bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does radiofrequency ablation of the lower oesophagus allow for clonal expansion of highly mutated neosquamous epithelium?
Authors: Akarca Fahire Goknur , Shaheen Nicholas J , Stachler Matthew D 
Published: October 2023

ObjectiveIn Barrett’s oesophagus (BE), after radiofrequency ablation (RFA), the oesophagus can be repopulated with a stratified ‘neosquamous epithelium’ (NeoSE). While histologically normal, the origin and clonal make-up of this NeoSE is unknown. An increased understanding of NeoSE is important as some studies suggest that NeoSE is biologically abnormal. The aim of this study was to determine whether there were major differences in the mutational landscape or clonal size in NeoSE versus normal squamous epithelium and determine whether NeoSE shares any pathogenic mutations with BE.Methods and analysis10 patients who underwent RFA and 10 samples from 8 control patients were sequenced using a clinical targeted sequencing platform (cohort 1). An additional, eight patients with paired preablation BE and postablation NeoSE were also sequenced (cohort 2). Patient advocates will be used to disseminate the findings of this study.ResultsNeoSE samples had a mean of 2.2 pathogenic mutations per sample, including 50% of samples with anNOTCH1and 30% of samples with aTP53mutation. The normal oesophagus samples had 1.5 mutations per sample, including 40% of samples withNOTCH1and 10% of samples withTP53mutations. There was no difference in mutational allele fractions between NeoSE and normal squamous samples. When we compared paired BE and NeoSE samples, no shared mutations were identified.ConclusionWhile there was a trend for moreTP53mutations in NeoSE, overall, the mutational profile and clonal sizes (allele fractions) were very similar, suggesting NeoSE is genomically similar to the normal oesophageal squamous epithelium.
The English National Lynch Syndrome transformation project: an NHS Genomic Medicine Service Alliance (GMSA) programme
Authors: Monahan Kevin J , Ryan Neil , Monje-Garcia Laura , Armstrong Ruth , Church David N , Cook Jackie , Elghobashy Alaa , Lalloo Fiona , Lane Sally , McDermott Frank D , Miles Tracie , Hardy Steven A , Tyson Adele , Wang Valerie Ya Wen , Kim Anna , Gelinas Simone , Faravelli Francesca , Elmslie Frances , Shaw Adam C 
Published: October 2023

ObjectiveIn England, through the Genomic Medicine Service Alliances (GMSAs), a national transformation project aims to embed robust pathways to deliver universal Lynch syndrome (LS) testing for patients with colorectal and endometrial cancers. Prior to commencement of the project, there was evidence of variation and low testing levels in eligible patients which is consistent with other health systems; however, we believe this is amenable to systematic improvement with responsibility for testing delivery by local cancer teams supported by regional infrastructure.Methods and analysisA project team and national oversight group was formed in May 2021 with membership including 21×cancer alliances, 7×GMSAs, charities and other stakeholders who agreed key performance indicators. ‘LS champions’ within each cancer team were identified and surveyed. Workforce training focused on effective identification of eligible patients, overcoming barriers and mainstreamed constitutional genetic testing. Comprehensive pathway data analysis was performed in conjunction with the National Disease Registration Service.ResultsSurvey and baseline testing data illustrated variation, and a disparity between practice and perception, in levels of testing. The main reported barriers related to funding streams and systematic approaches. Multifaceted training programmes were produced to support workforce development. Champions responsible for testing delivery were appointed in >95% of cancer teams. We identified >9000 historically diagnosed LS patients to support ascertainment for a nationally coordinated screening programme.ConclusionThis ongoing transformational project is strongly supported by stakeholders in England. Significant quality improvement has been implemented, facilitating systematic delivery of universal testing for LS nationally and reduction in variation in care.
Turning point in COVID-19 severity and fatality during the pandemic: a national cohort study in Qatar
Authors: Chemaitelly Hiam , Ayoub Houssein H , Faust Jeremy Samuel , Coyle Peter , Tang Patrick , Hasan Mohammad R , Yassine Hadi M , Al-Khatib Hebah A , Al Thani Asmaa A , Al-Kanaani Zaina , Al-Kuwari Einas , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali , Shaik Riyazuddin Mohammad , Abdul-Rahim Hanan F , Nasrallah Gheyath K , Al-Kuwari Mohamed Ghaith , Butt Adeel Ajwad , Al-Romaihi Hamad , Al-Thani Mohamed H , Al-Khal Abdullatif , Bertollini Roberto , Abu-Raddad Laith J 
Published: October 2023

ObjectiveTo assess the evolution of COVID-19 severity and fatality in a unique setting that consistently applied, throughout the pandemic, rigorous and standardised criteria for defining severe COVID-19 outcomes.Methods and analysisWe conducted a national cohort study on 312 109 Qatari citizens to investigate incidence of severe, critical or fatal COVID-19 classified according to the WHO criteria between 28 February 2020 and 21 April 2023. Incidence rates for severe, critical or fatal COVID-19 were estimated during the pre-omicron phase, first omicron wave, combined phases and throughout the pandemic.ResultsCumulative incidence of severe, critical or fatal COVID-19 after 3.14 years of follow-up was 0.45% (95% CI 0.43% to 0.47%). Incidence rate for severe, critical or fatal COVID-19 throughout the pandemic was 1.43 (95% CI 1.35 to 1.50) per 1000 person years. In the pre-omicron phase, first omicron wave, and combined phases, it was 2.01 (95% CI 1.90 to 2.13), 3.70 (95% CI 3.25 to 4.22) and 2.18 (95% CI 2.07 to 2.30) per 1000 person years, respectively. The post-first omicron phase saw a drastic drop to 0.10 (95% CI 0.08 to 0.14) per 1000 person years, a 95.4% reduction. Among all severe, critical and fatal cases, 99.5% occurred during the primary infection. Cumulative incidence of fatal COVID-19 was 0.042% (95% CI 0.036% to 0.050%), with an incidence rate of 0.13 (95% CI 0.11 to 0.16) per 1000 person years. In the post-first omicron phase, incidence rate of fatal COVID-19 decreased by 90.0% compared with earlier stages. Both severity and fatality exhibited an exponential increase with age and a linear increase with the number of coexisting conditions.ConclusionThe conclusion of the first omicron wave was a turning point in the severity of the pandemic. While vaccination and enhanced case management reduced severity gradually, the rapid accumulation of natural immunity during the first omicron wave appears to have played a critical role in driving this shift in severity.
Impact ofHelicobacter pyloriinfection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors
Authors: Magahis Patrick T , Maron Steven B , Cowzer Darren , King Stephanie , Schattner Mark , Janjigian Yelena , Faleck David , Laszkowska Monika 
Published: October 2023

BackgroundGut microbiota composition can influence cancer immunotherapy response. Recent evidence suggestsHelicobacter pyloriinfection may reduce immune checkpoint inhibitor (ICI) efficacy in lung cancer and melanoma, but thorough characterization of this association in patients with gastric cancer is lacking. We aimed to determine the impact ofH. pylorion survival in this population.MethodsThis single-center, retrospective study included all ICI-treated individuals with metastatic gastric cancer and documentedH. pyloristatus at Memorial Sloan Kettering between July 2013 and October 2021.H. pylori-positive status was defined as history of infection obtained via breath test, stool antigen test, histopathology, and/or chart documentation. Negative status was defined as explicitly negative testing, histopathology, and/or chart documentation. Primary outcomes were progression-free survival (PFS) and overall survival (OS).ResultsOf 215 included patients, 49 had documented history ofH. pyloriinfection. Compared withH. pylori-negative patients, positive individuals tended to be younger, non-white, and Hispanic with non-cardia and intestinal-type gastric cancer.H. pylori-positive patients had significantly shorter median PFS (3.2 vs 6.8 months, HR 1.96, p<0.01) and OS (9.8 vs 17.9 months, HR 1.54, p=0.02). Multivariable analysis confirmedH. pyloriinfection as an independent predictor of PFS (HR 3.04, p<0.01) and OS (HR 2.24, p=0.01).ConclusionsIn this largest study of its kind,H. pyloriinfection was associated with inferior survival in ICI-treated patients with gastric cancer. This suggestsH. pyloristatus may be a prognostic marker of immune responsiveness. Future studies are needed to elucidate immunoregulatory mechanisms and whether treatment of active infections would improve immunotherapy outcomes.
Efficacy of non-conventional synthetic DMARDs for patients with rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis
Authors: Yuan Haoming , Cui Shaoxin , Yang Lin , Cui Jiehan , Wang Xiaoping , Ding Meng , Jin Lu , Wang Yanru , Chang Fei , Jin Hongtao , Ma Jun , Shi Min , Liu Aijing 
Published: October 2023

ObjectivesWe conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD).MethodsPubMed, EMBASE, the Cochrane Library and Web of Science were searched for relevant articles from inception to 1 June 2022. The results obtained from the analysis were expressed as mean difference (MD), effect size and 95% CI.ResultsA total of 17 studies, including 1315 patients with RA-ILD, were eligible. The ncs-DMARDs included abatacept, rituximab, tocilizumab, tumour necrosis factor and Janus kinase inhibitors. Compared with the baseline, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) values in the pooled data after ncs-DMARD treatment (alone or combined with conventional therapy) (p=0.36 for FVC; p=0.96 for FEV1and p=0.46 for DLCO). Of note, FVC was obviously increased in rituximab subgroup (MD=−4.62, 95% CI −8.90 to −0.33, p=0.03). Also, high-resolution CT non-progression rate and fatality rate due to ILD progression in patients with RA-ILD were 0.792 (95% CI 0.746 to 0.834, p=0.015) and 0.049 (95% CI 0.035 to 0.065, p=0.000), respectively.Conclusionncs-DMARDs alone or combined with conventional therapy might be an optimal and promising treatment for stabilising or improving ILD in patients with RA-ILD.PROSPERO registration numberCRD42022356816.
Low micronutrient intake in nursing home residents, a cross-sectional study
Authors: Borkent J.W. , Manders M. , Nijhof A. , Naumann E. , Feskens E.J.M. , de van der Schueren M.A.E. 
Published: October 2023

Low intake of micronutrients is associated with health-related problems in nursing home residents. As their food intake is generally low, it is expected that their micronutrient intake will be low as well. The nutrient intake of 189 residents (mean age 85.0 years (SD: 7.4)) in five different Dutch nursing homes was measured based on 3-day direct observations of intake. Micronutrient intake, without supplementation, was calculated using the Dutch food composition table, and SPADE software was used to model habitual intake. Intake was compared to the estimated average requirement (EAR) or adequate intake (AI) as described in the Dutch dietary reference values. A low intake was defined as >10% not meeting the EAR or when the P50 (median) intake was below the AI. Vitamin A, thiamin, riboflavin, niacin, B6, folate, B12, C, D, E, copper, iron, zinc, calcium, iodine, magnesium, phosphorus, potassium, and selenium were investigated. Our data showed that vitamin and mineral intake was low for most assessed nutrients. An AI was only seen for vitamin B12 (men only), iodine (men only), and phosphorus. A total of 50% of the population had an intake below the EAR for riboflavin, vit B6, folate, and vitamin D. For reference values expressed in AI, P50 intake of vitamin E, calcium, iodine, magnesium, potassium, and selenium was below the AI. To conclude: micronutrient intake in nursing home residents is far too low in most of the nursing home population. A “food-first” approach could increase dietary intake, but supplements could be considered if the “food-first” approach is not successful.
Wave-packet effects: a solution for isospin anomalies in vector-meson decay
Authors: Ishikawa Kenzo , Jinnouchi Osamu , Nishiwaki Kenji , Oda Kin-ya 
Published: October 2023

AbstractThere is a long-standing anomaly in the ratio of the decay width for $$\psi (3770)\rightarrow D^0\overline{D^0}$$

ψ

(
3770
)

→

D
0

D
0

¯

to that for $$\psi (3770)\rightarrow D^+D^-$$

ψ

(
3770
)

→

D
+

D
-

at the level of $$9.5\,\sigma $$

9.5

σ

. A similar anomaly exists for the ratio of $$\phi (1020)\rightarrow K_\text {L}^0K_\text {S}^0$$

ϕ

(
1020
)

→

K
L
0

K
S
0

to $$\phi (1020)\rightarrow K^+K^-$$

ϕ

(
1020
)

→

K
+

K
-

at $$2.1\,\sigma $$

2.1

σ

. In this study, we reassess the anomaly through the lens of a Gaussian wave-packet formalism. Our comprehensive calculations include the localization of the overlap of the wave packets near the mass thresholds and the composite nature of the initial-state vector mesons. The results align within a $$\sim 1 \sigma $$

∼
1
σ

confidence level with the Particle Data Group’s central values for a physically reasonable value of the form-factor parameter, indicating a resolution to these anomalies. We also check the deviation of a wave-packet resonance from the Briet–Wigner shape and find that wide ranges of the wave-packet size are consistent with the experimental data.
The cryogenic RWELL: a stable charge multiplier for dual-phase liquid argon detectors
Authors: Tesi A. , Leardini S. , Moleri L. , Gonzalez-Diaz D. , Jash A. , Breskin A. , Bressler S. 
Published: October 2023

AbstractThe operation of a cryogenic Resistive WELL (RWELL) in liquid argon vapor is reported for the first time. It comprises a Thick Gas Electron Multiplier (THGEM) structure coupled to a resistive Diamond-Like Carbon (DLC) anode deposited on an insulating substrate. The multiplier was operated at cryogenic temperature (90 K, 1.2 bar) in saturated argon vapor and characterized in terms of charge gain and electrical stability. A comparative study with standard, non-resistive THGEM (a.k.a LEM) and WELL multipliers confirmed the RWELL advantages in terms of discharge quenching – i.e. superior gain and stability.
Obesity Modifies Clinical Outcomes of Right Ventricular Dysfunction
Authors: Ma Janet I. , Zern Emily K. , Parekh Juhi K. , Owunna Ndidi , Jiang Nona , Wang Dongyu , Rambarat Paula K. , Pomerantsev Eugene , Picard Michael H. , Ho Jennifer E. 
Published: October 2023

BACKGROUND:
Right ventricular (RV) dysfunction is associated with increased mortality across a spectrum of cardiovascular diseases. The role of obesity in RV dysfunction and adverse outcomes is unclear.

METHODS:
We examined patients undergoing right heart catheterization between 2005 and 2016 in a hospital-based cohort. Linear regression was used to examine the association of obesity with hemodynamic indices of RV dysfunction (pulmonary artery pulsatility index, right atrial pressure:pulmonary capillary wedge pressure ratio, RV stroke work index). Cox models were used to examine the association of RV function measures with clinical outcomes.

RESULTS:

Among 8285 patients (mean age, 63 years; 40% women), higher body mass index was associated with worse indices of RV dysfunction, including lower pulmonary artery pulsatility index (β, −0.23; SE, 0.01;
P
<0.001), higher right atrium:pulmonary capillary wedge pressure ratio (β, 0.25; SE, 0.01;
P
<0.001), and lower RV stroke work index (β, −0.05; SE, 0.01;
P
<0.001). Over median of 7.3 years of follow-up, we observed 3006 mortality and 2004 heart failure hospitalization events. RV dysfunction was associated with a greater risk of mortality (eg, pulmonary artery pulsatility index:hazard ratio, 1.11 per 1-SD increase [95% CI, 1.04–1.18]), with similar associations with risk of heart failure hospitalization. Body mass index modified the effect of RV dysfunction on all-cause mortality (
P
interaction
≤0.005 for PAPi and RA:PCWP ratio), such that the effect of RV dysfunction was more pronounced at higher body mass index.

CONCLUSIONS:
Patients with obesity had worse hemodynamic measured indices of RV function across a broad hospital-based sample. While RV dysfunction was associated with worse clinical outcomes including mortality and heart failure hospitalization, this association was especially pronounced among individuals with higher body mass index.
Preeclampsia Prediction Using Machine Learning and Polygenic Risk Scores From Clinical and Genetic Risk Factors in Early and Late Pregnancies
Authors: Kovacheva Vesela P. , Eberhard Braden W. , Cohen Raphael Y. , Maher Matthew , Saxena Richa , Gray Kathryn J. 
Published: October 2023

BACKGROUND:
Preeclampsia, a pregnancy-specific condition associated with new-onset hypertension after 20-weeks gestation, is a leading cause of maternal and neonatal morbidity and mortality. Predictive tools to understand which individuals are most at risk are needed.

METHODS:
We identified a cohort of N=1125 pregnant individuals who delivered between May 2015 and May 2022 at Mass General Brigham Hospitals with available electronic health record data and linked genetic data. Using clinical electronic health record data and systolic blood pressure polygenic risk scores derived from a large genome-wide association study, we developed machine learning (XGBoost) and logistic regression models to predict preeclampsia risk.

RESULTS:
Pregnant individuals with a systolic blood pressure polygenic risk score in the top quartile had higher blood pressures throughout pregnancy compared with patients within the lowest quartile systolic blood pressure polygenic risk score. In the first trimester, the most predictive model was XGBoost, with an area under the curve of 0.74. In late pregnancy, with data obtained up to the delivery admission, the best-performing model was XGBoost using clinical variables, which achieved an area under the curve of 0.91. Adding the systolic blood pressure polygenic risk score to the models did not improve the performance significantly based on De Long test comparing the area under the curve of models with and without the polygenic score.

CONCLUSIONS:
Integrating clinical factors into predictive models can inform personalized preeclampsia risk and achieve higher predictive power than the current practice. In the future, personalized tools can be implemented to identify high-risk patients for preventative therapies and timely intervention to improve adverse maternal and neonatal outcomes.
Hourly Air Pollution Exposure and Emergency Hospital Admissions for Stroke: A Multicenter Case-Crossover Study
Authors: Lv Xin , Shi Wanying , Yuan Kun , Zhang Yangchang , Cao Wangnan , Li Chunrong , Xu Lufei , Wu Lizhi , Sun Shengzhi , Hong Feng 
Published: October 2023

BACKGROUND:
Daily exposure to ambient air pollution is associated with stroke morbidity and mortality; however, the association between hourly exposure to air pollutants and risk of emergency hospital admissions for stroke and its subtypes remains relatively unexplored.

METHODS:

We obtained hourly concentrations of fine particulate matter (PM
2.5
), respirable particulate matter (PM
10
), nitrogen dioxide (NO
2
), sulfur dioxide (SO
2
), ozone (O
3
), and carbon monoxide (CO) from the China National Environmental Monitoring Center. We conducted a time-stratified case-crossover study among 86 635 emergency hospital admissions for stroke across 10 hospitals in 3 cities (Jinhua, Hangzhou, and Zhoushan) in Zhejiang province, China, between January 1, 2016 and December 31, 2021. Using a conditional logistic regression combined with a distributed lag linear model, we estimated the association between hourly exposure to multiple air pollutants and risk of emergency hospital admissions for total stroke, ischemic stroke, hemorrhagic stroke, and undetermined type.

RESULTS:

Hourly exposure to PM
2.5
, PM
10
, NO
2
, and SO
2
was associated with an increased risk of hospital admissions for total stroke and ischemic stroke. The associations were most pronounced during the concurrent hour of exposure and lasted for ≈2 hours. We found that the risk was more pronounced among male patients or those aged <65 years old.

CONCLUSIONS:

Our findings suggest that exposure to PM
2.5
, PM
10
, NO
2
, and SO
2
, but not CO and O
3
, is associated with emergency hospital admissions for total stroke or ischemic stroke shortly after exposure. Implementing targeted pollution emission reduction measures may have significant public health implications in controlling and reducing the burden of stroke.
Propofol-mediated Unconsciousness Disrupts Progression of Sensory Signals through the Cortical Hierarchy
Authors: Tauber John M. , Brincat Scott L. , Stephen Emily P. , Donoghue Jacob A. , Kozachkov Leo , Brown Emery N. , Miller Earl K. 
Published: October 2023

Abstract
A critical component of anesthesia is the loss of sensory perception. Propofol is the most widely used drug for general anesthesia, but the neural mechanisms of how and when it disrupts sensory processing are not fully understood. We analyzed local field potential and spiking recorded from Utah arrays in auditory cortex, associative cortex, and cognitive cortex of nonhuman primates before and during propofol-mediated unconsciousness. Sensory stimuli elicited robust and decodable stimulus responses and triggered periods of stimulus-related synchronization between brain areas in the local field potential of Awake animals. By contrast, propofol-mediated unconsciousness eliminated stimulus-related synchrony and drastically weakened stimulus responses and information in all brain areas except for auditory cortex, where responses and information persisted. However, we found stimuli occurring during spiking Up states triggered weaker spiking responses than in Awake animals in auditory cortex, and little or no spiking responses in higher order areas. These results suggest that propofol's effect on sensory processing is not just because of asynchronous Down states. Rather, both Down states and Up states reflect disrupted dynamics.
Is It Fitting to Divide Value? A Review of The Value Gap
Authors: Perrine Timothy 
Published: October 2023

Abstract
Rønnow-Rasmussen’s The Value Gap is an extended argument for Value Dualism, the view that both goodness and goodness for are coherent value concepts that are not fully understandable in terms of each other. In the first part of the book, he criticizes attempts to fully understand one type of value in terms of the other. In the second part of the book, he argues that both concepts are value concepts by appealing to a “Fitting Attitude” analysis of value concepts. This book review exposits Rønnow-Rasmussen’s argument for Dualism, and his proposed analysis of both goodness and goodness for. More critically, it briefly defends a strategy for understanding goodness for in terms of goodness and criticizes Rønnow-Rasmussen’s proposed analysis of goodness for.