Miracle-dz/UniFAR-FTUs huggingface dataset:
Focal adhesion kinase regulates tractional collagen remodeling, matrix metalloproteinase expression, and collagen structure, which in turn affects matrix‐induced signaling

Focal adhesion kinase (FAK) is critical for collagen expression but its regulation of collagen remodeling is not defined. We examined the role of FAK in the degradation and reorganization of fibrillar collagen. Compared with wild‐type (WT) mouse embryonic fibroblasts, FAK null (FAK−/−) fibroblasts generated twofold (p < .0001) higher levels of ¾ collagen I fragment and expressed up to fivefold more membrane‐type matrix metalloproteinase (MMP). When plated on stiff collagen substrates, compared with WT, FAK−/− cells were smaller (threefold reduced cell surface area; p < .0001) and produced fivefold fewer cell extensions (p < .0001) that were 40% shorter (p < .001). When cultured on soft collagen gels (stiffness of ~100 Pa) for 6–48 hr, cell spreading and cell extension formation were reduced by greater than twofold (p < .05 and p < .0001, respectively) while collagen compaction and alignment were reduced by approximately 30% (p < .0001) in FAK−/− cells. Similar results were found after treatment with PF573228, a FAK inhibitor. Reconstitution of FAK−/− cells with FAK mutants showed that compared with WT, cell extension formation was reduced twofold (p < .0001) in the absence of the kinase domain and sixfold (p < .0001) with a Y397F mutant. Enhanced collagen degradation was exhibited by the mutants (~threefold increase; p < .0001 of ¾ collagen fragments without kinase domain or Y397F mutant; p < .01). Compared with FAK+/+ cells, matrices produced by FAK−/− cells generated higher levels of β1 integrin activation (p < 0.05), extracellular‐signal‐regulated kinase (ERK) phosphorylation, and production of ¾ collagen I fragment by human gingival fibroblasts. Collectively these data indicate that (a) the kinase activity of FAK enhances collagen remodeling by tractional forces but inhibits collagen degradation by MMPs; (b) FAK influences the biological activity of fibroblast‐secreted extracellular matrices, which in turn impacts β1 integrin and ERK signaling, and collagen degradation.
Genetic Diversity and Demographic History of an Upper Hill Dipterocarp (Shoreaplatyclados): Implications for Conservation.

Southeast Asian rainforests at upper hill elevations are increasingly vulnerable to degradation because most lowland forest areas have been converted to different land uses. As such, understanding the genetics of upper hill species is becoming more crucial for their future management and conservation. Shoreaplatyclados is an important, widespread upper hill dipterocarp in Malaysia. To elucidate the genetic structure of S. platyclados and ultimately provide guidelines for a conservation strategy for this species, we carried out a comprehensive study of the genetic diversity and demographic history of S. platyclados. Twenty-seven populations of S. platyclados across its range in Malaysia were genotyped at 15 polymorphic microsatellite loci and sequenced at seven noncoding chloroplast DNA (cpDNA) regions. A total of 303 alleles were derived from the microsatellite loci, and 29 haplotypes were identified based on 2892 bp of concatenated cpDNA sequences. The populations showed moderately high genetic diversity (mean HE = 0.680 for microsatellite gene diversity and HT = 0.650 for total haplotype diversity) and low genetic differentiation (FST = 0.060). Bayesian clustering divided the studied populations into two groups corresponding to western and eastern Malaysia. Bottleneck analysis did not detect any recent bottleneck events. Extended Bayesian skyline analyses showed a model of constant size for the past population history of this species. Based on our findings, priority areas for in situ and ex situ conservation and a minimum population size are recommended for the sustainable utilization of S. platyclados.
Phase I trial of caudate deep brain stimulation for treatment-resistant tinnitus.

OBJECTIVE The objective of this open-label, nonrandomized trial was to evaluate the efficacy and safety of bilateral caudate nucleus deep brain stimulation (DBS) for treatment-resistant tinnitus. METHODS Six participants underwent DBS electrode implantation. One participant was removed from the study for suicidality unrelated to brain stimulation. Participants underwent a stimulation optimization period that ranged from 5 to 13 months, during which the most promising stimulation parameters for tinnitus reduction for each individual were determined. These individual optimal stimulation parameters were then used during 24 weeks of continuous caudate stimulation to reach the endpoint. The primary outcome for efficacy was the Tinnitus Functional Index (TFI), and executive function (EF) safety was a composite z-score from multiple neuropsychological tests (EF score). The secondary outcome for efficacy was the Tinnitus Handicap Inventory (THI); for neuropsychiatric safety it was the Frontal Systems Behavior Scale (FrSBe), and for hearing safety it was pure tone audiometry at 0.5, 1, 2, 3, 4, and 6 kHz and word recognition score (WRS). Other monitored outcomes included surgery- and device-related adverse events (AEs). Five participants provided full analyzable data sets. Primary and secondary outcomes were based on differences in measurements between baseline and endpoint. RESULTS The treatment effect size of caudate DBS for tinnitus was assessed by TFI [mean (SE), 23.3 (12.4)] and THI [30.8 (10.4)] scores, both of which were statistically significant (Wilcoxon signed-rank test, 1-tailed; alpha = 0.05). Based on clinically significant treatment response categorical analysis, there were 3 responders determined by TFI (≥ 13-point decrease) and 4 by THI (≥ 20-point decrease) scores. Safety outcomes according to EF score, FrSBe, audiometric thresholds, and WRS showed no significant change with continuous caudate stimulation. Surgery-related and device-related AEs were expected, transient, and reversible. There was only one serious AE, a suicide attempt unrelated to caudate neuromodulation in a participant in whom stimulation was in the off mode for 2 months prior to the event. CONCLUSIONS Bilateral caudate nucleus neuromodulation by DBS for severe, refractory tinnitus in this phase I trial showed very encouraging results. Primary and secondary outcomes revealed a highly variable treatment effect size and 60%-80% treatment response rate for clinically significant benefit, and no safety concerns. The design of a phase II trial may benefit from targeting refinement for final DBS lead placement to decrease the duration of the stimulation optimization period and to increase treatment effect size uniformity.Clinical trial registration no.: NCT01988688 (clinicaltrials.gov).
Lock Stock And Barrel of Wound Healing.

Any kind of injury may lead to wound formation. As per World Health Organization Report, "more than 5 million people die each year due to injuries. This accounts for 9% of world's population death, nearly 1.7 times the number of fatalities that result from HIV/ AIDS, tuberculosis and malaria combined. In addition, tens of millions people suffer with non fatal injuries which require treatment". This scenario leads to increased health and economic burden worldwide. Rapid wound healing is exigent subject-field in health care system. It is imperative to be updated on wound care strategies as impaired wound healing may lead to chronic, non-healing wounds and thus further contributes to national burden. This article is a comprehensive review of wound care strategies. The first and second part of this review article focuses on understanding of wound, its types, human body's healing mechanism. Wound healing is natural, highly coordinated process that starts on its own, immediately after injury. However, the individual health condition influences the healing process. Discussion of factors affecting wound healing has also been included. Next part includes the detailed review of diverse wound healing strategies that has already been developed for different types of wound. Detailed description of various polymers that may be used has been discussed. Amongst drug delivery systems, oligomers, dendrimeres, films, gels, different nano-formulations, like nanocomposites, nanofibers, nanoemulsions, nanoparticles are discussed. Emphasis on bandages has been made in this article.
A Case of Idiopathic Non-Cirrhotic Portal Hypertension in a Patient With a Left Ventricular Assist Device

Idiopathic non-cirrhotic portal hypertension is a rare diagnosis caused by an unknown etiology with elevated intrahepatic portal pressures in the absence of underlying liver disease. We present a unique case of a 57-year-old male with a left ventricular assist device and preserved right ventricular function that was found to have an elevated hepatic venous pressure gradient and sequelae of portal hypertension without underlying liver disease. There is limited treatment available as management is primarily aimed toward preventing complications of the disease. This case highlights the need for further investigative research of this disease entity and its pathogenesis.
Selectively bred oysters can alter their biomineralization pathways, promoting resilience to environmental acidification

Commercial shellfish aquaculture is vulnerable to the impacts of ocean acidification driven by increasing carbon dioxide (CO2) absorption by the ocean as well as to coastal acidification driven by land run off and rising sea level. These drivers of environmental acidification have deleterious effects on biomineralization. We investigated shell biomineralization of selectively bred and wild‐type families of the Sydney rock oyster Saccostrea glomerata in a study of oysters being farmed in estuaries at aquaculture leases differing in environmental acidification. The contrasting estuarine pH regimes enabled us to determine the mechanisms of shell growth and the vulnerability of this species to contemporary environmental acidification. Determination of the source of carbon, the mechanism of carbon uptake and use of carbon in biomineral formation are key to understanding the vulnerability of shellfish aquaculture to contemporary and future environmental acidification. We, therefore, characterized the crystallography and carbon uptake in the shells of S. glomerata, resident in habitats subjected to coastal acidification, using high‐resolution electron backscatter diffraction and carbon isotope analyses (as δ13C). We show that oyster families selectively bred for fast growth and families selected for disease resistance can alter their mechanisms of calcite crystal biomineralization, promoting resilience to acidification. The responses of S. glomerata to acidification in their estuarine habitat provide key insights into mechanisms of mollusc shell growth under future climate change conditions. Importantly, we show that selective breeding in oysters is likely to be an important global mitigation strategy for sustainable shellfish aquaculture to withstand future climate‐driven change to habitat acidification.
Proton theraPy sPecial feature: review article Physical advantages of particles: protons and light ions

Proton and ion beam therapy has been introduced in the Lawrence Berkeley National Laboratory in the mid- 1950s, when protons and helium ions have been used for the first time to treat patients. Starting in 1972, the scientists at Berkeley also were the first to use heavier ions (carbon, oxygen, neon, silicon and argon ions). The first clinical ion beam facility opened in 1994 in Japan and since then, the interest in radiotherapy with light ion beams has been increasing slowly but steadily, with 13 centers in clinical operation in 2019. All these centers are using carbon ions for clinical application. The article outlines the differences in physical properties of various light ions as compared to protons in view of the application in radiotherapy. These include the energy loss and depth dose properties, multiple scattering, range straggling and nuclear fragmentation. In addition, the paper discusses differences arising from energy loss and linear energy transfer with respect to their biological effects. the paper perspectives like
Overt Attention toward Appetitive Cues Enhances Their Subjective Value, Independent of Orbitofrontal Cortex Activity

Abstract Neural representations of value underlie many behaviors that are crucial for survival. Previously, we found that value representations in primate orbitofrontal cortex (OFC) are modulated by attention, specifically, by overt shifts of gaze toward or away from reward-associated visual cues (McGinty et al., 2016). Here, we investigate the influence of overt attention on behavior by asking how gaze shifts correlate with reward anticipatory responses and whether activity in OFC mediates this correlation. Macaque monkeys viewed pavlovian conditioned appetitive cues on a visual display, while the fraction of time they spent looking toward or away from the cues was measured using an eye tracker. Also measured during cue presentation were the reward anticipation, indicated by conditioned licking responses (CRs), and single-neuron activity in OFC. In general, gaze allocation predicted subsequent licking responses: the longer the monkeys spent looking at a cue at a given time point in a trial, the more likely they were to produce an anticipatory CR later in that trial, as if the subjective value of the cue were increased. To address neural mechanisms, mediation analysis measured the extent to which the gaze–CR correlation could be statistically explained by the concurrently recorded firing of OFC neurons. The resulting mediation effects were indistinguishable from chance. Therefore, while overt attention may increase the subjective value of reward-associated cues (as revealed by anticipatory behaviors), the underlying mechanism remains unknown, as does the functional significance of gaze-driven modulation of OFC value signals.
Patterns of medical student engagement in a second-year pathophysiology course: relationship to USMLE Step 1 performance.

Historically, attendance has been a marker of academic performance, but the current medical education literature has had mixed results. In addition, attendance is dropping in the preclinical curricula, whereas, at the same time, the focus on United States Medical Licensing Examination Step 1 performance is increasing. This present study is a mixed-method approach correlating student attendance and access to the formal curriculum in a second-year pathophysiology course to performance on Step 1. Additionally, survey and focus group data evaluated the usage and importance of both the formal curriculum and third-party resources. Out of 112 eligible students, 77 participated in the study. There was no correlation between attendance or access to the learning materials and Step 1 performance. There was a strong correlation between the performance on the final examination and that of Step 1 (r = 0.813; P < 0.001) and a moderate correlation between formative quiz (r = 0.321; P = 0.005) and individual readiness assessment test performance (r = 0.351; P = 0.002) and Step 1 performance. Survey and focus group data show that students place high importance on faculty-developed materials that they can use on their own, but not attendance. The third-party resources are highly used as an adjunct to the formal curriculum and to focus on Step 1 study. Attendance and access to the formal curriculum do not predict Step 1 performance, whereas performance on high- and low-stakes internal assessments do. Further study on how the lack of social interaction gained from attendance affects development of other competencies and the learning climate are warranted.
Reduced Salivary Mucin Binding and Glycosylation in Older Adults Influences Taste in an In Vitro Cell Model

Background: Taste loss is a significant problem in older adults, affecting quality of life and nutrition. Altered salivary rheology and loss of mucin function may contribute to taste loss by reducing mucosal defences in the oral cavity, impairing sensitivity to oral stimulants. This study aimed to investigate the effects of salivary rheology on taste loss in ageing. Salivary mucin glycosylation and binding to the oral epithelium was investigated in older and younger adults. A cell-based model was utilised to consider the role of saliva in taste loss. Methods: Human subjects aged >60 years (n = 25) and 18–30 (n = 30) provided saliva samples which were analysed for viscosity, mucin composition and mucin binding to oral epithelial cells (TR146/MUC1). Oral epithelial cells (TR146/MUC1 and SCC090) provided models for taste receptor activation. Results: Reduced levels and sialylation of MUC7 were evident in saliva of older adults which may lead to reduced viscoelasticity, while viscosity is unaffected. Impaired muco-adhesion of saliva from older adults was also observed. Saliva from older adults facilitated the bitter taste receptor activation less well than saliva from younger adults. The causes of taste dysfunction in older adults are unknown, but this study supports a role of saliva in facilitating the activation of taste receptors.
Evidence of chronic stroke rehabilitation interventions in activities and participation outcomes: systematic review of meta-analyses of randomized controlled trials.

INTRODUCTION Stroke is a leading cause of long-term disabilities worldwide. A great deal of meta-analyses of Randomized Controlled Trials (RCTs) address rehabilitation in chronic stroke, several of them with focus on activities and participation, considered critical outcomes of successful rehabilitation. Nevertheless, substantial heterogeneity might exist between studies, the reported associations may be causal, but they might also be flawed, as inherent study biases such as residual confounding and selective reporting of positive results may exaggerate the effect of interventions in chronic phase. Furthermore, most RCTs might focus on specific rehabilitation domains, not paying the same attention to others. EVIDENCE ACQUSITION Formal evaluation of published systematic reviews of meta- analyses (January 2008 to November 2018) of rehabilitation in chronic phase to 1) assess the strength of evidence: participants, publication biases, heterogeneity, prediction intervals (PIs) 2) grade the evidence to perform qualitative analysis on effects sizes and heterogeneity, 3) perform meta-regressions and sensitivity analysis on relevant covariates 4) map outcomes to activities and participation domain of the World Health Organization's International Classification of Functioning, Disability and Health (ICF). Systematic review on meta-analyses of RCTs addressing activities and participation will be performed in Medline, Web of Science, Scopus, Cochrane and Google Scholar. EVIDENCE SYNTHESIS A total of 97 meta-analyses on 31 different rehabilitation interventions involving 25,275 participants were included. Thirty-nine meta-analyses (40.74%) reported statistically significant findings (P < 0.05) in both fixed and random effects sizes. Their magnitude was small in 62.96% cases, moderate in 19.75% and large in 17.28%. Heterogeneity was low in 48,48%, moderate and high in 21.2%. The mean number ofparticipants is 815, far away from the convincing, highly suggestive, or suggestive required evidence levels. All PIs include the null value. Mobility is addressed by 87% of the identified meta-analyses, with 75% of them focusing exclusively in mobility. CONCLUSIONS The findings of this study show a clear need for high quality RCTs examining the effectiveness of rehabilitation interventions addressing activities and participation. The ICF framework may contribute to a holistic approach in chronic stroke rehabilitation, including not only motor functioning but also the ability to participate in everyday life activities.
Metabolic Disturbances of a High-Fat Diet Are Dependent on APOE Genotype and Sex

Abstract Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for Alzheimer’s disease (AD). APOE4 is also associated with an increased risk of metabolic syndrome. Obesity is a major environmental risk factor for AD. While APOE genotype and obesity independently affect metabolism and cognition, they may also have synergistic effects. Here, we examined the metabolic and behavioral alterations associated with a high-fat diet (HFD) in male and female APOE knock-in mice. Male and female mice were fed a 45% kcal HFD or a 10% kcal low-fat diet (LFD) for 12 weeks and adipose tissue accumulation, glucose levels, anxiety-like behavior, and spatial memory were examined. We found that with HFD, male APOE4 mice were more susceptible to metabolic disturbances, including visceral adipose tissue (VAT) accumulation and glucose intolerance when compared to APOE3 mice, while female APOE3 and APOE4 mice had similar metabolic responses. Behaviorally, there were no effects of HFD in mice of either genotype. Our results suggest that metabolic responses to HFD are dependent on both sex and APOE genotype.
A Study on the Application of Automated Essay Scoring in College English Writing Based on Pigai

—In recent years, Automated Essay Scoring (AES) has been more and more widely used in college English writing. This article takes Pigai as an example to introduce the advantages and disadvantages of AES, and though questionnaire survey and interviews, analyzes the influence of AES on college English writing. It proposes how to further apply AES in the practice and reform of college English writing.
Women’s Preferences for Maternal and Neonatal Morbidity and Mortality in Childbirth

Purpose. To measure utility values that describe women’s willingness to tradeoff maternal morbidity for fetal benefit among pregnant and nonpregnant women of reproductive age. Methods. We recruited English-speaking women aged 18 to 45 years in clinical and community-based settings. Eight health states were studied: 4 maternal (healthy, stroke, hysterectomy, death) and 4 neonatal (healthy, severe cerebral palsy [CP], severe mental retardation [MR], death). Utilities were assessed on a subset of 9 pairs of mom/baby delivery outcomes. Participants ranked the 9 pairs of outcomes in order of preference, then standard gamble methods were used to calculate utilities. Numeracy skills were assessed. Results. Utilities were obtained from 477 participants (recruitment rate = 94%). Twenty-one percent were pregnant, 63% were parents, and 54% were African American. Utilities did not differ significantly between pregnant and nonpregnant women or based on numeracy score. The highest (nonhealthy) values were assigned to baby healthy/mom hysterectomy (0.999), baby healthy/mom stroke (0.946), and baby CP/mom healthy (0.940). The lowest values were assigned to baby death/mom hysterectomy (0.203), baby MR/mom death (0.150), and baby death/mom stroke (0.087). Nonwhite participants assigned a significantly higher value to baby MR/mom death (P = 0.01), baby MR/mom stroke (P = 0.02), baby MR/mom healthy (P < 0.01), and baby MR/mom hysterectomy (P = 0.02) than white participants. Conclusion. When asked to value pairs of maternal/fetal outcomes that required a tradeoff of morbidity and mortality, women tended to assign the highest utility to combinations that resulted in a “healthy baby. ” They assigned the lowest values to combinations that resulted in a baby’s death or MR. Our findings highlight the importance of 1) assessing individual preferences and goals of care for pregnancy outcomes and 2) measuring utilities among reproductive-aged women when modeling obstetric decision making.