bluuebunny/crossref_metadata_2025_split huggingface dataset:
Over-prescription of short-acting beta agonists in the treatment of asthma
Authors: Looijmans-van den Akker Ingrid , Werkhoven Anouk , Verheij Theo 
Published: February 2021

Abstract

Background
Despite a clear guideline for asthma medication, excessive use of short-acting β2-agonists (SABAs) is common in clinical practice. Previous research has shown that excessive use of SABAs is associated with poor asthma control.

Objective
This study examines current use of asthma medication in primary care and whether excessive use of SABAs is associated with exacerbations.

Methods
The study design was a retrospective analysis using information from electronical medical records from patients aged 18 and older of five Julius Health Centers located in Utrecht, the Netherlands, in the period of 1 July 2018 through 1 July 2019. Excessive SABA use was defined as ≥400 inhalations per year. An exacerbation was defined as an acute worsening of asthma symptoms with the need for systemic corticosteroids.

Results
A total of 1161 patients were included in the study. Of the patients using SABAs (n = 766), 193 (25%) overused SABAs. Among the patients with inappropriate SABA use (n = 193), 19% had an exacerbation compared with 7% of the appropriate SABA users. For patients using asthma medication the odds of having an exacerbation were 2.9 times higher if they used an inappropriate number of SABAs than if SABAs were used appropriately (odds ratio, 2.897; 95% confidence interval, 1.87–4.48).

Conclusions
This study shows that overuse of SABAs is still common and that it is associated with asthma exacerbations. It highlights that clinicians need to be aware of inappropriate SABA use as it is a sign of and can even contribute to poor asthma control.
Soil microbial composition and carbon mineralization are associated with vegetation type and temperature regime in mesocosms of a semiarid ecosystem
Authors: Avitia Morena , Barrón-Sandoval Alberto , Hernández-Terán Alejandra , Benítez Mariana , A. Barron-Gafford Greg , Dontsova Katerina , A. Pavao-Zuckerman Mitchell , E. Escalante Ana 
Published: February 2021

ABSTRACTTransition from historic grasslands to woody plants in semiarid regions has led to questions about impacts on soil functioning, where microorganisms play a primary role. Understanding the relationship between microbes, plant diversity and soil functioning is relevant to assess such impacts. We evaluate the effect that plant type change in semiarid ecosystems has for microbial diversity and composition, and how this is related to carbon mineralization (CMIN) as a proxy for soil functioning. We followed a mesocosm experiment during 2 years within the Biosphere 2 facility in Oracle, AZ, USA. Two temperature regimes were established with two types of plants (grass or mesquite). Soil samples were analyzed for physicochemical and functional parameters, as well as microbial community composition using 16S rRNA amplicon metagenomics (Illumina MiSeq). Our results show the combined role of plant type and temperature regime in CMIN, where CMIN in grass has lower values at elevated temperatures compared with the opposite trend in mesquite. We also found a strong correlation of microbial composition with plant type but not with temperature regime. Overall, we provide evidence of the major effect of plant type in the specific composition of microbial communities as a potential result of the shrub encroachment.
Will high-speed railway influence the healthcare seeking behaviour of patients? Quasi-experimental evidence from China
Authors: Liu Gordon G , Tang Chengxiang , Liu Yahong , Bu Tao , Tang Daisheng 
Published: February 2021

Abstract
This study examines the impacts of high-speed railway (HSR) transportation on the healthcare-seeking behaviour of patients along newly integrated areas of Sichuan province, China. The opening of the Cheng–Mian–Le intercity HSR is considered as quasi-experimental evidence from China, and we make a propensity score matching the difference in differences research design, using data from the monthly report database of the Sichuan Province health statistical data collection and Decision Support System from 2014 to 2015. We find that, first, the opening of the HSR resulted in significant healthcare-seeking behaviour with great heterogeneity. Second, patients are more likely to go to areas with high-density healthcare resources, in which case HSR may mitigate the diagnostic inaccuracies that patients face locally. Third, the ‘distance enhancement effect’ was present, and its marginal effect is more significant for long-distance patients. Fourth, the tiered-network healthcare policy has no significant restrictive impact on patients seeking high-level medical services. Our results show that HSR establishment has a substantial impact on the behaviour of people seeking medical treatment and medicine. Furthermore, we discuss the results’ policy implications for the allocation and integration of China’s healthcare market, and the accessibility of medical and health services.
Promoting lung cancer awareness, help-seeking and early detection: a systematic review of interventions
Authors: Saab Mohamad M , FitzGerald Serena , Noonan Brendan , Kilty Caroline , Collins Abigail , Lyng Áine , Kennedy Una , O’Brien Maidy , Hegarty Josephine 
Published: February 2021

Summary
Lung cancer (LC) is the leading cause of cancer death. Barriers to the early presentation for LC include lack of symptom awareness, symptom misappraisal, poor relationship with doctors and lack of access to healthcare services. Addressing such barriers can help detect LC early. This systematic review describes the effect of recent interventions to improve LC awareness, help-seeking and early detection. This review was guided by the Cochrane Handbook for Systematic Reviews of Interventions. Electronic databases MEDLINE, CINAHL, ERIC, APA PsycARTICLES, APA PsycInfo and Psychology and Behavioral Sciences Collection were searched. Sixteen studies were included. Knowledge of LC was successfully promoted in most studies using educational sessions and campaigns. LC screening uptake varied with most studies successfully reducing decision conflicts using decision aids. Large campaigns, including UK-based campaign ‘Be Clear on Cancer’, were instrumental in enhancing LC awareness, promoting help-seeking and yielding an increase in chest X-rays and a decrease in the number of individuals diagnosed with advanced LC. Multimodal public health interventions, such as educational campaigns are best suited to raise awareness, reduce barriers to help-seeking and help detect LC early. Future interventions ought to incorporate targeted information using educational resources, face-to-face counselling and video- and web-based decision aids.
Polygenic risk score for alcohol drinking behavior improves prediction of inflammatory bowel disease risk
Authors: Di Narzo Antonio F , Hart Amy , Kosoy Roman , Peters Lauren , Stojmirovic Aleksandar , Cheng Haoxiang , Zhang Zhongyang , Shan Mingxu , Cho Judy , Kasarskis Andrew , Argmann Carmen , Peter Inga , Schadt Eric E , Hao Ke 
Published: February 2021

Abstract
Epidemiological studies have long recognized risky behaviors as potentially modifiable factors for the onset and flares of inflammatory bowel disease (IBD); yet, the underlying mechanisms are largely unknown. Recently, the genetic susceptibilities to cigarette smoking, alcohol and cannabis use [i.e. substance use (SU)] have been characterized by well-powered genome-wide association studies (GWASs). We aimed to assess the impact of genetic determinants of SU on IBD risk. Using Mount Sinai Crohn’s and Colitis Registry (MSCCR) cohort of 1058 IBD cases and 188 healthy controls, we computed the polygenic risk score (PRS) for SU and correlated them with the observed IBD diagnoses, while adjusting for genetic ancestry, PRS for IBD and SU behavior at enrollment. The results were validated in a pediatric cohort with no SU exposure. PRS of alcohol consumption (DrnkWk), smoking cessation and age of smoking initiation, were associated with IBD risk in MSCCR even after adjustment for PRSIBD and actual smoking status. One interquartile range decrease in PRSDrnkWk was significantly associated to higher IBD risk (i.e. inverse association) (with odds ratio = 1.65 and 95% confidence interval: 1.32, 2.06). The association was replicated in a pediatric Crohn’s disease cohort. Colocalization analysis identified a locus on chromosome 16 with polymorphisms in IL27, SULT1A2 and SH2B1, which reached genome-wide statistical significance in GWAS (P &lt; 7.7e-9) for both alcohol consumption and IBD risk. This study demonstrated that the genetic predisposition to SU was associated with IBD risk, independent of PRSIBD and in the absence of SU behaviors. Our study may help further stratify individuals at risk of IBD.
Single-cell RNA sequencing reveals species-specific time spans of cell cycle transitions in early oogenesis
Authors: Zhao Zheng-Hui , Meng Tie-Gang , Zhang Hong-Yong , Hou Yi , Schatten Heide , Wang Zhen-Bo , Sun Qing-Yuan 
Published: February 2021

Abstract
Oogenesis is a highly regulated process and its basic cellular events are evolutionarily conserved. However, the time spans of oogenesis differ substantially among species. To explore these interspecies differences in oogenesis, we performed single-cell RNA-sequencing on mouse and monkey female germ cells and downloaded the single-cell RNA-sequencing data of human female germ cells. The cell cycle analyses indicate that the period and extent of cell cycle transitions are significantly different between the species. Moreover, hierarchical clustering of critical cell cycle genes and the interacting network of cell cycle regulators also exhibit distinguished patterns across species. We propose that differences in the regulation of cell cycle transitions may underlie female germ cell developmental allochrony between species. A better understanding of the cell cycle transition machinery will provide new insights into the interspecies differences in female germ cell developmental time spans.
Transportation noise and risk of stroke: a nationwide prospective cohort study covering Denmark
Authors: Sørensen Mette , Poulsen Aslak Harbo , Hvidtfeldt Ulla Arthur , Münzel Thomas , Thacher Jesse Daniel , Ketzel Matthias , Brandt Jørgen , Christensen Jesper H , Levin Gregor , Raaschou-Nielsen Ole 
Published: February 2021

AbstractBackgroundStudies on transportation noise and incident stroke are few and inconclusive. We aimed to investigate associations between road-traffic and railway noise and the risk of incident stroke in the entire Danish population.MethodsWe estimated road-traffic and railway noise (Lden) at the most and least exposed façades for all residential addresses across Denmark (2.8 million) for the period 1990–2017. Based on this, we estimated the 10-year time-weighted mean noise exposure for 3.6 million Danes aged &gt;35 years, of whom 184 523 developed incident stroke during follow-up from 2000 to 2017. Analyses were conducted using Cox proportional-hazards models, with adjustment for various individual- and area-level demographic and socio-economic covariates collected from registries and air pollution [fine particulate matter with particles with a diameter of ≤2.5 µm (PM2.5) and nitrogen dioxide (NO2)].ResultsA 10-dB increase in the 10-year mean road-traffic noise at the most exposed façade was associated with an incidence rate ratio (IRR) of 1.04 [95% confidence interval (CI): 1.03–1.05] for all strokes. For road-traffic noise at the least exposed façade, the IRR per 10 dB was 1.03 (95% CI: 1.02–1.04) for all strokes. Railway noise was not associated with a higher risk of stroke.ConclusionRoad-traffic noise increased the risk of stroke. These findings add to the evidence of road-traffic noise as a cardiovascular risk factor.
Mycobacterium tuberculosis Peptidyl Prolyl Isomerase A Interacts With Host Integrin Receptor to Exacerbate Disease Progression
Authors: Dubey Neha , Khan Mehak Zahoor , Kumar Suresh , Sharma Aditya , Das Lahari , Bhaduri Asani , Singh Yogendra , Nandicoori Vinay Kumar 
Published: February 2021

Abstract
Attenuated intracellular survival of Mycobacterium tuberculosis (Mtb) secretory gene mutants exemplifies their role as virulence factors. Mtb peptidyl prolyl isomerase A (PPiA) assists in protein folding through cis/trans isomerization of prolyl bonds. Here, we show that PPiA abets Mtb survival and aids in disease progression by exploiting host-associated factors. While the deletion of PPiA has no discernable effect on bacillary survival in a murine infection model, it compromises the formation of granuloma-like lesions and promotes host cell death through ferroptosis. Overexpression of PPiA enhances the bacillary load and exacerbates pathology in mice lungs. Importantly, PPiA interacts with the integrin α5β1 receptor through a conserved surface-exposed RGD motif. The secretion of PPiA as well as interaction with integrin contributes to disease progression by upregulating multiple host matrix metalloproteinases. Collectively, we identified a novel nonchaperone role of PPiA that is critical in facilitating host–pathogen interaction and ensuing disease progression.
Whole-Proteome Differential Screening Identifies Novel Vaccine Candidates forSchistosomiasis japonica
Authors: Wu Hannah W , Park Sangshin , Pond-Tor Sunthorn , Stuart Ron , Zhou Sha , Hong Yang , Ruiz Amanda E , Acosta Luz , Jarilla Blanca , Friedman Jennifer F , Jiz Mario , Kurtis Jonathan D 
Published: February 2021

AbstractSchistosomiasis remains a leading cause of chronic morbidity in endemic regions despite decades of widespread mass chemotherapy with praziquantel. Using our whole proteome differential screening approach, and plasma and epidemiologic data from a longitudinal cohort of individuals living in a Schistosoma japonicum–endemic region of the Philippines, we interrogated the parasite proteome to identify novel vaccine candidates for Schistosoma japonicum. We identified 16 parasite genes which encoded proteins that were recognized by immunoglobulin G or immunoglobulin E antibodies in the plasma of individuals who had developed resistance to reinfection, but were not recognized by antibodies in the plasma of individuals who remained susceptible to reinfection. Antibody levels to Sj6-8 and Sj4-1 measured in the entire cohort (N = 505) 1 month after praziquantel treatment were associated with significantly decreased risk of reinfection and lower intensity of reinfection over 18 months of follow-up.
Human SLC15A4 is crucial for TLR-mediated type I interferon production and mitochondrial integrity
Authors: Kobayashi Toshihiko , Nguyen-Tien Dat , Ohshima Daisuke , Karyu Hitomi , Shimabukuro-Demoto Shiho , Yoshida-Sugitani Reiko , Toyama-Sorimachi Noriko 
Published: February 2021

Abstract
Solute carrier family 15 member 4 (SLC15A4) is an endolysosome-resident amino acid transporter that regulates innate immune responses, and is genetically associated with inflammatory diseases such as systemic lupus erythematosus (SLE) and colitis. SLC15A4-deficient mice showed the amelioration of symptoms of these model diseases, and thus SLC15A4 is a promising therapeutic target of SLE and colitis. For developing a SLC15A4-based therapeutic strategy, understanding human SLC15A4’s properties is essential. Here, we characterized human SLC15A4 and demonstrated that human SLC15A4 possessed pH- and temperature-dependent activity for the transportation of dipeptides or tripeptides. Human SLC15A4 localized in LAMP1+ compartments and constitutively associated with Raptor and LAMTORs. We also investigated SLC15A4’s role in inflammatory responses using the human plasmacytoid dendritic cell line, CAL-1. Knock down (KD) of the SLC15A4 gene in CAL-1 (SLC15A4-KD CAL-1) impaired Toll-like receptor (TLR) 7/8 or TLR9-triggered type I interferon (IFN-I) production and mTORC1 activity, indicating that human SLC15A4 is critical for TLR7/8/9-mediated inflammatory signaling. We also examined SLC15A4’s role in the autophagy response since SLC15A4 loss caused the decrease of mTORC1 activity, which greatly influences autophagy. We found that SLC15A4 was not required for autophagy induction, but was critical for autophagy sustainability. Notably, SLC15A4-KD CAL-1 severely decreased mitochondrial membrane potential in starvation conditions. Our findings revealed that SLC15A4 plays a key role in mitochondrial integrity in human cells, which might benefit immune cells in fulfilling their functions in an inflammatory milieu.
Establishment of a research policy for supportive and palliative care in Japan
Authors: Zenda Sadamoto , Uchitomi Yosuke , Morita Tatsuya , Yamaguchi Takuhiro , Inoue Akira 
Published: February 2021

Abstract

Background
While several small groups in Japan have attempted to conduct prospective studies in the field of supportive and palliative care, development of exploratory research into multicentre confirmatory studies has been difficult. The main reason for this is the difference in clinical research methodology in supportive and palliative care compared with medical oncology in terms of the style of multidisciplinary approaches, study design and endpoints. Here, we establish a new research policy for cancer supportive and palliative care in Japan.

Methods
The first draft was developed by a policy working group within the Japanese Supportive, Palliative and Psychosocial Care Study Group. A provisional draft was subsequently developed after review by nine Japanese scientific societies (Japanese Association of Supportive Care in Cancer, Japanese Society of Medical Oncology, Japanese Society of Clinical Oncology, Japanese Society of Palliative Medicine, Japanese Society of Cancer Nursing, Japanese Society of Pharmaceutical Oncology (JASPO), Japan Cancer Association (JCA), Japanese Society of Therapeutic Radiation Oncology and Japanese Cancer Association) and receipt of public comments. The final research policy in the area of supportive and palliative care in Japan (Ver1.0) was completed in December 2018 and underwent its first revision (Ver1.1) in February, 2020.

Results
The policy includes the following components of clinical research: (i) objective of the research policy in the areas of supportive and palliative care; (ii) definitions of supportive care and palliative care; (iii) characteristics of supportive and palliative care research; (iv) target population for research; (v) research design; (vi) endpoints and assessment measures; (vii) handling of the deaths of subjects and (viii) operational structure and quality management.

Conclusions
We hope that studies conducted according to this policy will play important roles in the future development of the supportive and palliative field.
A multi-institutional randomized phase III study comparing weekly carboplatin plus nab-paclitaxel and daily low-dose carboplatin as regimens for concurrent chemoradiotherapy in elderly patients with unresectable locally advanced non-small cell lung cancer: Japan Clinical Oncology Group Study JCOG1914
Authors: Shimoyama Ryo , Omori Shota , Nomura Shogo , Kenmotsu Hirotsugu , Takahashi Toshiaki , Harada Hideyuki , Ishikura Satoshi , Mizutani Tomonori , Ando Masahiko , Kataoka Tomoko , Fukuda Haruhiko , Ohe Yuichiro ,   the Lung Cancer Study Group in the Japan Clinical Oncology Group
Published: February 2021

Abstract
Daily low-dose carboplatin plus concurrent thoracic radiotherapy is the standard treatment for elderly patients with unresectable clinical stage (c-Stage) III non-small cell lung cancer (NSCLC) in Japan. However, a phase I study by Omori et al. suggests that weekly carboplatin and nab-paclitaxel plus concurrent thoracic radiotherapy have comparable efficacy outcomes with more manageable adverse events. In December 2020, we initiated a randomized controlled trial in Japan to confirm whether the weekly carboplatin plus nab-paclitaxel regimen is noninferior to the daily low-dose carboplatin regimen for concurrent chemoradiotherapy in elderly patients with unresectable c-Stage III NSCLC. We plan to enroll 166 patients from 50 institutions in 3.5 years. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, response rate, proportion of patients starting maintenance durvalumab therapy, adverse events, site of progression, Functional Assessment of Cancer Therapy–Trial Outcome Index deterioration and Instrumental Activities of Daily Living deterioration.
Effect of the p53 P72R Polymorphism on Mutant TP53 Allele Selection in Human Cancer
Authors: De Souza Cristabelle , Madden Jill , Koestler Devin C , Minn Dennis , Montoya Dennis J , Minn Kay , Raetz Alan G , Zhu Zheng , Xiao Wen-Wu , Tahmassebi Neeki , Kathi Harikumara R , Nelson Nina , Karnezis Anthony N , Chien Jeremy 
Published: February 2021

Abstract

Background
TP53 mutations occur in more than 50% of cancers. We sought to determine the effect of the intragenic P72R single nucleotide polymorphism (SNP; rs1042522) on the oncogenic properties of mutant p53.

Methods
P72R allelic selection in tumors was determined from genotype calls and a Gaussian distributed mixture model. The SNP effect on mutant p53 was determined in p53-negative cancer cell lines. RNA-sequencing, chromatin immunoprecipitation, and survival analysis were performed to describe the SNP effect. All statistical tests were 2-sided.

Results
Among 409 patients with germline heterozygous P72R SNP who harbored somatic mutations in TP53, we observed a selection bias against missense TP53 mutants encoding the P72 SNP (P = 1.64 x 10-13). Exogenously expressed hotspot p53 mutants with the P72 SNP were negatively selected in cancer cells. Gene expression analyses showed the enrichment of p53 pathway genes and inflammatory genes in cancer cells transduced with mutants encoding P72 SNP. Immune gene signature is enriched in patients harboring missense TP53 mutations with homozygous P72 SNP. These patients have improved overall survival as compared with those with the R72 SNP (P = .04).

Conclusion
This is the largest study demonstrating a selection against the P72 SNP. Missense p53 mutants with the P72 SNP retain partial wild-type tumor-suppressive functions, which may explain the selection bias against P72 SNP across cancer types. Ovarian cancer patients with the P72 SNP have a better prognosis than with the R72 SNP. Our study describes a previously unknown role through which the rs1042522 SNP modifies tumor suppressor activities of mutant p53 in patients.