bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single nucleotide variants in immune-response genes and the tumor microenvironment composition predict progression of mantle cell lymphoma
Authors: Assis-Mendonça Guilherme Rossi , Fattori André , Rocha Rafael Malagoli , Lourenço Gustavo Jacob , Delamain Márcia Torresan , Nonogaki Suely , de Lima Vladmir Cláudio Cordeiro , Colleoni Gisele Wally Braga , de Souza Cármino Antonio , Soares Fernando Augusto , Lima Carmen Silvia Passos , Vassallo José 
Published: March 2021

Abstract
Background
There is evidence to consider that the tumor microenvironment (TME) composition associates with antitumor immune response, and may predict the outcome of various non-Hodgkin lymphoma subtypes. However, in the case of mantle cell lymphoma (MCL), a rare and aggressive disease, there is lacking a detailed study of the TME components, as well as an integrative approach among them in patients’ samples. Also, from the genetic point of view, it is known that single nucleotide variants (SNVs) in immune-response genes are among important regulators of immunity. At present, it is uncertain whether SNVs in candidate immune-response genes and the TME composition are able to alter the prognosis in MCL.

Methods
We assessed a detailed TME composition in 88 MCL biopsies using immunohistochemistry, which was automatically analyzed by pixel counting (Aperio system). We also genotyped SNVs located in candidate immune-response genes (IL12A, IL2, IL10, TGFB1, TGFBR1, TGFBR2, IL17A, IL17F) in 95 MCL patients. We tested whether the SNVs could modulate the respective protein expression and TME composition in the tumor compartment. Finally, we proposed survival models in rituximab-treated patients, considering immunohistochemical and SNV models.

Results
High FOXP3/CD3 ratios (p = 0.001), high IL17A levels (p = 0.003) and low IL2 levels (p = 0.03) were individual immunohistochemical predictors of poorer survival. A principal component, comprising high quantities of macrophages and high Ki-67 index, also worsened outcome (p = 0.02). In the SNV model, the CC haplotype of IL10 (p < 0.01), the GG genotype of IL2 rs2069762 (p = 0.02) and the AA+AG genotypes of TGFBR2 rs3087465 (p < 0.01) were independent predictors of outcome. Finally, the GG genotype of TGFB1 rs6957 associated with lower tumor TGFβ levels (p = 0.03) and less CD163+ macrophages (p = 0.01), but did not modulate patients’ survival.

Conclusions
Our results indicate that the TME composition has relevant biological roles in MCL. In this setting, immunohistochemical detection of T-reg cells, IL17A and IL2, coupled with SNV genotyping in IL10, TGFBR2 and IL2, may represent novel prognostic factors in this disease, following future validations.
Surgical outcomes of transverse acetabular fractures and risk factors for poor outcomes
Authors: Jang Jae Hoon , Moon Nam Hoon , Rhee Seung Joon , Jung Seok Jin , Ahn Tae Young 
Published: March 2021

AbstractBackgroundTransverse acetabular fractures, although classified as elementary, have worse outcomes than other types of acetabular fractures. Prognostic factors for this fracture type are not clearly established. This study aimed to assess the surgical outcomes of transverse acetabular fractures and subtypes thereof and to investigate the prognostic factors.MethodsBetween 2014 and 2019, 39 patients (39 hips) had transverse fractures or subtypes thereof. We reviewed the surgical outcomes and evaluated patient factors, injury factors, and surgical factors in relation to osteoarthritis (OA) and conversion to total hip arthroplasty (THA). Additionally, we analyzed the cutoff values for postoperative residual gaps and steps.ResultsTwenty-three male patients and sixteen female with a mean age of 41.7 years (range, 18–78 years) were included. There were 29 satisfactory reductions (74.4%). Eleven hips (28.2%) developed OA, and five (12.8%) of them underwent THA. Dome impaction (odds ratio [OR], 41.173; 95% confidence interval [CI], 1.804–939.814;p = 0.020) and residual gaps (OR, 4.251; 95% CI, 1.248–14.479;p = 0.021) were correlated with poor outcomes. Residual gaps (≥3 mm) and residual steps (≥1 mm) were significantly associated with OA.ConclusionsRelatively poor reduction was found for transverse acetabular fractures and subtypes thereof. However, the rates of OA and conversion to THA were not high. Dome impaction and wide residual gaps were identified as risk factors for poor outcomes. The development of OA significantly increased if residual gap and step were more than 3 mm and 1 mm, respectively.
Evidence based processes to prevent readmissions: more is better, a ten-site observational study
Authors: Pugh Jacqueline , Penney Lauren S. , Noël Polly H. , Neller Sean , Mader Michael , Finley Erin P. , Lanham Holly J. , Leykum Luci 
Published: March 2021

Abstract
Background
30-day hospital readmissions are an indicator of quality of care; hospitals are financially penalized by Medicare for high rates. Numerous care transition processes reduce readmissions in clinical trials. The objective of this study was to examine the relationship between the number of evidence-based transitional care processes used and the risk standardized readmission rate (RSRR).

Methods
Design: Mixed method, multi-stepped observational study. Data collection occurred 2014–2018 with data analyses completed in 2021. Setting: Ten VA hospitals, chosen for 5-year trend of improving or worsening RSRR prior to study start plus documented efforts to reduce readmissions. Participants: During five-day site visits, three observers conducted semi-structured interviews (n = 314) with staff responsible for care transition processes and observations of care transitions work (n = 105) in inpatient medicine, geriatrics, and primary care. Exposure: Frequency of use of twenty recommended care transition processes, scored 0–3. Sites’ individual process scores and cumulative total scores were tested for correlation with RSRR. Outcome: best fit predicted RSRR for quarter of site visit based on the 21 months surrounding the site visits.

Results
Total scores: Mean 38.3 (range 24–47). No site performed all 20 processes. Two processes (pre-discharge patient education, medication reconciliation prior to discharge) were performed at all facilities. Five processes were performed at most facilities but inconsistently and the other 13 processes were more varied across facilities. Total care transition process score was correlated with RSRR (R2 = 0..61, p < 0.007).

Conclusions
Sites making use of more recommended care transition processes had lower RSRR. Given the variability in implementation and barriers noted by clinicians to consistently perform processes, further reduction of readmissions will likely require new strategies to facilitate implementation of these evidence-based processes, should include consideration of how to better incorporate activities into workflow, and may benefit from more consistent use of some of the more underutilized processes including patient inclusion in discharge planning and increased utilization of community supports. Although all facilities had inpatient social workers and/or dedicated case managers working on transitions, many had none or limited true bridging personnel (following the patient from inpatient to home and even providing home visits). More investment in these roles may also be needed.
Metformin activated AMPK signaling contributes to the alleviation of LPS-induced inflammatory responses in bovine mammary epithelial cells
Authors: Xu Tianle , Wu Xinyue , Lu Xubin , Liang Yusheng , Mao Yongjiang , Loor Juan J. , Yang Zhangping 
Published: March 2021

Abstract
Background
Lipopolysaccharides (LPS) derived from gram-negative bacterial are often regarded as primary inducer of bovine mammary inflammation. This study evaluated the biological response of metformin activated AMPK signaling on LPS-induced inflammatory responses and metabolic changes in primary bovine mammary epithelial cells (pbMEC). The pbMEC were exposed to either 3 mmol/L Metf. for 12 h as Metf. group (Metf.) or 2 μg/mL LPS for 6 h as LPS group (LPS). Cells pretreated with 3 mmol/L metformin for 12 h followed by washing and 2 μg/mL LPS exposure for 6 h were served as ML group (ML). PBS was added to cells as the control group (Con.).

Results
Pre-incubation with Metf. inhibited LPS-induced expression of pro-inflammatory genes (TNF, IL1B, IL6, CXCL8, MYD88 and TLR4) and proteins (IL-1β, TNF-α, NLRP3, Caspase1, ASC) and was accompanied by increased activation of AMPK signaling. Compared with the LPS group, phosphorylation of p65 and IκBα in the ML group were decreased and accumulation of NF-κB in the nucleus was significantly reduced by pretreatment with metformin. Metformin protects the cells from the increase of LPS-induced binding activity of NF-κB on both TNFA and IL1B promoters. Compared with the LPS group, genes (G6PC, PCK2) and proteins (SREBP1, SCD1) related to lipogenesis and carbohydrate metabolism were downregulated while catabolic ones (PPARA, ACSL1, Glut1, HK1) were upregulated in the ML group. Furthermore, increased acetylation of H3K14 by LPS challenge was reversed by pretreatment with metformin.

Conclusion
Altogether, our results indicated that pretreatment with metformin dampens LPS-induced inflammatory responses mediated in part by AMPK/NF-κB/NLRP3 signaling and modification of histone H3K14 deacetylation and metabolic changes.
Laparoscopic intragastric resection of gastric synovial sarcoma: report of the first ever case with video demonstration
Authors: Rivelli Matteo , Fernandes Eduardo , Conti Cristian , Bernardoni Laura , Pecori Sara , Cingarlini Sara , Pedrazzani Corrado 
Published: March 2021

Abstract
Background
Synovial sarcoma (SS) is a rare soft tissue tumor. Among different anatomical locations where it can be found, gastric localization is a very uncommon one. Based on soft tissue sarcoma guidelines, complete tumor excision is considered the main treatment approach. Depending on size and localization of the tumor, both wedge and major gastric resections have been performed in the past for the treatment of this condition.

Case presentation
We present the case of a 43-year-old woman who underwent a laparoscopic intragastric excision of a gastric 10-mm SS located nearby the esophagogastric junction. Pathology examination confirmed the presence of a SS. The resected specimen confirmed margin-free excision of a monophasic spindle cell neoplasm invading the submucosa and presenting the rearrangement of SS18 gene at fluorescence in situ hybridization (FISH). No adjuvant treatment was offered, and 18 months after surgery, the patient was alive and disease free.

Conclusions
This represents the first case reported in literature of a laparoscopic intragastric resection for a gastric SS. This approach allowed to obtain a full thickness radical tumor resection with the advantages of minimally invasive and organ preserving surgery.
A systems approach to scale-up for population health improvement
Authors: Koorts Harriet , Rutter Harry 
Published: March 2021

AbstractDespite a number of important global public health successes, for many health behaviours there is a continued lack of interventions that have been sufficiently scaled up to achieve system-wide integration. This has limited sustainable and equitable population health improvement. Systems change plays a major role in the relation between implementation processes and at-scale institutionalisation of public health interventions. However, in research, systems approaches remain underutilised in scaling up. Public health scale-up models have typically centred on intervention replication through linear expansion. In this paper, we discuss current conceptualisations and approaches used when scaling up in public health, and propose a new perspective on scaling that shifts attention away from the intervention to focus instead on achieving the desired population-level health outcomes. In our view, ‘scaling up’ exists on a continuum. At one end, effective scaling can involve a linear, intervention-orientated expansive approach that prioritises the spread of evidence-based interventions into existing systems in order to drive expansion in the application of that intervention. At the other end, we contend that scale-up can sit within a complex systems paradigm in which interventions are conceptualised as events in systems. In this case, implementation and scale-up activities should focus on generating changes within the system itself to achieve the desired outcome. This we refer to as ‘systems-orientated scale-up’ to achieving population health improvement, which can complement traditional approaches in relevant situations. We argue that for some health behaviours, our proposed approach towards scaling up could enhance intervention implementation, sustainability and population health impact.
Recombinant CCL17-dependent CCR4 activation alleviates neuroinflammation and neuronal apoptosis through the PI3K/AKT/Foxo1 signaling pathway after ICH in mice
Authors: Deng Shuixiang , Jin Peng , Sherchan Prativa , Liu Shengpeng , Cui Yuhui , Huang Lei , Zhang John H. , Gong Ye , Tang Jiping 
Published: March 2021

Abstract
Background
Intracerebral hemorrhage (ICH), a devastating subtype of stroke, is associated with high mortality and morbidity. Neuroinflammation is an important factor leading to ICH-induced neurological injuries. C-C Chemokine Receptor 4 (CCR4) plays an important role in enhancing hematoma clearance after ICH. However, it is unclear whether CCR4 activation can ameliorate neuroinflammation and apoptosis of neurons following ICH. The aim of the present study was to examine the effects of recombinant CCL17 (rCCL17)-dependent CCR4 activation on neuroinflammation and neuronal apoptosis in an intrastriatal autologous blood injection ICH model, and to determine whether the PI3K/AKT/Foxo1 signaling pathway was involved.

Methods
Two hundred twenty-six adult (8-week-old) male CD1 mice were randomly assigned to sham and ICH surgery groups. An intrastriatal autologous blood injection ICH model was used. rCCL17, a CCR4 ligand, was delivered by intranasal administration at 1 h, 3 h, and 6 h post-ICH. CCL17 antibody was administrated by intraventricular injection at 1 h post-ICH. C021, a specific inhibitor of CCR4 and GDC0068, an AKT inhibitor were delivered intraperitoneally 1 h prior to ICH induction. Brain edema, neurobehavioral assessments, western blotting, Fluoro-Jade C staining, terminal deoxynucleotidyl transferase dUTP nick end labeling, and immunofluorescence staining were conducted.

Results
Endogenous expression of CCL17 and CCR4 were increased following ICH, peaking at 5 days post-induction. CCR4 was found to co-localize with microglia, neurons, and astrocytes. rCCL17 treatment decreased brain water content, attenuated short- and long-term neurological deficits, deceased activation of microglia/macrophages and infiltration of neutrophils, and inhibited neuronal apoptosis in the perihematomal region post-ICH. Moreover, rCCL17 treatment post-ICH significantly increased the expression of CCR4, PI3K, phosphorylated AKT, and Bcl-2, while Foxo1, IL-1β, TNF-α, and Bax expression were decreased. The neuroprotective effects of rCCL17 were reversed with the administration of C021 or GDC0068.

Conclusions
rCCL17-dependent CCR4 activation ameliorated neurological deficits, reduced brain edema, and ameliorated neuroinflammation and neuronal apoptosis, at least in part, through the PI3K/AKT/Foxo1 signaling pathway after ICH. Thus, activation of CCR4 may provide a promising therapeutic approach for the early management of ICH.
Women’s sleep position during pregnancy in low- and middle-income countries: a systematic review
Authors: Rossiter Shania K. , Aziz Samia , Wilson Alyce N. , Comrie-Thomson Liz , Stacey Tomasina , Homer Caroline S. E. , Vogel Joshua P. 
Published: March 2021

Abstract
Background
Approximately 2.6 million babies are stillborn each year globally, of which 98% occur in low- and middle-income countries (LMICs). A 2019 individual participant data meta-analysis of 6 studies from high-income countries found that maternal supine going-to-sleep position increased the risk of stillbirth. It is not clear whether this impact would be the same in LMICs, and the normal sleep behaviour of pregnant women in LMICs is not well understood.

Objective
Determine the prevalence of different sleeping positions among pregnant women in LMICs, and what (if any) positions were associated with stillbirth using a systematic review.

Search strategy
We systematically searched the databases Medline, Embase, Emcare, CINAHL and Global Index Medicus for relevant studies, with no date or language restrictions on 4 April 2020. Reference lists of included studies were also screened.

Selection criteria
Observational studies of maternal sleep position during pregnancy in LMICs

Data collection and analysis
Recovered citations were screened and eligible studies were included for extraction. These steps were performed by two independent reviewers. Risk of bias was assessed using the Newcastle–Ottawa Scale.

Main results
A total of 3480 citations were screened but only two studies met the inclusion criteria. The studies were conducted in Ghana and India and reported on different maternal sleep positions: supine and left lateral. In Ghana, a prevalence of 9.7% for supine sleeping position amongst 220 women was found. The primary outcome could not be extracted from the Indian study as sleep position information was only reported for women who had a stillbirth (100 of the 300 participants).

Conclusion
There is limited information on maternal sleeping position in LMICs. Since sleep position may be a modifiable risk factor for stillbirth, there is a need for further research to understand the sleep practices and behaviours of pregnant women in LMICs.
PROSPERO registration: CRD42020173314
HIV-1 Vpr activates host CRL4-DCAF1 E3 ligase to degrade histone deacetylase SIRT7
Authors: Zhou Xiaohong , Monnie Christina , DeLucia Maria , Ahn Jinwoo 
Published: March 2021

AbstractBackgroundVpr is a virion-associated protein that is encoded by lentiviruses and serves to counteract intrinsic immunity factors that restrict infection. HIV-1 Vpr mediates proteasome-dependent degradation of several DNA repair/modification proteins. Mechanistically, Vpr directly recruits cellular targets onto DCAF1, a substrate receptor of Cullin 4 RING E3 ubiquitin ligase (CRL4) for poly-ubiquitination. Further, Vpr can mediate poly-ubiquitination of DCAF1-interacting proteins by the CRL4. Because Vpr-mediated degradation of its known targets can not explain the primary cell-cycle arrest phenotype that Vpr expression induces, we surveyed the literature for DNA-repair-associated proteins that interact with the CRL4-DCAF1. One such protein is SIRT7, a deacetylase of histone 3 that belongs to the Sirtuin family and regulates a wide range of cellular processes. We wondered whether Vpr can mediate degradation of SIRT7 via the CRL4-DCAF1.MethodsHEK293T cells were transfected with cocktails of plasmids expressing DCAF1, DDB1, SIRT7 and Vpr. Ectopic and endogeneous levels of SIRT7 were monitered by immunoblotting and protein–protein interactions were assessed by immunoprecipitation. For in vitro reconstitution assays, recombinant CRL4-DCAF1-Vpr complexes and SIRT7 were prepared and poly-ubiqutination of SIRT7 was monitored with immunoblotting.ResultsWe demonstrate SIRT7 polyubiquitination and degradation upon Vpr expression. Specifically, SIRT7 is shown to interact with the CRL4-DCAF1 complex, and expression of Vpr in HEK293T cells results in SIRT7 degradation, which is partially rescued by CRL inhibitor MNL4924 and proteasome inhibitor MG132. Further, in vitro reconstitution assays show that Vpr induces poly-ubiquitination of SIRT7 by the CRL4-DCAF1. Importantly, we find that Vpr from several different HIV-1 strains, but not HIV-2 strains, mediates SIRT7 poly-ubiquitination in the reconstitution assay and degradation in cells. Finally, we show that SIRT7 degradation by Vpr is independent of the known, distinctive phenotype of Vpr-induced cell cycle arrest at the G2 phase,ConclusionsTargeting histone deacetylase SIRT7 for degradation is a conserved feature of HIV-1 Vpr. Altogether,our findings reveal that HIV-1 Vpr mediates down-regulation of SIRT7 by a mechanism that does not involve novel target recruitment to the CRL4-DCAF1 but instead involves regulation of the E3 ligase activity.
Dramatic increase in water use efficiency with cumulative forest disturbance at the large forested watershed scale
Authors: Giles-Hansen Krysta , Wei Xiaohua , Hou Yiping 
Published: March 2021

AbstractBackgroundForest disturbance induced changes in the coupling of forest carbon and water have important implications for ecosystem functioning and sustainable forest management. However, this is rarely investigated at the large watershed scale with cumulative forest disturbance. We used a combination of techniques including modeling, statistical analysis, and machine learning to investigate the effects of cumulative forest disturbance on water use efficiency (WUE, a proxy for carbon and water coupling) in the 19,200 km2Chilcotin watershed situated in the central interior of British Columbia, Canada. Harvesting, wildfire, and a severe Mountain Pine Beetle (MPB) infestation have gradually cumulated over the 45-year study period, and the watershed reached a cumulative equivalent clear-cut area of 10% in 1999 and then 40% in 2016.ResultsSurprisingly, with the dramatic forest disturbance increase from 2000 to 2016 which was mainly due to MPB, watershed-level carbon stocks and sequestration showed an insignificant reduction. This resilience was mainly due to landscape-level carbon dynamics that saw a balance between a variety of disturbance rates and types, an accumulation of older stand types, and fast growing young regenerated forests. Watershed-level carbon sequestration capacity was sustained, measured by Net Primary Production (NPP). A concurrent significant decrease in annual evapotranspiration (ET), led to a 19% increase in WUE (defined as the ratio of NPP to ET), which is contrary to common findings after disturbance at the forest stand-level. During this period of high disturbance, ET was the dominant driver of the WUE increase.ConclusionsWe conclude that disturbance-driven forest dynamics and the appropriate scale must be considered when investigating carbon and water relationship. In contrast to the stand-level trade-off relationship between carbon and water, forested watersheds may be managed to maintain timber, carbon and water resources across large landscapes.