bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of CD27 expression on T-cells as a diagnostic and therapeutic tool for patients with smear-negative pulmonary tuberculosis
Authors: Xu Feifan , Zhang Haiyun , Si Xiaoyan , Chen Junlin , Chen Yuhao , Cui Xiaopeng , Qin Yongwei
Published: June 2021

Background

There is a global focus on illness diagnosis in smear-negative and latent tuberculosis infectious populations (SN-TB and LTBI). CD27 has been suggested to play a direct role in active TB. Little is known about smear-negative individuals. Here, we tried to investigate whether it has a role in smear-negative populations. The expression of CD27 and MTB-specific CD27 in CD4+ T cells (“CD27−CD4+” and “CD27−IFN-γ+CD4+”) was evaluated in MTB-unexposed controls (HC), TB contacts (TB-C) and SN-TB individuals by flow cytometry. The sensitivity, specificity and AUC (area under curve) of “CD27−IFN-γ+CD4+” cells to distinguish SN-TBs from HCs and TB-Cs were determined by receiver operating characteristic (ROC) curve analysis. The clinical index was selected from the clinical laboratory and evaluated for correlation with “CD27−IFN-γ+CD4+” cells by Spearman statistical analysis.

Results

We observed that the percentages of “CD27−IFN-γ+CD4+” cells were significantly increased in the SN-TB group compared with the HC and TB-C groups (AUC was 0.88, sensitivity was 82.14%, specificity was 80.00%, and P < 0.0001). The percentage of “CD27−IFN-γ+CD4+” cells was negatively correlated with WBC (white blood cell count) (r = − 0.3019, P = 0.0182) and positively correlated with IgE (immunoglobulin E) (r = 0.2805, P = 0.0362). Furthermore, “CD27−IFN-γ+CD4+” cells were significantly decreased, especially in the > 50 years group, after clinical treatment.

Conclusion

The present results demonstrated that the percentage of “CD27−IFN-γ+CD4+” cells might be a conceivable molecular indicator in the diagnosis of SN-TB and was influenced by its outcome of therapy.
Serum IL-35 is decreased in overweight patients with rheumatoid arthritis: its correlation with Th1/Th2/Th17-related cytokines
Authors: Li Yuxuan , Jie Yang , Wang Xiaofei , Lu Jing
Published: June 2021

Background

Obesity is correlated with worse drug responses and high disease activity in patients with rheumatoid arthritis (RA). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that mainly produced by regulatory T (Treg). This study was performed to analyze whether IL-35 was correlated with obesity in RA and investigate the correlation between other Th1/Th2/Th17-related cytokines and obesity in RA.

Results

The serum IL-35 level was analyzed in RA (n = 81) and healthy donors (n = 53) by ELISA assay, and was compared between three groups (body mass index (BMI) < 18.5,≥18.5 to 25, > 25). Serum cytokines including IL-2, IL-4, IL-10, IL-17, INF-γ, TNF-α levels were measured using Flowcytometry assay. Clinical information was extracted from medical records. Serum IL-35 level in overweight patients were significantly decreased than those in lean patients. Furthermore, Th1/Th2/Th17-related cytokines from overweight patients with RA showed the characteristic immunological features. Serum IL-6, IL-17 and TNF-α levels were positively correlated with BMI. However, serum IL-2, IL-4, IL-10 and IFN-γ concentrations were not correlated with BMI.

Conclusions

Quantitative changes in serum IL-35 level were characteristic in overweight patients with RA. These findings indicate that IL-35 plays an important role in the development of RA and may prove to be a potential biomarker of active RA.
Different aspects of frailty and COVID-19: points to consider in the current pandemic and future ones
Authors: Hussien Hani , Nastasa Andra , Apetrii Mugurel , Nistor Ionut , Petrovic Mirko , Covic Adrian
Published: June 2021

Background

Older adults at a higher risk of adverse outcomes and mortality if they get infected with Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). These undesired outcomes are because ageing is associated with other conditions like multimorbidity, frailty and disability. This paper describes the impact of frailty on coronavirus disease 2019 (COVID-19) management and outcomes. We also try to point out the role of inflamm-ageing, immunosenescence and reduced microbiota diversity in developing a severe form of COVID-19 and a different response to COVID-19 vaccination among older frail adults. Additionally, we attempt to highlight the impact of frailty on intensive care unit (ICU) outcomes, and hence, the rationale behind using frailty as an exclusion criterion for critical care admission. Similarly, the importance of using a time-saving, validated, sensitive, and user-friendly tool for frailty screening in an acute setting as COVID-19 triage.

We performed a narrative review. Publications from 1990 to March 2021 were identified by searching the electronic databases MEDLINE, CINAHL and SCOPUS.

Based on this search, we have found that in older frail adults, many mechanisms contribute to the severity of COVID-19, particularly cytokine storm; those mechanisms include lower immunological capacity and status of ongoing chronic inflammation and reduced gut microbiota diversity.

Higher degrees of frailty were associated with poor outcomes and higher mortality rates during and after ICU admission. Also, the response to COVID-19 vaccination among frail older adults might differ from the general population regarding effectiveness and side effects.

Researches also had shown that there are many tools for identifying frailty in an acute setting that could be used in COVID-19 triage, and before ICU admission, the clinical frailty scale (CFS) was the most recommended tool.

Conclusion

Older frail adults have a pre-existing immunopathological base that puts them at a higher risk of undesired outcomes and mortality due to COVID-19 and poor response to COVID-19 vaccination. Also, their admission in ICU should depend on their degree of frailty rather than their chronological age, which is better to be screened using the CFS.
Sociodemographic factors associated with the first administration of anti-seizure medication in patients with focal epilepsy in Western China
Authors: Zhu Qiong , Guo Yi , Ma Shuai , Yang Lili , Lin Zhonghua , Sun Hongbin , Li Guangzong , Yu Liang
Published: June 2021

Background

Epilepsy is a severe chronic neurologic disease with a prevalence of 0.7% worldwide; anti-seizure medications (ASMs) are the mainstay of epilepsy treatment. The effects of sociodemographic factors on the characteristics of initial treatment in patients with newly diagnosed focal epilepsy in Western China are unknown. This study was conducted to explore sociodemographic factors associated with initial treatment characteristics.

Methods

Patients with focal epilepsy on continuous ASM treatment who visited to our epilepsy center at Sichuan Provincial People’s Hospital between January 2018 and December 2019 were recruited. Data on initial treatment status and sociodemographic variables were obtained from the patients with a questionnaire designed by our researchers. We examined whether sociodemographic factors were associated with epileptic patients’ access to neurologists and prescriptions of individual ASMs.

Results

A total of 569 patients completed this study. We found that patients with a higher education level, aged < 16 years, and with a higher household disposable income were more likely to receive treatment from a neurologist than their counterparts. Patients with a lower personal income level and who were treated at a junior hospital were more likely to receive prescriptions for carbamazepine, and those who were younger than 16 years were less likely to receive prescriptions for carbamazepine and oxcarbazepine. Patients with a higher education level, with a higher household disposable income level, who were younger than 16 years, and who were treated at a senior hospital were more likely to receive prescriptions for levetiracetam than their counterparts. Adult, female patients with focal epilepsy treated at a senior hospital were more likely to receive prescriptions for lamotrigine.

Conclusions

This observation suggests that sociodemographic characteristics are associated with access to neurologists and prescriptions of individual antiepileptic drugs. These data may help public health officials establish guidelines for doctors and distribute resources according to the needs of different patient groups.
The experiences of postnatal women and healthcare professionals of a brief weight management intervention embedded within the national child immunisation programme
Authors: Tyldesley-Marshall Natalie , Greenfield Sheila M , Parretti Helen M , Jolly Kate , Jebb Susan , Daley Amanda J
Published: June 2021

Background

After childbirth, most women do not lose the extra weight gained during pregnancy. This is important because postnatal weight retention contributes to the development of obesity in later life. Research shows that postnatal women living with overweight would prefer to weigh less, are interested in implementing weight loss strategies, and would like support. Without evidence for the benefit of weight management interventions during pregnancy, postnatal interventions are increasingly important. Research has focused on intensive weight loss programmes, which cannot be offered to all postnatal women. Instead, we investigated the feasibility of a brief intervention delivered to postnatal women at child immunisation appointments. This qualitative study explored the views of women who received the intervention and healthcare professionals who delivered it.

Methods

The intervention was delivered within the context of the national child immunisation programme. The intervention group were offered brief support encouraging self-management of weight when attending general practices to have their child immunised at two, three and four months of age. The intervention involved motivation and support from practice nurses to encourage women to make healthier lifestyle choices through self-monitoring of weight and signposting to an online weight management programme. Nurses provided external accountability for weight loss. Women were asked to weigh themselves weekly and record this on a weight record card. Nested within this trial, semi-structured interviews explored the experiences of postnatal women who received the intervention and nurses who delivered it.

Results

The intervention was generally acceptable to participants and child immunisation appointments considered a suitable intervention setting. Nurses were hesitant to discuss maternal weight, viewing the postnatal period as a vulnerable time. Whilst some caveats to implementation were discussed by nurses, they felt the intervention was easy to deliver and would motivate postnatal women to lose weight.

Conclusions

Participants were keen to lose weight after childbirth. Overall, they reported that the intervention was acceptable, convenient, and, appreciated support to lose weight after childbirth. Although nurses, expressed concerns about raising the topic of weight in the early postnatal period, they felt the intervention was easy to deliver and would help to motivate women to lose weight.
Incidence of NUT carcinoma in Western Australia from 1989 to 2014: a review of pediatric and adolescent cases from Perth Children’s Hospital
Authors: Carter Tina , Crook Maxine , Murch Ashleigh , Beesley Alex H. , de Klerk Nick , Charles Adrian , Kees Ursula R.
Published: June 2021

Background

NUT carcinoma (NC), previously known as NUT midline carcinoma, is a rare and very aggressive cancer that occurs in both children and adults. NC is largely chemoresistant, with an overall survival of less than 7 months. Because the carcinoma is not restricted to a particular organ, diagnosis is often a challenge. In the absence of a clearly determined incidence for NC, we sought to study the diagnosis of patients in a well-defined population.

Methods

We systematically reviewed records of all patients that presented to the Oncology Department of the Princess Margaret Hospital for Children from 1989 to 2014. This institution in the geographically isolated state of Western Australia has a catchment population of around 2 million. We then identified all high grade undifferentiated sarcomas or carcinomas in the 0–16 year age group.

Results

Over 26 years, we found 14 patients of 16 years or younger with undifferentiated malignant tumors. Of these, five tumors were positive by immunohistochemistry for the NUT/NUTM1 (Nuclear Protein in Testis) protein and/or the translocation t(15;19). Three patients presented with thoracic tumors, one with a para-spinal tumor, and one had an upper airway nasopharyngeal carcinoma. In all five cases, there was an initial response to therapy and then progression. This 26-year survey was conducted in a geographically isolated state with a well-defined population, and we determined an estimated incidence of NC of around 0.41 per million child years (0–16 yrs. of age) at risk. From three patients it was feasible to derive cell lines for further genetic analyses and drug screening.

Conclusions

For the first time, the incidence of NC could be determined in a well-defined geographic area. The calculated rate of NC incidence is consistent with a history of under-recognition for this malignancy. These findings indicate that improved diagnostic detection of NC would enable better management and counselling of patients. Our findings emphasize the heterogeneity of NC, and they highlight the need to develop personalised therapy options, and to consider a diagnosis of NC in undifferentiated malignant tumors.
Factors to improve distress and fatigue in Cancer survivorship; further understanding through text analysis of interviews by machine learning
Authors: Yang Kyungmi , Kim Jina , Chun Mison , Ahn Mi Sun , Chon Eunae , Park Jinju , Jung Mijin
Published: June 2021

Background

From patient-reported surveys and individual interviews by health care providers, we attempted to identify the significant factors related to the improvement of distress and fatigue for cancer survivors by text analysis with machine learning techniques, as the secondary analysis using the single institute data from the Korean Cancer Survivorship Center Pilot Project.

Methods

Surveys and in-depth interviews from 322 cancer survivors were analyzed to identify their needs and concerns. Among the keywords in the surveys, including EQ-VAS, distress, fatigue, pain, insomnia, anxiety, and depression, distress and fatigue were focused. The interview transcripts were analyzed via Korean-based text analysis with machine learning techniques, based on the keywords used in the survey. Words were generated as vectors and similarity scores were calculated by the distance related to the text’s keywords and frequency. The keywords and selected high-ranked ten words for each keyword based on the similarity were then taken to draw a network map.

Results

Most participants were otherwise healthy females younger than 50 years suffering breast cancer who completed treatment less than 6 months ago. As the 1-month follow-up survey’s results, the improved patients were 56.5 and 58.4% in distress and fatigue scores, respectively. For the improvement of distress, dyspepsia (p = 0.006) and initial scores of distress, fatigue, anxiety, and depression (p < 0.001, < 0.001, 0.043, and 0.013, respectively) were significantly related. For the improvement of fatigue, economic state (p = 0.021), needs for rehabilitation (p = 0.035), initial score of fatigue (p < 0.001), any intervention (p = 0.017), and participation in family care program (p = 0.022) were significant. For the text analysis, Stress and Fatigue were placed at the center of the keyword network map, and words were intricately connected. From the regression anlysis combined survey scores and the quantitative variables from the text analysis, participation in family care programs and mention of family-related words were associated with the fatigue improvement (p = 0.033).

Conclusion

Common symptoms and practical issues were related to distress and fatigue in the survey. Through text analysis, however, we realized that the specific issues and their relationship such as family problem were more complicated. Although further research needs to explore the hidden problem in cancer patients, this study was meaningful to use personalized approach such as interviews.
Osteopontin isoform c promotes the survival of cisplatin-treated NSCLC cells involving NFATc2-mediated suppression on calcium-induced ROS levels
Authors: Huang Jing , Hu Mu , Niu Huan , Wang Jing , Si Yang , Cheng Shan , Ding Wei
Published: June 2021

Background

Tumor microenvironment (TME) critically contributed to the malignant progression of transformed cells and the chemical responses to chemotherapy reagents. Osteopontin (OPN) is a secretory onco-protein with several splicing isoforms, all of which were known to regulate tumor growth and able to alter cell-cell or cell-TME communication, however, the exact role and regulation of the OPN splicing isoforms was not well understood.

Methods

In this study, the effects of conditioned medium from the culture of OPN splicing isoforms overexpressing cells on cell functions were evaluated. The methods of nuclear calcium reporter assays and subcellular distribution of nuclear factor of activated T cells c2 (NFATc2) assays were used to investigate the molecular mechanism underlining the roles of OPN splicing isoforms.

Results

We found that the survival of NSCLC cells treated with cisplatin was increased by secretory OPNc in the condition medium, where reduction of apoptosis by OPNc was associated with the activation of cellular calcium signals and subsequent nuclear translocation of NFATc2.

Conclusions

The results revealed a mechanism of OPN and downstream signal for tumor cells to survive in chemo-stressed TME, which emphasized the importance of secretory proteins in alternative splicing isoforms. Our study not only demonstrated the importance of OPN neutralization for anti-tumor effects, but also implied that modulation in calcium/NFATc2/ROS axis could be a novel approach for improving the long-term outcome of NSCLC treatment.
Knowledge of a cancer diagnosis is a protective factor for the survival of patients with breast cancer: a retrospective cohort study
Authors: He Chen , Zhu Wen Xi , Tang Yunxiang , Bai Yonghai , Luo Zheng , Xu Jinfang , Wang Hao , Xu Shuyu , Xu Jingzhou , Xiao Lei , Zhang Ruike , Wang Yajing , Du Jing , Huang Yujia , Li Xiaopan , Su Tong
Published: June 2021

Background

The health burden of breast cancer is rising in China. The effect of informed diagnosis on long-term survival is not fully understood. This retrospective cohort study aims to explore the association between early informed diagnosis and survival time in breast cancer patients.

Methods

A total of 12,327 breast cancer patients were enrolled between October 2002 and December 2016. Potential factors, including knowing the cancer diagnosis status, sex, age, clinical stage, surgery history, grade of reporting hospital and diagnostic year were, analyzed. We followed up all participants every 6 months until June 2017. Propensity score matching (PSM) was used to balance the clinicopathologic characteristics between patients who knew their diagnosis and those who did not.

Results

By June 2017, 18.04% of the participants died of breast cancer. Before PSM, both the 3-year and 5-year survival rates of patients who knew their cancer diagnosis were longer (P < 0.001). After PSM, the above conclusion was still established. By stratified analysis, except for the subgroups of male patients and stage III patients, patients who knew their diagnosis showed a better prognosis in all the other subgroups (P < 0.05). Cox regression analysis showed that knowing a cancer diagnosis was an independent risk factor for survival in breast cancer patients (P < 0.001).

Conclusions

Being aware of their cancer diagnosis plays a protective role in extending the survival time of breast cancer patients, which suggests that medical staff and patients’ families should disclose the cancer diagnosis to patients in a timely manner. Further prospective studies need to be made to validate our findings.
Circulating ERBB3 levels are inversely associated with the risk of overweight-related hypertension: a cross-sectional study
Authors: Zhu Lijun , Fang Zhengmei , Jin Yuelong , Chang Weiwei , Huang Mengyun , Chen Yan , Yao Yingshui
Published: June 2021

Background

Hypertension and overweight are independent risk factors for cardiovascular disease, and overweight increase the risk of developing high blood pressure. ERBB3( also known as HER3) plays a considerable role in the development of cardiovascular diseases. However, the effect of ERBB3 levels in hypertensive overweight patients is unknown. The aim of this study was to assess the association between ERBB3 levels and hypertension in overweight Chinese patients.

Methods

We evaluated the height,weight, blood pressure, biochemical indicators, and ERBB3 levels in 128 Chinese adults aged 33–79 years. Plasma ERBB3 levels were assessed by the enzyme-linked immunosorbent assay, and body mass index(BMI) was calculated as body weight divided by height squared. Participants were allocated into three groups according to blood pressure and BMI: healthy control (CNT, n = 31; normotensive and non-overweight), hypertension (HT, n = 33; hypertension and non-overweight), and hypertension with overweight (HTO, n = 64; hypertension and overweight). Statistical significance was defined as a two-tailed P < 0.05.

Results

There was no significant difference in mean ERBB3 levels among the three groups, although a linear decrease from CNT (1.13 ± 0.36), HT (1.03 ± 0.36), to HTO (0.84 ± 0.26 ng/mL) was observed in men (P = 0.007). Among the drinking population, the ERBB3 level was significantly reduced in the HTO group as compared with those of the CNT and HT groups (0.76 ± 0.23 versus 1.18 ± 0.37 and 1.20 ± 0.30, respectively). ERBB3 levels were negatively correlated with diastolic blood pressure in men (r= − 0.293, P = 0.012), smoking (r= − 0.47, P = 0.004), and drinking (r = − 0.387, P = 0.008). BMI in men and among drinkers, and uric acid among drinkers were negatively correlated with ERBB3 levels. Multivariate conditional logistic regression showed that plasma ERBB3 levels were associated with a reduced risk of HTO in men [odds ratio (OR) 0.054; 95 % confidence interval (CI): 0.007–0.412) and drinkers (OR 0.002; 95 % CI: 0.000–0.101).

Conclusions

ERBB3 may contribute to the pathogenesis of hypertension in overweight patients, with BMI, gender, and drinking all potentially modulating the process.
Relationship between periodontal diseases and newly-diagnosed metabolic syndrome components in a sub-Saharan population: a cross sectional study
Authors: Ngoude Jean Xavier Ekouelkoum , Moor Vicky Jocelyne Ama , Nadia-Flore Tsobgny Tsague , Agoons Batakeh B. , Marcelle Gamgne Guiadem Catherine , MacBrain Elage Epie , Tcheutchoua Daryl Nzokou , Nkeck Jan René
Published: June 2021

Background

Oral health is a frequently ignored aspect of global health in sub-Saharan patients. Periodontitis, a very frequent oral disease has been proven to be associated to development of the metabolic syndrome. This study aims to evaluate the relationship between periodontal disease and metabolic syndrome components in a sub-Saharan population.

Methods

We performed a cross sectional study in 3 Yaounde hospitals. Consenting adults aged 21 years and above were recruited. Participants who presented with a tooth loss of at least 50% or any condition which could alter values of biological and periodontal parameters (tobacco smoking, pregnancy, chronic kidney disease, cancer) were excluded. Metabolic syndrome elements (glycaemia, arterial pressure, HDL cholesterol, abdominal circumference, triglycerides) and periodontal variables were recorded (plaque and gingival index of Silness and Loe, periodontal pocket depth and clinical attachment loss). These variables were compared using Fisher’s exact Test and odds ratio calculated with 95% confidence intervals.

Results

The prevalence of periodontitis and metabolic syndrome were 43.4% and 10.8% respectively. Age (37.75 ± 13.25,P < 0.001) and poor accessory brushing methods were associated risk factors for development of periodontal disease. Sub-Saharan sindividuals with periodontitis had increased odds of having obesity (OR 11.1 [95% CI 3.97–31.03],P < 0.001) and low HDL (OR 4.58 [95% CI 1.79–11.70],P = 0.001)

Conclusion

Our findings suggest an association between periodontal disease and metabolic syndrome in Sub-Saharan subjects. Increasing age and poor accessory brushing methods are associated risk indicators.
Dental effects of enzyme replacement therapy in case of childhood-type hypophosphatasia
Authors: Okawa Rena , Kokomoto Kazuma , Nakano Kazuhiko
Published: June 2021

Background

Hypophosphatasia (HPP), a skeletal disease characterized by hypomineralization of bone and teeth, is caused by an ALPL gene mutation that leads to low activity of the tissue non-specific alkaline phosphatase enzyme. Although enzyme replacement therapy (ERT) was recently introduced for affected patients, no known studies have been reported regarding its dental effects related to permanent teeth and jaw bones. In the present study, we examined the dental effects of ERT in a case of childhood-type hypophosphatasia, including panoramic radiography findings used to estimate the dental age of permanent teeth and mandibular bone density. Furthermore, the effects of that therapy on the periodontal condition of the patient were evaluated by comparing periodontal pocket depth before and after initiation.

Case presentation

An 11-year-1-month-old boy was referred to our clinic for consultation regarding oral management. Two primary incisors had spontaneously exfoliated at 1 year 8 months old and he had been diagnosed with childhood-type HPP at the age of 2 years 2 months. Obvious symptoms were localized in the dental region at the time of diagnosis, though later extended to other parts of the body such as bone pain. ERT was started at 11 years 7 months of age, after which bone pain disappeared, and motor functions and activities of daily living improved. We estimated dental age based on tooth development stage. The age gap between chronological and dental ages was expanded before treatment, and then showed a constant decrease after ERT initiation and finally disappeared. The index for mandibular bone density (mandibular cortical width / length from mesial buccal cusp to apex of first molar) was increased after ERT initiation. Furthermore, the periodontal condition for all teeth except those exfoliated was stable after starting therapy.

Conclusions

ERT resulted in improved tooth and mandibular bone mineralization, with notably good effects on teeth under formation. Acceleration of mineralization of roots associated with erupting teeth leads to stabilization of the periodontal condition. We concluded that ERT contributed to the improved dental condition seen in this patient.
Characterizing circulating nucleosomes in the plasma of dogs with hemangiosarcoma
Authors: Wilson-Robles Heather , Miller Tasha , Jarvis Jill , Terrell Jason , Kelly Theresa Kathleen , Bygott Thomas , Bougoussa Mhammed
Published: June 2021

Background

Nucleosomes consist of DNA wrapped around a histone octamer core like thread on a spool to condense DNA as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death, chromatin fragmentation and release of nucleosomes into the blood. The Nu.Q™ platform measures circulating nucleosomes in the blood of humans that result from disease and has been used to detect and identify cancer even at early stages. The objectives of this study are to quantify and better characterize nucleosomes in dogs with various stages of hemangiosarcoma (HSA) using this ELISA-based assay.

Samples from 77 dogs with a confirmed diagnosis of hemangiosarcoma and 134 healthy controls were utilized for this study. The HSA samples were recruited from the Texas A&M University Small Animal Clinic (TAMU-SAC) or purchased from biobanks. All control samples were recruited from the TAMU-SAC.

Results

Dogs with hemangiosarcoma had a 6.6-fold increase in their median plasma nucleosome concentrations compared to controls (AUC 92.9 %). Elevated nucleosome concentrations were seen at all stages of disease and nucleosome concentrations increased with the stage of the disease.

Conclusions

Plasma nucleosome concentrations are a reliable way to differentiate dogs with hemangiosarcoma from healthy dogs. Further testing is underway to better characterize cancer associated HSA circulating nucleosomes and optimize future diagnostics for canine HSA detection.
Association between STAT4 gene polymorphism and type 2 diabetes risk in Chinese Han population
Authors: Cui Jiaqi , Tong Rui , Xu Jing , Tian Yanni , Pan Juan , Wang Ning , Chen Huan , Peng Yanqi , Fei Sijia , Ling Wang , Guo Chaoying , Yao Juanchuan , Cui Wei
Published: June 2021

Background

Evidence from genetic epidemiology indicates that type 2 diabetes (T2D) has a strong genetic basis. Activated STAT4 has an inflammatory effect, and STAT4 is an important mediator of inflammation in diabetes. Our study aimed to study the association between STAT4 single nucleotide polymorphisms (SNPs) and T2D susceptibility in Chinese Han population.

Methods

We conducted a 'case–control' study among 500 T2D patients and 501 healthy individuals. 5 candidate STAT4 SNPs were successfully genotyped. The association between SNPs and T2D susceptibility under different genetic models was evaluated by logistic regression analysis. ‘SNP-SNP’ interaction was analyzed and completed by multi-factor dimensionality reduction (MDR). Finally, we evaluated the differences of clinical characteristics under different genotypes by one-factor analysis of variance.

Results

The overall results showed that STAT4 rs3821236 was associated with increasing T2D risk under allele (OR 1.23, p = 0.020), homozygous (OR 1.51, p = 0.025), dominant (OR 1.36, p = 0.029), and additive models (OR 1.23, p = 0.020). The results of stratified analysis showed that rs3821236, rs11893432, and rs11889341 were risk factors for T2D among participants ≤ 60 years old. Only rs11893432 was associated with increased T2D risk among female participants. There was also a potential association between rs3821236 and T2D with nephropathy risk. STAT4 rs11893432, rs7574865 and rs897200 were significantly associated with lysophosphatidic acid, cystatin C and thyroxine t4, respectively.

Conclusion

The genetic polymorphisms of STAT4 is potentially associated with T2D susceptibility of Chinese population. In particular, rs3821236 is significantly associated with T2D risk both in the overall and several subgroup analyses. Our study may provide new ideas for T2D individualized diagnosis/protection.
Advanced glycation end-products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre-diabetic and normoglycemic individuals: a cross-sectional study
Authors: Birukov Anna , Cuadrat Rafael , Polemiti Elli , Eichelmann Fabian , Schulze Matthias B.
Published: June 2021

Background

Advanced glycation end-products are proteins that become glycated after contact with sugars and are implicated in endothelial dysfunction and arterial stiffening. We aimed to investigate the relationships between advanced glycation end-products, measured as skin autofluorescence, and vascular stiffness in various glycemic strata.

Methods

We performed a cross-sectional analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, comprising n = 3535 participants (median age 67 years, 60% women). Advanced glycation end-products were measured as skin autofluorescence with AGE-Reader™, vascular stiffness was measured as pulse wave velocity, augmentation index and ankle-brachial index with Vascular Explorer™. A subset of 1348 participants underwent an oral glucose tolerance test. Participants were sub-phenotyped into normoglycemic, prediabetes and diabetes groups. Associations between skin autofluorescence and various indices of vascular stiffness were assessed by multivariable regression analyses and were adjusted for age, sex, measures of adiposity and lifestyle, blood pressure, prevalent conditions, medication use and blood biomarkers.

Results

Skin autofluorescence associated with pulse wave velocity, augmentation index and ankle-brachial index, adjusted beta coefficients (95% CI) per unit skin autofluorescence increase: 0.38 (0.21; 0.55) for carotid-femoral pulse wave velocity, 0.25 (0.14; 0.37) for aortic pulse wave velocity, 1.00 (0.29; 1.70) for aortic augmentation index, 4.12 (2.24; 6.00) for brachial augmentation index and − 0.04 (− 0.05; − 0.02) for ankle-brachial index. The associations were strongest in men, younger individuals and were consistent across all glycemic strata: for carotid-femoral pulse wave velocity 0.36 (0.12; 0.60) in normoglycemic, 0.33 (− 0.01; 0.67) in prediabetes and 0.45 (0.09; 0.80) in diabetes groups; with similar estimates for aortic pulse wave velocity. Augmentation index was associated with skin autofluorescence only in normoglycemic and diabetes groups. Ankle-brachial index inversely associated with skin autofluorescence across all sex, age and glycemic strata.

Conclusions

Our findings indicate that advanced glycation end-products measured as skin autofluorescence might be involved in vascular stiffening independent of age and other cardiometabolic risk factors not only in individuals with diabetes but also in normoglycemic and prediabetic conditions. Skin autofluorescence might prove as a rapid and non-invasive method for assessment of macrovascular disease progression across all glycemic strata.
Preimplantation factor modulates trophoblastic invasion throughout the decidualization of human endometrial stromal cells
Authors: Santos Esther Dos , Moindjie Hadia , Sérazin Valérie , Arnould Lucie , Rodriguez Yoann , Fathallah Khadija , Barnea Eytan R. , Vialard François , Dieudonné Marie-Noëlle
Published: June 2021

Background

Successful human embryo implantation requires the differentiation of endometrial stromal cells (ESCs) into decidual cells during a process called decidualization. ESCs express specific markers of decidualization, including prolactin, insulin-like growth factor-binding protein-1 (IGFBP-1), and connexin-43. Decidual cells also control of trophoblast invasion by secreting various factors, such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases. Preimplantation factor (PIF) is a recently identified, embryo-derived peptide with activities at the fetal-maternal interface. It creates a favorable pro-inflammatory environment in human endometrium and directly controls placental development by increasing the human trophoblastic cells’ ability to invade the endometrium. We hypothesized that PIF’s effects on the endometrium counteract its pro-invasive effects.

Methods

We tested sPIF effect on the expression of three decidualization markers by RT-qPCR and/or immunochemiluminescence assay. We examined sPIF effect on human ESC migration by performing an in vitro wound healing assay. We analyzed sPIF effect on endometrial control of human trophoblast invasion by performing a zymography and an invasion assay.

Results

Firstly, we found that a synthetic analog of PIF (sPIF) significantly upregulates the mRNA expression of IGFBP-1 and connexin-43, and prolactin secretion in ESCs - suggesting a pro-differentiation effect. Secondly, we showed that the HTR-8/SVneo trophoblastic cell line’s invasive ability was low in the presence of conditioned media from ESCs cultured with sPIF. Thirdly, this PIF’s anti-invasive action was associated with a specifically decrease in MMP-9 activity.

Conclusion

Taken as a whole, our results suggest that PIF accentuates the decidualization process and the production of endometrial factors that limit trophoblast invasion. By controlling both trophoblast and endometrial cells, PIF therefore appears to be a pivotal player in the human embryo implantation process.
Differential effect of statin use on coagulation markers: an active comparative analysis in the NEO study
Authors: Bordbar Mohammadreza , de Mutsert Renée , Cevval Melike , Rosendaal Frits R. , Jukema J. Wouter , Lijfering Willem M.
Published: June 2021

Background

Statins are a potential treatment for venous thromboembolism (VTE) prophylaxis complementary to conventional anticoagulants without associated bleeding complications. This study aimed to compare pro-thrombotic activities of different classes of lipid-lowering drugs in an active comparator design and determine whether there is a relation between statin versus fibrate/niacin use and pro-coagulant factor outcomes.

Methods

This is a cross-sectional analysis of participants from the Netherlands Epidemiology of Obesity study using any class of lipid-lowering drugs, including any types of statins, niacin, and fibrates. We performed linear regression analyses to determine fibrinogen, factor (F) VIII, FIX, and FXI activity in statins versus fibrate/niacin users and adjusted for age, sex, tobacco smoking, body mass index (BMI), hypertension, diabetes, and prevalent cardiovascular disease.

Results

Among 1043 participants, the mean age was 58.4 ± 5.2 years, 61% were men, and the mean BMI was 31.3 ± 4.5 kg/m2. Clinical characteristics were balanced between statin and fibrate/niacin users. Statin users had lower mean FXI (18.3 IU/dL, 95% confidence interval (CI) 9.4 to 27.3) levels compared to fibrate/niacin users. The level of FVIII (15.8 IU/dL, 95% CI − 0.003 to 31.6), and FIX (11.3 IU/dL, 95% CI − 0.4 to 23.2) were lower in statin users than fibrate/niacin users with marginal statistical significance.

Conclusion

Current statin use was associated with lower plasma levels of FXI than fibrate/niacin use. The effects on coagulation factors may, in part, explain the benefit of statin therapy rendered in primary and secondary prevention of VTE.
Utilization and associated factors of reproductive health services among 20–39-year-old women in rural China: a cross-sectional study
Authors: Yue Jing , Luo Yang , Xu Chen , Qin Si , Meng Yanting , Fan Ling , Nie Min
Published: June 2021

Background

The use of reproductive health (RH) services is important to promote RH. However, little is known about RH services in rural areas, especially in low- and middle-income countries. China is the most populous country in the world, and 40.4% of its population is rural. Our study determined the utilization of and factors associated with RH services in rural China.

Methods

A cross-sectional study of 978 20- to 39-year-old women was performed in four villages of four cities in Hunan Province. A researcher-created structured questionnaire was used to collect the data. The data were entered into EpiData v3.0 and analysed using SPSS v18.0. Statistical significance was defined as a two-sided P-value of less than 0.05. Descriptive statistics were used to examine the socio-demographic factors and the use of RH services by the sample population. Chi-square tests were used to assess associations between categorical variables. Logistic regression analyses were performed to examine factors that correlated with the use of RH services.

Results

The top three services used were antenatal examinations (90.2%), postpartum visits (73.0%) and free folic acid supplements (71.6%). Age, monthly household income, employment, spousal education level, and artificial abortion history were associated with RH service utilization (P < 0.05). The most desired RH service was cervical/breast cancer prevention services (58.9%). The most preferred method participants used to obtain information on RH services was the internet.

Conclusions

The utilization rate for RH services in rural China needs improvement. Future efforts should target high-risk populations of women by providing them with RH-related information and cultivating positive attitudes towards RH services.
Factors influencing access to and utilisation of youth-friendly sexual and reproductive health services in sub-Saharan Africa: a systematic review
Authors: Ninsiima Lesley Rose , Chiumia Isabel Kazanga , Ndejjo Rawlance
Published: June 2021

Background

Despite the global agreements on adolescents’ sexual and reproductive health and rights, access to and utilisation of these services among the youth/adolescents remain unsatisfactory in low- and middle-income countries which are a significant barrier to progress in this area. This review established factors influencing access and utilisation of youth-friendly sexual and reproductive health services (YFSRHS) among the youth in sub-Saharan Africa to inform programmatic interventions.

Methodology

A systematic review of studies published between January 2009 and April 2019 using PubMed, Web of Science, EMBASE, Medline, and Cochrane Library, and Google Scholar databases was conducted. Studies were screened based on the inclusion criteria of barriers and facilitators of implementation of YFSRHS, existing national policies on provision of YFSRHS, and youth’s perspectives on these services.

Findings

A total of 23,400 studies were identified through database search and additional 5 studies from other sources. After the full-text screening, 20 studies from 7 countries met the inclusion criteria and were included in the final review. Structural barriers were the negative attitude of health workers and their being unskilled and individual barriers included lack of knowledge among youth regarding YFSRHS. Facilitators of utilisation of the services were mostly structural in nature which included community outreaches, health education, and policy recommendations to improve implementation of the quality of health services and clinics for adolescents/youth to fit their needs and preferences.

Conclusion

Stakeholder interventions focusing on implementing YFSRHS should aim at intensive training of health workers and put in place quality implementation standard guidelines in clinics to offer services according to youth’s needs and preferences. In addition, educating the youth through community outreaches and health education programs for those in schools can facilitate utilisation and scale up of the service.
Biomechanical analysis of an unpowered hip flexion orthosis on individuals with and without multiple sclerosis
Authors: Neuman Ross M. , Shearin Staci M. , McCain Karen J. , Fey Nicholas P.
Published: June 2021

Background

Gait impairment is a common complication of multiple sclerosis (MS). Gait limitations such as limited hip flexion, foot drop, and knee hyperextension often require external devices like crutches, canes, and orthoses. The effects of mobility-assistive technologies (MATs) prescribed to people with MS are not well understood, and current devices do not cater to the specific needs of these individuals. To address this, a passive unilateral hip flexion-assisting orthosis (HFO) was developed that uses resistance bands spanning the hip joint to redirect energy in the gait cycle. The purpose of this study was to investigate the short-term effects of the HFO on gait mechanics and muscle activation for people with and without MS. We hypothesized that (1) hip flexion would increase in the limb wearing the device, and (2) that muscle activity would increase in hip extensors, and decrease in hip flexors and plantar flexors.

Methods

Five healthy subjects and five subjects with MS walked for minute-long sessions with the device using three different levels of band stiffness. We analyzed peak hip flexion and extension angles, lower limb joint work, and muscle activity in eight muscles on the lower limbs and trunk. Single-subjects analysis was used due to inter-subject variability.

Results

For subjects with MS, the HFO caused an increase in peak hip flexion angle and a decrease in peak hip extension angle, confirming our first hypothesis. Healthy subjects showed less pronounced kinematic changes when using the device. Power generated at the hip was increased in most subjects while using the HFO. The second hypothesis was not confirmed, as muscle activity showed inconsistent results, however several subjects demonstrated increased hip extensor and trunk muscle activity with the HFO.

Conclusions

This exploratory study showed that the HFO was well-tolerated by healthy subjects and subjects with MS, and that it promoted more normative kinematics at the hip for those with MS. Future studies with longer exposure to the HFO and personalized assistance parameters are needed to understand the efficacy of the HFO for mobility assistance and rehabilitation for people with MS.
Serum metabolomics study of the association between dairy intake and the anti-müllerian hormone annual decline rate
Authors: Moslehi Nazanin , Marzbani Rezvan , Rezadoost Hassan , Mirmiran Parvin , Ramezani Tehrani Fahimeh , Azizi Fereidoun
Published: June 2021

Background

Dairy intake has been implicated in later ovarian aging but mechanism underlying the association is unknown. This study aimed to investigate (1) associations between dairy intake and metabolites previously shown related to anti-müllerian hormone (AMH) decline rate; (2) mediating roles of these metabolites in the prospective association of total dairy consumption with odds of AMH fast decline rate.

Methods

The participants comprised 186 reproductive-aged women randomly selected from the Tehran Lipid and Glucose Study. AMH was measured at baseline (1999–2001) and the 5th follow-up (2014–2017), and dietary data was collected at the second follow-up (2005–2008) using a food frequency questionnaire. Untargeted metabolomics was performed by gas chromatography–mass spectrometry using fasting-serum samples of the second follow-up. We analyzed dairy intake in association with the eight metabolites linked to the higher odds of AMH fast decline rate using linear regression with the Benjamini–Hochberg false discovery correction. Mediatory roles of the metabolites were assessed by bootstrapping.

Results

Mean age and BMI of the participants at metabolomics assessment were 44.7 ± 5.87 years and 28.8 ± 4.88 kg/m2, respectively. Phosphate, branched-chain amino acids (BCAAs), and proline decreased significantly from the first to the third tertile of total dairy intake. Total dairy as a continuous variable inversely associated with phosphate (beta = −0.166;pvalue = 0.018), valine (beta = −0.176;pvalue = 0.016), leucine (beta = −0.226;pvalue = 0.002), proline (beta = −0.219;pvalue = 0.003), and urea (beta = −0.156;p = 0.035) after accounting for all potential covariates and correction for multiplicity (q-value < 0.1). Fermented dairy showed similar results, but milk did not associate with any of the metabolites. Simple mediation showed significant indirect effects for phosphate, proline, and BCAAs but not urea. Entering the sum of phosphate, proline, and BCAAs as a mediator, the metabolites' total indirect effects were significant [β = −0.12 (95% CIs − 0.26, − 0.04)]. In contrast, the direct association of total dairy intake with the fast decline in AMH was non-significant [β = −0.28 (95% CIs − 0.67, 0.10)].

Conclusions

Total dairy was inversely associated with AMH decline rate-related metabolites. Inverse association of dairy intakes with the odds of AMH fast decline rate was indirectly mediated by lower phosphate, proline, and BCAAs.