tbuckley/cabot-search huggingface dataset:
Effect of <i>Helicobacter pylori</i> on gastrointestinal microbiota: a population-based study in Linqu, a high-risk area of gastric cancer
Authors: Yang Guo, Yang Zhang, Markus Gerhard, Juan-Juan Gao, Raquel Mejias-Luque, Lian Zhang, Michael Vieth, Jun-Ling Ma, Monther Bajbouj, Stepan Suchanek, Wei-Dong Liu, Kurt Ulm, Michael Quante, Zhe-Xuan Li, Tong Zhou, Roland Schmid, Meinhard Classen, Wen-Qing Li, Wei-Cheng You, Kai-Feng Pan
Journal: Gut (2019)

Gastrointestinal microbiota may be involved in Helicobacter pylori-associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential dysbiosis arising from H. pylori infection.Deep sequencing of the microbial 16S ribosomal RNA gene was used to investigate alterations in paired gastric biopsies and stool samples in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment, relative to 49 H. pylori negative subjects.In H. pylori positive subjects, richness and Shannon indexes increased significantly (both p<0.001) after successful eradication and showed no difference to those of negative subjects (p=0.493 for richness and p=0.420 for Shannon index). Differential taxa analysis identified 18 significantly altered gastric genera after eradication. The combination of these genera into a Microbial Dysbiosis Index revealed that the dysbiotic microbiota in H. pylori positive mucosa was associated with advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia/dysplasia) and could be reversed by eradication. Strong coexcluding interactions between Helicobacter and Fusobacterium, Neisseria, Prevotella, Veillonella, Rothia were found only in advanced gastric lesion patients, and were absent in normal/superficial gastritis group. Changes in faecal microbiota included increased Bifidobacterium after successful H. pylori eradication and more upregulated drug-resistant functional orthologs after failed treatment.H. pylori infection contributes significantly to gastric microbial dysbiosis that may be involved in carcinogenesis. Successful H. pylori eradication potentially restores gastric microbiota to a similar status as found in uninfected individuals, and shows beneficial effects on gut microbiota.
Regulation of the Elevated T Cell Glycolysis May Alleviate Acute Graft-Versus-Host Disease Post-Allotransplant
Authors: Qi Wen, Song Yang, Zhong-Shi Lyu, Wei-Li Yao, Yu-Hong Chen, Ting-Ting Han, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Jun Huang, Yuan Kong
Journal: Blood (2019)
Revamping the ovarian tumour microenvironment with an oncolytic adenovirus yields enhanced tumour-infiltrating lymphocyte anti-tumour activity
Authors: J.M. Santos, C. Heiniö, V. Cervera-Carrascon, M. Siurala, D.C.A. Quixabeira, T. de Gruijl, H. Lassus, A. Kanerva, A. Hemminki
Journal: Annals of Oncology (2019)
Applying Causal Inference Methods in Psychiatric Epidemiology
Authors: Henrik Ohlsson, Kenneth S. Kendler
Journal: JAMA Psychiatry (2019)

Associations between putative risk factors and psychiatric and substance use disorders are widespread in the literature. Basing prevention efforts on such findings is hazardous. Applying causal inference methods, while challenging, is central to developing realistic and potentially actionable etiologic models for psychopathology.
Statins in Childhood May Reduce CVD From Familial Hypercholesterolemia
Authors: Anita Slomski
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A KHDC3L mutation resulting in recurrent hydatidiform mole causes genome-wide DNA methylation loss in oocytes and persistent imprinting defects post-fertilisation
Authors: Hannah Demond, Zahra Anvar, Bahia Namavar Jahromi, Angela Sparago, Ankit Verma, Maryam Davari, Luciano Calzari, Silvia Russo, Mojgan Akbarzadeh Jahromi, David Monk, Simon Andrews, Andrea Riccio, Gavin Kelsey
Journal: Genome Medicine (2019)

Abstract Background Maternal effect mutations in the components of the subcortical maternal complex (SCMC) of the human oocyte can cause early embryonic failure, gestational abnormalities and recurrent pregnancy loss. Enigmatically, they are also associated with DNA methylation abnormalities at imprinted genes in conceptuses: in the devastating gestational abnormality biparental complete hydatidiform mole (BiCHM) or in multi-locus imprinting disease (MLID). However, the developmental timing, genomic extent and mechanistic basis of these imprinting defects are unknown. The rarity of these disorders and the possibility that methylation defects originate in oocytes have made these questions very challenging to address. Methods Single-cell bisulphite sequencing (scBS-seq) was used to assess methylation in oocytes from a patient with BiCHM identified to be homozygous for an inactivating mutation in the human SCMC component KHDC3L. Genome-wide methylation analysis of a preimplantation embryo and molar tissue from the same patient was also performed. Results High-coverage scBS-seq libraries were obtained from five KHDC3L c.1A&gt;G oocytes, which revealed a genome-wide deficit of DNA methylation compared with normal human oocytes. Importantly, germline differentially methylated regions (gDMRs) of imprinted genes were affected similarly to other sequence features that normally become methylated in oocytes, indicating no selectivity towards imprinted genes. A range of methylation losses was observed across genomic features, including gDMRs, indicating variable sensitivity to defects in the SCMC. Genome-wide analysis of a pre-implantation embryo and molar tissue from the same patient showed that following fertilisation methylation defects at imprinted genes persist, while most non-imprinted regions of the genome recover near-normal methylation post-implantation. Conclusions We show for the first time that the integrity of the SCMC is essential for de novo methylation in the female germline. These findings have important implications for understanding the role of the SCMC in DNA methylation and for the origin of imprinting defects, for counselling affected families, and will help inform future therapeutic approaches.
Cytomegalovirus in Steroid-Refractory Immune Checkpoint Inhibition–Related Colitis
Authors: Sietze T. van Turenhout, Marieke Berghuis, Petur Snaebjornsson, Sofie Wilgenhof, J.A. Burgers, John B.A.G. Haanen, Jolanda M. van Dieren
Journal: Journal of Thoracic Oncology (2019)
Treatment with rapamycin can restore regulatory T-cell function in IPEX patients
Authors: Laura Passerini, Federica Barzaghi, Rosalia Curto, Claudia Sartirana, Graziano Barera, Francesca Tucci, Luca Albarello, Alberto Mariani, Pier Alberto Testoni, Elena Bazzigaluppi, Emanuele Bosi, Vito Lampasona, Olaf Neth, Daniele Zama, Manfred Hoenig, Ansgar Schulz, Markus G. Seidel, Ivana Rabbone, Sven Olek, Maria G. Roncarolo, Maria P. Cicalese, Alessandro Aiuti, Rosa Bacchetta
Journal: Journal of Allergy and Clinical Immunology (2019)
Interleukin-22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cells
Authors: Nick Powell, Eirini Pantazi, Polychronis Pavlidis, Anastasia Tsakmaki, Katherine Li, Feifei Yang, Aimee Parker, Carmen Pin, Domenico Cozzetto, Danielle Minns, Emilie Stolarczyk, Svetlana Saveljeva, Rami Mohamed, Paul Lavender, Behdad Afzali, Jonathan Digby-Bell, Tsui Tjir-Li, Arthur Kaser, Joshua Friedman, Thomas T MacDonald, Gavin A Bewick, Graham M Lord
Journal: Gut (2019)

Objective The functional role of interleukin-22 (IL22) in chronic inflammation is controversial, and mechanistic insights into how it regulates target tissue are lacking. In this study, we evaluated the functional role of IL22 in chronic colitis and probed mechanisms of IL22-mediated regulation of colonic epithelial cells. Design To investigate the functional role of IL22 in chronic colitis and how it regulates colonic epithelial cells, we employed a three-dimentional mini-gut epithelial organoid system, in vivo disease models and transcriptomic datasets in human IBD. Results As well as inducing transcriptional modules implicated in antimicrobial responses, IL22 also coordinated an endoplasmic reticulum (ER) stress response transcriptional programme in colonic epithelial cells. In the colon of patients with active colonic Crohn’s disease (CD), there was enrichment of IL22-responsive transcriptional modules and ER stress response modules. Strikingly, in an IL22-dependent model of chronic colitis, targeting IL22 alleviated colonic epithelial ER stress and attenuated colitis. Pharmacological modulation of the ER stress response similarly impacted the severity of colitis. In patients with colonic CD, antibody blockade of IL12p40, which simultaneously blocks IL12 and IL23, the key upstream regulator of IL22 production, alleviated the colonic epithelial ER stress response. Conclusions Our data challenge perceptions of IL22 as a predominantly beneficial cytokine in IBD and provide novel insights into the molecular mechanisms of IL22-mediated pathogenicity in chronic colitis. Targeting IL22-regulated pathways and alleviating colonic epithelial ER stress may represent promising therapeutic strategies in patients with colitis. Trial registration number NCT02749630 .
<i>Notes from the Field:</i> Methylmercury Toxicity from a Skin Lightening Cream Obtained from Mexico — California, 2019
Authors: Anita Mudan, Lori Copan, Richard Wang, Amy Pugh, Jacob Lebin, Tracy Barreau, Robert L. Jones, Sutapa Ghosal, Mai Lee, Timothy Albertson, Jeffery M. Jarrett, Jean Lee, David Betting, Cynthia D. Ward, Alfonsina De Leon Salazar, Craig G. Smollin, Paul D. Blanc
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Author(s): Mudan, Anita; Copan, Lori; Wang, Richard; Pugh, Amy; Lebin, Jacob; Barreau, Tracy; Jones, Robert L; Ghosal, Sutapa; Lee, Mai; Albertson, Timothy; Jarrett, Jeffery M; Lee, Jean; Betting, David; Ward, Cynthia D; De Leon Salazar, Alfonsina; Smollin, Craig G; Blanc, Paul D
White eggs and yellow-brown spots on the pubic-perineal hairs
Authors: Tian Wang, Yi-Ming Fan
Journal: BMJ (2019)

A 53 year old man presented with a two week history of pubic itch, which was worse at night, and small droplets of blood in his underwear. He reported that during winter he usually bathed once every two to three days (this presentation was during the month of February), and recalled staying at a small guesthouse with poor sanitation three weeks earlier. Cutaneous examination showed numerous white eggs and yellow-brown spots attached to the hair in the pubic-perineal area and adjacent hypogastrium and groin. Serological tests for HIV and syphilis were negative.

Dermatoscopy was performed (fig 1).



Fig 1 
Dermatoscopy …
Response to Comment on Norhammar et al. Undetected Dysglycemia Is an Important Risk Factor for Two Common Diseases, Myocardial Infarction and Periodontitis: A Report From the PAROKRANK Study. Diabetes Care 2019;42:1504–1511
Authors: Anna Norhammar, Barbro Kjellström, Natalie Habib, Anders Gustafsson, Björn Klinge, Åke Nygren, Per Näsman, Elisabet Svenungsson, Lars Rydén
Journal: Diabetes Care (2019)

We are grateful for the interest in our article (1) and the well-taken question raised by Li et al. (2). In previous reports from our group (3,4) we underlined that classification as impaired fasting glucose (IFG) will miss a large proportion of patients with dysglycemia (impaired …
TRK Fusions Are Enriched in Cancers with Uncommon Histologies and the Absence of Canonical Driver Mutations
Authors: Ezra Y. Rosen, Debra A. Goldman, Jaclyn F. Hechtman, Ryma Benayed, Alison M. Schram, Emiliano Cocco, Sophie Shifman, Yixiao Gong, Ritika Kundra, James P. Solomon, Alberto Bardelli, Maurizio Scaltriti, Alexander Drilon, Alexia Iasonos, Barry S. Taylor, David M. Hyman
Journal: Clinical Cancer Research (2019)

TRK inhibitors achieve marked tumor-agnostic efficacy in TRK fusion-positive cancers and consequently are now an established standard of care. Little is known, however, about the demographics, outcomes, response to alternative standard therapies, or genomic characteristics of TRK fusion-positive cancers.Utilizing a center-wide screening program involving more than 26,000 prospectively sequenced patients, genomic and clinical data from all cases with TRK fusions were extracted. An integrated analysis was performed of genomic, therapeutic, and phenomic outcomes.We identified 76 cases with confirmed TRK fusions (0.28% overall prevalence) involving 48 unique rearrangements and 17 cancer types. The presence of a TRK fusion was associated with depletion of concurrent oncogenic drivers (P < 0.001) and lower tumor mutation burden (P < 0.001), with the exception of colorectal cancer where TRK fusions cooccur with microsatellite instability (MSI-H). Longitudinal profiling in a subset of patients indicated that TRK fusions were present in all sampled timepoints in 82% (14/17) of cases. Progression-free survival on first-line therapy, excluding TRK inhibitors, administered for advanced disease was 9.6 months [95% confidence interval (CI), 4.8-13.2]. The best overall response rate achieved with chemotherapy containing-regimens across all lines of therapy was 63% (95% CI, 41-81). Among 12 patients treated with checkpoint inhibitors, a patient with MSI-H colorectal cancer had the only observed response.TRK fusion-positive cancers can respond to alternative standards of care, although efficacy of immunotherapy in the absence of other predictive biomarkers (MSI-H) appears limited. TRK fusions are present in tumors with simple genomes lacking in concurrent drivers that may partially explain the tumor-agnostic efficacy of TRK inhibitors.
Incidence of Hypoparathyroidism After Thyroid Cancer Surgery in South Korea, 2007-2016
Authors: Song Vogue Ahn, Joon-Hyop Lee, Erin Allana Bove-Fenderson, So Young Park, Michael Mannstadt, Sihoon Lee
Journal: JAMA (2019)

This study uses South Korean administrative database data to assess changes in incidence of postthyroidectomy hypoparathyroidism during a period of fluctuations in thyroid cancer screening and surgery between 2007 and 2016.
Clinical Evidence for Association of Acupuncture and Acupressure With Improved Cancer Pain
Authors: Yihan He, Xinfeng Guo, Brian H. May, Anthony Lin Zhang, Yihong Liu, Chuanjian Lu, Jun J. Mao, Charlie Changli Xue, Haibo Zhang
Journal: JAMA Oncology (2019)

Research into acupuncture and acupressure and their application for cancer pain has been growing, but the findings have been inconsistent.To evaluate the existing randomized clinical trials (RCTs) for evidence of the association of acupuncture and acupressure with reduction in cancer pain.Three English-language databases (PubMed, Embase, and CINAHL) and 4 Chinese-language biomedical databases (Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang) were searched for RCTs published from database inception through March 31, 2019.Randomized clinical trials that compared acupuncture and acupressure with a sham control, analgesic therapy, or usual care for managing cancer pain were included.Data were screened and extracted independently using predesigned forms. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. Random-effects modeling was used to calculate the effect sizes of included RCTs. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach.The primary outcome was pain intensity measured by the Brief Pain Inventory, Numerical Rating Scale, Visual Analog Scale, or Verbal Rating Scale.A total of 17 RCTs (with 1111 patients) were included in the systematic review, and data from 14 RCTs (with 920 patients) were used in the meta-analysis. Seven sham-controlled RCTs (35%) were notable for their high quality, being judged to have a low risk of bias for all of their domains, and showed that real (compared with sham) acupuncture was associated with reduced pain intensity (mean difference [MD], -1.38 points; 95% CI, -2.13 to -0.64 points; I2 = 81%). A favorable association was also seen when acupuncture and acupressure were combined with analgesic therapy in 6 RCTs for reducing pain intensity (MD, -1.44 points; 95% CI, -1.98 to -0.89; I2 = 92%) and in 2 RCTs for reducing opioid dose (MD, -30.00 mg morphine equivalent daily dose; 95% CI, -37.5 mg to -22.5 mg). The evidence grade was moderate because of the substantial heterogeneity among studies.This systematic review and meta-analysis found that acupuncture and/or acupressure was significantly associated with reduced cancer pain and decreased use of analgesics, although the evidence level was moderate. This finding suggests that more rigorous trials are needed to identify the association of acupuncture and acupressure with specific types of cancer pain and to integrate such evidence into clinical care to reduce opioid use.
Sustained Weight Loss and Risk of Breast Cancer in Women 50 Years and Older: A Pooled Analysis of Prospective Data
Authors: Lauren R Teras, Alpa V Patel, Molin Wang, Shiaw-Shyuan Yaun, Kristin Anderson, Roderick Brathwaite, Bette J Caan, Yu Chen, Avonne E Connor, A Heather Eliassen, Susan M Gapstur, Mia M Gaudet, Jeanine M Genkinger, Graham G Giles, I-Min Lee, Roger L Milne, Kim Robien, Norie Sawada, Howard D Sesso, Meir J Stampfer, Rulla M Tamimi, Cynthia A Thomson, Shoichiro Tsugane, Kala Visvanathan, Walter C Willett, Anne Zeleniuch-Jacquotte, Stephanie A Smith-Warner
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk. Methods Associations between weight change and risk of breast cancer were examined among women aged 50 years and older in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (interval 1 median = 5.2 years; interval 2 median = 4.0 years). Sustained weight loss was defined as no less than 2 kg lost in interval 1 that was not regained in interval 2. Among 180 885 women, 6930 invasive breast cancers were identified during follow-up. Results Compared with women with stable weight (±2 kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (&amp;gt;2–4.5 kg lost: hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70 to 0.96; &amp;gt;4.5–&amp;lt;9 kg lost: HR = 0.75, 95% CI = 0.63 to 0.90; ≥9 kg lost: HR = 0.68, 95% CI = 0.50 to 0.93). Women who lost at least 9 kg and gained back some (but not all) of it were also at a lower risk of breast cancer. Other patterns of weight loss and gain over the two intervals had a similar risk of breast cancer to women with stable weight. Conclusions These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged 50 years and older. Breast cancer prevention may be a strong weight-loss motivator for the two-thirds of American women who are overweight or obese.
Extensively Drug-Resistant Shigellosis in Australia among Men Who Have Sex with Men
Authors: Deborah Williamson, Danielle Ingle, Benjamin Howden
Journal: New England Journal of Medicine (2019)

Extensively Drug-Resistant Shigellosis in Australia among Men Who Have Sex with MenTo the Editor: In high-income countries, most shigellosis is associated with international travel to areas in which the condition is endemic or with sexual transmission among men who have sex with men (MSM).In cases of shigellosis in which oral antimicrobial treatment is indicated, the recommended first-line oral antimicrobial treatment for shigellosis is ciprofloxacin, with azithromycin as an alternative.Some studies have used whole-genome sequencing to describe the dissemination of antimicrobial-resistant Shigella sonnei and S. flexneri lineages among MSM. 1,2 Although resistant to multiple antimicrobials, MSM-related shigella lineages have generally remained susceptible to at least one orally available antimicrobial.To date, sporadic shigellosis clusters that are resistant to all orally available antimicrobials (i.e., extensively drug-resistant shigella) have been reported among MSM. 3,4 In the absence of oral antimicrobials, and in severe disease, intravenous treatment with ceftriaxone may be the only alternative treatment option.In Australia, shigellosis is a notifiable disease under public health legislation.The Microbiological Diagnostic Unit Public Health Laboratory receives all shigella isolates in the state of Victoria, Australia (population, approximately 6.4 million).Isolates undergo antimicrobial susceptibility testing and routine whole-genome sequencing.Details of the methods are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.Between February 1, 2018, and May 31, 2019, a total of 184 isolates of extensively drug-resistant S. sonnei were identified from 12 female patients and 172 male patients in Victoria (Fig. 1).Phylogenomic analysis indicated that 171 of the isolates formed a distinct clonal lineage within
CARsomes inhibit airway allergic inflammation in mice by inducing antigen‐specific Th2 cell apoptosis
Authors: Huan‐Ping Zhang, Ying‐Xue Sun, Zhi Lin, Gui Yang, Jiang‐Qi Liu, Li‐Hua Mo, Xiao‐Rui Geng, Yan‐Nan Song, Hao‐Tao Zeng, Miao Zhao, Guo‐Shun Li, Zhi‐Gang Liu, Ping‐Chang Yang
Journal: Allergy (2019)

Skewed T helper (Th)2 response plays a crucial role in the pathogenesis of allergic diseases. The therapeutic efficacy for allergic diseases is unsatisfactory currently. This study aims to regulate the skewed Th2 response with CARsomes.The CARsome consisted of an epitope of Dermatophagoides farina-1 (Derf1), a segment of the anti-DEC205 antibody, the scFv, and an open reading frame of perforin. This fusion protein binds to DEC205 molecule on the surface of exosomes derived from dendritic cells (DC). The effects of CARsome on inducing antigen (Ag)-specific Th2 cell apoptosis were assessed both in vivo and in vitro.Exposure to CARsomes in the culture induced Ag-specific Th2 cell apoptosis. Injection of CARsomes through the vein puncture also induced Ag-specific Th2 cell apoptosis in the lungs of sensitized mice. CARsomes could induce Ag-specific regulatory T cells. Administration of CARsomes efficiently inhibited experimental allergic airway inflammation.The CARsomes can inhibit allergic airway inflammation by inducing Ag-specific Th2 cell apoptosis and induce Ag-specific regulatory T cells. The data suggest that CARsomes have the translational potential to be used to treat allergic airway inflammation.