bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome wide association study on development and evolution of glutinous rice
Authors: Jiang Conghui , Rashid Muhammad Abdul Rehman , Zhang Yanhong , Zhao Yan , Pan Yinghua 
Published: May 2022

Abstract
Background
Glutinous rice as a special endosperm type is consumed as a staple food in East Asian countries by consumers’ preference. Genetic studies on glutinous rice could be conducive to improve rice quality and understand its development and evolution. Therefor, we sought to explore more genes related to glutinous by genome wide association study and research the formation history for glutinous.

Results
Here, genome-wide association study was performed to explore the associated loci/genes underlying glutinous rice by using 2108 rice accessions. Combining the expression patterns analysis, 127, 81, and 48 candidate genes were identified to be associated with endosperm type in whole rice panel, indica, and japonica sub-populations. There were 32 genes, including three starch synthesis-related genes Wx, SSG6, and OsSSIIa, detected simultaneously in the whole rice panel and subpopulations, playing important role in determining glutinous rice. The combined haplotype analyses revealed that the waxy haplotypes combination of three genes mainly distributed in Southeast Asia (SEA), SEA islands (SER) and East Asia islands (EAR). Through population structure and genetic differentiation, we suggest that waxy haplotypes of the three genes firstly evolved or were directly inherited from wild rice in japonica, and then introgressed into indica in SER, SEA and EAR.

Conclusions
The cloning and natural variation analysis of waxy-related genes are of great significance for the genetic improvement of quality breeding and comprehend the history in glutinous rice. This work provides valuable information for further gene discovery and understanding the evolution and formation for glutinous rice in SEA, SER and EAR.
P. aeruginosa type III and type VI secretion systems modulate early response gene expression in type II pneumocytes in vitro
Authors: Sen-Kilic Emel , Huckaby Annalisa B. , Damron F. Heath , Barbier Mariette 
Published: May 2022

Abstract
Background
Lung airway epithelial cells are part of innate immunity and the frontline of defense against bacterial infections. During infection, airway epithelial cells secrete proinflammatory mediators that participate in the recruitment of immune cells. Virulence factors expressed by bacterial pathogens can alter epithelial cell gene expression and modulate this response. Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, expresses numerous virulence factors to facilitate establishment of infection and evade the host immune response. This study focused on identifying the role of two major P. aeruginosa virulence factors, type III (T3SS) and type VI (T6SS) secretion systems, on the early transcriptome response of airway epithelial cells in vitro.

Results
We performed RNA-seq analysis of the transcriptome response of type II pneumocytes during infection with P. aeruginosa in vitro. We observed that P. aeruginosa differentially upregulates immediate-early response genes and transcription factors that induce proinflammatory responses in type II pneumocytes. P. aeruginosa infection of type II pneumocytes was characterized by up-regulation of proinflammatory networks, including MAPK, TNF, and IL-17 signaling pathways. We also identified early response genes and proinflammatory signaling pathways whose expression change in response to infection with P. aeruginosa T3SS and T6SS mutants in type II pneumocytes. We determined that T3SS and T6SS modulate the expression of EGR1, FOS, and numerous genes that are involved in proinflammatory responses in epithelial cells during infection. T3SS and T6SS were associated with two distinct transcriptomic signatures related to the activation of transcription factors such as AP1, STAT1, and SP1, and the secretion of pro-inflammatory cytokines such as IL-6 and IL-8.

Conclusions
Taken together, transcriptomic analysis of epithelial cells indicates that the expression of immediate-early response genes quickly changes upon infection with P. aeruginosa and this response varies depending on bacterial viability and injectosomes. These data shed light on how P. aeruginosa modulates host epithelial transcriptome response during infection using T3SS and T6SS.
Magnetically controlled capsule endoscopy in one-time gastro-small intestinal joint examination: a two-centre experience
Authors: Liu Ya-Wei , Wang Yuan-Chen , Zhu Jia-Hui , Jiang Xi , Zhou Wei , Zhang Jie , Liao Zhuan , Linghu En-Qiang 
Published: May 2022

Abstract
Background
The lesions of certain diseases are widely distributed in both stomach and small intestine, while the step-by-step strategy of gastroscopy followed by enteroscopy can be burdensome and costly. We aimed to determine if magnetically controlled capsule endoscopy (MCE) could be used in one-time gastro-small intestine (GSI) joint examination.

Methods
In this study, data of patients in Chinese PLA General Hospital and Changhai Hospital who underwent MCE GSI examination from January 2020 to August 2021 were retrospectively analysed. The primary outcome of this study was the success rate of one-time GSI joint examination, and secondary outcomes included visualization and cleanliness of gastrointestinal tract, gastrointestinal transit times, diagnostic yield and safety of MCE examination.

Results
A total of 768 patients were included. The success rate of one-time GSI joint examination was 92.58%. There were 94.92% MCEs observed > 90% gastric mucosa in the 6 anatomic landmarks. The rate of complete small bowel examination was 97.40%. The median gastric examination time, gastric transit time and small intestine transit time were 8.18 min, 63.89 min and 4.89 h, respectively. Magnetic steering of MCE significantly decreased gastric transit time (8.92 min vs. 79.68 min, P = 0.001) and increased duodenal lesion detection rate (13.47% vs. 6.26%, P = 0.001) when compared with non-magnetic steering group. Two capsules were retained and were removed by enteroscopy or spontaneously excreted.

Conclusions
MCE is feasible to complete GSI joint examination and the detection of both gastric and small intestinal diseases can be achieved simultaneously.
Trial registration Clinical Trial Registration ClinicalTrials.gov, ID: NCT05069233.
Novel subgroups of functional ability in older adults and their associations with adverse outcomes
Authors: Han Ying , Zhang Liangwen , Fang Ya 
Published: May 2022

Abstract
Background
There is no general agreement on a standard form of functional classification in older adults and is mainly assessed by Activities of Daily Living (ADL) and/or Instrument Activity of Daily Living. A refined classification based on evaluation the limitations of intrinsic capacity, environment and social interaction, could provide a basis to predict the future disability and identify individuals with increased risk of adverse outcomes.

Methods
A new functional classification among older adults aged 60 and over was conducted by latent class analysis and compared with the traditional classifications, based on the China Health and Retirement Longitudinal Study. To further investigate the scientific validity of this new classification, associations with 7-year mortality and ADLs impairments among categories were tested by using Survival curves and Cox proportional hazard models. This was followed by the confirmatory analysis related to the prospective data. Competing risk analysis was also performed to analysis the sensitivity to further support our conclusions.

Results
Five categories were identified among 5,992 older adults which gave the best fitting, yielding a significant Bootstrap Likelihood Ratio Test (p < 0.001) and Lo-Mendell-Rubin adjusted likelihood ratio test (p < 0.001), with an entropy over 0.80. The presence of five categories: “health” (34.0%), “sub-disorder status” (36.6%), “acute diseases” (10.3%), “somatic functional disorder” (7.7%), and “viability disorder” (11.4%), which matched well with the functional independence rates by the international classifications. Among them, those in “sub-disorder status” were considered as an intermediate status between disability and health. The findings also revealed that those who were in “acute disease”, “somatic functional disorders”, “health” and “sub-disorder status” had a significant lower risk of mortality and ADLs limitations than “viability disorder”. And the risks gradually increased towards the less functionally independent end of the classification. However, the distribution of characteristics among five categories were in a synchronous change, indicating a stable classification.

Conclusions
A new classification representing the functional heterogeneity of older adults could effectively stratify the risk of mortality and ADLs limitations. Identifying the clusters of functional decline might be useful in predicting subsequent ageing trends, designing personalized intervention, and delaying the progression of disability and preventing its occurrence.
Development, validation, and visualization of a web-based nomogram to predict 5-year mortality risk in older adults with hypertension
Authors: Zhang Huanrui , Tian Wen , Sun Yujiao 
Published: May 2022

AbstractBackgroundHypertension-related mortality has been increasing in older adults, resulting in serious burden to society and individual. However, how to identify older adults with hypertension at high-risk mortality remains a great challenge. The purpose of this study is to develop and validate the prediction nomogram for 5-year all-cause mortality in older adults with hypertension.MethodsData were extracted from National Health and Nutrition Examination Survey (NHANES). We recruited 2691 participants aged 65 years and over with hypertension in the NHANES 1999-2006 cycles (training cohort) and 1737 participants in the NHANES 2007-2010 cycles (validation cohort). The cohorts were selected to provide at least 5 years follow-up for evaluating all-cause mortality by linking National Death Index through December 31, 2015. We developed a web-based dynamic nomogram for predicting 5-year risk of all-cause mortality based on a logistic regression model in training cohort. We conducted internal validation by 1000 bootstrapping resamples and external validation in validation cohort. The discrimination and calibration of nomogram were evaluated using concordance index (C-index) and calibration curves.ResultsThe final model included eleven independent predictors: age, sex, diabetes, cardiovascular disease, body mass index, smoking, lipid-lowering drugs, systolic blood pressure, hemoglobin, albumin, and blood urea nitrogen. The C-index of model in training and validation cohort were 0.759 (bootstrap-corrected C-index 0.750) and 0.740, respectively. The calibration curves also indicated that the model had satisfactory consistence in two cohorts. A web-based nomogram was established (https://hrzhang1993.shinyapps.io/dynnomapp).ConclusionsThe novel developed nomogram is a useful tool to accurately predict 5-year all-cause mortality in older adults with hypertension, and can provide valuable information to make individualized intervention.
Impact of low-level viremia with drug resistance on CD4 cell counts among people living with HIV on antiretroviral treatment in China
Authors: Liu Pengtao , You Yinghui , Liao Lingjie , Feng Yi , Shao Yiming , Xing Hui , Lan Guanghua , Li Jianjun , Ruan Yuhua , Li Dan 
Published: May 2022

Abstract
Background
Maintaining plasma HIV RNA suppression below the limit of quantification is the goal of antiretroviral therapy (ART). When viral loads (VL) remain in low-level viremia (LLV), or between 201 and 999 copies/mL, the clinical consequences are still not clear. We investigated the occurrence of LLV with drug resistance and its effect on CD4 cell counts in a large Chinese cohort.

Methods
We analysed data of 6,530 ART-experienced patients (42.1 ± 10.9 years; 37.3% female) from the China’s national HIV drug resistance (HIVDR) surveillance database. Participants were followed up for 32.9 (IQR 16.7–50.5) months. LLV was defined as the occurrence of at least one viral load (VL) measurement of 50–200 copies/mL during ART. Outcomes were drug resistance associated mutations (DRAM) and CD4 cell counts levels.

Results
Among 6530 patients, 58.0% patients achieved VL less than 50 copies/mL, 27.8% with VL between 50 and 999 copies/mL (8.6% experienced LLV), and 14.2% had a VL ≥ 1000 copies/mL. Of 1818 patients with VL 50–999 copies/mL, 182 (10.0%) experienced HIVDR, the most common DRAM were M184I/V 28.6%, K103N 19.2%, and V181C/I/V 10.4% (multidrug resistance: 27.5%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/μL (AOR 3.8, 95% CI 2.6–5.5, p < 0.01) comparing with those without HIVDR. Of 925 patients with VL ≥ 1000 copies/mL, 495 (53.5%) acquired HIVDR, the most common DRAM were K103N 43.8%, M184I/V 43.2%, M41L 19.0%, D67N/G 16.4%, V181C/I/V 14.5%, G190A/S 13.9% and K101E 13.7% (multidrug resistance: 75.8%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/μL (AOR 5.8, 95% CI 4.6–7.4, p < 0.01) comparing with those without HIVDR.

Conclusion
Persistent with VL 50–999 copies/mL on ART is associated with emerging DRAM for all drug classes, and patients in this setting were at increased risk of CD4 cell counts < 200 cells/μL, which suggest resistance monitoring and ART optimization be earlier considered.
Measles immunity in medical center staff after changes in national and local hospital vaccination policies
Authors: Lin Meng-Yu , Shao Hsin-Hui , Tsou Meng-Ting 
Published: May 2022

Abstract
Background
Measles vaccination was introduced in Taiwan in 1978, and the disease was declared eliminated in Taiwan in 2007. However, new cases have been reported unpredictably since then. Hospital medical staff are at particularly high risk for measles. We evaluated the immunity status of hospital medical staff after changes in national and local hospital vaccination policies.

Methods
This retrospective study was conducted in a tertiary care medical center from January 2008 to June 2018. Data were retrieved from all healthcare workers receiving employment medical examinations. Those with a full medical record including the geometrical mean titer (GMT) of anti-measles IgG were included. Age and sex differences in the GMT were analyzed by Student’s t-tests and Chi-squared tests. Univariate and multivariate logistic regression analysis were used to determine the odds of immunity.

Results
The IgG positive rate increased with age group (p < 0.001). Seropositive rates for the birth before 1977 and after 1978 groups were 94.8% and 70.2% (p < 0.001). The odds ratio was also significantly different between both cohorts (1.000 vs. 0.423, p = 0.002). Staff in the examination department showed the lowest positive percentage of 70.3% (95% CI: 66.9–73.7%), whereas staff in preventive and long-term care services disclosed the highest positive percentage of 83.2% (95% CI: 76.1–90.2%). Subgroups 2015, 2017, and 2018 (p = 0.046, 0.046, 0.049), after the vaccination booster policy was launched, showed significant increases in seropositivity.

Conclusions
Immunity efficacy is better in birth groups before 1977, which was highly related to natural infection before national policy launched. The policy of vaccination is an effective method, but medical staff attains inadequate protective antibody levels for maintenance of herd immunity. A pre-employment policy of screening a third booster vaccine of measles (or MMR) is recommended to lower the incidence of disease spreading and avoid outbreaks.
Temperate climate malaria in nineteenth century Denmark
Authors: Ingholt Mathias Mølbak , Chen Tzu Tung , Hildebrandt Franziska , Pedersen Rasmus Kristoffer , Simonsen Lone 
Published: May 2022

Abstract
Background
Plasmodium vivax was endemic in northern Europe until the early twentieth century. Considering climate change and the recent emergence of other vector borne diseases in Europe, historical insight into the relationship between malaria and environmental factors in northern Europe is needed. This article describes malaria epidemiology in late-nineteenth century Denmark.

Methods
We described the seasonality and spatial patterns of malaria, and the relationship of the disease with environmental factors such as soil types, clay content and elevation for the period 1862–1914. We studied demographic and seasonal patterns and malaria mortality in the high-morbidity period of 1862–1880. Finally, we studied the relationship between malaria seasonality and temperature and precipitation using a Spearman correlation test.

Results
We found that the highest incidence occurred in eastern Denmark. Lolland-Falster medical region experienced the highest incidence (14.5 cases per 1000 pop.) and Bornholm medical region experienced the lowest incidence (0.57 cases per 1000 pop.). Areas with high malaria incidence also had high soil clay content, high agricultural production, and Lolland-Falster furthermore has a low elevation. Malaria incidence typically peaked in May and was associated with high temperatures in July and August of the previous year but not with precipitation. The case fatality rate was 0.17%, and the disease affected both sexes and all age groups except for infants. In 1873, a large epidemic occurred following flooding from a storm surge in November 1872.

Conclusions
Malaria gradually declined in Denmark during our study period and had essentially disappeared by 1900. The high adult and low child morbidity in 1862–1880 indicates that malaria was not highly endemic in this period, as malaria is most frequent among children in highly endemic areas today. The association of high malaria incidence in spring with warmer temperatures in the previous summer suggests that transmission took place in the previous summers. The close geographical connection between malaria and soil types, agricultural production and elevation suggests that these factors are detrimental to sustain endemic malaria. Our findings of a close connection between malaria and environmental factors such as climate and geography provides insights to address potential reintroduction of malaria in temperate climates.
Digital phenotyping in young breast cancer patients treated with neoadjuvant chemotherapy (the NeoFit Trial): protocol for a national, multicenter single-arm trial
Authors: Delrieu Lidia , Hamy Anne-Sophie , Coussy Florence , Kassara Amyn , Asselain Bernard , Antero Juliana , De Villèle Paul , Dumas Elise , Forstmann Nicolas , Guérin Julien , Hotton Judicael , Jouannaud Christelle , Milder Maud , Leopold Armand , Sedeaud Adrien , Soibinet Pauline , Toussaint Jean-François , Vercamer Vincent , Laas Enora , Reyal Fabien 
Published: May 2022

Abstract
Background
Breast cancer (BC) has particular characteristics in young women, with diagnosis at more advanced stages, a poorer prognosis and highly aggressive tumors. In NeoFit, we will use an activity tracker to identify and describe various digital profiles (heart rate, physical activity, and sleep patterns) in women below the age of 45 years on neoadjuvant chemotherapy for BC.

Methods
NeoFit is a prospective, national, multicenter, single-arm open-label study. It will include 300 women below the age of 45 years treated with neoadjuvant chemotherapy for BC. Participants will be asked to wear a Withing Steel HR activity tracker round the clock for 12 months. The principal assessments will be performed at baseline, at the end of neoadjuvant chemotherapy and at 12 months. We will evaluate clinical parameters, such as toxicity and the efficacy of chemotherapy, together with quality of life, fatigue, and parameters relating to lifestyle and physical activity. The women will complete REDCap form questionnaires via a secure internet link.

Discussion
In this study, the use of an activity tracker will enable us to visualize changes in the lifestyle of young women on neoadjuvant chemotherapy for BC, over the course of a one-year period. This exploratory study will provide crucial insight into the digital phenotypes of young BC patients on neoadjuvant chemotherapy and the relationship between these phenotypes and the toxicity and efficacy of treatment. This trial will pave the way for interventional studies involving sleep and physical activity interventions.

Trial registration
Clinicaltrials.gov identifier: NCT05011721. Registration date: 18/08/2021.
Trends, correlates, and disease patterns of sedative-hypnotic use among elderly persons in Taiwan
Authors: Kuo Chia-Lun , Chien I-Chia , Lin Ching-Heng 
Published: May 2022

Abstract
Objective
The population-based National Health Insurance database was adopted to investigate the prevalence, correlates, and disease patterns of sedative-hypnotic use in elderly persons in Taiwan.

Methods
The National Health Research Institutes provided a database of 1,000,000 random subjects in the National Health Insurance program. We adopted this sample of subjects who were older than 65 years from 1997 to 2005 and examined the proportions of psychiatric and nonpsychiatric disorders with regard to sedative-hypnotic use.

Results
The 1-year prevalence of sedative-hypnotic use in elderly individuals increased from 1.7% in 1997 to 5.5% in 2005. The 1-year prevalence rates of benzodiazepine (BZD) and non-BZD hypnotics were 3.2 and 3.1%, respectively, in 2005. The overall hypnotic use was highest in ≥85-year-olds, males, those with lower amounts of insurance or higher Charlson Comorbidity Index scores and those living in eastern Taiwan. Both BZD and non-BZD hypnotic use were most commonly used in nonpsychiatric disorders instead of psychiatric disorders. Among the psychiatric disorders, the disorders that accounted for higher BZD and non-BZD hypnotic use were senile and presenile organic psychotic conditions (3.4 and 3.4%, respectively). Higher BZD and non-BZD use was for diseases of the respiratory system (30.4 and 17.8%, respectively), the circulatory system (20.4 and 22.4%, respectively), and neoplasms (12.6 and 13.8%, respectively).

Conclusion
The prevalence rates of both BZD and non-BZD sedative-hypnotic use increased from 1997 to 2005 in the elderly. The risk factors for sedative-hypnotic use were aging, male sex, lower insurance amount, and higher Charlson Comorbidity Index scores. Most BZD and non-BZD sedative-hypnotic users were persons with nonpsychiatric disorders.