tbuckley/cabot-search huggingface dataset:
An Engineered Biomimetic Peptide Regulates Cell Behavior by Synergistic Integrin and Growth Factor Signaling
Authors: Lluís Oliver‐Cervelló, Helena Martin‐Gómez, Leslie Reyes, Fatima Noureddine, Elisabetta Ada Cavalcanti‐Adam, Maria‐Pau Ginebra, Carlos Mas‐Moruno
Journal: Advanced Healthcare Materials (2020)

Abstract Recreating the healing microenvironment is essential to regulate cell–material interactions and ensure the integration of biomaterials. To repair bone, such bioactivity can be achieved by mimicking its extracellular matrix (ECM) and by stimulating integrin and growth factor (GF) signaling. However, current approaches relying on the use of GFs, such as bone morphogenetic protein 2 (BMP‐2), entail clinical risks. Here, a biomimetic peptide integrating the RGD cell adhesive sequence and the osteogenic DWIVA motif derived from the wrist epitope of BMP‐2 is presented. The approach offers the advantage of having a spatial control over the single binding of integrins and BMP receptors. Such multifunctional platform is designed to incorporate 3,4‐dihydroxyphenylalanine to bind metallic oxides with high affinity in a one step process. Functionalization of glass substrates with the engineered peptide is characterized by physicochemical methods, proving a successful surface modification. The biomimetic interfaces significantly improve the adhesion of C2C12 cells, inhibit myotube formation, and activate the BMP‐dependent signaling via p38. These effects are not observed on surfaces displaying only one bioactive motif, a mixture of both motifs or soluble DWIVA. These data prove the biological potential of recreating the ECM and engaging in integrin and GF crosstalk via molecular‐based mimics.
Expansion and persistence of antibiotic-specific resistance genes following antibiotic treatment
Authors: Kang Kang, Lejla Imamovic, Maria-Anna Misiakou, Maria Bornakke Sørensen, Yoshitaro Heshiki, Yueqiong Ni, Tingting Zheng, Jun Li, Mostafa M. H. Ellabaan, Marta Colomer-Lluch, Anne A. Rode, Peter Bytzer, Gianni Panagiotou, Morten O.A. Sommer
Journal: Gut Microbes (2021)

Oral antibiotics are commonly prescribed to non-hospitalized adults. However, antibiotic-induced changes in the human gut microbiome are often investigated in cohorts with preexisting health conditions and/or concomitant medication, leaving the effects of antibiotics not completely understood. We used a combination of omic approaches to comprehensively assess the effects of antibiotics on the gut microbiota and particularly the gut resistome of a small cohort of healthy adults. We observed that 3 to 19 species per individual proliferated during antibiotic treatment and Gram-negative species expanded significantly in relative abundance. While the overall relative abundance of antibiotic resistance gene homologs did not significantly change, antibiotic-specific gene homologs with presumed resistance toward the administered antibiotics were common in proliferating species and significantly increased in relative abundance. Virome sequencing and plasmid analysis showed an expansion of antibiotic-specific resistance gene homologs even 3 months after antibiotic administration, while paired-end read analysis suggested their dissemination among different species. These results suggest that antibiotic treatment can lead to a persistent expansion of antibiotic resistance genes in the human gut microbiota and provide further data in support of good antibiotic stewardship.Abbreviation: ARG - Antibiotic resistance gene homolog; AsRG - Antibiotic-specific resistance gene homolog; AZY - Azithromycin; CFX - Cefuroxime; CIP - Ciprofloxacin; DOX - Doxycycline; FDR - False discovery rate; GRiD - Growth rate index value; HGT - Horizontal gene transfer; NMDS - Non-metric multidimensional scaling; qPCR - Quantitative polymerase chain reaction; RPM - Reads per million mapped reads; TA - Transcriptional activity; TE - Transposable element; TPM - Transcripts per million mapped reads.
Abstract 12911: Association of Lipoprotein (a) and Coronary Artery Calcification: Prospective Study Assessing Interactions With Other Risk Factors in the Multi-Ethnic Study of Atherosclerosis
Authors: Kwok Leung Ong, Robyn McClelland, Matthew A Allison, Mary Cushman, Parveen Garg, Michael Y Tsai, Kerry Anne Rye, Fatiha Tabet
Journal: Circulation (2020)

Introduction: Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular disease (CVD) risk factors that correlate with each other. In this study we hypothesized that other CVD risk factors could modify the relationship between baseline Lp(a) levels and CAC change over time. Methods: A total of 5975 participants from the Multi-Ethnic Study of Atherosclerosis were analyzed. All participants were 45-84 years old, free of apparent CVD at baseline and from one of four major ethnic groups (non-Hispanic white, African American, Hispanic American, and Chinese American). We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years. Results: Elevated Lp(a) was associated with larger annual absolute increase in CAC volume (3.21 and 4.45 mm 3 /year higher for Lp(a) ≥30 versus &lt;30 mg/dL, and Lp(a) ≥50 versus &lt;50 mg/dL, respectively, both P &lt;0.05), but not in CAC density. The association of elevated Lp(a) with absolute change in CAC volume was more prominent in African Americans and Hispanic Americans, than other ethnic groups ( P for interaction &lt;0.05). After multiple testing correction of 24 study variables, the association of elevated Lp(a) (≥30 mg/dL) with annual absolute change in CAC volume was greater in participants with higher levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor receptor 1 and fibrinogen (change = 15.33, 11.81 and 7.02 mm 3 /year in quartile 4, compared to -3.44, -0.59 and 1.91 mm 3 /year in quartile 1, respectively). A similar trend was seen when expressing Lp(a) ≥50 mg/dL as elevated levels. There were no associations for ln-transformed Lp(a) as a continuous variable, or when assessing the annual relative change in CAC volume and density. Conclusions: Elevated Lp(a) was associated with the progression of CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. This study suggests that inflammation and coagulation may modify the relation between Lp(a) and CAC.
Pembrolizumab for Non–Muscle-Invasive Bladder Cancer—A Costly Therapy in Search of Evidence
Authors: Jennifer Gill, Vinay Prasad
Journal: JAMA Oncology (2020)

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 Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
COVID-19 and the neurological disease therapeutic pipeline
Authors: Gregory A. Jicha, Erin L. Abner
Journal: Nature Reviews Neurology (2020)

From the interruption of clinical trials by shelter-in-place orders to the challenges involved in safely collecting biofluid samples, drug development for neurological disease was hit hard by the COVID-19 pandemic this year. However, the field has responded with innovative solutions, and 2021 could see the therapeutic pipeline flowing again.
Maternal immune activation in mice disrupts proteostasis in the fetal brain
Authors: Brian T. Kalish, Eunha Kim, Benjamin Finander, Erin E. Duffy, Hyunju Kim, Casey K. Gilman, Yeong Shin Yim, Lilin Tong, Randal J. Kaufman, Eric C. Griffith, Gloria B. Choi, Michael E. Greenberg, Jun R. Huh
Journal: Nature Neuroscience (2020)
Клинико-генетические особенности пациентов с ожирением и неалкогольной жировой болезнью печени
Authors: V.P. Shypulin, N.N. Rudenko, A.K. Koliada, N.Н. Melnyk
Journal: GASTROENTEROLOGY (2020)

Актуальность. В настоящее время важное значение в патогенезе ожирения и неалкогольной жировой болезни печени (НАЖБП) придается полиморфизму rs1801282 (Pro12Ala) гена PPAR-γ2 (гамма-рецептор, активируемый пролифераторами пероксисом). Однако в украинской популяции больных с сочетанной патологией не изучены клинико-лабораторные особенности пациентов с этим полиморфизмом. Цель — исследовать клинико-лабораторные особенности больных с ожирением и НАЖБП в зависимости от rs1801282 полиморфизма гена PPAR-γ2. Материалы и методы. В исследовании приняли участие 123 пациента с 1–3 степенью ожирения и НАЖБП. Всем пациентам проведено молекулярно-генетическое исследование rs1801282 полиморфизма гена PPAR-γ2, а также антропометрические измерения, лабораторное и инструментальное обследование (в том числе ультразвуковая стеатометрия). Результаты. У больных с ожирением и НАЖБП с генотипами CG и GG rs1801282 полиморфизма гена PPAR-γ2 выявлены достоверно более высокие показатели индекса массы тела (p = 0,03), глюкозы (p = 0,02), инсулина (p &lt; 0,0001) и С-пептида натощак (p = 0,02), АЛТ (p = 0,04), гамма-глутамилтранспептидазы (p &lt; 0,0001), общего холестерина (p = 0,03), триглицеридов (p = 0,002), холестерина липопротеидов низкой плотности (p = 0,004), холестерина липопротеидов очень низкой плотности (p = 0,001), коэффициента атерогенности (p &lt; 0,0001), а показатели контролируемого параметра затухания (p = 0,002), стимулированного инсулина (p &lt; 0,0001), мочевой кислоты (p = 0,008) и холестерина липопротеидов высокой плотности (p &lt; 0,0001) оказались достоверно ниже по сравнению с CC-генотипом. Выводы. В украинской популяции больных с сочетанием ожирения и НАЖБП у носителей аллели G rs1801282 полиморфизма гена PPAR-γ2 обнаружены достоверные метаболические различия, которые могут быть связаны с защитой от развития стеатоза и сахарного диабета 2 типа, но в то же время повышают сердечно-сосудистый риск.
中国人患者におけるHelicobacter pyloriの一次抗生物質耐性:多地域前向き7年間研究【JST・京大機械翻訳】
Authors: Liu D.-S., Wang Y.-H., Zeng Z.-R., Zhang Z.-Y., H Lu, Xu J.-M., Du Y.-Q., Y Li, Wang J.-B., Xu S.-P., Y Chen, Lan C.-H., H Cheng, Jiang M.-D., Zhang L.-X., Huo L.-J., Chen S.-Y., Zhang G.-X., Wu K.-C., X Zhu, Chen Y.-X., Y Zhu, X Shu, Y Xie, Lu N.-H.
Journal: Clinical Microbiology and Infection (2018)
Exercise Intensity and Risk of Coronary Heart Disease—Reply
Authors: Mihaela Tanasescu, Michael F. Leitzmann, Eric B. Rimm, Walter C. Willett, Meir J. Stampfer, Frank B. Hu
Journal: JAMA (2003)

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 Journals 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
Increasing the Specificity of AAV-Based Gene Editing through Self-Targeting and Short-Promoter Strategies
Authors: Camilo Breton, Thomas Furmanak, Alexa N. Avitto, Melanie K. Smith, Caitlin Latshaw, Hanying Yan, Jenny A. Greig, James M. Wilson
Journal: Molecular Therapy (2020)

Our group previously used adeno-associated viral vectors (AAVs) to express an engineered meganuclease specific for a sequence in the PCSK9 gene (M2PCSK9), a clinical target for treating coronary heart disease. Upon testing this nuclease in non-human primates, we observed specific editing characterized by several insertions and deletions (indels) in the target sequence as well as indels in similar genomic sequences. We hypothesized that high nuclease expression increases off-target editing. Here, we reduced nuclease expression using two strategies. The first was a self-targeting strategy that involved inserting the M2PCSK9 target sequence into the AAV genome that expresses the nuclease and/or fusing the nuclease to a specific peptide to promote its degradation. The second strategy used a shortened version of the parental promoter to reduce nuclease expression. Mice administered with these second-generation AAV vectors showed reduced PCSK9 expression due to the nuclease on-target activity and reduced off-target activity. All vectors induced a stable reduction of PCSK9 in primates treated with self-targeting and short-promoter AAVs. Compared to the meganuclease-expressing parental AAV vector, we observed a significant reduction in off-target activity. In conclusion, we increased the in vivo nuclease specificity using a clinically relevant strategy that can be applied to other genome-editing nucleases. Our group previously used adeno-associated viral vectors (AAVs) to express an engineered meganuclease specific for a sequence in the PCSK9 gene (M2PCSK9), a clinical target for treating coronary heart disease. Upon testing this nuclease in non-human primates, we observed specific editing characterized by several insertions and deletions (indels) in the target sequence as well as indels in similar genomic sequences. We hypothesized that high nuclease expression increases off-target editing. Here, we reduced nuclease expression using two strategies. The first was a self-targeting strategy that involved inserting the M2PCSK9 target sequence into the AAV genome that expresses the nuclease and/or fusing the nuclease to a specific peptide to promote its degradation. The second strategy used a shortened version of the parental promoter to reduce nuclease expression. Mice administered with these second-generation AAV vectors showed reduced PCSK9 expression due to the nuclease on-target activity and reduced off-target activity. All vectors induced a stable reduction of PCSK9 in primates treated with self-targeting and short-promoter AAVs. Compared to the meganuclease-expressing parental AAV vector, we observed a significant reduction in off-target activity. In conclusion, we increased the in vivo nuclease specificity using a clinically relevant strategy that can be applied to other genome-editing nucleases.
Ethical issues in using ambient intelligence in health-care settings
Authors: Nicole Martinez-Martin, Zelun Luo, Amit Kaushal, Ehsan Adeli, Albert Haque, Sara S Kelly, Sarah Wieten, Mildred K Cho, David Magnus, Li Fei-Fei, Kevin Schulman, Arnold Milstein
Journal: The Lancet Digital Health (2020)

Ambient intelligence is increasingly finding applications in health-care settings, such as helping to ensure clinician and patient safety by monitoring staff compliance with clinical best practices or relieving staff of burdensome documentation tasks. Ambient intelligence involves using contactless sensors and contact-based wearable devices embedded in health-care settings to collect data (eg, imaging data of physical spaces, audio data, or body temperature), coupled with machine learning algorithms to efficiently and effectively interpret these data. Despite the promise of ambient intelligence to improve quality of care, the continuous collection of large amounts of sensor data in health-care settings presents ethical challenges, particularly in terms of privacy, data management, bias and fairness, and informed consent. Navigating these ethical issues is crucial not only for the success of individual uses, but for acceptance of the field as a whole.
A Snapshot for Peritoneal Dialysis Clinic Visits: Addressing Hospitalization Rates with a Checklist
Authors: Samantha M. Saggese, Aditya V. Jain, Michael Bond, Janis Cho, Alexander S. Leidner, Tina S. Samuel, Harini Gurram, Vikram Aggarwal
Journal: Journal of the American Society of Nephrology (2020)

Saggese, Samantha M.; Jain, Aditya V.; Bond, Michael; Cho, Janis; Leidner, Alexander S.; Samuel, Tina S.; Gurram, Harini; Aggarwal, Vikram Author Information
A retrospective study of positive and negative determinants of gamete storage in transgender and gender-diverse patients
Authors: Chloë Rogers, Mike Webberley, Roxana Mateescu, Yasmeen El Rakhawy, Anaïs Daly-Gourdialsing, Helen Webberley
Journal: International Journal of Transgender Health (2020)

Background: GenderGP is a novel, online telemedicine service for transgender and gender-diverse individuals. As part of the service, people are offered fertility counseling in regard to gamete storage. Aims: This study aims to formally categorize the reasons that transgender and gender-diverse people do and not store gametes prior to hormonal treatments. We hope to use this data and subsequent research to inform healthcare policy, improve the healthcare experience for transgender and gender-diverse people, and inform legislation for permanent change in UK healthcare. Methods: Data sets (electronic medical records) from June 2015 - April 2020 were derived from the GenderGP patient database. All patients starting treatment with GenderGP and undergoing routine fertility counseling were included in the study. Results: Of 3667 patients aged 10-85, 2722 (74.2%) were aged 18-45. 151 (5.4%) patients stored gametes. 678 (18.5%) patients wanted to store: 268 (39.5%) could not afford gamete storage, 84 (12.4%) had no local services, 307 (45.3%) did not want to delay hormone treatment. 2085 patients did not want to undertake gamete storage, 480 (23.0%) hoped to adopt, 1605 (77.1%) did not want children. All ages showed similar patterns. Discussion: Financial barriers mean many transgender and gender-diverse people cannot access fertility healthcare. Many participants suffered low self-esteem and struggled to envisage an accepting healthcare system, making them less likely to seek advice. Many patients favored adoption over gamete storage. Younger patients (<18) often had very definite views on gamete storage. Many older patients without children would consider gamete storage and adoption, once their transition is complete.
Hyperuricemia and Gout
Authors: Gerry R. Boss, J. Edwin Seegmiller
Journal: New England Journal of Medicine (1979)

RECENT progress in the understanding of purine metabolism and uric acid disposition suggests a need to revise the traditional classification of hyperuricemia and gout. A rational classification based on uric acid production would provide the foundations for further genetic investigation and for a sound approach to the treatment of patients with gout.Hyperuricemia is difficult to define. The serum urate concentration is not distributed normally in the population but is slightly skewed toward higher values. A functional and useful definition is based on the physicochemical saturation of serum with urate, which at 37°C is about 7.0 mg per 100 ml. . . .
Associations of Menstrual Cycle Characteristics Across the Reproductive Life Span and Lifestyle Factors With Risk of Type 2 Diabetes
Authors: Yi-Xin Wang, Zhilei Shan, Mariel Arvizu, An Pan, JoAnn E. Manson, Stacey A. Missmer, Qi Sun, Jorge E. Chavarro
Journal: JAMA Network Open (2020)

Menstrual cycle dysfunction is associated with insulin resistance, a key feature early in the pathogenesis of type 2 diabetes. However, the evidence linking irregular and long menstrual cycles with type 2 diabetes is scarce and inconsistent.To evaluate the associations between menstrual cycle characteristics at different points throughout a woman's reproductive life span and risk of type 2 diabetes and the extent to which this association is modified by lifestyle factors.This prospective cohort study included 75 546 premenopausal US female nurses participating in the Nurses' Health Study II from 1993 to June 30, 2017. Data analysis was performed from February 1 to December 30, 2019.Self-reported usual length and regularity of menstrual cycles at the age ranges of 14 to 17 years, 18 to 22 years, and 29 to 46 years.Incident type 2 diabetes identified through self-report and confirmed by validated supplemental questionnaires.Among the 75 546 women in the study at baseline, the mean (SD) age was 37.9 (4.6) years (range, 29.0-46.0 years). A total of 5608 participants (7.4%) had documented new cases of type 2 diabetes during 1 639 485 person-years of follow-up. After adjustment for potential confounders, women reporting always having irregular menstrual cycles between the age ranges of 14 to 17 years, 18 to 22 years, and 29 to 46 years were, respectively, 32% (95% CI, 22%-44%), 41% (95% CI, 23%-62%), and 66% (95% CI, 49%-84%) more likely to develop type 2 diabetes than women reporting very regular cycles (within 3-4 days of expected period) in the same age range. Similarly, women reporting a usual cycle length of 40 days or more between the age ranges of 18 to 22 years and 29 to 46 years were, respectively, 37% (95% CI, 19%-57%) and 50% (95% CI, 36%-65%) more likely to develop type 2 diabetes during follow-up compared with women reporting a usual cycle length of 26 to 31 days in the same age ranges. These associations appeared to be stronger among women with overweight or obesity, a low-quality diet, and low levels of physical activity. The relative excess risk of type 2 diabetes due to the interaction between irregular and long menstrual cycles and the overall unhealthy lifestyle score was 0.73 (95% CI, 0.57-0.89) and 0.68 (95% CI, 0.54-0.83), respectively.In this cohort study of US female nurses participating in the Nurses' Health Study II, irregular and long menstrual cycles throughout life were associated with a greater risk of type 2 diabetes, particularly among women with overweight or obesity, a low-quality diet, and low levels of physical activity.