bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ROCK-ezrin signaling pathway mediates LPS-induced cytokine production in pulmonary alveolar epithelial cells
Authors: Ding Ning , Li Pibao , Li Huiqing , Lei Yunlong , Zhang Zengzhen 
Published: May 2022

AbstractBackgroundEzrin/radixin/moesin (ERM) proteins are members of the protein 4.1 superfamily and function as linkers that connect the actin cytoskeleton to the plasma membrane of cells. ERM also play critical role in the Lipopolysaccharide (LPS)-induced inflammatory response. However, the signaling mechanisms involved in this process remain unclear. In this study, we aimed to investigate the potential role of the rho-associated coiled-coil containing protein kinase (ROCK) pathway in LPS-induced ezrin phosphorylation and cytokine production in pulmonary alveolar epithelial cells.MethodsCultured A549 and HPAEpiC cells were treated with LPS. The expression and localization of ezrin in A549 and HPAEpiC cells were then analyzed by western blotting and immunoflurescence. Activation of RhoA/ROCK was assessed by western blotting and RhoA activity assays. The interaction of ezrin with Syk and myeloid differentiation factor 88 (MyD88)/IL-1R-associated kinase 1 (IRAK-1) was investigated by co-immunoprecipitation. The activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) was measured with electrophoretic mobility shift assays and by western blotting. ELISA and western blotting were performed to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and high mobility group box 1 protein (HMGB1) release into the culture supernatant, and cellular HMGB1 levels.ResultsLPS induced ezrin phosphorylation in a concentration- and time-dependent manner. The blockade of RhoA/ROCK inhibited LPS-induced ezrin phosphorylation and its translocation from the cytoplasm to the cell membrane. Co-immunoprecipitation assays further revealed that ezrin associated with Syk constitutively, but only associated with MyD88/IRAK-1 upon LPS challenge. Moreover, LPS-induced p38 and nuclear NF-κB activation was found to be ezrin dependent. The suppression of ezrin by siRNA or the blockade of ROCK activation with Y-27632 reduced the production of TNF-α, IL-1β, and HMGB1 in response to LPS.ConclusionsOur findings reveal a novel regulatory mechanism involving ezrin in the LPS-induced production of pro-inflammatory cytokines, and highlight the importance of the RhoA/ROCK-ezrin/Syk-MyD88/IRAK1 axis. Data presented in this manuscript provide novel insights into the signaling pathways activated in pulmonary alveolar epithelial cells by LPS.
A multilevel mixed effect analysis of neighbourhood and individual level determinants of risky sexual behaviour among young people in South Africa
Authors: Odimegwu Clifford Obby , Ugwu Nebechukwu Henry 
Published: May 2022

AbstractBackgroundDespite national and international commitments and efforts to prevent risky sexual behaviours, a high proportion of young people in South Africa are engaged in risky sexual behaviour. However, most efforts are currently directed toward addressing individual-level factors at the expense of not addressing neighbourhood-level determinants such as social disorganisation, contributing to risky sexual behaviour among young people in South Africa. This study investigated the multilevel factors of risky sexual behaviours among young people by gender in South Africa, using the lens of socio-ecological and social disorganisation frameworks.MethodsData from a nationally representative sample of 1268 males and 2621 females aged 15–24 years, giving a total of, 3889 never-married youths, were drawn from the 2016 South Africa Demographic and Health Survey. Analysis was conducted using multilevel mixed-effect logistic regressions with random community-level effects.ResultsFindings show that youth who were from a heterogeneous ethnic group (AOR = 0.49, CI: 0.35–0.67), household size of 5 + members (AOR = 0.78, CI: 0.54–1.15), community education (AOR = 0.97, CI: 0.72–1.32) were associated with low engagement in multiple sexual partnerships. Youths who were employed (AOR = 0.84, CI: 0.59–1.18), and from high-level community poverty (AOR = 0.76, CI: 0.58–1.00) were also associated with reduced odds of unprotected sex. In addition, older youth aged 20–24 years (AOR = 12.6, CI: 9.93–16.00); secondary education attainment (AOR = 1.01, CI 0.58–1.77); family structure (AOR = 1.37, CI: 0.75–1.15); Gauteng province (AOR = 1.45 CI: 0.92–2.28); residential mobility (AOR = 1.25, CI: 1.02–1.53), community media exposure to contraceptives (unprotected sex) (AOR = 1.38, CI: 1.09–1.76) were more likely to engage in risky sexual behaviour.ConclusionThe study revealed that neighbourhood and individual-level factors were important in explaining the factors associated with risky sexual behaviour among young people in South Africa. In addition, engagement in risky sexual behaviour was high, with minimal variation among young females and males in South Africa. It specifies that the practice of risky sexual behaviour is significantly associated with multilevel factors of social disorganisation that cut across gender. These results imply that there is a need to review policies of sexual risks reduction for each gender, which might help mitigate the adverse effects of social disorganisation for women and men youths in South Africa.
Characterizing the relationship between peak assistance torque and metabolic cost reduction during running with ankle exoskeletons
Authors: Miller Delaney E. , Tan Guan Rong , Farina Emily M. , Sheets-Singer Alison L. , Collins Steven H. 
Published: May 2022

Abstract
Background
Reducing the energy cost of running with exoskeletons could improve enjoyment, reduce fatigue, and encourage participation among novice and ageing runners. Previously, tethered ankle exoskeleton emulators with offboard motors were used to greatly reduce the energy cost of running with powered ankle plantarflexion assistance. Through a process known as “human-in-the-loop optimization”, the timing and magnitude of assistance torque was optimized to maximally reduce metabolic cost. However, to achieve the maximum net benefit in energy cost outside of the laboratory environment, it is also necessary to consider the tradeoff between the magnitude of device assistance and the metabolic penalty of carrying a heavier, more powerful exoskeleton.

Methods
In this study, tethered ankle exoskeleton emulators were used to characterize the effect of peak assistance torque on metabolic cost during running. Three recreational runners participated in human-in-the-loop optimization at four fixed peak assistance torque levels to obtain their energetically optimal assistance timing parameters at each level.

Results
We found that the relationship between metabolic rate and peak assistance torque was nearly linear but with diminishing returns at higher torque magnitudes, which is well-approximated by an asymptotic exponential function. At the highest assistance torque magnitude of 0.8 Nm/kg, participants’ net metabolic rate was 24.8 ± 2.3% (p = 4e–6) lower than running in the unpowered devices. Optimized timing of peak assistance torque was as late as allowed during stance (80% of stance) and optimized timing of torque removal was at toe-off (100% of stance); similar assistance timing was preferred across participants and torque magnitudes.

Conclusions
These results allow exoskeleton designers to predict the energy cost savings for candidate devices with different assistance torque capabilities, thus informing the design of portable ankle exoskeletons that maximize net metabolic benefit.
Evaporative flux method of leaf hydraulic conductance estimation: sources of uncertainty and reporting format recommendation
Authors: Wang Xiaoxiao , Zhao Jinfang , Huang Jianliang , Peng Shaobing , Xiong Dongliang 
Published: May 2022

Abstract
Background
The accurate estimation of leaf hydraulic conductance (Kleaf) is important for revealing leaf physiological characteristics and function. However, the Kleaf values are largely incomparable in previous studies for a given species indicating some uncertain influencing factors in Kleaf measurement.

Result
We investigated the potential impacts of plant sampling method, measurement setup, environmental factors, and transpiration steady state identification on Kleaf estimation in Oryza sativa and Cinnamomum camphora using evaporation flux method (EFM). The effects of sampling and rehydration time, the small gravity pressure gradients between water sources and leaves, and water degassing on Kleaf estimation were negligible. As expected, the estimated steady flow rate (E) was significantly affected by multiple environmental factors including airflow around leaf, photosynthetically active radiation (PARa) on leaf surfaces and air temperature. Kleaf decreased by 40% when PARa declined from 1000 to 500 µmol m−2 s−1 and decreased by 15.1% when air temperature increased from 27 to 37 °C. In addition, accurate steady-state flow rate identification and leaf water potential measurement were important for Kleaf estimation.

Conclusions
Based on the analysis of influencing factors, we provided a format for reporting the metadata of EFM-based Kleaf to achieve greater comparability among studies and interpretation of differences.
Exploring a novel method for optimising the implementation of a colorectal cancer risk prediction tool into primary care: a qualitative study
Authors: Milton Shakira , Emery Jon D. , Rinaldi Jane , Kinder Joanne , Bickerstaffe Adrian , Saya Sibel , Jenkins Mark A. , McIntosh Jennifer 
Published: May 2022

Abstract
Background
We developed a colorectal cancer risk prediction tool (‘CRISP’) to provide individualised risk-based advice for colorectal cancer screening. Using known environmental, behavioural, and familial risk factors, CRISP was designed to facilitate tailored screening advice to patients aged 50 to 74 years in general practice. In parallel to a randomised controlled trial of the CRISP tool, we developed and evaluated an evidence-based implementation strategy.

Methods
Qualitative methods were used to explore the implementation of CRISP in general practice. Using one general practice in regional Victoria, Australia, as a ‘laboratory’, we tested ways to embed CRISP into routine clinical practice. General practitioners, nurses, and operations manager co-designed the implementation methods with researchers, focussing on existing practice processes that would be sustainable. Researchers interviewed the staff regularly to assess the successfulness of the strategies employed, and implementation methods were adapted throughout the study period in response to feedback from qualitative interviews.
The Consolidated Framework for Implementation Research (CFIR) underpinned the development of the interview guide and intervention strategy. Coding was inductive and themes were developed through consensus between the authors. Emerging themes were mapped onto the CFIR domains and a fidelity checklist was developed to ensure CRISP was being used as intended.

Results
Between December 2016 and September 2019, 1 interviews were conducted, both face-to-face and via videoconferencing (Zoom). All interviews were transcribed verbatim and coded. Themes were mapped onto the following CFIR domains: (1) ‘characteristics of the intervention’: CRISP was valued but time consuming; (2) ‘inner setting’: the practice was open to changing systems; 3. ‘outer setting’: CRISP helped facilitate screening; (4) ‘individual characteristics’: the practice staff were adaptable and able to facilitate adoption of new clinical processes; and (5) ‘processes’: fidelity checking, and education was important.

Conclusions
These results describe a novel method for exploring implementation strategies for a colorectal cancer risk prediction tool in the context of a parallel RCT testing clinical efficacy. The study identified successful and unsuccessful implementation strategies using an adaptive methodology over time. This method emphasised the importance of co-design input to make an intervention like CRISP sustainable for use in other practices and with other risk tools.
Protective ileostomy increased the incidence of rectal stenosis after anterior resection for rectal cancer
Authors: Zhang Hui , Li Shanshan , Jin Xin , Wu Xian , Zhang Zhiyuan , Shen Lijun , Wan Juefeng , Wang Yan , Wang Yaqi , Yang Wang , Zhou Menglong , Zhang Jing , Lv Tao , Deng Yun , Xia Fan , Zhang Zhen 
Published: May 2022

Abstract
Background
In most of the views, rectal stenosis after anterior resection for rectal cancer results from pelvic radiotherapy. However, patients without receiving radiotherapy also suffer stenosis. In this study, we evaluated the factors associated with rectal stenosis after anterior rectal resection (ARR).

Methods
We conducted a retrospective study with ARR patients who underwent neoadjuvant chemoradiotherapy and the patients without radiotherapy. Patients who received watch and wait strategy with a clinical complete response after chemoradiotherapy were also included. Patients with colonoscopy follow-up were included for further analyses; 439 patients who underwent neoadjuvant chemoradiotherapy; 545 patients who received ARR without radiotherapy and 33 patients who received watch and wait strategy. Stenosis was diagnosed when a 12-mm diameter colonoscopy could not be passed through the rectum. Univariate and multivariate logistic regression analyses were performed to identify variables associated with rectal stenosis.

Results
According to the multivariate analysis in patients receiving ARR, both protective stoma and preoperative radiotherapy affected the occurrence of stenosis, with the odds ratios (ORs) of 3.375 and 2.251, respectively. According to the multivariate analysis, a preventive ileostomy was the only factor associated with stenosis both in patients receiving preoperative radiotherapy and without radiotherapy. Non-reversal ileostomy and long time between ileostomy and restoration increased the possibility of stenosis. In 33 patients who received watch and wait strategy, only one patient (3%) experienced stenosis.

Conclusion
Both surgery and radiotherapy are risk factors for rectal stenosis in rectal cancer patients. Compared to preoperative radiotherapy, a protective ileostomy is a more critical factor associated with rectal stenosis.
Resection and reconstruction of huge tumors in the chest wall
Authors: Dai Zhibing , Maihemuti Maierdanjiang , Sun Yachao , Jiang Renbing 
Published: May 2022

Abstract
Objective
To evaluate the experience and effects of resection and reconstruction of 4 cases of huge tumors in the chest wall.

Methods
The clinical data of 4 patients with huge tumors in the chest wall from July 2015 to January 2020 were collected and analyzed. There were 2 males and 2 females.Chondrosarcoma was diagnosed in 2 cases, giant cell tumor was diagnosed in 1 case,and metastasis from breast cancer was diagnosed in 1 case.All patients underwent extensive tumor resection and had thoracic exposure after tumor resection.Two patients underwent reconstruction with mesh and titanium mesh, and the incision was closed directly.The third patient underwent reconstruction with mesh and latissimus dorsi flap,and the fourth patient underwent reconstruction with mesh,titanium mesh and latissimus dorsi flap.

Result
One patient had incision infection after operation,which resolved after debridement.All patients were followed up for 2–6 years, no tumor recurrence or metastasis was noted during follow-up.None of patients had abnormal breathing, dyspnea or other physical discomfort.

Conclusion
It is difficult to resect the huge tumors in the chest wall,and it is more reasonable and safer to choose a reconstruction method using mesh and titanium mesh.The latissimus dorsi flap can achieve good results in repairing soft tissue defects.Close perioperative management and multidisciplinary team discussions can help to achieve better curative effects.
Dilated cardiomyopathy as the initial presentation of Becker muscular dystrophy: a systematic review of published cases
Authors: Del Rio-Pertuz Gaspar , Morataya Cristina , Parmar Kanak , Dubay Sarah , Argueta-Sosa Erwin 
Published: May 2022

AbstractThere are scarce publications regarding the presentation and outcome of Becker muscular dystrophy in adulthood when idiopathic dilated cardiomyopathy is the initial disease manifestation. We performed a systematic review using Medline, Embase, Cochrane, and Scopus to identify cases of adults with idiopathic dilated cardiomyopathy who were subsequently diagnosed with Becker muscular dystrophy from inception through August 2020. Six cases were found. We identified young males (Median age: 26 years) with Becker muscular dystrophy who first presented with dilated cardiomyopathy. Most patients initially presented with congestive heart failure symptoms (5/6, 83%), and had a median left ventricular ejection fraction of 23%. One case did have calf pseudohypertrophy. Musculoskeletal symptoms later appeared one to six years after the initial dilated cardiomyopathy presentation. Heart transplantation was the most common management strategy (4/6, 67%). A left ventricular assist device was used in one case as a bridge to heart transplant. Dilated cardiomyopathy can be the initial presentation of Becker muscular dystrophy in the third to fourth decades of life in adult patients, and musculoskeletal symptoms can be subclinical.
Psychological distress and social support among conflict refugees in urban, semi-rural and rural settlements in Uganda: burden and associations
Authors: Seruwagi Gloria , Nakidde Catherine , Lugada Eric , Ssematiko Maria , Ddamulira Dunstan P. , Masaba Andrew , Luswata Brian , Ochen Eric A. , Okot Betty , Muhangi Denis , Lawoko Stephen 
Published: May 2022

Abstract
Background
Recent research shows that psychological distress is on the rise globally as a result of the COVID-19 pandemic and restrictions imposed on populations to manage it. We studied the association between psychological distress and social support among conflict refugees in urban, semi-rural and rural settlements in Uganda during the COVID-19 pandemic.

Methods
Cross-sectional survey data on psychological distress, social support, demographics, socio-economic and behavioral variables was gathered from 1014 adult refugees randomly sampled from urban, semi-rural and rural refugee settlements in Uganda, using two-staged cluster sampling. Data was analyzed in SPSS-version 22, and statistical significance was assumed at p < 0.05.

Results
Refugees resident in rural/semi-rural settlements exhibited higher levels of psychological distress [F(2, 1011) = 47.91; p < 0.001], higher availability of social interaction [F(2, 1011) = 82.24; p < 0.001], lower adequacy of social interaction [F(2, 1011) = 54.11; p < 0.001], higher availability of social attachment [F(2, 1011) = 47.95; p < 0.001], and lower adequacy of social attachment [F(2, 1011) = 50.54; p < 0.001] than peers in urban settlements. Adequacy of social interaction significantly explained variations in psychological distress levels overall and consistently across settlements, after controlling for plausible confounders. Additionally, adequacy of social attachment significantly explained variations in psychological distress levels among refugees in rural settlements, after controlling for plausible confounders.

Conclusion
There is a settlement-inequality (i.e. rural vs. urban) in psychological distress and social support among conflict refugees in Uganda. To address psychological distress, Mental Health and Psychosocial Support Services (MHPSS) should focus on strategies which strengthen the existing social networks among refugees. Variations in social support are a key predictor of distress which should guide tailored need-adapted interventions instead of duplicating similar and generic interventions across diverse refugee settlements.
GABPA-activated TGFBR2 transcription inhibits aggressiveness but is epigenetically erased by oncometabolites in renal cell carcinoma
Authors: Fang Zhiqing , Zhang Ning , Yuan Xiaotian , Xing Xiangling , Li Xiaofeng , Qin Xin , Liu Zhengfang , Neo Shiyong , Liu Cheng , Kong Feng , Björkholm Magnus , Fan Yidong , Xu Dawei 
Published: May 2022

Abstract
Background
The ETS transcription factor GABPA has long been thought of as an oncogenic factor and recently suggested as a target for cancer therapy due to its critical effect on telomerase activation, but the role of GABPA in clear cell renal cell carcinoma (ccRCC) is unclear. In addition, ccRCC is characterized by metabolic reprograming with aberrant accumulation of L-2-hydroxyglurate (L-2HG), an oncometabolite that has been shown to promote ccRCC development and progression by inducing DNA methylation, however, its downstream effectors remain poorly defined.

Methods
siRNAs and expression vectors were used to manipulate the expression of GABPA and other factors and to determine cellular/molecular and phenotypic alterations. RNA sequencing and ChIP assays were performed to identify GABPA target genes. A human ccRCC xenograft model in mice was used to evaluate the effect of GABPA overexpression on in vivo tumorigenesis and metastasis. ccRCC cells were incubated with L-2-HG to analyze GABPA expression and methylation. We carried out immunohistochemistry on patient specimens and TCGA dataset analyses to assess the effect of GABPA on ccRCC survival.

Results
GABPA depletion, although inhibiting telomerase expression, robustly enhanced proliferation, invasion and stemness of ccRCC cells, whereas GABPA overexpression exhibited opposite effects, strongly inhibiting in vivo metastasis and carcinogenesis. TGFBR2 was identified as the GABPA target gene through which GABPA governed the TGFβ signaling to dictate ccRCC phenotypes. GABPA and TGFBR2 phenocopies each other in ccRCC cells. Higher GABPA or TGFBR2 expression predicted longer survival in patients with ccRCC. Incubation of ccRCC cells with L-2-HG mimics GABPA-knockdown-mediated phenotypic alterations. L-2-HG silenced the expression of GABPA in ccRCC cells by increasing its methylation.

Conclusions
GABPA acts as a tumor suppressor by stimulating TGFBR2 expression and TGFβ signaling, while L-2-HG epigenetically inhibits GABPA expression, disrupting the GABPA-TGFβ loop to drive ccRCC aggressiveness. These results exemplify how oncometabolites erase tumor suppressive function for cancer development/progression. Restoring GABPA expression using DNA methylation inhibitors or other approaches, rather than targeting it, may be a novel strategy for ccRCC therapy.