bluuebunny/crossref_metadata_2025_split huggingface dataset:
XPO1 expression worsens the prognosis of unfavorable DLBCL that can be effectively targeted by selinexor in the absence of mutant p53
Authors: Deng Manman , Zhang Mingzhi , Xu-Monette Zijun Y. , Pham Lan V. , Tzankov Alexandar , Visco Carlo , Fang Xiaosheng , Bhagat Govind , Zhu Feng , Dybkaer Karen , Chiu April , Tam Wayne , Zu Youli , Hsi Eric D. , Choi William W. L. , Huh Jooryung , Ponzoni Maurilio , Ferreri Andrés J. M. , Møller Michael B. , Parsons Benjamin M. , van Krieken J. Han , Piris Miguel A. , Winter Jane N. , Hagemeister Fredrick , Alinari Lapo , Li Yong , Andreeff Michael , Xu Bing , Young Ken H. 
Published: November 2020

Abstract
The XPO1 inhibitor selinexor was recently approved in relapsed/refractory DLBCL patients but only demonstrated modest anti-DLBCL efficacy, prompting us to investigate the prognostic effect of XPO1 in DLBCL patients and the rational combination therapies in high-risk DLBCL. High XPO1 expression (XPO1high) showed significant adverse prognostic impact in 544 studied DLBCL patients, especially in those with BCL2 overexpression. Therapeutic study in 30 DLBCL cell lines with various molecular and genetic background found robust cytotoxicity of selinexor, especially in cells with BCL2-rearranged (BCL2-R+) DLBCL or high-grade B-cell lymphoma with MYC/BCL2 double-hit (HGBCL-DH). However, expression of mutant (Mut) p53 significantly reduced the cytotoxicity of selinexor in overall cell lines and the BCL2-R and HGBCL-DH subsets, consistent with the favorable impact of XPO1high observed in Mut-p53-expressing patients. The therapeutic effect of selinexor in HGBCL-DH cells was significantly enhanced when combined with a BET inhibitor INCB057643, overcoming the drug resistance in Mut-p53-expressing cells. Collectively, these data suggest that XPO1 worsens the survival of DLBCL patients with unfavorable prognostic factors such as BCL2 overexpression and double-hit, in line with the higher efficacy of selinexor demonstrated in BCL2-R+ DLBCL and HGBCL-DH cell lines. Expression of Mut-p53 confers resistance to selinexor treatment, which can be overcome by combined INCB057643 treatment in HGBCL-DH cells. This study provides insight into the XPO1 significance and selinexor efficacy in DLBCL, important for developing combination therapy for relapsed/refractory DLBCL and HGBCL-DH.
Amputation rate of diabetic foot ulcer and associated factors in diabetes mellitus patients admitted to Nekemte referral hospital, western Ethiopia: prospective observational study
Authors: Bekele Firomsa , Chelkeba Legese 
Published: November 2020

AbstractBackgroundDiabetes foot ulcer is a devastating and much‐feared complication of diabetes. Diabetes foot ulcerations which developed gangrene can take weeks or months to heal and can sometimes not heal at all so that amputation for non‐traumatic causes is a frequent outcome in the diabetic foot. Despite this, there is no finding on predictors of the amputation rate of diabetes foot ulcers in Ethiopia. Hence this study was aimed to identify factors associated with the amputation rate of diabetes foot ulcer patients in Nekemte referral hospital.Patients and methodsA prospective observational study was conducted among adult diabetes foot ulcer patients admitted to Nekemte referral hospital from March 15 to June 15, 2018. A pus swab was obtained from the ulcers before any ulcer cleaning to conduct gram staining. The primary outcome was the amputation rate. Cox regression analysis was used to estimate the hazard ratios and time from study entry to healing was evaluated as censored event times by Kaplan‐Meier curves.ResultOver the study period, 115 diabetes foot ulcer patients were admitted to the NRH; of these patients, 64(55.65%) were males while the mean age of participants was 44.4 ± 14.7. A total of 34(29.57%) of the diabetes foot ulcer were overweight and 16(13.91%) were obese while the mean ± standard deviation of body mass index (BMI) was 24.94 ± 3.69 kg/m2 and a total of 56(48.69%) diabetic foot ulcer had a diabetic complication.Of patients with diabetic foot ulcer, 35(30.43%) were undergone lower extremity amputations (LEA). Patients who were prescribed with inappropriate antibiotics were unlikely to heal. A total of 18(46.15%) of the patients who were taken inappropriate antibiotics were healed whereas 21(53.85%) were not healed (P = 0.017). Besides, the higher the Wagner grade, the worse the outcome of healing. A total of 19(21.84%) and 16(57.14%) of patients with grade < 4 and grade ≥ 4, respectively, did not heal (P = 0.005).ConclusionThe amputation rate of diabetes foot ulcers was rapid for patients prescribed inappropriate antibiotics and higher grades of the foot ulcer. Therefore, the presence of clinical pharmacists plays a pivotal role to promote the appropriate use of antibiotics and besides the daily care, special attention should be given for patients having an advanced grade of diabetes foot ulcer.
Molecular detection of Dirofilaria spp. and host blood-meal identification in the Simulium turgaicum complex (Diptera: Simuliidae) in the Aras River Basin, northwestern Iran
Authors: Khanzadeh Fariba , Khaghaninia Samad , Maleki-Ravasan Naseh , Koosha Mona , Oshaghi Mohammad Ali 
Published: November 2020

AbstractBackgroundBlackflies (Diptera: Simuliidae) are known as effective vectors of human and animal pathogens, worldwide. We have already indicated that some individuals in theSimulium turgaicumcomplex are annoying pests of humans and livestock in the Aras River Basin, Iran. However, there is no evidence of host preference and their possible vectorial role in the region. This study was conducted to capture theS. turgaicum(s.l.), to identify their host blood-meals, and to examine their potential involvement in the circulation of zoonotic microfilariae in the study areas.MethodsAdult blackflies of theS. turgaicumcomplex were bimonthly trapped with insect net in four ecotopes (humans/animals outdoors, irrigation canals, lands along the river, as well as rice and alfalfa farms) of ten villages (Gholibaiglou, Gungormaz, Hamrahlou, Hasanlou, Khetay, Khomarlou, Larijan, Mohammad Salehlou, Parvizkhanlou and Qarloujeh) of the Aras River Basin. A highly sensitive and specific nested PCR assay was used for detection of filarial nematodes inS. turgaicum(s.l.), using nuclear18SrDNA-ITS1 markers. The sources of blood meals of engorged specimens were determined using multiplex and conventionalcytbPCR assays.ResultsA total of 2754 females ofS. turgaicum(s.l.) were collected. The DNA of filarial parasites was detected in 6 (0.62%) of 960 randomly examined individuals. Sequence analysis of 420 base pairs of18SrDNA-ITS1 genes identifiedDirofilariaspp. including 5D. immitisand 1D. repens. Importantly, all filarial positive specimens have been captured from humans and animals outdoors.Cytb-PCR assays showed that in all ecotypes studied, members of theS. turgaicumcomplex had preferably fed on humans, dogs, bovids, and birds, respectively.ConclusionsTo the best of our knowledge, this is the first report ofD. immitis/D. repensdetection in blackflies. Results showed thatS. turgaicum(s.l.) was the most abundant (97%) and anthropophilic (45%) blackfly in all studied ecotypes/villages and that DNA ofDirofilariaspp. was detected in the flies taken from six villages. Dirofilariasis is a common zoonosis between humans and carnivores, with mosquitoes (Culicidae) as the principal vectors. Further investigations are needed to demonstrate that blackflies are actual vectors ofDirofilariain the studied region.
Human umbilical cord mesenchymal stem cells restore the ovarian metabolome and rescue premature ovarian insufficiency in mice
Authors: Zhao Yan , Ma Jiao , Yi Peiye , Wu Jun , Zhao Feiyan , Tu Wan , Liu Wenjing , Li Tianda , Deng Yan , Hao Jie , Wang Hongmei , Yan Long 
Published: November 2020

Abstract

Background
Premature ovarian insufficiency (POI) is an ovarian dysfunction that seriously affects a woman’s physiological health and reproduction. Mesenchymal stem cell (MSC) transplantation offers a promising treatment option for ovarian restoration in rodent POI models. However, the efficacy and mechanism of it remain unclear.

Methods
POI mice model was generated by cyclophosphamide and busulfan, followed with the treatment of tail-vein injection of the human umbilical cord mesenchymal stem cells (hUCMSCs). Maternal physiological changes and offspring behavior were detected. To reveal the pathogenesis and therapeutic mechanisms of POI, we first compared the metabolite profiles of healthy and POI ovarian tissues using untargeted metabolomics analyses. After stem cell therapy, we then collected the ovaries from control, POI, and hUCMSC-treated POI groups for lipid metabolomics and pseudotargeted metabolomics analysis.

Results
Our results revealed remarkable changes of multiple metabolites, especially lipids, in ovarian tissues after POI generation. Following the transplantation of clinical-grade hUCMSCs, POI mice exhibited significant improvements in body weight, sex hormone levels, estrous cycles, and reproductive capacity. Lipid metabolomics and pseudotargeted metabolomics analyses for the ovaries showed that the metabolite levels in the POI group, mainly lipids, glycerophospholipids, steroids, and amino acids changed significantly compared with the controls’, and most of them returned to near-healthy levels after receiving hUCMSC treatment. Meanwhile, we also observed an increase of monosaccharide levels in the ovaries from POI mice and a decrease after stem cell treatment.

Conclusions
hUCMSCs restore ovarian function through activating the PI3K pathway by promoting the level of free amino acids, consequently improving lipid metabolism and reducing the concentration of monosaccharides. These findings provide potential targets for the clinical diagnosis and treatment of POI.
Too sweet: cheminformatics for deglycosylation in natural products
Authors: Schaub Jonas , Zielesny Achim , Steinbeck Christoph , Sorokina Maria 
Published: November 2020

AbstractSugar units in natural products are pharmacokinetically important but often redundant and therefore obstructing the study of the structure and function of the aglycon. Therefore, it is recommended to remove the sugars before a theoretical or experimental study of a molecule. Deglycogenases, enzymes that specialized in sugar removal from small molecules, are often used in laboratories to perform this task. However, there is no standardized computational procedure to perform this task in silico. In this work, we present a systematic approach for in silico removal of ring and linear sugars from molecular structures. Particular attention is given to molecules of biological origin and to their structural specificities. This approach is made available in two forms, through a free and open web application and as standalone open-source software.
Multi-task offloading scheme for UAV-enabled fog computing networks
Authors: Li Xujie , Zhou Lingjie , Sun Ying , Ulziinyam Buyankhishig 
Published: November 2020

AbstractIn unmanned aerial vehicle (UAV)-enabled fog computing networks, how to efficiently offload multiple tasks to the computing nodes is a challenging combinatorial optimization problem. In this paper, in order to optimize the total delay for the UAV-enabled fog computing networks, a simple scheduling algorithm and a multi-task offloading scheme based on fireworks algorithm (FWA) are proposed. First, the system model of multiple tasks offloading in UAV-enabled fog computing networks is described in detail. Then, a simple scheduling algorithm is proposed to optimize the delay of the tasks allocated to a single node. Based on the scheduling algorithm, a multi-task offloading scheme for all tasks and all computing nodes is presented. Finally, simulation results show that the performance of a proposed scheduling algorithm and offloading strategy outperforms than that of a genetic algorithm and a random algorithm. This result can provide an effective optimization for multi-task offloading in UAV-enabled fog computing networks.
Analgesic medicines for adults with low back pain: protocol for a systematic review and network meta-analysis
Authors:   The ANiMALIA investigators, Wewege Michael A. , Bagg Matthew K. , Jones Matthew D. , McAuley James H. 
Published: November 2020

AbstractBackgroundThere is limited evidence for the comparative effectiveness of analgesic medicines for adults with low back pain. This systematic review and network meta-analysis aims to determine the analgesic effect, safety, acceptability, effect on function, and relative rank according to analgesic effect, safety, acceptability, and effect on function of a single course of [an] analgesic medicine(s) or combination of these medicines for people with low back pain.MethodsWe will include published and unpublished randomised trials written in any language that compare an analgesic medicine to either another medicine, placebo/sham, or no intervention in adults with low back pain, grouped according to pain duration: acute (fewer than 6 weeks), sub-acute (6 to 12 weeks), and chronic (greater than 12 weeks). The co-primary outcomes are pain intensity following treatment and safety (adverse events). The secondary outcomes are function and acceptability (all-cause dropouts). We will perform a network meta-analysis to compare and rank analgesic medicines. We will form judgements of confidence in the results using the Confidence in Network Meta-Analysis (CINeMA) methodology.DiscussionThis network meta-analysis will establish which medicine, or combination of medicines, is most effective for reducing pain and safest for adults with low back pain.Systematic review registrationPROSPERO CRD42019145257
Guidance for overviews of reviews continues to accumulate, but important challenges remain: a scoping review
Authors: Gates Michelle , Gates Allison , Guitard Samantha , Pollock Michelle , Hartling Lisa 
Published: November 2020

Abstract

Background
Overviews of reviews (overviews) provide an invaluable resource for healthcare decision-making by combining large volumes of systematic review (SR) data into a single synthesis. The production of high-quality overviews hinges on the availability of practical evidence-based guidance for conduct and reporting.

Objectives
Within the broad purpose of informing the development of a reporting guideline for overviews, we aimed to provide an up-to-date map of existing guidance related to the conduct of overviews, and to identify common challenges that authors face when undertaking overviews.

Methods
We updated a scoping review published in 2016 using the search methods that had produced the highest yield: ongoing reference tracking (2014 to March 2020 in PubMed, Scopus, and Google Scholar), hand-searching conference proceedings and websites, and contacting authors of published overviews. Using a qualitative meta-summary approach, one reviewer extracted, organized, and summarized the guidance and challenges presented within the included documents. A second reviewer verified the data and synthesis.

Results
We located 28 new guidance documents, for a total of 77 documents produced by 34 research groups. The new guidance helps to resolve some earlier identified challenges in the production of overviews. Important developments include strengthened guidance on handling primary study overlap at the study selection and analysis stages. Despite marked progress, several areas continue to be hampered by inconsistent or lacking guidance. There is ongoing debate about whether, when, and how supplemental primary studies should be included in overviews. Guidance remains scant on how to extract and use appraisals of quality of the primary studies within the included SRs and how to adapt GRADE methodology to overviews. The challenges that overview authors face are often related to the above-described steps in the process where evidence-based guidance is lacking or conflicting.

Conclusion
The rising popularity of overviews has been accompanied by a steady accumulation of new, and sometimes conflicting, guidance. While recent guidance has helped to address some of the challenges that overview authors face, areas of uncertainty remain. Practical tools supported by empirical evidence are needed to assist authors with the many methodological decision points that are encountered in the production of overviews.
A QuESt for speed: rapid qualitative evidence syntheses as a response to the COVID-19 pandemic
Authors: Biesty Linda , Meskell Pauline , Glenton Claire , Delaney Hannah , Smalle Mike , Booth Andrew , Chan Xin Hui S. , Devane Declan , Houghton Catherine 
Published: November 2020

Abstract

Background
The COVID-19 pandemic has created a sense of urgency in the research community in their bid to contribute to the evidence required for healthcare policy decisions. With such urgency, researchers experience methodological challenges to maintain the rigour and transparency of their work. With this in mind, we offer reflections on our recent experience of undertaking a rapid Cochrane qualitative evidence synthesis (QES).

Methods
This process paper, using a reflexive approach, describes a rapid QES prepared during, and in response to, the COVID-19 pandemic.

Findings
This paper reports the methodological decisions we made and the process we undertook. We place our decisions in the context of guidance offered in relation to rapid reviews and previously conducted QESs. We highlight some of the challenges we encountered in finding the balance between the time needed for thoughtfulness and comprehensiveness whilst providing a rapid response to an urgent request for evidence.

Conclusion
The need for more guidance on rapid QES remains, but such guidance needs to be based on actual worked examples and case studies. This paper and the reflections offered may provide a useful framework for others to use and further develop.
A meta-analysis of the impact of COVID-19 on liver dysfunction
Authors: Wu Zeng-hong , Yang Dong‑liang 
Published: November 2020

Abstract
Background
The novel coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to a worldwide pandemic. Except representative manifestation of pneumonia and acute respiratory symptoms, COVID-19 patients have also shown different levels of liver injury or liver dysfunction. The aim of our study was to explore the probable clinical severity and mortality of COVID-19 patients and their liver dysfunction.

Method
A combination of computer and manual retrieval was used to search in Medline through PubMed, EMBASE and Web of Science. Review Manager 5.3 software was used to examine the heterogeneity among the studies and to calculate the combined effect value (OR, 95CI). Subgroup analysis, sensitivity analysis, and publication bias test were also performed.

Results
We found a significant connection between liver dysfunction and mortality of COVID-19 patients with a pooled OR of 1.98 (95% CI 1.39–2.82; P = 0.0002). There was a significant association between AST and severity of COVID-19 with a pooled OR of 4.48 (95% CI 3.24–7.21; P < 0.001), and a pooled WMD of 3.35 (95% CI, 2.07 to 4.64; P < 0.001). In addition, there was a significant difference between TBIL and severity of COVID-19, with a pooled OR of 1.91 (95% CI 1.40–2.60; P < 0.001), and with a pooled WMD of 1.18 (95% CI, 0.78 to 1.58; P < 0.001).

Conclusion
The mortality and severity of COVID-19 patients are significantly associated with liver dysfunction. The non-survivors and severe COVID-19 patients have elevated serum AST levels than the survivors and non-severe COVID-19 patients. The results of this study form a basis for better clinical liver management of patients with COVID-19.
A framework for estimating crime location choice based on awareness space
Authors: Curtis-Ham Sophie , Bernasco Wim , Medvedev Oleg N. , Polaschek Devon 
Published: November 2020

AbstractThis paper extends Crime Pattern Theory, proposing a theoretical framework which aims to explain how offenders’ previous routine activity locations influence their future offence locations. The framework draws on studies of individual level crime location choice and location choice in non-criminal contexts, to identify attributes of prior activities associated with the selection of the location for future crime. We group these attributes into two proposed mechanisms: reliability and relevance. Offenders are more likely to commit crime where they have reliable knowledge that is relevant to the particular crime. The perceived reliability of offenders’ knowledge about a potential crime location is affected by the frequency, recency and duration of their prior activities in that location. Relevance reflects knowledge of a potential crime location’s crime opportunities and is affected by the type of behaviour, type of location and timing of prior activities in that location. We apply the framework to generate testable hypotheses to guide future studies of crime location choice and suggest directions for further theoretical and empirical work. Understanding crime location choice using this framework could also help inform policing investigations and crime prevention strategies.
Probing time-dependent afterslip and viscoelastic relaxation following the 2015 Mw7.8 Gorkha earthquake based on the 3-D finite-element model
Authors: Su Lina , Shi Fuqiang , Gan Weijun , Su Xiaoning , Yan Junyi 
Published: November 2020

AbstractWe analyzed daily displacement time series from 34 continuous GPS stations in Nepal and 5 continuous GPS stations in South Tibet, China, and extracted the first 4.8 years of postseismic motion after the 2015 Mw7.8 Gorkha earthquake. With the longer duration GPS observations, we find that postseismic displacements mainly exhibit southward and uplift motion. To study the postseismic afterslip and viscoelastic relaxation, we built a 3-D spherical finite-element model (FEM) with heterogeneous material properties and surface topography across the Himalayan range, accounting for the strong variations in material properties and surface elevation along the central Himalayan arc. On the basis of the FEM, we reveal that the predicted viscoelastic relaxation of cm level moves southward to the north of the Gorkha earthquake rupture, but in an opposite direction to the observed postseismic deformation in the south; the postseismic deformation excluding viscoelastic relaxation is well explained by afterslip downdip of the coseismic rupture. The afterslip is dominant during 4.8 years after the 2015 Mw7.8 Gorkha earthquake; the contribution by the viscoelastic relaxation gradually increases slightly. The lack of slip on a shallow portion and western segment of the MHT during and after the 2015 Gorkha earthquake implies continued seismic hazard in the future.