bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic and genetically predicted leukocyte telomere length and prostate cancer risk: Results from a large-scale longitudinal cohort study.
Authors: Liu Xiaoyang , Liu Shengzhuo , Yan Xin , Zhou Jing , Yu Yunfei , Dong Qiang 
Published: February 2025

404

Background:
Previous studies on the correlation between leukocyte telomere length (LTL) and prostate cancer (PCa) have shown contradictory results. Our study aims to further explore the potential relationship between LTL and PCa.
Methods:
In this study, a total of 229,022 male individuals were enrolled from the UK Biobank to investigate this association . Both unadjusted and covariates-adjusted Cox proportional hazards regression models were employed. The primary outcome was defined as the diagnosis of incident prostate cancer using in-patient data and the death registry of the UKB cohort. To validate the reliability of the primary findings, secondary analyses, including Mendelian randomization (MR) were conducted.
Results:
The primary analysis demonstrated that longer LTL was substantially associated with higher risk of prostate cancer, with associations remaining robust after adjusting for potential covariates (HR: 1.444, 95% CI: 1.247-1.673, P < 0.001). Similar results were observed when LTL was analyzed as both a continuous and categorical variable, and the association were shown to be inversely U-shaped. At the genetic level, the association was further validated using MR across different prostate cancer databases, with results consistent with our primary analysis.
Conclusions:
Our findings offer compelling evidence that leukocyte telomere length is an important risk factor for prostate cancer.

Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between leukocyte telomere length (analyzed both as a continuous variable and by quartile categories) and prostate cancer risk in the UK Biobank study.

Model I
Model II
Model III

Cases

N

Median

HR

95%CI

HR

95%CI

HR

95%CI

10693
198830
0.810
1.505
1.301-1.741
1.454
1.256-1.683
1.444
1.247- 1.673

<0.001

<0.001

<0.001

2761
49708
0.683
ref
ref
ref

2782
49707
0.773
1.088
1.032 -1.147
1.087
1.031 - 1.145
1.084
1.029-1.143

2607
49707
0.849
1.090
1.033-1.151
1.086
1.029-1.146
1.084
1.028-1.144

2543
49708
0.960
1.187
1.124-1.253
1.174
1.112- 1.240
1.170
1.108-1.236

<0.001

<0.001

<0.001

Model I adjust for age; Model II adjust for demographic variables (age; ethnic background) and socioeconomic variables (socioeconomic status; education); Model III adjust for demographic variables (age class; ethnic background) socioeconomic variables (socioeconomic status; education) and lifestyle variables (alcohol intake frequency; smoking history; body mass index; duration of walks; sleep duration; blood pressure).
Clinicopathological characteristics of cancer of unknown primary (CUP) with renal profile using gene expression profiling (GEP) based cancer classification.
Authors: Allam Joelle , Ma Li , Zhao Jianping , Estrella Jeannelyn , Higbie Victoria , Willett Anneleis , Matamoros Aurelio , Lano Elizabeth A , Treuner Kai , Raghav Kanwal Pratap Singh , Huey Ryan W 
Published: February 2025

456

Background:
CUP is a rare and heterogenous clinicopathologic syndrome with unidentifiable origin at time of diagnosis. Based on immunophenotyping, specifically PAX8 staining, CUP with Renal profile (RCUP) is emerging as a distinct clinical subset. In addition to clinical presentation and immunohistochemistry (IHC), molecular profiling for tissue of origin may aid defining CUP subsets. Precision in diagnosis impacts therapeutics given that cytotoxic chemotherapy options for CUP do not overlap with tyrosine kinase inhibitors or checkpoint inhibitors used for renal cell carcinoma.
Methods:
We retrospectively (2018-2022) evaluated patients with CUP composed of cases (renal profile, N=100, clear cell or papillary) or controls (non-renal, N=200) identified using the 92-gene assay (CancerTYPE ID), a validated classifier for predicting tissue of origin. Clinicopathologic data including IHC and molecular profiling results were collected using pathology specimens and reports.
Results:
Baseline characteristics (age, gender, tumor grade) of cases and controls were comparable, except for histology, wherein adenocarcinoma was less common with RCUP (27% vs 48%, p<0.001). Median number of IHC stains performed was 11 (range 0-30) vs 9 (0-29) (p=0.04) in RCUP vs non-renal cases, respectively. While PAX8 was tested in 64% vs 39% (p<0.001) of cases, it was found to be strongly or focally positive in 87.5% vs 21.8% (p<0.001), respectively. In contrast to non-renal CUP, RCUP patients were more likely to have bone biopsies (24% vs 11.5%, OR 2.4, p=0.007), less likely to have high-TMB (2.8% vs 28.2%, OR 0.07, p=0.001), and had a lower proportion of TP53 mutations (18.8% vs 89.2%, OR 0.028, p<0.001), KRAS mutations (13.3% vs 77.4%, OR 0.045, p<0.001) and BRAF mutations (0% vs 42%, OR 0, p=0.015).
Conclusions:
RCUP appears to be a distinct subset of CUP with variable diagnostic workup. Critical IHC markers may be omitted in a considerable number of cases and despite positivity, may still confer an uncertain diagnosis. Key molecular factors appear to be different and may require tailored therapeutic approaches. This study further supports the clinical utility of GEP-based cancer classification with the 92-gene assay to predict RCUP and may be an important adjunct to IHC to improve diagnostic accuracy for CUP and to guide treatment selection for better clinical outcomes.

RCUP (N=100)
Non-renal CUP (N=200)

IHC

Cases Tested (%)

Cases Positive (%)

Cases Tested (%)

Cases Positive (%)

CK7
83
47
81
75*

CK20
75
11
77
24*

PAX8
64*
88*
39
22

Napsin
29
28*
25
8

RCC
26*
31
4
13

Vimentin
17
94
5.5
73

*Significantly (p<0.05) greater proportion of cases.
Subtyping of Primary Aldosteronism by Adrenal Venous Sampling
Authors: Rossi Gian Paolo , Battistel Michele , Seccia Teresa Maria , Rossi Federico Bernardo , Rossitto Giacomo 
Published: February 2025

Abstract
Primary aldosteronism (PA), the most common cause of arterial hypertension, is surgically curable if a unilateral source of the hyperaldosteronism is discovered. To identify the patients who are curable, all current guidelines recommend adrenal venous sampling (AVS), a procedure which, albeit simple in principle, remains scarcely available and markedly under-utilized, because it is still perceived as technically challenging, invasive, and difficult to interpret. The lack of uniformly accepted standards for performance and interpretation of AVS, alongside the diffuse concerns that, albeit quite rarely, it can be complicated by adrenal vein rupture, contribute to the scant utilization of AVS.
In the last decade, several major studies have contributed to a greater understanding of the use of AVS in PA patients, thus paving the way to a more rational and effective application that can allow to diagnose many more PA patients with a unilateral form of the disease to be referred for curative adrenalectomy. Moreover, microcatheters and androstenedione have been introduced to increase the success rate. This review provides updated information on the subtyping of PA by means of AVS and examines key issues on the selection and preparation of patients, the optimal performance of the procedure, and the interpretation of its results for diagnostic purposes, even in the most challenging cases. Situations when AVS can be omitted before surgery and alternative functional imaging techniques that have been proposed to identify unilateral surgical curable PA to circumvent the bottle-neck represented by the limited availability of AVS world-wide, are also discussed.
Effect of Painful Stimuli on PVNCRH Neurons: Implications for States of Consciousness Under Isoflurane Anesthesia
Authors: Yu Le , Zhu Xiaona , Duan Wenying , Yang Kexin , Hu Ji , Zhang Ye 
Published: February 2025

BACKGROUND:
Many patients undergoing surgery experience accompanying pain symptoms preoperatively. The impact of painful stimuli on general anesthesia remains largely unknown. Corticotrophin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVNCRH neurons) are crucial central stress hubs that respond to painful stimuli. These neurons also participate in regulating processes such as sleep and anesthesia. Natural reward can inhibit PVNCRH neurons to relieve stress-induced behavioral changes, but the effect of natural reward on the anesthesia process in patients with pain is not clear. In this study, we assessed the impact of painful stimuli on isoflurane anesthesia and its potential neural mechanism. We also investigated the potential of natural reward therapy for alleviating the impact of painful stimuli on isoflurane anesthesia.

METHODS:
The righting reflex test and cortical electroencephalography (EEG) were used as measures of consciousness in complete Freund’s adjuvant (CFA)-injected mice during isoflurane anesthesia. EEG and burst-suppression ratios (BSR) were used to assess the depth of anesthesia. The expression of c-Fos, fiber photometry recording, and brain slice electrophysiology were used to determine neuronal activity changes in PVNCRH neurons after CFA injection or 10% sucrose treatment. Finally, chemogenetic technology was used to specifically manipulate PVNCRH neurons.

RESULTS:
Compared to the saline-injected mice, the CFA-injected mice exhibited an increased the mean[SD] induction time of isoflurane anesthesia (354[48] s vs 258[30] s, P = .0001) and a reduced BSR of isoflurane anesthesia (60.1[10.3] % vs 81.5[9.76] %, P = .002). CFA injection increased PVN c-Fos expression (3667[706] vs 1735[407], P = .0002) and enhanced the population activity of PVNCRH neurons (33.4[13.6] % vs 1.23[3.57] %, P = .0009). Chemogenetic suppression of PVNCRH neurons reversed the anesthesia abnormalities in CFA-injected mice. Natural reward accelerated the induction time of isoflurane anesthesia (252[24] s vs 324[36] s, P = .003) and increased the BSR of isoflurane anesthesia (84.8[5.36] % vs 57.7[14.3] %, P = .0005). Chemogenetic activation of PVNCRH neurons reversed the effect of natural reward on isoflurane anesthesia in CFA-injected mice.

CONCLUSIONS:
Painful stimuli affect the process of isoflurane anesthesia by activating PVNCRH neurons, which implies that these neurons modulate isoflurane anesthesia. Additionally, natural reward alleviates the impact of painful stimuli on isoflurane anesthesia by inhibiting PVNCRH neurons.
Public Policy as Trans Harm
Authors: Sharrow Elizabeth 
Published: February 2025

Abstract
The observation that systems of state governance are more apt to do harm or violence to transgender and gender-diverse people is foundational to the field of trans studies. This article argues that public policy—including policy design, implementation, governance, and administration—is an important target for transfeminist sports studies. It illustrates the importance of attending to Title IX of the Education Amendments of 1972, a federal sex nondiscrimination policy in the United States. This case underscores how public policy through its widespread enactment in American school-sponsored sports and overreliance on binary logics of sex-segregated categories remains paramount, though underanalyzed, as a vehicle for trans harm.
Creating a Non–Gender Binary Sports Space
Authors: Yang Jinsun 
Published: February 2025

Abstract
Trans inclusion policies remain one of the major issues facing contemporary trans rights movements in the United States. In sports, where sex segregation has rarely been challenged, trans inclusionary policies have emerged as a public debate in which key values of liberal individualism such as fairness, meritocracy, and safety collide with trans athletes' rights to belong in a public arena. While queer feminists' scholarship on sports has criticized the notion that trans inclusion policies do not necessarily problematize a binary gender ideology and sports institutions' authority in policing athletes' bodies, few studies have investigated alternative sports spaces and policies to challenge the sexist culture and binary sex-based structure of mainstream sports. This article introduces the Queer Women Games, a non–gender binary sports competition in Korea, as an experimental site to imagine and implement gender justice in sports through organizational actions and collective involvement. First, the author compares the QWG's nonbinary policies with transgender inclusion policies in recreational sports in terms of their approaches to sex segregation, sports authorities governing athletes' genders, and transgender exclusion. Then the author argues that the nonbinary policy opened a dialogue, which seems to be foreclosed in inclusion-based approaches, by undoing sex segregation and building a consensus on rejecting gender policing.
Queer African Feminist Orientations for a Trans Sports Studies
Authors: Adjepong Anima 
Published: February 2025

Abstract
This commentary makes a case for developing trans sports studies out of queer African feminism. Queer African feminism is an epistemological orientation that affirms a flexible gender system, despite contemporary colonial gender ideologies, which insist on biological dimorphism. Queer African feminism offers to sports studies an analytical framework that attends to how colonialism, patriarchy, religion, and capitalism structure gender and sexual ideologies within sport and offers meaningful opportunities for disrupting these unjust systems. By centering the experiences of African athletes deemed intersex by sporting and medical authorities, the author demonstrates how current approaches to undermining sex segregation in sports still risk excluding certain athletes—intersex, nonbinary, and non-medically transitioning athletes. Ultimately, the author argues that if the goal of trans sports studies is to help bring about gender justice in sports, queer African feminism can offer a generative framework for attaining this goal.
The MBB Manifesto
Authors: Martins Raphael H. , Vieira Pedro , Snyder Cara 
Published: February 2025

Abstract
The Meninos Bons de Bola (MBB, or Soccer Star Boys) is Brazil's first trans soccer team. We are a collective that welcomes transgender men, transmasculine people, trans women, and travesti players. Our manifesto recognizes that the fight for trans inclusion in athletics is part of a larger struggle against repression and fascism, and as such, we demand full access to sport for people of any and all genders and sexual orientations.
Training on a 3D-Printed Simulation Model Improves Accuracy in External Ventricular Drain Placement
Authors: Kosterhon Michael , Turgut Merih Ö. , Gielisch Matthias , Graef Julian , Ringel Florian 
Published: February 2025

BACKGROUND AND OBJECTIVES:
External ventricular drain (EVD) placement is a critical, lifesaving procedure in cranial neurosurgery, often performed manually using anatomical landmarks that vary between individuals. This study evaluates the efficacy of a 3-dimensional (3D)–printed EVD training model designed to improve the accuracy of this procedure.

METHODS:
Computed tomography scans from 3 patients were used to create 3D-printed head models with narrow, wide, and normal ventricles. Twenty-five neurosurgeons participated in a three-round training protocol: pre-training, training with neuronavigation and a standardized protocol, and post-training. The accuracy of EVD placement was measured using an optical navigation system, and participants' confidence levels were assessed through questionnaires.

RESULTS:
Training significantly enhanced EVD placement accuracy. Pre-training, only 55.3% of placements were intraventricular (Kakarla grade 1), which increased to 84.0% post-training (P < .001). The distance to the ideal entry point improved from 5.8 mm (SD, ±3.7 mm) to 4.1 mm (SD, ±1.5 mm), and the distance to the target point improved from 12.6 mm (SD, ±5.8 mm) to 8.3 mm (SD, ±4.0 mm) (P < .001 for both). The time to identify entry points and puncture the ventricles also improved significantly. Left-sided EVDs were more frequently misplaced. In addition, right-handed participants (n = 24) performed better when placing left-sided EVDs with their right hand. Participants with more than 6 years of experience were more likely to misplace the EVD and overestimate their placement accuracy compared with less experienced participants. Post-training, both experienced and less experienced neurosurgeons achieved similar success rates. Confidence in EVD placement and puncture direction significantly increased post-training.

CONCLUSION:
A standardized training protocol using a 3D-printed model significantly improves the accuracy and confidence of neurosurgeons in EVD placement. Regular training is recommended to maintain high clinical performance, emphasizing the need for standardized procedures and the use of neuronavigation for complex cases.
An Anatomy of Crypto-Enabled Cybercrimes
Authors: Cong Will , Harvey Campbell , Rabetti Daniel , Wu Zong-Yu 
Published: February 2025

The advent of cryptocurrencies and digital assets holds the promise of improving financial systems by offering cheap, quick, and secure transfer of value. However, it also opens up new payment channels for cybercrimes. Assembling a diverse set of public on- and off-chain, proprietary, and hand-collected data, including attacker–victim negotiations and dark web conversations in Russian, we present an initial anatomy of crypto-enabled cybercrimes, highlighting relevant economic issues and proposing areas for future research. Among others, we find ransomware, as the most dominant organized crypto-enabled cybercrime, entails criminal gangs that operate like firms who adopt modern revenue models and carefully manage their reputations. We suggest that blanket restrictions on cryptocurrency usage may prove counterproductive. Instead, blockchain transparency enables effective forensics for tracking, monitoring, and shutting down dominant cybercriminal organizations, which potentially facilitates a more secure and reliable crypto ecosystem in the longer term. This paper was accepted by David Simchi-Levi, finance. Funding: This work was supported by the National University of Singapore (NUS), Ripple’s University Blockchain Research Initiative (UBRI), the Israel Science Foundation (ISF), and the Cornell FinTech Initiative. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.03691 .
Multichannel Advertising: Budget Allocation in the Presence of Spillover and Carryover Effects
Authors: Chen Huijun , Chen Ying-Ju , Park Sung-Hyuk , Shin Dongwook 
Published: February 2025

Problem definition: This paper explores budget allocation strategies for a multichannel ad campaign, where a marketing agency strives to maximize the total conversions by dynamically adjusting budget allocation over marketing channels. A salient feature of the problem is the interplay of spillover and carryover effects; namely, customers are exposed to ads through multiple channels, and thus ads from one channel affect the effectiveness of the subsequent ads from other channels. Methodology/results: We construct a simple model that captures the essential features of this problem. Our theoretical analysis yields two main insights. First, motivated by common practice based on the last-click attribution method, we examine a class of budget allocation policies that are oblivious to the spillover and carryover effects. If the agency decreases the budget on a channel based on past low conversions while neglecting to account for the fact that the ads from that channel induced conversions through other channels, then the conversions from that channel will decrease. Consequently, the agency will further decrease the budget on the channel. This pattern repeats, eventually leading to suboptimal performance in the long run. Second, we derive a fluid approximation to consumer dynamics across multiple channels, which lends itself to characterizing structural properties of optimal dynamic budget allocation policies that internalize the cross-channel interactions. To enable practical implementation, we propose a static budget allocation policy that is both tractable in practice and near optimal for long campaigns. Managerial implications: Our theoretical results provide normative guidance for budget allocation in multichannel ad campaigns. We illustrate the efficacy of our proposed method through a numerical study based on data from an online multichannel ad campaign. Funding: This work was supported by the Hong Kong Research Grants Council [ECS Grant 26504219, GRF Grant 16212821, C6020-21GF]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.0293 .
ANÁLISE DOS ESTILOS DE APRENDIZAGEM NA EDUCAÇÃO A DISTÂNCIA: USO DE ALGORITMOS INTELIGENTES
Authors: Nascimento Elizane Silva do , Rodrigues de Souza Míriam Síria , COSTA ROBERTO DOUGLAS DA 
Published: February 2025

A Inteligência Artificial (IA) é um tema em pauta nas pesquisas e estudos acadêmicos na área de Educação, embora ela já faça parte das nossas atividades cotidianas, tem atravessado, nos últimos anos, os processos educativos e ainda há muitas possibilidades de estudos que a utilizem na busca por soluções educacionais na modalidade de Educação a Distância (EAD). Este artigo busca analisar os resultados de um projeto institucional intitulado “A Teoria dos Estilos de Aprendizagem Aplicada ao Ensino a Distância”. A pesquisa foi desenvolvida no período de 2020 a 2023. Para a coleta dos dados foi utilizado um questionário CHAEA 32 e para análise dos dados foi adotado o método hipotético-dedutivo. A pesquisa foi desenvolvida em cinco fases: revisão literária sistemática; preenchimento do questionário CHAEA 32 (adaptado); análise dos dados (identificação dos Estilos de Aprendizagem predominantes dos alunos); implementação (reconhecimento dos comportamentos dos alunos); execução (correlacionar os Estilos de Aprendizagem identificados com os comportamentos conhecidos). Neste trabalho, como referencial teórico foi adotado o conceito de Estilos de Aprendizagem definido por Alonso, Gallego e Honey (2002), Cavellucci (2006) e Costa (2022). Para a definição de IA, foram utilizados os conceitos de Russell e Norvig (2013). Nos resultados, os dados apontam que, a partir do conjunto de 120 alunos divididos em cinco turmas de um curso de formação em EAD, que responderam voluntariamente o questionário CHEA32, observa-se que não há correlação entre esses estilos e as variáveis de comportamento utilizadas no estudo. Além do resultado da análise dos dados do Ambiente Virtual de Aprendizagem, uma contribuição importante deste trabalho foi poder comprovar que apenas a identificação dos comportamentos dos alunos no Ambiente Virtual de Aprendizagem é insuficiente para detectar o seu Estilo de Aprendizagem padrão, principalmente porque esses comportamentos sofrem influência de outros fatores externos como sociais, ambientais e fisiológicos.
Palavras-chave: Educação a Distância; Estilos de Aprendizagem; Algoritmos inteligentes.