bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterisation of Mycobacterium avium subsp. paratuberculosis in Australia
Authors: Hodgeman Rachel , Mann Rachel , Savin Keith , Djitro Noel , Rochfort Simone , Rodoni Brendan 
Published: April 2021

Abstract
Background
Mycobacterium avium subsp. paratuberculosis (Map) causes Johne’s disease (JD), a chronic enteritis widespread in ruminants, resulting in substantial economic losses, especially to the dairy industry. Understanding the genetic diversity of Map in Australia will assist epidemiological studies for tracking disease transmission and identify subtype characteristics for use in development of improved diagnostic typing methods. Here we investigated the phylogenetic relationships of 351 Map isolates and compared different subtyping methods to assess their suitability for use in diagnostics and accuracy.

Results
SNP-based phylogenetic analysis of 228 Australian isolates and 123 publicly available international isolates grouped Type S and Type C strains into two distinct lineages. Type C strains were highly monomorphic with only 20 SNP differences separating them. Type S strains, when aligned separately to the Telford strain, fell into two distinct clades: The first clade contained seven international isolates while the second clade contained one international isolate from Scotland and all 59 Australian isolates. The Australian Type B strain clustered with US bison strains. IS1311 PCR and Restriction Enzyme Analysis (REA) intermittently generated incorrect results when compared to Long Sequence Polymorphism (LSP) analysis, whole genome SNP-based phylogenetic analysis, IS1311 sequence alignment and average nucleotide identity (ANI). These alternative methods generated consistent Map typing results. A published SNP based assay for genotyping Map was found to be unsuitable for differentiating between Australian and international strain types of Map.

Conclusion
This is the first phylogenetic analysis of Australian Map isolates. The Type C lineage was highly monomorphic, and the Type S lineage clustered all Australian isolates into one clade with a single Scottish sheep strain. The Australian isolate classified as Type B by IS1311 PCR and REA is likely to be descended from bison and most closely related to US bison strains. Limitations of the current typing methods were identified in this study.
Photosynthesis acclimation under severely fluctuating light conditions allows faster growth of diatoms compared with dinoflagellates
Authors: Zhou Lu , Wu Songcui , Gu Wenhui , Wang Lijun , Wang Jing , Gao Shan , Wang Guangce 
Published: April 2021

Abstract
Background
Diatoms contribute 20% of the global primary production and are adaptable in dynamic environments. Diatoms always bloom earlier in the annual phytoplankton succession instead of dinoflagellates. However, how diatoms acclimate to a dynamic environment, especially under changing light conditions, remains unclear.

Results
We compared the growth and photosynthesis under fluctuating light conditions of red tide diatom Skeletonema costatum, red tide dinoflagellate Amphidinium carterae, Prorocentrum donghaiense, Karenia mikimotoi, model diatom Phaeodactylum tricornutum, Thalassiosira pseudonana and model dinoflagellate Dinophycae Symbiodinium. Diatoms grew faster and maintained a consistently higher level of photosynthesis. Diatoms were sensitive to the specific inhibitor of Proton Gradient Regulation 5 (PGR5) depending photosynthetic electron flow, which is a crucial mechanism to protect their photosynthetic apparatus under fluctuating light. In contrast, the dinoflagellates were not sensitive to this inhibitor. Therefore, we investigate how PGR5 functions under light fluctuations in the model diatom P. tricornutum by knocking down and overexpressing PGR5. Overexpression of PGR5 reduced the photosystem I acceptor side limitation (Y (NA)) and increased growth rate under severely fluctuating light in contrast to the knockdown of PGR5.

Conclusion
Diatoms acclimatize to fluctuating light conditions better than dinoflagellates. PGR5 in diatoms can regulate their photosynthetic electron flow and accelerate their growth under severe light fluctuation, supporting fast biomass accumulation under dynamic environments in pioneer blooms.
Gastrointestinal symptoms as the first manifestation of antiphospholipid syndrome
Authors: Zou Xiaojuan , Fan Zhongqi , Zhao Ling , Xu Weiling , Zhang Jin , Jiang Zhenyu 
Published: April 2021

Abstract
Background
Antiphospholipid syndrome (APS) is an acquired pre-thrombotic autoimmune condition, which produces autoantibodies called antiphospholipid antibodies (APL) against phospholipid-binding plasma proteins. The diagnosis of APS requires at least one of Sapporo standard clinical manifestations and one laboratory criteria (persistently medium/high titer anticardiolipin antibodies, and/or medium/high titer anti-β2-glycoprotein I antibodies, and/or a positive lupus anticoagulant test). Gastrointestinal lesions are rarely reported in APS patients. APS cases with recurrent abdominal pain as the first clinical manifestation are even rarer.

Case presentation
This report describes an APS case with recurrent abdominal pain as the first clinical manifestation of antiphospholipid syndrome. The patient has a history of two miscarriages. Computed tomography of the abdomen confirmed mesenteric thrombosis and intestinal obstruction while laboratory tests for serum antiphospholipid and anti-β2-glycoprotein I antibodies were positive. This led to the diagnosis of APS.

Conclusions
This paper provides useful information on gastrointestinal manifestations and APS, also including a brief literature review about possible gastrointestinal symptoms of APS.
Evaluation of circulating cell-free DNA in cholestatic liver disease using liver-specific methylation markers
Authors: Punia Sohan , Juran Brian D. , Ali Ahmad H. , Schlicht Erik M. , Moore Raymond M. , Sun Zhifu , Lazaridis Konstantinos N. 
Published: April 2021

Abstract
Background
Quantification of circulating organ-specific cell-free DNA (cfDNA) provides a sensitive measure of ongoing cell death that could benefit evaluation of the cholestatic liver diseases primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), which lack reliable non-invasive biomarkers. Our goal in this pilot study was to determine whether liver-specific cfDNA levels are increased in PBC and PSC patients relative to controls and in advanced versus early disease, to evaluate their potential as novel disease biomarkers.

Methods
Peripheral blood derived bisulfite-treated DNA was PCR amplified from patients with PBC (n = 48), PSC (n = 48) and controls (n = 96) to evaluate methylation status at 16 CpG sites reported to be specifically unmethylated in liver tissue near the genes IGF2R, ITIH4 and VTN. Amplicons were used to prepare paired end libraries which were sequenced on a MiSeq sequencer. Trimmed reads were aligned and used to determine unmethylation ratios and to calculate concentration of liver-specific cfDNA. Comparisons between groups were performed using the two-tailed Mann–Whitney Test and relationships between variables were evaluated using Pearson’s Correlation.

Results
Levels of liver-specific cfDNA, as measured at the 3 genetic loci, were increased in PBC and PSC patients relative to controls and in late-stage relative to early-stage patients. As well, cfDNA levels were correlated with levels of alkaline phosphatase, a commonly used biochemical test to evaluate disease severity in liver disease, in patients, but not in controls.

Conclusions
cfDNA offers promise as a non-invasive liquid-biopsy to evaluate liver-specific cell-death in patients with cholestatic liver diseases.
Activity of daily living upon admission is an independent predictor of in-hospital mortality in older patients with community-acquired pneumonia
Authors: Kang Yu , Fang Xiang-Yang , Wang Dong , Wang Xiao-Juan 
Published: April 2021

Abstract
Background
Older patients hospitalized with community-acquired pneumonia (CAP) are at high risk for short-term mortality. Activity of daily living (ADL) is associated with clinical outcomes in older patients. We aimed to investigate the prognostic value of ADL upon admission on the in-hospital mortality in older patients with CAP.

Methods
We conducted a retrospective cohort study involving patients aged ≥65 years admitted to Beijing Chao-Yang hospital due to CAP between June 2012 and June 2020. ADL evaluation upon admission was performed by Barthel Index (BI). Data from all patients were extracted from the electronic medical records.

Results
Four thousand eight hundred eighty patients were included, 131 patients (2.7%) died during their hospitalization. Median BI in the Deceased group was 45 (20–65), Deceased group had lower BI scores than Survivors group (p < 0.001). Low BI (< 60) was more frequent in patients who died in the hospital than in patients discharged alive (69.5% vs. 13%, p < 0.001). In-hospital mortality was higher among patients with worse ADL upon admission (BI< 60) compared to those BI≥60 (12.6% vs. 0.9%). The worse ADL upon admission (BI< 60) was associated with an increase in the risk of death during CAP hospitalization, worse ADL upon admission (BI< 60) showed an odds ratio (OR) for in-hospital mortality of 7.53 (95%CI: 2.77–20.48; P < 0.01). This association remained significant after adjustment for age, comorbid conditions, respiratory failure, pathogens and laboratory findings (OR, 3.74; 95%CI, 2.37–5.91; P < 0.01). Receiver operating characteristic (ROC) curve revealed that BI upon admission is a predictor related to in-hospital mortality in elderly patients, the area under the ROC curve of BI in predicting in-hospital mortality was 0.81 (with 95% confidence interval: 0.78–0.85). The predictive value of ADL upon admission was better than age in our study population.

Conclusion
Activity of daily living upon admission is an independent predictor of in-hospital mortality in older patients with community-acquired pneumonia.
Clinical factors associated with shorter durable response, and patterns of acquired resistance to first-line pembrolizumab monotherapy in PD-L1-positive non-small-cell lung cancer patients: a retrospective multicenter study
Authors: Hosoya Kazutaka , Fujimoto Daichi , Morimoto Takeshi , Kumagai Toru , Tamiya Akihiro , Taniguchi Yoshihiko , Yokoyama Toshihide , Ishida Tadashi , Matsumoto Hirotaka , Hirano Katsuya , Kominami Ryota , Tomii Keisuke , Suzuki Hidekazu , Hirashima Tomonori , Tanaka Satoshi , Uchida Junji , Morita Mitsunori , Kanazu Masaki , Mori Masahide , Nagata Kenji , Fukuda Ikue , Tamiya Motohiro 
Published: April 2021

Abstract
Background
Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved.

Methods
We conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions.

Results
Among 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR.

Conclusions
Patients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients.
Diagnostic measures for severe acute malnutrition in Indian infants under 6 months of age: a secondary data analysis
Authors: Chowdhury Ranadip , Nitika  , Choudhary Tarun Shankar , Taneja Sunita , Martines Jose , Bhandari Nita , Bahl Rajiv 
Published: April 2021

Abstract
Background
Weight for length z-score (WLZ) < − 3 is currently used to define severe acute malnutrition (SAM) among infants. However, this approach has important limitations for infants younger than 6 months of age as WLZ cannot be calculated using WHO growth standards if infant length is < 45 cm. Moreover, length for age z-score (LAZ) and weight for length z-score (WLZ) are least reliable measures, with high chances of variation, and less chances of detecting undernutrition in under 6 months infants. The objective of the current analysis was to compare WLZ with WAZ and LAZ in a cohort of Indian infants in predicting the deaths between 6 weeks and 6 months of age.

Methods
The data was from an individually randomized trial conducted in slums of Delhi, India in which infants’ weight and length were measured at 6 weeks of age (at the time of the first immunization visit). Vital status of the infants was documented from 6 weeks to 6 months of age. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated for WAZ < -3, WLZ < -3, and LAZ < -3 for deaths between 6 weeks and 6 months of age. The receiver operating characteristics curve was calculated for each of the above anthropometric indicators.

Results
For deaths occurring between 6 weeks to 6 months of age, the specificity ranged between 85.9–95.9% for all three anthropometric indicators. However, the sensitivity was considerably higher for WAZ; it was 64.6% for WAZ < -3, 39.1% for LAZ < -3, and 25.0% for WLZ < -3. WAZ < -3 had higher area under curve (0.75; 95% CI: 0.68, 0.82) and hence, better discriminated deaths between 6 weeks and 6 months of age than WLZ < -3. The adjusted relative risk (RR 10.6, 95% CI 5.9, 18.9) and the population attributable fraction (PAF 57.9, 95% CI 38.8, 71.0%) of mortality was highest for WAZ < -3.

Conclusions
We found WAZ < -3 at 6 weeks of age to be a better predictor of death in the 6 weeks to 6 months of life in comparison to WLZ < -3 and LAZ < -3 and propose that it should be considered to diagnose SAM in this age group.
Mental health of undocumented migrants and migrants undergoing regularization in Switzerland: a cross-sectional study
Authors: Fakhoury Julien , Burton-Jeangros Claudine , Consoli Liala , Duvoisin Aline , Courvoisier Delphine , Jackson Yves 
Published: April 2021

Abstract
Background
Undocumented migrants live and work in precarious conditions. Few studies have explored the mental health consequences of such environment. The objective of this study is to describe the mental health of migrants at different stages of a regularization program.

Methods
This cross-sectional study included migrants undocumented or in the process of regularization. We screened for symptoms of anxiety, depression and sleep disturbance using validated tools. We created a composite outcome of altered mental health including these components plus self-report of a recent diagnosis of mental health condition by a health professional.

Results
We enrolled 456 participants of whom 246 (53.9%) were undocumented. They were predominantly women (71.9%) with a median age of 43.3 (interquartile range: 15.5) years, from Latin America (63.6%) or Asia (20.2%) who had lived in Switzerland for 12 (IQR: 7) years. Overall, 57.2% presented symptoms of altered mental health. Prevalence of symptoms of anxiety, depression and sleep disturbance were 36% (95% confidence interval: 31.6–40.6%), 45.4% (95% CI: 40.8–50.1%) and 23% (95% CI: 19.2–27.2), respectively. Younger age (adjusted odd ratio: 0.7; 95% CI: 0.5–0.9 for each additional decade), social isolation (aOR: 2.4; 95% CI: 1.4–4.2), exposure to abuse (aOR: 1.9; 95% CI: 1.1–3.5), financial instability (aOR: 2.2; 95% CI: 1.4–3.7) and multi-morbidity (aOR: 3.2; 95% CI: 1.7–6.5) were associated with increased risk of having altered mental health while being in the early stages of the process of regularization had no effect (aOR: 1.3: 95% CI: 0.8–2.2).

Conclusions
This study highlights the need for multi-pronged social and health interventions addressing the various domains of undocumented migrants living difficulties as complement to legal status regularization policies. Protection against unfair working conditions and abuse, access to adequate housing, promoting social integration and preventive interventions to tackle the early occurrence of chronic diseases may all contribute to reduce the burden of altered mental health in this group. More research is needed to assess the long-term impact of legal status regularization on mental health.
Noise sensitivity associated with nonrestorative sleep in Chinese adults: a cross-sectional study
Authors: Li Sha , Fong Daniel Yee Tak , Wong Janet Yuen Ha , McPherson Bradley , Lau Esther Yuet Ying , Huang Lixi , Ip Mary Sau Man 
Published: April 2021

Abstract
Background
Nonrestorative sleep is a common sleep disorder with a prevalence ranging from 1.4 to 35%, and is associated with various psychological and physical health issues. Noise exposure and noise sensitivity have been proposed to contribute to nonrestorative sleep. This study aimed to examine the relationships among noise, noise sensitivity, nonrestorative sleep, and physiological sleep parameters in Chinese adults.

Methods
A cross-sectional household survey was conducted with randomly selected Chinese adults based on a frame stratified by geographical districts and types of quarters in Hong Kong. We administered a battery of questionnaires, including the Nonrestorative Sleep Scale, the Weinstein Noise Sensitivity Scale, the ENRICHD Social Support Instrument, the Patient Health Questionnaire, and the Perceived Stress Scale to assess nonrestorative sleep, noise sensitivity, social support, somatic symptoms and stress, respectively. Anxiety and depression were evaluated by the Hospital Anxiety and Depression Scale while sociodemographic and lifestyle characteristics were assessed with an investigator-developed sheet. Nocturnal noise level and physiological sleep parameters were measured during nighttime for a week by noise dosimetry and actigraphy, respectively. A structured multiphase linear regression was conducted to estimate associations.

Results
A total of 500 adults (66.4% female) with an average age of 39 years completed this study. Bivariate regressions showed that age, marital status, occupation, family income, season, exercise, cola and soda consumption, social support, somatic symptoms, stress, depression, noise sensitivity, total sleep time, and awakenings were associated with nonrestorative sleep. In the multivariable analysis, family income, season, exercise, social support, somatic symptoms, stress, and depression remained associated with nonrestorative sleep. Specifically, a one-unit increase of noise sensitivity was associated with 0.08 increase in nonrestorative sleep (95% confidence interval [CI]: 0.01, 0.15, p = 0.023). Nocturnal noise was negatively associated with time in bed (b = − 1.65, 95% CI: − 2.77, − 0.52, p = 0.004), total sleep time (b = − 1.61, 95% CI: − 2.59, − 0.62, p = 0.001), and awakenings (b = − 0.16, 95% CI: − 0.30, − 0.03, p = 0.018), but was not associated with nonrestorative sleep.

Conclusions
Nonrestorative sleep was predicted by noise sensitivity in addition to family income, season, exercise, social support, somatic symptoms, stress, and depression.
Correlation between loss of Smad4 and clinical parameters of non-small cell lung cancer: an observational cohort study
Authors: Guo Xiangjun , Li Mengmeng , Wang Xin , Pan Yun , Li Jiashu 
Published: April 2021

Abstract
Background
SMAD4 has been found to be inactivated to varying degrees in many types of cancer; the purpose of this study was to investigate the correlation between SMAD4 expression in non-small cell lung cancer (NSCLC) and clinical pathological parameters.

Methods
The serum concentration of SMAD4 was measured by enzyme-linked immunosorbent assay and its histological expression was quantified by immunohistochemistry.

Results
The serum concentration of Smad4 in patients with NSCLC was lower than that in benign lung disease patients and healthy individuals (P < 0.001) and its concentration was related to the histological classification, pathological differentiation, lymphatic metastasis and clinical stage of NSCLC. The sensitivity and specificity of serum Smad4 were 91.56% and 61.56% for screening NSCLC from healthy individuals and 84.55% and 60.36% for screening NSCLC from patients with benign lung disease. Logistic regression analysis showed that the degree of cell differentiation (P < 0.001), lymph node metastasis (P < 0.001) and clinical stage of NSCLC (P = 0.007) affected the expression of Smad4, and had a strong correlation with the expression of Smad4. The expression of Smad4 in NSCLC tissues was lower than that in normal lung tissues (P = 0.009) and its expression was related to the degree of tissue differentiation, lymph node metastasis and clinical stage (P < 0.05).

Conclusions
The downregulation or deletion of Smad4 is related to the malignant biological behavior of NSCLC and serum Smad4 could be considered as a potential molecular indicator for diagnosis and evaluation of NSCLC.
The effect of atorvastatin on inflammatory markers in sulfur mustard gas induced bronchitis: a randomized double-blinded, placebo-control clinical trial
Authors: Momeni Behrooz , Nazer Saeed , Masoompour Seyed Masoom , Geramizadeh Bita , Sajadi Seyed Vahid 
Published: April 2021

AbstractBackgroundThis study was performed to evaluate the anti-inflammatory effect of atorvastatin in patients with chronic bronchitis, exposed to sulfur mustard gas.MethodsIn this randomized double-blinded clinical trial we recruited patients with chronic bronchitis after exposure to sulfur mustard gas. Ninety men 45–75 years old diagnosed with chronic bronchitis after exposure to mustard gas during the Iran-Iraq war, were randomly assigned to receive either atorvastatin (40 mg) or placebo once a day for 3 months. The interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), procalcitonin, highly sensitive CRP and COPD assessment test (CAT) score was compared at baseline and after 12 weeks.ResultsAfter consuming atorvastatin for 12 weeks, IL-6 level (mean difference [95%CI]; 0.2 [− 0.05, 0.5]), TNF-α (mean difference [95%CI]; − 0.07 [− 0.2, 0.07]), high sensitive CRP (mean difference [95%CI] − 0.1 [− 1.2, 0.9]), and procalcitonin (mean difference [95%CI]; 0.003 [− 0.02, 0.03]) did not change significantly. However, in the placebo group, only IL-6 (mean difference [95%CI]; 0.6 [0.2, 1.05]) decreased significantly after 12 weeks, but levels of high sensitive CRP (mean difference [95%CI]; − 0.3 [− 1.4, 0.8]) TNF-α (mean difference [95%CI]; − 0.2 [− 0.34, − 0.06]) and procalcitonin (mean difference [95%CI]; 0.02 [− 0.001, 0.04]) did not change significantly. After 12 weeks, the mean differences in TNF- α, IL-6 level, high sensitive CRP, procalcitonin, and CAT score did not significantly differ between the two groups.ConclusionsThe administration of 40 mg atorvastatin for 3 months did not significantly change the inflammatory markers or the quality of life of patients exposed to mustard gas with chronic bronchitis.Trial registration: IRCT, IRCT138904144312N1. Registered 16 August 2014,https://en.irct.ir/trial/4577.