bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV
Authors: Rolle Charlotte-Paige , Nguyen Vu , Hinestrosa Federico , DeJesus Edwin 
Published: May 2021

AbstractBackgroundDolutegravir (DTG) monotherapy results in virologic failure and the development of DTG resistance. Here, we evaluated virologic outcomes of patients switched to DTG functional mono- or dual therapy with a non-cytosine nucleoside analog (NA).MethodsThis retrospective, single center study included treatment-experienced patients switched to regimens containing ≥ 2 antiretrovirals between 8/13/13–11/22/14 who were later found to be on DTG functional mono- or dual therapy with a non-cytosine NA based on historical genotypes. Eligible patients were either suppressed or viremic at baseline and had ≥ 2 HIV-1 RNA measurements at least 4 weeks apart following switch. Demographics, laboratory values and clinical parameters were extracted from the charts of all eligible patients during study treatment until 12/31/2018 and were summarized using descriptive statistics. The primary endpoint was the proportion of patients with HIV-1 RNA < 50 copies/mL following switch.ResultsOf 70 patients switched to DTG functional mono- or dual therapy, 39 were eligible; 19 (49%) were on DTG functional monotherapy and 20 (51%) were on DTG functional dual therapy with a non-cytosine NA. Historical genotypes indicated that all had an M184V/I, and 23 (59%) had an M184V/I and ≥ 1 additional NA mutation. The median duration of follow-up on study treatment was 50 weeks (range 12–244). Following switch, 32/39 (82%) patients achieved or maintained an HIV-1 RNA < 50 copies/mL and 7 (18%) had persistent HIV-1 RNA ≥ 50 copies/mL. Five viremic patients were found to be on functional dual therapy with DTG plus a non-cytosine NA and 2 were on DTG functional monotherapy. Five of these patients had post-switch genotypes ordered as a part of routine clinical care and there was no evidence of treatment-emergent resistance. Five were switched to a different DTG-containing regimen and achieved HIV-1 RNA < 50 copies/mL, 1 was switched to a non-DTG containing regimen and achieved HIV-1 RNA < 50 copies/mL and 1 was lost-to-follow up at week 36.ConclusionsIn this real-world cohort, the majority of whom had virus with the M184V/I and ≥ 1 additional NA mutation, switching to DTG functional mono-or dual therapy with a non-cytosine NA resulted in persistent HIV-1 RNA ≥ 50 copies/mL in 18%. None with post-switch genotypes developed treatment-emergent resistance.
Clinicopathological features of tumor mutation burden, Epstein-Barr virus infection, microsatellite instability and PD-L1 status in Chinese patients with gastric cancer
Authors: Zhang Li , Wang Yinkui , Li Zhongwu , Lin Dongmei , Liu Yiqiang , Zhou Linxin , Wang Dongliang , Wu Aiwen , Li Ziyu 
Published: May 2021

Abstract
Objectives
Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes have unique molecular features that may have different therapeutic methods. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in GC patients.

Methods
The data of 2504 GC patients, who underwent curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed. We analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS).

Results
Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p = 0.000, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a intestinal group (p = 0.012), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%).

Conclusions
Using IHC and NGS, MSI status, protein expression, tumor mutation burden (TMB) and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.
Stakeholder selected strategies for obesity prevention in childcare: results from a small-scale cluster randomized hybrid type III trial
Authors: Swindle Taren , McBride Nicole M. , Selig James P. , Johnson Susan L. , Whiteside-Mansell Leanne , Martin Janna , Staley Audra , Curran Geoffrey M. 
Published: May 2021

Abstract
Background
Together, We Inspire Smart Eating (WISE) is an intervention for the early care and education setting to support children’s exposure to and intake of fruits and vegetables. WISE emphasizes 4 evidence-based practices (EBPs): (1) use of a mascot; (2) educators’ role modeling; (3) positive feeding practices; and (4) hands-on exposures. The current study reports on a small-scale implementation trial aimed at improving the use of WISE EBPs by teachers.

Methods
A Hybrid Type III Cluster Randomized Design compared a Basic and Enhanced implementation strategy. The Basic Strategy included training and reminders only; the Enhanced strategy was a multi-faceted package of stakeholder-selected strategies including a leadership commitment, an implementation blueprint, a local champion, an environmental reminder of the EBPs, facilitation, and tailored educational resources and incentives. All study sites were Head Starts. Sites were randomized using a balancing technique that considered site characteristics; 4 sites (20 classrooms, 39 educators, 305 children) received Enhanced support; 5 sites (18 classrooms, 36 educators, 316 children) received Basic support. RE-AIM guided the evaluation, and implementation fidelity was the primary outcome. Strategies were assessed using examination of data distributions and unadjusted comparisons (t tests) as well as general linear and mixed effects models controlling for covariates.

Results
For the primary outcome of fidelity, the Enhanced group had significantly higher means for 3 of 4 EBPs. Multivariate models explained a significant portion of variance for both mascot use and hands-on exposure with a significant positive effect observed for treatment condition. The Enhanced group also had higher rates of Appropriateness and Organizational Readiness for Implementing Change (as indicators of implementation and adoption, respectively). There was no significant difference between groups for indicators of Reach, Effectiveness or Maintenance. Formative interviews indicated key targets for iteration and potential mechanisms. Key events were catalogued to provide context for interpretation (e.g., 61% of classrooms with turnover).

Conclusions
Findings were mixed but suggested promise for the Enhanced strategy, especially considering key events of the study. Implementation fidelity improvements occurred mainly in the last 3 months of the school year; additional time may be needed to translate to improvements in child outcomes.

Trial registration
NCT03075085 Registered 20 February 2017.
RETRACTED ARTICLE: Effect of a single intra-articular high molecular weight hyaluronan in a naturally occurring canine osteoarthritis model: a randomized controlled trial
Authors: Alves J. C. , dos Santos Ana Margarida Moniz Pereira , Jorge Patrícia , Lavrador Catarina Falcão Trigoso Vieira Bran , Carreira L. Miguel 
Published: May 2021

AbstractBackgroundOsteoarthritis (OA) is a complex joint disease and chronic pain source, affecting a patient’s quality of life and posing a financial burden. As the dog is considered a nearly ideal species for translation research of human OA and the most used model for research, exploring spontaneous dog OA under the One Health/One Medicine concept can improve both humans and dogs’ health and well-being.MethodsIn a clinical treatment experiment, forty (N=40) joints were selected and randomly assigned to a control group (CG), which received 0.9% NaCl or a treatment (HG), which received Hylan G-F 20. Evaluations were performed on treatment day (T0), 8, 15, 30, 90, and 180 days post-treatment. They consisted of four different Clinical Metrology Instruments (CMI), evaluation of weight distribution, joint range of motion, thigh girth, radiographic and digital thermography imaging, synovial fluid interleukin-1 (IL-1), and C-reactive protein concentrations. Results were compared with repeated measures ANOVA, with a Huynh-Feldt correction, Paired samplesT-test, or Wilcoxon signed-ranks test, withp<0.05.ResultsPatients had a mean age of 6.5±2.4 years and a bodyweight of 26.6±5.2kg, and joints graded as mild (n=28, 70%), moderate (n=6, 15%), and severe OA (n=6, 15%). No differences were found between groups at T0. Symmetry index and deviation showed significant improvements in HG from 30 days (p<0.01) up to 180 days (p=0.01). Several CMI scores, particularly pain scores, improved from 90 to 180 days. Radiographic signs progressed in both groups. In both groups, increasing body weight and age corresponded to worse clinical presentation. IA hyaluronan administration produced increased lameness in six cases, which resolved spontaneously.ConclusionsThis study characterizes the response to treatment with Hylan G-F 20, which can produce significant functional and pain level improvements in patients with OA, even those with factors related to worse response to treatment.
Application and effects of an early childhood education machine on analgesia and sedation in children after cardiothoracic surgery
Authors: Chen Li-Li , Lei Yu-Qing , Liu Jian-Feng , Cao Hua , Yu Xian-Rong , Chen Qiang 
Published: May 2021

Abstract
Objective
To study the effect of an early childhood education machine on sedation and analgesia in children after cardiothoracic surgery.

Methods
A prospective randomized controlled study was conducted in a provincial hospital in China. Fifty-two patients (aged from 1 to 5 years) underwent cardiothoracic surgery (including: ventricular septal defect, patent ductus arteriosus, atrial septal defect, pulmonary stenosis, pulmonary sequestration and congenital cystic adenomatoid lung malformation) were divided into the study group (n = 26) and the control group (n = 26). The patients in the study group underwent intervention with an early childhood education machine (uniform type) in addition to routine standard treatment and nursing, while the patients in the control group only received routine standard treatment and nursing. Richmond agitation sedation score (RASS) and face, legs, activity, cry, consolability (FLACC) score of all of the patients were evaluated, and the negative emotions (self-rating anxiety scale (SAS) score and self-rating depression scale (SDS) score) of the parents of the two groups were compared.

Results
There was no significant difference in the general clinical data between the two groups. The RASS and FLACC scores in the study group were significantly lower than those in the control group, and the SAS and SDS scores of the parents in the study group were significantly lower than those in the control group.

Conclusion
The application of an early childhood education machine for children after cardiothoracic surgery can effectively reduce postoperative agitation, improve sedation and analgesia of the patients, and ease the pessimistic mood of the patients’ parents.
Determination of the protective effects of Hua‐Zhuo‐Jie‐Du in chronic atrophic gastritis by regulating intestinal microbiota and metabolites: combination of liquid chromatograph mass spectrometer metabolic profiling and 16S rRNA gene sequencing
Authors: Zhou Pingping , Hao Xinyu , Liu Yu , Yang Zeqi , Xu Miaochan , Liu Shaowei , Zhang Shixiong , Yang Tianxiao , Wang Xiaomei , Wang Yangang 
Published: May 2021

AbstractBackgroundHua-Zhuo-Jie-Du (HZJD), a Chinese herbal prescription consisting of 11 herbs, is commonly used in China to treat chronic atrophic gastritis (CAG). We aimed to determine the effect of HZJD on the microbiome-associated metabolic changes in CAG rats.MethodsThe CAG rat models were induced by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) combined with irregular fasting and 2% sodium salicylate, which was intragastrically administrated in fasted animals for 24 weeks. The CAG rats in the Chinese medicine (CM) group were administered a daily dose of 14.81 g/kg/day HZJD, and the vitacoenzyme (V) group were administered a daily dose of 0.08 g/kg/day vitacoenzyme. All animals were treated for 10 consecutive weeks, consecutively. Hematoxylin and eosin (H&E) staining was used to assess the histopathological changes in the gastric tissues. An integrated approach based on liquid chromatograph mass spectrometer (LC-MS) metabolic profiling combined with 16S rRNA gene sequencing was carried out to assess the effects of HZJD on CAG rats. Spearman analysis was used to calculate the correlation coefficient between the different intestinal microbiota and the metabolites.ResultsThe H&E results indicated that HZJD could improve the pathological condition of CAG rats. The LC–MS results indicated that HZJD could significantly improve 21 gastric mucosal tissue perturbed metabolites in CAG rats; the affected metabolites were found to be involved in multiple metabolic pathways, such as the central carbon metabolism in cancer. The results of 16S rRNA gene sequencing indicated that HZJD could regulate the diversity, microbial composition, and abundance of the intestinal microbiota of CAG rats. Following HZJD treatment, the relative abundance ofTuricibacterwas increased, and the relative abundance ofDesulfococcusandEscherichiawere decreased in the CM group when compared with the M group. Spearman analysis revealed that perturbed intestinal microbes had a strong correlation with differential metabolites,Escherichiaexhibited a negative correlation with l-Leucine,Turicibacterwas negatively correlated with urea, andDesulfococcusexhibited a positive correlation with trimethylamine, and a negative correlation with choline.ConclusionsHZJD could protect CAG by regulating intestinal microbiota and its metabolites.
Drivers of carbon flux in drip irrigation maize fields in northwest China
Authors: Guo Hui , Li Sien , Wong Fuk-Ling , Qin Shujing , Wang Yahui , Yang Danni , Lam Hon-Ming 
Published: May 2021

Abstract
Background
Under the escalating threat to sustainable development from the global increase in carbon dioxide concentrations, the variations in carbon flux in the farmland ecosystem and their influencing factors have attracted global attention. Over the past few decades, with the development of eddy covariance technology, the carbon fluxes of farmlands have been determined in many countries. However, studies are very limited for drip irrigation maize the arid regions in northwestern China, which covers a large area where a mixed mode of agriculture and grazing is practiced.

Results
To study the effects of drip irrigation on the net ecosystem productivity (NEE), ecosystem respiration (ER), gross primary production (GPP) and net biome productivity (NBP) in the arid regions of northwestern China, we measured the carbon flux annually from 2014 to 2018 using an eddy covariance system. Our results showed that the maize field carbon flux exhibited single-peak seasonal patterns during the growing seasons. During 2014–2018, the NEE, ER and GPP of the drip-irrigated maize field ranged between − 407 ~ − 729 g C m−2, 485.46 ~ 975.46 g C m−2, and 1068.23 ~ 1705.30 g C m−2. In four of the 5 study years, the ER released back to the atmosphere was just over half of the carbon fixed by photosynthesis. The mean daily NEE, ER and GPP were significantly correlated with the net radiation (Rn), air temperature (Ta), leaf area index (LAI) and soil moisture (SWC). The results of path analysis showed that leaf area index is the main driving force of seasonal variation of carbon flux. When harvested removals were considered, the annual NBP was − 234 g C m−2, and the drip-irrigated maize field was a carbon source.

Conclusions
This study shows the variation and influencing factors of NEE, ER and GPP in the growth period of spring maize under film drip irrigation in arid areas of northwest China. The ecosystem was a carbon sink before maize harvest, but it was converted into a carbon source considering the carbon emissions after harvest. The variation of carbon flux was influenced by both environmental and vegetation factors, and its leaf area index was the main driver that affects the seasonal variation of carbon flux.
Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy
Authors: Gong Ying , Klein Wolterink Roel G. J. , Wang Jianxiang , Bos Gerard M. J. , Germeraad Wilfred T. V. 
Published: May 2021

AbstractDue to their efficient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune cells that can be genetically modified to obtain capable effector cells for adoptive cellular treatment of cancer patients. However, biological and technical hurdles related to gene delivery into NK cells have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 gene editing and enhanced viral transduction and electroporation, have endowed comprehensive generation and characterization of genetically modified NK cells. These promising developments assist scientists and physicians to design better applications of NK cells in clinical therapy. Notably, redirecting NK cells using CARs holds important promise for cancer immunotherapy. Various preclinical and a limited number of clinical studies using CAR-NK cells show promising results: efficient elimination of target cells without side effects, such as cytokine release syndrome and neurotoxicity which are seen in CAR-T therapies. In this review, we focus on the details of CAR-NK technology, including the design of efficient and safe CAR constructs and associated NK cell engineering techniques: the vehicles to deliver the CAR-containing transgene, detection methods for CARs, as well as NK cell sources and NK cell expansion. We summarize the current CAR-NK cell literature and include valuable lessons learned from the CAR-T cell field. This review also provides an outlook on how these approaches may transform current clinical products and protocols for cancer treatment.
Lower limb biomechanics in individuals with chronic ankle instability during gait: a case‐control study
Authors: Moisan Gabriel , Mainville Camille , Descarreaux Martin , Cantin Vincent 
Published: May 2021

AbstractBackgroundIndividuals with chronic ankle instability (CAI) exhibit many biomechanical changes to lower limbs during walking. However, only a few studies have investigated the differences in lower limb biomechanics of individuals with CAI compared to healthy controls using a comprehensive approach including kinematic, kinetic and electromyography (EMG) measures. Consequently, the theoretical framework explaining the biomechanical adaptations in individuals with CAI is mostly based on the results of studies including heterogenous methods and participants' specificities (e.g., level of disability). More studies using a comprehensive approach are needed to better understand the biomechanical adaptations associated with CAI. The objective of this case‐control study was to identify the kinematic, kinetic and EMG differences between individuals with CAI and healthy controls during walking.MethodsTwenty‐eight individuals with CAI and 26 healthy controls were recruited to walk at a self‐selected speed during which lower limb kinematics, kinetics and EMG were analysed. Ankle and knee angles and moments as well as gluteus medius, vastus lateralis, gastrocnemius lateralis, peroneus longus and tibialis anterior muscles activity were compared between the CAI and control groups using one‐dimensional statistical parametric mapping.ResultsThe CAI group exhibited greater ankle inversion angles from 14 to 48% of the stance phase (%SP) (p = 0.008), ankle eversion moments from 40 to 78%SP (p < 0.001), knee abduction moments from 3 to 6%SP and peroneus longus muscle activity from 0 to 15%SP (p = 0.003) and 60 to 76%SP (p = 0.003) compared to the control group. No significant between‐group differences in ankle sagittal and transverse angles and moments, knee angles, knee sagittal and transverse moments as well as gluteus medius, vastus lateralis, gastrocnemius lateralis and tibialis anterior muscles activity were found.ConclusionsDuring the first half of the stance phase, individuals with CAI could be at more risk of sustaining recurrent LAS mostly due to greater ankle inversion angles. However, the greater ankle eversion moments and peroneus longus muscle activity during the second half of the stance phase were an efficient mechanism to correct this maladaptive gait pattern and allowed to attenuate the faulty ankle movements during the pre‐swing phase.
Activation of SphK1 by adipocytes mediates epithelial ovarian cancer cell proliferation
Authors: Dai Lan , Wang Chen , Song Keqi , Wang Wenjing , Di Wen 
Published: May 2021

Abstract
Background
Adipocytes, active facilitators of epithelial ovarian cancer (EOC) growth, have been implicated in the link between obesity and EOC. However, the current understanding of the mechanisms underlying adipocyte-induced EOC cell proliferation remains incomplete.

Results
We provide the first evidence showing that sphingosine kinase (SphK) 1 is critical for adipocyte-induced EOC cell proliferation. Adipocytes are capable of activating SphK1, which then leads to extracellular signal-regulated kinase (ERK) phosphorylation. Moreover, adipocyte-induced SphK1 activation is ERK dependent. Furthermore, sphingosine 1-phosphate receptor (S1PR) 1 and S1PR3, key components of the SphK1 signalling pathway, participate in adipocyte-mediated growth-promoting action in EOC cells.

Conclusions
Our study reveals a previously unrecognized role of SphK1 in adipocyte-induced growth-promoting action in EOC, suggesting a new target for EOC therapy.