bluuebunny/crossref_metadata_2025_split huggingface dataset:
UBE2T promotes autophagy via the p53/AMPK/mTOR signaling pathway in lung adenocarcinoma
Authors: Zhu Jinhong , Ao Haijiao , Liu Mingdong , Cao Kui , Ma Jianqun 
Published: August 2021

Abstract
Background
Ubiquitin-conjugating enzyme E2T (UBE2T) acts as an oncogene in various types of cancer. However, the mechanisms behind its oncogenic role remain unclear in lung cancer. This study aims to explore the function and clinical relevance of UBE2T in lung cancer.

Methods
Lentiviral vectors were used to mediate UBE2T depletion or overexpress UBE2T in lung cancer cells. CCK8 analysis and western blotting were performed to investigate the effects of UBE2T on proliferation, autophagy, and relevant signaling pathways. To exploit the clinical significance of UBE2T, we performed immunohistochemistry staining with an anti-UBE2T antibody on 131 NSCLC samples. Moreover, we downloaded the human lung adenocarcinoma (LUAD) dataset from The Cancer Atlas Project (TCGA). Lasso Cox regression model was adopted to establish a prognostic model with UBE2T-correlated autophagy genes.

Results
We found that UBE2T stimulated proliferation and autophagy, and silencing this gene abolished autophagy in lung cancer cells. As suggested by Gene set enrichment analysis, we observed that UBE2T downregulated p53 levels in A549 cells and vice versa. Blockade of p53 counteracted the inhibitory effects of UBE2T depletion on autophagy. Meanwhile, the AMPK/mTOR signaling pathway was activated during UBE2T-mediated autophagy, suggesting that UBE2T promotes autophagy via the p53/AMPK/mTOR pathway. Interestingly, UBE2T overexpression increased cisplatin-trigged autophagy and led to cisplatin resistance of A549 cells, whereas inhibiting autophagy reversed drug resistance. However, no association was observed between UEB2T and overall survival in a population of 131 resectable NSCLC patients. Therefore, we developed and validated a multiple gene signature by considering UBE2T and its relevance in autophagy in lung cancer. The risk score derived from the prognostic signature significantly stratified LUAD patients into low- and high-risk groups with different overall survival. The risk score might independently predict prognosis. Interestingly, nomogram and decision curve analysis demonstrated that the signature’s prognostic accuracy culminated while combined with clinical features. Finally, the risk score showed great potential in predicting clinical chemosensitivity.

Conclusions
We found that UBE2T upregulates autophagy in NSCLC cells by activating the p53/AMPK/mTOR signaling pathway. The clinical predicting ability of UBE2T in LUAD can be improved by considering the autophagy-regulatory role of UBE2T.
Hair salons and stylist–client social relationships as facilitators of community-based contraceptive uptake in KwaZulu-Natal, South Africa: a qualitative analysis
Authors: Wara Nafisa J. , Psaros Christina , Govere Sabina , Dladla Nosipho , Stuckwisch Ashley , Zionts Dani , Jarolimova Jana , Bassett Ingrid V. 
Published: August 2021

Abstract
Background
South Africa faces a high burden of unmet contraceptive need, particularly among adolescent girls and young women. Providing contraception in community-based venues may overcome barriers to contraceptive access. Our objective was to explore the potential impact of the social environment and stylist–client interactions on perceived accessibility of contraceptives within hair salons.

Methods
We conducted 42 semi-structured, in-depth interviews with salon clients (100% identified as female, 100% identified as Black, median age 27.1 years) and 6 focus groups with 43 stylists (95% identified as female, 98% identified as Black, median age 29.6 years) in and around Umlazi Township, Durban, KwaZulu-Natal to explore perspectives on offering contraceptive services in hair salons. We used an inductive and deductive approach to generate the codebook, identified themes in the data, and then organized findings according to Rogers’ Individual Adoption Model as applied to community-based health prevention programs. Twenty-five percent of transcripts were coded by two independent coders to ensure reliability.

Results
We identified elements of the salon environment and stylist–client relationships as facilitators of and barriers to acceptability of salon-based contraceptive care. Factors that may facilitate perceived contraceptive accessibility in salons include: the anonymous, young, female-centered nature of salons; high trust and kinship within stylist–client interactions; and mutual investment of time. Stylists may further help clients build comprehension about contraceptives through training. Stylists and clients believe salon-based contraceptive delivery may be more accessible due to contraceptive need facilitating client buy-in for the program, as well as a salon environment in which clients may encourage other clients by voluntarily sharing their own contraceptive decisions. The non-judgmental nature of stylist–client relationships can empower clients to make contraceptive decisions, and stylists seek to support clients’ continued use of contraceptives through various adherence and support strategies. Some stylists and clients identified existing social barriers (e.g. confidentiality concerns) and made recommendations to strengthen potential contraceptive delivery in salons.

Conclusion
Stylists and clients were highly receptive to contraceptive delivery in salons and identified several social facilitators as well as barriers within this setting. Hair salons are community venues with a social environment that may uniquely mitigate barriers to contraceptive access in South Africa.
Assessment of H3K27me3 immunohistochemistry and combination of NF1 and p16 deletions by fluorescence in situ hybridization in the differential diagnosis of malignant peripheral nerve sheath tumor and its histological mimics
Authors: Sugita Shintaro , Aoyama Tomoyuki , Emori Makoto , Kido Tomomi , Takenami Tomoko , Sakuraba Kodai , Terai Kotomi , Sugawara Taro , Tsujiwaki Mitsuhiro , Hasegawa Tadashi 
Published: August 2021

Abstract
Background
A definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is challenging, especially in cases without neurofibromatosis 1 (NF1), because MPNST lacks specific markers on immunohistochemistry (IHC).

Methods
We performed IHC for histone 3 trimethylated on lysine 27 (H3K27me3) and evaluated the percentage of cells with H3K27me3 loss using measured values at 10% intervals, categorized as complete loss (100% of tumor cells lost staining), partial loss (10% to 90% of tumor cells lost staining), and intact (no tumor cells lost staining). We conducted fluorescence in situ hybridization (FISH) for NF1 and p16 deletions comparing 55 MPNSTs and 35 non-MPNSTs, consisting of 9 synovial sarcomas (SSs), 8 leiomyosarcomas (LMSs), 10 myxofibrosarcomas (MFSs), and 8 undifferentiated pleomorphic sarcomas (UPSs). We assessed the percentage of cells with homozygous and heterozygous deletions and defined “deletion” if the percentage of either the NF1 or p16 deletion signals was greater than 50% of tumor cells.

Results
Among the 55 MPNSTs, 23 (42%) showed complete H3K27me3 loss and 32 (58%) exhibited partial loss or intact. One each of the 9 SSs (11%), 8 LMSs (12%), and 8 UPSs (12%) showed complete H3K27me3 loss and many non-MPNSTs exhibited intact or partial H3K27me3 loss. Among the 55 MPNSTs, 33 (60%) and 44 (80%) showed NF1 or p16 deletion, respectively. Co-deletion of NF1 and p16 was observed in 29 (53%) MPNSTs. Among the 23 MPNTSs showing H3K27me3 complete loss, 18 (78%) and 20 (87%) exhibited NF1 or p16 deletion, respectively. Among the 32 MPNSTs with H3K27me3 partial loss or intact, 15 (47%) and 24 (75%) exhibited NF1 or p16 deletion, respectively. The frequency of NF1 and/or p16 deletion tended to be lower in non-MPNSTs than in MPNSTs. Approximately 90% of MPNSTs included cases with H3K27me3 complete loss and cases showing H3K27me3 partial loss or intact with NF1 and/or p16 deletion. Approximately 50% of MPNSTs showed co-deletion of NF1 and p16 regardless of H3K27me3 loss.

Conclusions
FISH for NF1 and p16 deletions, frequently observed in high-grade MPNSTs, might be a useful ancillary diagnostic tool for differentiating MPNST from other mimicking spindle cell and pleomorphic sarcomas.
Detection of bacterial DNA in synovial fluid in dogs with arthritis: a comparison between bacterial culture and 16S rRNA polymerase chain reaction
Authors: Vilén Alexandra , Nilson Bo , Petersson Ann-Cathrine , Cigut Mariana , Nielsen Christel , Ström Henriette 
Published: August 2021

AbstractBackgroundSeptic arthritis (SA) is a serious condition in dogs that requires a prompt diagnosis and treatment to minimize long-term joint pathology. Although bacterial detection in synovial fluid (SF) through culture or cytology is often performed to confirm diagnosis, the sensitivity of these tests is low. The need for a reliable diagnostic tool to confirm the presence of bacteria in SF in humans has led to the increased use of 16S rRNA (i.e., ribosomal RNA) gene sequencing by polymerase chain reaction (16S rRNA PCR). The aim of this prospective clinical study was to compare the sensitivity and specificity of 16S rRNA PCR with bacterial culture on blood agar plates after pre-incubation of SF in paediatric blood bacterial culture bottles to identify bacteria in dogs with clinical signs of SA and to investigate the usefulness of these methods as diagnostic tools.ResultsTen dogs with clinical signs of SA, nine with osteoarthritis (OA, control group) and nine with clinical signs of immune-mediated polyarthritis (IMPA, second control group) were examined. Bacterial culture was positive in seven of 10 dogs with clinical SA, of which only two were positive by 16S rRNA PCR. The sensitivity of 16S rRNA PCR and bacterial culture analysis for dogs with clinical SA were 20% and 70%, respectively. All SF samples collected from control group (n = 9) and second control group (n = 14) animals were negative on culture, and 16S rRNA PCR rendered a specificity of 100%.ConclusionsOur study showed a lower sensitivity of 16S rRNA PCR than bacterial culture for dogs with clinical SA. Our findings suggest that there is currently no advantage in using 16S rRNA PCR as a diagnostic tool for dogs with clinical SA. Furthermore, our study indicates that pre-incubation in paediatric blood bacterial culture bottles before bacterial cultivation on blood agar plates might enhance bacterial culture sensitivity compared to other culture methods.
The architecture of the primary mental healthcare system for older people in India: what public policies tell us
Authors: Kafczyk Tom , Hämel Kerstin 
Published: August 2021

AbstractBackgroundOld age mental healthcare is an issue that cuts across old age, general health, and mental healthcare policies. While strengthening the primary mental healthcare system in India is a common strategy across policy fields to improve the mental health of older persons, very little is known about the system’s planned architecture. This study explores public policy strategies for and approaches to the mental health of older persons, focusing on the primary healthcare (PHC) level and the role of the family.MethodsA document analysis of 39 key public national policy documents (2007 – 2019) from three thematically grouped policy fields (mental health, old age, and general health) was conducted.ResultsComprehensive community-based primary mental healthcare – focusing on vulnerable population groups including older persons – has been strengthened significantly since 2007. The promulgated approaches and strategies build on traditional community-based approaches to mental healthcare in India. They focus on (a) integrating community health workers into primary mental healthcare, (b) empowering the community to participate in healthcare planning, implementation, and monitoring, (c) supporting the family through a family-led approach to mental healthcare, and (d) integrating traditional Ayurveda, Yoga and Naturopathy, Unani, Siddha, Sowa-Rigpa and Homeopathy (AYUSH) services into primary mental healthcare.ConclusionsWhile all policy fields address mental PHC, they do so in different ways, and approaches and strategies that promote an integrated perspective across policy fields are lacking. To realize the policies vision, strengthening PHC will be essential. Further research should evaluate strategies and approaches in light of social developments, such as eroding family norms and the poor state of the public health system in India, in order to assess their opportunities, challenges, and overall feasibility, with the benefits older people would experience taking centre stage in these inquiries.
Modeling PTEN overexpression-induced microcephaly in human brain organoids
Authors: Dhaliwal Navroop , Choi Wendy W.Y. , Muffat Julien , Li Yun 
Published: August 2021

AbstractThe phosphatase and tensin homolog (PTEN) protein, encoded by the PTEN gene on chromosome 10, is a negative regulator of the phosphoinositide 3-kinase (PI3K) signaling pathway. Loss of PTEN has been linked to an array of human diseases, including neurodevelopmental disorders such as macrocephaly and autism. However, it remains unknown whether increased dosage of PTEN can lead to human disease. A recent human genetics study identifies chromosome 10 microduplication encompassing PTEN in patients with microcephaly. Here we generated a human brain organoid model of increased PTEN dosage. We showed that mild PTEN overexpression led to reduced neural precursor proliferation, premature neuronal differentiation, and the formation of significantly smaller brain organoids. PTEN overexpression resulted in decreased AKT activation, and treatment of wild-type organoids with an AKT inhibitor recapitulated the reduced brain organoid growth phenotypes. Together, our findings provide functional evidence that PTEN is a dosage-sensitive gene that regulates human neurodevelopment, and that increased PTEN dosage in brain organoids results in microcephaly-like phenotypes.
Point-of-care testing in out-of-hospital cardiac arrest: a retrospective analysis of relevance and consequences
Authors: Gruebl Tobias , Ploeger B. , Wranze-Bielefeld E. , Mueller M. , Schmidbauer W. , Kill C. , Betz S. 
Published: August 2021

Abstract
Background
Metabolic and electrolyte imbalances are some of the reversible causes of cardiac arrest and can be diagnosed even in the pre-hospital setting with a mobile analyser for point-of-care testing (POCT).

Methods
We conducted a retrospective observational study, which included analysing all pre-hospital resuscitations in the study region between October 2015 and December 2016. A mobile POCT analyser (Alere epoc®) was available at the scene of each resuscitation. We analysed the frequency of use of POCT, the incidence of pathological findings, the specific interventions based on POCT as well as every patient’s eventual outcome.

Results
N = 263 pre-hospital resuscitations were included and in n = 98 of them, the POCT analyser was used. Of these measurements, 64% were performed using venous blood and 36% using arterial blood. The results of POCT showed that 63% of tested patients had severe metabolic acidosis (pH < 7.2 + BE <  − 5 mmol/l). Of these patients, 82% received buffering treatment with sodium bicarbonate. Potassium levels were markedly divergent normal (> 6.0 mmol/l/ < 2.5 mmol/l) in 17% of tested patients and 14% of them received a potassium infusion. On average, the pre-hospital treatment time between arrival of the first emergency medical responders and the beginning of transport was 54 (± 20) min without POCT and 60 (± 17) min with POCT (p = 0.07). Overall, 21% of patients survived to hospital discharge (POCT 30% vs no POCT 16%, p = 0.01, Φ = 0.16).

Conclusions
Using a POCT analyser in pre-hospital resuscitation allows rapid detection of pathological acid–base imbalances and potassium concentrations and often leads to specific interventions on scene and could improve the probability of survival.
Identification of distinct clinical phenotypes of acute respiratory distress syndrome with differential responses to treatment
Authors: Liu Xiaowei , Jiang Yusheng , Jia Xiaonan , Ma Xiaohui , Han Ci , Guo Nana , Peng Yahui , Liu Haitao , Ju Yingnan , Luo Xiangfeng , Li Xueting , Bu Yue , Zhang Jin , Liu Yansong , Gao Yan , Zhao Mingyan , Wang Hongliang , Luo Ligang , Yu Kaijiang , Wang Changsong 
Published: August 2021

Abstract
Background
Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome, and the identification of homogeneous subgroups and phenotypes is the first step toward precision critical care. We aimed to explore whether ARDS phenotypes can be identified using clinical data, are reproducible and are associated with clinical outcomes and treatment response.

Methods
This study is based on a retrospective analysis of data from the telehealth intensive care unit (eICU) collaborative research database and three ARDS randomized controlled trials (RCTs) (ALVEOLI, FACTT and SAILS trials). We derived phenotypes in the eICU by cluster analysis based on clinical data and compared the clinical characteristics and outcomes of each phenotype. The reproducibility of the derived phenotypes was tested using the data from three RCTs, and treatment effects were evaluated.

Results
Three clinical phenotypes were identified in the training cohort of 3875 ARDS patients. Of the three phenotypes identified, phenotype I (n = 1565; 40%) was associated with fewer laboratory abnormalities, less organ dysfunction and the lowest in-hospital mortality rate (8%). Phenotype II (n = 1232; 32%) was correlated with more inflammation and shock and had a higher mortality rate (18%). Phenotype III (n = 1078; 28%) was strongly correlated with renal dysfunction and acidosis and had the highest mortality rate (22%). These results were validated using the data from the validation cohort (n = 3670) and three RCTs (n = 2289) and had reproducibility. Patients with these ARDS phenotypes had different treatment responses to randomized interventions. Specifically, in the ALVEOLI cohort, the effects of ventilation strategy (high PEEP vs low PEEP) on ventilator-free days differed by phenotype (p = 0.001); in the FACTT cohort, there was a significant interaction between phenotype and fluid-management strategy for 60-day mortality (p = 0.01). The fluid-conservative strategy was associated with improved mortality in phenotype II but had the opposite effect in phenotype III.

Conclusion
Three clinical phenotypes of ARDS were identified and had different clinical characteristics and outcomes. The analysis shows evidence of a phenotype-specific treatment benefit in the ALVEOLI and FACTT trials. These findings may improve the identification of distinct subsets of ARDS patients for exploration in future RCTs.
Teriparatide and stress fracture healing in young adults (RETURN – Research on Efficacy of Teriparatide Use in the Return of recruits to Normal duty): study protocol for a randomised controlled trial
Authors: Carswell Alexander T. , Eastman Katharine G. , Casey Anna , Hammond Matthew , Shepstone Lee , Payerne Estelle , Toms Andoni P. , MacKay James W. , Swart Ann Marie , Greeves Julie P. , Fraser William D. 
Published: August 2021

Abstract
Background
Stress fractures are a common and potentially debilitating overuse injury to bone and occur frequently among military recruits and athletes. Recovery from a lower body stress fracture typically requires several weeks of physical rehabilitation. Teriparatide, a recombinant form of the bioactive portion of parathyroid hormone (1–34 amino acids), is used to treat osteoporosis, prevent osteoporotic fractures, and enhance fracture healing due to its net anabolic effect on bone. The study aim is to investigate the effect of teriparatide on stress fracture healing in young, otherwise healthy adults undergoing military training.

Methods
In a two-arm, parallel, prospective, randomised controlled, intention-to-treat trial, Army recruits (n = 136 men and women, 18–40 years) with a magnetic resonance imaging (MRI) diagnosed lower body stress fracture (pelvic girdle, sacrum, coccyx, or lower limb) will be randomised to receive either usual Army standard care, or teriparatide and usual Army standard care. Teriparatide will be self-administered by subcutaneous injections (20 μg/day) for 16 weeks, continuing to 24 weeks where a fracture remains unhealed at week 16. The primary outcome will be the improvement in radiological healing by two grades or more, or reduction to grade zero, 8 weeks after randomisation, assessed using Fredericson grading of MRI by radiologists blind to the randomisation. Secondary outcomes will be time to radiological healing, assessed by MRI at 8, 10, 12, 14, 16, 20 and 24 weeks, until healed; time to clinical healing, assessed using a clinical severity score of injury signs and symptoms; time to discharge from Army physical rehabilitation; pain, assessed by visual analogue scale; health-related quality of life, using the Short Form (36) Health Survey; and adverse events. Exploratory outcomes will include blood and urine biochemistry; bone density and morphology assessed using dual-energy X-ray absorptiometry, peripheral quantitative computed tomography (pQCT), and high-resolution pQCT; physical activity measured using accelerometers; and long-term future fracture rate.

Discussion
This study will evaluate whether teriparatide, in addition to standard care, is more effective for stress fracture healing than standard care alone in Army recruits who have sustained a lower body stress fracture.

Trial registration
ClinicalTrials.govNCT04196855. Registered on 12 December 2019.
Establishment of a resource recycling strategy by optimizing isobutanol production in engineered cyanobacteria using high salinity stress
Authors: Wu Xiao-Xi , Li Jian-Wei , Xing Su-Fang , Chen Hui-Ting , Song Chao , Wang Shu-Guang , Yan Zhen 
Published: August 2021

Abstract
Background
Isobutanol is an attractive biofuel with many advantages. Third-generation biorefineries that convert CO2 into bio-based fuels have drawn considerable attention due to their lower feedstock cost and more ecofriendly refining process. Although autotrophic cyanobacteria have been genetically modified for isobutanol biosynthesis, there is a lack of stable and convenient strategies to improve their production.

Results
In this study, we first engineered Synechococcus elongatus for isobutanol biosynthesis by introducing five exogenous enzymes, reaching a production titer of 0.126 g/L at day 20. It was then discovered that high salinity stress could result in a whopping fivefold increase in isobutanol production, with a maximal in-flask titer of 0.637 g/L at day 20. Metabolomics analysis revealed that high salinity stress substantially altered the metabolic profiles of the engineered S. elongatus. A major reason for the enhanced isobutanol production is the acceleration of lipid degradation under high salinity stress, which increases NADH. The NADH then participates in the engineered isobutanol-producing pathway. In addition, increased membrane permeability also contributed to the isobutanol production titer. A cultivation system was subsequently developed by mixing synthetic wastewater with seawater to grow the engineered cyanobacteria, reaching a similar isobutanol production titer as cultivation in the medium.

Conclusions
High salinity stress on engineered cyanobacteria is a practical and feasible biotechnology to optimize isobutanol production. This biotechnology provides a cost-effective approach to biofuel production, and simultaneously recycles chemical nutrients from wastewater and seawater.