Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic Implications of Congestion on Physical Examination Among Contemporary Patients with Heart Failure and Reduced Ejection Fraction:PARADIGM-HF.

Background: The contemporary prognostic value of the physical examination, beyond traditional risk factors including natriuretic peptides (NPs), risk scores, and symptoms, in heart failure with reduced ejection fraction (HFrEF) is unknown. We sought to determine the association between physical signs of congestion at baseline and during study follow up with quality of life (QoL) and clinical outcomes and to assess the treatment effects of sacubitril/valsartan on congestion. Methods: We analyzed participants from PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in HF) with an available physical examination at baseline. We examined the association of the number of signs of congestion (jugular venous distention, edema, rales, and S3) with the primary outcome (cardiovascular death or HF hospitalization), its individual components, and all-cause mortality using time-updated, multivariable-adjusted Cox regression. We further evaluated whether sacubitril/valsartan reduced congestion during follow-up, and whether improvement in congestion is related to changes in clinical outcomes and QoL, assessed by Kansas City Cardiomyopathy Questionnaire clinical summary scores (KCCQ-OSS). Results: Among 8380 participants, 0, 1, 2, and 3+ signs of congestion were present in 70%, 21%, 7%, and 2%. Patients with baseline congestion were older, more often female, had higher Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk scores and lower KCCQ-OSS (p<0.05). After adjusting for baseline NPs, time-updated MAGGIC score, and time-updated New York Heart Association class, increasing time-updated congestion was associated with all outcomes (p<0.001). Sacubitril/valsartan reduced the risk of the primary outcome irrespective of clinical signs of congestion at baseline (p=0.16 for interaction), and treatment with the drug improved congestion to a greater extent than enalapril (p=0.011). Each 1-sign reduction was independently associated with a 5.1 (95%CI: 4.7-5.5) point improvement in KCCQ-OSS. Change in congestion strongly predicted outcomes even after adjusting for baseline congestion (p<0.001). Conclusions: In HFrEF, the physical exam continues to provide significant, independent prognostic value even beyond symptoms, NPs, and MAGGIC risk score. Sacubitril/valsartan improved congestion to a greater extent than enalapril. Reducing congestion in the outpatient setting is independently associated with improved QoL and reduced cardiovascular events, including mortality. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01035255.
Experience of telehealth in people with motor neurone disease using noninvasive ventilation

Abstract Introduction Evidence is emerging that telehealth provides timely and cost-effective support for individuals with motor neurone disease (MND). However, little is known about the subjective experience of using telehealth. This study was designed to examine the experiences of using telemonitoring in patients with MND on noninvasive ventilation (NIV). Methods Semi-structured interviews were conducted with seven patients (five males; mean age = 63 yrs; median illness duration = 14 m), who used a telemonitoring device for 24 weeks. Caregivers were present at five of the interviews; they supported communications and provided their feedback. Interviews were audio recorded and transcribed verbatim. Thematic analysis was conducted to find overarching themes. Results Five themes were identified: Benefits of Timely Intervention, Reducing the Unnecessary, Increased Self-Awareness, Taking Initiative, and Technical Challenges. Overall, timely interventions were observed as a result of regular monitoring, contributing to both physical and psychological well-being of the participants. The patient-caregiver dyads suggested that telemonitoring could reduce costs, save time and ameliorate hassles associated with attending hospital appointments. Participants articulated that telemonitoring enabled symptom awareness and interpretation; the device also enabled the participants to raise concerns and/or requests to the healthcare professionals via the messaging system. Participants confirmed that the telemonitoring device was easy to use, despite some technical issues. Conclusions Telemonitoring was positively experienced. The findings suggest this approach is empowering and effective in promoting patients’ well-being, while potentially reducing unnecessary clinical contact. Implications for Rehabilitation Care for people with MND demands a flexible approach to accommodate the diversity of clinical needs and relentless physical deterioration. Telehealth allows clinicians to provide person-centred care for everyone with MND through frequent monitoring. Holistic and rehabilitative service facilitated by telehealth is generally acceptable and preferred to routine appointments among MND NIV patients. Telehealth promotes time efficient engagement with professionals that leads to symptom awareness and interpretation, while benefiting physical and psychological well-being of MND NIV patients.
Evaluation of a Bioengineered Honey and Its Synthetic Equivalent as Novel Staphylococcus aureus Biofilm-Targeted Topical Therapies in Chronic Rhinosinusitis

Background Chronic rhinosinusitis (CRS) is a common condition which affects the quality of life of millions of patients worldwide and has a significant impact on health-care resources. While Staphylococcus aureus bacterial biofilms play an important role in this disease, antimicrobial therapy is rarely effective and may promote antibiotic resistance. Thus, development of novel biofilm-targeting and antibiotic-sparing therapies is highly desirable and urgently required. Objective This in vitro study evaluated the antimicrobial activity of a novel synthetic honey-equivalent product which was designed to have the same reactive oxygen release profile as the engineered honey SurgihoneyRO™. Methods Treatment efficacy was investigated by assessment of planktonic growth, biofilm viability, thickness, and biomass using 12 CRS-related S. aureus mucosal bacterial strains. Results Both SurgihoneyRO™ and the synthetic honey-equivalent product inhibited growth of planktonic methicillin-resistant and methicillin-sensitive S. aureus strains, with the synthetic honey-equivalent product exhibiting a lower minimum inhibitory concentration. Treatment of established S. aureus biofilms reduced biofilm viability with 24-hour treatment resulting in a 2-log reduction in viability of biofilms formed by methicillin-resistant strains and a 1-log reduction in biofilms formed by methicillin-sensitive strains. Conclusions This preliminary study shows that the synthetic honey-equivalent product provides marked antimicrobial activity against S. aureus biofilms, with the potential for development in the clinical setting as an adjunctive biofilm-targeted therapy in CRS. The ultimate aim of such a product would be to reduce the need for antibiotics, steroids, and invasive surgical procedures in CRS patients as well as improving clinical outcomes following endoscopic sinus surgery.
Superiority of DEAE-Dx stabilized cationic bile-based vesicles over conventional vesicles for enhanced hepatic delivery of Daclatasvir.

The aim of this study was to enhance the delivery of a direct acting antiviral drug; Daclatasvir to the site of action liver tissues using physically and biologically stable cationic bile based vesicles. Accordingly, cationic bile based vesicles were prepared as pro-bile based vesicles and DEAE-Dx stabilized bile based vesicles in order to increase its stability without negatively affecting their hepatic affinity. The prepared bile based vesicles were characterized for particle size, polydispersity index, zeta potential, in vitro Daclatasvir release and ex vivo permeation using non-everted gut sac intestine. The in vivo biodistribution was experimented after oral administration using radiolabeling assay where the liver scored the highest accumulation of the DEAE-Dx stabilized bile based vesicles after 4h reaching a value of 4.6% ID/g of the total oral administered dose of the labeled drug compared to drug solution, pro-bile based vesicles and cationic bile based vesicles where the accumulation percent was 0.19% ID/g, 1.3% ID/g and 0.31% ID/g, respectively. DEAE-Dx stabilized bile based vesicles increased the drug deposition into the liver about 42 folds compared to oral solution. The high physical stability and the high resistance to opsonization and clearance propose that DEAE-Dx stabilized bile based vesicles could be efficiently utilized as a successful platform for enhancing Daclatasvir delivery to the liver after oral administration.
At least two molecules of the RNA helicase Has1 are simultaneously present in pre-ribosomes during ribosome biogenesis

Abstract The RNA helicase Has1 is involved in the biogenesis of both small and large ribosomal subunits. How it performs these separate roles is not fully understood. Here we provide evidence that at least two molecules of Has1 are temporarily present at the same time in 90S pre-ribosomes. We identified multiple Has1 binding sites in the 18S, 5.8S and 25S rRNAs. We show that while the Has1 catalytic activity is not required for binding to 5.8S/25S region in pre-rRNA, it is essential for binding to 18S sites. After the cleavage of pre-rRNA at the A2 site, Has1 remains associated not only with pre-60S but, unexpectedly, also with pre-40S ribosomes. The recruitment to 90S/pre-40S and pre-60S ribosomes is mutually independent. Our data provides insight into how Has1 performs its separate functions in the synthesis of both ribosomal subunits.
Multimodal Stimuli Modulate Rapid Visual Responses during Reaching.

The reticulospinal tract plays an important role in primate upper limb function, but methods for assessing its activity are limited. One promising approach is to measure rapid visual responses (RVRs) in arm muscle activity during a visually-cued reaching task; these may arise from a tecto-reticulospinal pathway. We investigated whether changes in reticulospinal excitability can be assessed non-invasively using RVRs, by pairing the visual stimuli of the reaching task with electrical stimulation of the median nerve, galvanic vestibular stimulation or loud sounds, all of which are known to activate the reticular formation. Surface electromyogram recordings were made from the right deltoid of healthy human subjects as they performed fast reaching movements towards visual targets. Stimuli were delivered up to 200ms before target appearance and RVR was quantified as the EMG amplitude in a window 75-125ms after visual target onset. Median nerve, vestibular and auditory stimuli all consistently facilitated the RVRs, as well as reducing the latency of responses. We propose that this facilitation reflects modulation of tecto-reticulospinal excitability, which is consistent with the idea that the amplitude of RVRs can be used to assess changes in brainstem excitability non-invasively in humans.
Deep Brain Stimulation for Depression: Optimism for Continued Investigation

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA; Executive Division, National Center for PTSD, White River Junction, Vermont, USA; Departments of Psychiatry and Surgery, Dartmouth Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA. *Correspondence: Paul E. Holtzheimer (Paul.E.Holtzheimer@hitchcock.org)
Antimicrobial Carvacrol Incorporated in Flaxseed Gum-Sodium Alginate Active Films to Improve the Quality Attributes of Chinese Sea bass (Lateolabrax maculatus) during Cold Storage

The objective of this research was to explore the antimicrobial activity and mechanism of carvacrol against Vibrio Parahemolyticus, Shewanella putrefaciens, Staphylococcus aureus and Pseudomonas fluorescens and evaluate the effect of the addition of carvacrol/β-cyclodextrin emulsions to flaxseed gum (FSG)-sodium alginate (SA) edible films on the preservation of Chinese sea bass (Lateolabrax maculatus) fillets during refrigerated storage. The minimum inhibitory concentration (MIC) of carvacrol against V. parahemolyticus, S. putrefaciens, S. aureus and P. fluorescens were 0.5, 0.5, 0.125, and 0.5 mg/mL, respectively. Alkaline phosphatase activity assay, nucleotide and protein leakage, and scanning electron microscope demonstrated that carvacrol damaged the external structure of the tested bacterial cells causing leakage of cytoplasmic components. At the same time, when FSG-SA films containing carvacrol used as coating agents for Chinese sea bass fillets cold storage, FSG-SA films containing 1.0 or 2.0 mg/mL carvacrol could significantly reduce TVB-N content, K-value, the degree of microbial deterioration and maintain quality of sea bass fillets according to organoleptic evaluation results.
Sporotrichoid presentation of lupus vulgaris mimicking mycetoma

Most common form of cutaneous tuberculosis (TB) is lupus vulgaris (LV). Atypical presentation of LV is rare and may lead to delay in diagnosis and hence increase in morbidity. Here, we report a case of sporotrichoid form of LV in a 38 year old male who presented as cutaneous lesions mimicking mycetoma. High index of clinical suspicion and relevant investigations play a vital role in confirmation of diagnosis wherever atypical form of cutaneous TB is suspected.
Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

Over the last few decades, chitosan has become a good candidate for tissue engineering applications. Derived from chitin, chitosan is a unique natural polysaccharide with outstanding properties in line with excellent biodegradability, biocompatibility, and antimicrobial activity. Due to the presence of free amine groups in its backbone chain, chitosan could be further chemically modified to possess additional functional properties useful for the development of different biomaterials in regenerative medicine. In the current review, we will highlight the progress made in the development of chitosan-containing bioscaffolds, such as gels, sponges, films, and fibers, and their possible applications in tissue repair and regeneration, as well as the use of chitosan as a component for drug delivery applications.
Receipt of American Heart Association–Recommended Preconception Health Care Among Privately Insured Women With Congenital Heart Defects, 2007–2013

Background Our objective was to estimate receipt of preconception health care among women with congenital heart defects (CHD), according to 2017 American Heart Association recommendations, as a baseline for evaluating recommendation implementation. Methods and Results Using 2007 to 2013 IBM MarketScan Commercial Databases, we identified women with CHD diagnosis codes ages 15 to 44 years who became pregnant and were enrolled in health insurance for ≥11 months in the year before estimated conception. We assessed documentation of complete blood count, electrolytes, thyroid‐stimulating hormone, liver function, ECG, comprehensive echocardiogram, and exercise stress test, using procedural codes, and outpatient prescription claims for US Food and Drug Administration category D and X cardiac‐related medications. Differences were examined according to CHD severity, age, region of residence, year of conception, and documented encounters at obstetric and cardiology practices. We found 2524 pregnancies among 2003 women with CHD (14.4% severe CHD). In the 98.3% of women with a healthcare encounter in the year before conception, <1% received all and 22.6% received no American Heart Association–recommended tests or assessments (range: 54.4% for complete blood count to 3.1% for exercise stress test). Women with the highest prevalence of receipt of recommended care were 35 to 44 years old, pregnant in 2012 to 2013, or had a documented obstetric or cardiology encounter in the year before conception (P<0.05 for all). In 9.0% of pregnancies, ≥1 prescriptions for US Food and Drug Administration category D or X cardiac‐related medications were filled in the year before conception. Conclusions A low percentage of women with CHD received American Heart Association–recommended preconception health care in the year before conception.
Non‐alcoholic fatty liver disease and the incidence of myocardial infarction: A cohort study

Non‐alcoholic fatty liver disease (NAFLD) is a multisystem disease associated with an increased risk of cardiovascular disease (CVD), diabetes, and chronic kidney disease. Indeed, CVD is the most common cause of death in NAFLD patients. This study aimed to evaluate the association between NAFLD and the risk of incident myocardial infarction.
Combination of preoperative fibrinogen and neutrophil to lymphocyte ratio is a predictive prognostic factor in ESCC and AEG systematic review

Abstract Objective: Cancer-associated systemic inflammation response and hyperfibrinogenemia play crucial roles in cancer progression and prognosis. In the present study, we assessed the clinical value of the preoperative fibrinogen and the neutrophil to lymphocyte ratio (NLR) in patients with esophageal squamous cell carcinoma (ESCC) and adenocarcinoma of the esophagogastric junction (AEG). Methods: Three hundred and fifty-six patients who underwent curative surgery were retrospectively analyzed. Univariate and Multivariate Cox analyses were performed to evaluate the prognostic indicators for overall survival (OS). The optimization cut-off values for fibrinogen and the NLR were 3.09 g/l and 1.89, respectively. The fibrinogen and the NLR (F-NLR) index was 2 for patients with high fibrinogen (≥3.09 g/l) and elevated NLR (≥1.89), whereas those with one or neither were indexed as 1 or 0, respectively. Results: The F-NLR score was significantly associated with tumor size (P<0.001), and pathological stage (P=0.010). The 5-year OS rates in F-NLR groups 0, 1 and 2 were 69.1, 42.6, and 31.9%, respectively (P<0.001). Multivariate analysis showed that the tumor size (P<0.001), pathological stage (P<0.001), and F-NLR (P<0.001) were independent prognostic factors for OS. Conclusions: The preoperative F-NLR score is an independent prognosis indicator for patients with ESCC and AEG.
Jumping Tensegrity Robot Based on Torsionally Pre-Strained SMA Springs.

This paper introduces the addition of torsional pre-strain into the manufacturing process of shape memory alloy (SMA) springs to form torsionally pre-strained SMA (TPSMA) springs. These springs have higher performance at the same power input for the same loads and same coil dimensions as regular SMA springs. A modified thermoconstitutive model was presented that can predict the behavior of the actuator based on the amount of torsional pre-strain added into manufacturing process and a simple two-state model is used to predict its actuation stroke. These improved actuators were used in the development of a tensegrity robots capable of fast rolling motions and of jumping both vertically and horizontally. This robot is capable of rolling at 0.14 body length per second (BL/s) and can jump up to nearly a full body length.
hUC-MSCs Exert a Neuroprotective Effect via Anti-apoptotic Mechanisms in a Neonatal HIE Rat Model

In this study, we investigated how human umbilical cord mesenchymal stem cells exerted a neuroprotective effect via antiapoptotic mechanisms in a neonatal hypoxic-ischemic encephalopathy rat model. A total of 78 10-day old (P10) rats were used. After human umbilical cord mesenchymal stem cells were collected from human umbilical cords and amplified in culture, they were administered to rat subjects 1 h after induced hypoxic-ischemic encephalopathy treatment. The short-term (48 h) and long-term (28 day) outcomes were evaluated after human umbilical cord mesenchymal stem cells treatment using neurobehavioral function assessment. Triphenyltetrazolium chloride monohydrate staining was performed at 48 h. Beclin-2 and caspase-3 levels were evaluated with Western blot and real time polymerase chain reaction at 48 h. Human umbilical cord mesenchymal stem cells were collected and administrated to hypoxic-ischemic encephalopathy pups by intracerebroventricular injection. Hypoxic-ischemic encephalopathy typically induced significant delay in development and caused impairment in both cognitive and motor functions in rat subjects. Human umbilical cord mesenchymal stem cells were shown to ameliorate hypoxic-ischemic encephalopathy-induced damage and improve both cognitive and motor functions. Although hypoxic-ischemic encephalopathy induced significant expression of caspase-3 and Beclin-2, human umbilical cord mesenchymal stem cells decreased the expression of both of them. Human umbilical cord mesenchymal stem cells may serve as a potential treatment to ameliorate brain injury in hypoxic-ischemic encephalopathy patients.
Impact of HPV Infection on the Immune System in Oropharyngeal and Non-Oropharyngeal Squamous Cell Carcinoma: A Systematic Review

Objectives: To review the current knowledge regarding the involvement of human papilloma virus (HPV) infection and the immune system in the development of head and neck squamous cell carcinoma (HNSCC). Methods: An electronic literature search was conducted to identify articles published between 1990 and 2019 pertaining to tumor-infiltrating immune cells (TICs) in HNSCC using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Issues of clinical relevance, including tumor location, the number of tumor samples, the inclusion of additional specimens (dysplastic or normal mucosa), tumor size, methods used for HPV detection, relationship between antigen expression and patient characteristics (age, gender, smoking, alcohol consumption, etc.), and prognostic data (overall survival (OS) and recurrence-free survival (RFS)) were assessed by four blinded investigators. Results: The search identified 335 relevant studies, of which 41 met the inclusion criteria. Of these, 7 studies focused on the peripheral blood immune cell concentration in patients with HNSCC according to HPV status, and 36 studies investigated TICs in the intraepithelial and/or stromal compartment(s) according to HPV status. The immune cells studied were CD8+ T cells (N = 19), CD4+ T cells (N = 7), regulatory T cells (Tregs, N = 15), macrophages (N = 13), myeloid-derived suppressor cells (MDSCs, N = 4), and Langerhans cells (LCs, N = 2). Conclusions: Irrespective of tumor location, CD8+ and CD4+ T cells appear to play a key role in the development of HPV−related HNSCC, and their infiltration is likely associated with a significant impact on OS and RFS. To date, the roles and prognostic value of Tregs, macrophages, DCs and MDSCs remain unclear.