bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes, even newly defined by HbA1c testing, is associated with an increased risk of in-hospital death in adults with COVID-19
Authors: Liu Ye , Lu Ran , Wang Junhong , Cheng Qin , Zhang Ruitao , Zhang Shuisheng , Le Yunyi , Wang Haining , Xiao Wenhua , Gao Hongwei , Zeng Lin , Hong Tianpei 
Published: March 2021

Abstract
Background
Diabetes is associated with poor coronavirus disease 2019 (COVID-19) outcomes. However, little is known on the impact of undiagnosed diabetes in the COVID-19 population. We investigated whether diabetes, particularly undiagnosed diabetes, was associated with an increased risk of death from COVID-19.

Methods
This retrospective study identified adult patients with COVID-19 admitted to Tongji Hospital (Wuhan) from January 28 to April 4, 2020. Diabetes was determined using patients’ past history (diagnosed) or was newly defined if the hemoglobin A1c (HbA1c) level at admission was ≥6.5% (48 mmol/mol) (undiagnosed). The in-hospital mortality rate and survival probability were compared between the non-diabetes and diabetes (overall, diagnosed, and undiagnosed diabetes) groups. Risk factors of mortality were explored using Cox regression analysis.

Results
Of 373 patients, 233 were included in the final analysis, among whom 80 (34.3%) had diabetes: 44 (55.0%) reported a diabetes history, and 36 (45.0%) were newly defined as having undiagnosed diabetes by HbA1c testing at admission. Compared with the non-diabetes group, the overall diabetes group had a significantly increased mortality rate (22.5% vs. 5.9%, p <  0.001). Moreover, the overall, diagnosed, and undiagnosed diabetes groups displayed lower survival probability in the Kaplan-Meier survival analysis (all p <  0.01). Using multivariate Cox regression, diabetes, age, quick sequential organ failure assessment score, and D-dimer ≥1.0 μg/mL were identified as independent risk factors for in-hospital death in patients with COVID-19.

Conclusions
The prevalence of undiagnosed pre-existing diabetes among patients with COVID-19 is high in China. Diabetes, even newly defined by HbA1c testing at admission, is associated with increased mortality in patients with COVID-19. Screening for undiagnosed diabetes by HbA1c measurement should be considered in adult Chinese inpatients with COVID-19.
Clinical safety of total glucosides of paeony adjuvant therapy for rheumatoid arthritis treatment: a systematic review and meta-analysis
Authors: Liu Bin , Meng Xiang , Ma Yanfang , Li Huizhen , Liu Yuqi , Shi Nannan , Chen Yaolong , Wang Yanping , Lu Cheng 
Published: March 2021

Abstract
Background
Total glucosides of paeony (TGP), an active compound extracted from the roots of Paeonia lactiflora Pallas, has been increasingly used as the adjunctive therapy for rheumatoid arthritis (RA) patients. Though TGP could mitigate the unanticipated adverse effects during the conventional treatment of RA, high-quality evidence-based meta-analysis data on this subject are still insufficient. The objective of this study is to evaluate the clinical safety of TGP adjuvant therapy in the RA treatment.

Methods
PubMed, EMBASE, Web of Science, China Network Knowledge Infrastructure (CNKI), SinoMed and WanFang Data were retrieved for randomized controlled trials (RCTs) and cohort study about TGP adjuvant therapy in patients with RA up to 28 January 2021. Literatures with eligibility criteria and information were screened and extracted by two researchers independently. The RevMan5.3 software was used for data analysis with effect estimates as risk ratio (RR) with 95% confidence interval (CI).

Results
A total of 39 studies involving 3680 RA participants were included. There were 8 comparisons: TGP plus methotrexate (MTX) therapy versus MTX therapy, TGP plus leflunomide (LEF) therapy versus LEF therapy, TGP plus MTX and LEF therapy versus MTX plus LEF therapy, TGP plus tripterygium glycosides (TG) therapy versus TG therapy, TGP plus meloxicam (MLX) therapy versus MLX therapy and TGP plus sulfasalazine (SSZ) therapy versus SSZ therapy, TGP plus iguratimod (IGU) therapy versus IGU therapy, TGP plus prednisone acetate tablets (PAT) therapy versus PAT therapy. The meta-analysis results showed that the occurrence of hepatic adverse effect (RR = 0.31, 95% CI = 0.23–0.41, P < 0.00001) and leukopenia (RR = 0.41, 95% CI = 0.26–0.66, P = 0.0002) in TGP adjuvant therapy was significant decreased compared with non-TGP therapy. However, only TGP plus LEF therapy (RR = 0.22, 95% CI = 0.08–0.60, P = 0.003) and TGP plus MTX and LEF therapy (RR = 0.31, 95% CI = 0.22–0.42, P < 0.00001) had statistical difference in the subgroups of hepatic adverse effect. In leukopenia, TGP plus MTX and LEF therapy (RR = 0.47, 95% CI = 0.25–0.87, P = 0.02) had statistical difference.

Conclusions
This meta-analysis indicated that TGP adjuvant therapy might alleviate the incidence of hepatic adverse effect and leukopenia for the RA treatment compared to non-TGP therapy. The clinical safety of TGP adjuvant therapy warrant further investigation in experimental studies.
Using Mendelian randomization study to assess the renal effects of antihypertensive drugs
Authors: Zhao Jie V. , Schooling C. Mary 
Published: March 2021

Abstract
Background
Angiotensin-converting enzyme (ACE) inhibitors and/or in combination with calcium channel blockers (CCBs) are generally recommended as the first-line antihypertensive therapy for people with hypertension and kidney dysfunction. Evidence from large randomized controlled trials comprehensively comparing renal effects of different classes of antihypertensive drugs is lacking.

Methods
We used a Mendelian randomization study to obtain unconfounded associations of genetic proxies for antihypertensives with kidney function. Specifically, we used published genetic variants in genes regulating target proteins of these drugs and then applied to a meta-analysis of the largest available genome-wide association studies of kidney function (estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and albuminuria). Inverse variance weighting was used as the main analysis and to combine estimates from different sources.

Results
Genetically predicted ACE inhibition was associated with higher eGFR (effect size 0.06, 95% confidence interval (CI) 0.008, 0.11), while genetic proxies for beta-blockers were associated with lower eGFR (− 0.02, 95% CI − 0.04, − 0.004) when meta-analyzing the UK Biobank and CKDGen. Genetic proxies for CCBs were associated with lower UACR (− 0.15, 95% CI − 0.28, − 0.02) and lower risk of albuminuria (odds ratio 0.58, 95% CI 0.37, 0.90) in CKDGen. The associations were robust to using different analysis methods and different genetic instruments.

Conclusions
Our findings suggest the reno-protective associations of genetically proxied ACE inhibitors and CCBs, while genetic proxies for beta-blockers may be related to lower eGFR. Understanding the underlying mechanisms would be valuable, with implications for drug development and repositioning of treatments for kidney disease.
Novel biallelic variant in BBS9 causative of Bardet–Biedl syndrome: expanding the spectrum of disease-causing genetic alterations
Authors: Suárez-González Julia , Seidel Verónica , Andrés-Zayas Cristina , Izquierdo Elvira , Buño Ismael 
Published: March 2021

Abstract
Background
Bardet–Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy disorder. Many BBS disease-causing genetic variants have been identified due to the advancement of molecular diagnostic tools. We report on a novel pathogenic variant in a consanguineous Pakistani family with an affected child.

Case presentation
Clinical exome sequencing was used to search for BBS causing variants in the affected individual and identified a novel homozygous splice-site variant in the BBS9 gene (c.702 + 1del). Sanger sequencing was performed for variant validation and segregation studies. Expression analysis using mRNA levels to assess the functional impact of the novel variant demonstrated skipping of exon 7 in the affected alleles, suggesting a truncating effect. Three-dimensional structural modelling was used to predict pathogenicity of the variant residue and the alteration leads to a partial deletion of the PHTB1_N domain and a total deletion of the PHTB1_C domain.

Conclusion
The study of this case expands the spectrum of biallelic variants in the BBS9 gene associated with BBS and increased the knowledge on the molecular consequences of splicing variation c.702 + 1del.
Fibroblasts in cancer dormancy: foe or friend?
Authors: Dai Li , Li Mao , Zhang Wei-long , Tang Ya-Jie , Tang Ya-ling , Liang Xin-hua 
Published: March 2021

AbstractCancer dormancy is defined that the residual cancer cells could enter into a state of quiescence and patients remain asymptomatic for years or even decades after anti-tumor therapies. Fibroblasts, which represent a predominant cell type in tumor microenvironment, play a pivotal role in determining the ultimate fate of tumor cells. This review recapitulates the pleiotropic roles of fibroblasts which are divided into normal, senescent, cancer-associated fibroblasts (CAFs) and circulation CAFs in tumor dormancy, relapse, metastasis and resistance to therapy to help the treatment of cancer metastasis.
Gametocyte carriage after seasonal malaria chemoprevention in Plasmodium falciparum infected asymptomatic children
Authors: Ahmad Abdullahi , Prom Aurelia , Bradley John , Ndiath Mamadou , Etoketim Blessed , Bah Mamadou , Van Geertruyden Jean-Pierre , Drakeley Chris , Bousema Teun , Achan Jane , D’Alessandro Umberto 
Published: March 2021

Abstract
Background
Treatment of clinical Plasmodium falciparum malaria with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) is associated with increased post-treatment gametocyte carriage. The effect of seasonal malaria chemoprevention (SMC) with SP and AQ on gametocyte carriage was assessed in asymptomatic P. falciparum infected children.

Methods
The study was carried out in eastern Gambia. Asymptomatic P. falciparum malaria infected children aged 24–59 months old who were eligible to receive SMC (SMC group) and children 5–8 years that were not eligible to receive SMC (comparison group) were recruited. Gametocytaemia was determined by molecular methods before and after SMC administration. Gametocyte carriage between the groups was compared using the chi-squared test and within-person using conditional logistic regression.

Results
During the 2017 and 2018 malaria transmission seasons, 65 and 75 children were recruited in the SMC and comparison groups, respectively. Before SMC administration, gametocyte prevalence was 10.7% (7/65) in the SMC group and 13.3% (10/75) in the comparison group (p = 0.64). At day 13 (IQR 12, 13) after SMC administration, this was 9.4% (5/53) in children who received at least the first dose of SMC treatment and 12.7% (9/71) for those in the comparison group (p = 0.57). Similarly, there was no difference in prevalence of gametocytes between children that adhered to all 3-day doses of SMC treatment 15.6% (5/32) and those in the comparison group (p = 0.68). In the SMC group, within-group gametocyte carriage was similar before and after SMC administration in children that received at least the first dose of SMC treatment (OR 0.6, 95% CI 0.14–2.51; p = 0.48) and in those that adhered to all 3-day doses of SMC treatment (OR 1.0, 95% CI 0.20–4.95; p = 1.0).

Conclusion
In this study with relative low gametocyte prevalence prior to SMC treatment, no evidence was observed that SMC treatment increased gametocyte carriage in asymptomatic P. falciparum malaria infected children.
The interplay between environmental exposures and COVID-19 risks in the health of children
Authors: Sly Peter D. , Trottier Brittany A. , Bulka Catherine M. , Cormier Stephania A. , Fobil Julius , Fry Rebecca C. , Kim Kyoung-Woong , Kleeberger Steven , Kumar Pushpam , Landrigan Philip J. , Lodrop Carlsen Karin C. , Pascale Antonio , Polack Fernando , Ruchirawat Mathuros , Zar Heather J. , Suk William A. 
Published: March 2021

Abstract
Background
An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution.

Objectives
To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps.

Methods
An international group of researchers interested in children’s environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps.

Discussion
Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a “dirty” environment in conveying protection – an example of the “hygiene hypothesis”; and what are the long term health effects of SARS-Cov-2 infection in early life.

Conclusion
A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario.
A fifty percent leucine-restricted diet reduces fat mass and improves glucose regulation
Authors: Zhou Ziheng , Yin Hanrui , Guo Yajie , Fang Yuanyuan , Yuan Feixiang , Chen Shanghai , Guo Feifan 
Published: March 2021

Abstract
Background
Leucine deprivation modulates the dietary amino acid composition, reducing the fat content and improving the glucose tolerance, thus protecting the organism against obesity. However, a complete deprivation of leucine can lead to an extremely rapid fat loss in mice, accompanied by prolonged adverse effects such as weakness and mental fatigue. Therefore, in this study we aimed to seek the optimal concentration of dietary leucine that can reduce fat mass and improve the metabolism without the onset of severe effects.

Methods
To investigate whether there is a better concentration of diet leucine restriction (LR), based on the diet we conducted (A10021B), that can reduce fat mass and improve metabolism status without taking many negative effects, we fed 8 weeks old male C57Bl/6J mice with increasing degrees of leucine restriction diet 0% LR (control group), 25% LR, 50% LR, and 75% LR groups (4–6 mice each group). Fat mass and blood glucose levels were measured. The expression levels of genes involved in lipid metabolism in white adipose tissue (WAT) and liver, and proteins in insulin signaling were assessed in WAT, liver and muscle.

Results
We found that the 50% LR group is the most proper group here at the lowest leucine effective concentration, which reduced fat mass (p < 0.05) and improved glucose regulation in mice over a 90 days feeding. Further studies revealed that lipid synthesis pathway (Fas, Scd1and Srebp1, p < 0.05) was downregulated and lipolysis (Atgl, p < 0.05) was upregulated in WAT in 50% LR group, compared to that in control group. Furthermore, glucose regulation (glucose tolerance test, p < 0.05) was also improved, and insulin signaling (p < 0.05) in the muscle was enhanced in 50% LR group while in WAT and liver were not changed.

Conclusions
Collectively, a 50% LR in mice reduced fat mass and improved glucose regulation, which may function through modulating lipid synthesis and lipolysis pathway in adipose tissue as well as enhancing insulin signaling in muscle. So far, we provide a further consideration for carrying out the diet of leucine restriction to reduce fat and improve metabolism status before clinical study.
Vestibular dose correlates with dizziness after radiosurgery for the treatment of vestibular schwannoma
Authors: Ermiş Ekin , Anschuetz Lukas , Leiser Dominic , Poel Robert , Raabe Andreas , Manser Peter , Aebersold Daniel M. , Caversaccio Marco , Mantokoudis Georgios , Abu-Isa Janine , Wagner Franca , Herrmann Evelyn 
Published: March 2021

Abstract
Background
Stereotactic radiosurgery (SRS) has been recognized as a first-line treatment option for small to moderate sized vestibular schwannoma (VS). Our aim is to evaluate the impact of SRS doses and other patient and disease characteristics on vestibular function in patients with VS.

Methods
Data on VS patients treated with single-fraction SRS to 12 Gy were retrospectively reviewed. No dose constraints were given to the vestibule during optimization in treatment planning. Patient and tumor characteristics, pre- and post-SRS vestibular examination results and patient-reported dizziness were assessed from patient records.

Results
Fifty-three patients were analyzed. Median follow-up was 32 months (range, 6–79). The median minimum, mean and maximum vestibular doses were 2.6 ± 1.6 Gy, 6.7 ± 2.8 Gy, and 11 ± 3.6 Gy, respectively. On univariate analysis, Koos grade (p = 0.04; OR: 3.45; 95% CI 1.01–11.81), tumor volume (median 6.1 cm3; range, 0.8–38; p = 0.01; OR: 4.85; 95% CI 1.43–16.49), presence of pre-SRS dizziness (p = 0.02; OR: 3.98; 95% CI 1.19–13.24) and minimum vestibular dose (p = 0.033; OR: 1.55; 95% CI 1.03–2.32) showed a significant association with patient-reported dizziness. On multivariate analysis, minimum vestibular dose remained significant (p = 0.02; OR: 1.75; 95% CI 1.05–2.89). Patients with improved caloric function had received significantly lower mean (1.5 ± 0.7 Gy, p = 0.01) and maximum doses (4 ± 1.5 Gy, p = 0.01) to the vestibule.

Conclusions
Our results reveal that 5 Gy and above minimum vestibular doses significantly worsened dizziness. Additionally, mean and maximum doses received by the vestibule were significantly lower in patients who had improved caloric function. Further investigations are needed to determine dose-volume parameters and their effects on vestibular toxicity.
More weighted cancellous bone can be harvested from the proximal tibia with less donor site pain than anterior iliac crest corticocancellous bone harvesting: retrospective review
Authors: Kim Hanju , Kar Ajit Kumar , Kaja Aditya , Lim Eic Ju , Choi Wonseok , Son Whee Sung , Oh Jong-Keon , Sakong Seungyeob , Cho Jae-Woo 
Published: March 2021

Abstract
Background
Iliac crest is the most preferred autogenous bone graft harvesting donor site while it has sorts of complications like prolonged pain, hematoma, and fracture. Harvesting cancellous bone from proximal tibia is also increasingly being used because of lower complications and less donor site pain. However, there are lack of studies to compare these two donor sites in detail. Thus, we proposed to investigate the available amount of autogenous bone graft from the proximal tibia.

Methods
Fifty-one patients who underwent simultaneous bone graft harvest from the PT and the AIC to fill up the given critical sized bone defects were enrolled in this study. We prospectively collected data including the weight of the harvested bone, donor site pain using the visual analog scale (VAS) score, and complications between the two sites.

Results
The mean weight of cancellous bone harvested from the PT was greater than AIC (33.2g vs. 27.4g, p = 0.001). The mean VAS score was significantly lesser in the PT up to 60 days after harvesting (p < 0.001). There was persistent pain up to 90 days in four PT patients and in seven AIC patients. The major complication was reported only in AIC patients (11.8%).

Conclusions
Harvesting cancellous bone from the PT is an acceptable alternative to the AIC for autogenous bone grafting owing to availability of more weighted graft bone and less donor site pain.
Humanitarian led community-based surveillance: case study in Ekondo-titi, Cameroon
Authors: Metuge Alain , Omam Lundi-Anne , Jarman Elizabeth , Njomo Esther Omam 
Published: March 2021

Abstract
Background
Community-based surveillance (CBS) has been used successfully in many situations to strengthen existing health systems as well as in humanitarian crises. The Anglophone crisis of Northwest Southwest Cameroon, led to burning of villages, targeting of health personnel and destruction of health facilities which, in combination with distrust for the government services led to a collapse of surveillance for outbreak prone diseases.

Methods
We evaluated the ability of the CBS system to identify suspected cases of outbreak prone diseases (OPD) as compared to the facility-based surveillance, evaluated the timeliness of the CBS system in identifying an OPD, reporting of OPD to District Health Service (DHS) and timeliness in outbreak response. The paper also assessed the collaboration with the DHS and contribution of the CBS system with regards to strengthening the overall surveillance of the health district and also determine the interventions undertaken to contain suspected/confirmed outbreaks.

Results
In total 9 alerts of suspected OPDs were generated by the CBS system as compared to 0 by the DHS, with 8 investigated, 5 responses and 3 confirmed outbreaks. Average time from first symptoms to alert generation by the CBS system was 7.3 days. Average time lag from alert generation from the CBS to the DHS was 0.3 days which was essentially within 24 h. There was extensive and synergistic collaboration with the DHS.

Discussion
CBS generated a higher number of alerts than traditional outbreak reported used in the region, and had timely investigations and if appropriate, responses. Careful selection of CHWs with strong community engagement led to the success of the project, and the use of the mobile health team in situ allowed for rapid responses to potential outbreaks, as well as for feedback to CHWs and communities. CBS was also well utilized for identification of other events, such as displacement and malnutrition.

Conclusion
In conflict settings, CBS can help in outbreak identification as well as other events, and a mobile health team is crucial to the success of the CBS due to the ability to rapidly response to generated alerts. The mobile health team provided timely investigation of 8 of 9 alerts generated. Collaboration with existing DHS structures is important for systems strengthening in such settings.