bluuebunny/crossref_metadata_2025 huggingface dataset:
Governance frameworks for COVID-19 research ethics review and oversight in Latin America: an exploratory study
Authors: Palmero Ana , Carracedo Sarah , Cabrera Noelia , Bianchini Alahí
Published: November 2021

Background

Research has been an essential part of the COVID-19 pandemic response, including in Latin American (LA) countries. However, implementing research in emergency settings poses the challenge of producing valuable knowledge rapidly while upholding research ethical standards. Research ethics committees (RECs) therefore must conduct timely and rigorous ethics reviews and oversight of COVID-19 research. In the LA region, there is limited knowledge on how countries have responded to this need. To address this gap, the objective of our project is to explore if LA countries developed policies to streamline ethics review and oversight of research in response to the pandemic while ensuring its adherence to ethical standards, and to analyze to what extent these governance frameworks are in accordance with international guidance.

Methods

We conducted a descriptive and exploratory study assessing the COVID-19 research ethics governance frameworks of 19 LA countries, considering 4 dimensions based on international COVID-19 ethics guidance documents: (i) ethics review organizational model adopted, (ii) measures to coordinate between RECs and other research stakeholders, (iii) operational guidance for RECs, and (iv) key ethical issues for review and oversight of COVID-19 research.

Results

10 out of 19 LA countries have some policy to streamline ethics review of COVID-19 research. Of these countries only 6 issued comprehensive documents following international guidance that contemplate strategies with recommendations for concrete actions for a timely and rigorous review.

Conclusion

LA countries adopted partial strategies and operational guidance that may demonstrate a lack of a comprehensive view of research ethics for the review and oversight of COVID-19 research. Continuing efforts should be directed to strengthen LA countries' research capacity to respond timely and ethically to future health emergencies. Past lessons and the ones from this pandemic should be the basis to develop international standards and operational guidelines for ethics review and oversight of any research for public health emergencies.
Improving nurses’ knowledge, attitude, and performance in relation to ethical codes through group reflection strategy
Authors: Momennasab Marzieh , Ghanbari Marjan , Rivaz Mozhgan
Published: November 2021

Background

The most basic responsibility of nurses that even precedes their therapeutic role is respect for professional ethics in providing clinical care. The present study was conducted to determine the effect of group reflection on the knowledge, attitude and performance of nurses in relation to ethical codes.

Methods

The present blinded, before-after, educational trial was conducted on 86 nurses working at a general hospital in the south of Iran who were randomly divided into a intervention (n = 44) and a control (n = 42) group. Data were collected before and after the intervention using three tools, including a knowledge test, an attitude rating scale and a performance questionnaire. In the intervention group, the intervention given consisted of four sessions of group reflection, and the control group received a single lecture on ethical codes.

Results

The mean changes in the nurses’ score of knowledge after the intervention compared to before differed significantly in both intervention and control groups (P < 0.001), but there was no significant difference between the two groups in terms of the mean changes in the score of knowledge (2.73 ± 3.45 in intervention group vs. 2.57 ± 3.36 in control group, P = 0.83). Although the mean score of attitude differed significantly between the intervention and control groups in the posttest (34.7 ± 8.44 in intervention group vs. 29.95 ± 9.09 in control group, P < 0.014), the two groups were not significantly different in terms of the mean changes in the score of attitude in relation to ethical codes before and after the intervention (P < 0.14). Moreover, the two groups were significantly different in terms of the mean changes in the scores of performance in the two stages (9.07 ± 16.84 in intervention group vs. 0.67 ± 20.01 in control group, P < 0.001).

Conclusion

Group reflection can improve the knowledge, attitude and performance of nurses in relation to ethical codes. Although lectures can help improve nurses’ knowledge and attitude in this area, they have no significant effects on their performance.

Trial registration

Iranian Registry of Clinical Trials (No: IRCT2016070317546N6, registration date: 10 October 2016), https://www.irct.ir/trial/16112
Improving assessment of acute obstetric patients – introducing a Swedish obstetric triage system
Authors: Lindroos Linnéa , Korsoski Radha , Öhman Marie Ordéus , Elden Helen , Karlsson Ove , Sengpiel Verena
Published: November 2021

Background

Failure to identify severely ill obstetric patients seeking acute care, and hence delaying treatment, can lead to maternal morbidity and mortality. Triage is the prioritization of patients seeking emergency care, based on clinical decision-making tools assessing medical urgency. While triage has been applied in general emergency medicine for 30 years, there are only a few obstetric triage systems (OTS) and obstetric triage has hitherto been unknown in Sweden. Obstetric triage is more complex than general triage since both mother and fetus require assessment, and pregnancy-related physiological changes must be taken into account. This paper aims to describe the development and an initial evaluation of the first OTS in Sweden.

Methods

A multidisciplinary team surveyed reasons to seek acute obstetric care and the current patient flow at the largest obstetric unit in Scandinavia, Sahlgrenska University Hospital, Gothenburg, Sweden, with about 10,000 deliveries/year. A semi-structured literature review on obstetric triage was undertaken. Based on the survey and the literature review the first Swedish OTS was developed and implemented. Patient satisfaction was followed by electronical questionnaires. Initial validity evaluation was performed, defined by the system’s ability to identify patients with need for hospital admission, stratified by acuity level.

Results

The Gothenburg Obstetrical Triage System (GOTS) addresses the patient to one of five acuity levels based on both vital signs and 14 chief complaint algorithms. It entails recommendations for initial procedures of care as well as an acuity form for documentation. Initial evaluation of the system indicates good correlation between need for admission and acuity level. The implementation has provided the staff with an improved medical overview of the patients and patient flow and enabled the unit to monitor emergency care in a structured way. Implementation came along with increased patient and staff satisfaction.

Conclusion

The GOTS is the first OTS developed in and for Sweden and implementation has improved management of obstetric patients seeking acute care. Patients are now prioritized according to level of acuity and the time to assessment and treatment of severely ill patients can be structurally evaluated. Both patients and staff express improved satisfaction with obstetric triage.
Did the universal zero-markup drug policy lower healthcare expenditures? Evidence from Changde, China
Authors: Peng Zixuan , Zhan Chaohong , Ma Xiaomeng , Yao Honghui , Chen Xu , Sha Xinping , Coyte Peter C.
Published: November 2021

Background

The zero-markup drug policy (also known as the universal zero-markup drug policy (UZMDP)) was implemented in stages beginning with primary healthcare facilities in 2009 and eventually encompassing city public hospitals in 2016. This policy has been a central pillar of Chinese health reforms. While the literature has examined the impacts of this policy on healthcare utilization and expenditures, a more comprehensive and detailed assessment is warranted. The purpose of this paper is to explore the impacts of the UZMDP on inpatient and outpatient visits as well as on both aggregate healthcare expenditures and its various components (including drug, diagnosis, laboratory, and medical consumables expenditures).

Methods

A pre-post design was applied to a dataset extracted from the Changde Municipal Human Resource and Social Security Bureau comprising discharge data on 27,246 inpatients and encounter data on 48,282 outpatients in Changde city, Hunan province, China. The pre-UZMDP period for the city public hospitals was defined as the period from October 2015 to September 2016, while the post-UZMDP period was defined as the period from October 2016 to September 2017. Difference-in-Difference negative binomial and Tobit regression models were employed to evaluate the impacts of the UZMDP on healthcare utilization and expenditures, respectively.

Results

Four key findings flow from our assessment of the impacts of the UZMDP: first, outpatient and inpatient visits increased by 8.89 % and 9.39 %, respectively; second, average annual inpatient and outpatient drug expenditures fell by 4,349.00 CNY and 1,262.00 CNY, respectively; third, average annual expenditures on other categories of healthcare expenditures increased by 2,500.83 CNY, 417.10 CNY, 122.98 CNY, and 143.50 CNY for aggregate inpatient, inpatient diagnosis, inpatient laboratory, and outpatient medical consumables expenditures, respectively; and fourth, men and older individuals tended to have more inpatient and outpatient visits than their counterparts.

Conclusions

Although the UZMDP was effective in reducing both inpatient and outpatient drug expenditures, it led to a sharp rise in other expenditure categories. Policy decision makers are advised to undertake efforts to contain the growth in total healthcare expenditures, in general, as well as to evaluate the offsetting effects of the policy on non-drug components of care.
Policy, service, and training provision for women following a traumatic birth: an international knowledge mapping exercise
Authors: Thomson Gill , Diop Magali Quillet , Stuijfzand Suzannah , Horsch Antje ,   COST After birth Consortium, Lalor Joan G. , de Abreu Wilson , Avignon Valérie , Baranowska Barbara , Dikmen-Yildiz Pelin , El Hage Wissam , Fontein-Kuipers Yvonne , Horsch Antje , Garthus-Niegel Susan , Mesa Ernesto Gonzalez , Hadjigeorgiou Eleni , Healy Maria , Inci Figen , İsbir Gözde Gökçe , Jeličić Ljiljana , Karlsdóttir Sigfridur Inga , Kontosorou Georgia , Leahy-Warren Patricia , Leinweber Julia , Tighe Sylvia Murphy , Nagle Ursula , Patterson Jenny , Pehlke-Milde Jessica , Sovilj Mirjana , Stramrood Claire , Thomson Gill , Topalidou Anastasia , Węgrzynowska Maria
Published: November 2021

Background

High numbers of women experience a traumatic birth, which can lead to childbirth-related post-traumatic stress disorder (CB-PTSD) onset, and negative and pervasive impacts for women, infants, and families. Policies, suitable service provision, and training are needed to identify and treat psychological morbidity following a traumatic birth experience, but currently there is little insight into whether and what is provided in different contexts. The aim of this knowledge mapping exercise was to map policy, service and training provision for women following a traumatic birth experience in different European countries.

Methods

A survey was distributed as part of the COST Action “Perinatal mental health and birth-related trauma: Maximizing best practice and optimal outcomes”. Questions were designed to capture country level data; care provision (i.e., national policies or guidelines for the screening, treatment and/or prevention of a traumatic birth, service provision), and nationally mandated pre-registration and post-registration training for maternity professionals.

Results

Eighteen countries participated. Only one country (the Netherlands) had national policies regarding the screening, treatment, and prevention of a traumatic birth experience/CB-PTSD. Service provision was provided formally in six countries (33%), and informally in the majority (78%). In almost all countries (89%), women could be referred to specialist perinatal or mental health services. Services tended to be provided by midwives, although some multidisciplinary practice was apparent. Seven (39%) of the countries offered ‘a few hours’ professional/pre-registration training, but none offered nationally mandated post-registration training.

Conclusions

A traumatic birth experience is a key public health concern. Evidence highlights important gaps regarding formalized care provision and training for care providers.
Long-term dynamics of the human oral microbiome during clinical disease progression
Authors: Duran-Pinedo Ana , Solbiati Jose , Teles Flavia , Teles Ricardo , Zang Yanping , Frias-Lopez Jorge
Published: November 2021

Background

Oral microbiome dysbiosis is linked to overt inflammation of tooth-supporting tissues, leading to periodontitis, an oral condition that can cause tooth and bone loss. Microbiome dysbiosis has been described as a disruption in the symbiotic microbiota composition’s stability that could adversely affect the host’s health status. However, the precise microbiome dynamics that lead to dysbiosis and the progression of the disease are largely unknown. The objective of our study was to investigate the long-term dynamics of periodontitis progression and its connection to dysbiosis.

Results

We studied three different teeth groups: sites that showed disease progression, sites that remained stable during the study, and sites that exhibited a cyclic deepening followed by spontaneous recovery. Time-series analysis revealed that communities followed a characteristic succession of bacteria clusters. Stable and fluctuating sites showed high asynchrony in the communities (i.e., different species responding dissimilarly through time) and a reordering of the communities where directional changes dominated (i.e., sample distance increases over time) in the stable sites but not in the fluctuating sites.

Progressing sites exhibited low asynchrony and convergence (i.e., samples distance decreases over time). Moreover, new species were more likely to be recruited in stable samples if a close relative was not recruited previously. In contrast, progressing and fluctuating sites followed a neutral recruitment model, indicating that competition between closely related species is a significant component of species-species interactions in stable samples. Finally, periodontal treatment did not select similar communities but stabilized α-diversity, centered the abundance of different clusters to the mean, and increased community rearrangement.

Conclusions

Here, we show that ecological principles can define dysbiosis and explain the evolution and outcomes of specific microbial communities of the oral microbiome in periodontitis progression. All sites showed an ecological succession in community composition. Stable sites were characterized by high asynchrony, a reordering of the communities where directional changes dominated, and new species were more likely to be recruited if a close relative was not recruited previously. Progressing sites were characterized by low asynchrony, community convergence, and a neutral model of recruitment. Finally, fluctuating sites were characterized by high asynchrony, community convergence, and a neutral recruitment model.
FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling
Authors: Su Xiaoshan , Chen Junjie , Lin Xiaoping , Chen Xiaoyang , Zhu Zhixing , Wu Weijing , Lin Hai , Wang Jianming , Ye Xiangjia , Zeng Yiming
Published: November 2021

Background

Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial–mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated.

Methods

The present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT.

Results

Based on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling.

Conclusions

In summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.
Heart failure in type 2 diabetes: current perspectives on screening, diagnosis and management
Authors: Ceriello Antonio , Catrinoiu Doina , Chandramouli Chanchal , Cosentino Francesco , Dombrowsky Annique Cornelia , Itzhak Baruch , Lalic Nebojsa Malić , Prattichizzo Francesco , Schnell Oliver , Seferović Petar M. , Valensi Paul , Standl Eberhard ,   the D&CVD EASD Study Group
Published: November 2021

Type 2 diabetes is one of the most relevant risk factors for heart failure, the prevalence of which is increasing worldwide. The aim of the review is to highlight the current perspectives of the pathophysiology of heart failure as it pertains to type 2 diabetes. This review summarizes the proposed mechanistic bases, explaining the myocardial damage induced by diabetes-related stressors and other risk factors, i.e., cardiomyopathy in type 2 diabetes. We highlight the complex pathology of individuals with type 2 diabetes, including the relationship with chronic kidney disease, metabolic alterations, and heart failure. We also discuss the current criteria used for heart failure diagnosis and the gold standard screening tools for individuals with type 2 diabetes. Currently approved pharmacological therapies with primary use in type 2 diabetes and heart failure, and the treatment-guiding role of NT-proBNP are also presented. Finally, the influence of the presence of type 2 diabetes as well as heart failure on COVID-19 severity is briefly discussed.
Circ-RNF121 regulates tumor progression and glucose metabolism by miR-1224-5p/FOXM1 axis in colorectal cancer
Authors: Jiang Zhipeng , Hu Hao , Hu Wenli , Hou Zehui , Liu Wei , Yu Zhuomin , Liang Zhiqiang , Chen Shuang
Published: November 2021

Aim

Previous studies have reported that circular RNA (circRNA) is associated with the pathogenesis of CRC. This study was designed to reveal the mechanism of circ-ring finger protein 121 (circ-RNF121) in colorectal cancer (CRC).

Materials and methods

The levels of circ-RNF121, microRNA-1224-5p (miR-1224-5p) and forkhead box M1 (FOXM1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was detected by western blot. Cell proliferation was analyzed by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell colony formation assays. Flow cytometry analysis was performed to investigate cell apoptosis. Cell migration and invasion were investigated by transwell and wound-healing assays. Cell glycolysis was detected using glucose, lactate and ADP/ATP ratio assay kits. The binding relationship between miR-1224-5p and circ-RNF121 or FOXM1 was predicted by starBase online database, and identified by dual-luciferase reporter assay. The impacts of circ-RNF121 silencing on tumor formation in vivo were disclosed by in vivo tumor formation assay.

Key findings

Circ-RNF121 and FOXM1 expression were dramatically upregulated, while miR-1224-5p expression was downregulated in CRC tissues or cells compared with control groups. Circ-RNF121 silencing repressed cell proliferation, migration, invasion and glycolysis but induced cell apoptosis in CRC, which were attenuated by miR-1224-5p inhibitor. Additionally, circ-RNF121 acted as a sponge of miR-1224-5p and miR-1224-5p bound to FOXM1. Circ-RNF121 silencing inhibited tumor growth in vivo. Furthermore, circ-RNF121 was secreted through being packaged into exosomes.

Significance

The finding provided a novel insight into studying circRNA-mediated CRC therapy.
An empirical analysis of the impact of income inequality and social capital on physical and mental health - take China’s micro-database analysis as an example
Authors: He Yuanyuan , Zhou Lulin , Li Junshan , Wu Jun
Published: November 2021

Background

Income inequality is one of the important reflections of the unbalanced development of the world economy and can have adverse effects on physical and mental health.

Methods

This article used the 2018 China Family Panel Studies Database as an empirical analysis data source. The Kakwani index (KI) was used to measure income inequality, and social capital was broken into cognitive social capital and structural social capital. Our assessment was conducted by using STATA16 software for ordered logistic regression, verifying income inequality, social capital on correlation between physical and mental health firstly; then by gradual regression methods to verify intermediary effect, and demonstrate the social capital as an intermediary variable affecting physical and mental health as income inequality.

Result

The income inequality has a significant negative effect on physical and mental health (β = − 0.964, − 0.381; OR = 0.382, 0.758; P < 0.01), Social capital has a significant effect on physical and mental health (Cognitive SC(MH): β = 0.146 and 0.104, OR = 1.157 and 1.110, P < 0.01; Cognitive SC(PH): β = 0.046 and 0.069, OR = 1.047 and 1.071, P < 0.01; Structural SC(MH): β = − 0.005, 0.025 and 0.015, OR = 0.995, 1.025 and 1.015, P > 0.1, P < 0.01 and P < 0.01; Structural SC(PH): β = − 0.026, 0.009 and − 0.013, OR = 0.975, 1.009 and 0.987, P < 0.01, P > 0.1 and P < 0.01). Our analysis also showed that social capital (cognitive social capital and structural social capital) has an intermediary effect on physical and mental health due to income inequality.

Conclusion

This study shows that income inequality can not only directly affect physical and mental health, but also through social capital intermediary utility indirectly affect physical and mental health, social capital has positive effects on physical and mental health. At the same time, income inequality and social capital’s effects on physical and mental health exist regional differences, urban-rural differences, and gender differences. Therefore, in the development of special policies to support and take care of vulnerable groups, special attention needs to be paid to poor rural areas and female groups.
Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer
Authors: Zhu Gongmin , Pei Lijiao , Xia Hongwei , Tang Qiulin , Bi Feng
Published: November 2021

Colorectal cancer (CRC) is a heterogeneous disease at the cellular and molecular levels. Kirsten rat sarcoma (KRAS) is a commonly mutated oncogene in CRC, with mutations in approximately 40% of all CRC cases; its mutations result in constitutive activation of the KRAS protein, which acts as a molecular switch to persistently stimulate downstream signaling pathways, including cell proliferation and survival, thereby leading to tumorigenesis. Patients whose CRC harbors KRAS mutations have a dismal prognosis. Currently, KRAS mutation testing is a routine clinical practice before treating metastatic cases, and the approaches developed to detect KRAS mutations have exhibited favorable sensitivity and accuracy. Due to the presence of KRAS mutations, this group of CRC patients requires more precise therapies. However, KRAS was historically thought to be an undruggable target until the development of KRASG12C allele-specific inhibitors. These promising inhibitors may provide novel strategies to treat KRAS-mutant CRC. Here, we provide an overview of the role of KRAS in the prognosis, diagnosis and treatment of CRC.
Circulating ANGPTL3 and ANGPTL4 levels predict coronary artery atherosclerosis severity
Authors: Sun Ting , Zhan Wanlin , Wei Lijiang , Xu Zuojun , Fan Li , Zhuo Yang , Wang Changqian , Zhang Junfeng
Published: November 2021

Background

We investigated the role of ANGPTL3 and ANGPTL4 in atherosclerosis development and determined whether plasma concentrations of ANGPTL3 and ANGPTL4 are related to the degree of coronary stenosis.

Methods

A total of 305 consecutive patients with angina who underwent diagnostic coronary angiography were enrolled in the study between August 2017 and August 2018. The levels of ANGPTL3 and ANGPTL4 were measured by using competitive ELISA kits.

Results

According to the degree of coronary artery stenosis, patients were classified into four types: coronary artery stenosis of < 10%, 10-50%, 50-75, and > 75%. The plasma ANGPTL3 level was higher (51.71 ± 52.67 vs. 24.65 ± 10.32 ng/mL, P < 0.001) and that of ANGPTL4 was lower (454.66 ± 269.05 vs. 875.49 ± 961.15 ng/mL, P < 0.001) in the coronary artery stenosis ≥ 10% group than in the < 10% group. ANGPTL3 and ANGPTL4 levels were significantly associated with the severity of coronary vascular stenosis. ROC curve analyses indicated that ANGPTL3 concentrations above 30.5 ng/mL can predict atherosclerosis with a sensitivity of 71.2% and specificity of 75.3%, and that ANGPTL4 levels below 497.5 ng/mL can predict atherosclerosis with a sensitivity of 63.9% and specificity of 74.5%. ANGPTL3 and ANGPTL4 were determined to be independent risk factors for coronary atherosclerosis with odds ratios (ORs) of 0.189 (95% CI 0.097-0.368, P < 0.001) and 3.625 (95% CI 1.873-7.016, P < 0.001), respectively.

Conclusions

Increased ANGPTL3 or decreased ANGPTL4 shows an association with coronary atherosclerosis and, may become a predictor of coronary atherosclerosis in the future.
Positive effect of combined exercise on adipokines levels and pubertal signs in overweight and obese girls with central precocious puberty
Authors: Shokri Elnaz , Heidarianpour Ali , Razavi Zahra
Published: November 2021

Background

The prevalence of precocious puberty is increasing. Obesity has been demonstrated to be associated with changes in the adipokine profile and incidence of early puberty in girls. This study assessed the pubertal signs, the levels of adiponectin, resistin, and tumor necrosis factor-alpha (TNF-α) after 12 weeks of combined exercise and 4 weeks of detraining in overweight and obese girls with precocious puberty.

Methods

Thirty overweight and obese girls (aged 7–9) with precocious puberty, who had received Triptorelin, were randomly divided into two groups (15 exercise and 15 control). Initially, serum levels of adiponectin, resistin, TNF-α, luteinising hormone (LH), and follicle-stimulating hormone (FSH) and the signs of puberty progression (bone age, uterine length, and ovarian volume) were measured. The exercise group performed 60 min of combined (aerobic and resistance) exercise three times/week for 12 weeks. The control group did not receive any exercise. 48 h after the last training session and after 4 weeks of detraining, all research variables were measured (also in the control group). The statistical method used for data analysis was repeated measures ANOVA.

Results

In the exercise group, adiponectin significantly increased and resistin significantly decreased after 12 weeks. After 4 weeks of detraining, adiponectin significantly decreased, but resistin significantly increased. TNF-α levels did not change significantly during the study. There was no significant difference in all of the factors in the control group. Throughout the 16-week study period, the rate of puberty and LH significantly decreased in both exercise and control groups, but FSH, LH/FSH and ovarian volume significantly decreased in the exercise group alone (P<0.05).

Conclusions

Combined exercise increased adiponectin and decreased resistin and the rate of puberty. However, after 4 weeks of detraining, these effects diminished but did not disappear.

Trial registration

IRCT, IRCT56471. Registered 25 may 2021 - Retrospectively registered, https://fa.irct.ir/user/profile
Relationship of symptom stress, care needs, social support, and meaning in life to quality of life in patients with heart failure from the acute to chronic stages: a longitudinal study
Authors: Liu Min-Hui , Chiou Ai-Fu , Wang Chao-Hung , Yu Wen-Pin , Lin Mei-Hui
Published: November 2021

Background

Patients with heart failure (HF) experience continuous changes in symptom distress, care needs, social support, and meaning in life from acute decompensation to chronic phases. The longitudinal relationship between these four factors and quality of life (QOL) was not fully explored.

Aims

To simultaneously investigate the relationship between all factors and QOL from hospitalization to 6 months after discharge, and the impact of the changes in these factors on QOL at different time points.

Methods

A longitudinal design with panel research (4 time points) was used. From January 2017 to December 2019, patients hospitalized due to acute decompensated HF were consecutively enrolled and followed up for 6 months. Patients were interviewed with questionnaires assessing symptom distress, care needs, social support, meaning in life and QOL at hospitalization and 1, 3 and 6 months after discharge.

Results

A total of 184 patients completed 6 months of follow-up. From baseline to 6 months, QOL continuously improved along with decreases in symptoms and care needs, but increases in social support and meaning in life. Better QOL was associated with younger age, higher education level, economic independence, less symptom distress and care needs, and stronger meaning in life (p < 0.05). Compared with hospitalization, decreases in care needs and increases in meaning in life at 1, 3 and 6 months were associated with an increase in physical QOL (p < 0.01). The decrease in care needs and increase in meaning in life at 3 months were associated with an increase in mental QOL (p < 0.05). The increase in social support at 6 months was associated with increases in both physical and mental QOL (p < 0.01). Changes in symptom distress were not correlated with changes in QOL from baseline to all time points. In the multivariable analysis, these findings were independent of age, educational level and economic status.

Conclusions

Although symptom distress is associated with QOL after acute decompensated HF, QOL cannot be improved only by improvement in symptoms. With differential duration of improvement in each factor, the integration of alleviation in care needs and strengthening in social support and meaning in life might provide additional benefits in QOL.
Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells
Authors: Bernegger Sabine , Vidmar Robert , Fonovic Marko , Posselt Gernot , Turk Boris , Wessler Silja
Published: November 2021

Background

High temperature requirement A (HtrA) is an active serine protease secreted by the group-I carcinogen Helicobacter pylori (H. pylori). The human cell adhesion protein and tumor suppressor E-cadherin (hCdh1) expressed on the surface of gastric epithelial cells was identified as the first HtrA substrate. HtrA-mediated hCdh1 cleavage and subsequent disruption of intercellular adhesions are considered as important steps in H. pylori pathogenesis. In this study, we performed a proteomic profiling of H. pylori HtrA (HpHtrA) to decipher the complex mechanism of H. pylori interference with the epithelial barrier integrity.

Results

Using a proteomic approach we identified human desmoglein-2 (hDsg2), neuropilin-1, ephrin-B2, and semaphorin-4D as novel extracellular HpHtrA substrates and confirmed the well characterized target hCdh1. HpHtrA-mediated hDsg2 cleavage was further analyzed by in vitro cleavage assays using recombinant proteins. In infection experiments, we demonstrated hDsg2 shedding from H. pylori-colonized MKN28 and NCI-N87 cells independently of pathogen-induced matrix-metalloproteases or ADAM10 and ADAM17.

Conclusions

Characterizing the substrate specificity of HpHtrA revealed efficient hDsg2 cleavage underlining the importance of HpHtrA in opening intercellular junctions.
Mechanistically informed non-invasive peripheral nerve stimulation for peripheral neuropathic pain: a randomised double-blind sham-controlled trial
Authors: Johnson Selina , Marshall Anne , Hughes Dyfrig , Holmes Emily , Henrich Florian , Nurmikko Turo , Sharma Manohar , Frank Bernhard , Bassett Paul , Marshall Andrew , Magerl Walter , Goebel Andreas
Published: November 2021

Background

Induction of long-term synaptic depression (LTD) is proposed as a treatment mechanism for chronic pain but remains untested in clinical populations. Two interlinked studies; (1) A patient-assessor blinded, randomised, sham-controlled clinical trial and (2) an open-label mechanistic study, sought to examine therapeutic LTD for persons with chronic peripheral nerve injury pain.

Methods

(1) Patients were randomised using a concealed, computer-generated schedule to either active or sham non-invasive low-frequency nerve stimulation (LFS), for 3 months (minimum 10 min/day). The primary outcome was average pain intensity (0–10 Likert scale) recorded over 1 week, at 3 months, compared between study groups. (2) On trial completion, consenting subjects entered a mechanistic study assessing somatosensory changes in response to LFS.

Results

(1) 76 patients were randomised (38 per group), with 65 (31 active, 34 sham) included in the intention to treat analysis. The primary outcome was not significant, pain scores were 0.3 units lower in active group (95% CI − 1.0, 0.3; p = 0.30) giving an effect size of 0.19 (Cohen’s D). Two non-device related serious adverse events were reported. (2) In the mechanistic study (n = 19) primary outcomes of mechanical pain sensitivity (p = 0.006) and dynamic mechanical allodynia (p = 0.043) significantly improved indicating reduced mechanical hyperalgesia.

Conclusions

Results from the RCT failed to reach significance. Results from the mechanistic study provide new evidence for effective induction of LTD in a clinical population. Taken together results add to mechanistic understanding of LTD and help inform future study design and approaches to treatment.

Trial registration ISRCTN53432663.
Improving postural stability among people with lower-limb amputations by tactile sensory substitution
Authors: Chen Lijun , Feng Yanggang , Chen Baojun , Wang Qining , Wei Kunlin
Published: November 2021

Background

For people with lower-limb amputations, wearing a prosthetic limb helps restore their motor abilities for daily activities. However, the prosthesis's potential benefits are hindered by limited somatosensory feedback from the affected limb and its prosthesis. Previous studies have examined various sensory substitution systems to alleviate this problem; the prominent approach is to convert foot–ground interaction to tactile stimulations. However, positive outcomes for improving their postural stability are still rare. We hypothesized that the sensory substiution system based on surrogated tactile stimulus is capable of improving the standing stability among people with lower-limb amputations.

Methods

We designed a wearable device consisting of four pressure sensors and two vibrators and tested it among people with unilateral transtibial amputations (n = 7) and non-disabled participants (n = 8). The real-time measurements of foot pressure were fused into a single representation of foot–ground interaction force, which was encoded by varying vibration intensity of the two vibrators attached to the participants’ forearm. The vibration intensity followed a logarithmic function of the force representation, in keeping with principles of tactile psychophysics. The participants were tested with a classical postural stability task in which visual disturbances perturbed their quiet standing.

Results

With a brief familiarization of the system, the participants exhibited better postural stability against visual disturbances when switching on sensory substitution than without. The body sway was substantially reduced, as shown in head movements and excursions of the center of pressure. The improvement was present for both groups of participants and was particularly pronounced in more challenging conditions with larger visual disturbances.

Conclusions

Substituting otherwise missing foot pressure feedback with vibrotactile signals can improve postural stability for people with lower-limb amputations. The design of the mapping between the foot–ground interaction force and the tactile signals is essential for the user to utilize the surrogated tactile signals for postural control, especially for situations that their postural control is challenged.
Large cell morphology, CMYC+ tumour cells, and PD-1+ tumour cell/intense PD-L1+ cell reactions are important prognostic factors in nodal peripheral T-cell lymphomas with T follicular helper markers
Authors: Mihashi Yasuhito , Kimura Shoichi , Iwasaki Hiromi , Oshiro Yumi , Takamatsu Yasushi , Kawauchi Shigeto , Shimajiri Shohei , Ishizuka Kenji , Takeshita Morishige
Published: November 2021

Background

The clinicopathological characteristics and prognostic factors in nodal peripheral T-cell lymphomas (PTCLs) with two or more T follicular helper markers (TFH+) are not adequately investigated.

Methods

Immunohistologically, we selected 22 patients with TFH+ lymphoma (PTCL-TFH) in 47 of PTCL-not otherwise specified (NOS), and subclassified into large and small cell groups. We compared the two groups with 39 angioimmunoblastic T-cell lymphoma (AITL) and seven follicular T-cell lymphoma (F-TCL) patients. Prognostic factors were analysed by overall survival in patients with three types of TFH+ PTCLs.

Results

Thirteen large cell and nine small cell PTCL-TFH patients had more than two TFH markers including programmed cell death-1 (PD-1). Large cell PTCL-TFH showed frequent CMYC expression in 10 patients (77%), and four of 11 large cell group (36%) had somatic RHOA G17V gene mutation by Sanger sequencing. Large cell PTCL-TFH patients showed significantly worse prognosis than those of the small cell group, AITL, and F-TCL (p < 0.05). In TFH+ PTCLs, CMYC+ tumour cells, and combined PD-1 ligand 1 (PD-L1) + tumour cells and intense reaction of PD-L1+ non-neoplastic cells (high PD-L1+ cell group) were significantly poor prognostic factors (p < 0.05). Combinations of CMYC+ or PD-1+ tumour cells and high PD-L1+ cell group indicated significantly poor prognosis (p < 0.01).

Conclusion

Large cell PTCL-TFH indicated poor prognosis in TFH+ PTCLs. These data suggested that CMYC+ tumour cells and intense PD-L1+ cell reaction influenced tumour cell progression in TFH+ PTCLs, and PD-1+ tumour cell/intense PD-L1+ cell reactions may play a role in immune evasion.
Comparison of sliding window and field-in-field techniques for tangential whole breast irradiation using the Halcyon and Synergy Agility systems
Authors: Richter Anne , Wegener Sonja , Breuer Kathrin , Razinskas Gary , Weick Stefan , Exner Florian , Bratengeier Klaus , Flentje Michael , Sauer Otto , Polat Bülent
Published: November 2021

Background

To implement a tangential treatment technique for whole breast irradiation using the Varian Halcyon and to compare it with Elekta Synergy Agility plans.

Methods

For 20 patients two comparable treatment plans with respect to dose coverage and normal tissue sparing were generated. Tangential field-in-field treatment plans (Pinnacle/Synergy) were replanned using the sliding window technique (Eclipse/Halcyon). Plan specific QA was performed using the portal Dosimetry and the ArcCHECK phantom. Imaging and treatment dose were evaluated for treatment delivery on both systems using a modified CIRS Phantom.

Results

The mean number of monitor units for a fraction dose of 2.67 Gy was 515 MUs and 260 MUs for Halcyon and Synergy Agility plans, respectively. The homogeneity index and dose coverage were similar for both treatment units. The plan specific QA showed good agreement between measured and calculated plans. All Halcyon plans passed portal dosimetry QA (3%/2 mm) with 100% points passing and ArcCheck QA (3%/2 mm) with 99.5%. Measurement of the cumulated treatment and imaging dose with the CIRS phantom resulted in lower dose to the contralateral breast for the Halcyon plans.

Conclusions

For the Varian Halcyon a plan quality similar to the Elekta Synergy device was achieved. For the Halcyon plans the dose contribution from the treatment fields to the contralateral breast was even lower due to less interleaf transmission of the Halcyon MLC and a lower contribution of scattered dose from the collimator system.
LncRNA NONHSAT030515 promotes the chondrogenic differentiation of human adipose-derived stem cells via regulating the miR-490-5p/BMPR2 axis
Authors: Yang Qinqin , Guo Jiajia , Ren Zhijing , Li Bo , Huang Haifeng , Yang Zhen
Published: November 2021

Background

Chondrogenic differentiation of human adipose-derived stem cells (hADSCs) is important for cartilage generation and degradation. LncRNAs play an essential role in stem cell differentiation. However, the role and mechanism of lncRNA in hADSCs remain unclear. Our previous study showed that miR-490-5p was downregulated during chondrogenic differentiation of hADSCs. In this study, we investigated the effect and mechanism of lncRNA NONHSAT030515 interacting with miR-490-5p on chondrogenic differentiation of hADSCs.

Methods

Alcian blue staining was used to assess the deposition of chondromatrix proteins following chondrogenic differentiation of human adipose stem cells. Immunohistochemistry was used to evaluate the expression of collagenII. TargetScan, miRTarBase and miRDB database analyses were applied to find the miRNA and target genes of lncRNA NONHSAT030515. A dual luciferase experiment was conducted to identify the direct target of NONHSAT030515. pcDNA3.1- NONHSAT030515 transfection and sh- NONHSAT030515 treatment were conducted to verify the role of lncRNA NONHSAT030515 in chondrogenic differentiation. The levels of Aggrecan, SOX9 and COL2A1 were analyzed by qRT-PCR and Western blot assay.

Results

Alcian blue staining, immunocytochemical, qRT-PCR, and Western blot have determined that lncRNA NONHSAT030515 can promote the chondrogenic differentiation of hADSCs. MiR-490- 5p was the direct target of NONHSAT030515, while BMPR2 was the target gene. This result was confirmed by luciferase reporter assay. Up-regulation of NONHSAT030515 promoted BMPR2 protein expression and promoted chondrogenic differentiation, whereas down-regulation of NONHSAT030515 caused completely opposite results.

Conclusion

LncRNA NONHSAT030515 promotes the chondrogenic differentiation of hADSCs through increasing BMPR2 expression by regulating miR-490- 5p.
Total glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway
Authors: Zhou Yu-hu , Xie Qiang
Published: November 2021

Background

Osteoporosis (OP) is a well-known chronic degenerative disease, with impaired mesenchymal stem cells (MSCs) function and suppressed osteogenic differentiation. Total glycosides from Eucommia ulmoides seed (TGEUS) was a Chinese medicine and have rich pharmacological effects. This study was designed to explore the mechanism of TGEUS in promoting osteogenic differentiation and bone formation in ovariectomized (OVX) rats.

Methods

Adipose‐derived mesenchymal stem cells (ADSCs) were isolated and treated with different concentration of TGEUS. Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Osteogenic capacity was identified by ALP staining and ARS staining. Moreover, RNA sequencing between control and TGEUS treated ADSCs were further performed to reveal the mechanism of TGEUS in promoting osteogenic differentiation. The expression of Jag1, Lfng and Hey1 were measured using quantitative real-time polymerase chain reaction (qRTPCR). Osteogenic markers were further assessed by western blot. DAPT and NICD were further used to identify whether Notch signaling pathway involved into TGEUS promoting osteogenic differentiation of ADSCs. Ovariectomy-induced bone loss rats model was established and divided into three groups: sham, OVX and OVX + TGEUS groups. HE staining and immunohistochemical staining were further performed to identify whether TGEUS could promote bone formation.

Results

TGEUS treatment significantly enhanced the cell viability and ALP activity than control group, the optimal dose of TGEUS was 5 μM. We selected 5 μM TGEUS for further study. TGEUS significantly enhanced ALP activity and calcium deposition than that of control group. Activation of Notch signaling fully blocked TGEUS-induced osteogenic differentiation of ADSCs. Following TGEUS treatment, the trabecular bone of the rats was significantly increased, thickened, and more connected compared to the OVX group. With the treatment of TGEUS, the expression of Osterix (Osx), Osteocalcin (OCN) and RUNX Family Transcription Factor 2 (RUNX2) increased than OVX group.

Conclusion

TGEUS enhanced osteogenic differentiation of ADSCs and promoted bone formation in ovariectomy-induced bone loss rats. Our study broadened the understanding of TGEUS as a therapeutic target against osteoporosis.
LncRNA SCIRT is downregulated in atherosclerosis and suppresses the proliferation of human aortic smooth muscle cells (HAOSMCs) by sponging miR-146a in cytoplasm
Authors: Gao Wenhui , Li Rong , Yu Jingjing , He Xijie , Xu Duo , Zhong Hai , Dong Wenwen , Cui Hanbin
Published: November 2021

Background

SCIRT has been characterized as a key player in cancer biology, while its role in other human diseases is unclear. This study explored its role in atherosclerosis, with a specific focus on its interaction with SCIRT and miR-146a.

Methods

The expression of SCIRT and miR-146a in atherosclerosis-affected tissues and healthy tissues from 56 atherosclerosis patients were analyzed by RT-qPCR. The expression of SCIRT in nuclear and cytoplasm samples was detected by RNA fractionation assay. The direct interaction between SCIRT and miR-146a was detected by RNA pull-down assay. SCIRT and miR-146a were overexpressed in human aortic smooth muscle cells (HAOSMCs) to study the crosstalk between them. The role of SCIRT and miR-146a in the proliferation of HAOSMCs was analyzed with BrdU assay.

Results

SCIRT was downregulated by atherosclerosis, while miR-146a was upregulated by atherosclerosis. SCIRT was detected in both cytoplasm and nuclear samples, and it directly interacted with miR-146a. In HAOSMCs, overexpression of SCIRT and miR-146a did not affect the expression of each other. Interestingly, SCIRT suppressed the proliferation of HAOSMCs and reduced the enhancing effects of miR-146a on cell proliferation.

Conclusion

Therefore, SCIRT is downregulated in atherosclerosis and it suppresses the proliferation of HAOSMCs by sponging miR-146a in cytoplasm.