bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current opinion: an overview of sickle cell disease and chronic pain and perioperative considerations
Authors: Akintunde Dolapo , Ezihe-Ejiofor Ada , Ogbah Janefrances , Oso Tolulope 
Published: February 2025

Purpose
This review aims to provide the practicing anesthesiologist with information on the pathophysiology, physiology, and management of patients with sickle cell disease. This includes the evaluation of common intraoperative management issues as well as perioperative concerns related to the disease. This review will also discuss the outpatient care of sickle cell patients concerning disease-modifying agents and chronic pain management.

Recent findings
There has been less funding for research on sickle cell disease and a relative deficit in treatment options for patients and their vaso-occlusive crises (VOC). In the chronic pain setting, adjuvants to therapy have been utilized, such as anti-inflammatories, neuropathic agents, and antihistamines; however, the mainstay of therapy for pain crises is the use of opioids. New medications for the treatment of VOCs include crinaluzimab and L-glutamine. In terms of intraoperative management, it is imperative to maintain homeostasis for the patients, and research does not show a benefit in preoperative blood transfusions when not clinically indicated.

Summary
The sociopolitical context and pathophysiology of sickle cell disease make it a unique disease to manage for the practicing anesthesiologist. Tailoring management via developing a patient-specific approach to maintain homeostasis and minimize the perioperative prevalence of VOCs.
Parity, Age at Childbirth, and Later-Life Maternal Cardiovascular Disease in Postmenopausal Women in the Women's Health Initiative Study
Authors: Xing Zailing , Kirby Russell S. , Chen Henian , Cain Mary Ashley , Alman Amy C. 
Published: February 2025

OBJECTIVE:
To examine the associations of parity and age at childbirth with maternal cardiovascular disease (CVD).

METHODS:
The data were from the Women's Health Initiative (1993–2022), involving postmenopausal women aged 49–81 years without existing CVD. The exposures were parity, age at first childbirth, and age at last childbirth, all referring to pregnancy lasting at least 6 months. The outcome was incident CVD events, defined as the initial occurrence of coronary heart disease, heart failure, ischemic stroke, or death due to these conditions. We employed propensity score matching to generate matched samples, aligning each exposure group with a reference group according to their propensity scores. We used multilevel Cox proportional hazard models to calculate hazard ratios (HRs) and 95% CIs to estimate the associations among parity, age at childbirth, and CVD. We performed multiple mediation analyses to assess the effect of potential mediators on the associations.

RESULTS:
Compared with parity of two, there was no significant association between other parity levels and later-life maternal CVD. Compared with age at first childbirth of 25–29 years, the HRs (95% CIs) for the association between CVD and age at first childbirth was 1.32 (1.22–1.44) for individuals younger than age 20 years, 1.11 (1.05–1.17) for those aged 20–24 years, 1.03 (0.93–1.13) for those aged 30–34 years, and 0.93 (0.79–1.11) for those aged 35 years or older. When age at last childbirth was younger than 25 years, 30–34 years, 35–39 years, and 40 years or older, the HRs (95% CIs) for CVD were 1.02 (0.94–1.10), 1.05 (0.99–1.10), 1.10 (1.03–1.18), and 1.09 (0.96–1.24), respectively. In multiple mediation analyses, we identified the potential mediation pathway of age at first childbirth younger than 25 years→premature menopause→hypertension→CVD.

CONCLUSION:
Young age at first childbirth was associated with increased maternal CVD risk. Preventing premature menopause and hypertension may be important ways to lower the risk for postmenopausal women.
Diagnostic Stewardship of Endotracheal Aspirate Cultures in Hospitalized Children With Artificial Airways: Expert Consensus Statements From the BrighT STAR (Testing STewardship for Antibiotic Reduction) Respiratory Collaborative
Authors: Sick-Samuels Anna C. , Kelly Daniel P. , Woods-Hill Charlotte Z. , Arthur Abigail , Kumar Urmi , Koontz Danielle W. , Marsteller Jill A. , Milstone Aaron M. ,   and the BrighT STAR (Testing STewardship for Antibiotic Reduction) Respiratory Consensus Authorship group
Published: February 2025

Objective:
To develop consensus statements that clinicians can apply to standardize and optimize endotracheal aspirate culture (EAC) practices in hospitalized children with artificial airways who are being evaluated for a bacterial lower respiratory tract infection (LRTI).

Design:
A modified Delphi consensus process with expert panelists. Panelists conducted a “pre-survey” to itemize respiratory signs of bacterial LRTI. Round 1 included a literature summary and electronic survey of 50 potential statements sent to all panelists. We surveyed panelist opinions using a 5-point Likert scale. We grouped the responses “agree” and “strongly agree” as agreement. Consensus was defined as statements reaching greater than 75% agreement. Round 2 was moderated by an independent expert in consensus methodology. Panelists convened in person in November 2023, discussed any statements not reaching consensus or statements with disagreement, were resurveyed, and finalized statements in real time.

Setting:
Electronic surveys and in-person meetings in Baltimore, MD.

Subjects:
The BrighT STAR (Testing STewardship for Antibiotic Reduction) collaborative along with U.S.-based pediatric experts in critical care, cardiac critical care, infectious diseases, hospital medicine, otolaryngology, pulmonology, and clinical microbiology.

Interventions:
None.

Measurements and Main Results:
Thirty-eight of 40 invited panelists completed round 1. Of 50 initial statements, 28 reached greater than 90% agreement, 16 had 75–89% agreement, and 6 had less than 75% agreement. Twenty-eight statements were finalized. Round 2 involved 37 panelists: 23 statements were discussed, of which 17 reached an agreement and 6 did not reach consensus. We concluded with 30 statements and 15 sub-statements, 37 of which had greater than 90% agreement. Final statements informed a clinical decision support algorithm.

Conclusions:
The BrighT STAR collaborative group achieved consensus for 45 clinical practice statements that can standardize EAC practices, including indications to consider for testing, reasons to defer, optimal specimen collection, and result interpretation. These statements offer a starting point for clinical decision support tools and diagnostic stewardship programs for EAC practices in patients with artificial airways.
Long-Term Cytoreduction Outcomes With or Without Heated Intraperitoneal Chemotherapy (HIPEC) For Colorectal Peritoneal Metastases
Authors: White Michael G , Smith Paula Marincola , Bhutiani Neal , Helmink Beth , Galbraith Norman , Kopetz Scott , Overman Michael , Mansfield Paul , Fournier Keith , Uppal Abhineet 
Published: February 2025

Background:
Patients with peritoneal metastases (PM) from colorectal adenocarcinoma(CRC) benefit from cytoreductive surgery(CRS). The role of HIPEC, however, remains unclear. We studied associations between HIPEC, peritoneal disease-free survival (PDFS), and overall survival(OS) in CRC patients undergoing CRS.

Study Design:
All CRC patients undergoing CRS between 2008 and 2023 were retrospectively identified at our center. Patient clinicodemographic factors were determined by chart review. OS and PDFS were evaluated using the Kaplan-Meier method. Associations between clinical factors and survival were determined using Cox proportional hazard models.

Results:
One hundred forty-seven patients were identified with 24.5-month median follow-up. Most patients (111,75.5%) had a low PCI (<11), while 36 patients (24.5%) had high PCI(≥11). Eighty-three (55.8%) patients had CRS alone. Sixty-four patients underwent CRS with HIPEC (42(66%) MMC, 19(30%) OX, 3(4.7%) CIS). Median OS was 59.8 (95%CI:41.7-83.0) months. Median PDFS was 13.3 (95%CI:10.4-18.5) months. OS was equivalent comparing HIPEC with MMC, HIPEC with OX (HR 0.49, 95%CI: 0.22-1.09, p=0.08), and CRS alone (HR 0.74, 95%CI:0.41-1.32, p=0.31). Multivariable analysis showed only PCI was associated with OS (HR 1.08, 95%CI:1.03-1.14, p=0.003). Low PCI patients had similar PDFS after CRS/HIPEC (HR 1.07, 95%CI:0.61-1.87, p=0.814) compared to CRS alone. High PCI patients had improved OS comparing CRS/HIPEC to CRS (MMC: HR 0.17, 95%CI:0.04-0.76, p=0.02; OX: HR 0.048, 95%CI:0.006-0.37, p=0.004).

Conclusion:
HIPEC was not associated with OS or PDFS in patients with PCI≤10 but was associated with improved OS and PDFS in patients with PCI≥11. Use of HIPEC for high PCI may be warranted, though randomized prospective data is needed to confirm this.
Geometric Protein Optimization
Authors: Wirtz Dario , Horn Claus 
Published: February 2025

AbstractThe vastness of the space of possible protein variations is often regarded an insurmountable challenge for effective optimization. Traditional approaches focus primarily on substitutions near the binding pocket but are frequently hindered by epistatic effects and non-convex optimization landscapes. Current AI-aided methods can accelerate laboratory procedures but largely target the same substitutions. Here, we propose a complementary approach, Geometric Protein Optimization (GPO), an AI-native framework that fine-tunes the global geometry of the protein by combining a large number of substitutions from diverse locations along the sequence. GPO leverages the strong inverse power-law dependence of electrostatic forces where small adjustments can have large effects on binding affinity. We make the surprising discovery that the inclusion of distal substitutions leads to a smoother and approximately separable optimization landscape. Our empirical investigations reveal three stylized facts about this landscape that we use as a guide to develop BuildUp, a baseline algorithm for GPO. Results show that it is able to navigate this landscape much more effectively and achieve significant improvements in in silico binding affinity (Kd) across diverse protein-ligand complexes. Evaluations of the derived variants through protein-ligand interaction profiling, docking simulations, and molecular dynamics simulations confirm that GPO can achieve beneficial effects even with a sequence-based scoring function.
Impact of Dexmedetomidine on the Prognosis of Patients with Sepsis-Induced Myocardial Injury: A Retrospective Cohort Study
Authors: Xinyi Zhang , Xiaoyan Guo , Zhongxing Zhao , Wei Li , Huaiyu Chen , Hongyan Li , Jiandong Lin , Mingrui Lin 
Published: February 2025

AbstractBackgroundSepsis-Induced Myocardial Injury (SIMI) is a serious complication with high in-hospital and 28-day mortality. Dexmedetomidine (DEX), a selective α2-adrenergic receptor agonist, has shown anti-inflammatory and cardioprotective effects, but its impact on SIMI prognosis is unclear.MethodsThis retrospective study used the MIMIC-IV database, including SIMI patients diagnosed per Sepsis-3 criteria. Propensity score matching (PSM) balanced baseline characteristics, and Cox regression analyzed the association between DEX use and mortality outcomes. External validation was performed using the MIMIC-III database.ResultsAmong 3,921 SIMI patients (375 DEX, 3,546 non-DEX), DEX use showed a trend toward lower 28-day mortality (HR 0.49, 95% CI 0.23–1.05, p = 0.068) and in-hospital mortality (HR 0.45, 95% CI 0.20–1.02, p = 0.055). After PSM, mortality remained lower in the DEX group. ICU and hospital stays were longer in the DEX group, but CRRT use showed no significant differences. External validation confirmed these findings.ConclusionDEX use may reduce 28-day and in-hospital mortality in SIMI patients, providing preliminary evidence for its potential benefits. Further large-scale studies are needed to confirm these results.
The ClinGen Severe Combined Immunodeficiency Disease Variant Curation Expert Panel: Specifications for classification of variants inADA,DCLRE1C,IL2RG,IL7R,JAK3,RAG1, andRAG2
Authors: Jacovas Vanessa C. , Zelnick Michelle , McNulty Shannon , Ross Justyne E. , Khurana Namrata , Pan Xueyang , Nieto Alejandro , Martin Shiloh , McLean Benjamin , Elnagheeb Marwa A. , Cowan Morton J. , Puck Jennifer M. , Hershfield Mike , Verbsky James , Walter Jolan , Allenspach Eric , Chan Alice Y. , van Oers Nicolai S. C. , Ghosh Rajarshi , Piazza Megan , Yuan Bo , Notarangelo Luigi D. , Johnson Britt A. , Chinn Ivan K. 
Published: February 2025

ABSTRACTPurposeThis collaborative study, led by the Clinical Genome Resource Severe Combined Immunodeficiency Disease Variant Curation Expert Panel (ClinGen SCID-VCEP), implemented and adapted the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for interpreting germline variants in genes with established relationships to SCID. The effort focused on the 7 most common SCID-related genes identified by SCID newborn screening in North America:ADA,DCLRE1C,IL2RG,IL7R,JAK3,RAG1, andRAG2.MethodsThe SCID-VCEP conducted a rigorous review of variants that involved database analyses, literature review, and expert feedback to derive gene-specific modifications to the ACMG/AMP guidelines. These specifications were validated using a pilot set of 90 variants.Results:Of these 90 variants, 25 were classified as pathogenic, 21 as likely pathogenic, 14 as variants of uncertain significance (VUS), 18 as likely benign, and 12 as benign. Seventeen variants with conflicting classifications in ClinVar were successfully resolved. The criteria included modifications to 20 of the 28 original ACMG/AMP criteria specific to SCID-related genes.ConclusionThe SCID-specific variant curation guidelines developed by the SCID-VCEP will enhance the precision of SCID genetic diagnosis and provide a robust framework for interpreting variants in SCID-related genes, contributing to appropriate treatment of SCID.
Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: Results from EMBRACE
Authors: Mavaddat Nasim , Frost Debra , Zhao Emily , Barnes Daniel R , Ahmed Munaza , Barwell Julian , Brady Angela F , Brennan Paul , Conti Hector , Cook Jackie , Copeland Harriet , Davidson Rosemarie , Donaldson Alan , Douglas Emma , Gallagher David , Hart Rachel , Izatt Louise , Kemp Zoe , Lalloo Fiona , Miedzybrodzka Zosia , Morrison Patrick J , Murray Jennie E. , Murray Alex , Musgrave Hannah , Searle Claire , Side Lucy , Snape Katie , Tripathi Vishakha , Walker Lisa , Archer Stephanie , Evans D. Gareth , Tischkowitz Marc , Antoniou Antonis C , Easton Douglas F. 
Published: February 2025

ABSTRACTBackgroundCarriers of germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are at higher risk of developing breast and ovarian cancer than the general population. It is unclear if these PVs influence other breast or ovarian cancer risk factors, including age at menopause (ANM), age at menarche (AAM), menstrual cycle length, BMI or height. There is a biological rationale for associations between BRCA1 and BRCA2 PVs and reproductive and anthropomorphic traits, for example involving DNA damage and repair mechanisms. The evidence for or against such associations is limited.MethodsWe used data on 3,046 BRCA1 and 3,264 BRCA2 PV carriers, and 2,857 non-carrier female relatives of PV carriers from the Epidemiological Study of Familial Breast Cancer (EMBRACE). Associations between ANM and PV carrier status was evaluated using linear and Cox regression models allowing for censoring. AAM, menstrual cycle length, BMI, and height in carriers and non-carriers were compared using linear and multinomial logistic regression. Analyses were adjusted for potential confounders, and weighted analyses carried out to account for non-random sampling with respect to cancer status.ResultsNo statistically significant difference in ANM between carriers and non-carriers was observed in analyses accounting for censoring. Linear regression effect sizes for ANM were - -0.002 (95%CI: -0.401, 0.397) and -0.172 (95%CI: -0.531, 0.188), for BRCA1 and BRCA2 PV carriers respectively, compared with non-carrier women. The distributions of AAM, menstrual cycle length and BMI were similar between PV carriers and non-carriers, but BRCA1 PV carriers were slightly taller on average than non-carriers (0.5cm difference, p=0.003).ConclusionContrary to previous reports, we found no evidence that BRCA1 or BRCA2 PV are associated with hormonal or anthropometric factors, except for a weak association with height. These results inform the incorporation of risk factors into multifactorial cancer risk prediction algorithms.
Modelling the Dynamics of SARS-CoV-2 during early phase of infection
Authors: Xu Jingsi , López-García Martín , House Thomas , Hall Ian 
Published: February 2025

AbstractInterpreting viral mechanism of SARS-CoV-2 based on human body level is critical for developing more efficient interventions. Due to the limitation of data, limited models consider the viral dynamics of early phase of infection. The Human Challenge Study Killingley et al. (2022) enables us to garner data from the inoculation to the 14th day after the infection, which provides an overview of the SARS-CoV-2 within host infection dynamics. In the Human Challenge Study, each volunteer was inoculated with 10TCID50, approximately 55PFU, of a wild type of virus (Killingley et al. (2022)), and the data indicates that the viral load reduced below the detectable level within a day.The simplified within host models developed by Xu et al. (2023) explain the data from the Human Challenge Study (Killingley et al. (2022)). However, they do not explain the viral decay from Day 0 to Day 1. Hence, in this paper, we aim to develop a new viral mechanism to explain this phenomenon. Based on the simplified within host models developed by Xu et al. (2023), we consider that the virus will first go through an adjustment phase and then start to replicate. A new dose-response model is developed to evaluate the probability of infection by constructing a boundary problem. We will discuss this viral mechanism and fit the model to the data of the Human Challenge Study (Killingley et al. (2022)) by adopting AMC-SMC (approximate Bayesian computation-sequential Monte Carlo). Based on the results of parameter inference, we estimate that the adjusted viral load is around 1% of the inoculated viral load.
Return to work outcomes in solid organ transplant recipients: a protocol for a global scoping review
Authors: Pereira Vinícius Araújo , Martinez William Donegá , dos Santos-Neto Martins Fideles , Molina Thaysa Castro , Duca William José , Arroyo-Júnior Paulo César , Fortunato Allana C. , Pires Sciarra Adília Maria , Stefani Andressa Karina , Quitério Alex Bertolazzo , Lopes Sônia Maria Maciel , Lopes Luiz Otávio Maciel , Lázaro Lucian Borges , Custódio Flávia Cristina , de Almeida Bistafa Isabela Amaral , Rocha José Nathan Fernandes , De Souza Menezes João Daniel , da Silva Matheus Querino , dos Santos Emerson Roberto , Borges Licia Paula Schelbauer , Silva Gabriela Gouvea , Del Arco Paschoal Vania , Bianchin Maysa Alahmar , Spessoto Luís Cesar Fava , Caldas Heloísa Cristina , Facio Júnior Fernando Nestor , André Júlio César , da Silva Renato Ferreira 
Published: February 2025

AbstractSolid organ transplantation treats end-stage organ failure, improving longevity and quality of life. Return to work post-transplant is a positive indicator of treatment success. However, labor is influenced by multiple biopsychosocial factors, leading to complex barriers that affect recipients’ opportunities. Mapping return-to-work literature may reveal gaps in conceptualization, instruments, analyses, and key determinants. Following Joanna Briggs Institute methodology, this protocol aims to identify knowledge gaps and map the processes and outcomes in the literature on return to work after liver, kidney, heart, and lung transplantation. Following the Population, Concept, and Context strategy, this review is guided by the research question: “What has the literature shown about return to work after solid organ transplantation?”. This protocol was created and recorded on the Open Science Framework under DOI10.17605/OSF.IO/Q6HVT. Database selection and search strategy were determined by a librarian specializing in health sciences. The literature search will be conducted in PubMed, Scopus, EMBASE, LILACS, and Web of Science databases. Eligible studies include primary and secondary research, systematic reviews, meta-analyses, clinical trials, case studies, and observational studies on return-to-work post-transplant, in English or Portuguese, with no time restrictions. Two reviewers will independently perform the selection and data extraction. Discrepancies will be resolved through consensus, with a third researcher addressing conflicts. The data will be extracted using a standardized form developed for this review to collect key details about the studies’ origin, context, purpose, content, population, and variables related to the return-to-work process. These data will be synthesized following Synthesis Without Meta Analysis guidelines and summarized narratively using tables, graphs, thematic analysis, and, if feasible, a meta-analysis will be conducted. This scoping review protocol relies solely on publicly available data and does not involve human participants, so institutional review board approval was unnecessary. Ethical aspects of included studies will be assessed in our analysis.