bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review with meta‐analysis: efficacy of balloon‐assisted enteroscopy for dilation of small bowel Crohn's disease strictures
Authors: Bettenworth Dominik , Bokemeyer Arne , Kou Lei , Lopez Rocio , Bena James F. , El Ouali Sara , Mao Ren , Kurada Satya , Bhatt Amit , Beyna Torsten , Halloran Brendan , Reeson Matthew , Hosomi Shuhei , Kishi Masahiro , Hirai Fumihito , Ohmiya Naoki , Rieder Florian 
Published: December 2020

SummaryBackgroundEvidence for endoscopic balloon dilation of small intestinal strictures in Crohn's disease (CD) using balloon‐assisted enteroscopy is scarce.AimTo evaluate endoscopic balloon dilation for the treatment of small intestinal CD strictures using balloon‐assisted enteroscopy.MethodsCitations in Embase, MEDLINE, and Cochrane were systematically reviewed. In a meta‐analysis of 18 studies with 463 patients and 1189 endoscopic balloon dilations, technical success was defined as the ability to dilate a stricture. Individual data were also obtained on 218 patients to identify outcome‐relevant risk factors.ResultsIn the pooled per‐study analysis, technical success rate of endoscopic balloon dilation was 94.9%, resulting in short‐term clinical efficacy in 82.3% of patients. Major complications occurred in 5.3% of patients. During follow‐up, 48.3% of patients reported symptom recurrence, 38.8% were re‐dilated and 27.4% proceeded to surgery. On the per‐patient‐based multivariable analysis, that patients with disease activity in the small intestine had lower short‐term clinical efficacy (odds ratio 0.32; 95% confidence interval 0.14‐0.73, P = 0.007). Patients with concomitant active disease in the small and/or large intestine had an increased risk to proceed toward surgery (hazard ratio 1.85; 95% confidence interval 1.09‐3.13, P = 0.02 and hazard ratio 1.77; 95% confidence interval 1.34‐2.34, P < 0.001).ConclusionsBalloon‐assisted enteroscopy for dilatation of CD‐associated small intestinal strictures has high short‐term technical and clinical efficacy and low complication rates. However, up to two‐thirds of patients need re‐dilation or surgery.
Impact of circulating microRNA test (miRNA‐371a‐3p) on appropriateness of treatment and cost outcomes in patients with Stage I non‐seminomatous germ cell tumours
Authors: Bagrodia Aditya , Savelyeva Anna , Lafin John T. , Speir Ryan W. , Chesnut Gregory T. , Frazier Anne Lindsay , Woldu Solomon L. , Margulis Vitaly , Murray Matthew J. , Amatruda James F. , Lotan Yair 
Published: December 2020

ObjectivesTo determine whether utilisation of a serum microRNA (miRNA) test could improve treatment appropriateness and cost‐effectiveness for patients with Stage I non‐seminomatous germ cell tumours (NSGCTs).Patients and MethodsA decision tree model was built to investigate treatment course, clinical and cost outcomes for patients with Stage IA (T1N0M0S0) and IB (T2–4N0M0S0) NSGCT. The model compared outcomes and cost of standard approach using histopathology, conventional serum tumour markers and radiographic staging (standard model) to a miRNA‐based approach using the standard model + post‐orchidectomy serum miR‐371a‐3p (marker model). Probabilities of expected treatment and outcomes were based on presence/absence of cancer upon entering into the model. Overtreatment was defined as adjuvant chemotherapy or primary retroperitoneal lymph node dissection in a patient without cancer. Undertreatment was defined as initial surveillance for a patient with cancer.ResultsUtilising the miRNA marker‐based approach, 26% of patients avoid overtreatment and 8% avoid undertreatment in Stage IA NSGCT; 27% avoid overtreatment and 23% avoid undertreatment in Stage IB disease. Appropriate treatment decision‐making increased from 65% to 94% and 50% to 92% for Stage IA and IB, respectively. The miRNA‐based approach remained cost‐effective over a wide range of performance characteristics with savings of ~$1400 (American dollars)/patient for both Stage IA and IB disease.ConclusionA miRNA‐based approach may potentially select patients with Stage I NSGCT for correct treatment in a cost‐effective manner. Identification of residual teratoma‐only remains an issue. Prospective studies are necessary to validate these findings.
Predictors of local recurrence and its impact on survival after glansectomy for penile cancer: time to challenge the dogma?
Authors: Roussel Eduard , Peeters Eline , Vanthoor Joren , Bozzini Giorgio , Muneer Asif , Ayres Ben , Sri Denosshan , Watkin Nick , Bhattar Rohit , Parnham Arie , Sangar Vijay , Lau Maurice , Joice Gregory , Bivalacqua Trinity J. , Chipollini Juan , Spiess Philippe E. , Hatzichristodoulou Georgios , de Vries Lieke , Brouwer Oscar , Albersen Maarten ,   eUROGEN, the Young Academic Urologists (YAU) Working Group of Men’s Health
Published: December 2020

ObjectivesTo identify predictive pathological factors for local recurrence (LR) and to study the impact of LR on survival in patients treated with glansectomy for penile squamous cell carcinoma (pSCC).Patients and MethodsWe retrospectively studied patients treated with glansectomy at international, high‐volume reference centres. We analysed histopathological predictors of LR, stratified patients into risk groups based on the number of risk factors present, and studied the impact of LR on survival outcomes using Kaplan–Meier survival analysis and stepwise Cox proportional hazards regression models. Subsequently, we performed sensitivity analyses excluding margin‐positive cases, pT3 disease, and cN+ disease, or all of these factors.ResultsAcross nine institutions, 897 patients were included, of whom 94 experienced LR. On multivariable analysis, presence of high‐grade disease and pT3 stage were independent predictors of LR. LR‐free survival rates significantly differed according to the number of risk factors present, with a hazard ratio (HR) of 1.90 (95% confidence interval [CI] 1.17–3.07; P = 0.01) for the intermediate‐risk group (one risk factor) and 6.11 (95% CI 3.47–10.77; P < 0.001) for the high‐risk group (two risk factors), using the low‐risk group (no risk factors) as reference. Patients who experienced LR had significantly worse overall survival (OS; HR 2.89, 95% CI 2.02–4.14; P < 0.001) and cancer‐specific survival (CSS; HR 5.64, 95% CI 3.45–9.22; P < 0.001). LR (HR 3.82, 95% CI 2.14–6.8; P < 0.001), lymphovascular invasion and cN status were significant predictors of decreased CSS. LR remained a strong predictor of both OS and CSS in all sensitivity analyses.ConclusionsPathological T3 stage and presence of high‐grade disease were independent histopathological predictors of LR after glansectomy for primary pSCC, which allowed risk stratification into three groups with significantly different risk of developing LR. Additionally, LR is related to poor OS and CSS, indicating that LR is a manifestation of underlying aggressive disease and clearly challenging the dogma of using organ‐sparing surgery whenever possible since survival is unaffected by higher LR rates.
Potential type 2 diabetes mellitus drug HMPA promotes short‐chain fatty acid production by improving carbon catabolite repression effect of gut microbiota
Authors: Liu Huijuan , Qin Yuan , Li Kun , Li Meng , Yang Jiahuan , Tao Honglian , Tang Yuanhao , Yang Lan , Chen Shuang , Liu Yanrong , Yang Cheng , Gao Wenqing , Sun Tao 
Published: December 2020

Background and PurposeGut microbiota plays an important role in type 2 diabetes mellitus (T2DM) progression. From our previous work N‐(4‐Hydroxyphenethyl)‐3‐mercapto‐2‐methylpropanamide (HMPA) is a potential T2DM drug. We evaluated the effect of HMPA on gut microbiota and studied the molecular mechanism underlying HMPA's regulation of gut microbiota.Experimental ApproachThe pseudo germ‐free (PGF) T2DM model and faecal microbiota transplantation method were used to study whether gut microbiota mediates the actions of HMPA. The composition of gut microbiota was detected by using 16S rRNA sequence. Short‐chain fatty acids (SCFAs) content was detected by gas chromatography. The HMPA probe was synthesised for finding and identifying the target protein of HMPA. The effect of HMPA on the utilisation of carbon sources in Bifidobacterium was evaluated.Key ResultsHMPA has a slight effect on the PGF T2DM model. The gut microbiota changed by HMPA can also alleviate the symptoms of T2DM. HMPA can regulate gut microbiota structure, increase SCFAs production and reduce nitrate content in the intestinal tissues. The thickness of the mucus on colon tissues increases after HMPA treatment. The target protein of HMPA in gut microbiota is the nitrogen metabolism global transcriptional regulator (GlnR). HMPA promotes the utilisation of less preferred carbon source in the gut microbiota and increases the fermentation product of SCFAs.Conclusion and ImplicationsHMPA plays a hypoglycaemic role through the gut microbiota. HMPA improves the carbon catabolite repression effect of gut microbiota and increases SCFAs production by targeting GlnR. GlnR may be a target for gut microbiota regulation.
Efficacy and safety of imeglimin in Japanese patients with type 2 diabetes: A 24‐week, randomized, double‐blind, placebo‐controlled, dose‐ranging phase 2b trial
Authors: Dubourg Julie , Ueki Kohjiro , Grouin Jean‐Marie , Fouqueray Pascale 
Published: December 2020

AbstractAimTo assess the efficacy and safety of imeglimin monotherapy compared with placebo for 24 weeks in Japanese patients with type 2 diabetes (T2D).Materials and MethodsIn this 24‐week, randomized, double‐blind, placebo‐controlled, parallel‐group, dose‐ranging, phase 2b clinical trial, Japanese adults (age ≥ 20 years) with T2D either treatment‐naïve or previously treated with one oral antidiabetes agent were eligible for participation. Patients were randomly assigned (1:1:1:1) to receive orally imeglimin 500, 1000 or 1500 mg, or placebo twice‐daily over a 24‐week period. The primary endpoint was the placebo‐adjusted change at week 24 in HbA1c. Safety outcomes were assessed in all patients who received at least one dose of study drug.ResultsA total of 299 patients were randomized to receive double‐blind treatment with orally twice‐daily placebo (n = 75), imeglimin 500 mg (n = 75), 1000 mg (n = 74) or 1500 mg (n = 75). At week 24, imeglimin significantly decreased HbA1c (difference vs. placebo: imeglimin 500 mg −0.52% [95% CI: −0.77%, −0.27%], imeglimin 1000 mg −0.94% [95% CI: −1.19%, −0.68%], imeglimin 1500 mg −1.00% [95% CI: −1.26%, −0.75%]; P < .0001 for all). Treatment‐emergent adverse events were reported for 68.0%, 62.2%, 73.3% and 68.0% of patients receiving imeglimin 500, 1000 or 1500 mg and placebo, respectively. A small increase in gastrointestinal adverse effects (e.g. diarrhoea) occurred with the 1500 mg dose level. Hypoglycaemia was balanced among groups.ConclusionsImeglimin as monotherapy in Japanese patients with T2D was well tolerated and significantly improved glycaemic control with no significant increase in hypoglycaemic events versus placebo. Given the marginal increase in efficacy with the 1500 versus 1000 mg dose (along with the potential for gastrointestinal tolerability issues), a dose of 1000 mg twice‐daily was selected for subsequent phase 3 studies.
The digital competence framework for primary and secondary schools in Europe
Authors: Guitert Montse , Romeu Teresa , Baztán Pablo 
Published: December 2020

AbstractThere has been a lot of interest to competence‐based education in research and scholarship. How competence‐based education has been developed and implemented varies across education systems in Europe. The European Commission defines digital competence as one of the eight key competence standards for lifelong learning. The European digital competence framework DigComp provides a comprehensive and exhaustive framework for citizens; it has the potential to be adapted to the needs of specific target groups. Nevertheless, no current research has focused on the need for developing a common framework for primary and secondary education. To address this gap we present a digital competence framework for European primary and secondary students. DigComp and a set of European frameworks are analysed in this paper. Combining categorical analysis with the collaboration of teachers and experts in the field, we define performance criteria and components that contribute to competence by five categories, providing a framework to promote the acquisition and evaluation of digital competence. This framework can be implemented in any EU country, it incorporates the most recent theoretical advances in research on information and communication technologies.
‘The goal is not necessarily to sit at the table’—Resisting autocratic legalism in Hungarian academia
Authors: Labanino Rafael , Dobbins Michael 
Published: December 2020

AbstractThe article analyses the strategies of Hungarian higher education interest organisations against the encroachments on academic freedom by Viktor Orbán's governments. We contrast the 2012–2013 and 2017–2019 protest waves and find that innovations in strategy came from new organisations in both periods, whereas established ones were rather passive or opted for the status quo. However, in the second period, new actors consciously declined to pursue wider systemic goals and aimed at building up formal organisations instead of loose, movement‐like networks. The focus on keeping a unified front and interest representation on the workplace level did not change the overall outcome. Just like during the first period, the government was able to reach its goals without major concessions. Nevertheless, during the second protest wave the government was unable to divide and pacify its opponents, which stripped it of its legalistic strategy and revealed its authoritarianism.
How date type, freshness labelling and food category influence consumer rejection
Authors: Samotyja Urszula , Sielicka‐Różyńska Maria 
Published: December 2020

AbstractThe aim of this study was (a) to evaluate the influence of date type and freshness labelling on a consumer rejection of expired food, (b) to assess how product category influences a consumer who rejects expired food based on a given criterion and (c) to investigate if a consumer's handling of food is rational as pertains to ‘use by’ or ‘best before’ dating. A consumer sensory study was conducted among 180 participants from Poland in which their attitude towards eight different foods labelled with two date types (‘use by’ or ‘best before’) and four various freshness dates was examined. The results showed that date type (‘best before’ vs. ‘use by’), freshness labelling and food category significantly influenced consumer rejection of food products and the criteria of rejection changed as the product became expired. Consumer behaviour regarding edibility after expiration was irrational and was manifested in both the acceptance of potentially harmful food products (from 31.5% to 60.2% of expired food products labelled with the ‘use by’ date were accepted) and the rejection of edible foods (from 24.4% to 56.7% of expired foods labelled with the ‘best before’ date were rejected). This study provides new insight into the influence of shelf‐life labelling and sensory perception on discard intention which ultimately results in unnecessary food waste. Our findings that date labelling can contribute to consumer apprehension of the suitability of a given food product for consumption shed new light on the role of building awareness among consumers in order to encourage waste‐reducing behaviour.
The combinatorial diversity of KIR and HLA class I allotypes in Peninsular Malaysia
Authors: Tao Sudan , Kichula Katherine M. , Harrison Genelle F. , Farias Ticiana Della Justina , Palmer William H. , Leaton Laura Ann , Hajar Che Ghazali Norul , Zefarina Zulkafli , Edinur Hisham Atan , Zhu Faming , Norman Paul J. 
Published: December 2020

SummaryKiller cell immunoglobulin‐like receptors (KIRs) interact with polymorphic human leucocyte antigen (HLA) class I molecules, modulating natural killer (NK) cell functions and affecting both the susceptibility and outcome of immune‐mediated diseases. The KIR locus is highly diverse in gene content, copy number and allelic polymorphism within individuals and across geographical populations. To analyse currently under‐represented Asian and Pacific populations, we investigated the combinatorial diversity of KIR and HLA class I in 92 unrelated Malay and 75 Malaysian Chinese individuals from the Malay Peninsula. We identified substantial allelic and structural diversity of the KIR locus in both populations and characterized novel variations at each analysis level. The Malay population is more diverse than Malay Chinese, likely representing a unique history including admixture with immigrating populations spanning several thousand years. Characterizing the Malay population are KIR haplotypes with large structural variants present in 10% individuals, and KIR and HLA alleles previously identified in Austronesian populations. Despite the differences in ancestries, the proportion of HLA allotypes that serve as KIR ligands is similar in each population. The exception is a significantly reduced frequency of interactions of KIR2DL1 with C2+HLA‐C in the Malaysian Chinese group, caused by the low frequency of C2+HLA. One likely implication is a greater protection from preeclampsia, a pregnancy disorder associated with KIR2DL1, which shows higher incidence in the Malay than in the Malaysian Chinese. This first complete, high‐resolution, characterization of combinatorial diversity of KIR and HLA in Malaysians will form a valuable reference for future clinical and population studies.
Contestation over Development Policy in the European Parliament
Authors: Raunio Tapio , Wagner Wolfgang 
Published: December 2020

AbstractRecent rise of populist parties has brought about more contestation over development policy. There is also increasing diversity within the European Union: some countries allocate more development aid while the contributions of newer member states are on average smaller. But do such national interests surface more often than in other issue areas, and what is the structure of contestation over development policy in the European Parliament (EP)? Examining roll‐call votes and the processing of the 2017 European Consensus on Development, this article shows that opposition to development policy is restricted to the more Eurosceptical representatives. EP party groups attain similar levels of cohesion in votes on development aid as in other policy areas, with coalition patterns following the left–right dimension. Development policy is thus ‘business as usual’ in the Parliament, but the results suggest increasing politicization of aid through stronger horizontal linkages between immigration, security, and development policy.
Immunofluorescence mapping, electron microscopy and genetics in the diagnosis and sub‐classification of inherited epidermolysis bullosa: a single‐centre retrospective comparative study of 87 cases with long‐term follow‐up
Authors: Rossi S. , Castiglia D. , Pisaneschi E. , Diociaiuti A. , Stracuzzi A. , Cesario C. , Mariani R. , Floriddia G. , Zambruno G. , Boldrini R. , Abeni D. , Novelli A. , Alaggio R. , El Hachem M. 
Published: December 2020

AbstractBackgroundEpidermolysis bullosa (EB) comprises a heterogeneous group of skin fragility disorders, classified in four major types based on skin cleavage level, i.e. EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), Kindler EB, and in more than 30 subtypes defined by the combination of laboratory and clinical data, including disease course.ObjectivesOur aims were to address whether, in the age of genomics, electron microscopy (TEM) has still a role in diagnosing EB, and whether the genotype per se may be sufficient to sub‐classify EB.MethodsA thoroughly characterized single‐centre EB case series was retrospectively evaluated to compare the power of TEM with immunofluorescence mapping (IFM) in establishing the EB type, and the ability of TEM, IFM and genetics to predict selected EB subtypes, i.e. severe dominant EBS (DEBS), severe JEB, severe recessive DEB (RDEB) and DEB self‐improving, using genetic and final diagnosis, respectively, as gold standard.ResultsThe series consisted of 87 patients, including 44 newborns, with a median follow‐up of 54 months. Ninety‐five mutations were identified in EB‐associated genes, including 25 novel variants. Both IFM and TEM were diagnostic in about all cases of JEB (21/21 for both) and DEB (43/44 for IFM, 44/44 for TEM). TEM sensitivity was superior to IFM for EBS (19/20 vs. 16/19). As to EB subtyping, IFM performed better than genetics in identifying severe JEB cases due to laminin‐332 defect (14/14 vs. 10/14) and severe RDEB (eight/nine vs. seven/nine). Genetics had no role in self‐improving DEB diagnosis; it almost equalled TEM in predicting severe DEBS (eight/nine vs. nine/nine) and enabled to discriminate dominant from recessive non‐severe DEB phenotypes and to identify special subtypes, e.g. DEBS with KLHL24 mutations.ConclusionsTransmission electron microscopy remains relevant to the diagnosis of EBS. IFM and genetics are essential and complementary tools in the vast majority of EB cases.
A novel protein complex that regulates active DNA demethylation in Arabidopsis
Authors: Liu Pan , Nie Wen‐Feng , Xiong Xiansong , Wang Yuhua , Jiang Yuwei , Huang Pei , Lin Xueqiang , Qin Guochen , Huang Huan , Niu Qingfeng , Du Jiamu , Lang Zhaobo , Lozano‐Duran Rosa , Zhu Jian‐Kang 
Published: December 2020

AbstractActive DNA demethylation is critical for altering DNA methylation patterns and regulating gene expression. The 5‐methylcytosine DNA glycosylase/lyase ROS1 initiates a base‐excision repair pathway for active DNA demethylation and is required for the prevention of DNA hypermethylation at 1 000s of genomic regions in Arabidopsis. How ROS1 is regulated and targeted to specific genomic regions is not well understood. Here, we report the discovery of an Arabidopsis protein complex that contains ROS1, regulates ROS1 gene expression, and likely targets the ROS1 protein to specific genomic regions. ROS1 physically interacts with a WD40 domain protein (RWD40), which in turn interacts with a methyl‐DNA binding protein (RMB1) as well as with a zinc finger and homeobox domain protein (RHD1). RMB1 binds to DNA that is methylated in any sequence context, and this binding is necessary for its function in vivo. Loss‐of‐function mutations in RWD40, RMB1, or RHD1 cause DNA hypermethylation at several tested genomic regions independently of the known ROS1 regulator IDM1. Because the hypermethylated genomic regions include the DNA methylation monitoring sequence in the ROS1 promoter, plants mutated in RWD40, RMB1, or RHD1 show increased ROS1 expression. Importantly, ROS1 binding to the ROS1 promoter requires RWD40, RMB1, and RHD1, suggesting that this complex dictates ROS1 targeting to this locus. Our results demonstrate that ROS1 forms a protein complex with RWD40, RMB1, and RHD1, and that this novel complex regulates active DNA demethylation at several endogenous loci in Arabidopsis.