tbuckley/cabot-search huggingface dataset:
Neutral Theory Is the Foundation of Conservation Genetics
Authors: Anne D Yoder, Jelmer W Poelstra, George P Tiley, Rachel C Williams
Journal: Molecular Biology and Evolution (2018)

Kimura's neutral theory of molecular evolution has been essential to virtually every advance in evolutionary genetics, and by extension, is foundational to the field of conservation genetics. Conservation genetics utilizes the key concepts of neutral theory to identify species and populations at risk of losing evolutionary potential by detecting patterns of inbreeding depression and low effective population size. In turn, this information can inform the management of organisms and their habitat providing hope for the long-term preservation of both. We expand upon Avise's "inventorial" and "functional" categories of conservation genetics by proposing a third category that is linked to the coalescent and that we refer to as "process-driven." It is here that connections between Kimura's theory and conservation genetics are strongest. Process-driven conservation genetics can be especially applied to large genomic data sets to identify patterns of historical risk, such as population bottlenecks, and accordingly, yield informed intuitions for future outcomes. By examining inventorial, functional, and process-driven conservation genetics in sequence, we assess the progression from theory, to data collection and analysis, and ultimately, to the production of hypotheses that can inform conservation policies.
Misclassification of Upper Tract Urothelial Carcinoma in Patients With Lynch Syndrome
Authors: Surena F. Matin, Jonathan A. Coleman
Journal: JAMA Oncology (2018)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
A randomized phase II study of mFOLFOX6 plus bevacizumab versus mFOLFOX6 plus cetuximab for previously untreated, liver-limited metastatic colorectal cancer that is unsuitable for resection (ATOM trial).
Authors: Hiroyuki Uetake, Yasunori Emi, Takeharu Yamanaka, Kei Muro, Eiji Oki, Takao Takahashi, Takeshi Nagasaka, Etsuro Hatano, Hitoshi Ojima, Dai Manaka, Tetsuya Kusumoto, Yu Katayose, Toshiyoshi Fujiwara, Kazuhiro Yoshida, Michiaki Unno, Ichinosuke Hyodo, Naohiro Tomita, Kenichi Sugihara, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2018)

734 Background: It is still a topic of ongoing debate as to which of the two agents, anti-VEGF antibody or anti-EGFR antibody, is more effective in patients with KRAS Exon 2 or RAS wild-type metastatic colorectal cancer (mCRC) in the first-line setting. ATOM is a multicenter, randomized trial comparing mFOLFOX6 plus bevacizumab (Bmab arm) with mFOLFOX6 plus cetuximab (Cmab arm) in patients with liver-limited metastases unsuitable for upfront resection. Methods: Patients with previously untreated mCRC were eligible if they had ≥5 liver-limited metastatic lesions and/or had liver-limited metastases with the maximum lesion diameter of &gt; 5cm. Patients with KRAS Exon2-wild were registered but after Jan 2015 limited to those with all RAS-wild. Primary endpoint was progression-free survival (PFS), which was defined as the time from randomization to disease progression, recurrence after resection by surgery, or death from any cause (Central review). Key secondary endpoints included overall response rate (ORR), liver resection rate, and overall survival (OS). Results: A total of 122 pts were enrolled between May 2013 and April 2016. Of 116 eligible (59 in the Cmab arm and 57 in the Bmab arm), median age was 65/64 in the Cmab/Bmab arm; ECOG PS 0, 86/89%; all RAS wt, 98/95%; left-sided primary tumor, 76/84%. Efficacy results were summarized in the table. With a median follow-up of 24.3 months, the median PFS was 15.0 months in Cmab arm and 11.6 months in the Bmab arm with a hazard ratio of 0.803 (95%CI, 0.513–1.256), whereas ORR was 86% in the Cmab arm and 68% in the Bmab arm. Liver resection rate was 49% and 56% in the Cmab arm and the Bmab arm, respectively. Conclusions: In patients considered unsuitable for upfront resection of liver-limited metastasis, the two agents showed a similar efficacy. OS result will be presented elsewhere. Clinical trial information: NCT01836653. [Table: see text]
Independent cohort validation of hepatic metabolism, daily dose and comorbidities as features associated with delayed symptom onset in drug-induced liver injury
Authors: A. González-Jiménez, I. Medina-Caliz, M. Robles-Díaz, F. Bessone, N. Hernandez, A. Sánchez, M. Arrese, R.P. Filho, M. Lizarzábal, M. Tagle, M.I. Lucena, C. Stephens, R.J. Andrade
Journal: Journal of Hepatology (2018)
Children’s hospital must be allowed to withdraw life support from Alfie Evans, court rules
Authors: Clare Dyer
Journal: BMJ (2018)

Alder Hey Children’s Hospital in Liverpool must be allowed to withdraw artificial ventilation from the severely brain damaged toddler Alfie Evans without further delay, three UK Supreme Court justices have ruled.1

Lady Hale, Lord Kerr, and Lord Wilson refused to extend a stay imposed on the implementation of the hospital’s care plan while Alfie’s parents, Thomas Evans and Kate James, exhausted all avenues in the courts.

Refusing permission to appeal to the Supreme Court, the judges said, “There is . . . no reason for further delay. There will be no stay of the Court …
Abstract 20644: Association Between Sex Hormones and Ambulatory Blood Pressure
Authors: Monik C Jimenez, Lu Wang, Julie E Buring, JoAnn E Manson, John P Forman, Howard D Sesso
Journal: Circulation (2016)

Introduction:  Higher levels of free and total testosterone (TT) and lower levels of sex hormone binding globulin (SHBG) have been associated with increased blood pressure (BP) in women with an inverse association between TT and BP reported among men. Fewer studies have examined dehydroepiandrosterone sulfate (DHEAS) or the association between sex steroid hormones and 24-hr ambulatory blood pressure (ABP) or blunted nocturnal BP fall.   Methods:  Baseline blood samples were assayed for 267 normotensive racially diverse men (≥50 years) and women (≥55 years) participating in the VITamin D and OmegA-3 TriaL (VITAL). Standardized seated BP (systolic [SBP] and diastolic [DBP]) and 24-hr ABP were measured by trained technicians. All participants provided extensive baseline self-reported data on relevant cardiovascular risk factors and sociodemographic covariates. Linear regression models adjusted for age, sex, race, body mass index, smoking, alcohol, multivitamin use, and fruit and vegetable intake estimated the association between each sex hormone and measures of BP and 24-hr ABP separately by sex. We used logistic regression to estimate (OR, 95% CI) the association between each sex hormone and blunted nocturnal fall, defined as a >10% reduction in SBP or DBP during sleeping hours.   Results:  DHEAS, TT and SHBG were not significantly correlated with measures of BP when simultaneously adjusted for one another. In multivariable analyses stratified by sex, among women there was no association observed between sex hormones and measures of BP. Among men, each 10% increase in DHEAS was associated with a 0.45 mmHg increase in seated DBP (β=4.45, 95% CI: 0.71, 8.18) and each 10% increase in TT and SHBG was associated with a 0.67 mmHg (β=-6.73, 95% CI:-11.47, -1.99) and 0.72 mmHg (β=-7.23, 95% CI: -12.05, -2.41) decrease in seated DBP, respectively.   Conclusions:  We observed significant inverse cross-sectional associations between DHEAS, TT and SHBG with seated DBP in men, but not SBP, 24-hr ABP or blunted nocturnal BP. There was no association observed between sex hormones and measures of BP among women. Further research is needed to understand how sex hormones may impact BP measures over time.
Risk of skin cancer in people with vitiligo: a systematic review and meta-analysis
Authors: L. Ban, S. Labbouz, D. Grindlay, J. M. Batchelor, S. Ratib
Journal: British Journal of Dermatology (2018)

Vitiligo is a chronic disorder causing skin depigmentation with around 1% global prevalence, affecting people of all ages, skin types and genders.1 Due to the absence of melanin in lesional skin there is a theoretical concern that there might be a higher risk of skin cancer in people with vitiligo. However, some studies have shown that the genetic and autoimmune profiles of vitiligo patients may confer a degree of protection against the development of melanoma and non‐melanoma skin cancer (NMSC).2 Therefore, the aim of this systematic review was to quantify the risk of skin cancer (melanoma and NMSC) in people with vitiligo compared to those without vitiligo.
Comprehensive Assessment of Coronary Artery Disease in Sports-Related Sudden Cardiac Arrest
Authors: Nicole Karam, Louis Pechmajou, Florence Dumas, Wulfran Bougouin, Ardalan Sharifzadehgan, Frankie Beganton, Guillaume Bonnet, Daniel Jost, Lionel Lamhaut, Olivier Varenne, Pierre Aubry, Georgios Sideris, Christian Spaulding, Alain Cariou, Eloi Marijon, Xavier Jouven
Journal: Circulation (2018)
Voluntarily Stopping Eating and Drinking Among Patients With Serious Advanced Illness—A Label in Search of a Problem?
Authors: Paul S. Mueller, Jacob J. Strand, Jon C. Tilburt
Journal: JAMA Internal Medicine (2018)

To the Editor In a Special Communication published in a recent issue of JAMA Internal Medicine, Quill et al1 offer a thoughtful analysis of circumstances when dying patients voluntarily stop eating and drinking (VSED). We suggest several amendments to their analysis.
Brief Report: Anti–Calponin 3 Autoantibodies: A Newly Identified Specificity in Patients With Sjögren’s Syndrome
Authors: Julius Birnbaum, Ahmet Hoke, Aliya Lalji, Peter Calabresi, Pavan Bhargava, Livia Casciola‐Rosen
Journal: Arthritis & Rheumatology (2018)

Autoantibodies are clinically useful for phenotyping patients across the spectrum of autoimmune rheumatic diseases. Using serum from a patient with Sjögren's syndrome (SS), we detected a new specificity by immunoblotting. This study was undertaken to identify this autoantibody and to evaluate its disease specificity.A prominent 40-kd band was detected when immunoblotting was performed using SS patient serum and lysate from rat dorsal root ganglia (DRGs). Using 2-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry peptide sequencing, the autoantigen was identified as calponin 3. Anti-calponin 3 antibodies were evaluated in sera from patients with primary SS (n = 209), patients with systemic lupus erythematosus (SLE; n = 138), patients with myositis (n = 138), patients with multiple sclerosis (MS; n = 44), and healthy controls (n = 46) by enzyme-linked immunosorbent assay. Expression of calponin 3 was assessed by immunohistochemistry.Calponin 3 was identified as a new autoantigen. Anti-calponin 3 antibodies were detected in 23 (11.0%) of the 209 SS patients, 12 (8.7%) of the 138 SLE patients, 7 (5.1%) of the 138 myositis patients, 3 (6.8%) of the 44 MS patients, and 1 (2.2%) of the 46 healthy controls. Among SS patients, the frequency of anti-calponin 3 antibodies was highest in those with neuropathies (7 [17.9%] of 39). In this subset, the frequency of anti-calponin 3 antibodies differed significantly from that in the control group (P = 0.02). Calponin 3 was expressed primarily in rat DRG perineuronal satellite cells but not neurons.Calponin 3 is a novel autoantigen. Antibodies against this protein are found in SS and associate with the subset of patients experiencing neuropathies. Intriguingly, we found that calponin 3 is expressed in DRG perineuronal satellite cells, suggesting that these may be a target in SS.
Geriatric Dermatology—A Framework for Caring for Older Patients With Skin Disease
Authors: Eleni Linos, Mary-Margaret Chren, Ken Covinsky
Journal: JAMA Dermatology (2018)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Dermatology journal
Clinical usefulness of psoas muscle thickness for the diagnosis of sarcopenia in patients with liver cirrhosis
Authors: Dae Hoe Gu, Moon Young Kim, Yeon Seok Seo, Sang Gyune Kim, Han Ah Lee, Tae Hyung Kim, Young Kul Jung, Altay Kandemir, Ji Hoon Kim, Hyunggin An, Hyung Joon Yim, Jong Eun Yeon, Kwan Soo Byun, Soon Ho Um
Journal: Clinical and Molecular Hepatology (2018)

The most widely used method for diagnosing sarcopenia is the skeletal muscle index (SMI). Several studies have suggested that psoas muscle thickness per height (PMTH) is also effective for detecting sarcopenia and predicting prognosis in patients with cirrhosis. The aim of this study was to evaluate the optimal cutoff values of PMTH for detecting sarcopenia in cirrhotic patients.All cirrhotic patients who underwent abdominal computed tomography (CT) scan including L3 and umbilical levels for measuring SMI and transverse psoas muscle thickness, respectively, were included. Two definitions of sarcopenia were used: (1) sex-specific cutoffs of SMI (≤52.4 cm2 /m2 in men and ≤38.5 cm2 /m2 in women) for SMI-sarcopenia and (2) cutoff of PMTH (<16.8 mm/m) for PMTH-sarcopenia.Six hundred fifty-three patients were included. The average age was 53.6 ± 10.2 years, and 499 patients (76.4%) were men. PMTH correlated well with SMI in both men and women (P<0.001). Two hundred forty-one (36.9%) patients met the criteria for SMI-sarcopenia. The best PMTH cutoff values for predicting SMI-sarcopenia were 17.3 mm/m in men and 10.4 mm/m in women, and these were defined as sex-specific cutoffs of PMTH (SsPMTH). The previously published cutoff of PMTH was defined as sex-nonspecific cutoff of PMTH (SnPMTH). Two hundred thirty (35.2%) patients were diagnosed with SsPMTH-sarcopenia, and 280 (44.4%) patients were diagnosed with SnPMTH-sarcopenia. On a multivariate Cox regression analysis, SsPMTH-sarcopenia (hazard ratio [HR], 1.944; 95% confidence interval [CI], 1.144-3.304; P=0.014) was significantly associated with mortality, while SnPMTH-sarcopenia was not (HR, 1.446; 95% CI, 0.861-2.431; P=0.164).PMTH was well correlated with SMI in cirrhotic patients. SsPMTH-sarcopenia was an independent predictor of mortality in these patients and more accurately predicted mortality compared to SnPMTH-sarcopenia.
Role of bowel suspension technique to prevent early intestinal obstruction after radical cystectomy with ileal orthotopic neobladder: A retrospective cohort study
Authors: Wan Song, Hyun Suk Yoon, Kwang Hyun Kim, Hana Yoon, Woo Sik Chung, Bong Suk Sim, Dong Hyeon Lee
Journal: International Journal of Surgery (2018)
Differential Effects of Estrogen Receptor β Isoforms on Glioblastoma Progression
Authors: Jinyou Liu, Gangadhara R. Sareddy, Mei Zhou, Suryavathi Viswanadhapalli, Xiaonan Li, Zhao Lai, Rajeshwar R. Tekmal, Andrew Brenner, Ratna K. Vadlamudi
Journal: Cancer Research (2018)

Abstract The estrogen receptor β (ERβ) functions as a tumor suppressor in glioblastoma (GBM) cells. However, the in vivo significance of endogenous ERβ and the roles of its isoforms in GBM are incompletely understood. Using ERβ isoform-specific PCR screening, we found that GBM cells predominantly express ERβ1 and ERβ5, along with low levels of ERβ2 and ERβ4. We observed greater ERβ5 expression in higher grades of glioma than in lower grades. In CRISPR-based ERβ knockout (KO) cells and ERβ KO cells uniquely expressing ERβ1 or ERβ5 only, ERβ1 significantly reduced proliferation. Compared with parental GBM cells, ERβ KO cells exhibited high migratory and invasive potentials, and reexpression of ERβ1 resulted in the reduction of this phenotype. Interestingly, ERβ5 expression increased foci formation and anchorage-independent growth of NIH3T3 cells and increased motile structure formation, including filopodia and ruffles in GBM cells. Only ERβ1-expressing tumors resulted in longer mouse survival. RNA-Seq analysis revealed unique pathways modulated by ERβ1 and ERβ5. Compared with ERβ KO cells, ERβ1 cells exhibited lower activation of mTOR signaling molecules, including p-mTOR, p-S6K, and p-S6, and ERβ5-expressing cells had enhanced mTOR downstream signaling. Unique proteins including several that function as regulators of mTOR, immunomodulatory, and apoptosis pathways bound to ERβ1 and ERβ5 isoforms. Our work confirms the tumor-suppressive potential of ERβ1 and reveals the acquired oncogenic ability of ERβ5 in GBM cells. ERβ isoform status and their unique interactions with oncogenic pathways may have important implications in GBM progression. Significance: These findings suggest that only ERβ isoform 1 has tumor suppressor function in GBM and that ERβ isoform switching contributes to GBM progression. Cancer Res; 78(12); 3176–89. ©2018 AACR.
Abstract A33: Loss of Id4 initiates PIN-like lesions by maintaining stemness in mice prostate
Authors: Dhanushka Hewa Bostanthirige, Jugal Joshi, Shravan Kumar, Divya Patel, Jaideep Chaudhary
Journal: Cancer Research (2018)

Abstract Inhibitor of differentiation 4 (Id4), a member of the helix-loop-helix family of transcriptional regulators, has emerged as a tumor suppressor in prostate cancer (PCa). Recent studies have shown that Id4 is highly expressed in the normal prostate and decreases in prostate cancer (PCa) due to epigenetic silencing. Id4 knockdown in androgen-sensitive LNCaP cells has been shown to lead to castration-resistant prostate cancer (CRPC) in vitro and in vivo. Id4-/- mice leads to underdeveloped prostate without the loss of androgen receptor (AR) expression. In this study we demonstrate that prostates from the Id4 knockout (Id4-/-) mice show PIN-like lesions, suggesting that loss of Id4 plays a major role in initiation of prostate PCa. Histology of Id4 -/- mice prostate shows more PIN lesions at 3 months and 6 months without showing clear evidence of prostate cancer. Immunohistochemical analysis demonstrated increased expression of Amacr, which is a biomarker for PIN and PCa, only in Id4-/- 3-month- and 6-month-old prostate tissue. The expression of Nkx3.1 and Pten tumor suppressor genes in Id4-/-mouse prostate was undetectable, suggesting that loss of Id4 has potential to initiate or progress to PCa. Although PTEN protein was not present in Id4-/- mice, the presence of the corresponding PTEN mRNA suggested intact transcriptional program. These results suggested that Id4 plays a role in regulating the translation of the PTEN mRNA. We are currently investigating the ID4-regulated mechanisms involved in the translational control of PTEN. The results suggested that id4-/- results in PIN lesions that are in part due to a block in Pten translation. Sca-1 is a member of the Ly6 family of glycosyl phostidylinositol (GPI)-anchored cell surface proteins used as stem cell marker in murine prostate. According to cancer stem cell theory, stem cells in basal layer of the prostate tubules give rise to transient amplifying cells and differentiate into terminally differentiated secretory luminal epithelial cells. From the same pathway it gives rise to the tumor-promoting cells, which ultimately form prostate cancer. Sca-1 is expressed in Id4-/- mice 3-month- and 6-month-old prostate glands. These data suggest that loss of Id4 can initiate PIN like lesions by maintaining stemness through regulating transcriptional, translational mechanism via altering the expression of PTEN, NKX3.1, C-MYC and other regulatory molecules. Currently we are investigating that regulatory mechanism, mainly focusing on mRNA interference mechanisms. Citation Format: Dhanushka Hewa Bostanthirige, Jugal Joshi, Shravan Kumar, Divya Patel, Jaideep Chaudhary. Loss of Id4 initiates PIN-like lesions by maintaining stemness in mice prostate [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A33.
Risk of emergency hospital admission in children associated with mental disorders and alcohol misuse in the household: an electronic birth cohort study
Authors: Shantini Paranjothy, Annette Evans, Amrita Bandyopadhyay, David Fone, Behnaz Schofield, Ann John, Mark A Bellis, Ronan A Lyons, Daniel Farewell, Sara Jayne Long
Journal: The Lancet Public Health (2018)

BackgroundMental disorders and alcohol misuse are common in families but their effects on the physical health of children are not known. We investigated the risk of emergency hospital admissions during childhood associated with living with an adult who has a mental health disorder, or who had an alcohol-related hospital admission.MethodsWe did this cohort study in a total population electronic child cohort in Wales, UK, which includes all children who live in Wales or with a mother who is resident in Wales. We used Cox regression to model time to first emergency hospital admission during the first 14 years of life associated with living with an adult who has a mental health disorder, or who had an alcohol-related hospital admission. We adjusted our results for social deprivation and perinatal risk factors.FindingsWe included data for 253 717 children with 1 015 614 child-years of follow-up. Living with an adult with a mental disorder was associated with an increased risk of emergency admission for all causes (adjusted hazard ratio [aHR] 1·17, 95% CI 1·16–1·19), for injuries and external causes (1·14, 1·11–1·18), and childhood victimisation (1·55, 1·44–1·67). Children living with a household member who had an alcohol-related hospital admission had a significantly higher risk of emergency admissions for injuries and external causes (aHR 1·13, 95% CI 1·01–1 ·26) and victimisation (1·39, 1·00–1·94), but not for all-cause emergency admissions (1·01, 0·93–1·09).InterpretationThe increased risk of emergency admissions in children associated with mental disorders and alcohol misuse in the household supports the need for policy measures to provide support to families that are affected.FundingEconomic and Social Research Council, Medical Research Council, Alcohol Research UK, Public Health Wales.