bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low level light therapy/photobiomodulation for diabetic peripheral neuropathy: protocol of a systematic review and meta-analysis
Authors: Wang Jia-You , Huang Zou-Qin , Deng Hai-Ping , Zhao Ling , Deng Hong-Yong , Liu Jian-Ping , Shen Xue-Yong , Cheng Ke 
Published: September 2022

IntroductionDiabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes that strongly impact the patients’ quality of life and working ability. Evidence indicated that low level light therapy (LLLT)/photobiomodulation might be effective for neuropathy. However, the effect of LLLT for DPN is not clear. The objective of this systematic review and meta-analysis is to determine the effects and safety of LLLT/photobiomodulation for DPN, in comparison with other methods such as sham light, no treatment, other active treatment and LLLT as an additional treatment compared with another treatment alone.Methods and analysisWe will search eight databases from their inception to the date before the review submission. Randomised controlled trials (RCTs) will be included. Two reviewers will independently extract data using a structured data extraction method and assess the risk of bias in the included studies. Data will be synthesised using standardised mean difference or risk ratio with 95% CIs for continuous and dichotomous data, respectively. The primary outcome will be change in pain and secondary outcomes will include global symptom improvement, functional impairment and disability, impairment of sensation, quality of life, nerve conduction, and adverse events. Sensitivity and subgroup analysis will be employed to explore the influence of possible clinical and methodological characteristics. Publication bias will be assessed using funnel plot. We will conduct meta-analysis with RevMan V.5.4 and evaluate quality of the evidence using GRADE approach.Ethics and disseminationThis study does not require ethics approval. Our findings will be disseminated in the peer-reviewed publications.PROSPERO registration numberCRD42021276056.
Comparing asphyxia and unexplained causes of death: a retrospective cohort analysis of sleep-related infant death cases from a state child fatality review programme
Authors: Macdonald Megan , Thompson Daniel , Perry Robin , Brooks Robert 
Published: September 2022

ObjectivesTo examine the characteristics and circumstances of infants who died while sleeping or in a sleep environment and compare deaths classified as either unintentional asphyxia or an unexplained cause.DesignA retrospective cohort study.SettingData were extracted from the National Fatality Review Case Reporting System and Florida Vital Statistics databases.ParticipantsData on 778 sleep-related infant deaths occurring from 2014 to 2018 in Florida were analysed.Primary outcome measureCause of death classification as unintentional asphyxia or unexplained.ResultsOverall, 36% (n=276) of sleep-related infant deaths in this study sample were classified as resulting from an unexplained cause compared with unintentional asphyxia. Most infants were reported to be in an adult bed (60%; n=464) and sharing a sleep surface with a person or animal (60%; n=468); less than half (44%; n=343) were reportedly placed to sleep on their back. After controlling for the influence of other independent variables, female sex (adjusted risk ratio: 1.36; 95% CI 1.06 to 1.74) and fully obstructed airway condition (adjusted risk ratio: 0.30; 95% CI 0.18 to 0.50) were associated with an unexplained cause of death.ConclusionsThe results of this analysis indicate that sleep environment hazards remain prevalent among infants who die suddenly and unexpectedly, regardless of the cause of death determination. While significant differences were observed for some factors, in many others the distributions of both demographic and incident characteristics were similar between unexplained deaths and those resulting from asphyxia. The results of this study support growing evidence that unsafe sleep environments contribute to all forms of sudden unexpected infant death, underscoring the need for standardising cause of death determination practices and promoting consistent, high-quality forensic investigations to accurately explain, monitor and prevent these deaths.
Student and clinician perceptions of medical student mistreatment: a cross-sectional vignette survey
Authors: Peckston Dane Christopher , Urwin Rachel , McMullan Ryan , Westbrook Johanna 
Published: September 2022

ObjectivesThe mistreatment of medical students remains pervasive in medical education. Understanding the extent to which clinicians and students recognise mistreatment can assist in creating targeted interventions that reduce mistreatment. The objective of this study was to use clinical vignettes to assess perceptions of medical student mistreatment among medical students and clinical faculty at an Australian university.Design, setting and participantsThis cross-sectional study used a survey of medical students and clinical faculty in a Doctor of Medicine (MD) programme at Macquarie University in Sydney, Australia. Data were collected via an online survey between 13 July and 27 July 2020.Outcome measuresFourteen clinical vignettes were developed based on commonly reported themes of mistreatment. An additional control vignette was also included, and these 15 vignettes were distributed via email to all 169 MD students and 42 teaching faculty at this teaching site. Participants were asked to rate whether the vignettes portrayed mistreatment on a 5-point Likert scale (strongly disagree to strongly agree).ResultsRespondents included 83 MD students and 34 clinical faculty. On average, students perceived mistreatment in 9 of 14 vignettes and faculty in 8 of 14 vignettes. Faculty and student perceptions aligned in themes of sexual abuse, physical abuse and in the control vignette depicting a constructive teaching style. Perceptions differed significantly between faculty and students (p<0.05) for five vignettes across the themes of gender discrimination, requests of students to perform non-educational tasks, humiliation, specialty choice discrimination and requests to perform a task beyond the student’s capacity.ConclusionAgreement on what constitutes appropriate behaviour is crucial to ensuring that a culture of mistreatment can be replaced with one of kindness, equity and respect. This study demonstrated the successful use of vignettes to compare perceptions of mistreatment, with faculty and student perceptions differing across a variety of themes.
Quality assessment and comparative analysis on the recommendations of current guidelines on screening and diagnosis of peripheral arterial disease: a systematic review
Authors: Uyagu Oliseneku Damien , Ofoegbu Cosmas , Ikhidero Joseph , Chukwuka Emeka , Enwere Okezie , Ogierakhi Omokharo , Adelosoye Alex 
Published: September 2022

ObjectivesThere are several clinical practice guidelines available for peripheral artery disease (PAD). The paucity of strong evidence is known to give room for variations in recommendations across guidelines, with attendant confusion among clinicians in clinical practice. This study aims to conduct a quality assessment and comparative analysis on PAD screening and diagnostic recommendations in PAD management.SelectionClinical practice guidelines written after 2010 and on or before 2020 were targeted. An exhaustive search was conducted through the major medical databases and websites of specialist international organisations of interest, and selection was made using our inclusion/exclusion criteria.SettingGlobal. All guidelines written in English were included in this study.Selected guidelinesNine guidelines were selected.OutcomesThe primary outcomes were the guidelines’ quality and variations in screening and diagnostic recommendations in the selected guidelines.ResultsRegarding quality, the guidelines had the lowest scores across the applicability and stakeholder involvement domains with means (SD) of 62 (9.9) and 65.3 (13), respectively. The highest score was clarity of presentation, with a mean (SD) of 86.8 (5.1). Also, the trend showed guideline quality scores improved over time. The guidelines unanimously offered to screen ‘high-risk’ patients, although there were some discrepancies in the appropriate age range and unavailability of strong evidence backing this recommendation. The guidelines harmoniously adopted the Ankle-Brachial Index as the initial diagnostic investigation of choice. However, concerning further diagnostic investigations and imaging, we found several discrepancies among the recommendations in the absence of strong evidence.ConclusionThough the quality of the guidelines is shown to be improving over time, they perform poorly in stakeholder involvement and applicability domains, which could be influencing interest in research revolving around screening and diagnostic recommendations. Involving primary care providers and the public can be a possible solution.PROSPERO registration numberCRD42020219176.
Experiences of COVID-19 patients in a Fangcang shelter hospital in China during the first wave of the COVID-19 pandemic: a qualitative descriptive study
Authors: Zhong Yaping , Zhao Huan , Lee Tsorng-Yeh , Yu Tianchi , Liu Ming Fang , Ji Ji 
Published: September 2022

ObjectivesThis study aimed to examine COVID-19 patients’ experiences in a Fangcang shelter hospital in China, to provide insights into the effectiveness of this centralised isolation strategy as a novel solution to patient management during emerging infectious disease outbreaks.DesignThis study adopted a qualitative descriptive design. Data were collected by individual semistructured interviews and analysed using thematic analysis.SettingThis study was undertaken in 1 of the 16 Fangcang shelter hospitals in Wuhan, China between 28 February 2020 and 7 March 2020. Fangcang shelter hospitals were temporary healthcare facilities intended for large-scale centralised isolation, treatment and disease monitoring of mild-to-moderate COVID-19 cases. These hospitals were an essential component of China’s response to the first wave of the COVID-19 pandemic.ParticipantsA total of 27 COVID-19 patients were recruited by purposive sampling. Eligible participants were (1) COVID-19 patients; (2) above 18 years of age and (3) able to communicate effectively. Exclusion criteria were (1) being clinically or emotionally unstable and (2) experiencing communication difficulties.ResultsThree themes and nine subthemes were identified. First, COVID-19 patients experienced a range of psychological reactions during hospitalisation, including fear, uncertainty, helplessness and concerns. Second, there were positive and negative experiences associated with communal living. While COVID-19 patients’ evaluation of essential services in the hospital was overall positive, privacy and hygiene issues were highlighted as stressors during their hospital stay. Third, positive peer support and a trusting patient–healthcare professional relationship served as a birthplace for resilience, trust and gratitude in COVID-19 patients.ConclusionsOur findings suggest that, while sacrificing privacy, centralised isolation has the potential to mitigate negative psychological impacts of social isolation in COVID-19 patients by promoting meaningful peer connections, companionship and support within the shared living space. To our knowledge, this is the first study bringing patients’ perspectives into healthcare service appraisal in emergency shelter hospitals.
Physiological responses to ramp-incremental cycling tests performed at three simulated altitudes: a randomized crossover trial
Authors: Beever Austin T. , Zhuang Andrea Y. , Aboodarda Saied Jalal , Murias Juan M. , MacInnis Martin J. 
Published: September 2022

Hypoxia negatively impacts aerobic exercise, but exercise testing in hypoxia has not been studied comprehensively. To determine the effects of simulated altitude on the gas exchange threshold (GET), respiratory compensation point (RCP), and maximal oxygen uptake (V̇O2max), 24 participants (mean [SD]; 26 [4] years; 171.6 [9.7] cm; 69.2 [11.9] kg) acclimatized to mild altitude (MILD; ∼1100 m) performed three cycling ramp-incremental exercise tests (with verification stages performed at 110% of peak power output (PPO)) in simulated altitudes of 0 m (sea level, SL), 1111 m (MILD), and 2222 m (moderate altitude, MOD), in a randomized order. There were significant effects of condition (i.e., fraction of inspired oxygen [FIO2]) for GET ( p = 0.001), RCP ( p < 0.001), V̇O2max ( p < 0.001), and PPO ( p < 0.001). The V̇O2 corresponding to GET and RCP (mL·kg−1·min−1) in MOD (24.1 [4.3]; 37.3 [5.1]) were significantly lower ( p < 0.05) compared to SL (27.1 [4.4]; 41.8 [6.6]) and MILD (26.8 [5.7]; 40.7 [7.3]) but similar ( p > 0.05) between SL and MILD. For each increase in simulated altitude, V̇O2max (SL: 51.3 [7.4]; MILD: 50.0 [7.6]; MOD: 47.3 [7.1] mL·kg−1·min−1) and PPO (SL: 332 [80]; MILD: 327 [78]; SL: 316 [76] W) decreased significantly ( p < 0.05 for all comparisons). V̇O2max values from the verification stage were lower than those measured during the ramp-incremental test ( p = 0.017). Overall, a mild simulated altitude had a significant effect on V̇O2max and PPO but not GET and RCP, MOD decreased all four variables, and the inclusion of a verification stage had little effect on the determination of V̇O2max in a group of young healthy adults regardless of the FIO2. Trial registration: Open Science Framework 10.17605/OSF.IO/ZTC9E.
Quintessence Universe and cosmic acceleration in f (Q, T) gravity
Authors: Koussour M. , Myrzakulov N. , Shekh S. H. , Bennai M. 
Published: September 2022

The problem of cosmic acceleration and dark energy is one of the mysteries presently posed in the scientific society that general relativity has not been able to solve. In this work, we have considered alternative models to explain this late-time acceleration in a flat Friedmann–Lemaitre–Robertson–Walker (FLRW) Universe within the framework of the f (Q,T) modified gravity theory (where Q is the nonmetricity and T is the trace of the energy–momentum tensor) recently proposed by Y. Xu et al. [Eur. Phys. J. C 79 (2019) 708], which is an extension of f (Q) gravity with the addition of the T term. Here, we presume a specific form of [Formula: see text] where [Formula: see text], [Formula: see text] and [Formula: see text] are free model parameters, and obtained the exact solutions by assuming the cosmic time-redshift relation as [Formula: see text] which produces the Hubble parameter of the form [Formula: see text], where m and n are the nonnegative constants, we find the best values for them using 57 data points of the Hubble parameter H(z). Also, we find the behavior of different cosmological parameters as the deceleration parameter (q), energy density [Formula: see text], pressure (p) and equation of state (EoS) parameter [Formula: see text] and compare them with the observational results. To ensure the validity of the results, we studied the energy conditions along with jerk parameter. Finally, we found that our model behaves similarly to the quintessence Universe.
METTL1-Mediated m7G tRNA Modification Promotes Lenvatinib Resistance in Hepatocellular Carcinoma
Authors: Huang Manling , Long Jianting , Yao Zhijia , Zhao Yi , Zhao Yutong , Liao Junbin , Lei Kai , Xiao Han , Dai Zihao , Peng Sui , Lin Shuibin , Xu Lixia , Kuang Ming 
Published: September 2022

Abstract

The tyrosine kinase inhibitor lenvatinib is a first-line drug for treating patients with advanced hepatocellular carcinoma (HCC). However, its efficacy is severely hampered by drug resistance. Insights into the molecular mechanisms underlying lenvatinib resistance could provide new strategies to improve and prolong responses. Here, we performed unbiased proteomic screening of parental and lenvatinib-resistant HCC cells and discovered that methyltransferase-like protein-1 (METTL1) and WD repeat domain 4 protein (WDR4), the two key components of the tRNA N7-methylguanosine (m7G) methyltransferase complex, were dramatically upregulated in lenvatinib-resistant cells. METTL1 knockdown overrode resistance by impairing the proliferation capacity of HCC cells and promoting apoptosis under lenvatinib treatment. In addition, overexpression of wild-type METTL1 but not its catalytic dead mutant induced lenvatinib resistance. Animal experiments including hydrodynamic injection, subcutaneous implantation, and orthotopic xenograft mouse models further demonstrated the critical function of METTL1/WDR4-mediated m7G tRNA modification in promoting lenvatinib resistance in vivo. Mechanistically, METTL1 promoted translation of EGFR pathway genes to trigger drug resistance. This work reveals the important role of METTL1-mediated m7G tRNA modification in promoting lenvatinib resistance and provides a promising prediction marker and intervention target for resistance.

Significance:
Upregulation of tRNA m7G methyltransferase complex components METTL1 and WDR4 promotes lenvatinib resistance in HCC and confers a sensitivity to METTL1 targeting, providing a promising strategy to override resistance.
Quantitative Spatial Profiling of TILs as the Next Step beyond PD-L1 Testing for Immune Checkpoint Blockade
Authors: Anagnostou Valsamo , Luke Jason J. 
Published: September 2022

SummaryAnalysis of tumor-infiltrating lymphocyte (TIL) functional states, particularly tumor-reactive PD-1T TILs, within specific spatial context, can serve as a biologically informed predictive marker of immunotherapy that may be superior to standard clinical biomarkers. High-plex quantitative immune cell phenotyping within their spatial context has tremendous potential in immuno-oncology.See related article by Hummelink et al., p. 4893
Abstract A014: The novel anti-inflammatory agent GML (GM1-targeted linoleate-containing TLR2 ligand) inhibits sarcoma metastasis to the lung
Authors: Babes Liane , Wierenga Lauren A. , Dan Ngoc-Ha , Lun Xueqing , Goring Kimberly-Ann R. , Robbins Stephen M. , Senger Donna L. 
Published: September 2022

Abstract
Sarcomas are a heterogeneous group of cancers occurring in tissues derived from the mesenchyme. Despite improved treatment strategies that include surgery and broad-based chemotherapeutics, survival of patients with sarcoma remains unchanged in the last 40 years with 5-year overall survival less than 25%. In part, this high rate of mortality can be attributed to the development of pulmonary metastases, a process that occurs in up to 50% of patients. We propose that preventing the occurrence or growth of lung metastases can improve the outcome for many of these patients. Our growing understanding of the dynamic relationship between inflammation and cancer has led to the investigation of anti-inflammatory approaches to treat cancer, including metastasis. Specifically, recent studies suggest a role for neutrophils in cancer metastasis, identifying a promising target for therapeutic intervention. The aim of the present study is to investigate the role of myeloid cells in the metastatic process, and their potential to act as therapeutic targets during the development of lung metastases. Herein we used human and syngeneic osteosarcoma lung metastatic models together with in vitro assays to assess the role of neutrophils in this process. Our results demonstrate that neutrophils are essential to facilitate the development of osteosarcoma pulmonary metastases and that treatment with the novel anti-inflammatory agent GM1-targeted linoleate-containing TLR2 ligand (GML), known to inhibit neutrophil recruitment, diminishes their occurrence. Overall, our results suggest that neutrophils play a role in mediating osteosarcoma lung metastasis and reveal GML as a potential anti-metastatic drug therapy.
Citation Format: Liane Babes, Lauren A. Wierenga, Ngoc-Ha Dan, Xueqing Lun, Kimberly-Ann R. Goring, Stephen M. Robbins, Donna L. Senger. The novel anti-inflammatory agent GML (GM1-targeted linoleate-containing TLR2 ligand) inhibits sarcoma metastasis to the lung [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr A014.
Abstract A018: YAP signaling promotes resistance to MEK and AKT inhibition in NF1-related MPNSTs
Authors: McGee Lauren , Essenburg Curt , Turner Lisa , Hirbe Angela , Dey Anwesha , Zbieg Jason , Graveel Carrie , Steensma Matt 
Published: September 2022

Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are a rare and deadly sarcoma with few therapeutic options that are the leading cause of death for patients with Neurofibromatosis Type 1 (NF1). MPNSTs are characterized by a large burden of genomic alterations, chemoresistance, and a 5-year survival rate of 25-50%. NF1 is the major negative regulator of RAS, therefore a hallmark of MPNSTs is deregulated RAS/MAPK signaling. To date, no targeted therapies have been approved for MPNST treatment, highlighting the need for an understanding of adaptive signaling mechanisms that drive resistance. The HIPPO pathway is a key regulator of organ growth and cellular differentiation and is a central driver of resistance to RAS pathway inhibition in other cancers. The key HIPPO effector, YAP1, interacts with RAS and AKT signaling pathways, creating alternate routes for resistance in multiple cancers. In our studies, we identified strong YAP activation in response to MEK and AKT inhibition in MPNST cell lines. Since YAP acts as a transcriptional co-activator through interaction with TEAD transcription factors, we proposed that targeting the Hippo pathway in MPNST will abrogate MAPK inhibitor resistance. To investigate tumor signaling responses and efficacy in vivo, we utilized 3 genomically distinct MPNST patient-derived xenograft (PDX) models. To assess drivers of MPNST resistance, we have developed a preclinical model of drug resistance that simulates clinical treatment schedules. Using a cross-over and a drug holiday design, we are able to evaluate patterns of response and resistance to resumed treatment. We observed distinctive responses to MEK and AKT inhibitors in each PDX line; however, the impact on MPNST growth was minimal with single agent treatment. Comparison of pathway activation between the “drug holiday” biopsies and the treatment endpoint, demonstrated distinct YAP and RAS (pERK) activation levels in resistant tumors. For example, strong YAP activation is observed in correlation with decreased pERK in resistant tumors. YAP activation was strongest at the invasive edge of viable tumor regions. Currently, we are evaluating the efficacy and signaling adaptations to investigate the underlying molecular mechanisms in these MPNST models. Overall, we have demonstrated the development of a clinically relevant model of MPNST resistance and a potential switch between RAS and YAP signaling that promotes resistance to MEK or AKT inhibition.
Citation Format: Lauren McGee, Curt Essenburg, Lisa Turner, Angela Hirbe, Anwesha Dey, Jason Zbieg, Carrie Graveel, Matt Steensma. YAP signaling promotes resistance to MEK and AKT inhibition in NF1-related MPNSTs [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr A018.