bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a single-centre
Authors: Karaatmaca Betul , Cagdas Deniz , Esenboga Saliha , Erman Baran , Tan Cagman , Turul Ozgur Tuba , Boztug Kaan , van der Burg Mirjam , Sanal Ozden , Tezcan Ilhan 
Published: September 2023

Abstract
Recombination activating genes (RAG)1 and RAG2 deficiency leads to combined T/B-cell deficiency with varying clinical presentations. This study aimed to define the clinical/laboratory spectrum of RAG1 and RAG2 deficiency. We retrospectively reviewed the clinical/laboratory data of 35 patients, grouped them as severe combined immunodeficiency (SCID), Omenn syndrome (OS), and delayed-onset combined immunodeficiency (CID) and reported nine novel mutations. The male/female ratio was 23/12. Median age of clinical manifestations was 1 months (mo) (0.5–2), 2 mo (1.25–5), and 14 mo (3.63–27), age at diagnosis was 4 mo (3–6), 4.5 mo (2.5–9.75), and 27 mo (14.5–70) in SCID (n = 25; 71.4%), OS (n = 5; 14.3%), and CID (n = 5; 14.3%) patients, respectively. Common clinical manifestations were recurrent sinopulmonary infections 82.9%, oral moniliasis 62.9%, diarrhea 51.4%, and eczema/dermatitis 42.9%. Autoimmune features were present in 31.4% of the patients; 80% were in CID patients. Lymphopenia was present in 92% of SCID, 80% of OS, and 80% of CID patients. All SCID and CID patients had low T (CD3, CD4, and CD8), low B, and increased NK cell numbers. Twenty-eight patients underwent hematopoietic stem cell transplantation (HSCT), whereas seven patients died before HSCT. Median age at HSCT was 7 mo (4–13.5). Survival differed in groups; maximum in SCID patients who had an HLA-matched family donor, minimum in OS. Totally 19 (54.3%) patients survived. Early molecular genetic studies will give both individualized therapy options, and a survival advantage because of timely diagnosis and treatment. Further improvement in therapeutic outcomes will be possible if clinicians gain time for HSCT.
The Impact of Preventive Treatment for Multidrug- and Rifampin-Resistant Tuberculosis Exceeds Trial-Based Estimates
Authors: Kasaie Parastu , Pennington Jeff , Gupta Amita , Dowdy David W , Kendall Emily A 
Published: September 2023

Abstract

Background
Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug- or rifampin-resistant tuberculosis (MDR/RR-TB) are nearing completion. The potential benefits of delivering TPT to MDR/RR-TB contacts extend beyond the outcomes that clinical trials can measure.

Methods
We developed an agent-based, household-structured TB and MDR/RR-TB transmission model, calibrated to an illustrative setting in India. We simulated contact investigation in households of patients with MDR/RR-TB, comparing an MDR/RR-TPT regimen (assuming 6-month duration, 70% efficacy) and associated active case finding against alternatives of contact investigation without TPT or no household intervention. We simulated the TB and MDR/RR-TB incidence averted relative to placebo over 2 years, as measurable by a typical trial, as well as the incidence averted over a longer time horizon, in the broader population, and relative to no contact investigation.

Results
Observing TPT and placebo recipients for 2 years as in a typical trial, MDR/RR-TPT was measured to prevent 72% (interquartile range, 45%–100%) of incident MDR/RR-TB among recipients; the median number needed to treat (NNT) to prevent 1 MDR/RR-TB case was 73, compared to placebo. This NNT decreased to 54 with 13–18 years of observation, to 27 when downstream transmission effects were also considered, and to 12 when the effects of active TB screening were included by comparing to a no-household-contact-intervention scenario.

Conclusions
If forthcoming trial results demonstrate efficacy, the long-term population impact of TPT for MDR/RR-TB—including the large effect of increased active TB detection among MDR/RR-TB contacts—could be much greater than suggested by trial outcomes alone.
Management Practices and Quality of Care: Evidence from the Private Health Care Sector in Tanzania
Authors: Powell-Jackson Timothy , King Jessica J C , Makungu Christina , Quaife Matthew , Goodman Catherine 
Published: September 2023

Abstract
We measure the adoption of management practices in over 220 private for-profit and non-profit health facilities in 64 districts across Tanzania and link these data to process quality-of-care metrics, assessed using undercover standardised patients and clinical observations. We find that better managed health facilities are more likely to provide correct treatment in accordance with national treatment guidelines, adhere to a checklist of essential questions and examinations, and comply with infection prevention and control practices. Moving from the 10th to the 90th percentile in the management practice score is associated with a 48% increase in correct treatment. We then leverage a large-scale field experiment of an internationally recognised management support intervention in which health facilities are assessed against comprehensive standards, given an individually tailored quality improvement plan and supported through training and mentoring visits. We find zero to small effects on management scores, suggesting that improving management practices in this setting may be challenging.
The Welfare Effects of Greenbelt Policy: Evidence from England
Authors: Koster Hans R A 
Published: September 2023

Abstract
I measure the economic effects of greenbelts that prohibit new construction beyond a predefined urban fringe and therefore act as urban growth boundaries. I focus on England, where 13% of the land is designated as greenbelt land. I provide reduced-form evidence and estimate a quantitative equilibrium model that includes amenities, housing supply, a traffic congestion externality, agglomeration forces, productivity and household location choices. Greenbelt policy generates positive amenity effects, but also strongly reduces housing supply. I find that greenbelts increase welfare because amenity effects are sufficiently strong. At the same time, however, greenbelts decrease housing affordability by limiting housing supply.
Acquired risk factors and incident atrial fibrillation according to age and genetic predisposition
Authors: Wang Ningjian , Yu Yuefeng , Sun Ying , Zhang Haojie , Wang Yuying , Chen Chi , Tan Xiao , Wang Bin , Lu Yingli 
Published: September 2023

Abstract

Background and Aims
Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. Investigations of risk factor profiles for AF according to age and genetic risk groups are essential to promote individualized strategies for the prevention and control of AF.

Methods
A total of 409 661 participants (mean age, 56 years; 46% men) free of AF at baseline and with complete information about risk factors were included from the UK Biobank cohort. The hazard ratios and population-attributable risk (PAR) percentages of incident AF associated with 23 risk factors were examined, including 3 social factors, 7 health behaviours, 6 cardiometabolic factors, 6 clinical comorbidities, and the genetic risk score (GRS), across 3 age groups (40–49, 50–59, and 60–69 years) and 3 genetic risk groups (low, moderate, and high GRS).

Results
After a follow-up of 5 027 587 person-years, 23 847 participants developed AF. Most cardiometabolic factors and clinical comorbidities showed a significant interaction with age, whereby the associations were generally strengthened in younger groups (Pinteraction &lt; .002). However, only low LDL cholesterol, renal dysfunction, and cardiovascular disease showed a significant interaction with genetic risk, and the associations with these factors were stronger in lower genetic risk groups (Pinteraction &lt; .002). Cardiometabolic factors consistently accounted for the largest number of incident AF cases across all age groups (PAR: 36.2%–38.9%) and genetic risk groups (34.0%–41.9%), with hypertension and overweight/obesity being the two leading modifiable factors. Health behaviours (PAR: 11.5% vs. 8.7%) and genetic risk factors (19.1% vs. 14.3%) contributed to more AF cases in the 40–49 years group than in the 60–69 years group, while the contribution of clinical comorbidities remained relatively stable across different age groups. The AF risk attributable to overall cardiometabolic factors (PAR: 41.9% in the low genetic risk group and 34.0% in the high genetic risk group) and clinical comorbidities (24.7% and 15.9%) decreased with increasing genetic risk. The impact of social factors on AF was relatively low across the groups by age and genetic risk.

Conclusions
This study provided comprehensive information about age- and genetic predisposition-related risk factor profiles for AF in a cohort of UK adults. Prioritizing risk factors according to age and genetic risk stratifications may help to achieve precise and efficient prevention of AF.
Clinical course of hypertrophic cardiomyopathy patients implanted with a transvenous or subcutaneous defibrillator
Authors: Francia Pietro , Ziacchi Matteo , Adduci Carmen , Ammendola Ernesto , Pieragnoli Paolo , De Filippo Paolo , Rapacciuolo Antonio , Rella Valeria , Migliore Federico , Viani Stefano , Musumeci Maria Beatrice , Biagini Elena , Lovecchio Mariolina , Baldini Rossella , Falasconi Giulio , Autore Camillo , Biffi Mauro , Cecchi Franco 
Published: September 2023

Abstract

Aims
The implantable cardioverter-defibrillator (ICD) is a life-saving therapy in patients with hypertrophic cardiomyopathy (HCM) at risk of sudden cardiac death. Implantable cardioverter-defibrillator complications are of concern. The subcutaneous ICD (S-ICD) does not use transvenous leads and is expected to reduce complications. However, it does not provide bradycardia and anti-tachycardia pacing (ATP). The aim of this study was to compare appropriate and inappropriate ICD interventions, complications, disease-related adverse events and mortality between HCM patients implanted with a S- or transvenous (TV)-ICD.

Methods and results
Consecutive HCM patients implanted with a S- (n = 216) or TV-ICD (n = 211) were enrolled. Propensity-adjusted cumulative Kaplan–Meier curves and multivariate Cox proportional hazard ratios were used to compare 5-year event-free survival and the risk of events. The S-ICD patients had lower 5-year risk of appropriate (HR: 0.32; 95%CI: 0.15–0.65; P = 0.002) and inappropriate (HR: 0.44; 95%CI: 0.20–0.95; P = 0.038) ICD interventions, driven by a high incidence of ATP therapy in the TV-ICD group. The S- and TV-ICD patients experienced similar 5-year rate of device-related complications, albeit the risk of major lead-related complications was lower in S-ICD patients (HR: 0.17; 95%CI: 0.038–0.79; P = 0.023). The TV- and S-ICD patients displayed similar risk of disease-related complications (HR: 0.64; 95%CI: 0.27–1.52; P = 0.309) and mortality (HR: 0.74; 95%CI: 0.29–1.87; P = 0.521).

Conclusion
Hypertrophic cardiomyopathy patients implanted with a S-ICD had lower 5-year risk of appropriate and inappropriate ICD therapies as well as of major lead-related complications as compared to those implanted with a TV-ICD. Long-term comparative follow-up studies will clarify whether the lower incidence of major lead-related complications will translate into a morbidity or survival benefit.
Digest: Ecological and life-history drivers of avian skull evolution
Authors: Tanda Madeleine , Deal Ethan 
Published: September 2023

Abstract
What are the factors that drive the patterns and evolutionary rates of morphological characteristics? To answer this question, Hunt et al. explore shape variation and rates of change in modern avian skulls using morphometric measurements and phylogenetic analyses. They find that habitat density and migration have the strongest influences on avian skull variation and that denser habitats, longer migratory distances, and precocial developmental modes are all associated with faster rates of morphological evolution.
Novel ribotype/sequence type associations and diverse CRISPR-Cas systems in environmental Clostridioides difficile strains from northern Iraq
Authors: Rashid Srwa J , Nale Janet Y , Millard Andrew D , Clokie Martha R J 
Published: September 2023

Abstract
The environment is a natural reservoir of Clostridioides difficile, and here, we aimed to isolate the pathogen from seven locations in northern Iraq. Four of the sites yielded thirty-one isolates (ten from soils, twenty-one from sediments), which together represent ribotypes (RTs) 001 (five), 010 (five), 011 (two), 035 (two), 091 (eight), and 604 (nine). Twenty-five of the isolates (∼81%) are non-toxigenic, while six (∼19%) encode the toxin A and B genes. The genomes of eleven selected isolates represent six sequence types (STs): ST-3 (two), ST-15 (one), ST-107 (five), ST-137 (one), ST-177 (one), and ST-181 (one). Five novel RT/ST associations: RT011/ST-137, RT035/ST-107, RT091/ST-107, RT604/ST-177, and RT604/ST-181 were identified, and the first three are linked to RTs previously uncharacterized by multilocus sequence typing (MLST). Nine of the genomes belong to Clade 1, and two are closely related to the cryptic C-I clade. Diverse multiple prophages and CRISPR-Cas systems (class 1 subtype I-B1 and class 2 type V CRISPR-Cas systems) with spacers identical to other C. difficile phages and plasmids were detected in the genomes. Our data show the broader diversity that exists within environmental C. difficile strains from a much less studied location and their potential role in the evolution and emergence of new strains.
Association Between the Appendicular Extracellular-to-Intracellular Water Ratio and All-Cause Mortality: A 10-Year Longitudinal Study
Authors: Iwasaka Chiharu , Yamada Yosuke , Nishida Yuichiro , Hara Megumi , Yasukata Jun , Miyoshi Nobuyuki , Shimanoe Chisato , Nanri Hinako , Furukawa Takuma , Koga Kayoko , Horita Mikako , Higaki Yasuki , Tanaka Keitaro 
Published: September 2023

Abstract
The appendicular extracellular-to-intracellular water ratio (A-E/I) is a potential marker of skeletal muscle quality, reflecting the balance of water distribution between the extracellular and intracellular compartments of the appendicular limb regions. A-E/I has been increasingly used in recent studies; however, its association with adverse outcomes remains unclear. This study investigated the potential association between A-E/I and all-cause mortality. A prospective cohort study of 8 015 middle-aged and older adults (comprised of 4 755 women, aged 45–74 years) residing in a Japanese community was conducted. The baseline assessment was performed between 2010 and 2012, and the follow-up period lasted until July 2022. A-E/I and skeletal muscle mass were measured using segmental bioelectrical impedance spectroscopy. Handgrip strength (HGS) was measured using a Smedley-type dynamometer. Lifestyle, medical history, and physical activity were assessed by questionnaire and accelerometer. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for each quartile (Q) of A-E/I were estimated using the multivariable Cox regression model. During a 10.5-year median follow-up, the mortality rates were 8.9 and 3.6 per 1 000 person-years for men (292 deaths) and women (174 deaths), respectively. A-E/I quartiles were positively associated with all-cause mortality in both sexes (men: Q1, HR: 1.0 [95% CI: reference], Q4, HR: 1.8 [1.1–2.9], ptrend &lt; .05; women, Q4, HR: 2.2 [1.3–3.8], ptrend &lt; .01). This association remained significant after further adjustment for skeletal muscle mass and HGS (ptrend &lt; .05). Our findings suggest that A-E/I serves as an early predictive marker for mortality in middle-aged and older Japanese adults.
Residential Segregation, Perceived Neighborhood Environment, and All-Cause Mortality Among Community-Dwelling Older Chinese Americans
Authors: Jiang Yanping , Zhu Yuyang , Tang Fengyan , Chung Tammy , Wu Bei 
Published: September 2023

Abstract

Objectives
Residential segregation profoundly affects mental and physical health. However, impacts of residential segregation and other neighborhood characteristics on health among older Asian Americans are not fully understood. This study aimed to close this gap by examining effects of residential segregation, perceived neighborhood cohesion, and neighborhood disorder on all-cause mortality among older Chinese immigrants, as well as testing whether the association between residential segregation and mortality would be mediated by perceived neighborhood cohesion and neighborhood disorder.

Methods
Data were drawn from a subsample of 3,094 older Chinese Americans aged 60 and older (mean age = 72.8 years) from the Population Study of Chinese Elderly in Chicago. Residential segregation was derived using 2010–2014 American Community Survey data. Participants completed surveys on perceived neighborhood cohesion and neighborhood disorder between 2011 and 2013. All-cause mortality was tracked until December 2021.

Results
Residential segregation was associated with elevated all-cause mortality risk; this association, however, was no longer statistically significant after controlling for sociodemographic, behavioral, and health covariates. Perceived neighborhood cohesion, but not neighborhood disorder, was significantly associated with decreased mortality risks. There were no indirect effects of residential segregation on all-cause mortality through perceived neighborhood cohesion or neighborhood disorder. These effects were consistent across male and female participants.

Discussion
These results suggest the importance of neighborhood social environment, specifically perceptions of neighborhood cohesion, in influencing mortality risk among older Chinese immigrants. The findings also indicate the need to conduct further research to examine the health impact of residential segregation among this population.
The Relationship Between Cognitive Decline and All-Cause Mortality Is Modified by Living Alone and a Small Social Network: A Paradox of Isolation
Authors: Murayama Hiroshi , Sugiyama Mika , Inagaki Hiroki , Ura Chiaki , Miyamae Fumiko , Edahiro Ayako , Motokawa Keiko , Okamura Tsuyoshi , Awata Shuichi 
Published: September 2023

Abstract

Objectives
Although cognitive decline is a well-known mortality risk, it has not been adequately investigated, whether social relationships modify the relationship between cognitive decline and mortality. We examined the modifying effects of social relationships (household composition, social network [frequency of social contact with individuals outside the household], and social participation) on the association between cognitive decline and all-cause mortality in older Japanese people.

Methods
In 2015, a baseline questionnaire was distributed to all 132,005 independent community-dwelling individuals aged ≥65 years resident in Adachi Ward of the Tokyo Metropolitan area. The final sample analyzed comprised 74,872 participants (men: 44.9%; mean age: 73.7 ± 6.0 years). Cognitive decline was assessed using a self-administered dementia checklist that was validated using the Clinical Dementia Rating Scale.

Results
A Cox proportional hazard model with an average follow-up of 1,657 days revealed that cognitive decline was associated with higher mortality (hazard ratio [HR]: 1.37, 95% confidence interval [95% CI]: 1.25–1.50). We identified significant associations among household composition, social networks, and cognitive decline. Stratified analyses indicated that the cognitive decline–mortality association was stronger among participants with low contact frequency (HR = 1.60, 95% CI: 1.39–1.85) than high frequency (HR = 1.24, 95% CI: 1.11–1.39). Conversely, the association was weaker among individuals living alone (HR = 1.13, 95% CI: 0.90–1.40) than among cohabiting individuals (HR = 1.43, 95% CI: 1.29–1.57).

Conclusions
Although living alone and having a small social network represent an isolated status, their modifying effects were the opposite. These findings indicate that the isolation type should be considered when implementing support strategies for older adults with cognitive decline or dementia.
Poor oral health influences head and neck cancer patient survival: an International Head and Neck Cancer Epidemiology Consortium pooled analysis
Authors: Tasoulas Jason , Farquhar Douglas R , Sheth Siddharth , Hackman Trevor , Yarbrough Wendell G , Agala Chris B , Koric Alzina , Giraldi Luca , Fabianova Eleonora , Lissowska Jolanta , Świątkowska Beata , Vilensky Marta , Wünsch-Filho Victor , de Carvalho Marcos Brasilino , López Rossana Verónica Mendoza , Holcátová Ivana , Serraino Diego , Polesel Jerry , Canova Cristina , Richiardi Lorenzo , Zevallos Jose P , Ness Andy , Pring Miranda , Thomas Steve J , Dudding Tom , Lee Yuan-Chin Amy , Hashibe Mia , Boffetta Paolo , Olshan Andrew F , Divaris Kimon , Amelio Antonio L 
Published: September 2023

Abstract

Background
Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes.

Methods
Pooled analysis of 2449 head and neck squamous cell carcinoma participants from 4 studies of the International Head and Neck Cancer Epidemiology Consortium included data on periodontal disease, tooth brushing frequency, mouthwash use, numbers of natural teeth, and dental visits over the 10 years prior to diagnosis. Multivariable generalized linear regression models were used and adjusted for age, sex, race, geographic region, tumor site, tumor-node-metastasis stage, treatment modality, education, and smoking to estimate risk ratios (RR) of associations between measures of oral health and overall survival.

Results
Remaining natural teeth (10-19 teeth: RR = 0.81, 95% confidence interval [CI] = 0.69 to 0.95; ≥20 teeth: RR = 0.88, 95% CI = 0.78 to 0.99) and frequent dental visits (&gt;5 visits: RR = 0.77, 95% CI = 0.66 to 0.91) were associated with better overall survival. The inverse association with natural teeth was most pronounced among patients with hypopharyngeal and/or laryngeal, and not otherwise specified head and neck squamous cell carcinoma. The association with dental visits was most pronounced among patients with oropharyngeal head and neck squamous cell carcinoma. Patient-reported gingival bleeding, tooth brushing, and report of ever use of mouthwash were not associated with overall survival.

Conclusions
Good oral health as defined by maintenance of the natural dentition and frequent dental visits appears to be associated with improved overall survival among head and neck squamous cell carcinoma patients.