bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary factors and diabetes-related health outcomes in patients with type 2 diabetes: protocol for a systematic review and meta-analysis of prospective observational studies
Authors: Barbaresko Janett , Neuenschwander Manuela , Schwingshackl Lukas , Schlesinger Sabrina 
Published: July 2019

IntroductionType 2 diabetes (T2D) is a major health concern associated with several comorbidities such as diabetic chronic kidney disease, neuropathy and cardiovascular diseases. Many of these complications may be preventable by an adequate lifestyle, including a favourable dietary behaviour, additionally to pharmacological management. In general, dietary guidelines for patients with diabetes recommend a hypocaloric diet to achieve a normal weight, but there is a lack of detailed instructions on specific nutrients and foods to prevent diabetes-related outcomes. Therefore, the aim of this systematic review and meta-analysis is to summarise the available evidence on the association between dietary factors and health-related outcomes in patients with T2D.Methods and analysisA systematic literature search will be conducted in PubMed and Web of Science in May 2019 to identify prospective observational studies investigating dietary factors in association with major complications in patients with T2D. We will include studies investigating dietary patterns, food groups, foods, macronutrients and micronutrients as well as secondary plant compounds. As diabetes-related outcomes, we will include macrovascular (cardiovascular and cerebrovascular diseases) and microvascular outcomes (nephropathy, neuropathy and retinopathy), as well as cancer, quality of life, depression, cognitive disorders and mortality. We will conduct dose-response meta-analyses using random effects models. We will investigate heterogeneity across studies and publication bias. To assess the risk of bias and quality of the included studies, we will use the Cochrane risk of bias tool ROBINS-I and the quality of evidence will be assessed using Grades of Recommendation, Assessment, Development, and Evaluation.Ethics and disseminationAs the systematic review is based on published studies, ethical considerations are not required. The systematic review and meta-analysis will be published in a peer-reviewed Journal.PROSPERO registration numberCRD42018110669
Associative stigma among mental health professionals in Singapore: a cross-sectional study
Authors: Picco Louisa , Chang Sherilyn , Abdin Edimansyah , Chua Boon Yiang , Yuan Qi , Vaingankar Janhavi Ajit , Ong Samantha , Yow Kah Lai , Chua Hong Choon , Chong Siow Ann , Subramaniam Mythily 
Published: July 2019

Objectives(1) Investigate and explore whether different classes of associative stigma (the process by which a person experiences stigmatisation as a result of an association with another stigmatised person) could be identified using latent class analysis; (2) determine the sociodemographic and employment-related correlates of associative stigma and (3) examine the relationship between associative stigma and job satisfaction, among mental health professionals.DesignCross-sectional online survey.ParticipantsDoctors, nurses and allied health staff, working in Singapore.MethodsStaff (n=462) completed an online survey, which comprised 11 associative stigma items and also captured sociodemographic and job satisfaction-related information. Latent class analysis was used to classify associative stigma on patterns of observed categorical variables. Multinomial logistic regression was used to examine associations between sociodemographic and employment-related factors and the different classes, while multiple linear regression analyses were used to examine the relationship between associative stigma and job satisfaction.ResultsThe latent class analysis revealed that items formed a three-class model where the classes were classified as ‘no/low associative stigma’, ‘moderate associative stigma’ and ‘high associative stigma’. 48.7%, 40.5% and 10.8% of the population comprised no/low, moderate and high associative stigma classes, respectively. Multinomial logistic regression showed that years of service and occupation were significantly associated with moderate associative stigma, while factors associated with high associative stigma were education, ethnicity and occupation. Multiple linear regression analyses revealed that high associative stigma was significantly associated with lower job satisfaction scores.ConclusionAssociative stigma was not uncommon among mental health professionals and was associated with sociodemographic factors and poorer job satisfaction. Associative stigma has received comparatively little attention from empirical researchers and continued efforts to address this understudied yet important construct in conjunction with future efforts to dispel misconceptions related to mental illnesses are needed.
Loss of Setd2 promotes Kras-induced acinar-to-ductal metaplasia and epithelia–mesenchymal transition during pancreatic carcinogenesis
Authors: Niu Ningning , Lu Ping , Yang Yanlin , He Ruizhe , Zhang Li , Shi Juanjuan , Wu Jinghua , Yang Minwei , Zhang Zhi-Gang , Wang Li-Wei , Gao Wei-Qiang , Habtezion Aida , Xiao Gary Guishan , Sun Yongwei , Li Li , Xue Jing 
Published: July 2019

ObjectiveSETD2, the sole histone H3K36 trimethyltransferase, is frequently mutated or deleted in human cancer, including pancreatic ductal adenocarcinoma (PDAC). However, whether SETD2/H3K36me3 alteration results in PDAC remains largely unknown.DesignTCGA(PAAD) public database and PDAC tissue array with SETD2/H3K36me3 staining were used to investigate the clinical relevance of SETD2 in PDAC. Furthermore, to define the role of SETD2 in the carcinogenesis of PDAC, we crossed conditional Setd2 knockout mice (PdxcreSetd2flox/flox) together withKrasG12Dmice. Moreover, to examine the role of SETD2 after ductal metaplasia, Crisp/cas9 was used to depleteSetd2in PDAC cells. RNA-seq and H3K36me3 ChIP-seq were performed to uncover the mechanism.ResultsSETD2 mutant/low expression was correlated with poor prognosis in patients with PDAC. Next, we found that Setd2 acted as a putative tumour suppressor in Kras-driven pancreatic carcinogenesis. Mechanistically,Setd2loss in acinar cells facilitated Kras-induced acinar-to-ductal reprogramming, mainly through epigenetic dysregulation ofFbxw7. Moreover,Setd2ablation in pancreatic cancer cells enhanced epithelia–mesenchymal transition (EMT) through impaired epigenetic regulation ofCtnna1. In addition, Setd2 deficiency led to sustained Akt activation via inherent extracellular matrix (ECM) production, which would favour their metastasis.ConclusionTogether, our findings highlight the function of SETD2 during pancreatic carcinogenesis, which would advance our understanding of epigenetic dysregulation in PDAC. Moreover, it may also pave the way for development of targeted, patients-tailored therapies for PDAC patients with SETD2 deficiency.
Is high-risk cutaneous squamous cell carcinoma of the head and neck a suitable candidate for current targeted therapies?
Authors: Zilberg Catherine , Lee Matthew Weicai , Kraitsek Spiridoula , Ashford Bruce , Ranson Marie , Shannon Kerwin , Iyer N Gopalakrishna , Ch’ng Sydney , Low Tsu-Hui (Hubert) , Palme Carsten , Clark Jonathan , Gupta Ruta , Yu Bing 
Published: July 2019

ObjectiveCutaneous squamous cell carcinoma (cSCC) is the second most common malignancy, most frequently affecting the head and neck. Treatment often requires surgery and can have significant functional morbidity. Research into disease pathogenesis and second line medical management of cSCC is limited. We assess genetic mutations in high-risk, primary head and neck cutaneous squamous cell carcinomas (HNcSCC) that may hinder or be beneficial for use of targeted therapy in disease management.MethodsGenetic alterations and variant allele frequencies (VAFs) were analysed using a clinically relevant 48 gene panel in 10 primary high-risk non-metastatic treatment-naïve HNcSCC to evaluate applicability of targeted therapeutics. Variants present at all VAFs were evaluated for pathogenicity. Somatic mutation patterns of individual tumours were analysed.ResultsHigh-risk HNcSCC showed a high proportion (82%) of C to T transitions in keeping with ultraviolet-mediated damage. There was significant intratumour genetic heterogeneity in this cohort (MATH scores 20–89) with the two patients <45 years of age showing highest intratumour heterogeneity.TP53was altered at VAF >22% in all cases, and mutations with highest VAF were observed in tumour suppressor genes in 80%. 70% of cases demonstrated at least one mutation associated with treatment resistance (KITS821F,KITT670I,RASmutations at codons 12 and 13).ConclusionWe demonstrate high proportion tumour suppressor loss of function mutations, high intratumour genetic heterogeneity, and presence of well recognised resistance mutations in treatment naïve primary HNcSCC. These factors pose challenges for successful utilisation of targeted therapies.
One in three highly selected Greek patients with breast cancer carries a loss-of-function variant in a cancer susceptibility gene
Authors: Fostira Florentia , Kostantopoulou Irene , Apostolou Paraskevi , Papamentzelopoulou Myrto S , Papadimitriou Christos , Faliakou Eleni , Christodoulou Christos , Boukovinas Ioannis , Razis Evangelia , Tryfonopoulos Dimitrios , Barbounis Vasileios , Vagena Andromache , Vlachos Ioannis S , Kalfakakou Despoina , Fountzilas George , Yannoukakos Drakoulis 
Published: July 2019

BackgroundGene panel testing has become the norm for assessing breast cancer (BC) susceptibility, but actual cancer risks conferred by genes included in panels are not established. Contrarily, deciphering the missing hereditability on BC, through identification of novel candidates, remains a challenge. We aimed to investigate the mutation prevalence and spectra in a highly selected cohort of Greek patients with BC, questioning an extensive number of genes, implicated in cancer predisposition and DNA repair, while calculating gene-specific BC risks that can ultimately lead to important associations.MethodsTo further discern BC susceptibility, a comprehensive 94-cancer gene panel was implemented in a cohort of 1382 Greek patients with BC, highly selected for strong family history and/or very young age (<35 years) at diagnosis, followed by BC risk calculation, based on a case–control analysis.ResultsHerein, 31.5% of patients tested carried pathogenic variants (PVs) in 28 known, suspected or candidate BC predisposition genes. In total, 24.8% of the patients carriedBRCA1/2loss-of-function variants. An additional 6.7% carried PVs in additional genes, the vast majority of which can be offered meaningful clinical changes. Significant association to BC predisposition was observed forATM, PALB2, TP53, RAD51CandCHEK2PVs. Primarily, compared with controls,RAD51CPVs andCHEK2damaging missense variants were associated with high (ORs 6.19 (Exome Aggregation Consortium (ExAC)) and 12.6 (Fabulous Ladies Over Seventy (FLOSSIES)), p<0.01) and moderate BC risk (ORs 3.79 (ExAC) and 5.9 (FLOSSIES), p<0.01), respectively.ConclusionStudying a large and unique cohort of highly selected patients with BC, deriving from a population with founder effects, provides important insight on distinct associations, pivotal for patient management.
Curative treatment for low-grade arteriovenous malformations
Authors: Wang Arthur , Mandigo Grace K , Feldstein Neil A , Sisti Michael B , Connolly E Sander , Solomon Robert A , Lavine Sean D , Meyers Philip M 
Published: July 2019

BackgroundSpetzler-Martin (SM) grade I-II (low-grade) arteriovenous malformations (AVMs) are often considered safe for microsurgery or radiosurgery. The adjunctive use of preoperative embolization to reduce surgical risk in these AVMs remains controversial.ObjectiveTo assess the safety of combined treatment of grade I-II AVMs with preoperative embolization followed by surgical resection or radiosurgery, and determine the long-term functional outcomes.MethodsWith institutional review board approval, a retrospective analysis was carried out on patients with ruptured and unruptured SM I-II AVMs between 2002 and 2017. Details of the endovascular procedures, including number of arteries supplying the AVM, number of branches embolized, embolic agent(s) used, and complications were studied. Baseline clinical and imaging characteristics were compared. Functional status using the modified Rankin Scale (mRS) before and after endovascular and microsurgical treatments was compared.Results258 SM I-II AVMs (36% SM I, 64% SM II) were identified in patients with a mean age of 38 ± 17 years. 48% presented with hemorrhage, 21% with seizure, 16% with headache, 10% with no symptoms, and 5% with clinical deficits. 90 patients (68%) in the unruptured group and 74 patients (59%) in the ruptured group underwent presurgical embolization (p = 0.0013). The mean number of arteries supplying the AVM was 1.44 and 1.41 in the unruptured and ruptured groups, respectively (p = 0.75). The mean number of arteries embolized was 2.51 in the unruptured group and 1.82 in the ruptured group (p = 0.003). n-Butyl cyanoacrylate and Onyx were the two most commonly used embolic agents. Four complications were seen in four patients (4/164 patients embolized): two peri-/postprocedural hemorrhage, one dissection, and one infarct. All patients undergoing surgery had a complete cure on postoperative angiography. Patients were followed up for a mean of 55 months. Good long-term outcomes (mRS score ≤ 2) were seen in 92.5% of patients with unruptured AVMs and 88.0% of those with ruptured AVMs. Permanent neurological morbidity occurred in 1.2%.ConclusionsCurative treatment of SM I-II AVMs can be performed using endovascular embolization with microsurgical resection or radiosurgery in selected cases, with very low morbidity and high cure rates. Compared with other published series, these outcomes suggest that preoperative embolization is a safe and effective adjunct to definitive surgical treatment. Long-term follow-up showed that patients with low-grade AVMs undergoing surgical resection or radiosurgery have good functional outcomes.
The effect of anesthetic technique on mortality and major morbidity after hip fracture surgery: a retrospective, propensity-score matched-pairs cohort study
Authors: Malhas Laith , Perlas Anahi , Tierney Sarah , Chan Vincent W S , Beattie Scott 
Published: July 2019

IntroductionSpinal anesthesia (SA) has physiological benefits over general anesthesia (GA), but there is insufficient evidence regarding a mortality benefit. We performed a retrospective propensity score-matched cohort study to evaluate the impact of anesthetic technique on mortality and major morbidity in patients undergoing hip fracture surgery.Materials and methodsClinical, laboratory and outcome data were extracted from electronic databases for patients who underwent hip fracture surgery over a 13-year period at the University Health Network in Toronto, Ontario, Canada. The anesthetic technique was documented (SA or GA), and the primary outcome was 90-day mortality. Secondary outcomes included mortality at 30 and 60 days, hospital length of stay, pulmonary embolism (PE), major blood loss and major acute cardiac events. A propensity-score matched-pair analysis was performed following a non-parsimonious logistic regression model.ResultsOf the 2591 patients identified, 883 patients in the SA group were matched to patients in the GA group in a 1:1 ratio. There was a weak association between SA and lower 90-day mortality (risk ratio (RR) 0.74, 95% CI 0.52 to 0.96, 99% CI 0.48 to 1.00, p=0.037). SA was also associated with a lower incidence of both PE (1.3% vs 0.5%, p<0.001) and major blood loss (7.7% vs 4.8%, p<0.001) and a shorter hospital length of stay by about 2 days (median 11.9 vs 10 days, p=0.024). There was no difference in major cardiac events or mortality at 30 and 60 days.DiscussionThis propensity-score matched-pairs cohort study suggests that SA is weakly associated with a lower 90-day mortality following hip fracture surgery. SA was also associated with improved morbidity evidenced by a lower rate of PE and major blood loss and a shorter hospital length of stay. Given the retrospective nature of the study, these results are not proof of causality.
Randomized comparison between perineural dexamethasone and dexmedetomidine for ultrasound-guided infraclavicular block
Authors: Aliste Julián , Layera Sebastián , Bravo Daniela , Fernández Diego , Jara Álvaro , García Armando , Finlayson Roderick J , Tran De Q 
Published: July 2019

BackgroundThis randomized trial compared perineural dexamethasone (5 mg) and dexmedetomidine (100 µg) for ultrasound-guided infraclavicular brachial plexus block. We hypothesized that both adjuvants would result in similar durations of motor block and therefore designed the study as an equivalence trial (equivalence margin=3.0 hours).MethodsOne hundred and twenty patients undergoing upper limb surgery with ultrasound-guided infraclavicular block (using 35 mL of lidocaine 1%–bupivacaine 0.25% with epinephrine 5 µg/mL) were randomly allocated to receive perineural dexamethasone (5 mg) or dexmedetomidine (100 µg). Patients and operators were blinded to the nature of the perineural adjuvant. After the performance of the block, a blinded observer assessed the success rate (defined as a minimal sensorimotor composite score of 14 out of 16 points at 30 min) as well as the incidence of surgical anesthesia (defined as the ability to complete surgery without local infiltration, supplemental blocks, intravenous opioids, or general anesthesia). Heart rate and blood pressure were recorded before the block as well as during the first 2 hours after its performance. Furthermore, the level of sedation (using the Ramsay Sedation Scale) was recorded in the postanesthesia care unit. Postoperatively, the blinded observer contacted patients with successful blocks to inquire about the duration of motor block, sensory block, and postoperative analgesia.ResultsNo intergroup differences were observed in terms of success rate and surgical anesthesia. Compared with dexmedetomidine, dexamethasone provided longer durations of motor block (17.4 (4.0) vs 14.3 (3.0) hours; p<0.001; 95% CI 1.7 to 4.5), sensory block (19.0 (4.0) vs 15.0 (3.2) hours; p<0.001; 95% CI 2.6 to 5.4), and analgesia (22.2 (3.6) vs 16.9 (3.9) hours; p<0.001; 95% CI 3.7 to 6.9). Dexmedetomidine resulted in lower heart rate and blood pressure after the performance of the block, as well as an increased level of sedation postoperatively.ConclusionCompared with dexmedetomidine (100 µg), dexamethasone (5 mg) results in longer sensorimotor block and analgesic durations, as well as a decreased level of patient sedation. Further studies are required to compare dexamethasone and dexmedetomidine using different doses, local anesthetic agents, and approaches to the brachial plexus.Trial registration numberNCT03610893
A predictive grading scale for acute cholecystitis
Authors: Siada Sammy , Jeffcoach David , Dirks Rachel C , Wolfe Mary M , Kwok Amy M , Sue Lawrence P , Davis James W 
Published: July 2019

BackgroundAcute cholecystitis presents in a spectrum of severity, where acute disease may be complicated by severe inflammation, gangrene, and perforation. The goal of this study is to outline an evidence-based grading scale that predicts patient outcomes after laparoscopic cholecystectomy (LC).MethodsA retrospective review of all patients with a preoperative diagnosis of acute cholecystitis who underwent LC from August 2011 until June 2015 at a tertiary-level hospital was performed. Patients who underwent elective cholecystectomy, incidental cholecystectomy, a planned open cholecystectomy, had gallstone pancreatitis or choledocholithiasis, and those admitted to a non-surgical service were excluded. Severity of disease was obtained from operative and pathology reports, and patients were classified according to the following grading scale:Grade I: symptomatic cholelithiasis.Grade II: acute/chronic cholecystitis.Grade III: gangrenous/necrotizing cholecystitis.Grade IV: gallbladder perforation or abscess.The groups were compared on age, gender, body mass index, severity of gallbladder disease, presence of preoperative systemic inflammatory response syndrome, hospital length of stay, length of operation, complications within 30 days, conversion to open rate, and cost of hospitalization.ResultsDuring the study period, 1252 patients who underwent laparoscopic cholecystectomy were analyzed; 677 met inclusion criteria. The most common grade was grade 2, which was present in 80% of patients, followed by grade 3, which was found in 16% of patients. Grade 4 cholecystitis occurred in 1.2% of patients and grade 1 occurred in 3.2% of patients. There were statistically significant increases in age, presence of preoperative systemic inflammatory response syndrome, hospital length of stay, conversion to open rate, cost of hospitalization, and length of operation with increased cholecystitis grade.ConclusionsThe proposed grading scale is an accurate predictor of duration of operation, conversion to open rate, hospital length of stay, and cost of hospitalization.Level of evidenceIIIStudy typePrognostic
Charged Higgs bosons in the NMSSM under current LHC constraints
Authors: Heng Zhaoxia , Guo Lin , Sun Pengqiang , Wei Wei 
Published: July 2019

Charged Higgs boson is a crucial prediction of new physics beyond the SM. In this work, we perform a comprehensive scan over the parameter space of NMSSM considering various experimental constraints including the direct search limits from the 13 TeV LHC, and consider the scenario that the next-to-lightest CP-even Higgs boson is SM-like. We find that the masses of charged Higgs bosons can be as light as 350 GeV, the lightest CP-even Higgs boson [Formula: see text] is predominantly singlet and can be as light as 48 GeV, and the lightest CP-odd Higgs boson [Formula: see text] is also singlet-dominated and can be as light as 82 GeV. The charged Higgs bosons mainly decay to [Formula: see text] or [Formula: see text], but the branching ratio of the exotic decays [Formula: see text] and [Formula: see text] can maximally reach 20% and 11%, respectively, which can be used to distinguish the NMSSM from MSSM. Such a heavy charged Higgs boson is inaccessible at the 13 TeV LHC with a luminosity of 36.1 fb[Formula: see text] and its detection needs higher energy and/or higher luminosity.
Breakup of spatiotemporal pattern under electromagnetic radiation
Authors: Li Fan , Guo Linwei 
Published: July 2019

Stable wave propagation is important for heart health, however, the electromagnetic radiation could affect normal signal propagation of heart, even make a sudden cardiac arrest. In this paper, the effect of electromagnetic radiation on the propagation of stable target wave generated by linear feedback control is studied in detail. It is confirmed that there are different transitions of electrical activities in cardiac tissue, which are transitions from target wave to spiral wave, some isolated islands of pattern waves coexisted, broken pattern and even the quiescent state, are generated when the electromagnetic field is imposed on the cardiac tissue in three ways. Furthermore, it is interesting to find there are different real affected regions, in which the electrical activities of nodes are destroyed, when the radiation signal is imposed on the cardiac tissue in different ways. It is also found the kinds of dynamical behaviors in the media are dependent on the real affected region. These results state that electromagnetic radiation could change the electrical activities, even destroy and suppress the wave propagation of wave source, and the ways of electromagnetic radiation imposed on the media are also important.