compared Black and White patients using descriptive statistics, Welch t-tests, Fisher's exact tests, and odds ratios (ORs) with 95% confidence intervals (CIs). Among 789 adults with AAV, 84.8% were White and 8.2% were Black. Black patients were diagnosed at a younger mean age than White patients (55 ± 15 vs 64 ± 16 years; p<0.001). Dialysis dependence was more frequent among Black patients (21.5% vs 13.3%; OR: 1.79, CI: 0.88-3.45), as was hematuria (38.5% vs 28.1%; OR: 1.59, CI: 0.9-2.78). Proteinuria occurred at similar rates across groups. ANCA serologic testing was incompletely captured. In this multi-institutional cohort, Black patients with AAV presented at a younger age and tended to be more likely to require dialysis and have hematuria. These findings suggest that underrepresentation in rare disease cohorts may coexist with substantial disease burden at presentation, underscoring the importance of examining severity alongside prevalence in population-level studies.
The incidence of atypical femoral fractures in breast cancer patients is theoretically expected to be significantly higher than in those with primary osteoporosis. This is due to the prolonged and higher dosages of bisphosphonates used for post-operative bone protection and secondary osteoporosis. However, there is a notable lack of literature addressing this issue. Diagnosing and managing atypical femoral fractures in breast cancer patients presents unique challenges that differ substantially from those encountered in osteoporosis patients. We present a 58-year-old postmenopausal woman with a history of breast cancer who reported bilateral mid-thigh pain. From June 2015 to January 2017, she received zoledronic acid (4 mg) intravenously every 3 months, totaling seven doses. From 2017 to 2021, her regimen changed to a 4 mg infusion every 6 months, resulting in ten doses during this period. Overall, she underwent 17 zoledronic acid infusions over approximately 5.5 years. After minor trauma, she suffered sequential bilateral femoral shaft fractures. Bone metastases were initially suspected but ruled out through histopathological examination of both fracture sites, which showed no malignancy. Following her last infusion in June 2024, a multidisciplinary team (MDT) discussion was held. Considering her prolonged bisphosphonate exposure, the fracture sites, and imaging consistent with the 2013 American Society for Bone and Mineral Research (ASBMR) criteria, she was diagnosed with bisphosphonate-related atypical bilateral femoral fractures. Zoledronic acid was discontinued, and teriparatide treatment began, leading to significant pain relief, improved mobility, and radiological evidence of fracture healing after 9 months. However, due to mildly elevated tumor markers (CA19-9 and neuron-specific enolase [NSE]), teriparatide was switched to denosumab, which led to a prompt recurrence of bilateral thigh pain. This case underscores the critical importance of early and differential diagnosis of atypical femoral fractures in this patient population. The findings suggest that teriparatide can be effective in promoting atypical femoral fracture healing; however, its use in patients with a history of cancer remains controversial and requires individualized risk-benefit assessment under multidisciplinary guidance. Furthermore, switching to denosumab during active fracture healing may lead to symptomatic recurrence. This approach might also be relevant for patients with primary osteoporosis. Multidisciplinary management and long-term monitoring are crucial for managing such complex cases.
Oropouche virus (OROV) is an emerging virus that causes a wide spectrum of febrile illnesses in humans. In this study, we examined two of the most commonly used primer sets for the clinical diagnosis of OROV to identify potential reduction in diagnostic sensitivity or even escape due to genetic variability in the target regions of circulating strains. We also evaluated selective pressures on the S segment to determine the optimal region for selecting diagnostic targets. For this, a total of 225 OROV S segment sequences (2015-2024) from multiple American countries were retrieved from NCBI and aligned with commonly used RT-PCR primers to identify mismatches. Subsequently, sequences (1960-2024) were analyzed for evolutionary studies, using HyPhy (Datamonkey), applying aBSREL, MEME, and FUBAR to assess branch- and site-level selection. Alignment of 225 OROV S segment sequences revealed widespread mismatches in primer binding regions. Selection pressure analysis showed no branch-level positive selection, one site under episodic diversifying selection, and 81 sites under purifying selection. Notably, highly conserved regions did not overlap with commonly targeted primer sites. These findings suggest that current diagnostic assays may be vulnerable to reduced sensitivity due to genetic variability. Continuous genomic surveillance and comprehensive primer design studies are essential to ensure reliable detection of emerging OROV strains.
Familial glucocorticoid deficiency type 2 (FGD2) is a rare autosomal recessive disorder caused by pathogenic variants in the MRAP gene, typically characterized by isolated cortisol deficiency with markedly elevated ACTH levels. We report a term male neonate born to consanguineous parents who presented with striking scrotal hyperpigmentation at birth, despite an otherwise normal appearance and a normal newborn screening limited to classical congenital adrenal hyperplasia (CAH). Initial biochemical evaluations, including glucose and electrolytes, were unremarkable; however, due to severe hyperpigmentation, further endocrine workup was pursued. Laboratory findings revealed profoundly low serum cortisol and markedly elevated ACTH, supporting the diagnosis of primary adrenal insufficiency. Hydrocortisone therapy was initiated promptly, and during follow-up, transient hyperkalemia and low-normal aldosterone levels necessitated short-term fludrocortisone supplementation, suggesting partial mineralocorticoid involvement. Genetic analysis identified a homozygous MRAP in-frame deletion (c.88_90del; p.K30del), classified as likely pathogenic according to ACMG 2015 criteria and as a variant of uncertain significance according to the ClinGen SVI recommendations. Despite the dramatic initial presentation, the patient remained euglycemic and demonstrated normal neurodevelopment under appropriate hormone replacement, with gradual resolution of hyperpigmentation. This case highlights striking neonatal scrotal hyperpigmentation as a potential early clinical clue suggestive of familial glucocorticoid deficiency in a patient with a homozygous MRAP variant. Importantly, even when newborn screening for CAH is normal, marked hyperpigmentation should prompt evaluation for other causes of primary adrenal insufficiency to prevent life-threatening adrenal crises.
Interdisciplinary research is a cornerstone of global science policy, yet decades of research have reached conflicting conclusions about its association with citation impact. This inconsistency stems primarily from traditional indicators, which rely on reference diversity rather than genuine semantic knowledge integration, and from small, discipline-specific samples that limit generalizability. This study introduces a novel semantic interdisciplinarity measure based on Sentence-BERT (SBERT) embeddings, which directly captures cross-disciplinary knowledge integration at the textual level, and tests its heterogeneous relationship with citation impact across the full spectrum of scientific disciplines. We analyzed 121,194 articles published 2015-2025 across all 19 root-level disciplines in OpenAlex. We validated the reliability of OpenAlex disciplinary classification using multi-dimensional semantic analyses, and compared our SBERT-based indicator with the Simpson Diversity Index and Rao-Stirling Index. We employed OLS and negative binomial regressions with discipline and year fixed effects (standard errors clustered at the discipline level), journal tier heterogeneity analysis, and domain-specific decomposition analyses. The semantic interdisciplinarity indicator shows moderate convergent validity with conventional citation-based metrics (r = 0.333-0.347, p < 0.001) and provides a small but meaningful increase in explanatory power beyond traditional indicators (Δ adjusted R² = 0.003), although its coefficient is marginally significant and negative (β = -1.5565, p = 0.085). Overall, semantic interdisciplinarity is positively associated with citation impact in baseline models, but this effect is primarily driven by cross-domain integration between epistemically distant domains, particularly in the natural sciences. The positive effect is consistent across all journal influence tiers, with the strongest effect observed in mid-tier journals, and presents stark heterogeneity across individual disciplines. Boundary-spanning research bridging epistemically distant domains appears to deliver consistent citation rewards. Our findings address long-standing inconsistencies in the literature, and provide actionable insights for research evaluation and science policy.
Autologous breast reconstruction offers patients a durable and natural-appearing option after mastectomy. However, complication risks include flap loss, infection, and delayed wound healing. This study developed both traditional statistical and machine learning (ML) models to predict the risk of developing a 90-day postoperative complication after autologous reconstruction. Patient data were retrospectively collected for patients who underwent abdominal-based autologous breast reconstruction at Memorial Sloan Kettering Cancer Center (January 2015-September 2024). Multivariable logistic regression models and supervised ML models were developed to predict infection, hematoma, seroma, delayed wound healing, and flap compromise. 2,128 patients (3,249 flap reconstructions) were included. Overall, 90-day complications occurred in 475 (22.3%) patients, including infection (10%), hematoma (6%), delayed healing (4.1%), seroma (3.9%), and flap compromise (2.8%). AUCs ranged from 0.60 to 0.66 (logistic regression) and 0.64 to 0.73 (ML). Higher BMI was associated with increased risk for seroma (OR: 1.1, 95% CI: 1.04-1.13) and neoadjuvant chemotherapy for infection (OR:1.72, 95% CI: 1.17-2.51). Key ML model predictors on SHAP analysis included age, BMI, and pre-reconstruction radiation. Individualized risk prediction models for complications after autologous breast reconstruction were developed using traditional statistics and ML. These models may help personalize treatment; however, further research is needed to enhance model predictive performance and clinical utility.