bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of machine learning models predicting mortality using routinely collected observational health data from 0-59 months old children admitted to an intensive care unit in Bangladesh: critical role of biochemistry and haematology data
Authors: Das Subhasish , Erdman Lauren , Brals Daniella , Boczek Bartlomiej , Hasan S M Tafsir , Massara Paraskevi , Alam Md Ashraful , Fahim Shah Mohammad , Mahfuz Mustafa , Hoogendoorn Mark , Zuiderent-Jerak Teun , Bandsma Robert H J , Ahmed Tahmeed , Voskuijl Wieger 
Published: July 2024

IntroductionTreatment in the intensive care unit (ICU) generates complex data where machine learning (ML) modelling could be beneficial. Using routine hospital data, we evaluated the ability of multiple ML models to predict inpatient mortality in a paediatric population in a low/middle-income country.MethodWe retrospectively analysed hospital record data from 0-59 months old children admitted to the ICU of Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. Five commonly used ML models- logistic regression, least absolute shrinkage and selection operator, elastic net, gradient boosting trees (GBT) and random forest (RF), were evaluated using the area under the receiver operating characteristic curve (AUROC). Top predictors were selected using RF mean decrease Gini scores as the feature importance values.ResultsData from 5669 children was used and was reduced to 3505 patients (10% death, 90% survived) following missing data removal. The mean patient age was 10.8 months (SD=10.5). The top performing models based on the validation performance measured by mean 10-fold cross-validation AUROC on the training data set were RF and GBT. Hyperparameters were selected using cross-validation and then tested in an unseen test set. The models developed used demographic, anthropometric, clinical, biochemistry and haematological data for mortality prediction. We found RF consistently outperformed GBT and predicted the mortality with AUROC of ≥0.87 in the test set when three or more laboratory measurements were included. However, after the inclusion of a fourth laboratory measurement, very minor predictive gains (AUROC 0.87 vs 0.88) resulted. The best predictors were the biochemistry and haematological measurements, with the top predictors being total CO2, potassium, creatinine and total calcium.ConclusionsMortality in children admitted to ICU can be predicted with high accuracy using RF ML models in a real-life data set using multiple laboratory measurements with the most important features primarily coming from patient biochemistry and haematology.
Disability and long-term breathlessness: a cross-sectional, population study
Authors: Kochovska Slavica , Ferreira Diana , Chang Sungwon , Brunelli Vanessa , Morgan Deidre , Similowski Thomas , Johnson Miriam , Ekström Magnus , Currow David 
Published: July 2024

IntroductionDisability, resulting from altered interactions between individuals and their environment, is a worldwide issue causing inequities and suffering. Many diseases associated with breathlessness cause disability but the relationship between disability and the severity of breathlessness itself is unknown.This study evaluated associations between disability using the WHO’s Disability Assessment Schedule (WHODAS) 2.0 and levels of long-termbreathlessness limiting exertion.MethodsThis population-based, cross-sectional online survey (n=10 033) reflected the most recent national census (2016) by age, sex, state/territory of residence and rurality. Assessments included self-reported disability (WHODAS 2.0 12-item (range 12 (no disability) to 60 (most severe disability)) assessed in 6 domains) and long-termbreathlessness limiting exertion(modified Medical Research Council (mMRC) breathlessness scale; 0–4 (4—most severe)). Days in the last month affected by breathlessness were reported.ResultsOf respondents (52% women; mean age 45), mean total disability score was 20.9 (SD 9.5). 42% (n=4245) had mMRC >0 (mMRC1 31% (n=3139); mMRC2 8% (n=806); mMRC3,4 3% (n=300)). Every level of long-termbreathlessness limiting exertionwas associated with greater levels of disability (total p <0.001; each domain p <0.001). The most compromised domains wereMobilityandParticipation.In the last 30 days, people with severe breathlessness (mMRC 3–4): experienced disability (20 days); reduced activities/work (10 days); and completely forwent activities (another 5 days).ConclusionsDisability should be in the definition of persistent breathlessness as it is systematically associated with long-termbreathlessness limiting exertionin a grade-dependent, multidimensional manner. Disability should be assessed in people with long-term breathlessness to optimise their social well-being and health.
Circulating T cell status and molecular imaging may predict clinical benefit of neoadjuvant PD-1 blockade in oral cancer
Authors: Wondergem Niels E , Miedema Iris H C , van de Ven Rieneke , Zwezerijnen Gerben J C , de Graaf Pim , Karagozoglu K Hakki , Hendrickx Jan-Jaap , Eerenstein Simone E J , Bun Rolf J , Mulder Dorien C , Voortman Jens , Boellaard Ronald , Windhorst Albert D , Hagers J Pascal , Peferoen Laura A N , de Gruijl Tanja D , Bloemena Elisabeth , Brakenhoff Ruud H , Leemans C René , Menke-van der Houven van Oordt C Willemien 
Published: July 2024

BackgroundAddition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome.MethodsIn this study, 16 evaluable patients with stage III/IV oral cancer were treated with one dose of 480 mg nivolumab 3 weeks prior to surgery. Primary objectives were safety, feasibility, and suitability of programmed death receptor ligand-1 positron emission tomography (PD-L1 PET) as a biomarker for response. Imaging included18F-BMS-986192 (PD-L1) PET and18F-fluorodeoxyglucose (FDG) PET before and after nivolumab treatment. Secondary objectives included clinical and pathological response, and immune profiling of peripheral blood mononuclear cells (PBMCs) for response prediction. Baseline tumor biopsies and postnivolumab resection specimens were evaluated by histopathology.ResultsGrade III or higher adverse events were not observed and treatment was not delayed in relation to nivolumab administration and other study procedures. Six patients (38%) had a pathological response, of whom three (19%) had a major (≥90%) pathological response (MPR). Tumor PD-L1 PET uptake (quantified using standard uptake value) was not statistically different in patients with or without MPR (median 5.3 vs 3.4). All major responders showed a significantly postnivolumab decreased signal on FDG PET. PBMC immune phenotyping showed higher levels of CD8+T cell activation in MPR patients, evidenced by higher baseline expression levels of PD-1, TIGIT, IFNγ and lower levels of PD-L1.ConclusionTogether these data support that neoadjuvant treatment of advanced-stage oral cancers with nivolumab was safe and induced an MPR in a promising 19% of patients. Response was associated with decreased FDG PET uptake as well as activation status of peripheral T cell populations.
Non-cigarette tobacco products, aryl-hydrocarbon receptor repressor gene methylation and smoking-related health outcomes
Authors: Eckhardt Christina M , Balte Pallavi , Morris Jack E , Bhatt Surya P , Couper David , Fetterman Jessica , Freedman Neal , Jacobs David R , Hou Lifang , Kalhan Ravi , Liu Yongmei , Loehr Laura , Lutsey Pamela L , Schwartz Joseph E , White Wendy , Yende Sachin , London Stephanie J , Sanchez Tiffany R , Oelsner Elizabeth C 
Published: July 2024

Introduction
Cigarette smoking leads to altered DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) gene. However, it remains unknown whether pipe or cigar smoking is associated with AHRR methylation. We evaluated associations of non-cigarette tobacco use with AHRR methylation and determined if AHRR methylation was associated with smoking-related health outcomes.

Methods
Data were pooled across four population-based cohorts that enrolled participants from 1985 to 2002. Tobacco exposures were evaluated using smoking questionnaires. AHRR cg05575921 methylation was measured in peripheral blood leucocyte DNA. Spirometry and respiratory symptoms were evaluated at the time of methylation measurements and in subsequent visits. Vital status was monitored using the National Death Index.

Results
Among 8252 adults (mean age 56.7±10.3 years, 58.1% women, 40.6% black), 4857 (58.9%) participants used cigarettes and 634 (7.7%) used non-cigarette tobacco products. Exclusive use of non-cigarette tobacco products was independently associated with lower AHRR methylation (−2.44 units, 95% CI −4.42 to −0.45), though to a lesser extent than exclusive use of cigarettes (−6.01 units, 95% CI −6.01 to −4.10). Among participants who exclusively used non-cigarette tobacco products, reduced AHRR methylation was associated with increased respiratory symptom burden (OR 1.60, 95% CI 1.03 to 2.68) and higher all-cause mortality (log-rank p=0.02).

Conclusion
Pipe and cigar smoking were independently associated with lower AHRR methylation in a multiethnic cohort of US adults. Among users of non-cigarette tobacco products, lower AHRR methylation was associated with poor respiratory health outcomes and increased mortality. AHRR methylation may identify non-cigarette tobacco users with an increased risk of adverse smoking-related health outcomes.
Constraints on Tsallis cosmology using recent low and high redshift measurements
Authors: Mendoza-Martínez M. L. , Cervantes-Contreras A. , Trejo-Alonso J. J. , Hernandez-Almada A. 
Published: July 2024

AbstractRecently Tsallis cosmology has been presented as a novel proposal for alleviating both $$H_0$$

H
0

and $$\sigma _8$$

σ
8

tensions. Hence a universe filled with matter and radiation as perfect fluids and considering the Tsallis entropy is confronted using recent cosmological measurements coming from cosmic chronometers, type Ia supernovae, hydrogen II galaxies, quasars, and baryon acoustic oscillations. Following a Bayesian Markov Chain Monte Carlo analysis and combining the samples, we constrain the main characteristic parameters $$\alpha = 1.031^{+0.054}_{-0.051}$$

α
=
1
.

031

-
0.051

+
0.054

and $$\delta = 1.005^{+0.001}_{-0.001}$$

δ
=
1
.

005

-
0.001

+
0.001

where the uncertainties are $$1\sigma $$

1
σ

confidence level. Additionally, we estimate the current deceleration parameter $$q_0=-0.530^{+0.018}_{-0.017}$$

q
0

=
-
0
.

530

-
0.017

+
0.018

, the deceleration-acceleration transition redshift $$z_T=0.632^{+0.028}_{-0.028}$$

z
T

=
0
.

632

-
0.028

+
0.028

and the age of the universe $$\tau _U = 12.637^{+0.067}_{-0.066}\,\textrm{Gyrs}$$

τ
U

=
12
.

637

-
0.066

+
0.067

Gyrs

which are in agreement with the standard cosmology ($$\Lambda $$
Λ
CDM) within $$1.5\sigma $$

1.5
σ

. Furthermore, we find that the dark energy equation of state is consistent with both phantom and quintessence behaviors within $$1\sigma $$

1
σ

in the past and converging to $$\Lambda $$
Λ
CDM in the future. Additionally, we find agreement values of $$H_0$$

H
0

within $$1\sigma $$

1
σ

with the SH0ES values when the CMB distance priors are added to the analysis, suggesting that $$H_0$$

H
0

tension could be alleviated. Finally, Tsallis cosmology is preferred over $$\Lambda $$
Λ
CDM by the combined data that motives further studies at the perturbation level.
Transforming the Dark into Light: A Siglec-9 Switch
Authors: Abken Hinrich 
Published: July 2024

Tumor-associated immune repression dampens the success of T-cell therapy for cancer by a plethora of inhibitory mechanisms including aberrant glycosylation. In this issue, Eisenberg and colleagues show that IFNγ induces hyper-sialylation of cancer cells and that this acts as the “checkpoint” through binding to the inhibitory molecule Siglec-9 on immune cells. A chimeric Siglec-9 “switch” receptor converts the suppressive signal into a stimulatory signal, thereby restoring T-cell responses in the tumor tissue, which has multiple implications for the use of adoptive cell therapy in cancer.See related article by Eisenberg et al., p. 1380 (3)
Protein Identification for Stroke Progression via Mendelian Randomization in Million Veteran Program and UK Biobank
Authors: Elmore Andrew R. , Adhikari Nimish , Hartley April E. , Aparicio Hugo Javier , Posner Daniel C. , Hemani Gibran , Tilling Kate , Gaunt Tom R. , Wilson Peter W.F. , Casas Juan P. , Gaziano John Michael , Davey Smith George , Paternoster Lavinia , Cho Kelly , Peloso Gina M. 
Published: July 2024

BACKGROUND:
Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may identify effective therapeutic targets to improve prognosis after an incident stroke.

METHODS:

We performed genome-wide association studies for subsequent major adverse cardiovascular events (MACE; n
cases
=51 929; n
controls
=39 980) and subsequent arterial ischemic stroke (AIS; n
cases
=45 120; n
controls
=46 789) after the first incident stroke within the Million Veteran Program and UK Biobank. We then used genetic variants associated with proteins (protein quantitative trait loci) to determine the effect of 1463 plasma protein abundances on subsequent MACE using Mendelian randomization.

RESULTS:

Two variants were significantly associated with subsequent cardiovascular events: rs76472767 near gene
RNF220
(odds ratio, 0.75 [95% CI, 0.64–0.85];
P
=3.69×10
−8
) with subsequent AIS and rs13294166 near gene
LINC01492
(odds ratio, 1.52 [95% CI, 1.37–1.67];
P
=3.77×10
−8
) with subsequent MACE. Using Mendelian randomization, we identified 2 proteins with an effect on subsequent MACE after a stroke: CCL27 ([C-C motif chemokine 27], effect odds ratio, 0.77 [95% CI, 0.66–0.88]; adjusted
P
=0.05) and TNFRSF14 ([tumor necrosis factor receptor superfamily member 14], effect odds ratio, 1.42 [95% CI, 1.24–1.60]; adjusted
P
=0.006). These proteins are not associated with incident AIS and are implicated to have a role in inflammation.

CONCLUSIONS:
We found evidence that 2 proteins with little effect on incident stroke appear to influence subsequent MACE after incident AIS. These associations suggest that inflammation is a contributing factor to subsequent MACE outcomes after incident AIS and highlights potential novel targets.
Case-control study on challenges in loss of follow-up care and the limitations in the reach of HIV policies for women
Authors: Tizianel Aguilar Gabriela , Lamperti Thomazi Guilherme , Acosta Lisiane , Fernandes da Rocha Andrei , Rodrigues Ikeda Maria Leticia 
Published: July 2024

Introduction HIV has transitioned from a devastating 1980s epidemic to a manageable chronic condition with antiretroviral therapy. In Brazil, challenges persist, including high detection rates and loss of medical follow-up among people living with HIV/AIDS (PLHIV). Adherence, engagement, and avoiding loss to follow-up are critical for effective HIV/AIDS prevention and care. Objectives This case-control study within longitudinal research on PLHIV linkage and retention in Porto Alegre aims to analyze factors associated with treatment abandonment. Methods The study, based on patients from the Therapeutic Care Service for HIV and AIDS at Sanatorio Partenon Hospital, involved 360 PLHIV in a retention and linkage outpatient clinic. Results Risk factors for loss to follow-up include cisgender women, diagnosis between 1991 and 2005, and non-adherence to antiretroviral treatment (ART). Conversely, cisgender men, diagnosis between 2015 and 2023, and good ART adherence were protective factors. Conclusion Gender disparities and ART non-adherence pose significant challenges in comprehensive PLHIV care. Cisgender women diagnosed before 2005 face higher risk, while cisgender men diagnosed after 2015 with good ART adherence are more protected, influencing care and prevention strategies for PLHIV.
Childhood-onset systemic lupus erythematosus: A descriptive and comparative study of clinical, laboratory, and treatment characteristics in two populations
Authors: Kavrul Kayaalp Gülşah , Esencan Deren , Guliyeva Vafa , Arık Selen Duygu , Türkmen Şeyma , Şahin Sezgin , Bilginer Yelda , Kasapçopur Özgür , Sözeri Betül , Özen Seza , Aktay Ayaz Nuray , Sawalha Amr H. 
Published: July 2024

Objective The aim of this study was to characterize childhood-onset systemic lupus erythematosus (SLE) in two large cohorts from Turkey and the United States. Methods Patients diagnosed with childhood-onset SLE who fulfilled the 1997 American College of Rheumatology classification criteria for SLE from four reference centers in Turkey and the University of Pittsburgh School of Medicine in the United States were included in this study. A comparative analysis was conducted to evaluate the similarities and differences in clinical and laboratory features, damage accrual, and treatment experiences between the two populations. Results A total of 174 patients with childhood-onset SLE were included in this study (108 patients from Turkey and 66 patients from the United States). The female-to-male ratio was similar between the two cohorts (∼3:1, p = .73). The median age at diagnosis was 11.67 years (2.19-17.93) in the Turkish cohort and 13.68 years (2.74-17.93) in the U.S. cohort ( p < .001). Photosensitivity (45.4% and 21.2%; p = .007) and renal involvement (41.7% and 36.4%; p = .045) were higher in the Turkish cohort. Anti-Ro/SSA (34.8% and 15.7%; p < .001), anti-Sm (59.1% and 19.4%; p < .001), and anti-RNP (47.0% and 14.8%; p < .001) positivity was more frequent in the U.S. cohort. Current use of rituximab (37.9% and 1.9%; p < .001) and belimumab (19.7% and 0%; p < .001) was more prevalent in the U.S. cohort, while the use of cyclophosphamide (often according to the low dose Euro-Lupus protocol) throughout the disease course (24.1% and 4.5%; p < .001) was more frequent in the Turkish cohort. SLICC/ACR Damage Index scores were not different between the two cohorts. Conclusion This study provides detailed clinical and laboratory features of childhood-onset SLE in two independent and geographically divergent cohorts. Our findings suggest an earlier age of disease onset and a higher prevalence of kidney involvement in Turkish patients. Differences in treatment approaches were also noted. However, damage accrual related to SLE does not appear to be different between the two patient populations.
Psychological impact of life events in systemic lupus erythematosus patients – Differences between flares and remission
Authors: Faria Raquel , Guimarães de Oliveira Daniel , Alves Rute , Farinha Fátima , Pinho Costa Paulo , Vasconcelos Carlos , Figueiredo-Braga Margarida 
Published: July 2024

Background Stress has been linked to worsening symptoms and increased disease activity in patients with Systemic lupus erythematosus (SLE). Life-events are individual stress points, and there is conflicting evidence regarding their role in SLE activity and disease perception. Methods Adult SLE patients were recruited for the study. Clinical and laboratory features of SLE were recorded, and previous diagnosis of anxiety or depression were retrieved from patients’ electronic charts. Flares were defined by the Systemic Lupus Erythematosus Disease Activity (SLEDAI) flare Index, and flares during the previous year were documented. During a routine visit, they completed validated Portuguese translations of the 10-item Perceived Stress Scale (PSS-10), Hospital Anxiety and Depression Scale (HADS) and Life Experience Survey (LES) for the previous year. Results A total of 47 female SLE patients were recruited. Ten patients (21.3%) had experienced recent flares. Patients with recent flares reported fewer life events, with lower positive, negative, and total weightings sums compared to those without recent flares. Although 42.2% of patients perceived pathological levels of stress in the previous month, 48.9% had anxiety symptoms, and 34% were at high risk for an anxiety disorder, these psychometric measures did not differ significantly between the recent flare and no-flare groups. Conclusions There is a high prevalence of pathological levels of stress among SLE patients. SLE patients with recent flares report less psychological impact from life events, both positive and negative, independent of other psychological or pharmacological factors.
Preclinical Safety Evaluation of Etripamil Nasal Spray in Cynomolgus Macaques (Macaca fascicularis) to Assess for Safety in Patients With Paroxysmal Supraventricular Tachycardia
Authors: Pion Johanne , Lopez Mendez Carlos , Moreau Jean-Pierre , Boulanger Veronique , Wight Douglas 
Published: July 2024

Etripamil is a calcium channel blocker currently in Phase 3 trials for the treatment of paroxysmal supraventricular tachycardia (PSVT). Systemic and local toxicity following once-weekly intranasal administration of etripamil was evaluated in cynomolgus macaques to support clinical development. Groups of animals (N = 8, 4 males and 4 females) were administered etripamil into the left nostril weekly at dose levels of 0 (vehicle), 1.9, 3.8, or 5.7 mg/kg/dose for 26 doses. Persistence, reversibility, and progression of findings were examined following a 28-day recovery period. Clinical signs were transient and were related to the intranasal administration (e.g., nasal discharge, sneezing, etc.) of etripamil. There were no macroscopic or systemic microscopic findings at any dose. Etripamil-related adaptive and reactive local changes affecting the nasal cavity, larynx, and nasopharynx were observed at ≥1.9 mg/kg/dose. Minimal to severe dose-dependent nasal epithelial damage was observed, mainly affecting respiratory and transitional epithelium. Following the 28-day recovery period, microscopic changes were confined to the left nasal cavity and nasopharynx. These changes were significantly lower in incidence and severity, with noticeable reversal of the adaptive and reactive changes, indicating partial to complete recovery of the epithelial lining. Based on the lack of systemic toxicity and the minimal and transient nasal changes, the systemic, no observable adverse effect level (NOAEL) of etripamil in monkeys was the high dose, 5.7 mg/kg/dose. The NOAEL for local toxicity was 1.9 mg/kg/dose. Collectively, these data support further study of etripamil in human trials as a potential treatment for PSVT.