bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRImary care Management of lower Urinary tract Symptoms in men: protocol for development and validation of a diagnostic and clinical decision support tool (the PriMUS study)
Authors: Pell Bethan , Thomas-Jones Emma , Bray Alison , Agarwal Ridhi , Ahmed Haroon , Allen A Joy , Clarke Samantha , Deeks Jonathan J , Drake Marcus , Drinnan Michael , Dyer Calie , Hood Kerenza , Joseph-Williams Natalie , Marsh Lucy , Milosevic Sarah , Pickard Robert , Schatzberger Tom , Takwoingi Yemisi , Harding Chris , Edwards Adrian 
Published: June 2020

IntroductionLower urinary tract symptoms (LUTS) is a bothersome condition affecting older men which can lead to poor quality of life. General practitioners (GPs) currently have no easily available assessment tools to help effectively diagnose causes of LUTS and aid discussion of treatment with patients. Men are frequently referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinician decision tools are needed to facilitate accurate and effective patient management of LUTS in primary care.Methods and analysisPRImary care Management of lower Urinary tract Symptoms (PriMUS) is a prospective diagnostic accuracy study based in primary care. The study will determine which of a number of index tests used in combination best predict three urodynamic observations in men who present to their GP with LUTS. These are detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity. Two cohorts of participants, one for development of the prototype diagnostic tool and other for validation, will undergo a series of simple index tests and the invasive reference standard (invasive urodynamics). We will develop and validate three diagnostic prediction models based on each condition and then combine them with management recommendations to form a clinical decision support tool.Ethics and disseminationEthics approval is from the Wales Research Ethics Committee 6. Findings will be disseminated through peer-reviewed journals and conferences, and results will be of interest to professional and patient stakeholders.Trial registration numberISRCTN10327305.
Associations between multimorbidity and adverse clinical outcomes in patients with chronic kidney disease: a systematic review and meta-analysis
Authors: Sullivan Michael K. , Rankin Alastair J. , Jani Bhautesh D. , Mair Frances S. , Mark Patrick B. 
Published: June 2020

ObjectiveTo systematically review the literature exploring the associations between multimorbidity (the presence of two or more long-term conditions (LTCs)) and adverse clinical outcomes in patients with chronic kidney disease (CKD).DesignSystematic review and meta-analysis.Data sourcesMEDLINE, EMBASE, CINAHL, Cochrane Library and SCOPUS (1946–2019). The main search terms were ‘Chronic Kidney Failure’ and ‘Multimorbid*’.Eligibility criteriaObservational studies of adults over the age of 18 with CKD stages 3–5, that is, estimated glomerular filtration rate less than 60 mL/min/1.73 m2. The exposure was multimorbidity quantified by measures and the outcomes were all-cause mortality, renal progression, hospitalisation and cardiovascular events. We did not consider CKD as a comorbid LTC.Data extraction and synthesisNewcastle-Ottawa Scale for quality appraisal and risk of bias assessment and fixed effects meta-analysis for data synthesis.ResultsOf 1852 papers identified, 26 met the inclusion criteria. 21 papers involved patients with advanced CKD and no studies were from low or middle-income countries. All-cause mortality was an outcome in all studies. Patients with multimorbidity were at higher risk of mortality compared with patients without multimorbidity (total risk ratio 2.28 (95% CI 1.81 to 2.88)). The risk of mortality was higher with increasing multimorbidity (total HR 1.31 (95% CI 1.27 to 1.36)) and both concordant and discordant LTCs were associated with heightened risk. Multimorbidity was associated with renal progression in four studies, hospitalisation in five studies and cardiovascular events in two studies.LimitationsMeta-analysis could only include 10 of 26 papers as the methodologies of studies were heterogeneous.ConclusionsThere are associations between multimorbidity and adverse clinical outcomes in patients with CKD. However, most data relate to mortality risk in patients with advanced CKD. There is limited evidence regarding patients with mild to moderate CKD, outcomes such as cardiovascular events, types of LTCs and regarding patients from low or middle-income countries.PROSPERO registration numberCRD42019147424.
Efficacy of antiepileptic drugs in neonatal seizures: a systematic review protocol
Authors: He Yang , Tang Jun , Zhang Meng , Xiong Tao , Ojha Shalini , Choonara Imti , Mu Dezhi 
Published: June 2020

IntroductionSeizures are one of the most common neurological disorders of neonates, which is also an emergency in the neonatal intensive care unit. For neonates, the recommended first-line antiepileptic drugs (AEDs) include phenobarbitone, which may be effective in only 50% of seizures. Some new AEDs, such as levetiracetam, have been shown to be effective in adults and older children. However, their efficacy for neonatal seizures remains uncertain. The aim of this investigation is to conduct a systematic review to evaluate the efficacy of all AEDs in neonates. Additionally, the long-term outcomes following neonatal seizures, in relation to the development of cerebral palsy and epilepsy, will be studied.MethodWe will perform a systematic review including randomised controlled studies (RCTs), cohort studies, case-controlled studies and case series studies which evaluated the efficacy of AEDs and short-term and long-term outcomes in neonatal seizures. PubMed, Embase, Web of Science, Cochrane Library and Clinical trial.gov will be searched. There will be no language restriction. Risk bias in RCTs will be evaluated by the Cochrane risk-of-bias tool, while cohort and case-control studies will be evaluated by the Newcastle-Ottawa Scale. A network meta-analysis will be performed by the Bayesian model using WinBUGS V.1.4.3 and R software if there is a high degree of homogeneity among studies. Otherwise, we will perform a narrative review without pooling. Subgroup analyses will be performed in different AEDs and dosage groups.OutcomeThe primary outcomes will be seizure cessation confirmed by electroencephalogram and long-term neurodevelopmental outcome. Secondary outcomes will be neonatal mortality during hospitalisation and suspected drug toxicity.Ethics and disseminationFormal ethical approval is not required as no primary data are collected. This systematic review will be disseminated through a peer-reviewed publication.
CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancer
Authors: Huang Bing , Liu Rong , Wang Peiliang , Yuan Zhiwei , Yang Jianjian , Xiong Hui , Zhang Ni , Huang Qi , Fu Xiangning , Sun Wei , Li Lequn 
Published: June 2020

BackgroundThe repetitive antigen stimulation during chronic infection often leads to the accumulation of CD8+CD57+ T cells. These cells express high levels of interferon-γ, granzyme B and perforin with elevated cytolytic effect, and are considered as the most potent cells for combating chronical viral infection. The status of CD8+CD57+ T cells in non-small cell lung cancer (NSCLC) has not been well defined.MethodsWe used flow cytometry and undertook a systemic approach to examine the frequency, immunophenotyping and functional properties of CD8+CD57+ T cells in the peripheral blood, tumor tissue and the corresponding normal tissue, as well as lung draining lymph nodes, of patients with NSCLC.ResultsCD57+ T cells expressed high levels of programmed cell death-1 (PD-1) in all tested compartments and were predominantly CD8+ T cells. These cells in the peripheral blood displayed a terminally differentiated phenotype as defined by loss of CD27 and CD28 while expressing KLRG1. CD8+CD57+ T cells exhibited enhanced cytotoxic potencies and impaired proliferative capability. Unlike CD57+ T cells in the peripheral blood, a significant proportion of CD57+ T cells in the primary tumors expressed CD27 and CD28. CD8+CD57+ T cells in tumors lacked cytotoxic activity. The proliferative activity of these cells was also impaired. CD8+CD57+ T cells in the corresponding normal lung tissues shared similarities with their counterparts in peripheral blood rather than their counterparts in tumors. The vast majority of CD8+CD57+ T cells in lung draining lymph nodes were positive for CD27 and CD28. These cells were unable to produce perforin and granzyme B, but their proliferative activity was preserved. CD8+CD57+ T cells in tumors displayed an inferior response to PD-1 blockade compared with their CD8+CD57- counterparts. Interleukin (IL)-15 preferentially restored the effector function of these cells. Additionally, IL-15 was able to restore the impaired proliferative activity of CD8+CD57+ T cells in tumors and peripheral blood.ConclusionsOur data indicate that the failure of the immune system to fight cancer progression could be a result of impaired CD8+ T-cell functional maturation into fully differentiated effector T cells within the tumor microenvironment. Boosting IL-15 activity might promote tumor-reactive CD8+ T-cell functional maturation while preserving their proliferative activity.
Dialogue on a superconducting laser operating via nonequilibrium inversed population
Authors: Gulian Armen , Dulal Rajendra , Teknowijoyo Serafim , Chahid Sara 
Published: June 2020

In nonequilibrium states, the entropy is reduced from its maximum thermodynamic equilibrium value by virtue of an external energy supply. Such states are characterized by a higher ordering compared to the equilibrium. Human beings represent the highest level of nonequilibrium state, at least in the known part of the Universe. Other physical systems are also well-known, for example, quantum generators, e.g., lasers. Their operation requires a high level of deviation from equilibrium called inverse population. In turn, states out of equilibrium require energy influx for their maintenance, i.e., they should be open systems. In this short review we describe in the form of dialogue between Prof. A. M. Gulian and his younger colleagues Dr. Rajendra Dulal, Dr. Serafim Teknowijoyo and Dr. Sara Chahid the task of achieving inverse population in superconductors. Then, the dialogue moves towards experimental consequences that nonequilibrium superconductors can yield. These include topics related with deeper understanding of mechanisms of superconductivity in novel materials, in particular related to the “glue” which pairs electrons in Cooper pairs. Such understanding will facilitate development of Bose-field quantum generators like lasers, and coherent acoustic as well as paramagnon quantum sources, none of which are yet realized in nonequilibrium superconductors.
Leukemia Cell of Origin Influences Apoptotic Priming and Sensitivity to LSD1 Inhibition
Authors: Cai Sheng F. , Chu S. Haihua , Goldberg Aaron D. , Parvin Salma , Koche Richard P. , Glass Jacob L. , Stein Eytan M. , Tallman Martin S. , Sen Filiz , Famulare Christopher A. , Cusan Monica , Huang Chun-Hao , Chen Chun-Wei , Zou Lihua , Cordner Keith B. , DelGaudio Nicole L. , Durani Vidushi , Kini Mitali , Rex Madison , Tian Helen S. , Zuber Johannes , Baslan Timour , Lowe Scott W. , Rienhoff Hugh Y. , Letai Anthony , Levine Ross L. , Armstrong Scott A. 
Published: June 2020

Abstract

The cell of origin of oncogenic transformation is a determinant of therapeutic sensitivity, but the mechanisms governing cell-of-origin–driven differences in therapeutic response have not been delineated. Leukemias initiating in hematopoietic stem cells (HSC) are less sensitive to chemotherapy and highly express the transcription factor MECOM (EVI1) compared with leukemias derived from myeloid progenitors. Here, we compared leukemias initiated in either HSCs or myeloid progenitors to reveal a novel function for EVI1 in modulating p53 protein abundance and activity. HSC-derived leukemias exhibit decreased apoptotic priming, attenuated p53 transcriptional output, and resistance to lysine-specific demethylase 1 (LSD1) inhibitors in addition to classical genotoxic stresses. p53 loss of function in Evi1lo progenitor-derived leukemias induces resistance to LSD1 inhibition, and EVI1hi leukemias are sensitized to LSD1 inhibition by venetoclax. Our findings demonstrate a role for EVI1 in p53 wild-type cancers in reducing p53 function and provide a strategy to circumvent drug resistance in chemoresistant EVI1hi acute myeloid leukemia.

Significance:
We demonstrate that the cell of origin of leukemia initiation influences p53 activity and dictates therapeutic sensitivity to pharmacologic LSD1 inhibitors via the transcription factor EVI1. We show that drug resistance could be overcome in HSC-derived leukemias by combining LSD1 inhibition with venetoclax.
See related commentary by Gu et al., p. 1445.
This article is highlighted in the In This Issue feature, p. 1426
The Significance of Staging in the Treatment of Congenital Cholesteatoma in Children
Authors: Hao Jinsheng , Chen Min , Liu Bing , Yang Yang , Liu Wei , Zhang Jie , Ni Xin 
Published: June 2020

Objectives: To analyze the clinical characteristics of congenital cholesteatoma (CC), to explore the risk factors related to recurrence of the disease, and to clarify the importance of staging for treatment. Methods: A total of 87 patients were followed up for more than 5 years, who had undergone surgical procedures for CC from September 2010 to January 2017 in Beijing Children’s Hospital, Capital Medical University. Patients with CC were identified in accordance with the following Levenson’s criteria. The clinical characteristics of CC on different stage and risk factors related to recurrence of the disease were analyzed. Results: Canal wall up mastoidectomy and tympanoplasty (n = 45), transcanal endoscopic approach (n = 29), and canal wall down mastoidectomy and tympanoplasty (n = 13) was, respectively, performed depending on cholesteatoma extension. Between 2010 and 2013, 20.93% of patients had stage I-II disease, whereas 61.26% had stage I-II disease from 2014 to 2017. Meanwhile, the proportion with stage III-IV disease decreased from 79.07% to 38.64% between these 2 time periods. The preoperative air conduction threshold in patients with stage I, II, III, and IV was, respectively, 23.36 ± 8.20, 45.40 ± 12.82, 47.49 ± 12.03, and 50.37 ± 11.80 dB. The stage of disease was a significant risk factor regarding recurrence ( P = .02). Surgery on patients with stage III-IV disease was performed with the aid of a microscope from 2010 to 2013 and with a microscope and endoscope from 2014 to 2017, which reduced the recurrence rate from 26.92% in the former period to 8.33% in the latter period. Conclusion: Early detection of CC is crucial regarding the facilitation of minimally invasive surgery and reducing complication and recurrence rates. The stage of the disease is a significant risk factor regarding recurrence. The surgery shows us the possibility of reducing the recurrence rate of CC, which is performed under a microscope and an endoscope.
Glycoprotein Nonmetastatic Melanoma Protein B as Potential Imaging Marker in Posttherapeutic Metastatic Head and Neck Cancer
Authors: van Schaik Jeroen E. , Hanemaaijer Saskia H. , Halmos György B. , Witjes Max J. H. , van der Laan Bernard F. A. M. , van der Vegt Bert , Plaat Boudewijn E. C. 
Published: June 2020

ObjectiveTo evaluate expression of potential molecular imaging targets epidermal growth factor receptor (EGFR), glycoprotein nonmetastatic melanoma protein B (GPNMB), and vascular endothelial growth factor (VEGF) in lymph nodes (LNs) with or without head and neck squamous cell carcinoma (HNSCC) metastases after (chemo)radiation.Study DesignRetrospective study comparing receptor expression in paired lymph nodes after initial treatment.SettingA tertiary referral hospital.Subjects and MethodsSalvage neck dissection specimens of 40 patients treated with (chemo)radiation were selected. LNs that contained viable tumor, reactive changes after initial treatment, and normal LNs were analyzed using immunohistochemically determined H‐scores and by calculating sensitivity and specificity rates and positive/negative predictive values (PPVs/NPVs).ResultsEGFR expression was found in 86% and GPNMB expression in 100% of the LNs with viable tumor. VEGF expression was present in all lymph node types. For EGFR, the sensitivity rate was 86%, and specificity rate was 81%. For GPNMB, these were 100% and 75%, respectively. PPV of EGFR was 61.8% and NPV was 98.2%. These were 56.4% and 100% for GPNMB, respectively.ConclusionIn residual or recurrent HNSCC lymph node metastases, both EGFR and GPNMB show tumor‐specific expression in immunohistochemistry, which may prove useful in future molecular imaging in salvage neck dissections. Immunohistochemically detected VEGF expression indicates that this target is not feasible for imaging purposes in salvage surgery. Therefore, GPNMB could be a new potential imaging target showing comparable results to EGFR in immunohistochemistry.
Effect of Bumetanide on Facial Nerve Regeneration in Rat Model
Authors: Longur Ecem Sevim , Yiğit Özgür , Kalaycık Ertugay Çiğdem , Araz Server Ela , Adatepe Turgut , Akakın Dilek , Orun Oya , Karagöz Köroğlu Ayça 
Published: June 2020

ObjectiveWe investigated the effects of bumetanide alone and in combination with dexamethasone on facial nerve regeneration in rats with facial paralysis.Study DesignA prospective controlled animal study.SettingAn animal laboratory.Subjects and MethodsFacial paralysis was induced in 32 Wistar rats that we then divided into 4 groups: group 1, control; group 2, bumetanide; group 3, dexamethasone; group 4, bumetanide and dexamethasone. Electroneurography was performed 1, 2, and 4 weeks later, and nerve regeneration was evaluated by electron and light microscopy and Western blotting in week 4.ResultsRegarding the comparison between preoperative values and week 4, the latency difference in group 1 (1.25 milliseconds) was significantly higher than those of groups 2 to 4 (0.56, 0.34, and 0.10 milliseconds, respectively; P =. 001). The latency increment in groups 2 and 3 was higher than that of group 4 (P =. 002 and P =. 046) in week 4, whereas groups 2 and 3 did not differ significantly (P =. 291). Amplitude difference was not statistically significant from week 4 among all groups (all P >. 05). The number of myelinated axons was significantly higher in all treatment groups than in the control group (P =. 001). Axon number and intensity were significantly higher in group 4 as compared with groups 2 and 3 (P =. 009, P =. 005).ConclusionAfter primary neurorrhaphy, dexamethasone and bumetanide alone promoted nerve recovery based on electrophysiologic and histologic measures. Combination therapy was, however, superior.
In Vivo Accuracy of Ultrasound for Sizing Salivary Ductal Calculi
Authors: Badger Christopher D. , Patel Sahil , Romero Nahir J. , Fuson Andrew , Joshi Arjun S. 
Published: June 2020

ObjectivesThe present study was developed to evaluate the accuracy of in vivo ultrasound sizing for parotid and submandibular salivary gland calculi, as compared with ex vivo pathology sizing with a standard plastic ruler after extraction.Study DesignRetrospective chart review.SettingUltrasound is frequently used to size salivary calculi and make treatment decisions, but the accuracy of measurements from this modality has not been validated.Subjects and MethodsWe evaluated and reviewed the charts and ultrasound examinations of 167 patients who underwent procedures for the treatment of sialolithiasis involving the parotid and submandibular glands. US examinations were performed between 2009 and 2016 in a tertiary‐level hospital setting by the senior author. Measurements were collected from ultrasound evaluation before sialolithotomy, and pathology measurements were taken after removal. Ultrasound measurements in millimeters were compared with the measurements collected with a ruler. The differences were calculated and compared.ResultsA total of 167 calculi measurements were compared. Good concurrent validity between pathology and ultrasound measurements was suggested by a Pearson correlation of 0.92 (95% CI, 0.887‐0.937). On Bland‐Altman plot, correlation of the difference between US and pathology measurements showed a mean difference of 0.095 mm (95% CI, –0.19 to 0.38 mm) with a limit of agreement ranging from –3.59 mm (95% CI, –3.84 to –3.34 mm) to +3.78 mm (95% CI, +3.53 to +4.03 mm).ConclusionsUltrasound is an accurate, relatively precise, and minimally invasive imaging tool for salivary gland sialolithiasis. Preoperative size of calculi can be used to guide management and clinical decision making.Level of Evidence2C.
Efficacy of an innovative smartphone application for office workers with chronic non-specific low back pain: a pilot randomized controlled trial
Authors: Almhdawi Khader A , Obeidat Donia Saleh , Kanaan Saddam F , Oteir Alaa O , Mansour Zaid Modhi , Alrabbaei Hassan 
Published: June 2020

Objective: To evaluate the efficacy of a newly developed evidence-based low back pain (LBP) management smartphone application. Design: A double-blinded randomized controlled trial where participants randomly assigned to either an experimental group (EG) or a control group (CG). Setting: Governmental and private institutions. Participants: About 40 office workers, aged 30 to 55 years, had pain due to non-specific LBP > 3 on Visual Analogue Scale, and with pain chronicity > 3 months. Interventions: The EG received full version of the application ‘Relieve my back’ included evidence-based instructions and therapeutic exercises for LBP management, whereas the CG received placebo version included instructions about nutrition. Main measures: Primary outcome measures included pain measured by Visual Analogue Scale (VAS), disability measured by Oswestry Disability Index (ODI), and quality of life measured by Short-Form Health Survey (SF-12). Results: Following six weeks of using the application, compared to CG, the EG group demonstrated significant decrease in pain intensity (−3.45 (2.21) vs −0.11 (1.66), P < 0.001), in ODI score (−11.05 (10.40) vs −0.58 (9.0), P = 0.002), and significant increase in physical component of SF-12 (12.85 (17.20) vs −4.63 (12.04), P = 0.001). Conclusion: ‘Relieve my back’ application might be efficacious in reducing pain and disability and improving the quality of life of office workers with non-specific LBP.