Miracle-dz/UniFAR-FTUs huggingface dataset:
The GLP‐1/GIP dual‐receptor agonist DA5‐CH inhibits the NF‐κB inflammatory pathway in the MPTP mouse model of Parkinson's disease more effectively than the GLP‐1 single‐receptor agonist NLY01

The GLP‐1 receptor agonist exendin‐4 has recently shown good effects in a phase II clinical trial in Parkinson's disease (PD) patients. Here, a comparison of the new GLP‐1/GIP dual receptor agonist DA5‐CH and NLY01, a 40 kDa pegylated form of exendin‐4, on motor impairments and reducing inflammation in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) PD mouse model is provided. The drug groups received either DA5‐CH or NLY01 (25 nmol/kg) i.p. after daily MPTP intraperitoneal injection. Both drugs showed improvements in motor activity, open field experiments, rotarod tests, and gait analysis, but DA5‐CH was more potent. Tyrosine hydroxylase expression in dopaminergic neurons was much reduced by MPTP and improved by DA5‐CH, while NLY01 showed weak effects. When analyzing levels of α‐synuclein (α‐Syn), DA5‐CH reduced levels effectively while NLY01 had no effect. When measuring the levels of the inflammation markers Toll‐like receptor 4 (TLR4), specific markers of microglia activation (Iba‐1), the marker of astrocyte activation glial fibrillary acidic protein (GFAP), nuclear factor‐κB (NF‐κB), tumor necrosis factor (TNF‐α), and transforming growth factor β1 (TGF‐β1), DA5‐CH was very effective in reducing the chronic inflammation response, while NLY01 did not show significant effects. Levels of key growth factors such as Glial cell‐derived neurotrophic factor (GDNF) and Brain‐derived neurotrophic factor (BDNF) were much reduced by MPTP, and DA5‐CH was able to normalize levels in the brain, while NLY01 showed little effect. The levels of pro‐inflammatory cytokines (IL‐6 and IL‐Iβ) were much reduced by DA5‐CH, too, while NLY01 showed no effect. In a separate experiment, we tested the ability of the two drugs to cross the blood‐brain barrier. After injecting fluorescin‐labelled peptides peripherally, the fluorescence in brain tissue was measured. It was found that the pegylated NLY01 peptide did not cross the BBB in meaningful quantities while exendin‐4 and the dual agonist DA5‐CH did. The results show that DA5‐CH shows promise as a therapeutic drug for PD.
Relationships between RPE-derived internal training load parameters and GPS-based external training load variables in elite young soccer players

ABSTRACT This study aimed to identify the GPS-based external training load variables that influence the internal training loads (RPE-derived parameters: RPE and session RPE – sRPE), and generate a model to predict GPS-based external load variables from RPE and perceived wellness values. Training load data for 21 elite young players were collected over 72 training sessions and 23 matches from the same competitive season, and 564 observations (training sessions, 462; matches, 102) were analysed. Considering all observations (training sessions and matches), significant moderate and large correlations (p < 0.01) were detected between RPE values and EL measures. The correlation between the GPS outcomes with both the RPE and sRPE values was higher during training sessions than during matches. Moreover, increased RPE and perceived wellness measures had a significant positive effect on external load variables (p < 0.001). The present work provides preliminary evidence of the utility of the RPE and sRPE method to quantify the training loads in young soccer players since most of the GPS-based EL indicators were moderate to highly correlated with the RPE-derived parameters. Additionally, EL variables may be estimated when combining perceived IL and subjective wellness indicators in young soccer players.
Feasibility of Velocity‐Selective Arterial Spin Labeling in Breast Cancer Patients for Noncontrast‐Enhanced Perfusion Imaging

Dynamic contrast‐enhanced (DCE) MRI is the most sensitive method for detection of breast cancer. However, due to high costs and retention of intravenously injected gadolinium‐based contrast agent, screening with DCE‐MRI is only recommended for patients who are at high risk for developing breast cancer. Thus, a noncontrast‐enhanced alternative to DCE is desirable.
EMISSÕES DE ÓXIDO NITROSO E METANO DO SOLO EM ÁREAS DE RECUPERAÇÃO DE PASTAGENS NA AMAZÔNIA MATOGROSSENSE

This study evaluates the chemical processes responsible for the nitrous oxide (N2O) and methane (CH4) fluxes in the managed pasture (PM) and unmanaged pasture (PNM). In addition, the impact of nitrogen fertilization on the N2O and CH4 fluxes was assessed. The experiments were conducted on three farms in Alta Floresta city in the state of Mato Grosso. Both regular and intensive samples were collected from PM, PNM, and forest areas for each of the properties. The gases were sampled using static chambers in the morning. Higher N2O fluxes were recorded in the PMs, whereas the CH4 fluxes showed no influence of nitrogen fertilization in both regular and intensive samples. Low fertilizer levels resulted in low N2O emissions.
Preinfection laboratory parameters may predict COVID‐19 severity in tumor patients

Infection with SARS‐CoV‐2 leads to COVID‐19, the course of which is highly variable and depends on numerous patient‐specific risk factors. Patients with tumor diseases are considered to be more susceptible to severe COVID‐19; however, they also represent a heterogeneous group of individuals with variable risk. Identifying specific risk factors for a severe course of COVID‐19 in patients with cancer is of great importance.
Childhood loneliness as a specific risk factor for adult psychiatric disorders

Abstract Background Loneliness is a major risk factor for both psychological disturbance and poor health outcomes in adults. This study aimed to assess whether childhood loneliness is associated with a long-term disruption in mental health that extends into adulthood. Methods This study is based on the longitudinal, community-representative Great Smoky Mountains Study of 1420 participants. Participants were assessed with the structured Child and Adolescent Psychiatric Assessment interview up to eight times in childhood (ages 9–16; 6674 observations; 1993–2000) for childhood loneliness, associated psychiatric comorbidities and childhood adversities. Participants were followed up four times in adulthood (ages 19, 21, 25, and 30; 4556 observations of 1334 participants; 1999–2015) with the structured Young Adult Psychiatric Assessment Interview for psychiatric anxiety, depression, and substance use outcomes. Results Both self and parent-reported childhood loneliness were associated with adult self-reported anxiety and depressive outcomes. The associations remained significant when childhood adversities and psychiatric comorbidities were accounted for. There was no evidence for an association of childhood loneliness with adult substance use disorders. More associations were found between childhood loneliness and adult psychiatric symptoms than with adult diagnostic status. Conclusion Childhood loneliness is associated with anxiety and depressive disorders in young adults, suggesting that loneliness – even in childhood – might have long-term costs in terms of mental health. This study underscores the importance of intervening early to prevent loneliness and its sequelae over time.
Audiologic outcomes and complications of active middle ear implantation in older adults

Abstract Background A few studies have reported the use of middle ear implants (MEIs) in older adults. Objectives To evaluate the audiologic outcomes and postoperative complications of MEIs in older adults. Methods This retrospective study reviewed audiologic data and medical records from a single referral centre. We identified 34 patients aged ≥65 years who underwent middle ear implantation using the Vibrant SoundbridgeTM device. Preoperative audiometric testing and postoperative aided audiometric testing were performed to evaluate the functional hearing gain at 1 year postoperatively. Patients were divided into 2 groups depending on whether they underwent explantation because of poor hearing benefit. Results Follow-up duration ranged from <1 to 5.3 years. The functional gain with MEIs significantly improved relative to the preoperative air conduction thresholds at 0.5, 1, 2, and 4 kHz. Eight patients underwent explantation and 7 lost their external audio processor devices. Those who removed their implants because of the poor hearing (group 1) showed significantly worse hearing thresholds at 1 kHz and speech discrimination scores than the others (group 2). Conclusions and significance MEIs for auditory rehabilitation can provide improved speech recognition and significant functional gains in older adults. Patients must be given appropriate preoperative explanations regarding the expected outcomes.
Factors associated with early lung cancer mortality: a systematic review

ABSTRACT Introduction: Despite recent therapeutic advances, lung cancer remains the primary cause of cancer deaths worldwide, and early lung mortality was poorly studied. Area covered: Early lung-cancer mortality reflects local therapy (surgery or radiotherapy) impact (localized forms), and metastatic disease evolution, comorbidities and healthcare-system accessibility. The definition of early lung cancer mortality is not consensual; thresholds range from 1 to 12 months post-diagnosis. This systematic review was undertaken to identify and analyze factors significantly associated with early lung cancer mortality. Age, male sex, non-adenocarcinoma histology, advanced stage at diagnosis and ECOG performance status are the main clinical factors of early lung cancer mortality. Active/ex-smoking also seems to favor early mortality, despite heterogeneous definitions of smoker status. For radio-chemotherapy treated locally advance disease, the early mortality rate increases according to tumor volume. Less well studied, socioeconomic characteristics (rurality and social deprivation index) yielded contradictory results, partially because definitions vary over studies. However, early lung cancer mortality is significantly higher for lower socioeconomic class patients. Expert opinion: Prospective, observational, general population studies are needed to better evaluate early lung-cancer mortality. International consensus concerning the patient-, disease- or healthcare system-linked factors of interest to be collected would facilitate comparisons among countries.
Apical debris extrusion of full-sequenced rotary systems in narrow ribbon-shaped canals.

The apically extruded debris caused by TruNatomy System (TRN), RACE EVO system (RE) and VDW Rotate (VR) systems in mandibular anterior teeth with ribbon-shaped root canals were compared. The root canals (n = 20 in each group) were irrigated with NaOCl 2.5%, and the extruded debris was collected at pre-weighted Eppendorf tubes. The amount of apically extruded debris (mg) and the treatment time (s) were recorded. Tukey pairwise comparisons were performed to compare groups with a 95% confidence level. VR had significantly less debris extrusion values and treatment time than RE and TRN (P < 0.05). Although no difference was observed between RE and TRN in terms of apically extruded debris (P > 0.05), a significant difference in favour of RE was observed in terms of treatment time (P < 0.05). All the instruments extruded debris at varying weights.
The Association Between Traditional Chinese Medicine Body Constitution Deviation and Essential Hypertension: A Case–Control Study

ABSTRACT Background The prevention and treatment of hypertension is valued globally. The World Health Organization advocates combining traditional medicines in the prevention and treatment of diseases. Traditional Chinese medicine (TCM) assumes that diseases originate from the attenuation of one's body constitution. A few studies have found that hypertension is correlated with TCM body constitution. However, body constitution is also affected by living environment. Therefore, investigating the correlation between deviations in body constitution and essential hypertension in different living environments is necessary to provide the basis for using TCM in combination with conventional Western medicine to prevent and treat hypertension. Purpose The aim of this study was to explore the association between TCM body constitution deviation and essential hypertension. Methods A case–control study was designed. Participants were selected from the outpatient clinics and neighboring communities of a regional teaching hospital in southern Taiwan. The study included 210 hypertension and 210 nonhypertension cases. Blood pressures were measured using an electronic sphygmomanometer to confirm the presence or absence of hypertension. The TCM Body Constitution Questionnaire, demographic datasheet, and hypertension-related factors questionnaire were used to collect data. Results A higher proportion of patients with body constitution deviation were found in the hypertension group than the nonhypertension group. The proportions of patients with Yin-Xu, Yang-Xu, and stasis constitution were 44.8%, 32.4%, and 30.6%, respectively, in the hypertension group and 28.6%, 25.2%, and 19.6%, respectively, in the nonhypertension group. After performing univariate analysis, the results showed significant differences between the two groups in terms of average body mass index; emotional traits of anger, worry, and fear; hyperlipidemia; hyperuricemia; Yin-Xu constitution; and stasis constitution. However, the multivariate analysis revealed having a Yin-Xu constitution to be a risk factor of essential hypertension after adjusting for age, gender, body mass index, emotional traits, drinking habit, hyperlipidemia, and hyperuricemia. Conclusions/Implications for Practice The results suggest that Yin-Xu and stasis constitutions are respectively associated with essential hypertension. The findings offer a valuable reference to governments and healthcare professionals to prevent the risk of essential hypertension. Screening and healthcare measures for TCM Yin-Xu or stasis constitution may be included in related prevention plans to minimize public exposure to the risk factors of essential hypertension.
Co-mutation modules capture the evolution and transmission patterns of SARS-CoV-2

The rapid spread and huge impact of the COVID-19 pandemic caused by the emerging SARS-CoV-2 have driven large efforts for sequencing and analyzing the viral genomes. Mutation analyses have revealed that the virus keeps mutating and shows a certain degree of genetic diversity, which could result in the alteration of its infectivity and pathogenicity. Therefore, appropriate delineation of SARS-CoV-2 genetic variants enables us to understand its evolution and transmission patterns. By focusing on the nucleotides that co-substituted, we first identified 42 co-mutation modules that consist of at least two co-substituted nucleotides during the SARS-CoV-2 evolution. Then based on these co-mutation modules, we classified the SARS-CoV-2 population into 43 groups and further identified the phylogenetic relationships among groups based on the number of inconsistent co-mutation modules, which were validated with phylogenetic trees. Intuitively, we tracked tempo-spatial patterns of the 43 groups, of which 11 groups were geographic-specific. Different epidemic periods showed specific co-circulating groups, where the dominant groups existed and had multiple sub-groups of parallel evolution. Our work enables us to capture the evolution and transmission patterns of SARS-CoV-2, which can contribute to guiding the prevention and control of the COVID-19 pandemic. An interactive website for grouping SARS-CoV-2 genomes and visualizing the spatio-temporal distribution of groups is available at https://www.jianglab. tech/cmm-grouping/.
Psychological Resilience, Metacognitions, and Fear of Recurrence Among Cancer Survivors and Family Caregivers

Background Cancer is a life crisis that can have devastating consequences not only on the affected individual but also on his/her caregivers. Objective The aim of this study was to investigate the influence of psychological resilience and metacognitions of cancer survivors and their family caregivers (FCs) on fear of recurrence (FoR). Methods This study used a cross-sectional design while adhering to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Data were collected from 112 cancer survivors and 112 FCs recruited from 5 oncology hospitals. Results The cancer survivors and caregivers reported low levels of psychological resilience, which we found to be correlated with great fear of recurrence in cancer survivors and FCs. It was also in relation with metacognitions in cancer survivors and FCs. The findings showed that psychological resilience negatively predicted the fear of recurrence, whereas the metacognitions positively predicted the fear of recurrence in cancer survivors and FCs. The total effects of psychological resilience on the FoR in cancer survivors and FCs were 0.920 (confidence interval [CI], −2.059 to 0.072) and 0.061 (CI, −0.475 to 0.474), respectively. The total effects of metacognition on the FoR in cancer survivors and FCs were 1.164 (CI, 0.217-2.371) and 0.486 (CI, 0.016-1.058), respectively. Conclusions The findings underline the direct and indirect mediating role of psychological resilience and metacognition of cancer survivors and FCs on FoR. Implication for Practice The findings are particularly important to oncology nurses, who as 24-hour care providers are important sources of psychosocial care. Their awareness of factors influencing FoR is critical for achieving positive outcomes.
Assessing population diversity in phase III trials of cancer drugs supporting Food and Drug Administration approval in solid tumors

Our study aimed to assess inequities in the clinical trial participation for the selected patient groups. We searched the Food and Drug Administration (FDA) database and extracted phase‐III clinical trial data from MEDLINE for each approved drug by the FDA between January 1, 2006, and June 30, 2020. We analyzed the inclusion/exclusion criteria, participation according to gender, ethnic group, performance score, the positivity of HBV and HCV, and HIV, having comorbidities and brain metastasis. We compared the findings with that of the general population by retrieving data from the Surveillance, Epidemiology and End Results (SEER) database. We identified 142 phase III pivotal oncology trials that enrolled 105 397 patients. The proportion of female patients in trials was lower than their relative prevalence in the general population from SEER region (36% vs 49.6%, P < .001). The rates of black patients included were lower than their relative prevalence from SEER region (2.1% vs 9.8%, P < .001). 1.3% and 0.8% of patients had HBV and HCV infections, respectively. The patients' numbers with organ dysfunction were not established due to insufficient data from clinical trials. 1.6% of all patients had controlled brain metastasis. Black patients, women and patients with brain metastasis or with HBV and HCV were underrepresented. Our study underscores the importance of expanding the inclusion/exclusion criteria of pivotal oncology trials to be more representative of patients seen in clinical practice.
The Assessment of First Metatarsal Rotation in the Normal Adult Population Using Weightbearing Computed Tomography

Background: The importance of the rotational profile of the first metatarsal is increasingly recognized in the surgical planning of hallux valgus. However, rotation in the normal population has only been measured in small series. We aimed to identify the normal range of first metatarsal rotation in a large series using weightbearing computed tomography (WBCT). Methods: WBCT scans were retrospectively analyzed for 182 normal feet (91 patients). Hallux valgus angle, intermetatarsal angle, anteroposterior/lateral talus–first metatarsal angle, calcaneal pitch, and hindfoot alignment angle were measured using digitally reconstructed radiographs. Patients with abnormal values for any of these measures and those with concomitant pathology, previous surgery, or hallux rigidus were excluded. Final assessment was performed on 126 feet. Metatarsal pronation (MPA) and α angles were measured on standardized coronal computed tomography slices. Pronation was recorded as positive. Intraobserver and interobserver reliability were assessed using intraclass correlation coefficients (ICCs). Results: Mean MPA was 5.5 ± 5.1 (range, –6 to 25) degrees, and mean α angle was 6.9 ± 5.5 (range, –5 to 22) degrees. When considering the normal range as within 2 standard deviations of the mean, the normal range identified was −5 to 16 degrees for MPA and −4 to 18 degrees for α angle. Interobserver and intraobserver reliability were excellent for both MPA (ICC = 0.80 and 0.97, respectively) and α angle (ICC = 0.83 and 0.95, respectively). There was a moderate positive correlation between MPA and α angle (Pearson coefficient 0.68, P < .001). Conclusion: Metatarsal rotation is variable in normal feet. Normal MPA can be defined as less than 16 degrees, and normal α angle can be defined as less than 18 degrees. Both MPA and α angle are reproducible methods for assessing rotation. Further work is needed to evaluate these angles in patients with deformity and to determine their significance when planning surgical correction of hallux valgus. Level of Evidence: Level III, retrospective comparative study.
Efficacy and Safety of 25% Trichloroacetic Acid Peel Versus 30% Salicylic Acid Peel in Mild-to-Moderate Acne Vulgaris: A Comparative Study

Background Both salicylic acid (SA) and trichloroacetic acid (TCA) have proven efficacy with good safety profiles in the treatment of acne vulgaris. Objectives This study compared the clinical efficacy and safety of 25% TCA and 30% SA peels in the treatment of mild and moderate acne vulgaris. Methods Patients with mild or moderate acne vulgaris were randomized into 2 groups of 25 persons each, and treated with either the TCA peel or the SA peel at 2-week intervals for 12 weeks. Evaluation of active acne was done by individual lesion counts (comedones, papules and pustules) and calculation of the Michaelsson acne score (MAS). Results Both peels led to significant decrease in individual lesion counts and MAS compared to baseline values, without significant differences between the treatment groups. Thus, the peels had equivalent efficacy against acne vulgaris. The TCA peel was better in treating non-inflammatory lesions, while the SA peel was better for inflammatory lesions, but the differences were not significant. No serious adverse effects were recorded, but more patients in the TCA peel group experienced burning and stinging sensations. Conclusion The efficacy of 25% TCA is comparable to that of 30% SA in mild-to-moderate acne vulgaris, but safety and tolerability were better with the SA peel than TCA peel.