Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

Background—The lymphatic system regulates interstitial tissue fluid balance, and lymphatic malfunction causes edema. The heart has an extensive lymphatic network displaying a dynamic range of lymph flow in physiology. Myocardial edema occurs in many cardiovascular diseases, eg, myocardial infarction (MI) and chronic heart failure, suggesting that cardiac lymphatic transport may be insufficient in pathology. Here, we investigate in rats the impact of MI and subsequent chronic heart failure on the cardiac lymphatic network. Further, we evaluate for the first time the functional effects of selective therapeutic stimulation of cardiac lymphangiogenesis post-MI. Methods and Results—We investigated cardiac lymphatic structure and function in rats with MI induced by either temporary occlusion (n=160) or permanent ligation (n=100) of the left coronary artery. Although MI induced robust, intramyocardial capillary lymphangiogenesis, adverse remodeling of epicardial precollector and collector lymphatics occurred, le.
Impact of liquid hog manure applications on antibiotic resistance genes concentration in soil and drainage water in field crops.

Agricultural practices such as manure applications could contribute to the spread of antibiotic resistance genes (ARGs) within the environment. The objective was to assess the impact of some fertilization methods (mineral or manure) and tillage practices (reduced or conventional) on the presence of ARGs and bacteria in soil and drainage water under wheat and grain corn crops. Targeted ARGs such as tet(T), sul1, and blaCTX-M-1 genes were quantified by qPCR in liquid hog manure, soil and water samples. The detection of mcr-1 and mcr-2 was conducted using conventional PCR. ARGs in control plots were detected despite the absence of manure, representing an environmental reservoir of resistant microorganisms. The manure application rate higher than 39m3/ha increased tet(T) and sul1 gene concentrations in soil for more than 180 days. Tillage practices had no impact on ARG concentrations in soil and water samples. blaCTX-M-1 genes were only detected in seven water samples in 2016, but no link was established with the treatments. The mcr-1 and mcr-2 genes were not detected in all tested samples. This study demonstrated that tet(T) and sul1 gene concentrations increased in soil after liquid hog manure application as well as in drainage water in the next weeks.
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Ubiquitylation as a Novel Pharmaceutical Target for Cystic Fibrosis

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene decrease the structural stability and function of the CFTR protein, resulting in cystic fibrosis. Recently, the effect of CFTR-targeting combination therapy has dramatically increased, and it is expected that add-on drugs that modulate the CFTR surrounding environment will further enhance their effectiveness. Various interacting proteins have been implicated in the structural stability of CFTR and, among them, molecules involved in CFTR ubiquitylation are promising therapeutic targets as regulators of CFTR degradation. This review focuses on the ubiquitylation mechanism that contributes to the stability of mutant CFTR at the endoplasmic reticulum (ER) and post-ER compartments and discusses the possibility as a pharmacological target for cystic fibrosis (CF).
Biological Characterization, Mechanistic Investigation and Structure‐Activity Relationships of Chemically Stable TLR2 Antagonists

Toll‐like receptors (TLRs) build the first barrier in the innate immune response and therefore represent promising targets for the modulation of inflammatory processes. Recently, the pyrogallol‐containing TLR2 antagonists CU‐CPT22 and MMG‐11 were reported; however, their 1,2,3‐triphenol motif renders them highly susceptible to oxidation and excludes them from use in extended experiments under aerobic conditions. Therefore, we have developed a set of novel TLR2 antagonists (1–9) based on the systematic variation of substructures, linker elements, and the hydrogen‐bonding pattern of the pyrogallol precursors by using chemically robust building blocks. The novel series of chemically stable and synthetically accessible TLR2 antagonists (1–9) was pharmacologically characterized, and the potential binding modes of the active compounds were evaluated structurally. Our results provide new insights into structure‐activity relationships and allow rationalization of structural binding characteristics. Moreover, they support the hypothesis that this class of TLR ligands bind solely to TLR2 and do not directly interact with TLR1 or TLR6 of the functional heterodimer. The most active compound from this series (6), is chemically stable, nontoxic, TLR2‐selective, and shows a similar activity with regard to the pyrogallol starting points, thus indicating the variability of the hydrogen bonding pattern.
Population Pharmacokinetic and Pharmacokinetic/Pharmacodynamic Modeling of Weight‐Based Intravenous Reslizumab Dosing

Reslizumab 3.0 mg/kg has demonstrated efficacy in clinical studies of patients with eosinophilic asthma and a history of exacerbations. A population pharmacokinetic (PK) model was developed to determine whether 3.0 mg/kg weight‐based dosing is appropriate to obtain consistent reslizumab exposures in all patients. PK data in healthy volunteers and patients ≥12 years with moderate to severe asthma, eosinophilic asthma, or nasal polyposis were analyzed from 4 phase 1, 2 phase 2, and 2 phase 3 studies of intravenous (IV) reslizumab (N = 804). Covariates evaluated included age, race, sex, baseline weight, renal and liver function, concomitant medications, and antidrug antibody status. Exposure‐response models were developed to characterize key efficacy (blood eosinophil levels, forced expiratory volume in 1 second [FEV1], Asthma Control Questionnaire [ACQ‐7] scores), and safety end points (muscle disorder adverse events [AEs]). Vial‐based dosing was evaluated as an alternative to weight‐based dosing. IV reslizumab PK was accurately described by a 2‐compartment PK model with 0‐order input and first‐order elimination. Body weight was the only covariate that significantly influenced PK parameters. However, with weight‐based dosing, comparable steady‐state exposures were observed across high and low body weights. Greater eosinophil lowering and longer response duration were observed with increasing dose; exposure‐related effects on FEV1 and ACQ‐7 were also seen, demonstrating the clinical importance of a dosing regimen to optimize reslizumab exposure. The probability of a muscle disorder AE appeared to increase with increasing exposure. Steady‐state exposure measures were similar for both dosing regimens, showing vial‐based dosing as an alternative method of achieving the benefits of weight‐based dosing.
Sex/gender differences in brain function and structure in alcohol use: A narrative review of neuroimaging findings over the last 10 years

Over the last 10 years, rates of alcohol use disorder (AUD) have increased in women by 84% relative to a 35% increase in men. Rates of alcohol use and high‐risk drinking have also increased in women by 16% and 58% relative to a 7% and 16% increase in men, respectively, over the last decade. This robust increase in drinking among women highlights the critical need to identify the underlying neural mechanisms that may contribute to problematic alcohol consumption across sex/gender (SG), especially given that many neuroimaging studies are underpowered to detect main or interactive effects of SG on imaging outcomes. This narrative review aims to explore the recent neuroimaging literature on SG differences in brain function and structure as it pertains to alcohol across positron emission tomography, magnetic resonance imaging, and functional magnetic resonance imaging modalities in humans. Additional work using magnetic resonance spectroscopy, diffusion tensor imaging, and event‐related potentials to examine SG differences in AUD will be covered. Overall, current research on the neuroimaging of AUD, alcohol consumption, or risk of AUD is limited, and findings are mixed regarding the effect of SG on neurochemical, structural, and functional mechanisms associated with AUD. We address SG disparities in the neuroimaging of AUD and propose a call to action to include women in brain imaging research. Future studies are crucial to our understanding of the neurobiological underpinnings of AUD across neural systems and the vulnerability for AUD among women and men.
Frequency and risk factors of antibody-induced secondary failure of botulinum neurotoxin therapy

Objective To investigate the risk factors of neutralizing antibody (NAB)–induced complete secondary treatment failure (cSTF) during long-term botulinum neurotoxin (BoNT) treatment in various neurologic indications. Methods This monocenter retrospective cohort study analyzed the data of 471 patients started on BoNT therapy between 1995 and 2015. Blood samples of 173 patients were investigated for NABs using the mouse hemidiaphragm test (93 with suspected therapy failure, 80 prospective study participants). The frequency of NAB-cSTF was assessed for various indications: hemifacial spasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. A priori defined potential risk factors for NAB-cSTF were evaluated, and a stepwise binary logistic regression analysis was performed to identify independent risk factors. Results Treatment duration was 9.8 ± 6.2 years (range, 0.5–30 years; adherence, 70.6%) and number of treatment cycles 31.2 ± 22.5 (3–112). Twenty-eight of 471 patients (5.9%) had NAB-cSTF at earliest after 3 and at latest after 103 treatment cycles. None of the 49 patients treated exclusively with incobotulinumtoxinA over 8.4 ± 4.2 (1–14) years developed NAB-cSTF. Independent risk factors for NAB-cSTF were high BoNT dose per treatment, switching between onabotulinumtoxinA and other BoNT formulations (except for switching to incobotulinumtoxinA), and treatment of neck muscles. Conclusions We present a follow-up study with the longest duration to date on the incidence of NAB-cSTF in patients treated with various BoNT formulations, including incobotulinumtoxinA. Whereas the overall risk of NAB-cSTF is low across indications and BoNT formulations, our findings underpin the recommendations to use the lowest possible dose particularly in cervical dystonia, and to avoid unnecessary switching between different formulations.
Development of a transcranial direct current stimulation device based on current limiter for simultaneous measurement of electroencephalography: A feasibility study

BACKGROUND: Electroencephalography (EEG) measured during transcranial direct current stimulation (tDCS) can help understand the accurate impact of tDCS on the brain, but this has been hindered due to significant inflow of tDCS-induced electrical artifacts. OBJECTIVE: In this study, we introduce a novel tDCS device developed based on current limiter, which can prevent the generation of significant electrical artifacts. METHODS: To verify the feasibility of our developed tDCS device, we performed simultaneous measurement of EEG during tDCS application with five different current intensities (0, 500, 1,000, 1,500, and 2,000 μA). Changes in EEG power spectral density (PSD) and correlation between the PSD of non-stimulation and tDCS condition were investigated to see whether our tDCS device can be used for simultaneous EEG recording without significant inflow of tDCS-induced electrical artifacts. RESUTLS: The mean EEG-PSD differences between non-stimulation and tDCS condition were not significant for all stimulation current intensities. Furthermore, EEG-PSDs estimated during non-stimulation and tDCS application showed statistically high correlation for all comparison cases. CONCLUSION: Based on the results, we could demonstrate the feasibility of our tDCS device based on current limiter for simultaneous EEG measurement, which could potentially provide a way to investigate the impact of tDCS on the brain more accurately.
Odor Identification Impairment and Change with Cholinesterase Inhibitor Treatment in Mild Cognitive Impairment.

BACKGROUND Anticholinergic challenge can induce odor identification impairment that indicates Alzheimer's disease (AD) pathology, and short-term change in odor identification impairment with cholinesterase inhibitor (CheI) treatment may predict longer term cognitive outcomes. OBJECTIVE In patients with mild cognitive impairment (MCI) treated prospectively with donepezil, a CheI, for 52 weeks, to determine if 1) acute decline in odor identification ability with anticholinergic challenge can predict cognitive improvement, and 2) change in odor identification over 8 weeks can predict cognitive improvement. METHODS MCI was diagnosed clinically without AD biomarkers. At baseline, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge. Donepezil was started at 5 mg daily, increased to 10 mg daily if tolerated, and this dose was maintained for 52 weeks. Main outcomes were ADAS-Cog total score and Selective Reminding Test (SRT) total immediate recall score measured at baseline, 26 and 52 weeks. RESULTS In 100 study participants, mean age 70.14 (SD 9.35) years, atropine-induced decrease in UPSIT score at baseline was not associated with change in ADAS-Cog or SRT scores over 52 weeks. Change in UPSIT score from 0 to 8 weeks did not show a significant association with change in the ADAS-Cog or SRT measures over 52 weeks. CONCLUSION These negative findings in a relatively large sample of patients with MCI did not replicate results in much smaller samples. Change in odor identification with anticholinergic challenge, and over 8 weeks, may not be useful predictors of cognitive improvement with CheI in patients with MCI.
Effects of group cognitive-behavioral therapy on psychological distress of awaiting-trial prison inmates

Abstract Background/Objectives: The level of psychological distress among awaiting-trial inmates is rapidly increasing in Nigeria. Studies have recommended increasing attention and additional psychological intervention that could improve the psychological wellbeing of prisoners. This study evaluates the effect of cognitive behavioral therapy on psychological distress among awaiting-trial prison inmates in Nigeria. Methods: A total of 34 awaiting-trial prison inmates in Enugu state Nigeria were used as the study participants. Two measures (perceived emotional distress inventory and general health Questionnaire) were used for data collection. Repeated measures with analysis of variance (ANOVA) were used to examine the effects of the intervention. Effect sizes were also reported with partial Eta Squared (). Results: The result showed that there was no significant difference in psychological distress between the treatment and no-intervention groups. The results showed that CBT had a significant effect on psychological distress of awaiting-trial prison inmates when compared to their counterparts in the no-intervention group at Time 2. Additionally, the efficacy of CBT on the psychological distress of awaiting-trial prison inmates was significantly sustained at the follow-up measurements (Time 3). Conclusion: This study suggests that cognitive behavioral therapy is an effective intervention for decreasing psychological distress among awaiting-trial prison inmates. Additionally, the impactful benefit of the intervention can persist in overtime. Therefore, cognitive behavioral therapists can further explore the efficacy of CBT using various cultures.
Kv1.1 Channelopathies: Pathophysiological Mechanisms and Therapeutic Approaches

Kv1.1 belongs to the Shaker subfamily of voltage-gated potassium channels and acts as a critical regulator of neuronal excitability in the central and peripheral nervous systems. KCNA1 is the only gene that has been associated with episodic ataxia type 1 (EA1), an autosomal dominant disorder characterized by ataxia and myokymia and for which different and variable phenotypes have now been reported. The iterative characterization of channel defects at the molecular, network, and organismal levels contributed to elucidating the functional consequences of KCNA1 mutations and to demonstrate that ataxic attacks and neuromyotonia result from cerebellum and motor nerve alterations. Dysfunctions of the Kv1.1 channel have been also associated with epilepsy and kcna1 knock-out mouse is considered a model of sudden unexpected death in epilepsy. The tissue-specific association of Kv1.1 with other Kv1 members, auxiliary and interacting subunits amplifies Kv1.1 physiological roles and expands the pathogenesis of Kv1.1-associated diseases. In line with the current knowledge, Kv1.1 has been proposed as a novel and promising target for the treatment of brain disorders characterized by hyperexcitability, in the attempt to overcome limited response and side effects of available therapies. This review recounts past and current studies clarifying the roles of Kv1.1 in and beyond the nervous system and its contribution to EA1 and seizure susceptibility as well as its wide pharmacological potential.
Dendritic Cells, the T-cell-inflamed Tumor Microenvironment, and Immunotherapy Treatment Response

The development of the most successful cancer immunotherapies in solid tumors, immune-checkpoint blockade, has focused on factors regulating T-cell activation. Until recently, the field has maintained a predominately T-cell centric view of immunotherapy, leaving aside the impact of innate immunity and especially myeloid cells. Dendritic cells (DC) are dominant partners of T cells, necessary for initiation of adaptive immune responses. Emerging evidence supports a broader role for DCs in tumors including the maintenance and support of effector functions during T-cell responses. This relationship is evidenced by the association of activated DCs with immune-checkpoint blockade responses and transcriptional analysis of responding tumors demonstrating the presence of type I IFN transcripts and DC relevant chemokines. T-cell-inflamed tumors preferentially respond to immunotherapies compared with non–T-cell-inflamed tumors and this model suggests a potentially modifiable spectrum of tumor microenvironmental immunity. Although host and commensal factors may limit the T-cell-inflamed phenotype, tumor cell intrinsic factors are gaining prominence as therapeutic targets. For example, tumor WNT/β-catenin signaling inhibits production of chemokine gradients and blocking DC recruitment to tumors. Conversely, mechanisms of innate immune nucleic acid sensing, normally operative during pathogen response, may enhance DC accumulation and make tumors more susceptible to cancer immunotherapy. Elucidating mechanisms whereby DCs infiltrate and become activated within tumors may provide new opportunities for therapeutic intervention. Conceptually, this would facilitate conversion of non–T-cell-inflamed to T-cell-inflamed states or overcome secondary resistance mechanisms in T-cell-inflamed tumors, expanding the proportion of patients who benefit from cancer immunotherapy.
Exercise-induced hypertension can increase the prevalence of coronary artery plaque among middle-aged male marathon runners

Abstract Marathon runners demonstrate a high incidence of coronary artery plaque; however, studies on runners with exercise-induced hypertension (EIH) are sparse. We aimed to investigate the prevalence of coronary artery plaque among marathon runners with EIH. Veteran male marathon runners (≥40 and <60 years) underwent an exercise stress test. They were divided into 2 groups: normal blood pressure group (NBPG, n = 22), with resting systolic blood pressure (SBP)/diastolic blood pressure <140/90 mm Hg and maximal exercise SBP <210 mm Hg, and EIH group (EIHG, n = 28), with resting blood pressure <140/90 mm Hg and maximal exercise SBP ≥210 mm Hg. Coronary artery plaque and stenosis were compared using multi-detector computed tomography. The proportion of subjects with a coronary artery calcium (CAC) score ≥10 or ≥100 units, 1 or ≥2 plaques, or plaques in ≥2 blood vessels was higher in the EIHG than in the normal blood pressure group (NBPG) (P<.05). The absolute CAC score was higher in the EIHG (42.6 ± 67.8) than in the NBPG (2.8 ± 6.0; P < .05). The CAC score distribution was higher in the EIHG (5–300 units) than in the NBPG (P < .05). The prevalence of coronary plaques and maximal luminal artery stenosis was higher in the EIHG than in the NBPG (P < .05). The EIHG showed 12 cases of stenosis, whereas the NBPG showed only 1 case (P < .05). In marathon runners, EIH was associated with increased prevalence of coronary artery plaques and could be a new risk factor for coronary artery plaque formation. Therefore, preventive measures and EIH monitoring using an exercise stress test, alongside multi-detector computed tomography, are recommended.
Work-to-Family Conflict, Job Burnout, and Project Success among Construction Professionals: The Moderating Role of Affective Commitment

This study explored the effects of work-to-family conflict on job burnout and project success in the construction industry. First, a theoretical model with affective commitment as a moderating variable was developed according to the conservation of resources theory. A structured questionnaire survey was then performed with Chinese construction professionals, with 309 valid responses received. In the valid data, the proportion of male construction professionals is 73% and that of female construction professionals is 27%. The analysis of the valid data used structural equation modeling. The results indicate that: (i) work-to-family conflict has a positive and significant effect on job burnout, and a negative and significant effect on project success; (ii) job burnout negatively affects project success; (iii) affective commitment negatively moderates the relationship between work-to-family conflict and job burnout. This study extends the existing body of knowledge on work-to-family conflict and helps us to better understand the functional and moderating roles of affective commitment in the context of construction projects. Furthermore, this study provides theoretical guidance and a decision-making reference to help construction enterprises manage the work-to-family conflict and job burnout of construction professionals and advance their levels of affective commitment.
Echocardiographic Assessment of Right Ventricular Function by Two-Dimensional Strain In Patients with Left-Sided Valvular Heart Disease: Comparison with Three-Dimensional Echocardiography

Abstract Background: Right ventricular (RV) dysfunction is a well-known predictor of mortality in patients with valvular heart disease (VHD). The assessment of RV function is often difficult due to complex geometry and hemodynamic factors. We aim to analyze RV function in patients with severe mitral and/or aortic valve disease using two-dimensional strain (2DS) imaging and conventional echocardiographic parameters, comparing it with right ventricular ejection fraction (RVEF) measured by three-dimensional echocardiography (3DE). Methods: Fifty-three patients with severe mitral and/or aortic VHD [. ]