Miracle-dz/UniFAR-FTUs huggingface dataset:
Information booklet for promoting self-efficacy in childhood asthma: construction and validity

ABSTRACT Objective: To construct and validate the content and appearance of an information booklet to promote self-efficacy of parents and/or caregivers in childhood asthma management and control. Method: This is a methodological study, developed from educational material elaboration, validity and assessment by 25 content judges and three technical judges. Language clarity, practical pertinence and theoretical relevance were used, calculating the Content Validity Coefficient (CVC) for validity, and the Suitability Assessment of Materials (SAM) instrument was applied for assessment. Judges were also able to make suggestions for modifications on each page of the booklet. Pages that reached a CVC ≥ 0.80 for content judges and CVC ≥ 0.70 for technical judges were considered validated. Results: The total CVC of the booklet was 0.96 for content judges and 0.83 for technical judges. The educational material was considered superior according to the SAM, with a total score of 92.67% for content judges and 73.81% for technical judges. Changes were made to the booklet after the validity process, according to judges’ suggestions, resulting in a second version. Conclusion: The information booklet is valid and has a high degree of recommendation for use with parents and/or caregivers in childhood asthma control and management.
An updated review on the genetics of arteriovenous malformations

Arteriovenous malformations (AVM) are congenital malformations of the cerebral vasculature resulting in pathological shunting of blood through dilated arteries and veins. The most common clinical manifestations of AVM are intracerebral hemorrhage, due to rupture of these lesions as they continue to expand, which can have devastating neurological consequences and residual deficits. The genetic underpinnings of AVM have been explored for their role in the angiogenesis of these lesions in both its sporadic and inherited forms. In recent times, our understanding of the genetic variation involved in the pathogenesis AVM has advanced in both the preclinical and clinical realms. The current review highlights in detail these advancements, namely, the genetic underpinnings of diagnostic testing and profiling of AVM, and the preclinical epigenetic and genetic data on AVM pathogenesis and growth. In addition, we review the current candidate genes implicated in AVM pathogenesis in the literature. Finally, we provide a discussion on the genetic conditions associated with AVM and the advancements in treatment paradigms influenced by the genetic profiles of these lesions.
Real world use of lanreotide in neuroendocrine tumors

Background Treatment for metastatic neuroendocrine tumors (NETs) is often with somatostatin analogues (SSA) such as lanreotide in the first-line setting. Real world use of lanreotide in Canada is not well studied. Methods We performed a retrospective chart review of 69 patients to study real world use of lanreotide at our centre. Results Lanreotide was the first-line of systemic treatment in 60 patients. Watch-and-wait was a common strategy and was seen in 31 patients. SSA switch strategy was seldom applied. Majority of patients on lanreotide had low-grade NETs. Standard starting dose of lanreotide 120 mg every 28 days was used in 66 patients. Dose escalation to 120 mg every 21 days occurred in 7 patients. The primary intention for treatment was tumor control in 32 patients, and both tumor and symptom control in 34 patients. Median time on treatment was 21.6 months. Conclusions Overall, our findings were in keeping with current guidelines. It will be interesting to assess how clinical practice evolves in the future and to determine the role of dose escalation for disease control.
Seroprevalence of Toxoplasma gondii infection among patients of a tertiary hospital in Guangzhou, Guangdong province, PR China

Purpose This study aimed to explore the prevalence of Toxoplasma gondii (T. gondii) among patients in Guangzhou city, South China, and to identify susceptible patient populations and analyze the causes of infection differences. Methods From May 2020 to May 2022, a total of 637 sera were collected from patients, and 205 sera were collected from health participants as health control. All sera were examined by colloidal gold kits to detect the positivity of antibodies against T. gondii. And the positivity of antibodies in sera was confirmed with ARCHITECT i2000SR system. Results The prevalence of T. gondii infection in patients was 7.06% (45/637), which was lower than the prevalence in health participants 4.88% (10/205). Among patients, 34 (5.34%) were positive only for IgG, 10 (1.57%) were only for IgM, and 1 (0.16%) was positive for both IgG and IgM. There was a significant difference in prevalence between male and female patients, but not among different age groups or diseases groups. The prevalence of T. gondii infection in diseases groups varied. The prevalence was relatively high in patients with the disorders of thyroid gland and the malignant neoplasms of digestive organs, which suggests that caution should be taken to avoid T. gondii infection in these patients. Surprisingly, the prevalence was quite low in diffuse Large B-cell Lymphoma (DLBC) patients. This may be due to the overexpression of TNF-α in tumor tissues of DLBC patients and the higher protein level of TNF-α in sera of DLBC patients. Conclusion This study provides a systematic exploration of the prevalence of T. gondii infection in patients in a tertiary hospital. Our data contributes to a better understanding of the epidemic investigation of T. gondii among patients in South China, which can help the prevention and treatment of the disease caused by T. gondii infection.
Metabolomics in Acute Kidney Injury: The Experimental Perspective

Acute kidney injury (AKI) affects increasing numbers of in-hospital patients in Central Europe and the USA, the prognosis remains poor. Although substantial progress has been achieved in the identification of molecular/cellular processes that induce and perpetuate AKI, more integrated pathophysiological perspectives are missing. Metabolomics enables the identification of low-molecular-weight (< 1.5 kD) substances from biological specimens such as certain types of fluid or tissue. The aim of the article was to review the literature on metabolic profiling in experimental AKI and to answer the question if metabolomics allows the integration of distinct pathophysiological events such as tubulopathy and microvasculopathy in ischemic and toxic AKI. The following databases were searched for references: PubMed, Web of Science, Cochrane Library, Scopus. The period lasted from 1940 until 2022. The following terms were utilized: “acute kidney injury” OR “acute renal failure” OR “AKI” AND “metabolomics” OR “metabolic profiling” OR “omics” AND “ischemic” OR “toxic” OR “drug-induced” OR “sepsis” OR “LPS” OR “cisplatin” OR “cardiorenal” OR “CRS” AND “mouse” OR “mice” OR “murine” OR “rats” OR “rat”. Additional search terms were “cardiac surgery”, “cardiopulmonary bypass”, “pig”, “dog”, and “swine”. In total, 13 studies were identified. Five studies were related to ischemic, seven studies to toxic (lipopolysaccharide (LPS), cisplatin), and one study to heat shock-associated AKI. Only one study, related to cisplatin-induced AKI, was performed as a targeted analysis. The majority of the studies identified multiple metabolic deteriorations upon ischemia/the administration of LPS or cisplatin (e.g., amino acid, glucose, lipid metabolism). Particularly, abnormalities in the lipid homeostasis were shown under almost all experimental conditions. LPS-induced AKI most likely depends on the alterations in the tryptophan metabolism. Metabolomics studies provide a deeper understanding of pathophysiological links between distinct processes that are responsible for functional impairment/structural damage in ischemic or toxic or other types of AKI.
Multivariate analysis of variance for functional data

ABSTRACT Functional data are being observed frequently in many scientific fields, and therefore most of the standard statistical methods are being adapted for functional data. The multivariate analysis of variance problem for functional data is considered. It seems to be of practical interest similarly as the one-way analysis of variance for such data. For the MANOVA problem for multivariate functional data, we propose permutation tests based on a basis function representation and tests based on random projections. Their performance is examined in comprehensive simulation studies, which provide an idea of the size control and power of the tests and identify differences between them. The simulation experiments are based on artificial data and real labeled multivariate time series data found in the literature. The results suggest that the studied testing procedures can detect small differences between vectors of curves even with small sample sizes. Illustrative real data examples of the use of the proposed testing procedures in practice are also presented.
The nature of psychopathology

Abstract Readers of JCPP Advances known that the dominant classification system (Diagnostic and Statistical Manual of Mental Disorders) in psychiatry and psychology conceptualizes psychopathology as discrete diagnostic categories. This measurement model builds on a strong assumption of a clear discontinuity between individuals who meet criteria for a diagnosis and those who don't fulfill diagnostic criteria. During the past decades we have seen huge efforts to test this assumption and explore alternative models, such as research from the hierarchical taxonomy of psychopathology consortia. Key findings of these efforts are reviewed and discussed in the December issue of JCPP Advances.
Impact of the covid-19 pandemic on mental health and sexuality of female doctors

Background COVID-19 pandemic has changed people’s lives around the world due to restrictive measures adopted by governments. The impact of this change on female sexuality needs to be further investigated, particularly between female doctors who are more at risk as they are directly involved with health care services. Methods An online survey has been filled out by female doctors. The questionnaire evaluates sexual function, depression, anxiety, burnout, sociodemographic and professional data, and it was answered during the peak of COVID-19 pandemic in Brazil. The main outcome is female doctors’ sexual function during COVID-19 pandemic, which was evaluated by analyzing FSFI questionnaires. The secondary outcome is related to their mental health, assessed via depression, anxiety and burnout questionnaires. Results A sample of 388 female doctors filled out the questionnaire. The median age was 34.0 (29.0, 43.0) years old. The total FSFI median score was 23.8 [18.9, 26.8] with desire domain median of 5.0 [3.0, 7.0]. In our sample, 231 (59.5%) women had depression and/or anxiety, out of these, 191 (82.7%) had depression and 192 (83.2%), anxiety. From these samples of doctors with depression and/or anxiety, 183 (79.2%) had sexual dysfunction. Conclusion This finding suggests that doctors are experiencing a high risk of sexual dysfunction and mental illness during the COVID-19 outbreak. A high index of depression and/or anxiety was shown in the studied population, with almost 80% of them reaching criteria for sexual dysfunction. Working in the frontline is related to worse mental health conditions. Depression and anxiety were found as potential mediators of burnout effect on sexual function.
Impact of Lateral Mixing in the Ocean on El Nino in a Suite of Fully Coupled Climate Models

We examine the dependence of the amplitude of the El Nino‐Southern Oscillation (ENSO) on the mixing coefficient parameterizing the lateral mixing of tracers (ARedi) The value of this coefficient is very uncertain, ranging in Earth System Models between a few hundred and a few thousand m2 s−1, with some observational estimates showing even higher values. A suite of simulations is made with two spatially varying distributions of ARedi derived from satellite observations as well as four simulations where a spatially constant ARedi is varied over a factor of 6. Surprisingly, larger values of ARedi result in stronger ENSO variability despite the higher mixing coefficients producing more efficient lateral diffusive damping of anomalies. This is because lateral mixing also warms the cold tongue, increasing vertical temperature gradients and decreasing horizontal temperature gradients. Larger vertical temperature gradients make sea surface temperatures more responsive to atmospheric forcing, while smaller horizontal temperature gradients shift the location of convection and make the atmosphere more responsive to sea surface temperature anomalies. The last effect holds across simulations as well as within individual simulations and thus also helps to explain interdecadal variability in ENSO amplitude. By contrast, a previously proposed anticorrelation between the amplitude interannual and annual variability does not hold across simulations, although it does hold within simulations. The propagation of thermocline depth anomalies is relatively insensitive to the value of ARedi. Properly specifying the lateral mixing along the equator (including distinguishing the impacts of subgridscale turbulence and tropical instability waves) appears essential to simulating ENSO.
Modulatory Effects of Communicative Gaze on Attentional Orienting Are Driven by Dorsomedial Prefrontal Cortex but Not Right Temporoparietal Junction

Abstract Communicative gaze (e.g., mutual or averted) has been shown to affect attentional orienting. However, no study to date has clearly separated the neural basis of the pure social component that modulates attentional orienting in response to communicative gaze from other processes that might be a combination of attentional and social effects. We used TMS to isolate the purely social effects of communicative gaze on attentional orienting. Participants completed a gaze-cueing task with a humanoid robot who engaged either in mutual or in averted gaze before shifting its gaze. Before the task, participants received either sham stimulation (baseline), stimulation of right TPJ (rTPJ), or dorsomedial prefrontal cortex (dmPFC). Results showed, as expected, that communicative gaze affected attentional orienting in baseline condition. This effect was not evident for rTPJ stimulation. Interestingly, stimulation to rTPJ also canceled out attentional orienting altogether. On the other hand, dmPFC stimulation eliminated the socially driven difference in attention orienting between the two gaze conditions while maintaining the basic general attentional orienting effect. Thus, our results allowed for separation of the pure social effect of communicative gaze on attentional orienting from other processes that are a combination of social and generic attentional components.
PSW1, an LRR receptor kinase, regulates pod size in peanut

Summary Pod size is a key agronomic trait that greatly determines peanut yield, the regulatory genes and molecular mechanisms that controlling peanut pod size are still unclear. Here, we used quantitative trait locus analysis to identify a peanut pod size regulator, POD SIZE/WEIGHT1 (PSW1), and characterized the associated gene and protein. PSW1 encoded leucine‐rich repeat receptor‐like kinase (LRR–RLK) and positively regulated pod stemness. Mechanistically, this allele harbouring a 12‐bp insertion in the promoter and a point mutation in the coding region of PSW1 causing a serine‐to‐isoleucine (S618I) substitution substantially increased mRNA abundance and the binding affinity of PSW1 for BRASSINOSTEROID INSENSITIVE1‐ASSOCIATED RECEPTOR KINASE 1 (BAK1). Notably, PSW1 HapII (super‐large pod allele of PSW1) expression led to up‐regulation of a positive regulator of pod stemness PLETHORA 1 (PLT1), thereby resulting in larger pod size. Moreover, overexpression of PSW1 HapII increased seed/fruit size in multiple plant species. Our work thus discovers a conserved function of PSW1 that controls pod size and provides a valuable genetic resource for breeding high‐yield crops.
Patterns of Referral and Postdischarge Utilization of Cardiac Rehabilitation Among Patients Hospitalized With Heart Failure: An Analysis From the GWTG-HF Registry

BACKGROUND: Coverage for cardiac rehabilitation (CR) for patients with heart failure with reduced ejection fraction was expanded in 2014, but contemporary referral and participation rates remain unknown. METHODS: Patients hospitalized for heart failure with reduced ejection fraction (≤35%) in the American Heart Association Get With The Guidelines–Heart Failure registry from 2010 to 2020 were included, and CR referral status was described as yes, no, or not captured. Temporal trends in CR referral were assessed in the overall cohort. Patient and hospital-level predictors of CR referral were assessed using multivariable-adjusted logistic regression models. Additionally, CR referral and proportional utilization of CR within 1-year of referral were evaluated among patients aged >65 years with available Medicare administrative claims data who were clinically stable for 6-weeks postdischarge. Finally, the association of CR referral with the risk of 1-year death and readmission was evaluated using multivariable-adjusted Cox models. RESULTS: Of 69,441 patients with heart failure with reduced ejection fraction who were eligible for CR (median age 67 years; 33% women; 30% Black), 17,076 (24.6%) were referred to CR, and referral rates increased from 8.1% in 2010 to 24.1% in 2020 (Ptrend<0.001). Of 8310 patients with Medicare who remained clinically stable 6-weeks after discharge, the CR referral rate was 25.8%, and utilization of CR among referred patients was 4.1% (mean sessions attended: 6.7). Patients not referred were more likely to be older, of Black race, and with a higher burden of comorbidities. In adjusted analysis, eligible patients with heart failure with reduced ejection fraction who were referred to CR (versus not referred) had a lower risk of 1-year death (hazard ratio, 0.84 [95% CI, 0.70–1.00]; P=0.049) without significant differences in 1-year readmission. CONCLUSIONS: CR referral rates have increased from 2010 to 2020. However, only 1 in 4 patients are referred to CR. Among eligible patients who received CR referral, participation was low, with <1 of 20 participating in CR.
KLF4 targets RAB26 and decreases 5-FU resistance through inhibiting autophagy in colon cancer

ABSTRACT Background Accumulating studies demonstrated that resistance of colon cancer (CC) to 5-fluorouracil (5-FU) contributes to adverse prognosis. We investigated how Kruppel-like factor 4 (KLF4) affected 5-FU resistance and autophagy in CC cells. Methods KLF4 expression and its downstream target gene RAB26 in CC tissues was analyzed by bioinformatics analysis, and the effect of abnormal KLF4 expression on prognoses of CC patients was predicted. Luciferase reporter assay detected the targeted relationship between KLF4 and RAB26. The viability and apoptosis of CC cells were analyzed by CCK-8 and flow cytometry. The formation of intracellular autophagosomes was detected by confocal laser scanning microscopy and immunofluorescence staining. The mRNA and protein levels were assayed by qRT-PCR and western blot. A xenograft animal model was constructed to verify the function of KLF4. Rescue assay was employed to verify whether KLF4/RAB26 could affect 5-FU resistance in CC cells through autophagy. Results KLF4 and RAB26 were lowly expressed in CC. KLF4 correlated with patients’ survival. KLF4 was down-regulated in 5-FU resistant CC cells. KLF4 overexpression suppressed the proliferation and 5-FU resistance of CC cells, and inhibited LC3 II/I expression and autophagosome formation. Autophagy activator Rapamycin or sh-RAB26 treatment reversed the impact of KLF4 overexpression on 5-FU resistance. In vivo assay verified that KLF4 inhibited 5-FU resistance in CC cells. Rescue experiments revealed that KLF4 targeted RAB26 to inhibit CC cell autophagy, resulting in decreasing the resistance to 5-FU. Conclusion KLF4 strengthened the sensitivity of CC cells to 5-FU by targeting RAB26 to restrain autophagy pathway.
On Distribution and Quantile Functions, Ranks and Signs in R_d

Unlike the real line, the d-dimensional space Rd, for d ≥ 2, is not canonically ordered. As a consequence, such fundamental and strongly order-related univariate concepts as quantile and distribution functions, and their empirical counterparts, involving ranks and signs, do not canonically extend to the multivariate context. Palliating that lack of a canonical ordering has remained an open problem for more than half a century, and has generated an abundant literature, motivating, among others, the development of statistical depth and copula-based methods. We show here that, unlike the many definitions that have been proposed in the literature, the measure transportation-based ones introduced in Chernozhukov et al. (2017) enjoy all the properties (distribution-freeness and preservation of semiparametric efficiency) that make univariate quantiles and ranks successful tools for semiparametric statistical inference. We therefore propose a new center-outward definition of multivariate distribution and quantile functions, along with their empirical counterparts, for which we establish a Glivenko-Cantelli result. Our approach, based on results by McCann (1995), is geometric rather than analytical and, contrary to the Monge-Kantorovich one in Chernozhukov et al. (2017) (which assumes compact supports or finite second-order moments), does not require any moment assumptions. The resulting ranks and signs are shown to be strictly distribution-free, and maximal invariant under the action of transformations (namely, the gradients of convex functions, which thus are playing the role of order-preserving transformations) generating the family of absolutely continuous distributions; this, in view of a general result by Hallin and Werker (2003), implies preservation of semiparametric efficiency. The resulting quantiles are equivariant under the same transformations, which confirms the order-preserving nature of gradients of convex function.
Fucoidan and microtopography on polyvinyl alcohol hydrogels guided axons and enhanced neuritogenesis of pheochromocytoma 12 (PC12) cells

Artificial nerve grafts that support axon growth hold promises in promoting nerve regeneration and function recovery. However, current artificial nerve grafts are insufficient to regenerate axons across long nerve gaps. Specific biochemical and biophysical cues are required to be incorporated to artificial nerve grafts to promote neural cell adhesion and guide neurite outgrowth. Polyvinyl alcohol (PVA) nerve conduits have been clinically approved, but the applicability of PVA nerve conduits is limited to short injuries due to low cell binding. In this study, we explored the incorporation of biochemical cues and topographical cues for promoting neuritogenesis and axon guidance. PVA was conjugated with extracellular matrix proteins and fucoidan, a bioactive sulfated polysaccharide, to improve cell adhesion. Micro-sized topographies, including 1.8 μm convex lenses, 2 μm gratings, and 10 μm gratings were successfully fabricated on PVA by nanofabrication, and the synergistic effects of topography and biochemical molecules on pheochromocytoma 12 (PC12) neuritogenesis and neurite alignment were studied. Conjugated fucoidan promoted the percentage of PC12 with neurite outgrowth from 0% to 2.8% and further increased to 5% by presenting laminin on the surface. Additionally, fucoidan was able to bind nerve growth factor (NGF) on the surface and allow for PC12 to extend neurites in NGF-free media. The incorporation of 2 μm gratings could double the percentage of PC12 with neurite outgrowth and neurite length, and guided the neurites to extend along the grating axis. The work presents a promising strategy to enhance neurite formation and axon guidance, presenting significant value in promoting nerve regeneration.