Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of remdesivir on viral dynamics in COVID-19 hospitalized patients: a modelling analysis of the randomized, controlled, open-label DisCoVeRy trial

Abstract Background The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial. Objectives To estimate the effect of remdesivir in blocking viral replication. Methods We analysed nasopharyngeal normalized viral loads from 665 hospitalized patients included in the DisCoVeRy trial (NCT 04315948; EudraCT 2020-000936-23), randomized to either standard of care (SoC) or SoC + remdesivir. We used a mathematical model to reconstruct viral kinetic profiles and estimate the antiviral efficacy of remdesivir in blocking viral replication. Additional analyses were conducted stratified on time of treatment initiation (≤7 or >7 days since symptom onset) or viral load at randomization (< or ≥3.5 log10 copies/104 cells). Results In our model, remdesivir reduced viral production by infected cells by 2-fold on average (95% CI: 1.5–3.2-fold). Model-based simulations predict that remdesivir reduced time to viral clearance by 0.7 days compared with SoC, with large inter-individual variabilities (IQR: 0.0–1.3 days). Remdesivir had a larger impact in patients with high viral load at randomization, reducing viral production by 5-fold on average (95% CI: 2.8–25-fold) and the median time to viral clearance by 2.4 days (IQR: 0.9–4.5 days). Conclusions Remdesivir halved viral production, leading to a median reduction of 0.7 days in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.
INTRAVITREAL NESVACUMAB (ANTIANGIOPOIETIN 2) PLUS AFLIBERCEPT IN DIABETIC MACULAR EDEMA

Supplemental Digital Content is Available in the Text. In a Phase 2 study of patients with diabetic macular edema, combination treatment with intravitreal nesvacumab (antiangiopoietin 2) plus aflibercept (antivascular endothelial growth factor) demonstrated some evidence of anatomic improvements but did not demonstrate superior visual acuity benefits over intravitreal aflibercept alone. Purpose: The purpose of this study was to compare intravitreal nesvacumab (anti-angiopoietin 2) plus aflibercept with intravitreal aflibercept injection (IAI) in diabetic macular edema. Methods: The eyes (n = 302) were randomized (1:2:3) to nesvacumab 3 mg + aflibercept 2 mg (LD combo), nesvacumab 6 mg + aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, Weeks 4 and 8. LD combo continued every 8 weeks (q8w). HD combo was rerandomized at Week 12 to q8w or every 12 weeks (q12w); IAI to q8w, q12w, or HD combo q8w through Week 32. Results: Week 12 best-corrected visual acuity gains for LD and HD combo versus IAI were 6.8, 8.5, and 8.8 letters; Week 36 changes were similar. Central subfield retinal thickness reductions at Week 12 were −169.4, −184.0, and −174.6 µm (nominal P = 0.0183, HD combo vs. IAI); Week 36 reductions for LD combo and HD combo q8w and q12w versus IAI were −210.4, −223.4, and −193.7 versus −61.9 µm (nominal P < 0.05). At Week 12, 13.3% and 21.3% versus 15.2% had ≥2-step Diabetic Retinopathy Severity Scale improvement (LD and HD combos vs. IAI) and 59.6% and 66.3% versus 53.7% had complete foveal center fluid resolution. Safety was comparable across groups. Conclusion: Nesvacumab + aflibercept demonstrated no additional visual benefit over IAI. Anatomic improvements with HD combo may warrant further investigation.
A Bayesian Network Analysis of the Probabilistic Relationships Between Various Obesity Phenotypes and Cardiovascular Disease Risk in Chinese Adults: Chinese Population-Based Observational Study

Background Cardiovascular disease (CVD) risk among individuals with different BMI levels might depend on their metabolic health. The extent to which metabolic health status and BMI affect CVD risk, either directly or through a mediator, in the Chinese population remains unclear. Objective In this study, the Bayesian network (BN) perspective is adopted to characterize the multivariable probabilistic connections between CVD risk and metabolic health and obesity status and identify potential factors that influence these relationships among Chinese adults. Methods The study population comprised 6276 Chinese adults aged 30 to 74 years who participated in the China Health and Nutrition Survey 2009. BMI was used to categorize participants as normal weight, overweight, or obese, and metabolic health was defined by the Adult Treatment Panel-3 criteria. Participants were categorized into 6 phenotypes according to their metabolic health and BMI categorization. The 10-year risk of CVD was determined using the Framingham Risk Score. BN modeling was used to identify the network structure of the variables and compute the conditional probability of CVD risk for the different metabolic obesity phenotypes with the given structure. Results Of 6276 participants, 64.67% (n=4059), 20.37% (n=1279), and 14.95% (n=938) had a low, moderate, and high 10-year CVD risk. An averaged BN with a stable network structure was constructed by learning 300 bootstrapped networks from the data. Using BN reasoning, the conditional probability of high CVD risk increased as age progressed. The conditional probability of high CVD risk was 0.43% (95% CI 0.2%-0.87%) for the 30 to 40 years age group, 2.25% (95% CI 1.75%-2.88%) for the 40 to 50 years age group, 16.13% (95% CI 14.86%-17.5%) for the 50 to 60 years age group, and 52.02% (95% CI 47.62%-56.38%) for those aged ≥70 years. When metabolic health and BMI categories were instantiated to their different statuses, the conditional probability of high CVD risk increased from 7.01% (95% CI 6.27%-7.83%) for participants who were metabolically healthy normal weight to 10.47% (95% CI 7.63%-14.18%) for their metabolically healthy obese (MHO) counterparts and up to 21.74% and 34.48% among participants who were metabolically unhealthy normal weight and metabolically unhealthy obese (MUO), respectively. Sex was a significant modifier of the conditional probability distribution of metabolic obesity phenotypes and high CVD risk, with a conditional probability of high CVD risk of only 2.02% and 22.7% among MHO and MUO women, respectively, compared with 21.92% and 48.21% for their male MHO and MUO counterparts, respectively. Conclusions BN modeling was applied to investigate the relationship between CVD risk and metabolic health and obesity phenotypes in Chinese adults. The results suggest that both metabolic health and obesity status are important for CVD prevention; closer attention should be paid to BMI and metabolic status changes over time.
Gamma-band enhancement of functional brain connectivity following transcutaneous electrical nerve stimulation

Objective. Transcutaneous electrical nerve stimulation (TENS) has been suggested as a possible non-invasive pain treatment. However, the underlying mechanism of the analgesic effect of TENS and how brain network functional connectivity (FC) is affected following the use of TENS is not yet fully understood. The purpose of this study was to investigate the effect of high-frequency TENS on the alteration of functional brain network connectivity and the corresponding topographical changes, besides perceived sensations. Approach. Forty healthy subjects participated in this study. Electroencephalography (EEG) data and sensory profiles were recorded before and up to an hour following high-frequency TENS (100 Hz) in sham and intervention groups. Brain source activity from EEG data was estimated using the LORETA algorithm. In order to generate the functional brain connectivity network, the Phase Lag Index was calculated for all pair-wise connections of eight selected brain areas over six different frequency bands (i.e. δ, θ, α, β, γ, and 0.5–90 Hz). Main results. The results suggested that the FC between the primary somatosensory cortex (SI) and the anterior cingulate cortex, in addition to FC between SI and the medial prefrontal cortex, were significantly increased in the gamma-band, following the TENS intervention. Additionally, using graph theory, several significant changes were observed in global and local characteristics of functional brain connectivity in gamma-band. Significance. Our observations in this paper open a neuropsychological window of understanding the underlying mechanism of TENS and the corresponding changes in functional brain connectivity, simultaneously with alteration in sensory perception.
Home-Based Palliative Care Organizations Struggle to Survive and Thrive in a Competitive Market

Background New opportunities to expand home-based palliative care (HBPC) highlight the need for novel data that explores how HBPC providers currently navigate this nascent business. Objectives To investigate how HBPC providers and their organizations sustain their operations in a rapidly evolving market. Study Design This was an exploratory, qualitative study. Setting We conducted focus groups with staff of nine HBPC organizations that held provider contracts with a large California insurance provider. Measurement A research team member experienced in qualitative methods conducted semi-structured focus group interviews with HBPC agency staff who were knowledgeable about their agency’s patient recruitment and enrollment processes. Interview sessions of roughly an hour long were audio-recorded and transcribed verbatim. We used thematic analysis procedures to identify codes and themes. Results We identified seven themes: market competition, market diversity, HBPC reimbursement, service standardization, hiring practices, marketing, strategic enrollment processes, and outcomes monitoring. The participants called for more standardization in their field. In discussing key business operations—hiring, marketing, patient enrollment, outcomes monitoring—they demonstrated inventiveness and willingness to innovate in order to succeed in a complex healthcare sector. Conclusion Our study expands on the literature by providing a glimpse of the challenges encountered by HBPC providers and their organizations and the myriad strategies they undertake to navigate a health-service area that lacks standardized practice and payment guidelines. Our findings suggest that HBPC agencies will continue to struggle in the absence of standardization in practice, payment, and quality oversight.
Measurement of Gastric Emptying Using a 13 C-octanoic Acid Breath Test with Wagner-Nelson Analysis and Scintigraphy in Type 2 Diabetes

Abstract Introduction Breath tests utilising 13 C-labelled substrates for the assessment of gastric emptying have been applied widely. Wagner-Nelson analysis is a pharmacokinetic model that can be utilised to generate a gastric emptying curve from the % 13 CO 2 measured in breath samples. We compared Wagner-Nelson analysis with (i) scintigraphy and (ii) conventional breath test modelling to quantify gastric emptying in type 2 diabetes. Methods Thirteen patients (age 68.1±1.5 years, body mass index 31.0±0.9 kg/m 2 , HbA1c 6.3±0.2%) consumed a mashed potato meal comprising 65 g powdered potato, 20 g glucose, 250 ml water, an egg yolk labelled with 100 μL 13 C-octanoic acid and 20MBq 99m Tc-calcium phytate. Scintigraphic data were acquired and breath samples collected for 4 hours after the meal. Gastric emptying curves were derived based on each technique; the 50% emptying time and intragastric retention at 60 min were also calculated. Results With Wagner-Nelson analysis, a K el =0.60 (the elimination constant) best approximated the scintigraphic gastric emptying curve. There was a relationship between the T50 calculated with scintigraphy and by both Wagner-Nelson K el =0.60 (r 2 =0.45, P<0.05) and conventional analysis (r 2 =0.44, P<0.05). There was no significant difference in the 50% gastric emptying time for scintigraphy (68.5±4.8 min) and Wagner-Nelson K el =0.60 (71.3±4.5 min), however, the 50% gastric emptying time calculated by conventional analysis was much greater at 164.7±6.0 min (P<0.001). Conclusion In type 2 diabetes, gastric emptying of a mashed potato meal measured using a 13 C-octanoic acid breath test analysed with Wagner-Nelson K el =0.60 closely reflects measurements obtained with scintigraphy, whereas, in absolute terms, the conventional breath test analysis does not.
Barriers and facilitators to accessing effective clinical supervision and the implementation of a clinical supervision exchange model in the Australian alcohol and other drugs sector

Abstract Introduction Internationally, clinical/practice supervision is considered essential in the development and maintenance of professional proficiency across health disciplines. Among alcohol and other drug (AOD) workers, however, access to effective clinical supervision is limited. This study examined perceived barriers and facilitators to: (i) AOD workers accessing effective clinical supervision; and (ii) effective implementation of a clinical supervision exchange model in the AOD sector. Methods Qualitative interviews with frontline workers (n = 10) and managers (n = 11) employed by eight government and non‐government AOD treatment services in Brisbane, Australia were undertaken. Interviews were audio recorded, transcribed and data were thematically analysed. Results Frontline workers and managers shared similar views. Reported barriers and facilitators to accessing effective clinical supervision included limited time, the high cost of providers, availability of skilled clinical supervisors, supervisor–supervisee matching and supervision modality. Participants considered the implementation of a clinical supervision exchange model to be a resource‐effective strategy to increase access to external, individual clinical supervision while also exposing workers to a greater diversity of perspectives, increasing sector collaboration and improving the perceived value of clinical supervision among the workforce. Discussion and Conclusions The findings of this study suggest that limited time, cost and availability of skilled supervisors are primary barriers to AOD workers accessing high‐quality clinical supervision. Implementation of a clinical supervision exchange model is perceived by frontline workers and service delivery managers to be a resource‐effective strategy for increasing access to high‐quality clinical supervision among workers.
HRAS germline mutations impair LKB1/AMPK signaling and mitochondrial homeostasis in Costello syndrome models

Germline mutations that activate genes in the canonical RAS/MAPK signaling pathway are responsible for rare human developmental disorders known as RASopathies. Here, we analyzed the molecular determinants of Costello syndrome (CS) using a mouse model expressing HRAS p.G12S, patient skin fibroblasts, hiPSC-derived human cardiomyocytes, a HRAS p.G12V zebrafish model, and human fibroblasts expressing lentiviral constructs carrying HRAS p.G12S or HRAS p.G12A mutations. The findings revealed alteration of mitochondrial proteostasis and defective oxidative phosphorylation in the heart and skeletal muscle of CS mice that were also found in the cell models of the disease. The underpinning mechanisms involved the inhibition of the AMPK signaling pathway by mutant forms of HRAS, leading to alteration of mitochondrial proteostasis and bioenergetics. Pharmacological activation of mitochondrial bioenergetics and quality control restored organelle function in HRAS p.G12A and p.G12S cell models, reduced left ventricle hypertrophy in CS mice, and diminished the occurrence of developmental defects in the CS zebrafish model. Collectively, these findings highlight the importance of mitochondrial proteostasis and bioenergetics in the pathophysiology of RASopathies and suggest that patients with CS may benefit from treatment with mitochondrial modulators.
Nonspecific Effects of Normal Aging on Taxonomic and Thematic Semantic Processing

ABSTRACT Objective This study aimed to assess the effect of normal aging on the processing of taxonomic and thematic semantic relations. Method We used the Visual-World-Paradigm coupled with eye-movement recording. We compared performance of healthy younger and older adults on a word-to-picture matching task in which participants had to identify each target among semantically related (taxonomic or thematic) and unrelated distractors. Results Younger and older participants exhibited similar patterns of gaze fixations in the two semantic conditions. The effect of aging took the form of an overall reduction in sensitivity to semantic competitors, with no difference between the taxonomic and thematic conditions. Moreover, comparison of the proportions of fixations between the younger and older participants indicated that targets were identified equally quickly in both age groups. This was not the case when mouse-click reaction times were analyzed. Conclusions Findings argue in favor of nonspecific effects of normal aging on semantic processing that similarly affect taxonomic and thematic processing. There are important clinical implications, as pathological aging has been repeatedly shown to selectively affect either taxonomic or thematic relations. Measuring eye-movements in a semantic task is also an interesting approach in the elderly, as these seem to be less impacted by aging than other motor responses.
The Study on Shear Strength of Facial Soil-in-Root of Biotechnological Protection on Side Slope

According to the direct shear strength tests of soil-in-root, the direct shear strength of the facial soil-in-root of rocky slope has been studied, the difference of the direct shear strength between soil-in-root and soil which is in the same condition has also been discussed and analyzed. Finally, drew a conclusion that the quantity of the root is a very important factor for the direct shear strength and other engineering characteristics of soil increased.
Preventive Efficiency of Chelidonium majus Ethanolic Extract Against Aflatoxin B1 Induced Neurochemical Deteriorations in Rats.

Background and Objective: Aflatoxins affect many species including humans and animals, therefore the present study was designed to investigate the protective effect of Chelidonium majus Ethanolic Extract (CMEE) on neurotoxicity induced by Aflatoxin B1 (AFB1) in rats. Materials and Methods: Four groups of male Albino rats were treated orally for 28 days as follows: (1) Control group was daily given DMSO-PBS buffer (1.0 mL per rat), (2) CMEE (300 mg kg1/day) dissolved in DMSO-PBS buffer, (3) AFB1 (80 μg kg1/day) dissolved in DMSO-PBS buffer and (4) Received daily AFB1 (300 mg kg1) in combination with CMEE (300 mg kg1). Results: CMEE exhibits antioxidant activity in vitro and neuroameliorative efficiency in vivo as its administration in combination with AFB1 succeeded significantly in down regulating the elevated levels of inflammatory and apoptotic markers and restoring the values of neurochemical markers (AChE-ase, dopamine and serotonin) that were deteriorated by AFB1 intake. Conclusion: In conclusion, the neuroprotective effect of CMEE may be mediated through its antioxidant and free radical scavenging activity that proved from the data of ferric-reducing power ability and DPPH radical scavenging activity.
Positive Urgency, Drinking Preoccupation, and Alcohol Problems in College Students

Abstract Objective Individuals high in positive urgency (i.e., impulsiveness stemming from high positive mood) may be more preoccupied with alcohol-related cognitions. Our aim was to examine how positive urgency, drinking preoccupation, and consumption patterns concurrently influence the endorsement of alcohol-related problems. Method We sampled 756 students enrolled in a large, public U.S. university, who completed a cross-sectional survey online. Their mean age was 19.6 (SD = 1.72), 71.3% identified as female, and participants largely identified as Caucasian (65.5%) and Hispanic/Latinx (22.1%). Self-report measurements of trait positive urgency and drinking preoccupation and retrospective data of alcohol use and alcohol-related problems were collected. A series of linear regressions tested for a hypothesized indirect effect between variables. Results We discovered an indirect effect in the relationship between positive urgency and alcohol-related problems via drinking preoccupation. A significant conditional effect showed that this relationship was influenced by past 30-day alcohol consumption, with the effect gaining strength as consumption days increased. Conclusions Students with high positive urgency may be more engrossed with alcohol-related drinking cognitions, leading to negative consequences as their alcohol consumption increases. This potential association can inform tailored intervention plans for college student alcohol control, such as successfully managing intense positive moods and alcohol-related cognitions and triggers.
Maternal postnatal depression and anxiety and the risk for mental health disorders in adolescent offspring: Findings from the Avon Longitudinal Study of Parents and Children cohort

Objective: The impacts of postnatal psychiatric disorders on different types of mental health problems in offspring are unclear. We investigated the prospective associations of maternal postnatal depression, and anxiety, with offspring depression, anxiety, psychotic-like experiences and Borderline Personality Disorder symptoms, in adolescence, and examined whether these were independent of each other. Methods: Data were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Maternal postnatal depression and anxiety at 8 weeks were measured using the Edinburgh Postnatal Depression Scale and Crown-Crisp Index, respectively. Offspring mental health outcomes were measured at 10–13 years old, using a variety of questionnaire-based and interview assessments. Logistic regression analyses were used to assess the associations between maternal postnatal risk factors and offspring mental health, and path analysis was used to investigate the pathways of maternal postnatal factors to adolescent offspring outcomes. Results: Data were available for 14,054 mothers with information reported on postnatal depression and 13,892 on postnatal anxiety. Logistic regression analyses found significant associations between maternal postnatal depression and offspring anxiety at 10 years old (odds ratio = 1.039, 95% confidence interval = [1.005, 1.073], p = 0.022) and between maternal postnatal anxiety and offspring psychotic experiences at 12/13 years old (odds ratio = 1.042, 95% confidence interval = [1.008, 1.077], p = 0.016). These significant associations remained after applying path analyses, when we controlled for potential offspring psychopathological overlay. Conclusion: These findings suggest that mothers with postnatal depression are more likely to have offspring with anxiety at 10 years old, and that mothers with postnatal anxiety are more likely to have offspring with psychotic experiences at 12/13 years old. Our findings suggest specific pathways in the association between postnatal anxiety/depression and offspring mental health and contribute to the importance of identifying mothers and their offspring with increased vulnerability to adverse outcomes resulting from postnatal mental health disorders.