Miracle-dz/UniFAR-FTUs huggingface dataset:
Atopic dermatitis in West Highland white terriers - part I: natural history of atopic dermatitis in the first three years of life.

BACKGROUND Canine atopic dermatitis (cAD) is a common allergic skin disease that is known to affect individuals early in life; the natural history of its initial development has not been documented. Some breeds such as West Highland white terriers (WHWTs) are highly predisposed to cAD. OBJECTIVES To follow 100 WHWT puppies during their first three years and to record the onset of clinical signs of cAD. ANIMALS One hundred and eight puppies from 29 litters were included and 90 were followed for three years. METHODS AND MATERIALS Puppies were examined initially while with their breeders. After adoption, the owners were contacted twice each year and dogs were examined by veterinarians if signs compatible with cAD were detected; diagnosis of cAD was by two different definitions. The onset, location of the clinical signs and severity of cAD, as well as co-morbidities were recorded. RESULTS The prevalence of cAD in the cohort was 52%. Most affected dogs (60%) developed signs of cAD during their first year of life and males were over-represented. The location of clinical signs mirrored those of previous descriptions. The severity of cAD was mild in 36% and severe in 13% of affected WHWTs. Dogs with cAD often exhibited other atopic diseases, but only gastro-intestinal signs were significantly different between WHWTs with and without cAD. Adverse reaction to foods was diagnosed in 24% of dogs. CONCLUSION AND CLINICAL IMPORTANCE This longitudinal study of puppies from a predisposed breed sheds new light on the early development of cAD in WHWTs.
Combined with ticagrelor, 50 mg aspirin daily can reduce bleeding events without increasing ischemic risk compared with 75–100 mg aspirin daily in coronary artery disease patients: insights from the TIFU (Ticagrelor in Fuwai Hospital) study

Abstract Patients treated with ticagrelor and aspirin usually suffer from bleeding events, especially mild bleeding which is one of the main factors reducing patients’ adherence to ticagrelor. The objective of this study is to investigate the efficacy and safety of ticagrelor combined with a lower dose of aspirin (50 mg) than that recommended by guidelines (75–100 mg). In this study, we prospectively enrolled 1220 patients who take ticagrelor in the hospital. After excluding the patients who did not take ticagrelor after discharge or lost to follow-up, the remaining 1066 patients were divided into two aspirin dose groups: 75–100 mg (n = 744) and 50 mg (n = 322). The rates of major adverse cardiovascular events (MACEs), bleeding events and ticagrelor adherence were compared between the two groups. MACEs risk was not significantly different between the two groups (OR = 0.563, 95% CI: 0.244–1.300, P = .179). However, 50 mg aspirin was associated with a lower risk of any Bleeding Academic Research Consortium (BARC) bleeding events (OR = 0.605, 95% CI: 0.399–0.713, P = .001), also lower BARC bleeding events (OR = 0.639, 95% CI: 0.468–0.872, P = .005). Moreover, lower-dose aspirin was associated with a lower rate of ticagrelor withdrawal (OR = 0.459, 95% CI: 0.279–0.754, P = .002), mainly because of the decrease in ticagrelor withdrawal due to bleeding (OR = 0.378, 95% CI: 0.156–0.916, P = .031). After propensity score matching (PSM), a total of 317 patients in each group were matched. The MACEs composite was not significantly different between the two matched groups and 50 mg aspirin was associated with a lower risk of bleeding events and low ticagrelor withdrawal before and after multivariate adjustment. In conclusion, among patients who took ticagrelor (90 mg twice daily), 50 mg aspirin daily is associated with a lower rate of bleeding events and ticagrelor withdrawal but does not increase the MACE risk compared with 75–100 mg aspirin daily.
Loss-of-Function Mutations in Human Regulator of G Protein Signaling RGS2 Differentially Regulate Pharmacological Reactivity of Resistance Vasculature

Regulator of G protein signaling 2 (RGS2) plays a role in reducing vascular contraction and promoting relaxation due to its GTPase accelerating protein activity toward Gαq. Previously, we identified four human loss-of-function (LOF) mutations in RGS2 (Q2L, D40Y, R44H, and R188H). This study aimed to investigate whether those RGS2 LOF mutations disrupt the ability of RGS2 to regulate vascular reactivity. Isolated mesenteric arteries (MAs) from RGS2−/− mice showed an elevated contractile response to 5 nM angiotensin II and a loss of acetylcholine (ACh)–mediated vasodilation. Reintroduction of a wild-type (WT) RGS2-GFP plasmid into RGS2−/− MAs suppressed the vasoconstrictor response to angiotensin II. RGS2 LOF mutants failed to suppress the angiotensin II constriction response compared with RGS2 WT. In contrast, ACh-mediated vasoconstriction was restored by expression of RGS2 WT, D40Y, and R44H but not by RGS2 Q2L or R188H. Phosphorylation of RGS2 D40Y and R44H by protein kinase G (PKG) may explain their maintained function to support relaxation in MAs. This is supported by phosphomimetic mutants and suppression of vasorelaxation mediated by RGS2 D40Y by a PKG inhibitor. These results demonstrate that RGS2 attenuates vasoconstriction in MAs and that RGS2 LOF mutations cannot carry out this effect. Among them, the Q2L and R188H mutants supported less relaxation to ACh, whereas relaxation mediated by the D40Y and R44H mutant proteins was equal to that with WT protein. Phosphorylation of RGS2 by PKG appears to contribute to this vasorelaxation. These results provide insights for precision medicine targeting the rare individuals carrying these RGS2 mutations. SIGNIFICANCE STATEMENT Regulator of G protein signaling 2 (RGS2) has been implicated in the control of blood pressure; rare mutations in the RGS2 gene have been identified in large-scale human gene sequencing studies. Four human mutations in RGS2 that cause loss of function (LOF) in cell-based assays were examined in isolated mouse arteries for effects on both vasoconstriction and vasodilation. All mutants showed the expected LOF effects in suppressing vasoconstriction. Surprisingly, the D40Y and R44H mutant RGS2 showed normal control of vasodilation. We propose that this is due to rescue of the mislocalization phenotype of these two mutants by nitric oxide–mediated/protein kinase G–dependent phosphorylation. These mechanisms may guide drug discovery or drug repurposing efforts for hypertension by enhancing RGS2 function.
Transgenic minipig model of Huntington's disease exhibiting gradually progressing neurodegeneration

ABSTRACT Recently developed therapeutic approaches for the treatment of Huntington's disease (HD) require preclinical testing in large animal models. The minipig is a suitable experimental animal because of its large gyrencephalic brain, body weight of 70-100 kg, long lifespan, and anatomical, physiological and metabolic resemblance to humans. The Libechov transgenic minipig model for HD (TgHD) has proven useful for proof of concept of developing new therapies. However, to evaluate the efficacy of different therapies on disease progression, a broader phenotypic characterization of the TgHD minipig is needed. In this study, we analyzed the brain tissues of TgHD minipigs at the age of 48 and 60-70 months, and compared them to wild-type animals. We were able to demonstrate not only an accumulation of different forms of mutant huntingtin (mHTT) in TgHD brain, but also pathological changes associated with cellular damage caused by mHTT. At 48 months, we detected pathological changes that included the demyelination of brain white matter, loss of function of striatal neurons in the putamen and activation of microglia. At 60-70 months, we found a clear marker of neurodegeneration: significant cell loss detected in the caudate nucleus, putamen and cortex. This was accompanied by clusters of structures accumulating in the neurites of some neurons, a sign of their degeneration that is also seen in Alzheimer's disease, and a significant activation of astrocytes. In summary, our data demonstrate age-dependent neuropathology with later onset of neurodegeneration in TgHD minipigs. Summary: Longitudinal phenotyping of the minipig model for Huntington's disease demonstrates a slow and age-dependent neurodegeneration.
Seroprevalence of herpes simplex virus types 1 and 2 in Nigeria: a systematic review and meta-analyses

ABSTRACT A source of comprehensive information on the prevalence of herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) can help researchers and policymakers address HSV related burden in the society. At the moment, this is not readily available. This study aims to fill this gap by attempting to estimate the seroprevalence of HSV-1 and HSV-2 infections in Nigeria on the basis of published data. A systematic review and meta-analysis including cross-sectional studies on HSV-1 and HSV-2 in Nigeria was conducted. Electronic databases including PubMed/MEDLINE, CENTRAL, African Journals Online (AJOL), ScienceDirect, WHO-Afro Library, WHO-IRIS and African Index Medicus were searched for English Language publications on HSV-1 and HSV-2. Seven relevant publications were identified. Seroprevalence measures of 3 and 23 for HSV-1 and HSV-2, respectively, were extracted. The pooled mean seroprevalences for HSV-1 and HSV-2 were 74.0% (37.4–99.4%) and 63.4% (56.1–70.4%) respectively. The mean seroprevalence of HSV-1 was higher among females, 82.4% (n = 509, CI, 36.6–100.0%), than males, 54.5% (n = 198, CI, 47.6–61.4%). The mean seroprevalence of HSV-2 were 51.8% (n = 1414, CI: 39.4–64.0%) and 86.5% (n = 162, CI: 80.8–91.3%) among healthy and clinical populations, respectively. The study was limited by the paucity of quality studies, variations in diagnostic methods and high heterogeneity in seroprevalence estimates. In conclusion, the seroprevalence of HSV-1 and HSV-2 remain high in Nigeria. Large and representative national epidemiological surveys covering all regions and specific groups are recommended.
Spatial analysis of the effects of PM2.5 on hypertension among the middle-aged and elderly people in China

ABSTRACT Hypertension is currently one of the most common chronic diseases with high global prevalence associated with a huge social and economic burden. In recent years, air pollution has become a focus of research, especially the effects of PM2.5 on hypertension. However, few studies have considered the spatial properties of the sample; thus, the results might be unreliable. Based on the China Health and Retirement Longitudinal Study (CHARLS) and the Environmental Status Bulletin for each province in China, we used the extended shared component model (SCM) to fit the spatial variation of hypertension risk and to reveal the impact of PM2.5 on hypertension in males and females. Our results revealed that the crude prevalence of hypertension for the whole population in China was 32.74% in 2015, with the prevalence in men experiencing slightly higher than that in women (32.92% vs. 32.58%). We found that the distribution of hypertension prevalence exhibited obvious spatial aggregation for the whole population in China (Moran’s I = 0.39, P = 0.001), with similar results in both men (Moran’s I = 0.18, P = 0.027) and women (Moran’s I = 0.52, P = 0.001). Furthermore, the smoothed results obtained using the SCM indicated that some eastern and central provinces had relatively higher hypertension risk, while the risk in southeastern provinces was much lower. The risk was also relatively lower in most western provinces, except for some northwestern regions. Notably, our results showed that PM2.5 was a risk factor for hypertension, and the impact of PM2.5 on women was slightly greater than that on men, with odds ratios (OR) of 1.063 (1.041, 1.086) and 1.048 (1.025, 1.071), respectively. Our findings suggest the existence of distinct spatial differences in the prevalence of hypertension and small sex-related differences in the risk of hypertension in China.
Trajectories of depression symptom change during and following treatment in adolescents with unipolar major depression

Objective To classify a cohort of depressed adolescents recruited to the UK IMPACT trial, according to trajectories of symptom change. We examined for predictors and compared the data‐driven categories of patients with a priori operational definitions of treatment response. Method Secondary data analysis using growth mixture modelling (GMM). Missing data were imputed. Trajectories of self‐reported depressive symptoms were plotted using scores taken at six nominal time points over 86 weeks from randomisation in all 465 patients. Results A piecewise GMM categorised patients into two classes with initially similar and subsequently distinct trajectories. Both groups had a significant decline in depressive symptoms over the first 18 weeks. Eighty‐four per cent (84.1%, n = 391) of patients were classed as ‘continued‐improvers’ with symptoms reducing over the duration of the study. A further class of 15.9% (n = 74) of patients were termed ‘halted‐improvers’ with higher baseline depression scores, faster early recovery but no further improvement after 18 weeks. Presence of baseline comorbidity somewhat increased membership to the halted‐improvers class (OR = 1.40, CI: 1.00–1.96). By end of study, compared with classes, a clinical remission cut‐off score (≤27) and a symptom reduction score (≥50%) indexing treatment response misclassified 15% and 31% of cases, respectively. Conclusions A fast reduction in depressive symptoms in the first few weeks of treatment may not indicate a good prognosis. Halted improvement is only seen after 18 weeks of treatment. Longitudinal modelling may improve the precision of revealing differential responses to treatment. Improvement in depressive symptoms may be somewhat better in the year after treatment than previously considered.
Physician Renewal of Chronically Prescribed Controlled Substances Based on Urine Drug Test Results

Objective: The effect of specific urine drug testing (UDT) results on physician prescribing habits has not been well described. The primary objective was to report renewal rates of chronically prescribed controlled substances based on types of inconsistent UDT results. Methods: We conducted a retrospective chart review over a 5-month period comparing prescription renewals rates for patients with consistent versus inconsistent UDTs. Inconsistent UDTs were defined by prescribed drug not detected or the presence of heroin, cocaine, nonprescribed opioids, nonprescribed benzodiazepines, or marijuana. Results: Of the 474 UDTs reviewed, 214 (45.1%) were inconsistent. The most common findings among inconsistent UDTs, including overlapping results, were prescribed drug not detected (26.8%) and the presence of marijuana (20.7%), nonprescribed opioids (9.9%), and nonprescribed benzodiazepines (6.1%). In contrast, cocaine (5.5%) and heroin (0.4%) were less likely to be found on UDTs for this population. The relative risk (RR) of prescription renewal was 0.64 (95% CI 0.57-0.71) for inconsistent UDTs versus consistent UDTs. Within the inconsistent UDTs, the renewal rates when marijuana (79.6%) or nonprescribed opioids or benzodiazepines (63.6%) were present were much higher than when heroin or cocaine were present (0.0%; P < .001). Patients whose prescribed controlled substance was not detected had a 55.8% renewal rate. Conclusions: Prescription renewal rates were high when patient UDTs contained nonprescribed marijuana, opioids, and benzodiazepines, or when the prescribed drug was not detected. Prescription renewal rates were low when illicit drugs, such as heroin and cocaine, were detected.
Efficacy and safety of cariprazine in the treatment of bipolar disorder

ABSTRACT Introduction: Cariprazine, a D3-preferring, dopamine D2/D3 partial agonist, has efficacy in treating both acute phases of bipolar I disorder (BD-I). It has been approved by the FDA for treatment of acute manic, mixed and depressive episodes associated with BD-I. Areas covered: In this review, the authors discuss the unique pharmacological properties and clinical efficacy profile of cariprazine, and their relevance in the context of routine clinical decision-making for BD-I. For the purpose of this review, the authors searched for clinical trials in BD published in the PubMed, Web of Science, Embase and PsychInfo databases as well as for studies registered in the ClinicalTrials.gov database. Expert opinion: Based on evidence from RCTs in manic and mixed episodes, cariprazine in a dose-range of 3–12 mg is effective for treating acute mania and mixed states associated with BD-I. Importantly, evidence from placebo-controlled trials in bipolar depression suggests that cariprazine is also effective as a monotherapy in treating acute bipolar depression in doses of 1.5–3 mg/day. It is overall well tolerated; however, clinicians need to monitor patients for akathisia.
Permanent education for good practices in the prevention of pressure injury: almost-experiment.

OBJECTIVE To verify the effectiveness of the educational intervention through the evaluation of nurses' knowledge about prevention of pressure injury. METHOD A quasi-experimental study with a single group, carried out with 95 nurses from a teaching hospital in the interior of Minas Gerais, in August and September 2017. As a teaching strategy, the active methodology and hybrid teaching were used, based on the reference of the Method of the Arch of Charles Maguerez. Data were collected from a validated instrument, called the Pieper Knowledge Test, and analyzed by descriptive statistics and Student's t-test with significance level of p <0.001. RESULTS The mean number of correct answers obtained by the nurses was 78.8% in the pre-test and 88.8% in the post-test, and the difference was statistically significant (p <0.001). CONCLUSION The educational intervention developed was effective, since it contributed to the improvement of nurses' knowledge.
Bacteriophage applications for fresh produce food safety

ABSTRACT Foodborne illnesses, mainly bacteria, are a major cause of morbidity and mortality worldwide. Pathogenic bacteria are involved in almost every step within the fresh produce chain compromising the companies’ food safety programs and generating an ascending number of foodborne outbreaks in various regions of the world. Recently, bacteriophages return to the status of biocontrol agents. These bacteria-killing viruses are able to reduce or eliminate pathogenic bacterial load from raw and ready to eat foods. Phages are efficient, strain specific, easy to isolate and manipulate, and for that reasons, they have been used in pre and post harvest processes alone or mixed with antimicrobial agents for biocontrolling pathogenic bacteria. In this review, we focused on the feasibility of using lytic bacteriophage on fresh fruits and vegetables industry, considering challenges and perspectives mainly at industrial production level (packinghouses, supermarkets), where high volume of phage preparations and consequently high costs may be required.
Trajectories of violent victimization predicting PTSD and comorbidities among urban ethnic/racial minorities.

OBJECTIVE To examine the effect of long-term violent victimization from late adolescence to the mid-30s on posttraumatic stress disorder (PTSD) and comorbid psychiatric disorders in adulthood among urban African Americans and Puerto Ricans. METHOD Data were collected from a large urban community sample (N = 674) at 4 time points associated with mean ages of 19, 24, 29, and 36 years. Trajectories of violent victimization were extracted using growth mixture modeling and used to predict psychiatric disorders and comorbidities in adulthood. RESULTS The sample was 52.8% African American and 47.2% Puerto Rican, with 60% females. Three trajectory groups of violent victimization were identified: high, intermediate, and low. Over half of the sample reported relatively high- and intermediate-level violent victimization experiences from adolescence to adulthood. Group comparisons showed that participants belonging to the relatively high-victimization group had greater odds of having PTSD, major depressive episode (MDE), and substance use disorder (SUD) separately, as well as comorbid PTSD-SUD and PTSD-MDE, compared with those classified as having relatively low levels of victimization. Having intermediate-level victimization experiences, compared with low-level victimization experiences, over time was associated with higher odds of PTSD and MDE separately and comorbid PTSD-MDE. CONCLUSIONS Long-term exposure to relatively high levels of violent victimization during emerging and young adulthood is associated with PTSD and comorbid psychiatric disorders in the 30s. Social, structural, and interpersonal factors underlying the differential patterns of violent victimization in urban African American and LatinX youth need to be identified to adequately inform prevention efforts. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Continuous Description of Human 3D Motion Intent Through Switching Mechanism

Post-stroke motor recovery highly relies on voluntarily participating in active rehabilitation as early as possible for promoting the reorganization of the patient’s brain. In this paper, a new method is proposed which manipulates cable-based rehabilitation robots to assist multi-joint body motions. This uses an electromyography (EMG) decoder for continuous estimation of voluntary motion intention to establish a cooperative human-machine interface for promoting the participation in rehabilitation exercises. In particular, for multi-joint complex tasks in three-dimensional space, a switching mechanism has been developed which can carve up tasks into separate simple motions. For each simple motion, a linear six-inputs and three-outputs time-invariant model is established respectively. The inputs are the processed muscle activations of six arm muscles, and the outputs are voluntary forces of participants when executing a multi-directional tracking task with visual feedback. The experiments for examining the decoder model and EMG-based controller include model training, testing and controller application phases with seven healthy participants. Experimental results demonstrate that the decoder model with the switching mechanism could effectively recognize arm movement intention and provide appropriate assistance to the participants. This study finds that the switching mechanism can improve both the model estimation accuracy and the completeness for executing complex tasks.
Classroom versus individual working memory assessment: predicting academic achievement and the role of attention and response inhibition

ABSTRACT Working memory (WM) is an important predictor for academic learning and achievement. Typically, children’s WM is assessed in controlled testing situations, which might not reflect functioning in typical classroom learning situations with natural distractions. In this study, we compared WM performance in controlled and classroom situations and their predictive value for academic achievement. Also, we examined whether performance differences between situations were moderated by attention or response inhibition. In a within-subjects design, primary school children completed visuospatial and verbal WM tasks in two settings (classroom versus controlled individual setting). First, WM functioning was lower in the classroom setting. Second, attention moderated individual differences in this discrepancy between settings, but response inhibition did not. Third, classroom obtained verbal WM scores were the strongest predictors of academic achievement. Our results indicate that classroom assessment of verbal WM provides a more ecologically valid measurement of WM abilities in a real-life learning situation.