tbuckley/cabot-search huggingface dataset:
Health platform for self-management of pediatric cystic fibrosis: Impact on patient-reported outcomes and patient-centered care
Authors: G. R. Oates, S. B. Rutland, R. Geurs, C. Mims, R. Bergquist, A. Hager, H. H. Gutierrez
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Mobile health (mHealth) applications present opportunities for patients to play an active role in their care. Previously, we adapted an mHealth platform for self-management of cystic fibrosis (CF) to the needs of families in a pediatric CF center the United States. In this feasibility study, we tested the impact of the platform (Genia) on patient-reported outcomes and patient-centered care.Methods: In a one-group pre-post study with adolescents with CF and caregivers of children with CF, we tested Genia's effect over 6 months on CF-related quality of life measured with the CFQ-R, patient satisfaction with chronic illness care measured with PACIC, and shared decision-making measured with CollaboRate. Exit interviews assessed usefulness of and satisfaction with Genia's features. App analytics were used to assess feasibility and acceptability of the platform. Results: The intervention included 40 participants: 30 familial caregivers of children with CF and 10 patients with CF age ≥15 years. Half of the pre-test instruments were administered pre-COVID;all post-test instruments were administered during the pandemic. The platform was acceptable, with 95% retention rate;and feasible, with participants recording more than 4,400 observations and submitting 496 weekly reports (mean 13.8, range 1-26) and 70 pre-visit reports (mean 1.8, range 0-2). The most useful app feature was sending pre-visit reports (66.7%). The top trackers were for cough (23.7%), appetite (21.1%), energy (18.4%), medicines (18.4%), and stools (15.8%). The use of Genia was associated with improvements in all QOL domains and symptom scales, with highest increases in school and digestive symptoms scores (7.8% each) in patients age 6-14, and treatment burden and body image scores (7.8 and 8.9, respectively) in patients age ≥15. The use of Genia was associated with increased satisfaction with care (total score 3.90 [0.75] to 4.14 [0.67], p=0.024), including delivery system and decision support (8.3%, p=0.017), goal setting (10.5%, p=0.006), overall chronic illness care (12%, p=0.053), and shared decision-making (16.0% overall, 38.5% among adolescents, p<0.001). Shared decisionmaking increased for each category, with the total score improving from 68.4 to 84.2 (p<0.001). Across all measures, those enrolled pre-COVID had higher pre-post scores than those enrolled during COVID.Conclusions: The use of Genia over 6 months was feasible, acceptable, and associated with improved QOL, satisfaction with care, and shared decision-making despite the COVID-19 pandemic. Study results support wider use of Genia in clinical settings. A randomized controlled trial will access efficacy for clinical outcomes over 12 months.
GxEsum: a novel approach to estimate the phenotypic variance explained by genome-wide GxE interaction based on GWAS summary statistics for biobank-scale data
Authors: Jisu Shin, Sang Hong Lee
Journal: Genome biology (2021)

Genetic variation in response to the environment, that is, genotype-by-environment interaction (GxE), is fundamental in the biology of complex traits and diseases. However, existing methods are computationally demanding and infeasible to handle biobank-scale data. Here, we introduce GxEsum, a method for estimating the phenotypic variance explained by genome-wide GxE based on GWAS summary statistics. Through comprehensive simulations and analysis of UK Biobank with 288,837 individuals, we show that GxEsum can handle a large-scale biobank dataset with controlled type I error rates and unbiased GxE estimates, and its computational efficiency can be hundreds of times higher than existing GxE methods.
Abstract 15307: Gender-Based Trends in Cardiac Transplant Complications and Related Outcomes in Heart Failure Patients in the United States - A 10 Year Analysis From a National Inpatient Database
Authors: Abhishek Chaturvedi, Craig Alpert, Matthew Lander, Manreet Kanwar, Raymond Benza, Amresh Raina
Journal: Circulation (2019)

Introduction: Immediate post-transplant complications (PTC) remain a significant cause of morbidity and mortality in heart failure patients undergoing cardiac transplant (CT). Hypothesis: We sought...
Machine Learning‐Reinforced Noninvasive Biosensors for Healthcare
Authors: Kaiyi Zhang, Jianwu Wang, Tianyi Liu, Yifei Luo, Xian Jun Loh, Xiaodong Chen
Journal: Advanced Healthcare Materials (2021)

The emergence and development of noninvasive biosensors largely facilitate the collection of physiological signals and the processing of health-related data. The utilization of appropriate machine learning algorithms improves the accuracy and efficiency of biosensors. Machine learning-reinforced biosensors are started to use in clinical practice, health monitoring, and food safety, bringing a digital revolution in healthcare. Herein, the recent advances in machine learning-reinforced noninvasive biosensors applied in healthcare are summarized. First, different types of noninvasive biosensors and physiological signals collected are categorized and summarized. Then machine learning algorithms adopted in subsequent data processing are introduced and their practical applications in biosensors are reviewed. Finally, the challenges faced by machine learning-reinforced biosensors are raised, including data privacy and adaptive learning capability, and their prospects in real-time monitoring, out-of-clinic diagnosis, and onsite food safety detection are proposed.
Intracerebral administration of CTLA-4 and PD-1 immune checkpoint blocking monoclonal antibodies in patients with recurrent glioblastoma: a phase I clinical trial
Authors: Johnny Duerinck, Julia Katharina Schwarze, Gil Awada, Jens Tijtgat, Freya Vaeyens, Cleo Bertels, Wietse Geens, Samuel Klein, Laura Seynaeve, Louise Cras, Nicky D’Haene, Alex Michotte, Ben Caljon, Isabelle Salmon, Michaël Bruneau, Mark Kockx, Sonia Van Dooren, Anne-Marie Vanbinst, Hendrik Everaert, Ramses Forsyth, Bart Neyns
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Patients with recurrent glioblastoma (rGB) have a poor prognosis with a median overall survival (OS) of 30–39 weeks in prospective clinical trials. Intravenous administration of programmed cell death protein 1 and cytotoxic T-lymphocyte-associated antigen 4 inhibitors has low activity in patients with rGB. In this phase I clinical trial, intracerebral (IC) administration of ipilimumab (IPI) and nivolumab (NIVO) in combination with intravenous administration of NIVO was investigated. Methods Within 24 hours following the intravenous administration of a fixed dose (10 mg) of NIVO, patients underwent a maximal safe resection, followed by injection of IPI (10 mg; cohort-1), or IPI (5 mg) plus NIVO (10 mg; cohort-2) in the brain tissue lining the resection cavity. Intravenous administration of NIVO (10 mg) was repeated every 2 weeks (max. five administrations). Next generation sequencing and RNA gene expression profiling was performed on resected tumor tissue. Results Twenty-seven patients were enrolled (cohort-1: n=3; cohort-2: n=24). All patients underwent maximal safe resection and planned IC administrations and preoperative NIVO. Thirteen patients (cohort-1: n=3; cohort-2: n=10) received all five postoperative intravenous doses of NIVO. In cohort-2, 14 patients received a median of 3 (range 1–4) intravenous doses. Subacute postoperative neurological deterioration (n=2) was reversible on steroid treatment; no other central nervous system toxicity was observed. Immune-related adverse events were infrequent and mild. GB recurrence was diagnosed in 26 patients (median progression-free survival (PFS) is 11.7 weeks (range 2–152)); 21 patients have died due to progression. Median OS is 38 weeks (95% CI: 27 to 49) with a 6-month, 1-year, and 2-year OS-rate of, respectively, 74.1% (95% CI: 57 to 90), 40.7% (95% CI: 22 to 59), and 27% (95% CI: 9 to 44). OS compares favorable against a historical cohort (descriptive Log-Rank p&gt;0.003). No significant difference was found with respect to PFS (descriptive Log-Rank test p&gt;0.05). A higher tumor mRNA expression level of B7-H3 was associated with a significantly worse survival (multivariate Cox logistic regression, p&gt;0.029). Conclusion IC administration of NIVO and IPI following maximal safe resection of rGB was feasible, safe, and associated with encouraging OS. Trial registration NCT03233152 .
Emerging pro-drug and nano-drug strategies for gemcitabine-based cancer therapy
Authors: Haijie Han, Su Li, Yueyang Zhong, Yue Huang, Kai Wang, Qiao Jin, Jian Ji, Ke Yao
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless, the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivation mainly because of its rapid deamination, deficiencies in deoxycytidine kinase (DCK), and alterations in nucleoside transporter. On this account, repeated injections with a high concentration of gemcitabine are adopted, leading to severe systemic toxicity to healthy cells. Accordingly, it is highly crucial to fabricate efficient gemcitabine delivery systems to obtain improved therapeutic efficacy of gemcitabine. A large number of gemcitabine pro-drugs were synthesized by chemical modification of gemcitabine to improve its biostability and bioavailability. Besides, gemcitabine-loaded nano-drugs were prepared to improve the delivery efficiency. In this review article, we introduced different strategies for improving the therapeutic performance of gemcitabine by the fabrication of pro-drugs and nano-drugs. We hope this review will provide new insight into the rational design of gemcitabine-based delivery strategies for enhanced cancer therapy.
Cardiopulmonary exercise capacity and limitations 3 months after COVID-19 hospitalisation
Authors: Ingunn Skjørten, Odd Andre Wathne Ankerstjerne, Divna Trebinjac, Eivind Brønstad, Øystein Rasch-Halvorsen, Gunnar Einvik, Tøri Vigeland Lerum, Knut Stavem, Anne Edvardsen, Charlotte Björk Ingul
Journal: European Respiratory Journal (2021)

Background This study aimed to describe cardiopulmonary function during exercise 3 months after hospital discharge for COVID-19 and compare groups according to dyspnoea and intensive care unit (ICU) stay. Methods Participants with COVID-19 discharged from five large Norwegian hospitals were consecutively invited to a multicentre, prospective cohort study. In total, 156 participants (mean age 56.2 years, 60 females) were examined with a cardiopulmonary exercise test (CPET) 3 months after discharge and compared with a reference population. Dyspnoea was assessed using the modified Medical Research Council (mMRC) dyspnoea scale. Results Peak oxygen uptake ( V ′ O 2 peak ) &lt;80% predicted was observed in 31% (n=49). Ventilatory efficiency was reduced in 15% (n=24), while breathing reserve &lt;15% was observed in 16% (n=25). Oxygen pulse &lt;80% predicted was found in 18% (n=28). Dyspnoea (mMRC ≥1) was reported by 47% (n=59). These participants had similar V ′ O 2 peak (p=0.10) but lower mean± sd V ′ O 2 peak ·kg −1 % predicted compared with participants without dyspnoea (mMRC 0) (76±16% versus 89±18%; p=0.009) due to higher body mass index (p=0.03). For ICU- versus non-ICU-treated participants, mean± sd V ′ O 2 peak % predicted was 82±15% and 90±17% (p=0.004), respectively. Ventilation, breathing reserve and ventilatory efficiency were similar between the ICU and non-ICU groups. Conclusions One-third of participants experienced V ′ O 2 peak &lt;80% predicted 3 months after hospital discharge for COVID-19. Dyspnoeic participants were characterised by lower exercise capacity due to obesity and lower ventilatory efficiency. Ventilation and ventilatory efficiency were similar between ICU- and non-ICU-treated participants.
Abstract 267: Activation of a Novel Estrogen Receptor Ameliorates Experimental Pulmonary Hypertension in Male Rats
Authors: Gisele Zapata-Sudo, Allan K Alencar, Guilherme C Montes, Sabrina T Martinez, Aline G Fraga, Hao Wang, Leanne Groban, Roberto T Sudo
Journal: Circulation Research (2016)

Introduction: Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling that leads to uncompensated RV failure, and premature death. Preclinical studies have demonstrated that activation of the G protein-coupled estrogen receptor (GPER) is cardioprotective in male rats, and that a selective agonist G1, elicits vascular relaxation in rats of either sex. This work investigated the effects of G1 in male rats with monocrotaline (MCT)-induced PAH. Methods and Results: Male Wistar rats received a single intraperitoneal injection of MCT (60 mg/kg) for PAH induction. Experimental groups were: control, MCT + vehicle, and MCT + G1 (400 μg/kg/day s.c.). Animals were treated with vehicle or G1 for 14 days after the onset of disease (n = 5 per group). Treadmill test and transthoracic echocardiography were performed to access exercise capacity and cardiac function, respectively. RV systolic pressure (RVSP) and mean arterial pressure (MAP) were measured. Time to exhaustion in the treadmill (s) was reduced from 1042.0 ± 66.4 to 188.0 ± 53.1 (MCT + vehicle) and recovered to 809.4 ± 61.5 after G1 treatment. Pulmonary acceleration time (PAT) (ms) was reduced from 44.7 ± 1.4 to 24.7 ± 1.2 in MCT + vehicle group and restored to 41.8 ± 1.0 in MCT + G1 group. RVSP (mmHg) was increased from 24.6 ± 0.6 to 41.1 ± 1.4 (MCT + vehicle) and was reduced to 27.5 ± 0.7 (MCT + G1). MAP (mmHg) was reduced from 100.9 ± 1.1 to 77.1 ± 2.4 (MCT + vehicle), indicating HF induced by the RV dysfunction, and G1 normalized it to 92.4 ± 1.4. G1 decreased pulmonary vascular remodeling and normalized endothelial nitric oxide enzyme levels in lungs from PAH rats. PLB/SERCA2a ratio increased, as a sign of contractility dysfunction, in PAH rats and tumor necrosis factor alpha upregulation was significantly correlated with these Ca 2+ handling proteins impairment. Activation of GPER beneficially reduced PLB/SERCA2a ratio and TNF-α levels in RV tissue of MCT-induced PAH rats. Conclusions: G1 was effective to reverse PAH-induced RV dysfunction and exercise intolerance in male rats, a finding that may have important implications for ongoing clinical evaluation of new drugs for the treatment of the disease.
Zonulin as a biomarker and potential therapeutic target in multisystem inflammatory syndrome in children
Authors: Tiffany Hensley-McBain, Jennifer A. Manuzak
Journal: Journal of Clinical Investigation (2021)

Multisystem inflammatory syndrome in children (MIS-C) occurs during or recently following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is characterized by persistent fever, inflammation, and severe illness requiring hospitalization. The majority of patients with MIS-C also present with gastrointestinal (GI) symptoms, including abdominal pain, vomiting, and diarrhea. In this issue of the JCI, Yonker, Gilboa, and colleagues identified zonulin as a biomarker of GI permeability in children with MIS-C and present the results of an intriguing proof-of-concept study indicating that zonulin may represent a potential therapeutic target for MIS-C treatment and prevention. Their findings suggest that intestinal mucosal dysfunction and epithelial barrier breakdown may represent a biological mechanism underlying the development of MIS-C in SARS-CoV-2-infected children.
Understanding the Preferences of Patients and Caregivers for Relapsed/Refractory Multiple Myeloma Treatment: A Mixed-Mode Patient-Centric Approach
Authors: Daniel Auclair, Carol Mansfield, Ajai Chari, Craig E. Cole, Mark A. Fiala, Jonathan L. Kaufman, Gregory Orloff, David Siegel, Jeff A. Zonder, Brennan Mange, Jennifer Yesil, Mehul Dalal, Joseph Mikhael
Journal: Blood (2017)
OP18. CORRELATING FLUORESCENCE AND CONVENTIONAL MRI WITH PROLIFERATION MARKERS IN GLIOBLASTOMA
Authors: Mr Fahid Rasul, Dr Talal Al-Mayhani, Mr Stephen Price, Mr Colin Watts
Journal: Neuro-Oncology (2017)

BACKGROUND: Glioblastoma is the commonest primary brain cancer and is associated with a devastating prognosis. Median survival is just 14 months with surgery, chemoradiotherapy. Tumour heterogeneity likely underlies poor prognosis and treatment resistance. We sought to correlate imaging and biological features of tumour heterogeneity. METHODS: We used contrast enhancement on conventional MRI and fluorescence as markers for proliferation in glioblastoma. We quantified the expression of three cell surface receptors CD133, EGFR and NG2 in fluorescent positive and fluorescent negative areas using flow cytometry. We also quantified the expression of these three cell surface receptors according to their contrast enhancement status (positive or negative). RESULTS: Eight patients with histologically confirmed glioblastoma were studied. Nineteen tumour samples were acquired. We found a statistically significant correlation between fluorescence and expression of all three cell surface receptors (CD 133 p-value = 0.015 (p <0.05), EGFR p-value = 0.035, NG2 p-value 0.015). We observed a statistically non-significant decrease in expression of all three cell surface receptors in contrast enhancing areas of tumour. CONCLUSIONS: Flourescence may be used as a guide to identify areas of high proliferation in glioblastoma. Contrast enhancement does not identify areas of high proliferation. Further work is required to confirm these findings.
Caring in wards without water
Authors: Alison Shepherd
Journal: BMJ (2021)

Dennis Lupenga/WaterAid/Wimbledon Foundation

Loveness Saulosi prepares food for her daughter, a patient in Mkunzi health centre in Ntchisi district in central Malawi.

As covid-19 continues to hit Malawi, more than half its health facilities lack handwashing facilities, almost two thirds have no decent toilets, and almost a fifth do not have clean water on site.

Ntchisi, a rural district of 300 000 people, has …
Abstract 315: Efficacy and Safety of Rivaroxaban in <i>in vitro</i> Experiments With the Endothelial Cells
Authors: Kaname Seki, Yosuke Mizuno, Toku Sakashita, Jun Tanno, Shintaro Nakano, Toshihiro Muramatsu, Shigeyuki Nishimura, Takaaki Senbonmatsu
Journal: Circulation Research (2016)

Aim: Activated factor X (FXa) plays important roles in the thrombin generation and in inflammation, which is evoked during the endothelial damage. Although rivaroxaban is a selective FXa antagonist, it is one of the key therapies in ischemic heart disease, and yet its function in the state of inactivated coagulation cascade is uncertain. Rivaroxaban blocks FXa in the blood but not the tissue, while factor X is converted to FXa only when glutamic acid is changed to γ-carboxyglutamic acid by vitamin K following the intrinsic clotting factors and/or cellular injury activation. To uncover this aspect, we performed the following experiments. Methods and results: Human umbilical vein endothelial cells (HUVECs) were obtained from Lonza Co., Ltd. The cells were grown to 80% confluence and were treated with rivaroxaban (100nM, 500nM, 1000nM, 2000nM respectively) without FXa stimulation for 4 h, 10 h or 24 h. Cells and medium were collected and then their RNA was extracted from the cells. The qPCR of MCP-1, PAR1-4 and the DNA micro arrays (The GeneChip Human Gene 2.0 ST Array, Affymetrix) were performed. There was neither increased nor decreased gene expression significantly in either experimental time course of the qPCRs or the the DNA micro arrays. The ELISA assay of MCP-1 with medium showed non-activated MCP-1. As a next step, cells were treated with 100nM FXa and with/without rivaroxaban in same time course, and cells and medium were collected for further experiments. FXa evoked induction of mRNA levels for several pro-inflammatory cytokines including MCP-1 maximally at 4h, whereas MCP-1 was maximally evoked at 24 h in ELISA assay. Interestingly rivaroxaban inhibited both in all time course, at 4 hour inflammatory phase and at 24 hour inflammatory phase. Conclusion: Collectively, these results suggest that rivaroxaban may be safe in the inactivated coagulation state, and has the efficacy to attenuate the endothelial damage evoked by FXa and by pro-inflammatory cytokine genes.
The Interface of <i>Vibrio cholerae</i> and the Gut Microbiome
Authors: Jennifer Y. Cho, Rui Liu, John C. Macbeth, Ansel Hsiao
Journal: Gut Microbes (2021)

The bacterium Vibrio cholerae is the etiologic agent of the severe human diarrheal disease cholera. The gut microbiome, or the native community of microorganisms found in the human gastrointestinal tract, is increasingly being recognized as a factor in driving susceptibility to infection, in vivo fitness, and host interactions of this pathogen. Here, we review a subset of the emerging studies in how gut microbiome structure and microbial function are able to drive V. cholerae virulence gene regulation, metabolism, and modulate host immune responses to cholera infection and vaccination. Improved mechanistic understanding of commensal–pathogen interactions offers new perspectives in the design of prophylactic and therapeutic approaches for cholera control.
<i>WNT10A</i> , dermatology and dentistry
Authors: B. J. Doolan, A. Onoufriadis, P. Kantaputra, J. A. McGrath
Journal: British Journal of Dermatology (2021)

WNTs (Wingless-related integration sites) are secreted glycoproteins that are involved in signalling pathways critical to organ development and tissue regeneration. Of the 19 known WNT ligands, one member of this family, WNT10A, appears to have specific relevance to skin, its appendages and teeth. This review focuses on how variants in the WNT10A gene have been associated with various ectodermal disorders and how such changes may have clinical relevance to dermatologists and dentists. Germline mutations in WNT10A underlie several forms of autosomal recessive ectodermal dysplasia in which heterozygous carriers may also display some lesser ectodermal anomalies. Within the general population, multiple heterozygous variants in WNT10A can cause skin, hair, sweat gland or dental alterations, also known as ectodermal derivative impairments. WNT10A variants have also been implicated in hair thickness, male androgenetic alopecia, hair curl, acne vulgaris, lipodystrophy, keloids, wound healing, tooth size, tooth agenesis, hypodontia, taurodontism and oral clefting. Beyond dermatology and dentistry, WNT10A abnormalities have also been identified in kidney fibrosis, keratoconus, certain malignancies (particularly gastrointestinal) and neuropathic pain pathways. In this review, we detail how WNT10A is implicated as a key physiological and pathological contributor to syndromic and nonsyndromic disorders, as well as population variants, affecting the skin and teeth, and document all reported mutations in WNT10A with genotype–phenotype correlation.