bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gerontologic Biostatistics and Data Science: Aging Research in the Era of Big Data
Authors: Chen Chixiang , Murphy Terrence E , Speiser Jaime Lynn , Bandeen-Roche Karen , Allore Heather , Travison Thomas G , Griswold Michael , Shardell Michelle 
Published: November 2024

Abstract
Introduced in 2010, the subdiscipline of gerontologic biostatistics was conceptualized to address the specific challenges of analyzing data from clinical research studies involving older adults. Since then, the evolving technological landscape has led to a proliferation of advancements in biostatistics and other data sciences that have significantly influenced the practice of gerontologic research, including studies beyond the clinic. Data science is the field at the intersection of statistics and computer science, and although the term “data science” was not widely used in 2010, the field has quickly made palpable effects on gerontologic research. In this Review in Depth, we describe multiple advancements of biostatistics and data science that have been particularly impactful. Moreover, we propose the subdiscipline of “gerontologic biostatistics and data science,” which subsumes gerontologic biostatistics into a more encompassing practice. Prominent gerontologic biostatistics and data science advancements that we discuss herein include cutting-edge methods in experimental design and causal inference, adaptations of machine learning, the rigorous quantification of deep phenotypic measurement, and analysis of high-dimensional -omics data. We additionally describe the need for integration of information from multiple studies and propose strategies to foster reproducibility, replicability, and open science. Lastly, we provide information on software resources for gerontologic biostatistics and data science practitioners to apply these approaches to their own work and propose areas where further advancement is needed. The methodological topics reviewed here aim to enhance data-rich research on aging and foster the next generation of gerontologic researchers.
Picking the juiciest cherries from the blockchain tree: Is the hype still alive?
Authors: Flórez Rojas María Lorena , Langer Philipp 
Published: November 2024

Abstract
Over the last years, blockchain technology has been promoted to revolutionize industries through trustless transactions. However, it has recently faced scrutiny for its failure to deliver on its alleged potential. This paper shows how blockchain applications have fallen short of their claims, including trustless and fraud-less transactions, as well as transparency systems. Building on this analysis, this research inspects how Blockchain’s building blocks, such as the Merkle tree and digital signatures, are still highly relevant technological concepts since their introduction decades ago. The paper examines these aspects, the unfulfilled claims, and the salvageable features through a critical analysis, offering insights into various sectors and jurisdictions, using as an example case a public project developed in Colombia. From cases of wrongful implementations, the paper demonstrates the necessity to put specific needs and requirements of real-world applications before the urge to apply blockchain technology without diligent social analysis, especially considering public funds.
Trending in the right direction: critical access hospitals increased adoption of advanced electronic health record functions from 2018 to 2023
Authors: Apathy Nate C , Holmgren A Jay , Nong Paige , Adler-Milstein Julia , Everson Jordan 
Published: November 2024

Abstract

Objectives
We analyzed trends in adoption of advanced patient engagement and clinical data analytics functionalities among critical access hospitals (CAHs) and non-CAHs to assess how historical gaps have changed.

Materials and Methods
We used 2014, 2018, and 2023 data from the American Hospital Association Annual Survey IT Supplement to measure differences in adoption rates (ie, the “adoption gap”) of patient engagement and clinical data analytics functionalities across CAHs and non-CAHs. We measured changes over time in CAH and non-CAH adoption of 6 “core” clinical data analytics functionalities, 5 “core” patient engagement functionalities, 5 new patient engagement functionalities, and 3 bulk data export use cases. We constructed 2 composite measures for core functionalities and analyzed adoption for other functionalities individually.

Results
Core functionality adoption increased from 21% of CAHs in 2014 to 56% in 2023 for clinical data analytics and 18% to 49% for patient engagement. The CAH adoption gap in both domains narrowed from 2018 to 2023 (both P &lt; .01). More than 90% of all hospitals had adopted viewing and downloading electronic data and clinical notes by 2023. The largest CAH adoption gaps in 2023 were for Fast Healthcare Interoperability Resources (FHIR) bulk export use cases (eg, analytics and reporting: 63% of CAHs, 81% of non-CAHs, P &lt; .001).

Discussion
Adoption of advanced electronic health record functionalities has increased for CAHs and non-CAHs, and some adoption gaps have been closed since 2018. However, CAHs may continue to struggle with clinical data analytics and FHIR-based functionalities.

Conclusion
Some crucial patient engagement functionalities have reached near-universal adoption; however, policymakers should consider programs to support CAHs in closing remaining adoption gaps.
Evaluating gradient-based explanation methods for neural network ECG analysis using heatmaps
Authors: Storås Andrea Marheim , Mæland Steffen , Isaksen Jonas L , Hicks Steven Alexander , Thambawita Vajira , Graff Claus , Hammer Hugo Lewi , Halvorsen Pål , Riegler Michael Alexander , Kanters Jørgen K 
Published: November 2024

Abstract

Objective
Evaluate popular explanation methods using heatmap visualizations to explain the predictions of deep neural networks for electrocardiogram (ECG) analysis and provide recommendations for selection of explanations methods.

Materials and Methods
A residual deep neural network was trained on ECGs to predict intervals and amplitudes. Nine commonly used explanation methods (Saliency, Deconvolution, Guided backpropagation, Gradient SHAP, SmoothGrad, Input × gradient, DeepLIFT, Integrated gradients, GradCAM) were qualitatively evaluated by medical experts and objectively evaluated using a perturbation-based method.

Results
No single explanation method consistently outperformed the other methods, but some methods were clearly inferior. We found considerable disagreement between the human expert evaluation and the objective evaluation by perturbation.

Discussion
The best explanation method depended on the ECG measure. To ensure that future explanations of deep neural networks for medical data analyses are useful to medical experts, data scientists developing new explanation methods should collaborate tightly with domain experts. Because there is no explanation method that performs best in all use cases, several methods should be applied.

Conclusion
Several explanation methods should be used to determine the most suitable approach.
Pollen limitation influences the divergences in mating system and floral traits between two sympatric Halenia species
Authors: Yang Ming-Liu , Liu Jin-Chun , Gao Meng-Ke , Sun Yu-Rong , Zhang Zhi-Qiang 
Published: November 2024

Abstract
The mating systems and floral traits often among relatives of hermaphroditic plants can exhibit considerable diversity. This diversity can be influenced by the evolution of selfing and associated floral traits as a form of reproductive assurance (RA) when pollen limitation (PL) results from insufficient pollinator availability. To explore whether the degree of PL primarily drives differences in mating systems and floral traits, we conducted a comprehensive study involving two closely related species, Halenia elliptica and Halenia grandiflora, in three sympatric sites. We investigated floral characteristics, pollinator visitation, PL, autonomous selfing ability, RA and mating system in studied populations. Our findings show that H. elliptica produces smaller flowers and less nectar production than H. grandiflora, making it less attractive to pollinators. Compared with H. grandiflora, H. elliptica experienced more severe outcross pollen limitation (OPL), but compensates with a higher capacity for autonomous selfing, ensuring seed production under natural conditions. Moreover, significant differences in mating systems were detected between them, with H. elliptica exhibiting a higher selfing rate than H. grandiflora across all studied sympatric populations. These differences are also reflected in variations in herkogamy and dichogamy. Our study suggested that the degree of OPL impacts the divergence in mating systems and floral traits between sympatric closely related species, offering valuable insights into the evolution of plant mating systems and floral traits.
Potential of ex vivo organotypic slice cultures in neuro-oncology
Authors: Steindl Ariane , Valiente Manuel 
Published: November 2024

Abstract
Over recent decades, in vitro and in vivo models have significantly advanced brain cancer research; however, each presents distinct challenges for accurately mimicking in situ conditions. In response, organotypic slice cultures have emerged as a promising model recapitulating precisely specific in vivo phenotypes through an ex vivo approach. Ex vivo organotypic brain slice models can integrate biological relevance and patient-specific variability early in drug discovery, thereby aiming for more precise treatment stratification. However, the challenges of obtaining representative fresh brain tissue, ensuring reproducibility, and maintaining essential central nervous system (CNS)-specific conditions reflecting the in situ situation over time have limited the direct application of ex vivo organotypic slice cultures in robust clinical trials. In this review, we explore the benefits and possible limitations of ex vivo organotypic brain slice cultures in neuro-oncological research. Additionally, we share insights from clinical experts in neuro-oncology on how to overcome these current limitations and improve the practical application of organotypic brain slice cultures beyond academic research.
Private but Misunderstood? Evidence on Measuring Intimate Partner Violence via Self-Interviewing in Rural Liberia and Malawi
Authors: Park David Sungho , Aggarwal Shilpa , Jeong Dahyeon , Kumar Naresh , Robinson Jonathan , Spearot Alan 
Published: November 2024

Abstract
Women may underreport intimate partner violence (IPV) in surveys. In an experiment in rural Liberia and Malawi, women were asked IPV questions via self-interviewing (SI) or face-to-face interviewing. Many respondents appear to misunderstand questions in SI, and significant effects of SI were observed on innocuous placebo questions. Because the prevalence of IPV is typically well below 50 percent, such measurement error will tend to bias IPV reporting upwards. Indeed, the results show that SI increases reported incidence of IPV, but it cannot be ruled out that these increases are spurious.
Inhibition of Phosphodiesterase 10A Alleviates Pain-like Behavior in Mice
Authors: Gross Tilman , Stehle Daniel , Nagel Chantal , Zhou Fangyuan , Duman Emre , Hernandez-Olmos Victor , Sinderwald Rekia , Gerninghaus Hannah , Petersen Jonas , Feil Susanne , Kallenborn-Gerhardt Wiebke , Lu Ruirui , Metzner Katharina , Feil Robert , Proschak Ewgenij , Schmidtko Achim 
Published: November 2024

Background:
Emerging evidence indicates that cyclic nucleotide phosphodiesterases exert distinct functions in pain processing and that targeting phosphodiesterases might be a novel strategy for pain relief. This study hypothesized that the phosphodiesterase isoform phosphodiesterase 10A (PDE10A) might be a target for analgesic therapy.

Methods:

In situ hybridization, immunostaining, cyclic nucleotide enzyme immunoassays, real-time cyclic guanosine monophosphate imaging, and real-time quantitative reverse transcription polymerase chain reaction were performed to investigate the expression and activity of PDE10A in the dorsal root ganglia and spinal cord. Mice of both sexes were assessed in multiple pain models after the administration of specific PDE10A inhibitors.

Results:
PDE10A is distinctly expressed in nociceptive neurons in the dorsal root ganglia and spinal cord of mice. Incubation of cultured sensory neurons with the PDE10A inhibitor, TAK-063 (150 nM), increased cyclic guanosine monophosphate levels in enzyme immunoassays and real-time imaging at the single-cell level. Strikingly, treatment with TAK-063 (0.3 mg/kg intraperitoneal) ameliorated the pain-like behavior of female and male mice in models of acute nociceptive pain after intraplantar injection of capsaicin (mean ± SD, 8.87 ± 8.78 s [TAK-063] vs. 51.24 ± 36.36 s [vehicle], P = 0.020) or allyl isothiocyanate (2.46 ± 3.43 s [TAK-063] vs. 10.36 ± 4.87 s [vehicle]; P = 0.018). Furthermore, TAK-063 (0.3 mg/kg intraperitoneal) reduced established pain-like behavior in models of inflammatory pain induced by intraplantar injection of zymosan (two-way ANOVA, group, F[1,18] = 48.51, TAK-063 vs. vehicle; P ≤ 0.0001) or complete Freund’s adjuvant (F[1,14] = 46.10, TAK-063 vs. vehicle; P ≤ 0.0001), without the development of antinociceptive tolerance. The antinociceptive effects were recapitulated using the PDE10A inhibitor PF-2545920.

Conclusions:
Collectively, the data support the idea that PDE10A is a suitable target for the development of efficacious analgesic drugs.
Safety and efficacy of Angong Niuhuang Pills in patients with moderate-to-severe acute ischemic stroke (ANGONG TRIAL): A randomized double-blind placebo-controlled pilot clinical trial
Authors: Li Shengde , Wang Anxin , Shi Lin , Liu Qin , Guo Xiaoling , Liu Kun , Wang Xiaoli , Li Jie , Zhu Jianming , Wu QiuYi , Yang QingCheng , Zhuang Xianbo , You Hui , Feng Feng , Luo Yishan , Li Huiling , Ni Jun , Peng Bin 
Published: November 2024

Abstract

Background:
Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke.

Methods:
This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days.

Results:
There were 57 and 60 patients in the ANP and placebo groups finally included respectively for modified intention-to-treat analysis. The median age was 66 years, and the median NIHSS score at baseline was 12. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: –7.1 mL; interquartile range [IQR]: −18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively (median difference: 3.0 mL, IQR: −1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups (P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: –12.3 mL; IQR: –27.7 to –0.3 mL, P = 0.03).

Conclusions:
ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis.

Trail Registration:

Clinicaltrials.gov, No. NCT04475328.
Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells
Authors: Chen Rongrong , Jin Chunxiang , Liu Kai , Zhao Mengyu , Yang Tingting , Zhang Mingming , Xiao Pingnan , Feng Jingjing , Hong Ruimin , Fu Shan , Cui Jiazhen , Huang Simao , Wei Guoqing , Huang He , Hu Yongxian 
Published: November 2024

Abstract

Background:
B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.

Methods:
Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.

Results:
In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS.

Conclusion:
Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

Registeration:
Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).
The Regulation of Innate Antiviral Immunity by TRIM56
Authors: Li Kui , Lee Jacob Z. 
Published: November 2024

Abstract
A member of the tripartite-motif (TRIM) protein family of E3 ligases, TRIM56 has increasingly been recognized as a versatile player in innate antiviral immunity that operates via catalytically-dependent and catalytically-independent mechanisms. Herein, we provide a concise overview of the various roles that TRIM56 has been demonstrated to play in host interactions with viruses, including its "direct" virus-restricting activities and "indirect" antiviral effects resulting from its positive regulation of innate immune signaling. In addition, we discuss the current understanding of the molecular determinants and underlying biology by which TRIM56 functions in these processes.
Streamlining Atrial Fibrillation Care: Building a Comprehensive Program to Provide High-Quality, Individualized Care
Authors: Lam David , Farrell Jen , Fletcher Bob , Zivin Adam 
Published: November 2024

ABSTRACT
Atrial fibrillation is the most common sustained arrhythmia with a variable presentation ranging from asymptomatic incidental diagnosis by physical examination or electrocardiogram screening, to severely symptomatic requiring emergent treatment. The variation in care represents an opportunity to build a comprehensive center of excellence within a hospital system. We present our experience building the Swedish Comprehensive AFib Network and a dedicated AFib clinic at a large quaternary urban medical center. We focused on patient and referral engagement, standardized protocols to promote best practices, data collection to improve quality of care, and broad evaluation of a single but multidisciplinary disease process. We hope this can offer insight into how other programs can be started for atrial fibrillation or other disease-focused clinics. We report our experience in the first 2 years, having evaluated over 700 new patients, and demonstrated an improvement in the rate of anticoagulation usage and a reduction in hospitalizations among patients included in our program.
Investigating the impact of metabolic syndrome and its components on pancreas fat: a Bidirectional Mendelian randomization study
Authors: Su Bohan , Gao Xin , Pang Chaoyu , Dong Peng , Fan Zhiyao , Zhan Hanxiang 
Published: November 2024

Objective:
Metabolic syndrome (MetS) and fatty pancreas are two prevalent health conditions that are strongly associated with an elevated risk of developing type 2 diabetes, cardiovascular disease, and pancreatic cancer. Understanding the causal relationship between these conditions is important for developing effective prevention and treatment strategies. In this study, we performed a bidirectional Mendelian randomization analysis to investigate the potential causal relationship between MetS and fatty pancreas.

Methods:
This study undertook bidirectional Mendelian randomization. Genetic instruments for obesity, glycemic, lipid, and blood pressure were identified as instrumental variables for MetS traits in order to evaluate their causal role in pancreatic fat etiology. Summary level data for pancreas fat (PF) were obtained from a genome-wide association study conducted in the UK Biobank.

Results:
There was no causal relationship between MetS as a binary trait and PF. In addition, a causal association of increasing Waist-to-Hip Ratio (WHR) with pancreatic fat risk was found [odds ratio (OR)=1.173, 95% confidence interval (CI): 1.067-1.288, p=9*10-4]. Notably, there is no evidence of a causal relationship between PF and glycemic, lipid, and blood pressure. Sensitivity analyses did not indicate that pleiotropy was an important source of bias.

Conclusion:
MetS had no causal relationship with pancreatic fat. Of the components of the metabolic syndrome, only abdominal obesity and pancreatic fat were observed to be causally related.
Integration of point-of-care ultrasound in a nurse practitioner–led heart failure clinic
Authors: Craigo Christina Light , Brown Theresa , Kedan Ilan , Koniak-Griffin Deborah , DeVon Holli A. 
Published: November 2024

ABSTRACT

Background:
Despite improved survival, one in five patients with heart failure (HF) is readmitted within 30 days of discharge. Assessing fluid status is challenging, with an estimated 50% accuracy when relying on physical examination alone. Pulmonary congestion is a risk factor for readmission and can manifest weeks before symptoms occur.

Purpose:
To conduct a pilot study to assess for pleural effusion with point-of-care ultrasound (POCUS) and to evaluate inferior vena cava (IVC) noncollapsibility as a marker of volume status.

Methods:
A convenience sample of adults with HF (n = 21) were seen in a nurse practitioner (NP)-led postdischarge clinic within 12 days of hospitalization. The setting was a large tertiary care hospital. Inclusion criteria were patients with an HF diagnosis and Medicare insurance. The NP measured IVC diameter, assessed for collapsibility, and examined pleural cavities using a VSCAN POCUS device. Data were analyzed descriptively.

Results:
Pleural effusions were identified in three (14.3%) patients with POCUS and referred for thoracentesis. Inferior vena cava was noncollapsible in 5 (23.8%) patients; each of these patients required intervention for volume overload.

Conclusions:
Point-of-care ultrasound can be used by NPs to identify patients with pleural effusions who may benefit from thoracentesis. Inferior vena cava noncollapsibility may be a predictor for volume overload.

Implications:
Point-of-care ultrasound equips NPs with an extra tool to effectively manage HF.