bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geo-analysis: the distribution of community health workers in relation to the HIV prevalence in KwaZulu-Natal province, South Africa
Authors: Khumalo G. E. , Ntuli S. , Lutge E. , Mashamba-Thompson T. P. 
Published: March 2022

Abstract
Background
The South African Ward Based Primary Health Care Outreach Team (WBPHCOT) policy framework states that the distribution of community health workers (CHWs) should be proportional to levels of poverty and disease within the population. We aimed to describe the spatial distribution of CHWs in relation to the prevalence of the Human Immunodeficiency Virus (HIV) which has itself been associated with poverty in previous studies.

Methods
This was a descriptive, cross-sectional study in which secondary data was used for geospatial analysis. Based on the extrapolation from the norm of one WBPHCOT per 6000 individuals, we utilized geographic information system (GIS) methods to visualize the distribution of CHWs in relation to the prevalence of HIV in KwaZulu-Natal (KZN). Dot density mapping was used to visualize the random distribution of CHWs in relation to HIV prevalence and population in the districts. The districts’ HIV prevalence, number of PLWH, ratio of CHW: people living with HIV (PLWH), ratio of CHW: population and poverty scores were mapped using choropleth mapping. MapInfo Pro 17.0 was used to map geospatial presentation of the data.

Results
Overall, KZN province showed under allocation of CHWs with a CHW: people ratio of 1: 1156 compared to the estimated norm of 1: 600–1000. At district level, only two of 11 districts met the suggested norm of CHW: PLWH (1: 109–181). This indicates shortages and misallocation of CHWs in the nine remaining districts. Furthermore, our findings showed extensive geospatial heterogeneity with no clear pattern in the distribution of CHWs. There was no relationship between CHW distribution and HIV prevalence or poverty scores in the districts.

Conclusion
This study shows inequality in the distribution of CHWs which may be associated with inequalities in the provision of HIV related services. It is critical to strengthen the response to the HIV epidemic through the appropriate distribution of CHWs especially in those districts with high levels of HIV prevalence and poverty.
The evolution of dam-litter microbial flora from birth to 60 days of age
Authors: Del Carro Angela , Corrò Michela , Bertero Alessia , Colitti Barbara , Banchi Penelope , Bertolotti Luigi , Rota Ada 
Published: March 2022

Abstract
Background
Early bacterial colonization in puppies is still a poorly understood phenomenon. Although the topic is of considerable interest, a big gap in knowledge still exists on the understanding of timing and features of neonatal gut colonization. Thence, the purpose of this study was to evaluate the relationship between dam and litter microbial flora, in vaginally delivered puppies, from birth to two months of age. Bacteria were identified using MALDI-TOF, an accurate and sensitive method, and cluster analysis of data provided a new insight on the investigated topic.

Methods
Six dam-litter units of two medium size breeds were enrolled in the study. Vaginal and colostrum/milk samples were collected from dams after delivery and 48h post-partum, while rectal samples were taken from dams and puppies after delivery and at day 2, 30 and 60 (T2, T30 and T60, respectively) post-partum. Bacterial isolation and identification were performed following standard techniques, then the data were analyzed using a new approach based on bacterial genus population composition obtained using a wide MALDI-TOF screening and cluster analysis.

Results
Forty-eight bacteriological samples were collected from the dams and 145 from their 42 puppies. Colostrum/milk samples (n = 12) showed a bacterial growth mainly limited to few colonies. Staphylococci, Enterococci, E. coli, Proteus spp. were most frequently isolated. All vaginal swabs (n = 12) resulted in bacteria isolation (medium to high growth). Streptococci, Enterococci, E. coli were the most frequently detected. E. coli, Proteus mirabilis, Enterococcus spp., Streptococcus spp. were often obtained from dams’ and puppies’ rectal swabs. Clostridia, not isolated in any other sampling site, were rarely found (n = 3) in meconium while they were more frequently isolated at later times (T2: n = 30; T30: n = 17; T60: n = 27).
Analysis of the bacterial genus pattern over time showed a statistically significant reduction (P < 0.01) in the heterogeneity of microbial composition in all time points if compared to birth for each dam-litter unit. These results were confirmed with cluster analysis and two-dimensional scaling.

Conclusion
This novel data analysis suggests a fundamental role of the individual dam in seeding and shaping the microbiome of the litter. Thus, modulating the dam’s microbiota may positively impact the puppy microbiota and benefit their health.
Whole exome sequencing revealed 14 variants in NDP, FZD4, LRP5, and TSPAN12 genes for 20 families with familial exudative vitreoretinopathy
Authors: Dan Handong , Wang Dongdong , Huang Zixu , Shi Qianqian , Zheng Miao , Xiao Yuanyuan , Song Zongming 
Published: March 2022

Abstract
Background
Familial exudative vitreoretinopathy (FEVR) is a complex form of blindness-causing retinal degeneration. This study investigated the potential disease-causing variants in 20 Chinese families with FEVR.

Methods
All available family members underwent detailed ophthalmological examinations, including best-corrected visual acuity and fundus examination. All probands and most family members underwent fluorescein fundus angiography. Twenty probands underwent whole exome sequencing; 16 of them also underwent copy number variant and mitochondrial genome analysis. Bioinformatics analysis and Sanger sequencing of available family members were used to confirm the disease-causing gene variant.

Results
Twenty families were diagnosed with FEVR based on clinical symptoms, fundus manifestations, and fundus fluorescein angiography. Whole exome sequencing revealed 14 variants in NDP, FZD4, LRP5, and TSPAN12 genes among the 13 families. These variants were predicted to be damaging or deleterious according to multiple lines of prediction algorithms; they were not frequently found in multiple population databases. Seven variants had not previously been reported to cause FEVR: c.1039T>G p.(Phe347Val) in the FZD4 gene; c.1612C>T p.(Arg538Trp) and c.3237-2A>C in the LRP5 gene; and c.77T>A p.(Ile26Asn), c.170dupT p.(Leu57Phe fsTer60), c.236T>G p.(Met79Arg) and c.550dupA p.(Arg184Lys fsTer16) in the TSPAN12 gene. We did not detect any variants in the remaining seven families.

Conclusions
These results expand the spectrum of variants in the NDP, FZD4, LRP5, and TSPAN12 genes and provide insights regarding accurate diagnosis, family genetic counseling, and future gene therapy for FEVR.
Heterogeneous effects of COVID-19 control measures on tuberculosis in South Korea: an analysis of case notification data
Authors: Kim Honghyok , Kang Young Ae , Kim Hee-Jin , Choi Hongjo 
Published: March 2022

AbstractCoronavirus disease (COVID-19) responses such as social distancing practices can decrease health care access and tuberculosis (TB) notification, particularly among individuals aged 60 years or older. Conversely, they can increase TB notification among younger individuals. These results may be attributable to household transmission and the similarity of TB respiratory symptoms to COVID-19.
Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss
Authors: Simeone Paola , Tripaldi Romina , Michelsen Annika , Ueland Thor , Liani Rossella , Ciotti Sonia , Birkeland Kåre I. , Gulseth Hanne L. , Di Castelnuovo Augusto , Cipollone Francesco , Aukrust Pål , Consoli Agostino , Halvorsen Bente , Santilli Francesca 
Published: March 2022

Abstract
Background
Soluble suppression of tumorigenesis-2 (sST2) and galectin (Gal)-3 are two biomarkers related to inflammation, metabolic disturbances and to myocardial fibrosis that characterize several cardiac pathological conditions. Increased circulating levels of these molecules have been associated with risk of cardiovascular death. Treatment with liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We wanted to assess (I) potential differences between subjects with prediabetes or type 2 diabetes mellitus (T2DM) and healthy controls in sST2 and Gal-3 circulating levels, and their relationship with glycemic control and markers of beta cell function and myocardial injury; (II) whether liraglutide treatment modulates these markers in subjects with prediabetes or early T2DM independently of weight loss; (III) whether baseline levels of any of these two molecules may predict the response to liraglutide treatment.

Methods
Forty metformin-treated obese subjects (BMI ≥ 30) with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n = 23)] or newly diagnosed T2DM (n = 17), were randomized to liraglutide or lifestyle counseling until achieving a comparable weight loss (7% of initial body weight). Thirteen subjects were enrolled as healthy controls for baseline sST2 and Gal-3 levels.

Results
Baseline sST2 levels were comparable between controls and obese patients (p = 0.79) whereas Gal-3 levels were significantly higher in patients as compared to controls (p < 0.001). Liraglutide treatment, but not weight loss achieved by lifestyle counseling, decreased plasma sST2 levels (− 9%, beta = − 14.9, standard deviation 6.9, p = 0.037) while Gal-3 levels did not change. A reduction in serum hs-Troponin I was observed after intervention, due to a 19% (p = 0.29) increase in the lifestyle arm, and a 25% decrease (p = 0.033) in the liraglutide arm (between-group difference p = 0.083). Lower baseline Gal-3 levels predicted a better improvement in beta cell function after liraglutide treatment.

Conclusions
Liraglutide-induced reduction in sST2 and possibly hs-TnI suggests that in obese patients with prediabetes or early T2DM this drug may have a positive effect on (cardiac) fibrosis, whereas plasma level of Gal-3 before liraglutide initiation may predict response to the drug in terms of beta cell function improvement.
Trial registration Eudract: 2013-001356-36
Effects of short-term ambient PM2.5 exposure on cardiovascular disease incidence and mortality among U.S. hemodialysis patients: a retrospective cohort study
Authors: Xi Yuzhi , Richardson David B. , Kshirsagar Abhijit V. , Wade Timothy J. , Flythe Jennifer E. , Whitsel Eric A. , Peterson Geoffrey C. , Wyatt Lauren H. , Rappold Ana G. 
Published: March 2022

AbstractBackgroundAmbient PM2.5is a ubiquitous air pollutant with demonstrated adverse health impacts in population. Hemodialysis patients are a highly vulnerable population and may be particularly susceptible to the effects of PM2.5exposure. This study examines associations between short-term PM2.5exposure and cardiovascular disease (CVD) and mortality among patients receiving maintenance in-center hemodialysis.MethodsUsing the United State Renal Data System (USRDS) registry, we enumerated a cohort of all US adult kidney failure patients who initiated in-center hemodialysis between 1/1/2011 and 12/31/2016. Daily ambient PM2.5exposure estimates were assigned to cohort members based on the ZIP code of the dialysis clinic. CVD incidence and mortality were ascertained through 2016 based on USRDS records. Discrete time hazards regression was used to estimate the association between lagged PM2.5exposure and CVD incidence, CVD-specific mortality, and all-cause mortality 1 t adjusting for temperature, humidity, day of the week, season, age at baseline, race, employment status, and geographic region. Effect measure modification was assessed for age, sex, race, and comorbidities.ResultsAmong 314,079 hemodialysis patients, a 10 µg/m3increase in the average lag 0–1 daily PM2.5exposure was associated with CVD incidence (HR: 1.03 (95% CI: 1.02, 1.04)), CVD mortality (1.05 (95% CI: 1.03, 1.08)), and all-cause mortality (1.04 (95% CI: 1.03, 1.06)). The association was larger for people who initiated dialysis at an older age, while minimal evidence of effect modification was observed across levels of sex, race, or baseline comorbidities.ConclusionsShort-term ambient PM2.5exposure was positively associated with incident CVD events and mortality among patients receiving in-center hemodialysis. Older patients appeared to be more susceptible to PM2.5-associated CVD events than younger hemodialysis patients.
Genome editing via non-viral delivery platforms: current progress in personalized cancer therapy
Authors: Lan Tianxia , Que Haiying , Luo Min , Zhao Xia , Wei Xiawei 
Published: March 2022

AbstractCancer is a severe disease that substantially jeopardizes global health. Although considerable efforts have been made to discover effective anti-cancer therapeutics, the cancer incidence and mortality are still growing. The personalized anti-cancer therapies present themselves as a promising solution for the dilemma because they could precisely destroy or fix the cancer targets based on the comprehensive genomic analyses. In addition, genome editing is an ideal way to implement personalized anti-cancer therapy because it allows the direct modification of pro-tumor genes as well as the generation of personalized anti-tumor immune cells. Furthermore, non-viral delivery system could effectively transport genome editing tools (GETs) into the cell nucleus with an appreciable safety profile. In this manuscript, the important attributes and recent progress of GETs will be discussed. Besides, the laboratory and clinical investigations that seek for the possibility of combining non-viral delivery systems with GETs for the treatment of cancer will be assessed in the scope of personalized therapy.
Rare occurrence of pseudomyxoma peritonei (PMP) syndrome arising from a malignant transformed ovarian primary mature cystic teratoma treated by cytoreductive surgery and HIPEC: a case report
Authors: Ponzini Francesca , Kowal Luke , Ghafoor Mariam , Goldberg Allison , Chan Joanna , Lamm Ryan , Cannaday Shawnna M. , Richard Scott D. , Nevler Avinoam , Lavu Harish , Bowne Wilbur B. , Rosenblum Norman G. 
Published: March 2022

Abstract
Background
Pseudomyxoma peritonei (PMP) syndrome is a disease process that typically occurs from ruptured appendiceal mucocele neoplasms. PMP syndrome arising from malignant transformation of an ovarian primary mature cystic teratoma (MCT) is a pathogenesis rarely encountered.

Case Presentation
Herein, we report a 28-year-old patient evaluated and treated for a right ovarian mass and large volume symptomatic abdominopelvic mucinous ascites. Molecular profiling and genetic analysis revealed mutations in ATM, GNAS, and KRAS proteins while IHC demonstrated gastrointestinal-specific staining for CK20, CDX2, CK7, and SATB2. Peritoneal cytology showed paucicellular mucin. Diffuse peritoneal adenomucinosis (DPAM) variant of PMP arising from a ruptured ovarian primary MCT after malignant transformation to a low-grade appendiceal-like mucinous neoplasm was ultimately confirmed. Treatment included staged therapeutic tumor debulking and right salpingo-oophorectomy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

Conclusions
Our report builds upon the existing literature supporting this aggressive treatment option reserved for advanced abdominal malignancies utilized in this patient with a rare clinical entity.
A novel inflammation-related prognostic biomarker for predicting the disease-free survival of patients with colorectal cancer
Authors: Cai Xiaoling , Chen Fa , Liang Lisheng , Jiang Weizhong , Liu Xing , Wang Dong , Wu Yunli , Chen Jinyan , Guan Guoxian , Peng Xian-e 
Published: March 2022

AbstractBackgroundTo develop and evaluate the prognostic value of a comprehensive inflammatory biomarker for postoperative colorectal cancer (CRC) patients.MethodsA total of 646 CRC patients were recruited between August 2017 and December 2019 from Fujian Medical University Union Hospital, with follow-up data up to 2021. The least absolute shrinkage and selection operator method (LASSO) was used to select inflammation indicators in order to construct a comprehensive biomarker (named NSAP). The Cox regression model was utilized to analyze the association between the NSAP and the disease-free survival (DFS) of CRC. Predictive performance and clinical utility of prognostic models were evaluated by area under the curve (AUC) and decision curve analyses (DCAs).ResultsDuring a median follow-up of 23 months, 95 clinical outcomes were observed, with a 1-year survival rate is 89.47%. A comprehensive inflammatory biomarker (NSAP) was established based on four blood indicators (including neutrophil-to-lymphocyte ratio (NLR), neutrophil×monocyte-to-lymphocyte ratio (SIRI), albumin-to-globulin ratio (AGR), and platelet-to-lymphocytes ratio (PLR)). Patients with a lower NSAP had significantly associated with better DFS of CRC (HR=0.53, 95%CI 0.32–0.89). Moreover, compared to a previously established model, the traditional TNM staging system or/and tumor markers, the nomogram based on NSAP displayed more excellent predictive ability (0.752 vs 0.597, 0.711 and 0.735,P< 0.05). DCAs also demonstrated that the established nomogram had better utility for decision making.ConclusionsOur study suggests that NSAP may be a useful comprehensive prognostic biomarker for predicting the DFS of CRC patients. The nomogram based on NSAP can be considered a valuable tool to estimate the prognosis of patients with CRC.
Transcriptomic characterization of tissues from patients and subsequent pathway analyses reveal biological pathways that are implicated in spastic ataxia
Authors: Kakouri Andrea C. , Votsi Christina , Oulas Anastasis , Nicolaou Paschalis , Aureli Massimo , Lunghi Giulia , Samarani Maura , Compagnoni Giacomo M. , Salani Sabrina , Di Fonzo Alessio , Christophides Thalis , Tanteles George A. , Zamba-Papanicolaou Eleni , Pantzaris Marios , Spyrou George M. , Christodoulou Kyproula 
Published: March 2022

Abstract
Background
Spastic ataxias (SAs) encompass a group of rare and severe neurodegenerative diseases, characterized by an overlap between ataxia and spastic paraplegia clinical features. They have been associated with pathogenic variants in a number of genes, including GBA2. This gene codes for the non-lysososomal β-glucosylceramidase, which is involved in sphingolipid metabolism through its catalytic role in the degradation of glucosylceramide. However, the mechanism by which GBA2 variants lead to the development of SA is still unclear.

Methods
In this work, we perform next-generation RNA-sequencing (RNA-seq), in an attempt to discover differentially expressed genes (DEGs) in lymphoblastoid, fibroblast cell lines and induced pluripotent stem cell-derived neurons derived from patients with SA, homozygous for the GBA2 c.1780G > C missense variant. We further exploit DEGs in pathway analyses in order to elucidate candidate molecular mechanisms that are implicated in the development of the GBA2 gene-associated SA.

Results
Our data reveal a total of 5217 genes with significantly altered expression between patient and control tested tissues. Furthermore, the most significant extracted pathways are presented and discussed for their possible role in the pathogenesis of the disease. Among them are the oxidative stress, neuroinflammation, sphingolipid signaling and metabolism, PI3K-Akt and MAPK signaling pathways.

Conclusions
Overall, our work examines for the first time the transcriptome profiles of GBA2-associated SA patients and suggests pathways and pathway synergies that could possibly have a role in SA pathogenesis. Lastly, it provides a list of DEGs and pathways that could be further validated towards the discovery of disease biomarkers.
Association between insomnia and subclinical atherosclerosis among Chinese steelworkers: a cross-sectional survey
Authors: Wang Lihua , Zhang Shengkui , Yu Miao , Yuan Juxiang 
Published: March 2022

Abstract
Background
Insomnia is a common prevalent sleep disorder. Difficulty maintaining sleep or poor in quality in insomnia caused by disrupted or misaligned circadian rhythms may play an important role in the development of atherosclerosis. This study aimed to examine the association between insomnia and subclinical atherosclerosis in Chinese steelworkers.

Methods
A total of 3240 subjects from a large enterprise located in northern China were included in this study. The Athens Insomnia Scale (AIS) was used to assess the status of insomnia. Subclinical atherosclerosis was evaluated using ultrasonographic measurements of carotid plaque. Multivariable logistic regression was used to identify association between insomnia and carotid atherosclerosis.

Results
The overall prevalence of insomnia and carotid plaque were 35.3 and 31.7% in the study population. Compared with non-insomnia workers, significantly increased odds of carotid plaque were observed among insomnia workers after adjusting for potential confounders, odds ratio (OR) = 1.38, 95% confidence interval (CI): 1.17 to 1.63. Exposure to current shift work and insomnia simultaneously can significantly elevated the odds of carotid plaque.

Conclusion
Insomnia is associated with elevated odds of carotid atherosclerosis in male steelworkers. Insomnia problems of workers should receive further attention in occupational worker health interventions.
Serum cystatin C, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, klotho and fibroblast growth factor-23 in the early prediction of acute kidney injury associated with sepsis in a Chinese emergency cohort study
Authors: Pei Yuanyuan , Zhou Guangping , Wang Pengfei , Shi Fang’e , Ma Xiaolu , Zhu Jihong 
Published: March 2022

Abstract
Background
Acute kidney injury (AKI) is a common and critical complication of sepsis, and is associated with unacceptable morbidity and mortality. Current diagnostic criteria for AKI was insensitive for early detection. Novel biomarkers including cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), klotho and fibroblast growth factor-23 (FGF-23) can predict AKI earlier and allow immediate interventions. We aimed to determine the diagnostic performance of these biomarkers for detecting AKI in sepsis patients.

Methods
This prospective observational study was conducted between May 2018 and November 2020, enrolling 162 sepsis patients eventually. The AKI was defined in accordance with 2012 KDIGO criteria and we divided patients into non-AKI (n = 102) and AKI (n = 60) groups. Serum levels of several AKI biomarkers were detected by ELISA. The relationship between biomarker levels on admission of AKI was analyzed and discrimination performances comparison were performed.

Results
AKI incidence was up to 37.0% (60/162) during hospitalization. Compared with non-AKI group, both serum cystatin C, KIM-1, NGAL and FGF-23 were significantly elevated at admission in septic AKI patients. The areas under the receiver operating curves demonstrated that serum cystatin C had modest discriminative powers for predicting AKI after sepsis, and cystatin C combined with serum creatinine in the prediction of septic AKI increased the diagnostic sensitivity prominently.

Conclusion
Serum cystatin C, KIM-1, NGAL and FGF-23 levels were both increased in septic AKI patients. Our study provided reliable evidence that cystatin C solely and combined with serum creatinine may accurately and sensitively predict septic AKI of patients on admission.