bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disseminated Bacillus Calmette–Guérin (BCG) infection and acute exacerbation of interstitial pneumonitis: an autopsy case report and literature review
Authors: Shimizu Gen , Amano Ryota , Nakamura Itaru , Wada Akane , Kitagawa Masanobu , Toru Shuta 
Published: September 2020

Abstract
Background
Intravesical administration of Bacillus Calmette–Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy.

Case presentation
A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident.

Conclusions
We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.
Hemophagocytic syndrome associated with Mycobacterium bovis in a patient with X-SCID: a case report
Authors: Shi Buyun , Chen Ming , Xia Zhi , Xiao Shuna , Tang Wen , Qin Chenguang , Cheng Ying , Huang Tao , Huang Chengjiao , Li Yong , Xu Hui 
Published: September 2020

Abstract
Background
Mycobacterium bovis could infect patients with immunodeficiency or immunosuppressive conditions via Bacillus Calmette-Guérin (BCG) vaccination. Tuberculosis-related hemophagocytic syndrome (HPS) is reported, but not HPS caused by Mycobacterium bovis in children.

Case presentation
A 4-month Chinese boy presented fever and cough. The initial laboratory investigation showed the lymphocyte count of 0.97 × 109/L, which decreased gradually. HPS was diagnosed based on the test results that fulfilled the HLH-2004 criteria. In addition, Mycobacterium tuberculosis complex was detected from his peripheral blood via metagenomic next-generation sequencing (mNGS) and M. bovis was identified by polymerase chain reaction-reverse dot blot (PCR-RDB). Thus, the patient was treated with Isoniazid, Rifampin, and Pyrazinamide, but not improved. However, parents refused to accept further therapy, and was discharged on the day 12 of admission. To confirm the pathogenesis, genetic analysis was performed. Mutation in the interleukin-2 receptor subunit gamma gene: Exon 6: c.854G > A; p. Arg285Gln was detected in the patient and the mother, which could underlie X-linked severe combined immunodeficiency.

Conclusions
A boy with X-SCID was diagnosed with M. bovis-associated HPS, emphasizing that X-SCID should be considered when M. bovis is detected in a male infant with low lymphocyte counts.
Novel FHL1 mutation variant identified in a patient with nonobstructive hypertrophic cardiomyopathy and myopathy – a case report
Authors: Giucă Adrian , Mitu Cristina , Popescu Bogdan Ovidiu , Bastian Alexandra Eugenia , Capşa Răzvan , Mursă Adriana , Rădoi Viorica , Popescu Bogdan Alexandru , Jurcuţ Ruxandra 
Published: September 2020

Abstract
Background
Hypertrophic cardiomyopathy (HCM) is a genetic disorder mostly caused by sarcomeric gene mutations, but almost 10% of cases are attributed to inherited metabolic and neuromuscular disorders. First described in 2008 in an American-Italian family with scapuloperoneal myopathy, FHL1 gene encodes four-and-a-half LIM domains 1 proteins which are involved in sarcomere formation, assembly and biomechanical stress sensing both in cardiac and skeletal muscle, and its mutations are responsible for a large spectrum of neuromuscular disorders (mostly myopathies) and cardiac disease, represented by HCM, either isolated, or in conjunction with neurologic and skeletal muscle impairment. We thereby report a novel mutation variant in FHL1 structure, associated with HCM and type 6 Emery-Dreifuss muscular dystrophy (EDMD).

Case presentation
We describe the case of a 40 year old male patient, who was referred to our department for evaluation in the setting of NYHA II heart failure symptoms and was found to have HCM. The elevated muscular enzymes raised the suspicion of a neuromuscular disease. Rigid low spine and wasting of deltoidus, supraspinatus, infraspinatus and calf muscles were described by the neurological examination. Electromyography and muscle biopsy found evidence of chronic myopathy. Diagnosis work-up was completed by next-generation sequencing genetic testing which found a likely pathogenic mutation in the FHL1 gene (c.157-1G > A, hemizygous) involved in the development of X-linked EDMD type 6.

Conclusion
This case report highlights the importance of multimodality diagnostic approach in a patient with a neuromuscular disorder and associated hypertrophic cardiomyopathy by identifying a novel mutation variant in FHL1 gene. Raising awareness of non-sarcomeric gene mutations which can lead to HCM is fundamental, because of diagnostic and clinical risk stratification challenges.
Reconstruction of lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveals functional lncRNAs in skin cutaneous melanoma
Authors: Zhu Junyou , Deng Jin , Zhang Lijun , Zhao Jingling , Zhou Fei , Liu Ning , Cai Ruizhao , Wu Jun , Shu Bin , Qi Shaohai 
Published: September 2020

Abstract
Background
Human skin cutaneous melanoma is the most common and dangerous skin tumour, but its pathogenesis is still unclear. Although some progress has been made in genetic research, no molecular indicators related to the treatment and prognosis of melanoma have been found. In various diseases, dysregulation of lncRNA is common, but its role has not been fully elucidated. In recent years, the birth of the “competitive endogenous RNA” theory has promoted our understanding of lncRNAs.

Methods
To identify the key lncRNAs in melanoma, we reconstructed a global triple network based on the “competitive endogenous RNA” theory. Gene Ontology and KEGG pathway analysis were performed using DAVID (Database for Annotation, Visualization, and Integration Discovery). Our findings were validated through qRT-PCR assays. Moreover, to determine whether the identified hub gene signature is capable of predicting the survival of cutaneous melanoma patients, a multivariate Cox regression model was performed.

Results
According to the “competitive endogenous RNA” theory, 898 differentially expressed mRNAs, 53 differentially expressed lncRNAs and 16 differentially expressed miRNAs were selected to reconstruct the competitive endogenous RNA network. MALAT1, LINC00943, and LINC00261 were selected as hub genes and are responsible for the tumorigenesis and prognosis of cutaneous melanoma.

Conclusions
MALAT1, LINC00943, and LINC00261 may be closely related to tumorigenesis in cutaneous melanoma. In addition, MALAT1 and LINC00943 may be independent risk factors for the prognosis of patients with this condition and might become predictive molecules for the long-term treatment of melanoma and potential therapeutic targets.
Immunological and clinicopathological characteristics of C1RL in 2120 glioma patients
Authors: Wang Junyou , Tong Luqing , Lin Gaojun , Wang Hui , Zhang Liang , Yang Xuejun 
Published: September 2020

Abstract
Background
Glioma is a deadly and immunosuppressive brain tumour. Complement C1r subcomponent like (C1RL), a prognostic biomarker in several kinds of tumours, has attracted increasing attention from oncologists. However, the role of C1RL in glioma remains unclear.

Methods
Through analysis of 2120 glioma patients from 5 public datasets, the relationships between C1RL expression and clinicopathological characteristics were evaluated. Furthermore, the C1RL-associated genes were screened, and Gene Ontology (GO) analysis was conducted to investigate biological process enrichment. In addition, tumour purity, leukocyte infiltration and overall survival were evaluated based on C1RL expression.

Results
We found that C1RL expression was upregulated in glioblastoma (GBM), especially mesenchymal GBM and primary GBM. Increased C1RL expression accompanied the IDH1-wt phenotype in both lower grade glioma (LGG) and GBM. C1RL- associated genes were mainly enriched in biological processes related to the immune response. C1RL expression was also correlated with reduced tumour purity and increased M2 macrophage infiltration. Higher C1RL expression predicted unfavourable survival in patients with glioma and therapeutic resistance in GBM.

Conclusions
Our results imply that C1RL is involved in immunological activities and is an independent unfavourable prognostic biomarker in patients with glioma. C1RL is a potential clinical immunotherapeutic target for glioma treatment in the future.
Quantifying the direct secondary health care cost of seasonal influenza in England
Authors: Moss Joe W. E. , Davidson Craig , Mattock Richard , Gibbons Ilana , Mealing Stuart , Carroll Stuart 
Published: September 2020

Abstract
Background
The winter pressure often experienced by NHS hospitals in England is considerably contributed to by severe cases of seasonal influenza resulting in hospitalisation. The prevention planning and commissioning of the influenza vaccination programme in the UK does not always involve those who control the hospital budget. The objective of this study was to describe the direct medical costs of secondary care influenza-related hospital admissions across different age groups in England during two consecutive influenza seasons.

Methods
The number of hospital admissions, length of stay, and associated costs were quantified as well as determining the primary costs of influenza-related hospitalisations. Data were extracted from the Hospital Episode Statistics (HES) database between September 2017 to March 2018 and September 2018 to March 2019 in order to incorporate the annual influenza seasons. The use of international classification of disease (ICD)-10 codes were used to identify relevant influenza hospitalisations. Healthcare Resource Group (HRG) codes were used to determine the costs of influenza-related hospitalisations.

Results
During the 2017/18 and 2018/19 seasons there were 46,215 and 39,670 influenza-related hospital admissions respectively. This resulted in a hospital cost of £128,153,810 and £99,565,310 across both seasons. Results showed that those in the 65+ year group were associated with the highest hospitalisation costs and proportion of in-hospital deaths. In both influenza seasons, the HRG code WJ06 (Sepsis without Interventions) was found to be associated with the longest average length of stay and cost per admission, whereas PD14 (Paediatric Lower Respiratory Tract Disorders without Acute Bronchiolitis) had the shortest length of stay.

Conclusion
This study has shown that influenza-related hospital admissions had a considerable impact on the secondary healthcare system during the 2017/18 and 2018/19 influenza seasons, before taking into account its impact on primary health care.
Determinants of malaria among under-five children in Ethiopia: Bayesian multilevel analysis
Authors: Aychiluhm Setognal Birara , Gelaye Kassahun Alemu , Angaw Dessie Abebaw , Dagne Getachew Asfaw , Tadesse Abay Woday , Abera Adugna , Dillu Dereje 
Published: September 2020

Abstract
Background
In Ethiopia, malaria is one of the public health problems, and it is still among the ten top leading causes of morbidity and mortality among under-five children.
However, the studies conducted in the country have been inconclusive and inconsistent. Thus, this study aimed to assess factors associated with malaria among under-five children in Ethiopia.

Methods
We retrieved secondary data from the malaria indicator survey data collected from September 30 to December 10, 2015, in Ethiopia. A total of 8301 under-five-year-old children who had microscopy test results were included in the study. Bayesian multilevel logistic regression models were fitted and Markov chain Monte Carlo simulation was used to estimate the model parameters using Gibbs sampling. Adjusted Odd Ratio with 95% credible interval in the multivariable model was used to select variables that have a significant association with malaria.

Results
In this study, sleeping under the insecticide-treated bed nets during bed time (ITN) [AOR 0.58,95% CI, 0.31–0.97)], having 2 and more ITN for the household [AOR 0.43, (95% CI, 0.17–0.88)], have radio [AOR 0.41, (95% CI, 0.19–0.78)], have television [AOR 0.19, (95% CI, 0.01–0.89)] and altitude [AOR 0.05, (95% CI, 0.01–0.13)] were the predictors of malaria among under-five children.

Conclusions
The study revealed that sleeping under ITN, having two and more ITN for the household, altitude, availability of radio, and television were the predictors of malaria among under-five children in Ethiopia. Thus, the government should strengthen the availability and utilization of ITN to halt under-five mortality due to malaria.
Individual-level factors attributable to urban-rural disparity in mortality among older adults in China
Authors: Zhao Yuan , Xu Xin , Dupre Matthew E. , Xie Qianqian , Qiu Li , Gu Danan 
Published: September 2020

AbstractBackgroundUrban-rural disparity in mortality at older ages is well documented in China. However, surprisingly few studies have systemically investigated factors that contribute to such disparity. This study examined the extent to which individual-level socioeconomic conditions, family/social support, health behaviors, and baseline health status contributed to the urban-rural difference in mortality among older adults in China.MethodsThis research used the five waves of the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2014, a nationally representative sample of older adults aged 65 years or older in China (n = 28,235). A series of hazard regression models by gender and age group examined the association between urban-rural residence and mortality and how this association was modified by a wide range of individual-level factors.ResultsOlder adults in urban areas had 11% (relative hazard ratio (HR) = 0.89,p < 0.01) lower risks of mortality than their rural counterparts when only demographic factors were taken into account. Further adjustments for family/social support, health behaviors, and health-related factors individually or jointly had a limited influence on the mortality differential between urban and rural older adults (HRs = 0.89–0.92,p < 0.05 top < 0.01). However, we found no urban-rural difference in mortality (HR = 0.97,p > 0.10) after adjusting for individual socioeconomic factors. Similar results were found in women and men, and among the young-old and the oldest-old populations.ConclusionsThe urban-rural disparity in mortality among older adults in China was largely attributable to differences in individual socioeconomic resources (i.e., education, income, and access to healthcare) regardless of gender and age group.
Forecasting disability-adjusted life years for chronic diseases: reference and alternative scenarios of salt intake for 2017–2040 in Japan
Authors: Nomura Shuhei , Yoneoka Daisuke , Tanaka Shiori , Ishizuka Aya , Ueda Peter , Nakamura Keiji , Uneyama Hisayuki , Hayashi Naoki , Shibuya Kenji 
Published: September 2020

Abstract
Background
In Japan, a high-sodium diet is the most important dietary risk factor and is known to cause a range of health problems. This study aimed to forecast Japan’s disability-adjusted life year (DALYs) for chronic diseases that would be associated with high-sodium diet in different future scenarios of salt intake. We modelled DALY forecast and alternative future scenarios of salt intake for cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), and stomach cancer (SC) from 2017 to 2040.

Methods
We developed a three-component model of disease-specific DALYs: a component on the changes in major behavioural and metabolic risk predictors including salt intake; a component on the income per person, educational attainment, and total fertility rate under 25 years; and an autoregressive integrated moving average model to capture the unexplained component correlated over time. Data on risk predictors were obtained from Japan’s National Health and Nutrition Surveys and from the Global Burden of Disease Study 2017. To generate a reference forecast of disease-specific DALY rates for 2017–2040, we modelled the three diseases using the data for 1990–2016. Additionally, we generated better, moderate, and worse scenarios to evaluate the impact of change in salt intake on the DALY rate for the diseases.

Results
In our reference forecast, the DALY rates across all ages were predicted to be stable for CVDs, continuously increasing for CKDs, and continuously decreasing for SC. Meanwhile, the age group-specific DALY rates for these three diseases were forecasted to decrease, with some exceptions. Except for the ≥70 age group, there were remarkable differences in DALY rates between scenarios, with the best scenario having the lowest DALY rates in 2040 for SC. This represents a wide scope of future trajectories by 2040 with a potential for tremendous decrease in SC burden.

Conclusions
The gap between scenarios provides some quantification of the range of policy impacts on future trajectories of salt intake. Even though we do not yet know the policy mix used to achieve these scenarios, the result that there can be differences between scenarios means that policies today can have a significant impact on the future DALYs.
Novel kinase platform for the validation of the anti-tubercular activities of Pelargonium sidoides (Geraniaceae)
Authors: Lukman V. , Odeyemi S. W. , Roth R. L. , Mbabala L. , Tshililo N. , Vlok N. M. , Dewar M. J. B. , Kenyon C. P. 
Published: September 2020

Abstract
Background
Pelargonium sidoides is an important traditional medicine in South Africa with a well-defined history of both traditional and documented use of an aqueous-ethanolic formulation of the roots of P. sidoides (EPs 7630), which is successfully employed for the treatment of respiratory tract infections. There is also historical evidence of use in the treatment of tuberculosis. The aim of this study was to develop a platform of Mycobacterium tuberculosis (Mtb) kinase enzymes that may be used for the identification of therapeutically relevant ethnobotanical extracts that will allow drug target identification, as well as the subsequent isolation of the active compounds.

Results
Mtb kinases, Nucleoside diphosphokinase, Homoserine kinase, Acetate kinase, Glycerol kinase, Thiamine monophosphate kinase, Ribokinase, Aspartokinase and Shikimate kinase were cloned, produced in Escherichia coli and characterized. HPLC-based assays were used to determine the enzyme activities and subsequently the inhibitory potentials of varying concentrations of a P. sidoides extract against the produced enzymes. The enzyme activity assays indicated that these enzymes were active at low ATP concentrations. The 50% inhibitory concentration (IC50) of an aqueous root extract of P. sidoides against the kinases indicated SK has an IC50 of 1.2 μg/ml and GK 1.4 μg/ml. These enzyme targets were further assessed for compound identification from the P. sidoides literature.

Conclusion
This study suggests P. sidoides is potentially a source of anti-tubercular compounds and the Mtb kinase platform has significant potential as a tool for the subsequent screening of P. sidoides extracts and plant extracts in general, for compound identification and elaboration by selected extract target inhibitor profiling.
Long-term preoperative glycemic control restored the perioperative neutrophilic phagocytosis activity in diabetic mice
Authors: Fujimoto Daichi , Nomura Yuki , Egi Moritoki , Obata Norihiko , Mizobuchi Satoshi 
Published: September 2020

Abstract
Background
The risk of surgical site infection has been reported to be higher in patients with poorly controlled diabetes. Since chronic hyperglycemia impairs neutrophil functions, preoperative glycemic control may restore neutrophil function. However, long-term insulin therapy may lead to a delay in surgery, which may be a problem, especially in cancer surgery. It is therefore unfortunate that there have been few studies in which the optimal duration of perioperative glycemic control for diabetes with chronic hyperglycemia was investigated. Therefore, we investigated the effects of preoperative long-term insulin therapy and short-term insulin therapy on perioperative neutrophil functions in diabetic mice with chronic hyperglycemia.

Methods
Five-week-old male C57BL/6 J mice were divided into four groups (No insulin (Diabetes Mellitus: DM), Short-term insulin (DM), Long-term insulin (DM), and Non-diabetic groups). Diabetes was established by administrating repeated low-dose streptozotocin. The Short-term insulin (DM) group received insulin therapy for 6 h before the operation and the Long-term insulin (DM) group received insulin therapy for 5 days before the operation. The No insulin (DM) group and the Non-diabetic group did not receive insulin therapy. At 14 weeks of age, abdominal surgery with intestinal manipulation was performed in all four groups. We carried out a phagocytosis assay with fluorescent microspheres and a reactive oxygen species (ROS) production assay with DCFH-DA (2′,7′-dichlorodihydrofluorescein diacetate) before and 24 h after the operation using FACSVerse™ with BD FACSuite™ software.

Results
Blood glucose was lowered by insulin therapy in the Short-term insulin (DM) and Long-term insulin (DM) groups before the operation. Neutrophilic phagocytosis activities before and after the operation were significantly restored in the Long-term insulin (DM) group compared with those in the No insulin (DM) group (before: p = 0.0008, after: p = 0.0005). However, they were not significantly restored in the Short-term insulin (DM) group. Neutrophilic ROS production activities before and after the operation were not restored in either the Short-term insulin (DM) group or Long-term insulin (DM) group.

Conclusions
Preoperative and postoperative phagocytosis activities are restored by insulin therapy for 5 days before the operation but not by insulin therapy for 6 h before the operation.