bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Gamma Knife surgery, omitting adjunct whole brain radiation treatment, feasible for patients with 20 or more brain metastases?
Authors: Jiani Sherry Liu , Karlsson Bengt , Vellayappan Balamurugan , Ang Yvonne , Wu Peng , Yeo Tseng Tsai , Nga Vincent 
Published: March 2024

Abstract

Background
The importance of the number of brain metastases (BM) when deciding between whole brain radiation treatment (WBRT) and radiosurgery is controversial. We hypothesized that the number of BM is of limited importance when deciding radiation strategy, and offered Gamma Knife surgery (GKS) also for selected patients with 20 or more BM.

Methods
The outcome following single session GKS for 75 consecutive patients harboring 20 or more (20+) BM was analyzed. Data was collected both retro- and prospectively.

Results
The median survival time was 9 months. Two grade 3 complications occurred, 1 resolved and 1 did not. Sex and clinical condition at the time of GKS (ECOG value) were the only parameters significantly related to survival time. Eighteen patients developed leptomeningeal dissemination with or without distant recurrences (DR), and another 32 patients developed DR a total of 73 times. DR was managed with GKS 24 times, with WBRT 3 times and with systemic treatment or best supportive care 46 times. The median time to developing DR was unrelated to the number of BM, but significantly longer for patients older than 65 years, as well as for patients with NSCLC.

Conclusions
GKS is a reasonable treatment option for selected patients with 20 or more BM. It is better to decide the optimal management of post-GKS intracranial disease progression once it occurs rather than trying to prevent it by using adjunct WBRT.
H3K4me1 recruits DNA repair proteins in plants
Authors: Quiroz Daniela , Oya Satoyo , Lopez-Mateos Diego , Zhao Kehan , Pierce Alice , Ortega Lissandro , Ali Alissza , Carbonell-Bejerano Pablo , Yarov-Yarovoy Vladimir , Suzuki Sae , Hayashi Gosuke , Osakabe Akihisa , Monroe Grey 
Published: March 2024

Abstract
DNA repair proteins can be recruited by their histone reader domains to specific epigenomic features, with consequences on intragenomic mutation rate variation. Here, we investigated H3K4me1-associated hypomutation in plants. We first examined 2 proteins which, in plants, contain Tudor histone reader domains: PRECOCIOUS DISSOCIATION OF SISTERS 5 (PDS5C), involved in homology-directed repair, and MUTS HOMOLOG 6 (MSH6), a mismatch repair protein. The MSH6 Tudor domain of Arabidopsis (Arabidopsis thaliana) binds to H3K4me1 as previously demonstrated for PDS5C, which localizes to H3K4me1-rich gene bodies and essential genes. Mutations revealed by ultradeep sequencing of wild-type and msh6 knockout lines in Arabidopsis show that functional MSH6 is critical for the reduced rate of single-base substitution (SBS) mutations in gene bodies and H3K4me1-rich regions. We explored the breadth of these mechanisms among plants by examining a large rice (Oryza sativa) mutation data set. H3K4me1-associated hypomutation is conserved in rice as are the H3K4me1-binding residues of MSH6 and PDS5C Tudor domains. Recruitment of DNA repair proteins by H3K4me1 in plants reveals convergent, but distinct, epigenome-recruited DNA repair mechanisms from those well described in humans. The emergent model of H3K4me1-recruited repair in plants is consistent with evolutionary theory regarding mutation modifier systems and offers mechanistic insight into intragenomic mutation rate variation in plants.
Elevated pain sensitivity is associated with reduced rapid eye movement (REM) sleep in females with comorbid temporomandibular disorder and insomnia
Authors: Reid Matthew J , Hamilton Katrina R , Nilsson Sophie J , Owens Michael Alec , Phillips Jane L , Finan Patrick H , Campbell Claudia M , Giagtzis Alexandros , Abhishek Dave , Haythornthwaite Jennifer A , Smith Michael T 
Published: March 2024

Abstract

Objective
Patients with chronic pain disorders, including Temporomandibular Disorders (TMDs) endorse high levels of sleep disturbances, frequently reporting reduced sleep quality. Despite this, little is known about the effect that daytime pain has on the microstructure and macro-architecture of sleep. Therefore, we aimed to examine the extent to which daytime pain sensitivity, measured using quantitative sensory testing (QST), is associated with objective sleep parameters the following night, including sleep architecture and power spectral density, in women with TMD.

Methods
144 females with myalgia and arthralgia by examination using the Diagnostic criteria for TMD completed a comprehensive QST battery consisting of General Pain Sensitivity, Central Sensitization Index, and Masseter Pressure Pain Threshold assessments. Polysomnography was collected the same night to measure sleep architecture and calculate relative power in delta, theta, alpha, sigma, and beta power bands.

Results
Central Sensitization (B = −3.069, P = .009), General Pain Sensitivity Indices (B = −3.069, P = .007), and Masseter Pain Pressure Threshold (B = 0.030, P = .008) were significantly associated with lower REM% both before and after controlling for covariates. Pain sensitivity measures were not significantly associated with relative power in any of the spectral bands nor with any other sleep architectural stages.

Conclusions
Our findings demonstrate that higher generalized pain sensitivity, masseter pain pressure threshold, as well as central sensitization were associated with a lower percentage of REM in participants with myofascial pain and arthralgia of the masticatory system. These findings provide an important step toward understanding the mechanistic underpinnings of how chronic pain interacts with sleep physiology.
One step too far: social cerebellum in norm-violating navigation
Authors: Li Meijia , Pu Min , Ma Qianying , Heleven Elien , Baeken Chris , Baetens Kris , Deroost Natacha , Van Overwalle Frank 
Published: March 2024

Abstract
Social norms are pivotal in guiding social interactions. The current study investigated the potential contribution of the posterior cerebellum, a critical region involved in perceiving and comprehending the sequential dynamics of social actions, in detecting actions that either conform to or deviate from social norms. Participants engaged in a goal-directed task in which they observed others navigating towards a goal. The trajectories demonstrated either norm-violating (trespassing forbidden zones) or norm-following behaviors (avoiding forbidden zones). Results revealed that observing social norm-violating behaviors engaged the bilateral posterior cerebellar Crus 2 and the right temporoparietal junction (TPJ) from the mentalizing network, and the parahippocampal gyrus (PHG) to a greater extent than observing norm-following behaviors. These mentalizing regions were also activated when comparing social sequences against non-social and non-sequential control conditions. Reproducing norm-violating social trajectories observed earlier, activated the left cerebellar Crus 2 and the right PHG compared to reproducing norm-following trajectories. These findings illuminate the neural mechanisms in the cerebellum associated with detecting norm transgressions during social navigation, emphasizing the role of the posterior cerebellum in detecting and signaling deviations from anticipated sequences.
Performance of Outbreak Management Plans for Emerging Plant Diseases: The Case of Almond Leaf Scorch Caused by Xylella fastidiosa in Mainland Spain
Authors: Cendoya Martina , Lázaro Elena , Navarro-Quiles Ana , López-Quílez Antonio , Conesa David , Vicent Antonio 
Published: March 2024

Outbreak response to quarantine pathogens and pests in the European Union (EU) is regulated by the EU Plant Health Law, but the performance of outbreak management plans in terms of their effectiveness and efficiency has been quantified only to a limited extent. As a case study, the disease dynamics of almond leaf scorch, caused by Xylella fastidiosa, in the affected area of Alicante, Spain, were approximated using an individual-based spatial epidemiological model. The emergence of this outbreak was dated based on phylogenetic studies, and official surveys were used to delimit the current extent of the disease. Different survey strategies and disease control measures were compared to determine their effectiveness and efficiency for outbreak management in relation to a baseline scenario without interventions. One-step and two-step survey approaches were compared with different confidence levels, buffer zone sizes, and eradication radii, including those set by the EU legislation for X. fastidiosa. The effect of disease control interventions was also considered by decreasing the transmission rate in the buffer zone. All outbreak management plans reduced the number of infected trees (effectiveness), but large differences were observed in the number of susceptible trees not eradicated (efficiency). The two-step survey approach, high confidence level, and the reduction in the transmission rate increased the efficiency. Only the outbreak management plans with the two-step survey approach removed infected trees completely, but they required greater survey efforts. Although control measures reduced disease spread, surveillance was the key factor in the effectiveness and efficiency of the outbreak management plans. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Alcohol-Related Care Among Veterans With Unhealthy Alcohol Use: The Role of Long-Term Opioid Therapy Receipt
Authors: Joudrey Paul J. , Wang Melinda , DeRycke Eric , Williams Emily C. , Edelman Eva Jennifer 
Published: March 2024

Objectives
Long-term opioid therapy (LTOT) is potentially dangerous among patients with unhealthy alcohol use because of possible adverse interactions. We examined receipt of alcohol-related care among patients with unhealthy alcohol use receiving LTOT and without opioid receipt.

Methods
We use data collected from 2009 to 2017 in the Women Veterans Cohort Study, a national cohort of Veterans engaged in Veterans Health Administration care. We included patients who screened positive for unhealthy alcohol use (score ≥5) using the Alcohol Use Disorder Identification Consumption questionnaire. Our primary exposure was LTOT (receipt of prescribed opioids for ≥90 days) versus no opioid receipt at the time of the first positive Alcohol Use Disorder Identification Consumption. Our primary outcome was receipt of brief intervention within 14 days of positive alcohol screen. Unadjusted and 4 adjusted modified Poisson regression models assessed prevalence and relative rates (RRs) of outcomes.

Results
Among eligible veterans, 6222 of 113,628 (5.5%) received LTOT at screening. Among patients receiving LTOT, 67.5% (95% confidence interval [CI], 66.3%–68.6%) had a documented brief intervention within 14 days of positive screen, compared with 70.1% (95% CI, 69.8%–70.4%) among patients without opioid receipt (RR, 0.96; 95% CI, 0.95–0.98; P < 0.001). Within adjusted models, the rate of brief intervention among patients receiving LTOT remained lower than patients without opioid receipt.

Conclusions
Among patients with unhealthy alcohol use, patients receiving LTOT had significantly lower rates of brief intervention receipt compared with those without opioid receipt, and they should be a focus for interventions to improve alcohol-related care and safer opioid prescribing.
Artificial intelligence and machine learning in axial spondyloarthritis
Authors: Adams Lisa C. , Bressem Keno K. , Poddubnyy Denis 
Published: March 2024

Purpose of review
To evaluate the current applications and prospects of artificial intelligence and machine learning in diagnosing and managing axial spondyloarthritis (axSpA), focusing on their role in medical imaging, predictive modelling, and patient monitoring.

Recent findings
Artificial intelligence, particularly deep learning, is showing promise in diagnosing axSpA assisting with X-ray, computed tomography (CT) and MRI analyses, with some models matching or outperforming radiologists in detecting sacroiliitis and markers. Moreover, it is increasingly being used in predictive modelling of disease progression and personalized treatment, and could aid risk assessment, treatment response and clinical subtype identification. Variable study designs, sample sizes and the predominance of retrospective, single-centre studies still limit the generalizability of results.

Summary
Artificial intelligence technologies have significant potential to advance the diagnosis and treatment of axSpA, providing more accurate, efficient and personalized healthcare solutions. However, their integration into clinical practice requires rigorous validation, ethical and legal considerations, and comprehensive training for healthcare professionals. Future advances in artificial intelligence could complement clinical expertise and improve patient care through improved diagnostic accuracy and tailored therapeutic strategies, but the challenge remains to ensure that these technologies are validated in prospective multicentre trials and ethically integrated into patient care.
Machine Learning Identifies Higher Survival Profile In Extracorporeal Cardiopulmonary Resuscitation*
Authors: Crespo-Diaz Ruben , Wolfson Julian , Yannopoulos Demetris , Bartos Jason A. 
Published: March 2024

OBJECTIVES:
Extracorporeal cardiopulmonary resuscitation (ECPR) has been shown to improve neurologically favorable survival in patients with refractory out-of-hospital cardiac arrest (OHCA) caused by shockable rhythms. Further refinement of patient selection is needed to focus this resource-intensive therapy on those patients likely to benefit. This study sought to create a selection model using machine learning (ML) tools for refractory cardiac arrest patients undergoing ECPR.

DESIGN:
Retrospective cohort study.

SETTING:
Cardiac ICU in a Quaternary Care Center.

PATIENTS:
Adults 18–75 years old with refractory OHCA caused by a shockable rhythm.

METHODS:
Three hundred seventy-six consecutive patients with refractory OHCA and a shockable presenting rhythm were analyzed, of which 301 underwent ECPR and cannulation for venoarterial extracorporeal membrane oxygenation. Clinical variables that were widely available at the time of cannulation were analyzed and ranked on their ability to predict neurologically favorable survival.

INTERVENTIONS:
ML was used to train supervised models and predict favorable neurologic outcomes of ECPR. The best-performing models were internally validated using a holdout test set.

MEASUREMENTS AND MAIN RESULTS:
Neurologically favorable survival occurred in 119 of 301 patients (40%) receiving ECPR. Rhythm at the time of cannulation, intermittent or sustained return of spontaneous circulation, arrest to extracorporeal membrane oxygenation perfusion time, and lactic acid levels were the most predictive of the 11 variables analyzed. All variables were integrated into a training model that yielded an in-sample area under the receiver-operating characteristic curve (AUC) of 0.89 and a misclassification rate of 0.19. Out-of-sample validation of the model yielded an AUC of 0.80 and a misclassification rate of 0.23, demonstrating acceptable prediction ability.

CONCLUSIONS:
ML can develop a tiered risk model to guide ECPR patient selection with tailored arrest profiles.
Defining Spatial Epidemiology: A Systematic Review and Re-orientation
Authors: Morrison Christopher N. , Mair Christina F. , Bates Lisa , Duncan Dustin T. , Branas Charles C. , Bushover Brady R. , Mehranbod Christina A. , Gobaud Ariana N. , Uong Stephen , Forrest Sarah , Roberts Leah , Rundle Andrew G. 
Published: March 2024

Background:
Spatial epidemiology has emerged as an important subfield of epidemiology over the past quarter century. We trace the origins of spatial epidemiology and note that its emergence coincided with technological developments in spatial statistics and geography. We hypothesize that spatial epidemiology makes important contributions to descriptive epidemiology and analytic risk-factor studies but is not yet aligned with epidemiology’s current focus on causal inference and intervention.

Methods:
We conducted a systematic review of studies indexed in PubMed that used the term “spatial epidemiolog*” in the title, abstract, or keywords. Excluded articles were not written in English, examined disease in animals, or reported biologic pathogen distribution only. We coded the included papers into five categories (review, demonstration of method, descriptive, analytic, and intervention) and recorded the unit of analysis (i.e., individual vs. ecological). We additionally examined articles coded as analytic ecologic studies using scales for lexical content.

Results:
A total of 482 articles met the inclusion criteria, including 76 reviews, 117 demonstrations of methods, 122 descriptive studies, 167 analytic studies, and 0 intervention studies. Demonstration studies were most common from 2006 to 2014, and analytic studies were most common after 2015. Among the analytic ecologic studies, those published in later years used more terms relevant to spatial statistics (incidence rate ratio =1.3; 95% confidence interval [CI] = 1.1, 1.5) and causal inference (incidence rate ratio =1.1; 95% CI = 1.1, 1.2).

Conclusions:
Spatial epidemiology is an important and growing subfield of epidemiology. We suggest a re-orientation to help align its practice with the goals of contemporary epidemiology.
Genetic variation in severe cystic fibrosis liver disease is associated with novel mechanisms for disease pathogenesis
Authors: Stonebraker Jaclyn R. , Pace Rhonda G. , Gallins Paul J. , Dang Hong , Aksit Melis A. , Faino Anna V. , Gordon William W. , MacParland Sonya , Bamshad Michael J. , Gibson Ronald L. , Cutting Garry R. , Durie Peter R. , Wright Fred A. , Zhou Yi-Hui , Blackman Scott M. , O’Neal Wanda K. , Ling Simon C. , Knowles Michael R. 
Published: March 2024

Background and Aims:
It is not known why severe cystic fibrosis (CF) liver disease (CFLD) with portal hypertension occurs in only ~7% of people with CF. We aimed to identify genetic modifiers for severe CFLD to improve understanding of disease mechanisms.

Approach and Results:
Whole-genome sequencing was available in 4082 people with CF with pancreatic insufficiency (n = 516 with severe CFLD; n = 3566 without CFLD). We tested ~15.9 million single nucleotide polymorphisms (SNPs) for association with severe CFLD versus no-CFLD, using pre-modulator clinical phenotypes including (1) genetic variant (SERPINA1; Z allele) previously associated with severe CFLD; (2) candidate SNPs (n = 205) associated with non-CF liver diseases; (3) genome-wide association study of common/rare SNPs; (4) transcriptome-wide association; and (5) gene-level and pathway analyses. The Z allele was significantly associated with severe CFLD (p = 1.1 × 10−4). No significant candidate SNPs were identified. A genome-wide association study identified genome-wide significant SNPs in 2 loci and 2 suggestive loci. These 4 loci contained genes [significant, PKD1 (p = 8.05 × 10−10) and FNBP1 (p = 4.74 × 10−9); suggestive, DUSP6 (p = 1.51 × 10−7) and ANKUB1 (p = 4.69 × 10−7)] relevant to severe CFLD pathophysiology. The transcriptome-wide association identified 3 genes [CXCR1 (p = 1.01 × 10−6), AAMP (p = 1.07 × 10−6), and TRBV24 (p = 1.23 × 10−5)] involved in hepatic inflammation and innate immunity. Gene-ranked analyses identified pathways enriched in genes linked to multiple liver pathologies.

Conclusion:
These results identify loci/genes associated with severe CFLD that point to disease mechanisms involving hepatic fibrosis, inflammation, innate immune function, vascular pathology, intracellular signaling, actin cytoskeleton and tight junction integrity and mechanisms of hepatic steatosis and insulin resistance. These discoveries will facilitate mechanistic studies and the development of therapeutics for severe CFLD.
Obstacles to Screening Today
Authors: Quigley Harry A. 
Published: March 2024

Purpose:
To introduce a discussion of glaucoma screening.

Methods/Results:
Glaucoma screening faces challenges, including not satisfying important ethical principles for medical screening.

Conclusions:
Approaches that would better provide care for glaucoma patients include eliminating the loss of follow-up and identifying glaucoma among family members of known glaucoma patients.
A Phase Three Study of the Safety and Immunogenicity of a Four-dose Series of 20-Valent Pneumococcal Conjugate Vaccine in Healthy Infants
Authors: Senders Shelly , Klein Nicola P. , Tamimi Noor , Thompson Allison , Baugher Gary , Trammel James , Peng Yahong , Giardina Peter , Scully Ingrid L. , Pride Michael , Center Kimberly J. , Gruber William C. , Scott Daniel A. , Watson Wendy 
Published: March 2024

Background:
The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend pneumococcal disease protection beyond 13-valent PCV (PCV13).

Methods:
This phase 3, double-blind study conducted in the United States/Puerto Rico evaluated PCV20 safety and immunogenicity. Healthy infants were randomized to receive a 4-dose series of PCV20 or PCV13 at 2, 4, 6 and 12–15 months old. Objectives included demonstrating noninferiority (NI) of PCV20 to PCV13 immunoglobulin G (IgG) geometric mean concentrations after doses 3 and 4 and percentages of participants with predefined IgG concentrations after dose 3, with 7 additional PCV20 serotypes compared with the lowest result among vaccine serotypes in the PCV13 group. Safety assessments included local reactions, systemic events, adverse events, serious adverse events and newly diagnosed chronic medical conditions.

Results:
Overall, 1991 participants were vaccinated (PCV20, n = 1001; PCV13, n = 990). For IgG geometric mean concentrations 1 month after both doses 3 and 4, all 20 serotypes met NI criteria (geometric mean ratio lower 2-sided 95% confidence interval > 0.5). For percentages of participants with predefined IgG concentrations after dose 3, NI (percentage differences lower 2-sided 95% confidence interval > –10%) was met for 8/13 matched serotypes and 6/7 additional serotypes; 4 serotypes missed the statistical NI criterion by small margins. PCV20 also elicited functional and boosting responses to all 20 serotypes. The safety profile of PCV20 was similar to PCV13.

Conclusion:
A 4-dose series of PVC20 was well tolerated and elicited robust serotype-specific immune responses expected to help protect infants and young children against pneumococcal disease due to the 20 vaccine serotypes. Clinical trial registration: NCT04382326.
The Covid-19 Pandemic and The Future of Work
Authors: Ezeilo Chidimma Ogechukwu , Green-McKenzie Judith 
Published: March 2024

Introduction
The “future of work” refers to workplace modifications projected to occur following large scale events impacting workforce health and safety such as pandemics, technological advancements, or economic shifts. This paper examines the influence of the COVID-19 pandemic on the future of work.

Methods
The electronic databases PubMed, Google Scholar, and Scopus were explored using search terms such as “post-pandemic,” “working force,” and “future of work” to retrieve papers published between 2000 and 2023.

Results
The main characteristics of the future of work modification revealed are blurring of work-home boundaries, increase in telework and the gig economy, demand for artificial intelligence, smart working, quiet hiring, diversity and inclusion, and algocratic governance. Needed skills include virtual collaboration capability, cross-cultural competency, computational thinking, news media literacy, transdisciplinarity, sense making, and focusing on mental health and well-being.

Conclusions
Organizations are remodeling workforces to meet employee, employer, regulatory, and market expectations to adapt to future workplace needs.