bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends of Overactive Bladder and Pharmacologic Treatment Among U.S. Women
Authors: King Lauren A. , Pruszynski Jessica E. , Wai Clifford Y. , Florian-Rodriguez Maria E. 
Published: September 2024

Importance
To evaluate and consider how prescribing practices have changed in relation to high-risk overactive bladder (OAB) medications.

Objective
The objective of this study was to evaluate trends in the prevalence of OAB and pharmacologic treatment over time in the United States.

Study Design
Data from the National Health and Nutrition Examination Survey (NHANES, 2001–2018, n = 30,478) and the National Ambulatory Medical Care Survey (NAMCS, 2003–2019, n = 251,330) were used to identify women with symptomatic incontinence and overactive bladder (OAB) (NHANES) as well as determine the frequency of prescription use for OAB medications (NHANES and NAMCS) using sampling-based weights. Joinpoint regression was used to determine adjusted annual percent change (APC, adjusting for race, age, body mass index, and insurance status). Trends were assessed overall and by race, age, body mass index, and insurance status.

Results
The prevalence of OAB was 31.2% in the final survey year of NHANES (2017–2018). Women aged >65 years had the highest prevalence of OAB at 54% compared with other age groups. There was an overall increase in OAB (APC 1.24 [0.64, 1.84], P = 0.002) over time. Overall, only 3.5% of patients with symptoms of OAB reported pharmacologic treatment in NHANES. The NAMCS demonstrated a significant decrease in anticholinergic prescriptions from 2003 until 2019 (APC −6.44 [−9.77, −2.98], P = 0.001). However, in NHANES, there was no significant change in anticholinergic use (APC 0.62 [−20.2, 26.8], P = 0.944). There was a stable prevalence of β3-adrenergic agonist prescriptions since they were introduced to market (APC 0.65 [−2.24, 3.62], P = 0.616).

Conclusion
This study demonstrates an increasing prevalence of OAB and highlights the likely undertreatment of symptomatic patients. The high and increasing prevalence coupled with the relative undertreatment of OAB underscores the importance of screening for this condition.
Organizational models and patient-reported outcomes for palliative care across five tertiary hospitals in Nigeria: an Environmental Scan
Authors: Ogbenna Ann A. , Caputo Matthew , Onyeka Tonia C , Ohanete Debora O. , Johnson Lyra S. , Sam-Agudu Nadia A. , Obiezu-Umeh Chisom , Akodu Babatunde , Drane Denise , Evans Charlesnika , Akinwale Mukaila O. , Ndukwu Geraldine U. , Kolawole Israel K. , Ayilara Saheed A. , Eke Gracia K. , Akinsete Adeseye M. , Ogunseitan Adeboye , Doobay-Persaud Ashti 
Published: September 2024

ABSTRACTBackgroundPalliative care (PC) is an essential, effective, and affordable component of health care. Global need is rising, with the greatest burden in low-and-middle-income countries. This is especially true in Nigeria where the need is growing rapidly, as are PC services; however, current organizational models have not yet been examined.MethodsThis was a cross-sectional, descriptive study of five PC sites at tertiary hospitals in four of Nigeria’s six geopolitical zones. Surveys, informed by a Centre for Palliative Care, Nigeria (CPCN) needs assessment checklist and the Consolidated Framework for Implementation Research (CFIR), were administered at each site to leadership, frontline workers, patients, and caregivers. Surveys varied by participant group and inquired about organizational models and personal experiences of both providers and recipients of care.ResultsAcross five sites, there was a total of 282 survey respondents: five leaders, nine frontline workers, 132 patients, and 136 caregivers. The most common diagnoses of PC patients were cancer, sickle cell disease, and HIV. Most sites reported sub-optimal administrative support (80%), hospital management support (60%), and building space (60%). Leadership responses highlighted variations in PC training requirements and opportunities. Frontline workers desired additional training, sponsorship, and governmental support. Most patients and their caregivers reported satisfaction with PC, though high levels of worry and hopelessness were reported.ConclusionIncreased organizational support appears necessary to facilitate improvements in administrative resources, staffing, and training. Emotional and spiritual wellbeing likely require prioritization when designing palliative care delivery services in Nigeria. Further research is needed to refine current services and inform implementation efforts.
ChatGPT-o1 and the Pitfalls of Familiar Reasoning in Medical Ethics
Authors: Soffer Shelly , Sorin Vera , Nadkarni Girish N , Klang Eyal 
Published: September 2024

AbstractLarge language models (LLMs) like ChatGPT often exhibit Type 1 thinking—fast, intuitive reasoning that relies on familiar patterns—which can be dangerously simplistic in complex medical or ethical scenarios requiring more deliberate analysis. In our recent explorations, we observed that LLMs frequently default to well-known answers, failing to recognize nuances or twists in presented situations. For instance, when faced with modified versions of the classic “Surgeon’s Dilemma” or medical ethics cases where typical dilemmas were resolved, LLMs still reverted to standard responses, overlooking critical details. Even models designed for enhanced analytical reasoning, such as ChatGPT-o1, did not consistently overcome these limitations. This suggests that despite advancements toward fostering Type 2 thinking, LLMs remain heavily influenced by familiar patterns ingrained during training. As LLMs are increasingly integrated into clinical practice, it is crucial to acknowledge and address these shortcomings to ensure reliable and contextually appropriate AI assistance in medical decision-making.
A Differential Ion Mobility Acoustic Ejection Mass Spectrometer System for Screening Isomerization-Mediating Enzyme Drug Targets
Authors: Bazargan Samad , Dranchak Patricia , Liu Chang , Inglese James , Janiszewski John , Schneider Bradley B. , Covey Thomas R. 
Published: September 2024

AbstractWe report the first implementation of ion mobility mass spectrometry combined with an ultra-high throughput sample introduction technology for high throughput screening (HTS). The system integrates differential ion mobility (DMS) with acoustic ejection mass spectrometry (AEMS), termed DAEMS, enabling the simultaneous quantitation of structural isomers that are the sub-strates and products of isomerase mediated reactions in intermediary metabolism. We demonstrate this potential by comparing DAEMS to a luminescence assay for the isoform of phosphoglycerate mutase (iPGM) distinctively present in pathogens offering an opportunity as a drug target for a variety of microbial and parasite borne diseases. The metabolome consists of many structural isomers that require for separation a mobility resolving power of more than 300. Resolving powers measured in collision cross section space of 1588 and 1948 for 2- and 3-phosphoglycerate and the citrate/isocitrate isomeric pairs respectively are shown. These are the highest reported ion mobility resolving powers for molecules from the metabolome reported to date. The potential for DAEMS as a generalized screening tool is demonstrated with the separation of the substrates and products of two additional isomerases that present as potential therapeutic targets, chorismate mutase and triosephosphate isomerase. The separations are achieved at speeds compatible with the sample introduction rates of AEMS providing sufficient data points to integrate the peaks for quantitation without the use of internal standards. DMS hyphenated with acoustic sample ejection MS provides a unique solution to high throughput mass spectrom-etry applications where isomer and other types of separations are required.
Four-dimensional label-free live cell image segmentation for predicting live birth potential of mouse embryos
Authors: Kanazawa Taichi , Yao Tatsuma , Takeshita Sora , Hirai Tatsuki , Suenaga Ryo , Yamada Takahiro G , Tokuoka Yuta , Yamagata Kazuo , Funahashi Akira 
Published: September 2024

1AbstractSelection of high-quality embryos is critical in assisted reproductive technology (ART), but it relies on visual assessment by experts, and the birth rate remains low. We previously developed a deep learning method to predict the birth of mouse embryos by quantifying the morphological features of cell nuclei. This method involves cell nuclear segmentation on fluorescence microscopy images, but fluorescence labeling of nuclei is not feasible in medical applications. Here, we developed FL2-Net, a nuclear segmentation method for time-series three-dimensional bright-field microscopy images of mouse embryos without fluorescence labeling. FL2-Net outperformed existing state-of-the-art segmentation methods. We predicted the birth potential of mouse embryos from the nuclear features quantified by bright-field microscopy image segmentation. Birth prediction accuracy of FL2-Net (81.63%) exceeded those of other methods and experts (55.32%). We expect that FL2-Net, which can quantify nuclear features of embryos non-invasively and with high accuracy, might be useful in ART.
Somatic mtDNA Mutation Burden Shapes Metabolic Plasticity in Leukemogenesis
Authors: Li-Harms Xiujie , Lu Jingjun , Fukuda Yu , Lynch John , Sheth Aditya , Pareek Gautam , Kaminski Marcin , Ross Hailey , Wright Christopher W. , Wu Huiyun , Wang Yong-Dong , Neal Geoff , Smith Amber , Vogel Peter , Pounds Stanley , Schuetz John , Ni Min , Kundu Mondira 
Published: September 2024

ABSTRACTThe role of somatic mitochondrial DNA (mtDNA) mutations in leukemogenesis remains poorly characterized. To determine the impact of somatic mtDNA mutations on the process, we assessed the leukemogenic potential of hematopoietic progenitor cells (HPCs) from mtDNA mutator mice (Polg D257A) with or without NMyc overexpression. We observed a higher incidence of spontaneous leukemogenesis in recipients transplanted with heterozygous Polg HPCs and a lower incidence of NMyc-driven leukemia in those with homozygous Polg HPCs compared to controls. Although mtDNA mutations in heterozygous and homozygous HPCs caused similar baseline impairments in mitochondrial function, only heterozygous HPCs responded to and supported altered metabolic demands associated with NMyc overexpression. Homozygous HPCs showed altered glucose utilization with pyruvate dehydrogenase inhibition due to increased phosphorylation, exacerbated by NMyc overexpression. The impaired growth of NMyc-expressing homozygous HPCs was partially rescued by inhibiting pyruvate dehydrogenase kinase, highlighting a relationship between mtDNA mutation burden and metabolic plasticity in leukemogenesis.TEASERSomatic mtDNA mutations as drivers of metabolic change in the development of leukemia.
Water use efficiency ofCupressus giganteais higher in mountain slope habitats compared to riverside habitats
Authors: Jiang Yueliang , Luan Li , Zuo Youlu , Liu Shengyun , He Qiaoling , He Jingyu , Wu Ruru , Jiang Gaoming , Liu Meizhen 
Published: September 2024

ABSTRACTCupressus giganteais an endemic species of the Yarlung Zangbo River in Tibet, China, and is designated as a national key protected wild plant. It is only distributed in the narrow area along Yarlung Zangbo River from Jiacha County to Danniang village Milin City in various habitats such as the waterline along the Yarlung Zangbo River, terraces, and mountain slopes. In this study, we utilized stable isotope technology (δD, δ18O, and δ13C), combined with the IsoSource model, to quantitatively determined the sources of water absorption and the water use efficiency ofC. giganteain various habitats, including riverside area, terraces and mountain slopes. The results showed that the content of soil total nitrogen, soil nitrate nitrogen, soil ammonium nitrogen, and soil organic carbon are significantly higher on mountain slope than in the other two habitats, while the total carbon content, water content, and total nitrogen content ofC. gigantealeaves are significantly lower on mountain slope than in the other two habitats (P<0.05). The water use efficiency (WUE) ofC. giganteain the mountain slope habitats is 107.8 μmol mol-1, which is significantly higher than that of other habitats (P<0.05), with the WUE ofC. giganteain the riverside habitat being the lowest at 35.7 μmol mol-1.C. giganteadistributed on the mountain slope and terrace uses soil water as the main water source. During the normal rainy season, the proportion of soil water utilization is the highest, accounting for more than 60%; in the dry season, the utilization of river water and groundwater increases, while soil water utilization decreases.C. giganteadistributed along the riverside mainly absorbs water from the Yarlung Zangbo River, about 63%. In August when the rainfall increases in the rainy season, the use of soil moisture increases, and in the dry season, river water becomes the main water source. This indicates that with the alternation of rainy and dry seasons, the water absorption sources and strategies ofC.giganteaadjusted accordingly. The research results provide an important scientific basis for the protection and management measures of theC. giganteapopulation.
Crosstalk between the aryl hydrocarbon receptor and hypoxia inducible factor 1α pathways impairs downstream dioxin response in human islet models
Authors: Gang Noa , van Allen Kyle A. , Willmore William G. , Lynn Francis C. , Bruin Jennifer E. 
Published: September 2024

AbstractThe incidence of type 2 diabetes (T2D) is increasing globally at a rate that cannot be explained solely by genetic predisposition, diet, or lifestyle. Epidemiology studies report positive associations between exposure to persistent organic pollutants, such as dioxins, and T2D. We previously showed that 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) activates the xenobiotic-sensitive aryl hydrocarbon receptor (AHR) in pancreatic islets. The AHR is known to crosstalk with the hypoxia inducible factor 1α (HIF1α) in hepatocytes but whether this crosstalk occurs in islet cells remains unknown. We assessed AHR-HIF1α pathway crosstalk by treating human donor islets and stem cell-derived islets (SC-islets) with TCDD +/- hypoxia and examined the changes in downstream targets of both AHR (e.g.,CYP1A1) and HIF1α (e.g.,HMOX1).SC-islets showed consistent crosstalk between AHR and HIF1α pathways; co-treatment of SC-islets with TCDD + hypoxia robustly suppressed the magnitude ofCYP1A1induction compared with TCDD treatment alone. In human islets, only 2 of 6 donors showing suppressedCYP1A1induction following TCDD + hypoxia co-treatment. In both SC-islets and human donor islets we observed an unexpected hypoxia-mediated suppression of glucose-6-phosphate catalytic subunit 2 (G6PC2) expression.Our study shows AHR-HIF1α crosstalk occurs in both SC-islets and primary human donor islets, but the response of human islets varied between donors. In both models, the HIF1α pathway dominated over the AHR pathway during TCDD + hypoxia co-treatment. Our study is the first to examine whether AHR-HIF1α crosstalk occurs in islet cells and presents novel data on the impact of hypoxia onG6PC2gene expression.
Interpreting Sleep Activity Through Neural Contrastive Learning
Authors: Chen Zhongtao , Zheng Hui , Zhou Jianyang , Zheng Lin , Lin Peiyang , Wang Haiteng , Dolan Ray , Behrens Tim , Liu Yunzhe 
Published: September 2024

AbstractMemories are spontaneously replayed during sleep, but capturing this process in the human brain has been challenging due to the dominance of slow, rhythmic background activity in sleep, which differs significantly from wakefulness. Each sleep stage, such as NREM and REM, has distinct rhythms, making it even harder for models trained on awake tasks to generalise and decode memory replay during sleep. To overcome this, we developed the Sleep Interpreter (SI), an artificial neural network. We first collected a large EEG dataset from 135 participants, recording brain activity during both awake tasks and overnight sleep. Using a Targeted Memory Reactivation (TMR) technique with 15 pairs of auditory cues and visual images, we tracked when specific memories were reactivated during sleep. The SI model was then trained separately for NREM and REM stages, using contrastive learning to align neural patterns between wakefulness and sleep while filtering out the background rhythms that previously hindered decoding. We also examined how specific sleep rhythms, such as slow oscillations and their coupling with spindles, influenced decoding performance. In a 15-way classification task during sleep, our model achieved a Top-1 accuracy of up to 40.05% on unseen subjects, surpassing all other available decoding models. Finally, we developed a real-time sleep decoding system by integrating an online automatic sleep staging process with the SI model for each sleep stage. This ability to decode brain activity during sleep opens new avenues for exploring the functional roles of sleep. By making our dataset and decoding system publicly available, we provide a valuable resource for advancing research into sleep, memory, and related disorders.
The Neural Correlates of Alcohol Approach Bias – New Insights from a Whole-Brain Network Analysis Perspective
Authors: Muller Angela M. , Manning Victoria , Wong Christy Y.F. , Pennington David L. 
Published: September 2024

AbstractAlcohol approach bias, a tendency to approach rather than to avoid alcohol and alcohol-related cues regardless of associated negative consequences, is an emerging key characteristic of alcohol use disorder (AUD). Reaction times from the Approach-Avoidance Task (AAT) can be used to quantify alcohol approach bias. However, only a handful of studies have investigated the neural correlates of implicit alcohol approach behavior. Graph Theory Analysis (GTA) metrics, specifically, weighted global efficiency (wGE), community detection, and inter-community information integration were used to analyze functional magnetic resonance imaging (fMRI) data of an in-scanner version of the AAT from 31 heavy drinking Veterans with AUD (HDV) engaged in out-patient treatment and 19 healthy Veterans as controls (HC). We found a functional imprint of alcohol approach bias in HDVs. HDVs showed significantly higher wGE values for approaching than for avoiding alcohol, indicating that their brain was more efficiently organized or functionally set to approach alcohol in the presence to alcohol-related external cues. In contrast, Brains of HCs did not show such a processing advantage for either the approach or avoid condition. Further post-hoc analyses revealed that HDVs and HCs differed in how they implemented top-down control when approaching/avoiding alcohol and in how the fronto-parietal control network interacted with subsystems of the default mode network. These findings contribute to understanding the complex neural underpinnings of alcohol approach bias and lay the foundation for developing more potent and targeted interventions to modify these neural patterns in AUD patients.
Cost-effectiveness analysis of COVID-19 mRNA XBB.1.5 Fall 2023 vaccination in the Netherlands
Authors: Zeevat Florian , van der Pol Simon , Westra Tjalke , Beck Ekkehard , Postma Maarten J. , Boersma Cornelis 
Published: September 2024

AbstractObjectiveThis study aims to assess the cost-effectiveness of the Fall 2023 COVID-19 mRNA XBB.1.5 vaccination campaign in the Netherlands, comparing the XBB1.5 updated mRNA-1273.222 with the XBB1.5 updated BNT162b2 vaccine.MethodsA one-year decision tree-based cost-effectiveness model was developed, considering three scenarios: no Fall 2023 vaccination, BNT162b2 vaccination and mRNA-1273 vaccination in the COVID-19 high-risk population in the Netherlands. The high-risk population includes everyone of 60 and older, and younger adults at high risk as identified by the Dutch Health Council. Costs were included from a societal perspective and the modelled period started in October 2023 and ended in September 2024, including life years lost with a lifetime horizon. Sensitivity and scenario analyses were conducted to evaluate model robustness.ResultsIn the base case, mRNA-1273 demonstrated substantial benefits over BNT162b2, potentially averting 20,629 symptomatic cases, 924 hospitalizations (including 32 ICU admissions), 207 deaths, and 2,124 post-COVID cases. Societal cost savings were €12.9million (excluding vaccination costs), with 1,506 QALYs gained. The break-even incremental price of mRNA-1273 compared to BNT162b2 was €16.72 or €34.32 considering a willingness to pay threshold (WTP) of 20,000 or 50,000 euro per QALY gained.ConclusionThis study provides a comprehensive cost-effectiveness analysis supporting the adoption of the mRNA-1273 vaccine in the national immunization programme in the Netherlands, provided that the Dutch government negotiates a vaccine price that is at most €34.32 per dose higher than BNT162b2. Despite limitations, the findings emphasize the substantial health and economic benefits of mRNA-1273 over BNT162b2 in the high-risk population.
Reducing Functional Dysconnectivity in Schizophrenia Spectrum Disorders
Authors: Wunderlich Stephan , Keeser Daniel , Spaeth Johanna , Maurus Isabel , Alici Cagatay , Schmitt Andrea , Falkai Peter , Stoecklein Sophia , Roell Lukas 
Published: September 2024

ABSTRACTBackgroundAs a condition of dysconnectivity, schizophrenia spectrum disorders (SSD) are characterized by positive, negative, and cognitive symptoms. To improve these symptoms in SSD, physical exercise interventions show promise. We examined if reductions of functional dysconnectivity following exercise therapy are associated with clinical improvements in SSD and explored potential genetic underpinnings.MethodsThe study utilized data from the ESPRIT C3 trial, investigating the effects of aerobic exercise versus flexibility, strengthening, and balance training on different health outcomes in individuals with SSD. Functional dysconnectivity in 23 patients relative to a healthy reference sample, was assessed both pre- and post-intervention. Changes of functional dysconnectivity after exercise and their clinical relevance were evaluated. An imaging transcriptomics approach was used to study the link between changes in functional dysconnectivity and gene expression profiles.ResultsWe observed substantial reductions of functional dysconnectivity on the whole-brain level linked to enhanced gene expression mainly in oligodendrocytes. With regard to the clinical implications, decreases of dysconnectivity in the default-mode network were associated with improvements in global functioning. Reductions of dysconnectivity within the salience network were linked to improvements in symptom severity. Lastly, reductions of functional dysconnectivity in language regions such as Broca’s area were related to cognitive benefits.ConclusionsOur study supports a recent theory of oligodendrocyte pathology in SSD and suggests that reducing functional dysconnectivity in the default-mode, salience, and language network reflect a potential therapeutic target to improve global functioning, total symptom severity, and cognitive impairments in post-acute SSD.Trial name: ESPRIT C3Registry: International Clinical Trials Database,ClinicalTrials.govRegistration number:NCT03466112URL:https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1