bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal eye movements in spinocerebellar ataxia type 3
Authors: Lin Junyu , Zhang Lingyu , Cao Bei , Wei Qianqian , Ou Ruwei , Hou Yanbing , Xu Xinran , Liu Kuncheng , Gu Xiaojing , Shang Huifang 
Published: January 2021

Abstract
Background
Abnormal eye movements are common in spinocerebellar ataxias Type 3 (SCA3). We conducted the research to explore the frequency of abnormal eye movements in Chinese patients with SCA3, to compare the demographic and clinical characteristics between SCA3 patients with and without each type of abnormal eye movement, and to explore the correlation between abnormal eye movements and the severity of ataxia.

Methods
Seventy-four patients with SCA3 were enrolled in this cross-sectional study. Six types of abnormal eye movements including impaired smooth pursuit, increased square-wave jerks (SWJ), gaze-evoked nystagmus (GEN), slowing of saccades, saccadic hypo/hypermetria and supranuclear gaze palsy were evaluated by experienced neurologists. The severity of ataxia was evaluated by Scale for the Assessment and Rating of Ataxia (SARA).

Results
The prevalence of impaired smooth pursuit, increased SWJ, GEN, slowing of saccades, saccadic hypo/hypermetria and supranuclear gaze palsy in Chinese SCA3 patients was 28.4, 13.5, 78.4, 41.9, 23.0, and 5.4%, respectively. SCA3 patients with GEN had higher scores of International Cooperative Ataxia Rating Scale (ICARS-IV) and total ICARS, and longer length of CAG repeat than patients without GEN. SCA3 patients with slowing of saccades had a longer disease duration, higher scores of ICARS-I, ICARS-II, total ICARS and SARA than patients without slowing of saccades. SCA3 patients with saccadic hypo/hypermetria had higher scores of ICARS-III, ICARS-IV, and SARA than patients without saccadic hypo/hypermetria. The demographic and clinical characteristics did not differ significantly between SCA3 patients with and without impaired smooth pursuit, increased SWJ, or supranuclear gaze palsy. Multivariate linear regression showed that the number of abnormal eye movements (0–6), disease duration, Hamilton Depression Rating Scale-24 (HDRS-24) score, and CAG repeat length were positively correlated with SARA score, whereas Montreal Cognitive Assessment (MoCA) score was negatively correlated with SARA score in SCA3.

Conclusions
An increased number of abnormal eye movement types correlated with the severity of ataxia in SCA3.
Sexual function in Chinese women from pregnancy to postpartum: a multicenter longitudinal prospective study
Authors: Zhang Qiuxiang , Shen Min , Zheng Yaning , Jiao Shimei , Gao Shangxiao , Wang Xiaoling , Zou Li , Shen Miao 
Published: January 2021

Abstract
Background
The aims of our research were as follows: First, to estimate the prevalence of female sexual dysfunction in early, middle, late stages of pregnancy, and postpartum 6 months after delivery. Second, to discuss relevant factors associated with female sexual dysfunction among women in 6 months after delivery in Nanjing, Yangzhou and Huaian Main, China.

Methods
Our multicenter longitudinal study was carried out from September 2017 to March 2019, with participants recruited from Southeast China: Nanjing, Yangzhou and Huaian. Participants were recruited when they built their Record of Prenatal Care in community hospitals. The online questionnaires included a set of validated tools, sociodemographic information as wells as medical history data. In the meantime, qualitative interviews were conducted during different periods of pregnancy (from the first trimester to the third trimester of pregnancy and following up to six-month postpartum) respectively. All participants have obtained written informed consent.

Results
By qualitative interview, the vast majority of the participants were inactive in having sex from pregnancy to postpartum. There were negative aspects of sexual experiences, emotional responses closely related to self-attitudes toward sexual behavior during this period. Through quantitative analysis, pre pregnancy BMI (OR = 1.15, P = 0.012), postpartum weight gain (OR = 1.057, P = 0.033) and partnership quality (OR = 1.181, P = 0.04) were associated with postpartum sexual dysfunction 6 months after delivery.

Conclusions
Women are at the risk of significantly different FSD with regard to pre-pregnancy BMI, postpartum weight gain and partnership quality. The impaired sexual function from pregnancy to postpartum period indicated the requirement for further survey as well as extensive investigation.
The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis
Authors: Huo Xingfa , Li Jinming , Zhao Fuxing , Ren Dengfeng , Ahmad Raees , Yuan Xinyue , Du Feng , Zhao Jiuda 
Published: January 2021

AbstractBackgroundThe role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety.MethodsPubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed usingI2test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs).ResultsA total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65–0.86;P < 0.001) and OS (HR = 0.63; 95% CI, 0.53–0.77;P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53–0.78;P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63–0.85;P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44–0.86;P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23–3.74,P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53–2.64,P < 0.001) and hand–foot syndrome (OR = 8.67, 95% CI 6.70–11.22,P < 0.001).ConclusionThis meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.
Perception of healthcare workers on mobile app-based clinical guideline for the detection and treatment of mental health problems in primary care: a qualitative study in Nepal
Authors: Pokhrel P. , Karmacharya R. , Taylor Salisbury T. , Carswell K. , Kohrt B. A. , Jordans M. J. D. , Lempp H. , Thornicroft G. , Luitel N. P. 
Published: January 2021

Abstract
Background
In recent years, a significant change has taken place in the health care delivery systems due to the availability of smartphones and mobile software applications. The use of mobile technology can help to reduce a number of barriers for mental health care such as providers’ workload, lack of qualified personnel, geographical and attitudinal barriers to seek treatment. This study assessed the perception of Nepali primary healthcare workers about the feasibility, acceptability, and benefits of using a mobile app-based clinical guideline for mental health care.

Method
A qualitative study was conducted in two districts Chitwan and Ramechhap of Nepal with purposively selected medical officers (n = 8) and prescribing primary healthcare workers (n = 35) who were trained in the World Health Organization mental health Gap Action Program Intervention Guide. Semi-structured interviews and focus group discussions were conducted in Nepali, audio recorded, transcribed and translated into English for data analysis. Data were analysed manually using a thematic analysis approach.

Results
The majority of the healthcare workers and medical officers reported a high level of interest, motivation and positive attitudes towards the mobile app-based clinical guidelines for detection and treatment of people with mental disorders in primary care. They respondents suggested that several features and functions should be included in the app: suggestive diagnosis and treatment options; clinical data recording system; sending messages to patients to promote follow-up visits; allow offline functions; minimal typing options and content to be available in Nepali language. The study participants reported that the app could help in bringing uniformity in diagnosis and management of mental disorders across all health facilities, enabling remote supervision, helping verification of health workers’ diagnosis and treatment; and increasing patients’ trust in the treatment. Lack of reliable internet connection in health facilities, possibility of distracting interaction between patient and provider, and confidentiality were the key factors potentially hindering the use of the app.

Conclusion
The suggested functions and features as well as the potential risk factors highlighted by the health workers, will be considered when further developing the mobile app-based clinical guidelines, training modality and materials, and the supervision system.
Palaeoecological differences underlie rare co-occurrence of Miocene European primates
Authors: DeMiguel Daniel , Domingo Laura , Sánchez Israel M. , Casanovas-Vilar Isaac , Robles Josep M. , Alba David M. 
Published: January 2021

Abstract
Background
The two main primate groups recorded throughout the European Miocene, hominoids and pliopithecoids, seldom co-occur. Due to both their rarity and insufficiently understood palaeoecology, it is currently unclear whether the infrequent co-occurrence of these groups is due to sampling bias or reflects different ecological preferences. Here we rely on the densely sampled primate-bearing sequence of Abocador de Can Mata (ACM) in Spain to test whether turnovers in primate assemblages are correlated with palaeoenvironmental changes. We reconstruct dietary evolution through time (ca. 12.6–11.4 Ma), and hence climate and habitat, using tooth-wear patterns and carbon and oxygen isotope compositions of enamel of the ubiquitous musk-deer Micromeryx.

Results
Our results reveal that primate species composition is strongly correlated with distinct environmental phases. Large-bodied hominoids (dryopithecines) are recorded in humid, densely-forested environments on the lowermost portion of the ACM sequence. In contrast, pliopithecoids inhabited less humid, patchy ecosystems, being replaced by dryopithecines and the small-bodied Pliobates toward the top of the series in gallery forests embedded in mosaic environments.

Conclusions
These results support the view that pliopithecoid primates preferred less humid habitats than hominoids, and reveal that differences in behavioural ecology were the main factor underpinning their rare co-occurrence during the European Miocene. Our findings further support that ACM hominoids, like Miocene apes as a whole, inhabited more seasonal environments than extant apes. Finally, this study highlights the importance of high-resolution, local investigations to complement larger-scale analyses and illustrates that continuous and densely sampled fossiliferous sequences are essential for deciphering the complex interplay between biotic and abiotic factors that shaped past diversity.
rs1990622 variant associates with Alzheimer’s disease and regulates TMEM106B expression in human brain tissues
Authors: Hu Yang , Sun Jing-yi , Zhang Yan , Zhang Haihua , Gao Shan , Wang Tao , Han Zhifa , Wang Longcai , Sun Bao-liang , Liu Guiyou 
Published: January 2021

Abstract
Background
It has been well established that the TMEM106B gene rs1990622 variant was a frontotemporal dementia (FTD) risk factor. Until recently, growing evidence highlights the role of TMEM106B in Alzheimer’s disease (AD). However, it remains largely unclear about the role of rs1990622 variant in AD.

Methods
Here, we conducted comprehensive analyses including genetic association study, gene expression analysis, eQTLs analysis, and colocalization analysis. In stage 1, we conducted a genetic association analysis of rs1990622 using large-scale genome-wide association study (GWAS) datasets from International Genomics of Alzheimer’s Project (21,982 AD and 41,944 cognitively normal controls) and UK Biobank (314,278 participants). In stage 2, we performed a gene expression analysis of TMEM106B in 49 different human tissues using the gene expression data in GTEx. In stage 3, we performed an expression quantitative trait loci (eQTLs) analysis using multiple datasets from UKBEC, GTEx, and Mayo RNAseq Study. In stage 4, we performed a colocalization analysis to provide evidence of the AD GWAS and eQTLs pair influencing both AD and the TMEM106B expression at a particular region.

Results
We found (1) rs1990622 variant T allele contributed to AD risk. A sex-specific analysis in UK Biobank further indicated that rs1990622 T allele only contributed to increased AD risk in females, but not in males; (2) TMEM106B showed different expression in different human brain tissues especially high expression in cerebellum; (3) rs1990622 variant could regulate the expression of TMEM106B in human brain tissues, which vary considerably in different disease statuses, the mean ages at death, the percents of females, and the different descents of the selected donors; (4) colocalization analysis provided suggestive evidence that the same variant contributed to AD risk and TMEM106B expression in cerebellum.

Conclusion
Our comprehensive analyses highlighted the role of FTD rs1990622 variant in AD risk. This cross-disease approach may delineate disease-specific and common features, which will be important for both diagnostic and therapeutic development purposes. Meanwhile, these findings highlight the importance to better understand TMEM106B function and dysfunction in the context of normal aging and neurodegenerative diseases.
Cost-effectiveness of GLP-1 receptor agonists versus insulin for the treatment of type 2 diabetes: a real-world study and systematic review
Authors: Yang Chen-Yi , Chen Ying-Ren , Ou Huang-Tz , Kuo Shihchen 
Published: January 2021

Abstract
Background
To conduct a real-word-study-based cost-effectiveness analysis of a GLP-1 receptor agonist (GLP-1RA) versus insulin among type 2 diabetes patients requiring intensified injection therapy and a systematic review of cost-effectiveness studies of GLP-1RAs versus insulin.

Methods
Individual-level analyses incorporating real-world effectiveness and cost data were conducted for a cohort of 1022 propensity-score-matched pairs of GLP-1RA and insulin users from Taiwan’s National Health Insurance Research Database, 2007–2016. Study outcomes included the number needed to treat (NNT) to prevent one case of clinical events, healthcare costs, and cost per case of event prevented. Costs were in 2019 US dollars. Analyses were performed from a third-party payer and healthcare sector perspectives. Structured systematic review procedures were conducted to synthesize updated evidence on the cost-effectiveness of GLP-1RAs versus insulin.

Results
Over a mean follow-up of 2.3 years, the NNT using a GLP-1RA versus insulin to prevent one case of all-cause mortality and hospitalized hypoglycemia was 57 and 30, respectively. Using GLP-1RAs instead of insulin cost US$54,851 and US$29,115 per case of all-cause mortality and hospitalized hypoglycemia prevented, respectively, from the payer perspective, and saved US$19,391 and US$10,293, respectively, from the healthcare sector perspective. Sensitivity analyses showed that the probability of using GLP-1RAs versus insulin being cost-effective for preventing one case of all-cause mortality or hospitalized hypoglycemia ranged from 60 to 100%. The systematic review revealed a cost-effective profile of using GLP-1RAs versus insulin.

Conclusions
Using GLP-1RAs versus insulin for type 2 diabetes patients requiring intensified injection therapy in clinical practice is cost-effective.
Production of biologically active human interleukin-10 by Bifidobacterium bifidum BGN4
Authors: Hong Nayoun , Ku Seockmo , Yuk Kyungjin , Johnston Tony V. , Ji Geun Eog , Park Myeong Soo 
Published: January 2021

AbstractBackgroundBifidobacteriumspp. are representative probiotics that play an important role in the health of their hosts. Among variousBifidobacteriumspp.,B. bifidumBGN4 exhibits relatively high cell adhesion to colonic cells and has been reported to have various in vivo and in vitro bio functionalities (e.g., anti-allergic effect, anti-cancer effect, and modulatory effects on immune cells). Interleukin-10 (IL-10) has emerged as a major suppressor of immune response in macrophages and other antigen presenting cells and plays an essential role in the regulation and resolution of inflammation. In this study, recombinantB. bifidumBGN4 [pBESIL10] was developed to deliver human IL-10 effectively to the intestines.ResultsThe vector pBESIL10 was constructed by cloning the human IL-10 gene under agappromoter and signal peptide fromBifidobacteriumspp. into theE. coli-Bifidobacteriumshuttle vector pBES2. The secreted human IL-10 fromB. bifidumBGN4 [pBESIL10] was analyzed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), Western Blotting, and enzyme-linked immunosorbent assay (ELISA). More than 1,473 ± 300 ng/mL (n = 4) of human IL-10 was obtained in the cell free culture supernatant ofB. bifidumBGN4 [pBESIL10]. This productivity is significantly higher than other previously reported human IL-10 level from food grade bacteria. In vitro functional evaluation of the cell free culture supernatant ofB. bifidumBGN4 [pBESIL10] revealed significantly inhibited interleukin-6 (IL-6) production in lipopolysaccharide (LPS)-induced Raw 264.7 cells (n = 6,p < 0.0001) and interleukin-8 (IL-8) production in LPS-induced HT-29 cells (n = 6,p < 0.01) or TNFα-induced HT-29 cells (n = 6,p < 0.001).ConclusionB. bifidumBGN4 [pBESIL10] efficiently produces and secretes significant amounts of biologically active human IL-10. The human IL-10 production level in this study is the highest of all human IL-10 production reported to date. Further research should be pursued to evaluateB. bifidumBGN4 [pBESIL10] producing IL-10 as a treatment for various inflammation-related diseases, including inflammatory bowel disease, rheumatoid arthritis, allergic asthma, and cancer immunotherapy.
Efficient whole-cell oxidation of α,β-unsaturated alcohols to α,β-unsaturated aldehydes through the cascade biocatalysis of alcohol dehydrogenase, NADPH oxidase and hemoglobin
Authors: Qiao Yan , Wang Can , Zeng Yin , Wang Tairan , Qiao Jingjing , Lu Chenze , Wang Zhao , Ying Xiangxian 
Published: January 2021

Abstract
Background
α,β-Unsaturated aldehydes are widely used in the organic synthesis of fine chemicals for application in products such as flavoring agents, fragrances and pharmaceuticals. In the selective oxidation of α,β-unsaturated alcohols to the corresponding α,β-unsaturated aldehydes, it remains challenging to overcome poor selectivity, overoxidation and a low atom efficiency in chemical routes.

Results
An E. coli strain coexpressing the NADP+-specific alcohol dehydrogenase YsADH and the oxygen-dependent NADPH oxidase TkNOX was constructed; these components enabled the NADP+ regeneration and catalyzed the oxidation of 100 mM 3-methyl-2-buten-1-ol to 3-methyl-2-butenal with a yield of 21.3%. The oxygen supply was strengthened by introducing the hemoglobin protein VsHGB into recombinant E. coli cells and replacing the atmosphere of the reactor with pure oxygen, which increased the yield to 51.3%. To further improve catalytic performance, the E. coli cells expressing the multifunctional fusion enzyme YsADH-(GSG)-TkNOX-(GSG)-VsHGB were generated, which completely converted 250 mM 3-methyl-2-buten-1-ol to 3-methyl-2-butenal after 8 h of whole-cell oxidation. The reaction conditions for the cascade biocatalysis were optimized, in which supplementation with 0.2 mM FAD and 0.4 mM NADP+ was essential for maintaining high catalytic activity. Finally, the established whole-cell system could serve as a platform for the synthesis of valuable α,β-unsaturated aldehydes through the selective oxidation of various α,β-unsaturated alcohols.

Conclusions
The construction of a strain expressing the fusion enzyme YsADH-(GSG)-TkNOX-(GSG)-VsHGB achieved efficient NADP+ regeneration and the selective oxidation of various α,β-unsaturated alcohols to the corresponding α,β-unsaturated aldehydes. Among the available redox enzymes, the fusion enzyme YsADH-(GSG)-TkNOX-(GSG)-VsHGB has become the most recent successful example to improve catalytic performance in comparison with its separate components.
Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study
Authors: Fang Haiming , Fu Lian , Li Xuejun , Lu Chunxia , Su Yuan , Xiong Kangwei , Zhang Lijiu 
Published: January 2021

Abstract
Background
To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC).

Results
Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were randomized to the FMT group (n = 10) and the control group (n = 10); 80% were females (F/M = 16/4), the mean age was 48 ± 14 years, and the mean duration was 6.4 ± 8.2 years. The mean length of post-FMT follow-up was 19.1 ± 10.1 months (6–38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n = 10) when reassessed at week 4 (P = 0.001) and week 8 (P = 0.019) after FMT; there was no significant difference 6 months after treatment. The median remission time was 24 months (95% CI 68.26–131.7%) in both the FMT (range 6–38 months) and control groups (range 7–35 months), with no significant difference (P = 0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2 weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation.

Conclusions
Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recurrent UC or even primary UC.