bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of parity/live birth number with incident type 2 diabetes among women: over 15 years of follow-up in The Tehran Lipid and Glucose Study
Authors: Moazzeni Seyyed Saeed , Hizomi Arani Reyhane , Asgari Samaneh , Azizi Fereidoun , Hadaegh Farzad 
Published: October 2021

Abstract
Background
Childbearing may increase the future risk of developing type 2 diabetes mellitus (T2DM) in mothers. However, the issue is not clear completely and not investigated in the Middle East, a region with a high burden of T2DM. In the current study, we examined the association of parity/live birth number with incident T2DM among Iranian women.

Methods
The study population included 2552 women aged 30–65 years recruited in 1999–2001 and were followed for incident T2DM by 3-year intervals. Multivariable Cox proportional hazard models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the parity/live birth number for incident T2DM. Parity number was defined as the number of live childbirth (number of live birth) plus the number of stillbirth (defined as birth of an infant that died after the 20th week of pregnancy in the uterus).

Results
During a median follow-up of 15.4 years, 557 incident T2DM cases have occurred. After adjustment for potential T2DM risk factors and reproductive factors, each additional parity caused a 9% higher risk for incident T2DM. Moreover, compared to women with one parity, those with 3 and ≥ 4 parity had HRs of 1.73 [95% CI: 1.06–2.83] and 2.23 [1.36–3.65], respectively. After further adjustment for body mass index (BMI) and waist circumference, although the HRs were attenuated prominently, parity ≥ 4 was associated with significantly higher risk (HR: 1.72 [1.05–2.83]); even after further adjustment for triglycerides (TG)/ high-density lipoprotein cholesterol (HDL-C), the risk remained marginally significant (HR: 1.64 [1.00–2.70; P value: 0.051]). For the number of live birth, the results were also similar. Moreover, in a sensitivity analysis, when we considered BMI change during follow-up as another covariate, generally, the effect sizes did not change; the trend of HRs across categories of parity number remained marginally significant (P value: 0.064).

Conclusions
During a long-term follow-up, after adjustment for potential T2DM risk factors, reproductive factors, obesity indices, and TG/HDL-C (insulin resistance surrogate), we demonstrated that higher parity/live birth numbers could be associated with increased risk of T2DM development among Iranian women. Moreover, even after further adjustment for BMI change, the suggestive higher risk was still found.
Curriculum development on the human rights of people with disabilities for future medical education: using a modified Delphi
Authors: Lee Bomyee , Park So-Youn 
Published: October 2021

Abstract
Background
In order for doctors to effectively provide medical services to patients with disabilities, an understanding of this population is necessary, along with the knowledge, attitudes, and technical abilities necessary to address health problems associated with each type of disability. One way of doing this is by educating doctors about disabilities and ensuring their frequent contact with people with disabilities while they are in medical school. Therefore, this study aimed to develop a systematic medical education curriculum to enhance doctors’ understanding of people with disabilities.

Methods
The authors conducted a systematic literature review to develop and verify the basic framework of the educational content and curriculum. Two surveys were also developed using the Delphi method to evaluate the adequacy and necessity of educational topics. Items with a content validity ratio equal to or greater than the minimum value were considered valid. Survey panels comprised academic experts and health care practitioners who were working with people with disabilities. We conducted two surveys, one for a basic and the other for an advanced course, in which 13 to 16 respondents took part.

Results
The authors selected 13 topics for the ‘Basic Introductory Course’ and included general educational content on the health rights of people with disabilities focused on improving students’ knowledge of disabilities. The authors also selected 12 topics for the ‘Care and Communication for Patients with Disabilities Course’ designed to improve students’ understanding of interviewing and communicating with patients with disabilities.

Conclusions
In Korea, disability has received little attention in the medical curriculum to date. The curriculum developed in this study provides preliminary data for guiding future directions in medical education and developing specific support plans for an education that promotes people with disabilities’ health rights.
The value of a new prognostic model developed by lymphocyte-monocyte ratio and platelet-monocyte ratio in peripheral T-cell lymphoma
Authors: Zhang Yan , Shi Yuanfei , Shen Huafei , Shou Lihong , Fang Qiu , Zheng Xiaolong , Zhu Mingyu , Huang Xin , Huang Jiansong , Li Li , Zhou De , Zhu Lixia , Zhu Jingjing , Ye Xiujin , Jin Jie , Xie Wanzhuo 
Published: October 2021

AbstractPeripheral T-cell lymphoma(PTCL) is a group of lymphoproliferative tumors originated from post-thymic T cells or mature natural killer (NK) cells. It shows highly aggressive clinical behaviour, resistance to conventional chemotherapy, and a poor prognosis. Although a few prognostic models of PTCL have been established in retrospective studies, some high-risk patients still can not be screened out. Therefor we retrospectively studied 347 newly diagnosed PTCL patients and assessed the prognostic role of lymphocyte-monocyte ratio (LMR) and platelet-monocyte ratio (PMR) in the complete response (CR) and survival of PTCL patients. Patients with LMR ≤ 1.68 and PMR ≤ 300 achieved a lower CR rate and a poor survival. In multivariate analysis, LMR ≤ 1.68 (HR = 1.751, 95% CI 1.158–2.647, p < 0.05) and PMR ≤ 300 (HR = 1.762, 95% CI 1.201–2.586, p < 0.05) were independently associated with short survival. On this basis, a new prognostic model of PTCL was established to screen out high-risk patients. In our "Peripheral Blood Score (PBS)" model, three groups were identified at low risk (178 patients, 51.3%, score 0), intermediate risk (85 patients, 24.5%, score 1), and high risk (84 patients, 24.2%, score 2), having a 1-year OS of 86%, 55.3% and 22.6% (p < 0.05), and a 3-year OS of 43.4%, 20% and 13.1% (p < 0.05), respectively. Optimal strategies for identifying high-risk patients with PTCL are urgently needed. Our new PBS model is simple, inexpensive and widely available to screen out the high risk patients.
Chemoprotective and chemosensitizing effects of apigenin on cancer therapy
Authors: Nozhat Zahra , Heydarzadeh Shabnam , Memariani Zahra , Ahmadi Amirhossein 
Published: October 2021

Abstract
Background
Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties.

Methods
We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms.

Results
In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells.

Conclusion
Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy.

Graphical Abstract
Gene augmented nuclear-targeting sonodynamic therapy via Nrf2 pathway-based redox balance adjustment boosts peptide-based anti-PD-L1 therapy on colorectal cancer
Authors: Wan Guoyun , Chen Xuheng , Wang Haijiao , Hou Shenglei , Wang Qian , Cheng Yuanyuan , Chen Qian , Lv Yingge , Chen Hongli , Zhang Qiqing 
Published: October 2021

AbstractBackgroundColorectal cancer is known to be resistant to immune checkpoint blockade (ICB) therapy. Sonodynamic therapy (SDT) has been reported to improve the efficacy of immunotherapy by inducing immunogenic cell death (ICD) of cancer. However, the SDT efficacy is extremely limited by Nrf2-based natural redox balance regulation pathway in cancer cells in response to the increased contents of reactive oxygen species (ROS). Nuclear-targeting strategy has shown unique advantages in tumor therapy by directly destroying the DNA. Thus it can be seen that Nrf2-siRNA augmented nuclear-targeting SDT could boost ICB therapy against colorectal cancer.ResultsThe nuclear-targeting delivery system TIR@siRNA (TIR was the abbreviation of assembled TAT-IR780) with great gene carrier capacity and smaller diameter (< 60 nm) was designed to achieve the gene augmented nuclear-targeting SDT facilitating the anti-PD-L1 (programmed cell death-ligand-1) therapy against colorectal cancer. In CT26 cells, TIR@siRNA successfully delivered IR780 (the fluorescent dye used as sonosensitizer) into cell nucleus and Nrf2-siRNA into cytoplasm. Under US (utrasound) irradiation, TIR@siRNA notably increased the cytotoxicity and apoptosis-inducing activity of SDT through down-regulating the Nrf2, directly damaging the DNA, activating mitochondrial apoptotic pathway while remarkably inducing ICD of CT26 cells. In CT26 tumor-bearing mice, TIR@siRNA mediated gene enhanced nuclear-targeting SDT greatly inhibited tumor growth, noticeably increased the T cell infiltration and boostedDPPA-1 peptide-based anti-PD-L1 therapy to ablate the primary CT26 tumors and suppress the intestinal metastases.ConclusionsAll results demonstrate that TIR@siRNA under US irradiation can efficiently inhibit the tumor progression toward colorectal CT26 cancer in vitro and in vivo by its mediated gene augmented nuclear-targeting sonodynamic therapy. Through fully relieving the immunosuppressive microenvironment of colorectal cancer by this treatment, this nanoplatform provides a new synergistic strategy for enhancing the anti-PD-L1 therapy to ablate colorectal cancer and inhibit its metastasis.Graphical Abstract
Potential causal effect of physical activity on reducing the risk of dementia: a 6-year cohort study from the Japan Gerontological Evaluation Study
Authors: Sato Koryu , Kondo Naoki , Hanazato Masamichi , Tsuji Taishi , Kondo Katsunori 
Published: October 2021

AbstractBackgroundThe causal effect of physical activity on reducing dementia risk has been questioned due to the possibility of reverse causation. This study examined the potential causal effects of physical activity on reducing dementia risk using residency in a snowy area as an instrumental variable (IV) representing the physical activity of older adults.MethodsWe used cohort data from the Japan Gerontological Evaluation Study, a longitudinal cohort enrolling people aged 65 or older who were physically and cognitively independent in 2013; study participants were followed for an average of 5.7 years. Participants in the present study included 73,260 individuals living in 19 municipalities in Japan. Physical activity was measured by self-report questionnaires and the incidence of dementia was ascertained by linking participants to the public registries of long-term care insurance. IV estimation was obtained from a piecewise Cox proportional hazard model using a two-stage regression procedure.ResultsDuring the study period, we ascertained 8714 cases (11.9%) of dementia onset. In the IV analysis, we found that the frequency of physical activity per week was negatively associated with dementia risk, though the association weakened over time (Year 1: hazard ratio = 0.53, 95% confidence interval: 0.39–0.74; Year 4: 0.69, 0.53–0.90; Year 6: 0.85, 0.66–1.10).ConclusionsOur IV analysis indicated a potential causal effect of physical activity on reducing dementia risk that persisted for at least 4 years of follow-up. Thus, we conclude that physical activity should be recommended for older adults to reduce dementia risk.
Molecular identification and prevalence of trypanosomes in cattle distributed within the Jebba axis of the River Niger, Kwara state, Nigeria
Authors: Habeeb Issa Funsho , Chechet Gloria Dada , Kwaga Jacob K. P. 
Published: October 2021

AbstractBackgroundTrypanosomiasis is a fatal disease that threatens the economy of at least 37 countries in sub-Saharan Africa, particularly with regard to livestock farming. In this study, we investigated the prevalence of trypanosome infection in cattle, and molecularly identified the species of trypanosomes in infected cattle and the spatial distribution of trypanosome-infected herds along the Jebba axis of the River Niger.MethodsA randomized cross-sectional study was conducted along the Jebba axis of the River Niger by screening cattle from 36 herd clusters by nested PCR using ITS-1 generic primers. Data generated were analysed using the Chi-square test at a 95% confidence interval.ResultsMicroscopic examination revealed three infected cattle out of 398 examined, representing 0.8% prevalence. Twelve animals (3.0%) were positive by PCR. Our results showed a decline in the packed cell volume of infected animals (24.7%). The infection rates were categorized as single infection in 11/12 (91.7%) and mixed infection in 1/12 (8.3%). Animals were most frequently infected byTrypanosoma congolense(50.0%), withT. congolenseSavannah being the most prevalent subspecies (71.4%). Aside from the infection rate by age (10.0%) and relative distance of animals from the River Niger (56.2%), statistical differences in every other parameter tested were based on mere probabilistic chance. Spatial data showed that the disease was prevalent among herds located less than 3 km from the River Niger.ConclusionsSix species of trypanosomes were identified in cattle herds along the Jebba axis of the River Niger, withT. congolensebeing the most prevalent. Age and relative distance of herds from the River Niger may be risk factors for trypanosome infection in cattle herds in this area.Graphical abstract
Predictors of long-term clinical response in patients with non-radiographic axial spondyloarthritis receiving certolizumab pegol
Authors: Maksymowych Walter P. , Kumke Thomas , Auteri Simone E. , Hoepken Bengt , Bauer Lars , Rudwaleit Martin 
Published: October 2021

Abstract
Background
Identification of predictive clinical factors of long-term treatment response may contribute to improved management of non-radiographic axSpA (nr-axSpA) patients. This analysis aims to identify whether any baseline characteristics or Week 12 clinical outcomes in nr-axSpA patients with elevated C-reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI) enrolled in the C-axSpAnd study are predictive of achieving clinical response after 1 year of certolizumab pegol (CZP).

Methods
C-axSpAnd (NCT02552212) was a phase 3, multicentre study, including a 52-Week double-blind, placebo-controlled period. Enrolled patients were randomised to CZP 200 mg Q2W or placebo. Predictors of Week 12 (CZP group only) and Week 52 clinical response were identified using a multivariate stepwise logistic regression analysis. Response variables included Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI), Assessment of SpondyloArthritis International Society 40% response (ASAS40), Bath Ankylosing Spondylitis Disease Activity Index 50% response (BASDAI50) and ASDAS inactive disease (ASDAS-ID). Predictive factors assessed included demographic and baseline characteristics and clinical outcomes at Week 12. A p-value <0.05 was required for forward selection into the model and p ≥0.1 for backward elimination. Missing data or values collected after switching to open-label treatment were accounted for using non-responder imputation. Sensitivity analyses accounted for patients with changes in non-biologic background medication.

Results
Of 317 enrolled patients, 159 and 158 were randomised to CZP and placebo, respectively. Younger age and male sex were identified as predictors of Week 12 response across all assessed efficacy outcomes in CZP-treated patients. Consistent predictors of Week 52 response, measured by ASDAS-MI, ASAS40 and BASDAI50, included human leukocyte antigen (HLA)-B27 positivity and sacroiliitis on MRI at baseline. MRI positivity was also predictive of achieving ASDAS-ID at Week 52. Sensitivity analyses were generally consistent with the primary analysis. In placebo-treated patients, no meaningful predictors of Week 52 response were identified.

Conclusions
In this 52-Week, placebo-controlled study in nr-axSpA patients with elevated CRP and/or active sacroiliitis on MRI at baseline, MRI sacroiliitis and HLA-B27 positivity, but not elevated CRP or responses at Week 12, were predictive of long-term clinical response to CZP. Findings may support rheumatologists to identify patients suitable for TNFi treatment.

Trial registration
ClinicalTrials.gov, NCT02552212. Registered on 15 September 2015
Dysregulation of miR-638 in diabetic nephropathy and its role in inflammatory response
Authors: Lin Mei , Song Dan , Zhang Suo , Li Ping 
Published: October 2021

Abstract
Background
MicroRNA (miRNA) can be used as a biomarker for the early diagnosis of diabetic nephropathy (DN). The purpose of this study was to evaluate the diagnostic value of miR-638 in DN and to analyse its regulatory effect on inflammation.

Methods
This retrospective study involved 98 subjects, including non-diabetic healthy controls (n = 30), patients with type 2 diabetes (T2DM, n = 36) without complications and patients with DN (n = 32). After the anthropometric and biochemical evaluation, serum miR-638 levels were assessed by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The levels of inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-alpha [TNF-α]) were detected using enzyme-linked immunosorbent assay. The Spearman correlations were used to analyze the correlation between miR-638 and urinary albumin excretion (UAE), estimated glomerular filtration rate (eGFR), and inflammatory factors. Furthermore, the receiver operating characteristic (ROC) curve was used to measure the diagnostic value of miR-638 in DN. Human mesangial cells (HMCs) were treated with normal glucose (NG, 5.5 mM glucose), high glucose (HG, 30 mM glucose), or high osmotic pressure solution (HO, 5.5 mM glucose + 24.5 mM mannitol) in vitro to simulate the hyperglycamic state in vivo. Subsequently, the HMCs were transfected with miR-638 mimics to regulate the level of miR-638 in the cells and detect its regulation on cell inflammation and proliferation.

Results
Compared with healthy controls and patients with T2DM, serum miR-638 in patients with DN was significantly lower. The reduced miR-638 expression has a significant diagnostic value, which can significantly distinguish patients with DN from healthy controls or patients with T2DM. Inflammatory factors were significantly upregulated in patients with DN and negatively correlated with miR-638 levels. In addition, miR-638 was negatively correlated with UAE and positively correlated with eGFR. HG decreased the level of miR-638 and promoted the expression of inflammatory factors and proliferation in HMCs. However, miR-638 mimic significantly decreased the levels of inflammatory factors and inhibited the proliferative ability induced by HG.

Conclusions
Serum miR-638 expression was low in DN and can be a potentially valuable biomarker for DN. This miRNA seems to influence inflammatory responses and participate in the progression of DN by regulating proliferation.
Comparative genomic and transcriptomic analyses of transposable elements in polychaetous annelids highlight LTR retrotransposon diversity and evolution
Authors: Filée Jonathan , Farhat Sarah , Higuet Dominique , Teysset Laure , Marie Dominique , Thomas-Bulle Camille , Hourdez Stephane , Jollivet Didier , Bonnivard Eric 
Published: October 2021

Abstract
Background
With the expansion of high throughput sequencing, we now have access to a larger number of genome-wide studies analyzing the Transposable elements (TEs) composition in a wide variety of organisms. However, genomic analyses often remain too limited in number and diversity of species investigated to study in depth the dynamics and evolutionary success of the different types of TEs among metazoans. Therefore, we chose to investigate the use of transcriptomes to describe the diversity of TEs in phylogenetically related species by conducting the first comparative analysis of TEs in two groups of polychaetes and evaluate the diversity of TEs that might impact genomic evolution as a result of their mobility.

Results
We present a detailed analysis of TEs distribution in transcriptomes extracted from 15 polychaetes depending on the number of reads used during assembly, and also compare these results with additional TE scans on associated low-coverage genomes. We then characterized the clades defined by 1021 LTR-retrotransposon families identified in 26 species. Clade richness was highly dependent on the considered superfamily. Copia elements appear rare and are equally distributed in only three clades, GalEa, Hydra and CoMol. Among the eight BEL/Pao clades identified in annelids, two small clades within the Sailor lineage are new for science. We characterized 17 Gypsy clades of which only 4 are new; the C-clade largely dominates with a quarter of the families. Finally, all species also expressed for the majority two distinct transcripts encoding PIWI proteins, known to be involved in control of TEs mobilities.

Conclusions
This study shows that the use of transcriptomes assembled from 40 million reads was sufficient to access to the diversity and proportion of the transposable elements compared to those obtained by low coverage sequencing. Among LTR-retrotransposons Gypsy elements were unequivocally dominant but results suggest that the number of Gypsy clades, although high, may be more limited than previously thought in metazoans. For BEL/Pao elements, the organization of clades within the Sailor lineage appears more difficult to establish clearly. The Copia elements remain rare and result from the evolutionary consistent success of the same three clades.