tbuckley/cabot-search huggingface dataset:
Association of Severe Hydrocephalus With Congenital Zika Syndrome
Authors: Vanessa van der Linden, Natacha Calheiros de Lima Petribu, Andre Pessoa, Igor Faquini, Alex R. Paciorkowski, Hélio van der Linden, Laura Silveira-Moriyama, Marli Tenório Cordeiro, Adriano Nassri Hazin, A. James Barkovich, Charles Raybaud, Marilia de Brito Abath, Erlane Ribeiro, Carlos Eduardo Barros Jucá, Maria de Fátima Viana Vasco Aragão, Patrícia Teresa Coelho Travassos, Patrícia Jungmann
Journal: JAMA Neurology (2018)

Hydrocephalus is a treatable but potentially fatal complication that has not been previously described in congenital Zika syndrome (CZS).To describe the clinical features and imaging findings in 24 patients with congenital Zika syndrome (CZS) who developed hydrocephalus.This case series included patients with hydrocephalus who were born in October and November 2015 and followed up until mid-2017 in the 2 largest national referral centers for CZS in Brazil. The participants included consecutively enrolled children with a clinical and laboratorial diagnosis of CZS who developed clinical and/or image findings suggestive of hydrocephalus and who were confirmed to experience increased intracranial hypertension during ventriculoperitoneal shunt procedures.To retrospectively describe clinical and image findings in these 24 patients.This multicenter cohort included 308 patients with CZS; 24 consecutive children were enrolled in this study. These children were aged between 3 to 18 months, and 13 of 24 (54%) were female. All patients presented with at least 1 positive test result for anti-Zika antibodies in cerebrospinal fluid or serum and had classic signs of CZS. At the time of hydrocephalus diagnosis, only 14 of 24 patients (58%) had symptoms and signs suggestive of hydrocephalus (mainly worsening seizures, vomiting, irritability, and/or sudden increase of head circumference percentile). Two of 24 patients (8%) had no symptoms suggestive of hydrocephalus but were found to have reduced brain volume on repeated imaging. Cerebellar or brainstem hypoplasia on baseline imaging were found in 18 of 23 patients (78%). At the second computed tomographic scan, all patients showed a marked increase of ventricular volume, compatible with communicating hydrocephalus, and reduction of brain tissue that was visibly worse than on baseline imaging for the 23 patients with repeated scans.We present evidence that hydrocephalus is a complication of CZS in at least a proportion of patients. The clinical spectrum of this condition continues to evolve, but given that presenting signs and symptoms of hydrocephalus can be challenging to recognize in CZS, we provisionally recommend that high suspicion and appropriate monitoring for hydrocephalus should be part of the standard care of patients with CZS.
Molecular mechanisms of azole resistance in Candida tropicalis isolates causing invasive candidiasis in China
Authors: X. Fan, M. Xiao, D. Zhang, J.-J. Huang, H. Wang, X. Hou, L. Zhang, F. Kong, S.C.-A. Chen, Z.-H. Tong, Y.-C. Xu
Journal: Clinical Microbiology and Infection (2018)
Novel metallic stent designed for endoscopic bilateral stent-in-stent placement in patients with hilar malignant biliary obstruction
Authors: Mamoru Takenaka, Kentaro Yamao, Kosuke Minaga, Atsushi Nakai, Shunsuke Omoto, Ken Kamata, Masatoshi Kudo
Journal: Endoscopy (2018)

In endoscopic bilateral stent-in-stent placement (SIS) in patients with hilar malignant biliary obstruction (HMBO), success depends on second stenting [1] [2] [3]. Some metallic stents employed in SIS are designed to be larger to allow easier second stenting [4] [5]. However, these large cells also increase the risk of ingrowth, resulting in weaker radial force and making it impossible for the stent to expand fully, thereby making second stenting difficult.
Gut microbiota dynamics and uraemic toxins: one size does not fit all
Authors: Marie Joossens, Karoline Faust, Tessa Gryp, Anh Thi Loan Nguyen, Jun Wang, Sunny Eloot, Eva Schepers, Annemieke Dhondt, Anneleen Pletinck, Sara Vieira-Silva, Gwen Falony, Mario Vaneechoutte, Raymond Vanholder, Wim Van Biesen, Geert Roger Bertrand Huys, Jeroen Raes, Griet Glorieux
Journal: Gut (2018)

In the recent paper by Chu and colleagues,1 the potential role of microbiota-related metabolites in the progression of non-alcoholic fatty liver disease is discussed. This topic has been studied in the context of chronic kidney disease (CKD), characterised by changes in gut microbiota composition,2 accumulation of microbiota-derived metabolites,3 interruption of intestinal barrier function and chronic inflammation.4 In line with this, we focused, in a cohort of 17 patients with end-stage kidney disease (ESKD), on the role of gut microbiota in the generation of precursors of specific uraemic toxins which are associated with negative outcomes in these patients.5 By collecting multiple samples over time, assessment of variability within and between patients in relation to disease progress and clinical variables was possible. Faecal and serum samples were collected at eight time-points over a 4-month period (online supplementary table 1). Uraemic metabolites and microbial profiling were determined by HPLC and 16S rRNA amplicon sequencing, respectively (see Supplementary data). Variation in microbial profiles of patients with ESKD was compared with that of 1106 subjects from a population-based cohort, the Flemish Gut Flora Project (FGFP),6 which have a similar genetic and environmental background as well as to a subset of age-matched controls of comparable health status (n=32).

### Supplementary data

[gutjnl-2018-317561supp001.pdf] 

In this longitudinal study, within-patient analyses showed that variations in peripheral levels of p -cresyl conjugates (the composite of p -cresyl sulfate (pCS)/glucuronide (pCG); p C), indoxyl sulfate (IxS), indole acetic acid and …
Disseminated Vegetating Plaques and Pustules
Authors: Divya Seth, Samson K. Kiprono, Aileen Y. Chang
Journal: JAMA Dermatology (2018)

A teenaged male in Kenya presented with painful vegetating, bleeding plaques and pustules on his face, scalp, trunk, and extremities. He continued to develop new lesions despite prescribed daily medications. He was HIV negative. What is your diagnosis?
Self-Expanding Transcatheter Aortic Valve Replacement in Patients With Low-Gradient Aortic Stenosis
Authors: Stanley J Chetcuti, G Michael Deeb, Jeffrey J Popma, Steven J Yakubov, P Michael Grossman, Himanshu J Patel, Alfred Casale, Harold L Dauerman, Jon R Resar, Michael J Boulware, Jessica L Dries-Devlin, Shuzhen Li, Jae K Oh, Michael J Reardon
Journal: JACC. Cardiovascular imaging (2018)
Disentangling the heterogeneity of allergic respiratory diseases by latent class analysis reveals novel phenotypes
Authors: Rita Amaral, Jean Bousquet, Ana M. Pereira, Luís M. Araújo, Ana Sá‐Sousa, Tiago Jacinto, Rute Almeida, Luís Delgado, Joao A. Fonseca
Journal: Allergy (2018)

Abstract Background Refined phenotyping of allergic diseases may unravel novel phenotypes. Conjunctivitis as an independent disorder has never been approached. Aim To identify distinct classes of allergic respiratory diseases using latent class analysis ( LCA ) and distinguish each class using classification and regression tree ( CART ) analysis. Methods Seven hundred and twenty‐eight adults from the Portuguese general population study ICAR had a structured medical interview combined with blood collection, skin prick tests, spirometry with bronchodilation, and exhaled nitric oxide. LCA was applied to 19 variables. The CART algorithm selected the most likely variables distinguishing LCA ‐classes. Results A six‐class model was obtained. Class 1 (25%): nonallergic participants without bronchial or ocular symptoms. Classes 2 (22%) and 3 (11%): nasal and ocular (low levels) symptoms without nasal impairment, monosensitized (Class 2) or polysensitized (Class 3). Class 4 (13%): polysensitized participants with high levels of nasal and ocular symptoms, and nasal impairment. Classes 5 (16%) and 6 (14%): high level of nasal, bronchial and ocular symptoms with nasal impairment (non‐allergic or polysensitized, respectively). Participants in classes 5 and 6 had more bronchial exacerbations and unscheduled medical visits ( P &lt; 0.001). Ocular symptoms were significantly higher in classes with nasal impairment, compared to those without impairment ( P &lt; 0.001) or no nasal symptom ( P &lt; 0.001). CART highlighted ocular symptoms as the most relevant variable in distinguishing LCA ‐classes. Conclusion Novel severe phenotypes of participants with co‐occurrence of ocular, nasal and bronchial symptoms, and exacerbation‐prone were identified. The tree algorithm showed the importance of the ocular symptoms in the expression of allergic diseases phenotypes.
Differences in Risk of Sudden Cardiac Death Between Blacks and Whites
Authors: Rajat Deo, Monika M. Safford, Yulia A. Khodneva, Deanna P. Jannat-Khah, Todd M. Brown, Suzanne E. Judd, William M. McClellan, J. David Rhodes, Michael G. Shlipak, Elsayed Z. Soliman, Christine M. Albert
Journal: Journal of the American College of Cardiology (2018)
<i>BRCA</i> Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma
Authors: Kevin K. Lin, Maria I. Harrell, Amit M. Oza, Ana Oaknin, Isabelle Ray-Coquard, Anna V. Tinker, Elena Helman, Marc R. Radke, Carmen Say, Lan-Thanh Vo, Elaina Mann, Jeffrey D. Isaacson, Lara Maloney, David M. O'Malley, Setsuko K. Chambers, Scott H. Kaufmann, Clare L. Scott, Gottfried E. Konecny, Robert L. Coleman, James X. Sun, Heidi Giordano, James D. Brenton, Thomas C. Harding, Iain A. McNeish, Elizabeth M. Swisher
Journal: Cancer Discovery (2018)

A key resistance mechanism to platinum-based chemotherapies and PARP inhibitors in BRCA-mutant cancers is the acquisition of BRCA reversion mutations that restore protein function. To estimate the prevalence of BRCA reversion mutations in high-grade ovarian carcinoma (HGOC), we performed targeted next-generation sequencing of circulating cell-free DNA (cfDNA) extracted from pretreatment and postprogression plasma in patients with deleterious germline or somatic BRCA mutations treated with the PARP inhibitor rucaparib. BRCA reversion mutations were identified in pretreatment cfDNA from 18% (2/11) of platinum-refractory and 13% (5/38) of platinum-resistant cancers, compared with 2% (1/48) of platinum-sensitive cancers (P = 0.049). Patients without BRCA reversion mutations detected in pretreatment cfDNA had significantly longer rucaparib progression-free survival than those with reversion mutations (median, 9.0 vs. 1.8 months; HR, 0.12; P < 0.0001). To study acquired resistance, we sequenced 78 postprogression cfDNA, identifying eight additional patients with BRCA reversion mutations not found in pretreatment cfDNA. SIGNIFICANCE: BRCA reversion mutations are detected in cfDNA from platinum-resistant or platinum-refractory HGOC and are associated with decreased clinical benefit from rucaparib treatment. Sequencing of cfDNA can detect multiple BRCA reversion mutations, highlighting the ability to capture multiclonal heterogeneity.This article is highlighted in the In This Issue feature, p. 151.
Argx-110 for Treatment of CD70-Positive Advanced Cutaneous T-Cell Lymphoma in a Phase 1/2 Clinical Trial
Authors: Martine Bagot, Marie Maerevoet, Pier Luigi Zinzani, Fritz Offner, Franck Morschhauser, Jean-Marie Michot, Vincent Ribrag, Maxime Battistella, Helene Moins, Angelica Calleri, Stéphane Dalle, Marie Beylot-Barry, Karen Zwaenepoel, Koen De Winnie, Anne Marie-Cardine, Jean-Michel Cayuela, Valentina Tabanelli, Giovanna Motta, Federica Melle, Anna Hultberg, Domenica Gandini, Teresa Marafioti, Mahan Moshir, Tim Delahaye, Piotr Zabrocki, Karen Silence, Luc Van Rompaey, Armand Bensussan, Hans De Haard, Patrick Pauwels, Nicolas Leupin, Stefano A. Pileri
Journal: Blood (2018)
SGLT Inhibitors for Type 1 Diabetes: An Obvious Choice or Too Good to Be True?
Authors: Matthew C. Riddle, William T. Cefalu
Journal: Diabetes Care (2018)

In the recent past we have been fortunate to find new treatments based on entirely new mechanisms . . . or is that really so? The sodium–glucose cotransporter inhibitors (SGLTi) offer an instructive case in point. These apparently “ new” agents were preceded by phlorizin, a naturally occurring compound that has been used for physiologic studies for over 100 years (1). Given orally it interferes with intestinal absorption of carbohydrates and causes glucosuria. Studies in animal models of diabetes have provided useful insights, such as evidence that reduction of hyperglycemia can restore insulin sensitivity toward normal (2). However, phlorizin was considered unsuited for use by humans due to undesirable side effects. Recently its mechanism of action has been traced to effects on sodium–glucose cotransporters (SGLT) in the intestinal mucosa and the renal proximal tubule (3), and drugs with more nuanced effects on these transporters have been developed (4,5). These newer agents have greater affinity for SGLT2, which is expressed mainly in the kidney, and less for SGLT1, which facilitates intestinal absorption of glucose. Clinical effects of the newer SGLTi drugs in type 2 diabetes (T2D) include modest reductions of plasma glucose and A1C, weight, and blood pressure and are mediated in large part by glucosuria and sodium diuresis. These agents are taken once daily by mouth and do not require dose titration. Symptomatic side effects—mostly urinary or genital irritation or infections—are common but tolerated by most patients.

Importantly, the new SGLTi drugs have highly desirable—and somewhat unexpected—cardiac and renal protective effects, as least in selected cohorts. Large trials of empagliflozin and canagliflozin, aiming to demonstrate safety in patients with T2D and high cardiovascular risk, have shown favorable effects on heart failure, cardiovascular death, and progression of albuminuria (6–9). Unwanted effects have been reported as well, including …
Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signalling
Authors: Martina Rauner, Ulrike Baschant, Antonella Roetto, Rosa Maria Pellegrino, Sandra Rother, Juliane Salbach-Hirsch, Heike Weidner, Vera Hintze, Graeme Campbell, Andreas Petzold, Regis Lemaitre, Ian Henry, Teresita Bellido, Igor Theurl, Sandro Altamura, Silvia Colucci, Martina U. Muckenthaler, Georg Schett, Davide S. K. Komla-Ebri, J. H. Duncan Bassett, Graham R. Williams, Uwe Platzbecker, Lorenz C. Hofbauer
Journal: Nature Metabolism (2018)
Abstract 20041: Differences in the Clinical Features and Outcomes According to the Disease Entity of Acute Aortic Syndrome: A 22-year Experience in a Single Tertiary Referral Center
Authors: Hoyun Kim, Jinyoung Kim, Sang Yong Om, Osung Kwon, Ran Heo, Sahmin Lee, Dae-Hee Kim, Jong-Min Song, Duk-Hyun Kang, Jae-Kwan Song
Journal: Circulation (2017)

Background: Along with clinical introduction of non-invasive imaging modalities in daily practice, intramural hematoma (IMH) has been successfully incorporated as a disease entity of acute aortic s...
Association of Multiple Biomarkers With Risk of All-Cause and Cause-Specific Mortality After Acute Coronary Syndromes
Authors: Daniel Lindholm, Stefan K. James, Katja Gabrysch, Robert F. Storey, Anders Himmelmann, Christopher P. Cannon, Kenneth W. Mahaffey, Philippe Gabriel Steg, Claes Held, Agneta Siegbahn, Lars Wallentin
Journal: JAMA Cardiology (2018)

<h3>Importance</h3> Mortality remains at about 5% within a year after an acute coronary syndrome event. Prior studies have assessed biomarkers in relation to all-cause or cardiovascular deaths but not across multiple causes. <h3>Objective</h3> To assess if different biomarkers provide information about the risk for all-cause and cause-specific mortality. <h3>Design, Setting, and Participants</h3> The Platelet Inhibition and Patient Outcomes (PLATO) trial randomized 18 624 patients with acute coronary syndrome to ticagrelor or clopidogrel from October 2006 through July 2008. In this secondary analysis biomarker substudy, 17 095 patients participated. <h3>Main Outcomes and Measures</h3> Death due to myocardial infarction, heart failure, sudden cardiac death/arrhythmia, bleeding, procedures, other vascular causes, and nonvascular causes, as well as all-cause death. <h3>Exposures</h3> At baseline, levels of cystatin-C, growth differentiation factor-15 (GDF-15), high-sensitivity C-reactive protein, high-sensitivity troponin I and T, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were determined. <h3>Results</h3> The median (interquartile range) age of patients was 62.0 (54.0-71.0) years. Of 17 095 patients, 782 (4.6%) died during follow-up. The continuous associations between biomarkers and all-cause and cause-specific mortality were modeled using Cox models and presented as hazard ratio (HR) comparing the upper vs lower quartile. For all-cause mortality, NT-proBNP and GDF-15 were the strongest markers with adjusted HRs of 2.96 (95% CI, 2.33-3.76) and 2.65 (95% CI, 2.17-3.24), respectively. Concerning death due to heart failure, NT-proBNP was associated with an 8-fold and C-reactive protein, GDF-15, and cystatin-C, with a 3-fold increase in risk. Regarding sudden cardiac death/arrhythmia, NT-proBNP was associated with a 4-fold increased risk and GDF-15 with a doubling in risk. Growth differentiation factor-15 had the strongest associations with other vascular and nonvascular deaths and was possibly associated with death due to major bleeding (HR, 4.91; 95% CI, 1.39-17.43). <h3>Conclusions and Relevance</h3> In patients with acute coronary syndrome, baseline levels of NT-proBNP and GDF-15 were strong markers associated with all-cause death based on their associations with death due to heart failure as well as due to arrhythmia and sudden cardiac death. Growth differentiation factor-15 had the strongest associations with death due to other vascular or nonvascular causes and possibly with death due to bleeding. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT00391872.
Methods for Estimating Demography and Detecting Between-Locus Differences in the Effective Population Size and Mutation Rate
Authors: Kai Zeng, Benjamin C Jackson, Henry J Barton
Journal: Molecular Biology and Evolution (2018)

It is known that the effective population size (Ne) and the mutation rate (u) vary across the genome. Here, we show that ignoring this heterogeneity may lead to biased estimates of past demography. To solve the problem, we develop new methods for jointly inferring past changes in population size and detecting variation in Ne and u between loci. These methods rely on either polymorphism data alone or both polymorphism and divergence data. In addition to inferring demography, we can use the methods to study a variety of questions: 1) comparing sex chromosomes with autosomes (for finding evidence for male-driven evolution, an unequal sex ratio, or sex-biased demographic changes) and 2) analyzing multilocus data from within autosomes or sex chromosomes (for studying determinants of variability in Ne and u). Simulations suggest that the methods can provide accurate parameter estimates and have substantial statistical power for detecting difference in Ne and u. As an example, we use the methods to analyze a polymorphism data set from Drosophila simulans. We find clear evidence for rapid population expansion. The results also indicate that the autosomes have a higher mutation rate than the X chromosome and that the sex ratio is probably female-biased. The new methods have been implemented in a user-friendly package.
Triclosan, a common antimicrobial ingredient, on gut microbiota and gut health
Authors: Katherine Z. Sanidad, Hang Xiao, Guodong Zhang
Journal: Gut Microbes (2018)

Triclosan (TCS) is an antimicrobial compound incorporated into more than 2,000 consumer products. This compound is frequently detected in the human body and causes ubiquitous contamination in the environment, raising concerns about its impact on human health and environmental pollution. Our recent research showed that exposure to TCS exaggerates colonic inflammation and exacerbates development of colitis-associated colon tumorigenesis, via gut microbiome-dependent mechanisms. In this review, we discussed recent research about TCS, as well as other consumer antimicrobials, on the gut microbiome and gut health.
Long non-coding RNAs in hematological malignancies: translating basic techniques into diagnostic and therapeutic strategies
Authors: Nonthaphat Kent Wong, Chien-Ling Huang, Rashidul Islam, Shea Ping Yip
Journal: Journal of Hematology & Oncology (2018)

Recent studies have revealed that non-coding regions comprise the vast majority of the human genome and long non-coding RNAs (lncRNAs) are a diverse class of non-coding RNAs that has been implicated in a variety of biological processes. Abnormal expression of lncRNAs has also been linked to different human diseases including cancers, yet the regulatory mechanisms and functional effects of lncRNAs are still ambiguous, and the molecular details also need to be confirmed. Unlike protein-coding gene, it is much more challenging to unravel the roles of lncRNAs owing to their unique and complex features such as functional diversity and low conservation among species, which greatly hamper their experimental characterization. In this review, we summarize and discuss both conventional and advanced approaches for the identification and functional characterization of lncRNAs related to hematological malignancies. In particular, the utility and advancement of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system as gene-editing tools are envisioned to facilitate the molecular dissection of lncRNAs via different knock-in/out strategies. Besides experimental considerations specific to lncRNAs, the roles of lncRNAs in the pathogenesis and progression of leukemia are also highlighted in the review. We expect that these insights may ultimately lead to clinical applications including development of biomarkers and novel therapeutic approaches targeting lncRNAs.
In vivo hematopoietic stem cell gene therapy ameliorates murine thalassemia intermedia
Authors: Hongjie Wang, Aphrodite Georgakopoulou, Nikoletta Psatha, Chang Li, Chrysi Capsali, Himanshu Bhusan Samal, Achilles Anagnostopoulos, Anja Ehrhardt, Zsuzsanna Izsvák, Thalia Papayannopoulou, Evangelia Yannaki, André Lieber
Journal: Journal of Clinical Investigation (2018)

Current thalassemia gene therapy protocols require the collection of hematopoietic stem/progenitor cells (HSPCs), in vitro culture, lentivirus vector transduction, and retransplantation into myeloablated patients. Because of cost and technical complexity, it is unlikely that such protocols will be applicable in developing countries, where the greatest demand for a β-thalassemia therapy lies. We have developed a simple in vivo HSPC gene therapy approach that involves HSPC mobilization and an intravenous injection of integrating HDAd5/35++ vectors. Transduced HSPCs homed back to the bone marrow, where they persisted long-term. HDAd5/35++ vectors for in vivo gene therapy of thalassemia had a unique capsid that targeted primitive HSPCs through human CD46, a relatively safe SB100X transposase–based integration machinery, a micro-LCR–driven γ-globin gene, and an MGMT(P140K) system that allowed for increasing the therapeutic effect by short-term treatment with low-dose O6-benzylguanine plus bis-chloroethylnitrosourea. We showed in "healthy" human CD46–transgenic mice and in a mouse model of thalassemia intermedia that our in vivo approach resulted in stable γ-globin expression in the majority of circulating red blood cells. The high marking frequency was maintained in secondary recipients. In the thalassemia model, a near-complete phenotypic correction was achieved. The treatment was well tolerated. This cost-efficient and "portable" approach could permit a broader clinical application of thalassemia gene therapy.