bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myoepithelioma-like tumor of the vulvar region: a case report in China and review of the literature
Authors: Xu Yan , Gao Hui , Gao Jin-Li 
Published: January 2020

AbstractBackgroundMyoepithelioma-like tumor of the vulvar region (MELTVR) is a recently described mesenchymal neoplasm which typically arising in vulvar regions of adult women.Case presentationHere we report a case of a 65-year-old woman who presented with a 6-year history of subcutaneous mass in the vulvar region. The mass had recently increased in size continuously. Histologically, the tumor cells had an epithelioid to spindled shape. Epithelioid tumor cells proliferated singly or in a loosely cohesive manner with myxoid areas, while spindled tumor cells grew in diffuse sheets or storiform arrangements mainly in nonmyxoid areas. Immunohistochemically, the tumor cells were positive for vimentin, epithelial membrane antigen, calponin, and were partially mild to moderate positive for estrogen receptor, but completely negative for S100 protein, glial fibrillary acidic protein, CD34, desmin, SMA and cytokeratin. INI1/SMARCB1 expression was deficient.EWSR1andFUSgenes were intact tested by fluorescence in situ hybridization analysis. Based on these findings, we diagnose this case as MELTVR. The patient remained relapse-free after the lesion was widely excised during 8 months follow-up.ConclusionsThis disease should be included in the differential diagnostic list of vulvar tumors with epithelioid to spindled morphology. Recognition of its histopathological features and immunohistochemical reactivity will help to understand the tumor better.
Impact of genetic variant of HIPK2 on the risk of severe radiation pneumonitis in lung cancer patients treated with radiation therapy
Authors: Tang Yang , Yang Li , Qin Wan , Yi Min’ Xiao , Liu Bo , Yuan Xiang’Lin 
Published: January 2020

Abstract
Background
Homeodomain-interacting protein kinase 2 (HIPK2) has increasingly drawn attention as recent researches demonstrated its unique role in the regulation of multiple fundamental processes such as apoptosis, proliferation and DNA damage repair. Most importantly, HIPK2 was shown to play regulatory role in inflammation and influence the phenotype and activity of fibroblasts. In this study, we aimed to evaluate the impact of HIPK2 gene variant on risk of radiation pneumonitis for patients with pulmonary malignancies.

Methods
169 lung cancer patients with radiotherapy were included in our prospective study and genotyped by Sanger Sequence method. Multivariable Cox hazard analysis and multiple testing were applied to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of all factors possibly related to the risk of radiation pneumonitis (RP).

Results
Patients with Mean Lung Dose (MLD) ≥ 15Gy, Lung V20 ≥ 24% had higher risk of RP ≥ grade 2 compared with those counterparts (HR = 1.888, 95% CI: 1.186–3.004, P = 0.007; HR = 2.126, 95% CI: 1.338–3.378, P = 0.001, respectively). Importantly, CC genotype of HIPK2: rs2030712 were strongly related to an increased occurrence of RP ≥ grade 2 (HR = 2.146, 95% CI: 1.215–3.791, P = 0.009).

Conclusion
HIPK2: rs2030712 was found to be significantly related to RP of grade ≥ 2 in our cohort, and may thus be one of the important predictors of severe RP before radiotherapy, if further validated in larger population.

Trial registration
Our study was prospective and observational. The research was registered in ClinicalTrials.gov database as NCT02490319.
Two cases of granuloma mimicking local recurrence after pulmonary segmentectomy
Authors: Okazaki Mikio , Sano Yoshifumi , Mori Yu , Sakao Nobuhiko , Yukumi Syungo , Shigematsu Hisayuki , Izutani Hironori 
Published: January 2020

Abstract
Background
Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT is the most sensitive non-invasive imaging method for the detection of tumor metastasis and recurrence, but sometimes reveals false-positive results. Herein, we report two cases of false-positive results on PET/CT scans along with elevated serum carcinoembryonic antigen (CEA) levels, mimicking local recurrence after pulmonary segmentectomy.

Case presentation
Case 1; A 75-year-old woman underwent thoracoscopic left basal segmentectomy for primary lung cancer. Follow-up at 6 months after the surgery revealed serum CEA level elevation and chest CT showed a nodule measuring 25 × 22 mm in the residual left lower lobe. PET/CT revealed FDG uptake in the nodule diagnosed as local recurrence of lung cancer, and the patient underwent partial resection of the nodule. Microscopic examination of the resected specimen revealed granuloma caused by polyglycolic acid (PGA) sheet. Case 2; A 58-year-old man underwent VATS right S1 segmentectomy for lung metastasis from rectal carcinoma. Serum CEA levels gradually increased after surgery, and PET/CT revealed FDG uptake in the stump diagnosed as local recurrence of the lung metastasis. The patient underwent completion lobectomy 6 months after the segmentectomy, and the pathology of the resected specimen revealed an inflammatory granuloma caused by PGA suture.

Conclusions
Although suture and stapler granulomas have been reported, granuloma caused by PGA sheets has never been reported. Postoperative recurrence of lung cancer should be diagnosed with not only PET/CT scans and serum tumor markers but also pathological findings, to avoid unnecessary treatment such as chemotherapy, radiation, and difficult reoperation.
Contribution of GABAergic interneurons to amyloid-β plaque pathology in an APP knock-in mouse model
Authors: Rice Heather C. , Marcassa Gabriele , Chrysidou Iordana , Horré Katrien , Young-Pearse Tracy L. , Müller Ulrike C. , Saito Takashi , Saido Takaomi C. , Vassar Robert , de Wit Joris , De Strooper Bart 
Published: January 2020

AbstractThe amyloid-β (Aβ) peptide, the primary constituent of amyloid plaques found in Alzheimer’s disease (AD) brains, is derived from sequential proteolytic processing of the Amyloid Precursor Protein (APP). However, the contribution of different cell types to Aβ deposition has not yet been examined in an in vivo, non-overexpression system. Here, we show that endogenous APP is highly expressed in a heterogeneous subset of GABAergic interneurons throughout various laminae of the hippocampus, suggesting that these cells may have a profound contribution to AD plaque pathology. We then characterized the laminar distribution of amyloid burden in the hippocampus of an APP knock-in mouse model of AD. To examine the contribution of GABAergic interneurons to plaque pathology, we blocked Aβ production specifically in these cells using a cell type-specific knock-out of BACE1. We found that during early stages of plaque deposition, interneurons contribute to approximately 30% of the total plaque load in the hippocampus. The greatest contribution to plaque load (75%) occurs in the stratum pyramidale of CA1, where plaques in human AD cases are most prevalent and where pyramidal cell bodies and synaptic boutons from perisomatic-targeting interneurons are located. These findings reveal a crucial role of GABAergic interneurons in the pathology of AD. Our study also highlights the necessity of using APP knock-in models to correctly evaluate the cellular contribution to amyloid burden since APP overexpressing transgenic models drive expression in cell types according to the promoter and integration site and not according to physiologically relevant expression mechanisms.
Lessening Organ dysfunction with VITamin C (LOVIT): protocol for a randomized controlled trial
Authors:   on behalf of the Canadian Critical Care Trials Group, Masse Marie-Hélène , Ménard Julie , Sprague Sheila , Battista Marie-Claude , Cook Deborah J. , Guyatt Gordon H. , Heyland Daren K. , Kanji Salmaan , Pinto Ruxandra , Day Andrew G. , Cohen Dian , Annane Djillali , McGuinness Shay , Parke Rachael , Carr Anitra , Arabi Yaseen , Vijayaraghavan Bharath Kumar Tirupakuzhi , D’Aragon Frédérick , Carbonneau Élaine , Maslove David , Hunt Miranda , Rochwerg Bram , Millen Tina , Chassé Michaël , Lebrasseur Martine , Archambault Patrick , Deblois Estel , Drouin Christine , Lellouche François , Lizotte Patricia , Watpool Irene , Porteous Rebecca , Clarke France , Marinoff Nicole , Belley-Côté Émilie , Bolduc Brigitte , Walker Scott , Iazzetta John , Adhikari Neill K. J. , Lamontagne François 
Published: January 2020

Abstract
Background
Sepsis is a health problem of global importance; treatments focus on controlling infection and supporting failing organs. Recent clinical research suggests that intravenous vitamin C may decrease mortality in sepsis. We have designed a randomized controlled trial (RCT) to ascertain the effect of vitamin C on the composite endpoint of death or persistent organ dysfunction at 28 days in patients with sepsis.

Methods
LOVIT (Lessening Organ dysfunction with VITamin C) is a multicenter, parallel-group, blinded (participants, clinicians, study personnel, Steering Committee members, data analysts), superiority RCT (minimum n = 800). Eligible patients have sepsis as the diagnosis for admission to the intensive care unit (ICU) and are receiving vasopressors. Those admitted to the ICU for more than 24 h are excluded. Eligible patients are randomized to high-dose intravenous vitamin C (50 mg/kg every 6 h for 96 h) or placebo. The primary outcome is a composite of death or persistent organ dysfunction (need for vasopressors, invasive mechanical ventilation, or new and persisting renal replacement therapy) at day 28. Secondary outcomes include persistent organ dysfunction-free days to day 28, mortality and health-related quality of life at 6 months, biomarkers of dysoxia, inflammation, infection, endothelial function, and adverse effects (hemolysis, acute kidney injury, and hypoglycemia). Six subgroup analyses are planned.

Discussion
This RCT will provide evidence of the effect of high-dose intravenous vitamin C on patient-important outcomes in patients with sepsis.

Trial registration
clinicaltrials.gov, NCT03680274, first posted 21 September 2018.
What does soil-transmitted helminth elimination look like? Results from a targeted molecular detection survey in Japan
Authors:   the DeWorm3 Project Team, Hasegawa Mitsuko , Pilotte Nils , Kikuchi Mihoko , Means Arianna R. , Papaiakovou Marina , Gonzalez Andrew M. , Maasch Jacqueline R. M. A. , Ikuno Hiroshi , Sunahara Toshihiko , Ásbjörnsdóttir Kristjana H. , Walson Judd L. , Williams Steven A. , Hamano Shinjiro 
Published: January 2020

Abstract
Background
Japan is one of the few countries believed to have eliminated soil-transmitted helminths (STHs). In 1949, the national prevalence of Ascaris lumbricoides was 62.9%, which decreased to 0.6% in 1973 due to improvements in infrastructure, socioeconomic status, and the implementation of national STH control measures. The Parasitosis Prevention Law ended in 1994 and population-level screening ceased in Japan; therefore, current transmission status of STH in Japan is not well characterized. Sporadic cases of STH infections continue to be reported, raising the possibility of a larger-scale recrudescence of STH infections. Given that traditional microscopic detection methods are not sensitive to low-intensity STH infections, we conducted targeted prevalence surveys using sensitive PCR-based assays to evaluate the current STH-transmission status and to describe epidemiological characteristics of areas of Japan believed to have achieved historical elimination of STHs.

Methods
Stool samples were collected from 682 preschool- and school-aged children from six localities of Japan with previously high prevalence of STH. Caregivers of participants completed a questionnaire to ascertain access to water, sanitation and hygiene (WASH), and potential exposures to environmental contamination. For fecal testing, multi-parallel real-time PCR assays were used to detect infections of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale and Trichuris trichiura.

Results
Among the 682 children, no positive samples were identified, and participants reported high standards of WASH.

Conclusions
To our knowledge, this is the first STH-surveillance study in Japan to use sensitive molecular techniques for STH detection. The results suggest that recrudescence of STH infections has not occurred, and that declines in prevalence have been sustained in the sampled areas. These findings suggest that reductions in prevalence below the elimination thresholds, suggestive of transmission interruption, are possible. Additionally, this study provides circumstantial evidence that multi-parallel real-time PCR methods are applicable for evaluating elimination status in areas where STH prevalence is extremely low.
Global evaluation of taxonomic relationships and admixture within the Culex pipiens complex of mosquitoes
Authors: Aardema Matthew L. , vonHoldt Bridgett M. , Fritz Megan L. , Davis Steven R. 
Published: January 2020

AbstractBackgroundWithin theCulex pipiensmosquito complex, there are six contemporarily recognized taxa:Cx.quinquefasciatus,Cx.pipiensf.pipiens,Cx.pipiensf.molestus,Cx.pipiens pallens,Cx.australicusandCx.globocoxitus. Many phylogenetic aspects within this complex have eluded resolution, such as the relationship of the two Australian endemic taxa to the other four members, as well as the evolutionary origins and taxonomic status ofCx.pipiens pallensandCx.pipiensf.molestus. Ultimately, insights into lineage relationships within the complex will facilitate a better understanding of differential disease transmission by these mosquitoes. To this end, we have combined publicly available data with our own sequencing efforts to examine these questions.ResultsWe found that the two Australian endemic complex members,Cx.australicusandCx.globocoxitus, comprise a monophyletic group, are genetically distinct, and are most closely related to the cosmopolitanCx.quinquefasciatus. Our results also show thatCx.pipiens pallensis genetically distinct, but may have arisen from past hybridization. Lastly, we observed complicated patterns of genetic differentiation within and betweenCx.pipiensf.pipiensandCx.pipiensf.molestus.ConclusionsTwo Australian endemicCulextaxa,Cx.australicusandCx.globocoxitus, belong within theCx. pipienscomplex, but have a relatively older evolutionary origin. They likely diverged fromCx.quinquefasciatusafter its colonization of Australia. The taxonCx.pipiens pallensis a distinct evolutionary entity that likely arose from past hybridization betweenCx.quinquefasciatusandCx.pipiensf.pipiens/Cx. pipiensf.molestus. Our results do not suggest it derives from ongoing hybridization. Finally, genetic differentiation within theCx.pipiensf.pipiensandCx.pipiensf.molestussamples suggests that they collectively form two separate geographic clades, one in North America and one in Europe and the Mediterranean. This may indicate that theCx.pipiensf.molestusform has two distinct origins, arising fromCx.pipiensf.pipiensin each region. However, ongoing genetic exchange within and between these taxa have obscured their evolutionary histories, and could also explain the absence of monophyly among our samples. Overall, this work suggests many avenues that warrant further investigation.
Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients
Authors: Meyer Alain , Troyanov Yves , Drouin Julie , Oligny-Longpré Geneviève , Landon-Cardinal Océane , Hoa Sabrina , Hervier Baptiste , Bourré-Tessier Josiane , Mansour Anne-Marie , Hussein Sara , Morin Vincent , Rich Eric , Goulet Jean-Richard , Chartrand Sandra , Hudson Marie , Nehme Jessica , Makhzoum Jean-Paul , Zarka Farah , Villeneuve Edith , Raynauld Jean-Pierre , Landry Marianne , O’Ferrall Erin K. , Ferreira Jose , Ellezam Benjamin , Karamchandani Jason , Larue Sandrine , Massie Rami , Isabelle Catherine , Deschênes Isabelle , Leclair Valérie , Couture Hélène , Targoff Ira N. , Fritzler Marvin J. , Senécal Jean-Luc 
Published: January 2020

Abstract
Objective
To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy.

Methods
Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies.

Results
A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment.

Conclusion
While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.
Carvacrol ameliorates acute campylobacteriosis in a clinical murine infection model
Authors: Mousavi Soraya , Schmidt Anna-Maria , Escher Ulrike , Kittler Sophie , Kehrenberg Corinna , Thunhorst Elisa , Bereswill Stefan , Heimesaat Markus M. 
Published: January 2020

Abstract
Background
The prevalence of human infections with the zoonotic pathogen Campylobacter jejuni is rising worldwide. Therefore, the identification of compounds with potent anti-pathogenic and anti-inflammatory properties for future therapeutic and/or preventive application to combat campylobacteriosis is of importance for global health. Results of recent studies suggested carvacrol (4-isopropyl-2-methylphenol) as potential candidate molecule for the treatment of campylobacteriosis in humans and for the prevention of Campylobacter colonization in farm animals.

Results
To address this in a clinical murine infection model of acute campylobacteriosis, secondary abiotic IL-10−/− mice were subjected to synthetic carvacrol via the drinking water starting 4 days before peroral C. jejuni challenge. Whereas at day 6 post-infection placebo treated mice suffered from acute enterocolitis, mice from the carvacrol cohort not only harbored two log orders of magnitude lower pathogen loads in their intestines, but also displayed significantly reduced disease symptoms. Alleviated campylobacteriosis following carvacrol application was accompanied by less distinct intestinal apoptosis and pro-inflammatory immune responses as well as by higher numbers of proliferating colonic epithelial cells. Remarkably, the inflammation-ameliorating effects of carvacrol treatment were not restricted to the intestinal tract, but could also be observed in extra-intestinal organs such as liver, kidneys and lungs and, strikingly, systemically as indicated by lower IFN-γ, TNF, MCP-1 and IL-6 serum concentrations in carvacrol versus placebo treated mice. Furthermore, carvacrol treatment was associated with less frequent translocation of viable C. jejuni originating from the intestines to extra-intestinal compartments.

Conclusion
The lowered C. jejuni loads and alleviated symptoms observed in the here applied clinical murine model for human campylobacteriosis highlight the application of carvacrol as a promising novel option for both, the treatment of campylobacteriosis and hence, for prevention of post-infectious sequelae in humans, and for the reduction of C. jejuni colonization in the intestines of vertebrate lifestock animals.
Characterization of Arcobacter strains isolated from human stool samples: results from the prospective German prevalence study Arcopath
Authors: Brückner Vanessa , Fiebiger Ulrike , Ignatius Ralf , Friesen Johannes , Eisenblätter Martin , Höck Marlies , Alter Thomas , Bereswill Stefan , Heimesaat Markus M. , Gölz Greta 
Published: January 2020

Abstract
Background
Arcobacter constitute emerging food- and waterborne pathogens causing gastroenteritis in humans, but the underlying mechanisms are only incompletely understood. We therefore characterized Arcobacter isolates derived from human stool samples that had been collected during a prospective prevalence study in Germany in vitro. Thirty-six bacterial isolates belonging to the species A. butzleri (n = 24), A. cryaerophilus (n = 10) and A. lanthieri (n = 2) were genotyped by ERIC-PCR, the presence of 10 putative virulence genes was assessed and cytotoxic effects on the human intestinal cell line HT-29/B6 were analyzed applying the WST-assay.

Results
Genotyping revealed high genetic diversity within the species A. butzleri, A. cryaerophilus and A. lanthieri. Both, A. butzleri and A. lanthieri encoded for a large number of putative virulence genes, while fewer genes were detectable in A. cryaerophilus isolates. Notably, the three cytolethal distending toxin (CDT) genes cdtA, cdtB and cdtC were abundant in both A. lanthieri isolates. Furthermore, all A. butzleri and A. lanthieri, but only one of the A. cryaerophilus isolates exerted cytotoxic effects.

Conclusions
Our study provides evidence for the abundance of putative virulence genes in Arcobacter isolates and prominent cytotoxic effects of A. butzleri and A. lanthieri in vitro. The presence of cdtA, cdtB, cdtC in A. lanthieri points towards CDT secretion as potential mechanism underlying cytotoxicity as opposed to A. butzleri. However, the association of the Arcobacter virulence factors detected and human morbidity should be addressed in future studies.
Epigenome-wide association study of seizures in childhood and adolescence
Authors: Caramaschi Doretta , Hatcher Charlie , Mulder Rosa H. , Felix Janine F. , Cecil Charlotte A. M. , Relton Caroline L. , Walton Esther 
Published: January 2020

AbstractThe occurrence of seizures in childhood is often associated with neurodevelopmental impairments and school underachievement. Common genetic variants associated with epilepsy have been identified and epigenetic mechanisms have also been suggested to play a role. In this study, we analyzed the association of genome-wide blood DNA methylation with the occurrence of seizures in ~ 800 children from the Avon Longitudinal Study of Parents and Children, UK, at birth (cord blood), during childhood, and adolescence (peripheral blood). We also analyzed the association between the lifetime occurrence of any seizures before age 13 with blood DNA methylation levels. We sought replication of the findings in the Generation R Study and explored causality using Mendelian randomization, i.e., using genetic variants as proxies. The results showed five CpG sites which were associated cross-sectionally with seizures either in childhood or adolescence (1–5% absolute methylation difference at pFDR< 0.05), although the evidence of replication in an independent study was weak. One of these sites was located in theBDNFgene, which is highly expressed in the brain, and showed high correspondence with brain methylation levels. The Mendelian randomization analyses suggested that seizures might be causal for changes in methylation rather than vice-versa. In conclusion, we show a suggestive link between seizures and blood DNA methylation while at the same time exploring the limitations of conducting such study.