bluuebunny/crossref_metadata_2025_split huggingface dataset:
Second-Generation Antipsychotic–Associated Serious Adverse Events in Women
Authors: McCall Kenneth L. , Leppien Emily E. , Piper Brian J. , Falco Bridgette M. , Fleck Kara K. , Govel Jacob C. , Nasta Gianna N. , Zheng Steven R. 
Published: January 2025

Abstract

Purpose
Women have historically been underrepresented in second-generation antipsychotic (SGA) clinical trials, accounting for less than 35% of participants, which raises concerns about the generalizability of the safety profile for these medications.

Methods
The US adverse event reporting system was queried for the dates January 1, 2019, to July 8, 2024, to examine the following 6 SGAs: aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Reports were excluded if patients were under 18 years old, contained an unknown age or gender, or were duplicated. Five adverse events were examined: Torsades de pointes (TdP), neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), agranulocytosis (AG), and cerebrovascular adverse events (CVAE). Counts of these events were noted, and reporting odds ratios (ROR) were calculated.

Results
The total study cohort was 87,356 reports, consisting of aripiprazole (n = 10,715, 12.2%), clozapine (n = 25,096, 28.7%), olanzapine (n = 11,587, 13.3%), quetiapine (n = 28,746, 32.9%), risperidone (n = 10,467, 12%), and ziprasidone (n = 745, 0.9%). The cohort's mean age was 48.6 ± 18.5 years and comprised 42,584 females (48.7%). Most cases were reported by healthcare professionals (74,836, 85.7%). A total of 3,754 reports contained at least 1 of the 5 adverse events. The RORs among females compared to males for TdP (5.55, 95% confidence interval [CI] = 3.78–8.47), NMS (0.59, 95% CI = 0.53–0.65), TD (0.88, 95% CI = 0.76–1.02), AG (0.59, 95% CI = 0.51–0.70), and CVAE (1.12, 95% CI = 0.89–1.41) were observed. Females had a significantly higher odds of hospitalization or death with TdP compared to males (ROR = 3.09, 95% CI = 1.36–7.01).

Conclusions
Our findings suggest higher odds of TdP and worse TdP-associated outcomes among females exposed to SGAs compared to males. Further studies are needed to confirm these preliminary findings.
Deep learning for kidney trauma detection: CT image algorithm performance and external validation: experimental study
Authors: Liao Chien-Hung , Ouyang Chun-Hsiang , Chen Chih-Chi , Lin Hou-Shian , Li Yi-Liam , Kang Shih-Chin , Chen Huan-Wu , Kao Kuo-Chin , Cheng Chi-Tung 
Published: January 2025

Background:
Detecting kidney trauma on CT scans can be challenging and is sometimes overlooked. While deep learning (DL) has shown promise in medical imaging, its application to kidney injuries remains underexplored. This study aims to develop and validate a DL algorithm for detecting kidney trauma, using institutional trauma data and the Radiological Society of North America (RSNA) dataset for external validation.

Methods:
We developed RenoTrNet, a DL model trained on institutional data. We evaluated the model’s performance through external validation on randomly selected cases from the RSNA dataset. Performance metrics included the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Heatmap visualizations were used to aid interpretability.

Results:
In the internal testing dataset, the model achieved an accuracy of 0.88 (95% CI: 0.82–0.92), with a sensitivity of 0.75 (95% CI: 0.62–0.85) and a specificity of 0.95 (95% CI: 0.89–0.98). PPV and NPV were 0.89 (95% CI: 0.76–0.95) and 0.88 (95% CI: 0.81–0.93), respectively. In external RSNA validation, the algorithm c demonstrated robust performance with an accuracy of 0.93 (0.91–0.95), a sensitivity of 0.73 (0.60–0.83), a specificity of 0.94 (0.93–0.96), a PPV of 0.45 (0.35–0.56), and an NPV of 0.98 (0.97–0.99).

Conclusion:
The RenoTrNet DL algorithm demonstrated high accuracy in detecting kidney trauma on CT scans, both in internal and external validation. By optimizing image segmentation and computational efficiency, this model has potential for clinical deployment, potentially aiding in trauma diagnosis in real-world clinical scenarios.
The development and evaluation of nine obesity-based indices for gallstones in U.S. adults
Authors: Wu Xiaodong , Song Yanhong , Wu Shuodong 
Published: January 2025

Objective:
Gallstones have gradually become a highly prevalent digestive disease worldwide. This study aimed to investigate the association of nine different obesity-related indicators (BRI, RFM, BMI, WC, LAP, CMI, VAI, AIP, TyG) with gallstones and to compare their predictive properties for screening gallstones.

Methods:
Data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) for the 2017-2020 cycle, and weighted logistic regression analyses with multi-model adjustment were conducted to explore the association of the nine indicators with gallstones. Subject working curves were analyzed to assess the screening ability of the nine indicators. In addition, the association between the most predictive indicator and gallstones was investigated with smooth curve fitting, and differences in risk across populations were explored with subgroup analyses.

Results:
In total, 3654 participants were involved in the final analysis and 383 (10.48%) carried gallstones. The results of weighted multifactorial logistic regression analysis indicated that BRI, RFM, BMI, WC, LAP, and CMI were independent risk factors for gallstones. The ORs for the highest quartile were 4.13 for RFM, 3.13 for BRI, 2.85 for BMI, 2.86 for WC, 2.45 for LAP, and 1.49 for CMI. The area under the ROC curve for RFM was 0.70. The Delong test compared the performance of different ROCs and revealed that the difference between the area under the curve of RFM and the other metrics was significant (P < 0.05). Smooth curve fitting suggested a linear positive correlation between RFM and gallstones (LLR > 0.05), especially in women, non-Hispanic White, insufficient physical activity, hypertensive, and diabetic populations.

Conclusion:
RFM, BRI, BMI, WC, LAP, and CMI were essential indicators for recognizing gallstones. By comparison, we realized that RFM was a better predictor of gallstones.
Exploring the landscape of exosomes in heart failure: a bibliometric analysis
Authors: Li Hui , Li Zhitao , Fu Qinghui , Fu Shuiqiao , Xiang Tao 
Published: January 2025

Background:
Exosomes, which carry bioactive RNAs, proteins, lipids, and metabolites, have emerged as novel diagnostic markers and therapeutic agents for heart failure (HF). This study aims to elucidate the trends, key contributors, and research hotspots of exosomes in HF.

Methods:
We collected publications related to exosomes in HF from the Web of Science Core Collection. Using VOSviewer, CiteSpace, Excel, and SRplot software, we performed a visualization analysis of authors, countries, institutions, keywords, and references.

Results:
The publications on exosomes in the field of HF (N = 2127) has grown rapidly. China (N = 245, 42.683%) and the United States (N = 170, 29.617%) are the leading contributors in this area. Wang L (N = 14, 2.443%) is the most prolific author in the field. Key areas of exosome research in HF include mesenchymal stem cells (MSCs), angiogenesis, and microRNAs. Additionally, keywords and references analysis reveal that exosome research in HF is primarily focused on the role of exosomes in intercellular communication in HF, the value of miRNAs in exosomes as diagnostic markers, and the therapeutic mechanisms of MSC-derived exosomes.

Conclusion:
Exosomes are receiving increasing attention in the field of HF. Mapping the development landscape of exosomes in HF will help researchers accelerate progress in this area.
Case Report: ESR1::CITED2 Fusion in a Malignant Uterine Tumor Resembling Ovarian Sex Cord Tumor
Authors: Abbasi Ferheen , Nucci Marisa R. , Doron Ben , Ruskin Rachel , Chien Jeremy , Watkins Jaclyn C. , Karnezis Anthony N. 
Published: January 2025

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare, typically benign uterine tumor occurring over a wide age range (mean 52.4 yr). UTROSCTs often harbor translocations between ESR1 and nuclear receptor coactivators NCOA1-NCOA3. Here, we present a 21-yr-old woman with a 16 cm complex uterine mass on CT. Grossly, the tumor had an infiltrative appearance. Histologically, it consisted of mild to moderately atypical, spindled cells with ovoid nuclei, growing in fascicles and cords within fibrous to myxohyaline stroma, with tongue-like infiltration of the myometrium. Immunohistochemically, tumor cells were positive for AE1/AE3, ER, PR, vimentin, WT-1, and CD56, and negative for inhibin, calretinin, SMA, desmin, and CD10. Whole exome and whole transcriptome sequencing identified a pathogenic ESR1::CITED2 fusion. The tumor recurred twice (15 and 21 mo after initial surgery) in the abdomen and pelvis. Taken together, the findings suggest this tumor may represent a malignant UTROSCT variant with a novel translocation.
Verruciform Acanthotic Vulvar Intraepithelial Neoplasia Harbors Recurrent Genomic Alterations Found in HPV-independent Squamous Cell Carcinoma
Authors: Cook Eleanor , Kramer Claire J.H. , Bosse Tjalling , van Poelgeest Mariette , Van de Vijver Koen , Nucci Marisa R. , Parra-Herran Carlos 
Published: January 2025

The term verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN) was coined to describe HPV-independent p53-wildtype lesions with characteristic clinicopathologic characteristics and association with vulvar squamous cell carcinoma (vSCC). We aimed to expand on the molecular landscape of vaVIN using comprehensive sequencing and copy number variation profiling. vaVIN diagnosis in institutional cases was confirmed by a second review, plus negative p16 and wildtype p53 by immunohistochemistry. Multigene next-generation sequencing and shallow-whole genome sequencing were used to survey for single-nucleotide variants (SNV), copy number alterations, and structural variants. Targeted TERT promoter sequencing was also carried out. Nineteen patients with vaVIN were included; 4 had concurrent vSCC. The median patient age was 74 (range 56–90) years. Genomic aberrations were noted in 18 cases (95%) as follows: PIK3CA in 10 (53%), CDKN2A in 7 (37%), HRAS in 6 (32%), FAT1 and NOTCH1-2 in 5 each (26%), TSC2 in 2 (11%), and PTEN, ARID2, and KRAS in 1 (5%) each. TERT promoter variants were detected in 11 of 13 cases successfully tested (85%). Five vaVINs harbored a TP53 variant but showed wild-type p53 immunohistochemical expression. In one of these, the concurrent carcinoma showed abnormal p53 and biallelic TP53 mutations. Out of 15 patients with follow-up (mean: 20, range: 2–50 mo), vaVIN persistence/recurrence was seen in 8 (53%), and subsequent vSCC in 2 (13%). At the last encounter, 3 (20%) patients had persistent disease and 1 (7%) died of vSCC. vaVIN is characterized by a wider molecular spectrum, beyond known alterations in PIK3CA, HRAS, and ARID2, to include TERT promoter, CDKN2A, FAT1, and NOTCH1-2, which are characteristic of HPV-independent vSCC. vaVIN can occur with concurrent or subsequent carcinoma, sometimes with fatal outcomes. These findings support the concept of vaVIN as a neoplastic process within the family of HPV-independent vulvar neoplasia.
Mesonephric and Mesonephric-like Adenocarcinomas of the Gynecologic Tract: A Case Series and a Review of the Literature
Authors: Liu Lisa , Storino Morgan , Chen Yiting Stefanie , Walker Allison , Da Costa Deline , Shukla Shivani , Graul Ashley 
Published: January 2025

We sought to present and describe all cases of mesonephric adenocarcinoma (MNAC) and mesonephric-like adenocarcinomas (MLAs) at our institution. These cancers are rare, morphologically similar tumors of the female reproductive tract. In this case series, we present 13 new cases of MNAC/MLA that were identified at St. Luke’s University Health Network from 2016 to 2024. Demographics, clinical characteristics, and pathologic findings were collected from chart review. There were 6 uterine, 5 ovarian, and 2 cervical MNAC/MLAs. At presentation, more than half of the patients presented at early stages with 7, 2, 3, and 1 diagnosed at stages I, II, III, and IV, respectively. All patients underwent upfront surgical resection and were recommended adjuvant therapy. One patient declined adjuvant treatment. At the time of writing, 9 of 13 patients have completed treatment and have no evidence of disease, 1 is alive with disease, 1 is currently undergoing treatment, and 2 died of disease. Median overall survival (OS) was 15 mo (95% CI: 2.2–27.8 mo). Current literature regarding MNACs/MLAs suggests an overall poor prognosis, with the majority presenting at advanced stages. This case series describes patients diagnosed with early-stage disease and reports on their histopathology, treatment regimens, and clinical outcomes. The majority of these patients are without recurrence after upfront treatment. Continued surveillance of these patients to determine long-term outcomes is necessary to further elucidate overall prognosis.
Rising Rates of Urethral Bulking: A Retrospective Study of a National Database
Authors: Whitaker Taylor , DeAndrade Samantha , Douglass K. Marie , Yazdany Tajnoos 
Published: January 2025

Importance
Stress urinary incontinence (SUI) affects approximately 50% of women. There are limited data regarding trends in management as treatment options have changed.

Objective
This study aimed to analyze trends in the surgical management of SUI, including slings and urethral bulking, from 2012 to 2022.

Study Design
Patients from the American College of Surgeons National Surgical Quality Improvement Program database who had undergone a sling or urethral bulking procedure were identified by Current Procedural Terminology code. Descriptive statistics and independent paired t tests were performed.

Results
A total of 81,657 patients received either slings or urethral bulking from 2012 to 2022. The number of slings performed peaked in 2017, decreased in 2020, and has subsequently increased. The rate of urethral bulking increased from 2019 to 2022. The average age patients who received urethral bulking was 64 years versus 56 years for sling patients (P < 0.05). These patients were more likely to be American Society of Anesthesiology class III compared to those receiving slings (39% vs 25%, respectively, P < 0.05). Readmission and reoperation rates were not statistically different. Less invasive procedures were more likely to be performed concurrently with bulking.

Conclusions
Sling placement is the most common surgical procedure for SUI but it decreased in 2020, likely due to COVID-19-related delays, and has not yet returned to prepandemic levels. Urethral bulking has become more common, possibly due to new agents available in U.S. markets. Patients who received urethral bulking were more likely to be older, have severe systemic disease, and underwent a less invasive concurrent procedure. Further research is needed to understand these trends.
Left ventricular transcriptome and extracellular vesicle-derived miRNAs in porcine donation after circulatory death (DCD) hearts undergoing prolonged working modeex situperfusion
Authors: Wang Fulin , Lucchinetti Eliana , Lou Phing-How , Freed Darren H. , Zaugg Michael 
Published: January 2025

ABSTRACTDonation after circulatory death (DCD) hearts suffer from warm ischemia-reperfusion injury, which compromises graft quality. We have previously demonstrated that a postconditioning-based cardioprotective treatment (1% Intralipid, 2% (v/v) sevoflurane, 3 nM remifentanil) improved the function and viability of porcine DCD hearts undergoingex situheart perfusion (ESHP). However, transcriptional changes in DCD hearts subjected to prolonged working mode ESHP as compared with healthy hearts, and more so transcriptional changes in the presence or absence of cardioprotection, as well as the early reperfusion profile of extracellular vesicle (EV)-derived miRNAs, critical regulators of the transcriptional control, have not been investigated. A total of 5,483 differentially expressed transcripts were identified in left ventricular tissue samples of DCD hearts (N=10) collected after 6 hours of ESHP when compared with healthy hearts not subjected to ESHP (N=8), irrespective of cardioprotection. Downregulation of protein synthesis, metabolic, and DNA repair gene sets was most prominent, while inflammatory and remodeling gene sets were upregulated. Between DCD hearts that were treated with (pDCD_ESHP, N=5) or without (uDCD_ESHP, N=5) cardioprotection, only 43 transcripts were differentially regulated. Specifically, lipid breakdown, beta-oxidation, and DNA repair gene sets were upregulated in pDCD_ESHP, whereas lipid accumulation, inflammation, oxidative stress, and maladaptive remodeling gene sets were upregulated in uDCD_ESHP. Predominantly cardioprotective EV-derived miRNAs were released into the perfusate in pDCD_ESHP, while predominantly cardiac injury-associated miRNAs were released into the perfusate in uDCD_ESHP. Cardioprotection promoted adaptive rather than maladaptive transcriptional changes and enabled the release of potentially beneficial miRNAs.
Longitudinal changes in infant attention-related brain networks and fearful temperament
Authors: Filippi Courtney A. , Massera Alice , Xing Jiayin , Park Hyung G. , Valadez Emilio , Elison Jed , Kanel Dana , Pine Daniel S. , Fox Nathan A. , Winkler Anderson 
Published: January 2025

AbstractAnxiety disorders are hypothesized to stem in part from altered development of attention-related brain networks. These networks, including the dorsal attention network (DAN), frontal parietal network (FPN), salience network (SN), and default mode network (DMN), are crucial for regulating attention to salient environmental cues. Altered resting-state functional connectivity (rsFC) among these networks in the first months of life relates to fearful temperament, a risk marker for anxiety. Nevertheless, it remains unclear how these networks develop beyond these initial months, particularly in fearful infants. This study characterizes the development of attention-related brain networks over the first two years of life and identifies rsFC changes associated with fearful temperament. Using data from the Baby Connectome Project (from 180 infants across 396 sessions), we analyzed rsFC among the DMN, SN, DAN, and FPN. We examined age-related changes in rsFC across these networks and their relations with fearful temperament at age 2. Results demonstrated age-related decreases in rsFC in DAN – FPN and DMN – SN. Less decrease in DAN – FPN rsFC over time related to greater fear at age 2. This pattern manifested in analyses relating longitudinal trajectories of rsFC and fearful temperament across all available timepoints. Low initial DAN – SN rsFC related to increasing fearfulness over time. This study provides novel insights into the neurodevelopmental origins of fearful temperament.
Evaluation of out-of-distribution detection methods for data shifts in single-cell transcriptomics
Authors: Theunissen Lauren , Mortier Thomas , Saeys Yvan , Waegeman Willem 
Published: January 2025

AbstractAutomatic cell type annotation methods assign cell type labels to new, unlabeled datasets by leveraging relationships from a reference RNA-seq atlas. However, new datasets may include labels absent from the reference dataset or exhibit feature distributions that diverge from it. These scenarios can significantly affect the reliability of annotation predictions, a factor often overlooked in current automatic annotation methods. The field of out-of-distribution detection (OOD), primarily focused on computer vision, addresses the identification of instances that differ from the training distribution. Implementing OOD methods in the context of novel cell type annotation and data shift detection for single-cell transcriptomics may enhance annotation accuracy and trustworthiness. We evaluate 6 OOD detection methods: LogitNorm, MC dropout, Ensembles, Energy- based OOD, Deep NN and Posterior networks, for their annotation and OOD detection performance in both synthetical and real-life application settings. We show that OOD detection methods are able to accurately detect novel cell types and show their promise to detect severe data shifts on non-integrated datasets. Moreover, integration of the OOD datasets improves annotation performance, but interferes with OOD detection, diminishing novel cell type capabilities of the OOD methods.
Investigating the Structural Effects of Anti-Thrombin Anticoagulant Aptamers on Activation of Human Prothrombin
Authors: Troisi Romualdo , Cangiano Alessandro , Cowieson Nathan , Spiridonova Vera , Del Vecchio Pompea , Paduano Luigi , Sica Filomena 
Published: January 2025

AbstractDisorders of the blood coagulation remain a leading cause of death and disability worldwide raising the search for therapeutic agents able to modulate the coagulation cascade. Different oligonucleotide aptamers have been selected against different coagulation factors and some of them are in preclinical or clinical studies. In particular, anti-thrombin aptamers are promising drugs as they inhibit the activity of the α-thrombin and, simultaneously, limit thrombin production via prothrombinase by binding its precursor prothrombin. To investigate the interaction of these aptamers with prothrombin, we performed extensive analyses using calorimetric and spectroscopic techniques, which suggested that they recognize proexosite I of prothrombin and exosite I of thrombin with comparable affinity. SAXS experiments performed on the complex formed by the protein and NU172, the only anti-thrombin aptamer in advanced clinical trials, provided structural insights into aptamer-prothrombin recognition. Interestingly, the aptamer binding to proexosite I shifts the open-closed equilibrium of prothrombin toward the open conformation. A reasonable mechanism underlying the effects of anti-thrombin aptamers towards prothrombin conversion into thrombin has been proposed. Altogether, these results definitively qualify these aptamers as bitargeted drugs, being able to modulate both thrombin function and generation, and supply structural bases to design new anticoagulants, which lack health side effects.
Centromeres in the thermotolerant yeastK. marxianusmediate attachment to a single microtubule
Authors: Barrero Daniel J. , Hedouin Sabrine , Mao Yizi , Asbury Charles L. , Stergachis Andrew , O’Toole Eileen , Biggins Sue 
Published: January 2025

AbstractEukaryotic chromosome segregation requires spindle microtubules to attach to chromosomes through kinetochores. The chromosomal locus that mediates kinetochore assembly is the centromere and is epigenetically specified in most organisms by a centromeric histone H3 variant called CENP-A. An exception to this is budding yeast which have short, sequenced-defined point centromeres. InS. cerevisiae, a single CENP-A nucleosome is formed at the centromere and is sufficient for kinetochore assembly. The thermophilic budding yeastKluyveromyces marxianusalso has a point centromere but its length is nearly double theS. cerevisiaecentromere and the number of centromeric nucleosomes and kinetochore attachment sites is unknown. Purification of native kinetochores fromK. marxianusyielded a mixed population, with one subpopulation that appeared to consist of doublets, making it unclear whetherK. marxianusshares the same attachment architecture asS. cerevisiae.Here, we demonstrate that though the doublet kinetochores have a functional impact on kinetochore strength, kinetochore localization throughout the cell cycle appears conserved between these two yeasts. In addition, whole spindle electron tomography demonstrates that a single microtubule binds to each chromosome. Single-molecule nucleosome mapping analysis suggests the presence of a single centromeric nucleosome. Taken together, we propose that theK. marxianuspoint centromere assembles a single centromeric nucleosome that mediates attachment to one microtubule.