bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virologic response of treatment experienced HIV-infected Ugandan children and adolescents on NNRTI based first-line regimen, previously monitored without viral load
Authors: Kibalama Ssemambo Phionah , Nalubega-Mboowa Mary Gorrethy , Owora Arthur , Serunjogi Robert , Kironde Susan , Nakabuye Sarah , Ssozi Francis , Nannyonga Maria , Musoke Philippa , Barlow-Mosha Linda 
Published: March 2021

Abstract
Background
Many HIV-infected African children gained access to antiretroviral treatment (ART) through expansion of PEPFAR programs since 2004 and introduction of “Test and Treat” WHO guidelines in 2015. As ART access increases and children transition from adolescence to adulthood, treatment failure is inevitable. Viral load (VL) monitoring in Uganda was introduced in 2016 replacing clinical monitoring. However, there’s limited data on the comparative effectiveness of these two strategies among HIV-infected children in resource-limited settings (RLS).

Methods
HIV-infected Ugandan children aged 1–12 years from HIV-care programs with > 1 year of first-line ART using only immunologic and clinical criteria to monitor response to treatment were screened in 2010. Eligible children were stratified by VL ≤ 400 and > 400 copies/ml randomized to clinical and immunological (control) versus clinical, immunological and VL monitoring to determine treatment failure with follow-up at 12, 24, 36, and 48 weeks. Plasma VL was analyzed retrospectively for controls. Mixed-effects logistic regression models were used to compare the prevalence of viral suppression between study arms and identify factors associated with viral suppression.

Results
At baseline all children (n = 142) were on NNRTI based ART (75% Nevirapine, 25% efavirenz). One third of ART-experienced children had detectable VL at baseline despite high CD4%. Median age was 6 years (interquartile range [IQR]: 5–9) and 43% were female. Overall, the odds of viral suppression were not different between study arms: (arm by week interaction, p = 0.63), adjusted odds ratio [aOR]: 1.07; 95%CI: 0.53, 2.17, p = 0.57) and did not change over time (aOR: 0 vs 24 week: 1.15; 95% CI: 0.91, 1.46, p = 0.24 and 0 vs 48 weeks: 1.26; 95%CI: 0.92, 1.74, p = 0.15). Longer duration of a child’s ART exposure was associated with lower odds of viral suppression (aOR: 0.61; 95% CI: 0.42, 0.87, p < .01). Only 13% (9/71) of children with virologic failure were switched to second-line ART, in spite of access to real-time VL.

Conclusion
With increasing ART exposure, viral load monitoring is critical for early detection of treatment failure in RLS. Clinicians need to make timely informed decisions to switch failing children to second-line ART.

Trial registration
ClinicalTrials.gov NCT04489953, 28 Jul 2020. Retrospectively registered. (https://register.clinicaltrials.gov).
Interactive association of maternal education and peer relationship with oppositional defiant disorder: an observational study
Authors: Liu Ming-Chia , Chang Jung Chen , Lee Chau-Shoun 
Published: March 2021

Abstract
Background
The objectives of this research were to gain insights on the interactive effects, by measuring familial and peer-related risk factors in youths with oppositional defiant disorder (ODD).

Methods
Participants were college students recruited nationwide, with age between 18 and 25. Through the consensus of expert meetings, a set of questionnaires were used to evaluate the familial status, participant’s peer group conditions, high-risk environment of illicit substance use, and oppositional symptoms. The logistic regression was performed to see the independent and interactive risk factors for ODD.

Results
A total of 981 subjects were enrolled. Six variables significantly associated with ODD at the multivariate logistic regression, including male, night division, poor academic performance, high risk environment, peer with illicit substance use and high maternal education level. High maternal education exerted independent protective effect on the development of ODD (adjusted odds ratio, aOR = 0.65, 95% CI = 0.44–0.99). Peer with illicit substance use was more likely to associate with ODD in the low maternal education group. The 2-way interactive effect of maternal education and peer with substance use on the development of ODD was OR = 4.96 (2.96, 8.31).

Conclusion
The present study highlights the influence of maternal education level to ODD and its interaction with peer of illicit substance use. Our findings imply that the familial attachment and peer interaction are essential stages for the development of human behavior.

Trial registration
The research protocol was reviewed and approved by the ethical review committee of National Taiwan University Hospital (number 201505057RINC) and registered at clinical trial systems at National Taiwan University. In addition, subjects’ information was anonymous and de-identified prior to any analysis.
Improving cause of death certification in the Philippines: implementation of an electronic verbal autopsy decision support tool (SmartVA auto-analyse) to aid physician diagnoses of out-of-facility deaths
Authors: Joshi Rohina , Hazard R. H. , Mahesh Pasyodun Koralage Buddhika , Mikkelsen L. , Avelino F. , Sarmiento Carmina , Segarra A. , Timbang T. , Sinson F. , Diango Patrick , Riley I. , Chowdhury H. , Asuncion Irma L. , Khanom G. , Lopez Alan D. 
Published: March 2021

Abstract
Background
The majority of deaths in the Philippines occur out-of-facility and require a medical certificate of cause of death by Municipal Health Officers (MHOs) for burial. MHOs lack a standardised certification process for out-of-facility deaths and when no medical records are available, certify a high proportion of ill-defined causes of death. We aimed to develop and introduce SmartVA Auto-Analyse, a verbal autopsy (VA) based electronic decision support tool in order to assist the MHOs in certifying out-of-facility deaths.

Method
We conducted a stakeholder consultation, process mapping and a pre-test to assess feasibility and acceptability of SmartVA Auto-Analyse. MHOs were first asked to conduct an open-ended interview from the family members of the deceased, and if they were not able to arrive at a diagnosis, continue the interview using the standardised SmartVA questionnaire. Auto-Analyse then presented the MHO with the three most likely causes of death. For the pilot, the intervention was scaled-up to 91 municipalities. We performed a mixed-methods evaluation using the cause of death data and group discussions with the MHOs.

Results
Of the 5649 deaths registered, Auto-Analyse was used to certify 4586 (81%). For the remaining 19%, doctors believed they could assign a cause of death based on the availability of medical records and the VA open narrative. When used, physicians used the Auto-Analyse diagnosis in 85% of cases to certify the cause of death. Only 13% of the deaths under the intervention had an undetermined cause of death. Group discussions identified two themes: Auto-Analyse standardized the certification of home deaths and assisted the MHOs to improve the quality of death certification.

Conclusion
Standardized VA combined with physician diagnosis using the SmartVA Auto-Analyse support tool was readily used by MHOs in the Philippines and can improve the quality of death certification of home deaths.
Double-trajectory lumbar screw placement guided by a set of 3D-printed surgical guide templates: a cadaver study
Authors: Zhao Yonghui , Liang Jinlong , Luo Haotian , Xu Yongqing , Lu Sheng 
Published: March 2021

AbstractBackgroundTo improve the strength of posterior spine fixation in patients with osteoporosis, some scholars have proposed a method of simultaneously inserting traditional pedicle screws and cortical bone trajectory screws into the pedicle. However, due to the difficulty of the operation and few clinical applications, the safety and accuracy of this method are still unclear. The purpose of this study was to investigate the safety and accuracy of double-trajectory lumbar screw placement guided by surgical guide templates.MethodsSix wet lumbar specimens were selected for computed tomography (CT) scanning, a three-dimensional (3D) model of the lumbar spine was established using computer software, and surgical guide templates for double-trajectory [traditional pedicle trajectory (TPT) and cortical bone trajectory (CBT)] lumbar screw placement at various segments of the lumbar spine were designed and printed using a 3D printer. Screw placement was guided only by the surgical guide template, with no fluoroscopy. Postoperative CT examination was performed to determine whether the screw penetrated the screw path and the location and depth of penetration of the cortex. The preoperative and postoperative sagittal and axial angles of CBT screws or TPT screws were also measured and compared.ResultsFour screws were placed in each vertebral body of six lumbar specimens for a total of 120 screws. Screw grades: 99 screws as grade 0, 15 as grade 1, six as grade 2, and zero as grade 3. Thus, grade 0 accounted for 82.5% of the screws. No significant differences in the preoperative and postoperative angles of the screws were found (P > 0.05).Conclusions3D-printed surgical guide templates for double-trajectory screw placement can reduce the difficulty of surgery and the use of intraoperative fluoroscopy. Using such templates is a safe, feasible, and accurate screw placement method.
The technique for less infectious and earlier healing of stoma closure wound: negative pressure wound therapy with instillation and dwelling followed by primary closure
Authors: Yane Yoshinori , Hida Jin-ichi , Makutani Yusuke , Ushijima Hokuto , Yoshioka Yasumasa , Iwamoto Masayoshi , Wada Toshiaki , Daito Koji , Tokoro Tadao , Ueda Kazuki , Kawamura Junichiro 
Published: March 2021

Abstract
Background
Temporary stomas have been widely used to avoid the risk of complications such as anastomotic leakage after colorectal resection. Stoma closure is relatively easy; however, postoperative surgical site infection (SSI) may be a problem. Various methods have been used to reduce the incidence of SSI. We aimed to evaluate a new technique for stoma wound closure.

Methods
We enrolled patients who underwent stoma closure at our hospital between September 2019 and May 2020. We selected patients who lived far from our hospital and had difficulty visiting the hospital regularly and who agreed to undergo this surgical technique. We used negative pressure wound therapy with instillation and dwelling (NPWTi-d) and delayed primary closure for these patients.

Results
Four patients underwent NPWTi-d and delayed primary closure without the occurrence of SSI. The median postoperative hospital stay was 9 days (range: 7–14 days), and the median number of days to confirmation of epithelialization was 11.5 days (range: 10–16 days).

Conclusion
The combined use of NPWTi-d and delayed primary closure for the stoma wound was very effective. This method may be a valuable new technique for wound management after stoma closure.
Tanshinone IIA combined with CsA inhibit myocardial cell apoptosis induced by renal ischemia-reperfusion injury in obese rats
Authors: Tai He , Jiang Xiao-lin , Lan Zhi-ming , Li Yue , Kong Liang , Yao Si-cheng , Song Nan , Lv Mei-jun , Wu Jin , Yang Ping , Xiao Xuan-si , Yang Guan-lin , Kuang Jin-song , Jia Lian-qun 
Published: March 2021

Abstract
Background
Acute myocardial injury (AMI), which is induced by renal ischemia-reperfusion (IR), is a significant cause of acute kidney injury (AKI)-related associated death. Obesity increases the severity and frequency of AMI and AKI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) pretreatment was used to alleviate myocardial cell apoptosis induced by renal IR, and to determine whether TIIA combined with CsA would attenuate myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

Methods
Male rates were fed a high fat diet for 8 weeks to generate obesity. AKI was induced by 30 min of kidney ischemia followed 24 h of reperfusion. Obese rats were given TIIA (10 mg/kg·d) for 2 weeks and CsA (5 mg/kg) 30 min before renal IR. After 24 h of reperfusion, the rats were anaesthetized, the blood were fetched from the abdominal aorta and kidney were fetched from abdominal cavity, then related indicators were examined.

Results
TIIA combined with CsA can alleviate the pathohistological injury and apoptosis induced by renal IR in myocardial cells. TIIA combined with CsA improved cardiac function after renal ischemia (30 min)-reperfusion (24 h) in obese rats. At the same time, TIIA combined with CsA improved mitochondrial function. Abnormal function of mitochondria was supported by decreases in respiration controlling rate (RCR), intracellular adenosine triphosphate (ATP), oxygen consumption rate, and mitochondrial membrane potential (MMP), and increases in mitochondrial reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore (mPTP), mitochondrial DNA damage, and mitochondrial respiratory chain complex enzymes. The injury of mitochondrial dynamic function was assessed by decrease in dynamin-related protein 1 (Drp1), and increases in mitofusin1/2 (Mfn1/2), and mitochondrial biogenesis injury was assessed by decreases in PPARγ coactivator-1-α (PGC-1), nucleo respiratory factor1 (Nrf1), and transcription factor A of mitochondrial (TFam).

Conclusion
We used isolated mitochondria from rat myocardial tissues to demonstrate that myocardial mitochondrial dysfunction occurred along with renal IR to induce myocardial cell apoptosis; obesity aggravated apoptosis. TIIA combined with CsA attenuated myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.
Prioritising ‘already-scarce’ intensive care unit resources in the midst of COVID-19: a call for regional triage committees in South Africa
Authors: Naidoo Reshania , Naidoo Kantharuben 
Published: March 2021

Abstract
Background
The worsening COVID-19 pandemic in South Africa poses multiple challenges for clinical decision making in the context of already-scarce ICU resources. Data from national government and the last published national audit of ICU resources indicate gross shortages. While the Critical Care Society of Southern Africa (CCSSA) guidelines provide a comprehensive guideline for triage in the face of overwhelmed ICU resources, such decisions present massive ethical and moral dilemmas for triage teams. It is therefore important for the health system to provide clinicians and critical care facilities with as much support and resources as possible in the face of impending pandemic demand. Following a discussion of the ethical considerations and potential challenges in applying the CCSSA guidelines, the authors propose a framework for regional triage committees adapted to the South African context.

Discussion
Beyond the national CCSSA guidelines, the clinician has many additional ethical and clinical considerations. No single ethical approach to decision-making is sufficient, instead one which considers multiple contextual factors is necessary. Scores such as the Clinical Frailty Score and Sequential Organ Failure Assessment are of limited use in patients with COVID-19. Furthermore, the clinician is fully justified in withdrawing ICU care based on medical futility decisions and to reallocate this resource to a patient with a better prognosis. However, these decisions bear heavy emotional and moral burden compounded by the volume of clinical work and a fear of litigation.

Conclusion
We propose the formation of Provincial multi-disciplinary Critical Care Triage Committees to alleviate the emotional, moral and legal burden on individual ICU teams and co-ordinate inter-facility collaboration using an adapted framework. The committee would provide an impartial, broader and ethically-sound viewpoint which has time to consider broader contextual factors such as adjusting rationing criteria according to different levels of pandemic demand and the latest clinical evidence. Their functioning will be strengthened by direct feedback to national level and accountability to a national monitoring committee. The potential applications of these committees are far-reaching and have the potential to enable a more effective COVID-19 health systems response in South Africa.
Cardiorenal and other diabetes related outcomes with SGLT-2 inhibitors compared to GLP-1 receptor agonists in type 2 diabetes: nationwide observational study
Authors: Lugner Moa , Sattar Naveed , Miftaraj Mervete , Ekelund Jan , Franzén Stefan , Svensson Ann-Marie , Eliasson Björn 
Published: March 2021

AbstractBackgroundMajor prospective randomized clinical safety trials have demonstrated beneficial effects of treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose co-transporter-2 inhibitors (SGLT-2i) in people with type 2 diabetes and elevated cardiovascular risk, and recent clinical treatment guidelines therefore promote early use of these classes of pharmacological agents. In this Swedish nationwide observational study, we compared cardiorenal outcomes and safety of new treatment with GLP-1RA and SGLT-2i in people with type 2 diabetes.MethodsWe linked data from national Swedish databases to capture patient characteristics and outcomes and used propensity-score based matching to account for differences between the two groups. The treatments were compared using Cox regression models.ResultsWe identified 9648 participants starting GLP-1RA and 12,097 starting SGLT-2i with median follow-up times 1.7 and 1.1 years, respectively. The proportion of patients with a history of MACE were 15.8%, and 17.0% in patients treated with GLP-1RA and SGLT-2i, respectively. The mean age was 61 years with 7.6 years duration of diabetes. Mean HbA1c were 8.3% (67.6 mmol/mol) and 8.3% (67.2 mmol/mol), and mean BMI 33.3 and 32.5 kg/m2in patients treated with GLP-1RA or SGLT-2i, respectively. The cumulative mortality risk was non-significantly lower in the group treated with SGLT-2i, HR 0.78 (95% CI 0.61–1.01), as were incident heart failure outcomes, but the risks of cardiovascular or renal outcomes did not differ. The risks of stroke and peripheral artery disease were higher in the SGLT-2i group relative to GLP-1RA, with HR 1.44 (95% CI 0.99–2.08) and 1.68 (95% CI 1.04–2.72), respectively.ConclusionsThis observational study suggests that treatment with GLP-1RA and SGLT-2i result in very similar cardiorenal outcomes. In the short term, treatment with GLP-1RA seem to be associated with lower risks of stroke and peripheral artery disease, whereas SGLT-2i seem to be nominally associated with lower risk of heart failure and total mortality.
Silenced lncRNA DDX11-AS1 or up-regulated microRNA-34a-3p inhibits malignant phenotypes of hepatocellular carcinoma cells via suppression of TRAF5
Authors: Ding Gangqiang , Zeng Yanli , Yang Dongqiang , Zhang Can , Mao Chongshan , Xiao Erhui , Kang Yi , Shang Jia 
Published: March 2021

Abstract
Background
Studies have discussed long noncoding RNA DDX11-AS1 (DDX11-AS1)-mediated downstream mechanism in hepatocellular carcinoma (HCC). The goal of this study was to investigate the regulatory mechanism of DDX11-AS1-mediated microRNA-34a-3p (miR-34a-3p)/tumor necrosis factor receptor-associated factor 5 (TRAF5) axis on HCC cells.

Methods
DDX11-AS1, miR-34a-3p and TRAF5 expression levels in HCC were detected. The correlation of DDX11-AS1, miR-34a-3p and TRAF5 in HCC patients was analyzed by Pearson test. HCC cells were transfected with corresponding plasmid/oligonucleotide, and cell proliferation, migration, invasion, apoptosis and tumor formation ability were detected. Bioinformatics software, dual luciferase report experiment and RNA-pull down experiment analysis were applied to verify the targeting relationship between DDX11-AS1, miR-34a-3p and TRAF5.

Results
Elevated DDX11-AS1 and TRAF5 and reduced miR-34a-3p exhibited in HCC. Silenced DDX11-AS1 or up-regulated miR-34a-3p inhibited the proliferation, migration, invasion, promoted apoptosis of HCC cells and repressed the tumor growth in nude mice. In addition, DDX11-AS1 bound to miR-34a-3p to target TRAF5. Silencing TRAF5 or elevating miR-34a-3p expression mitigated up-regulated DDX11-AS1-mediated promotion of tumor growth.

Conclusion
Silenced DDX11-AS1 or up-regulated miR-34a-3p inhibits HCC cell growth via elevation of TRAF5, which could be of great benefit to find early diagnostic markers for HCC patients.
A rodent model of human dose-equivalent progestin-only implantable contraception
Authors: Allaway Heather C. M. , Pierson Roger A. , Invik Jesse , Bloomfield Susan A. 
Published: March 2021

AbstractBackgroundLong-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. The overall objective was to develop and validate a rodent model of implanted etonogestrel (ENG) LARC, at body size equivalent doses to the average dose received by women during each of the first 3 years of ENG subdermal rod LARC use.MethodsIntact, virgin, female Sprague-Dawley rats (16-wk-old) were randomized to 1 of 4 groups (n = 8/group) of ENG LARC (high-0.30μg/d, medium-0.17μg/d, low-0.09μg/d, placebo-0.00μg/d) via a slow-release pellet implanted subcutaneously. Animals were monitored for 21 days before and 29 days following pellet implantation using vaginal smears, ultrasound biomicroscopy (UBM), saphenous blood draws, food consumption, and body weights. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA.ResultsPrior to pellet implantation there was no difference in time spent in estrus cycle phases among the treatment groups (p > 0.30). Following pellet implantation there was a dose-dependent impact on the time spent in diestrus and estrus (p < 0.05), with the high dose group spending more days in diestrus and fewer days in estrus. Prior to pellet insertion there was not an association between treatment group and estrus cycle classification (p = 0.57) but following pellet implantation there was a dose-dependent association with cycle classification (p < 0.02). Measurements from the UBM (ovarian volume, follicle count, corpora lutea count) indicate an alteration of ovarian function following pellet implantation.ConclusionAssessment of estrus cyclicity indicated a dose-response relationship in the shift to a larger number of acyclic rats and longer in duration spent in the diestrus phase. Therefore, each dose in this model mimics some of the changes observed in the ovaries of women using ENG LARC and provides an opportunity for investigating the impacts on non-reproductive tissues in the future.