tbuckley/cabot-search huggingface dataset:
Sulforaphane elicts dual therapeutic effects on Renal Inflammatory Injury and crystal deposition in Calcium Oxalate Nephrocalcinosis
Authors: Haoran Liu, Xiaoqi Yang, Kun Tang, Tao Ye, Chen Duan, Peng Lv, Libin Yan, Xiaoliang Wu, Zhiqiang Chen, Jianhe Liu, Yaoliang Deng, Guohua Zeng, Jinchun Xing, Zhangqun Ye, Hua Xu
Journal: Theranostics (2020)

Intrarenal calcium oxalate (CaOx) crystals induce renal tubular epithelial cells (TECs) injury and inflammation, which involve Toll-like receptor 4 (TLR4)/interferon regulatory factor 1 (IRF1) signaling. Additionally, infiltrating macrophages (Mϕs) might influence intrarenal CaOx crystals and CaOx-induced renal injury. Although the roles of nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating inflammation and macrophage polarization are well characterized, its potential mechanisms in regulating CaOx nephrocalcinosis remain undefined. Methods: We used a Gene Expression Omnibus dataset to analyze gene-expression profiles. Luciferase reporter, western blot, quantitative polymerase chain reaction, immunofluorescence staining, fluorescence in situ hybridization, positron emission tomography computed tomography imaging, flow cytometry, and chromatin immunoprecipitation assays were employed to study the mechanism of miR-93-TLR4/IRF1 regulation by Nrf2. Anti-inflammatory activity and regulation of macrophage polarization by Nrf2 were investigated in vitro and in vivo. Results: We found that stone-mediated kidney inflammation significantly affected stone growth, and that sulforaphane attenuated CaOx nephrocalcinosis-induced kidney injury and renal CaOx crystals deposition. Additionally, Nrf2 levels significantly increased and negatively correlated with TLR4 and IRF1 levels in a mouse model of CaOx nephrocalcinosis following sulforaphane treatment. Moreover, Nrf2 suppressed TLR4 and IRF1 levels and decreased M1-macrophage polarization which induced by supernatants from COM-stimulated TECs in vitro. In terms of mechanism, transcription factor analyses, microRNA microarray, and chromatin immunoprecipitation assays showed that Nrf2 exhibited positive transcriptional activation of miR-93-5p. In addition, Luciferase reporter, qRT-PCR, and western blot validated that miR-93-5p targets TLR4 and IRF1 mRNA. Furthermore, suppressed miR-93-5p expression partially reversed Nrf2-dependent TLR4/IRF1 downregulation. Conclusions: The results suggested that sulforaphane might promote M2Mϕ polarization and inhibit CaOx nephrocalcinosis-induced inflammatory injury to renal tubular epithelial cells via the Nrf2-miR-93-TLR4/IRF1 pathway in vitro and in vivo.
Human CRY1 variants associate with attention deficit/hyperactivity disorder
Authors: O. Emre Onat, M. Ece Kars, Şeref Gül, Kaya Bilguvar, Yiming Wu, Ayşe Özhan, Cihan Aydın, A. Nazlı Başak, M. Allegra Trusso, Arianna Goracci, Chiara Fallerini, Alessandra Renieri, Jean-Laurent Casanova, Yuval Itan, Cem E. Atbaşoğlu, Meram C. Saka, İ. Halil Kavaklı, Tayfun Özçelik
Journal: Journal of Clinical Investigation (2020)

Attention deficit/hyperactivity disorder (ADHD) is a common and heritable phenotype frequently accompanied by insomnia, anxiety, and depression. Here, using a reverse phenotyping approach, we report heterozygous coding variations in the core circadian clock gene cryptochrome 1 in 15 unrelated multigenerational families with combined ADHD and insomnia. The variants led to functional alterations in the circadian molecular rhythms, providing a mechanistic link to the behavioral symptoms. One variant, CRY1Δ11 c.1657+3A>C, is present in approximately 1% of Europeans, therefore standing out as a diagnostic and therapeutic marker. We showed by exome sequencing in an independent cohort of patients with combined ADHD and insomnia that 8 of 62 patients and 0 of 369 controls carried CRY1Δ11. Also, we identified a variant, CRY1Δ6 c.825+1G>A, that shows reduced affinity for BMAL1/CLOCK and causes an arrhythmic phenotype. Genotype-phenotype correlation analysis revealed that this variant segregated with ADHD and delayed sleep phase disorder (DSPD) in the affected family. Finally, we found in a phenome-wide association study involving 9438 unrelated adult Europeans that CRY1Δ11 was associated with major depressive disorder, insomnia, and anxiety. These results defined a distinctive group of circadian psychiatric phenotypes that we propose to designate as "circiatric" disorders.
Abstract 11315: Relation of Systolic Blood Pressure on the Next Day to Post Discharge Mortality in Hospitalized Heart Failure Patients With Preserved Ejection Fraction - A Report From the JASPER Registry
Authors: Yu Sato, Akiomi Yoshihisa, Masayoshi Oikawa, Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Kazuhiro Yamamoto, Yasuchika Takeishi, Toshihisa Anzai
Journal: Circulation (2018)

Introduction: Acute decompensated heart failure (HF) requires urgent assessments and treatments. Decompensated HF patients are classified into the clinical scenario, which is based on initial systo...
Abstract 15723: Vitamin Deficiency is Associated With a Higher Risk for Hospitalizations in Veterans With Heart Failure
Authors: Raquel Aparicio-Ugarriza, Douglas Salguero, Yaqub Nadeem Mohammed, Juliana Ferri-Guerra, Dhanya Baskaran, Seyed Abbas Mirabbasi, Alexis Rodriguez, Jorge G Ruiz
Journal: Circulation (2019)

Introduction: Vitamin D (VitD) deficiency is associated with cardiovascular risk factors, myocardial dysfunction, mortality and sudden cardiac death in patients with heart failure (HF). Frailty inc...
<i>H pylori</i> treatment reduced risk for gastric cancer in patients with a family history of gastric cancer
Authors: Joseph J. Jennings
Journal: Annals of Internal Medicine (2020)

Choi IJ, Kim CG, Lee JY, et al. Family history of gastric cancer andHelicobacter pyloritreatment. N Engl J Med. 2020;382:427-36. 31995688.
Film: Filmmaker focuses on female infanticide
Authors: Sanjit Bagchi
Journal: BMJ (2005)

Aworld without women might sound absurd, but in parts of rural India, where female infanticide is on the increase, it might not seem such a distant scenario. The feature film Matrubhoomi, subtitled A Nation Without Women and set for general release in India this month, explores the hypothetical consequences of widespread female infanticide and, unsurprisingly, finds them devastating. Directed by the up and coming Manish Jha, Matrubhoomi is a horrifying tale of gender discrimination and violence against women in India.

In one scene a man waits outside the family home while his wife is in labour. He gets excited by the birth of the child, but the mood changes with the announcement that it's a girl. The newborn is brutally killed, dipped into a large vat of milk. “Next year, a boy,” a gruff voice commands.

In the near womanless world of Matrubhoomi, men seek to release their sexual desire through rape, pornography, homosexuality, and bestiality. Against this backdrop, a desperate family hunts down a pretty teenager, who is sold by her father at a good price. She is forced to marry five brothers, who, along with their father, repeatedly rape her. Only the youngest brother begins to grow emotionally close to her, but then he is murdered by the eldest brother. When the girl plans to escape with a servant from a lower caste the pair are caught. This triggers a caste war, and the teenager is chained up in a cowshed and gang raped by men from both the castes. When she becomes pregnant everyone claims paternity.

Much more brutal than Shekhar Kapur's Bandit Queen, Matrubhoomi could be seen as providing the false sense of comfort that the film is a mere exaggeration. But it could also be regarded as a worrying reminder of the systematic infanticide that has plagued India for years. The killing of girl children has increased in the past couple of decades, thanks in part to illegal sex selection using ultrasonography, and it is thought that some doctors have promoted sex selective abortions (www.indiafemalefoeticide.org/technology.htm).

Despite legal prohibitions, India's girl to boy ratio (aged 0-6 years) has declined from 945 to 1000 in 1991, to 927 to 1000 in 2001 (http://www.censusindia.net/data/chapter6.pdf). And in the north Indian state of Punjab, the ratio has declined from 875 to 1000 in 1991, to 793 to 1000 in 2001. While Matrubhoomi is clearly a cinematic exaggeration, the country's shortage of women has led to a rise in the abduction and kidnapping of girls, forced polyandry, gang rape, and child prostitution in various Indian provinces (www.indiatogether.org/2003/aug/wom-sexratio.htm).
Cytogenetic risk score maintains its prognostic significance in <scp>AML</scp> patients with detectable measurable residual disease undergoing transplantation in remission: On behalf of the acute leukemia working party of the European society for blood and marrow transplantation
Authors: Arnon Nagler, Myriam Labopin, Jonathan Canaani, Riitta Niittyvuopio, Gerard Socié, Nicolaus Kröger, Maija Itäla‐Remes, Ibrahim Yakoub‐Agha, Hélène Labussière‐Wallet, Maria P. Gallego‐Hernanz, Eric Deconinck, Patrice Chevallier, Jürgen Finke, Jordi Esteve, Mohamad Mohty
Journal: American Journal of Hematology (2020)

While evidence for measurable residual disease (MRD) is a harbinger of inferior outcome in acute myeloid leukemia (AML) patients referred for allogeneic stem cell transplantation (allo-SCT), the exact clinical trajectory of specific patient subsets in this clinical setting is undefined. Using a recently published prognostic cytogenetic model (Canaani et al. Leukemia 2019) we evaluated whether this model applied also to studies of patients with positive MRD. The analysis comprised MRD+ patients in first complete remission undergoing allo-SCT from a matched sibling donor or unrelated donor. Seven hundred and seventy-five patients were evaluated with a median follow-up duration of 22 months. Cytogenetic risk score was favorable, intermediate/FLT3wt intermediate/FLT3-ITD3, and adverse in 15%, 28.3%, 37% and 19.7% of the patients, respectively. Favorable and intermediate/FLT3wt risk patients had 2-year leukemia-free survival rates of 78% and 61%, respectively, compared with only 50% and 37% for intermediate/FLT3-ITD3 and adverse risk patients, respectively (P < .001). In multivariate analysis adverse and intermediate/FLT3-ITD3 risk patients were more likely to experience disease relapse compared with favorable risk patients [hazard ratio (HR) = 3.9, 95% confidence interval (CI), 2.1-7.3; P < .001, and HR = 4.4, CI 95%, 2.4-7.8; P < .001, respectively]. The European society for blood and marrow transplantation cytogenetic risk score is a valuable adjunct for risk stratification of MRD+ AML patients.
Initial clinical experience with simple orchiectomy procedures in the context of transition-related surgeries
Authors: Tommy Hana, Lucshman Raveendran, Ethan Grober, Emery Potter, Nolan Blodgett, Yonah Krakowsky
Journal: International Journal of Transgender Health (2020)

Background : One of the more common procedures conducted through the transition-related surgeries (TRSs) program is simple orchiectomy. Due to the relative novelty of TRS in Canada, national perioperative guidelines for simple orchiectomy in the context of TRS are yet to be developed. Furthermore, there is a void in the literature describing the indications and outcomes of simple orchiectomy among transgender individuals. Aims : This study is the first descriptive case series in Canada highlighting our experience with simple orchiectomy in the context of TRS. Methods : This study retrospectively assessed data from electronic patient medical records of 16 patients who had simple orchiectomy procedures at Women's College Hospital in Toronto, Canada from August 2018 to April 2019. Data were collected using a standardized data collection form which includes patient baseline demographic data, and objective and subjective clinical outcomes. Results : Mean age at surgery was 32.6 ± 10.4 years and mean time to surgery following the initial approval of referral was 9.9 ± 8.5 weeks. A majority of referrals (n = 13, 81.3%) were from urban areas with specialized TRS services. The average time on hormones was 3.1 ± 1.9 years. In terms of post-surgical complications at the 30-day day follow-up visit, there was a single post-operative sperm granuloma reported. There were no other complications identified post-surgery in our patient case series. Discussion : In Ontario, the growing recognition of the benefits of TRS has led to the development of a publicly funded pathway to TRS surgery. This study is the first assessment of simple orchiectomy performed for TRS in Canada, and it has shown that the procedure is safe and reproducible. Due to its benefits, coordinating safe and efficient access of care for this procedure should be an important action item for health systems. This study is limited by its low sample size.
Predictive Value of Molecular Subtypes in Premenopausal Women with Hormone Receptor–positive Early Breast Cancer: Results from the ABCSG Trial 5
Authors: Zsuzsanna Bago-Horvath, Margaretha Rudas, Christian F. Singer, Richard Greil, Marija Balic, Sigurd F. Lax, Werner Kwasny, Wolfgang Hulla, Michael Gnant, Martin Filipits
Journal: Clinical Cancer Research (2020)

Abstract Purpose: To assess the predictive value of molecular breast cancer subtypes in premenopausal patients with hormone receptor–positive early breast cancer who received adjuvant endocrine treatment or chemotherapy. Experimental Design: Molecular breast cancer subtypes were centrally assessed on whole tumor sections by IHC in patients of the Austrian Breast and Colorectal Cancer Study Group Trial 5 who had received either 5 years of tamoxifen/3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Luminal A disease was defined as Ki67 &amp;lt;20% and luminal B as Ki67 ≥20%. The luminal B/HER2-positive subtype displayed 3+ HER2-IHC or amplification by ISH. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic factors. Results: 185 (38%), 244 (50%), and 59 (12%) of 488 tumors were classified as luminal A, luminal B/HER2-negative and luminal B/HER2-positive, respectively. Luminal B subtypes were associated with poor outcome. Patients with luminal B tumors had a significantly shorter RFS [adjusted HR for recurrence: 2.22; 95% confidence interval (CI), 1.41–3.49; P = 0.001] and OS (adjusted HR for death: 3.51; 95% CI, 1.80–6.87; P &amp;lt; 0.001). No interaction between molecular subtypes and treatment was observed (test for interaction: P = 0.84 for RFS; P = 0.69 for OS). Conclusions: Determination of molecular subtypes by IHC is an independent prognostic factor for recurrence and death in premenopausal women with early-stage, hormone receptor–positive breast cancer but is not predictive for outcome of adjuvant treatment with tamoxifen/goserelin or CMF. See related commentary by Hunter et al., p. 5543
THU0454 SOMATIC SYMPTOMS IN FIBROMYALGIA AND THEIR CORRELATION WITH DRUG TREATMENT
Authors: M. Antivalle, M. Agosti, A. Batticciotto, S. Costi, V. Giorgi, P. Sarzi Puttini
Journal: Annals of the Rheumatic Diseases (2020)

Background: Drug treatment in fibromyalgia (FM) is often disappointingly ineffective, and there are currently very few data to support therapeutic choices towards a personalized medicine approach. Objectives: To evaluate the prevalence of selected somatic symptoms in FM, and to study their relationship with drug treatments. Methods: The study population consisted of 526 patients (471 F 55 M, mean age 47.31±11.33 yrs) affected by FM not associated with other rheumatic diseases. All patients were required to compile a questionnaire reporting the presence of 42 somatic symptoms -as suggested (1) – in the last 7 days. Drug usage was assessed by interview. Results: On average, patients reported the presence of 17.04±6.68 symptoms (range 4-35), with ample variations in the prevalence of different symptoms (Fig. 1), ranging from over 95% (fatigue and muscle pain) to less than 10 %, seizures being reported by only 2 patients (0.4%). 31.1% of patients were not taking any drug for their FM. The most frequently used drugs were analgesics (ANA, 41.7%) followed by benzodiazepines (BD, 29.1%), SSRIs (16%), gabapentinoids (GABA, 14,4%), and NSRI (14.3%) (Fig. 2). Different drugs were associated with a different spectrum of somatic symptoms: as compared to non users, BD users reported a significantly higher (p&lt; 0.05 by chi-square test) prevalence of irritable bowel (65.4% vs 52.3%), fatigue (98.7% vs 94.9%), thinking difficulties (78.4% vs 68.5%), muscle weakness (94.1% vs 81.7%), abdominal pain (55.6% vs 43.9%), insomnia (73.9% vs 56.6%), depression (63.4 % vs 37.2%), constipation (60.1% vs 42.9%), pain in upper abdomen (50.3% vs 40.2%), nausea (53.6% vs 38.3%), nervousness (71.9% vs 61.5%), chest pain (49.0 vs 37.75), blurred vision (65.4% vs 53.6%), dry mouth (72.5% vs 52.3%), itching (56.2% vs 44.5%), vomiting (13.7% vs 7.8%), taste change (22.2% vs 12.7%), dry eyes (55.6% vs 41.0%), breath shortness (56.9% vs 47.7%), appetite loss (33.3% vs 19.7%), painful urination (15.0% vs 8.4%), and bladder spasms (18.3% vs 8.6%). NRSI users reported a significantly higher prevalence of thinking difficulties, constipation, blurred vision, dry mouth, wheezing, dry eyes, easy bruising. Among GABA users, there was a higher prevalence of thinking difficulties, numbness, insomnia, constipation, nausea, dry mouth, dry eyes, appetite loss, sun sensitivity, easy bruising, and bladder spasms. In no cases a higher prevalence of symptoms was recorded in drug non users vs users. Conclusion: The usage of different drugs in FM is associated with different somatic symptoms. The higher prevalence of symptoms in drug users as compared to non users raises serious questions concerning the opportunity or the appropriateness of drug selection in FM. References: [1]Wolfe F., et al. Arthritis Care Res (Hoboken). 2010 May;62(5):600-10 Disclosure of Interests: : None declared
A novel miR-1291-ERRα-CPT1C axis modulates tumor cell proliferation, metabolism and tumorigenesis
Authors: Yixin Chen, Yanying Zhou, Fangwei Han, Yingyuan Zhao, Meijuan Tu, Yongtao Wang, Can Huang, Shicheng Fan, Panpan Chen, Xinpeng Yao, Lihuan Guan, Ai-Ming Yu, Frank J. Gonzalez, Min Huang, Huichang Bi
Journal: Theranostics (2020)

Rationale: MicroRNAs are known to influence the development of a variety of cancers.Previous studies revealed that miR-1291 has antiproliferative functions in cancer cells.Carnitine palmitoyltransferase 1C (CPT1C) has a vital role in mitochondrial energy metabolism and modulation of cancer cell proliferation.Since both miR-1291 and CPT1C regulate tumor cell metabolism and cancer progression, we hypothesized that they might be regulated synergistically.Methods: A series of cell phenotype indicators, such as BrdU, colony formation, cell cycle, ATP production, ROS accumulation and cell ability to resist metabolic stress, were performed to clarify the effects of miR-1291 and ERRα expression on tumor cell proliferation and metabolism.A xenograft tumor model was used to evaluate cell tumorigenesis.Meta-analysis and bioinformatic prediction were applied in the search for the bridge-link between miR-1291 and CPT1C.RT-qPCR, western-blot and IHC analysis were used for the detection of mRNA and protein expression.Luciferase assays and ChIP assays were conducted for in-depth mechanism studies.Results: The expression of miR-1291 inhibited growth and tumorigenesis as a result of modulation of metabolism.CPT1C expression was indirectly and negatively correlated with miR-1291 levels.ESRRA was identified as a prominent differentially expressed gene in both breast and pancreatic cancer samples, and estrogen-related receptor α (ERRα) was found to link miR-1291 and CPT1C.MiR-1291 targeted ERRα and CPT1C was identified as a newly described ERRα target gene.Moreover, ERRα was found to influence cancer cell metabolism and proliferation, consistent with the cellular changes caused by miR-1291. Conclusion:This study demonstrated the existence and mechanism of action of a novel miR-1291-ERRα-CPT1C cancer metabolism axis that may provide new insights and strategies for the development of miRNA-based therapies for malignant cancers.
Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1
Authors: Sofiane Ouerd, Noureddine Idris-Khodja, Michelle Trindade, Nathanne S Ferreira, Olga Berillo, Suellen C Coelho, Mario F Neves, Karin A Jandeleit-Dahm, Pierre Paradis, Ernesto L Schiffrin
Journal: Cardiovascular Research (2020)

Abstract Aims NADPH oxidase (NOX) 1 but not NOX4-dependent oxidative stress plays a role in diabetic vascular disease, including atherosclerosis. Endothelin (ET)-1 has been implicated in diabetes-induced vascular complications. We showed that crossing mice overexpressing human ET-1 selectively in endothelium (eET-1) with apolipoprotein E knockout (Apoe−/−) mice enhanced high-fat diet-induced atherosclerosis in part by increasing oxidative stress. We tested the hypothesis that ET-1 overexpression in the endothelium would worsen atherosclerosis in type 1 diabetes through a mechanism involving NOX1 but not NOX4. Methods and results Six-week-old male Apoe−/− and eET-1/Apoe−/− mice with or without Nox1 (Nox1−/y) or Nox4 knockout (Nox4−/−) were injected intraperitoneally with either vehicle or streptozotocin (55 mg/kg/day) for 5 days to induce type 1 diabetes and were studied 14 weeks later. ET-1 overexpression increased 2.5-fold and five-fold the atherosclerotic lesion area in the aortic sinus and arch of diabetic Apoe−/− mice, respectively. Deletion of Nox1 reduced aortic arch plaque size by 60%; in contrast, Nox4 knockout increased lesion size by 1.5-fold. ET-1 overexpression decreased aortic sinus and arch plaque alpha smooth muscle cell content by ∼35% and ∼50%, respectively, which was blunted by Nox1 but not Nox4 knockout. Reactive oxygen species production was increased two-fold in aortic arch perivascular fat of diabetic eET-1/Apoe−/− and eET-1/Apoe−/−/Nox4−/− mice but not eET-1/Apoe−/−/Nox1y/− mice. ET-1 overexpression enhanced monocyte/macrophage and CD3+ T-cell infiltration ∼2.7-fold in the aortic arch perivascular fat of diabetic Apoe−/− mice. Both Nox1 and Nox4 knockout blunted CD3+ T-cell infiltration whereas only Nox1 knockout prevented the monocyte/macrophage infiltration in diabetic eET-1/Apoe−/− mice. Conclusion Endothelium ET-1 overexpression enhances the progression of atherosclerosis in type 1 diabetes, perivascular oxidative stress, and inflammation through NOX1.