Miracle-dz/UniFAR-FTUs huggingface dataset:
Current and Historical Trends in Diversity by Race, Ethnicity, and Sex Within the US Pathology Physician Workforce.

OBJECTIVES This study assessed historical and current gender, racial, and ethnic diversity trends within US pathology graduate medical education (GME) and the pathologist workforce. METHODS Data from online, publicly available sources were assessed for significant differences in racial, ethnic, and sex distribution in pathology trainees, as well as pathologists in practice or on faculty, separately compared with the US population and then each other using binomial tests. RESULTS Since 1995, female pathology resident representation has been increasing at a rate of 0.45% per year (95% confidence interval [CI], 0.29-0.61; P < .01), with pathology now having significantly more females (49.8%) compared to the total GME pool (45.4%; P < .0001). In contrast, there was no significant trend in the rate of change per year in black or American Indian, Alaskan Native, Native Hawaiian, and Pacific Islander (AI/AN/NH/PI) resident representation (P = .04 and .02). Since 1995, underrepresented minority (URM) faculty representation has increased by 0.03% per year (95% CI, 0.024-0.036; P < .01), with 7.6% URM faculty in 2018 (5.2% Hispanic, 2.2% black, 0.2% AI/AN/NH/PI). CONCLUSIONS This assessment of pathology trainee and physician workforce diversity highlights significant improvements in achieving trainee gender parity. However, there are persistent disparities in URM representation, with significant underrepresentation of URM pathologists compared with residents.
FOXP3, CD208, and CD206 Expression in Canine Cutaneous Histiocytoma

Canine cutaneous histiocytoma (CCH) is a noninfectious tumor that spontaneously regresses. It is suggested that this regression is due to tumor cell maturation, which is responsible for CD8 lymphocyte activation and tumor cell destruction. Nevertheless, the possible role of the immune microenvironment in tumor regression has not been investigated to date. The aim of this study was to investigate the expression of CD208 and FoxP3 as markers of dendritic cells and regulatory T lymphocytes, respectively, and tumor cell expression of CD206 as a marker of Langerhans cell activation, and relate these parameters to the different phases of CCH and to intratumoral T cell infiltration. Formalin-fixed, paraffin-embedded samples from 31 CCH were evaluated. In each case, the mitotic count and regression phase were recorded. Within the tumor, a quantitative evaluation of immunolabeled CD208+ cells, FoxP3+ cells, and CD3+ lymphocytes was performed, as well as the CD206+ tumor cell location. Intratumoral CD208+ cells correlated with CD3+ lymphocytic infiltration. The possible role of dendritic cells in tumor regression was not confirmed since CD208 seemed to be a nonspecific marker for canine dendritic cells. FoxP3+ lymphocyte density was not correlated with any parameter. Neoplastic Langerhans cells presented progressive CD206 expression, from the bottom of the tumor to the epidermis, which correlated with the tumor regression phase and with intratumoral T lymphocyte infiltration. In conclusion, we confirmed a CD206 phenotype change in tumor cells in a spatial group-related pattern, supporting the hypothesis that tumoral Langerhans cells acquire a mature phenotype with tumor regression.
Safety of a quadrivalent influenza vaccine in Vietnamese healthy subjects aged 6 months and older

ABSTRACT Quadrivalent influenza vaccines (QIVs) provide protection against the two influenza A viruses (H1N1 and H3N2) and both co-circulating influenza B lineages. QIVs have been found safe, immunogenic, and efficacious in several phase III clinical trials. Here we assess the safety of QIV after vaccination in Vietnamese infants, children, and adults. Participants (n = 228) were asked to report any solicited adverse events (AEs) occurring within 7 days, unsolicited non-serious AEs occurring within 28 days post-vaccination, and serious adverse events (SAEs) at any time during the study. The study was completed by 224 participants (97.4%). Thirty-one children (39.7%) aged 6 − 35 months, 32 children (40.0%) aged 3 − 8 years, 2 participants (9.0%) aged 9 − 17 years, 5 participants (17.9%) aged 18 − 60 years, and 3 participants (15.0%) aged ≥60 years reported ≥1 solicited reaction within 7 days following vaccination. The most frequent-solicited AEs were injection-site tenderness or pain, appetite loss, fever, and abnormal crying in 6 − 35 month-olds, and fever, headache, and myalgia in other age groups. No severe-unsolicited AEs or vaccine-related SAEs were reported. These results suggest that QIV is well tolerated across age groups in Vietnam, and can be safely used to protect the Vietnamese population against influenza and its potentially serious complications.
Arteriosclerosis, Thrombosis, and Vascular Biology Antiplatelet Effect of Carbon Monoxide Is Mediated by NAD + and ATP Depletion

OBJECTIVES: Carbon monoxide (CO) produced by haem oxygenases or released by CO-releasing molecules (CORM) affords antiplatelet effects, but the mechanism involved has not been defined. Here, we tested the hypothesis that CO–induced inhibition of human platelet aggregation is mediated by modulation of platelet bioenergetics. APPROACH AND RESULTS: To analyze the effects of CORM-A1 on human platelet aggregation and bioenergetics, a light transmission aggregometry, Seahorse XFe technique and liquid chromatography tandem-mass spectrometry–based metabolomics were used. CORM-A1–induced inhibition of platelet aggregation was accompanied by the inhibition of mitochondrial respiration and glycolysis. Interestingly, specific inhibitors of these processes applied individually, in contrast to combined treatment, did not inhibit platelet aggregation considerably. A CORM-A1–induced delay of tricarboxylic acid cycle was associated with oxidized nicotinamide adenine dinucleotide (NAD + ) depletion, compatible with the inhibition of oxidative phosphorylation. CORM-A1 provoked an increase in concentrations of proximal (before GAPDH [glyceraldehyde 3-phosphate dehydrogenase]), but not distal glycolysis metabolites, suggesting that CO delayed glycolysis at the level of NAD + –dependent GAPDH; however, GAPDH activity was directly not inhibited. In the presence of exogenous pyruvate, CORM-A1–induced inhibition of platelet aggregation and glycolysis were lost, but were restored by the inhibition of lactate dehydrogenase, involved in cytosolic NAD + regeneration, pointing out to the key role of NAD + depletion in the inhibition of platelet bioenergetics by CORM-A1. CONCLUSIONS: The antiplatelet effect of CO is mediated by inhibition of mitochondrial respiration—attributed to the inhibition of cytochrome c oxidase, and inhibition of glycolysis—ascribed to cytosolic NAD + depletion. GRAPHIC ABSTRACT: A graphic abstract is available for this article. in positive and negative ionization MRM (multiple reaction mode. For the analysis in positive using (pH and were used as a mobile phase using gradient The total run time was and 10 minutes for negative and positive ionization modes, respectively. have been analyzed for normality, and 1-way ANOVA test was performed with Benferroni test; with P values being provided in the legends (* P <0.05, # P <0.01, $ P <0.001, and & P <0.0001).
Swedish parents' experiences of their role in treatment for children with congenital limb reduction deficiency: Decision‐making and treatment support

Abstract Background Parents of children with congenital limb reduction deficiency have an essential role in making treatment decisions during their child's first years of life. Treatment options usually concern surgical and/or prosthetic treatment. To tailor treatment options to fit different family values and priorities, the family‐centred approach indicates the importance of understanding the parental role in partnership with health care professionals. The aim of this study was to describe parents' experiences of their role in decision‐making and treatment for children with congenital limb reduction deficiency. Methods A descriptive design with a qualitative approach was used. Semi‐structured interviews were conducted with 17 parents (12 mothers and 5 fathers) of children with upper and/or lower limb deficiency (mean age 5.9 years). The interview data were analysed using qualitative content analysis with an inductive approach. Results Two major themes emerged from the data. The first theme, being a decision maker for someone else, was described as an ambivalent parental role, including collaboration within the family and with health care professionals. The second theme, becoming and being a treatment supporter in the child's everyday life, was made up of four categories: being a supporter of the child in everyday activities, mentoring the child to handle encounters with others, becoming a coordinator of information and being an ‘extended arm’ of the health care provision for the child. Conclusions This study enhances our understanding of the parental role in decision‐making and treatment for children with congenital limb reduction deficiency. The results may contribute to the continued development of the family‐centred service approach by providing guidelines for treatment programmes, with the goal of improving decision support and broadening the support for parents during treatment for these children.
Dollar Spot Suppression on Creeping Bentgrass in Response to Repeated Foliar Nitrogen Applications.

Dollar spot is caused by the fungus Clarireedia spp. and is the most economically important disease of golf course turfgrass in temperate regions of the United States. Previous research has demonstrated that nitrogen (N) fertilization may reduce dollar spot severity, however the results have been inconsistent and the impact of N as part of repeated foliar fertilization applications to golf course putting greens remains unclear. Two independent trials were replicated in Madison, WI and Glenview, IL during the 2015, 2016, and 2017 growing seasons. The objective of the first trial was to evaluate the effect of four different N rates applied as urea (4.9, 9.8, 19.4, and 29.3 kg N ha-1 applied every two weeks) on dollar spot severity, and the objective of the second trial was to evaluate the effect of three N sources (calcium nitrate, ammonium sulfate, and ammonium nitrate applied every two weeks) on dollar spot severity. Results from the N rate trial at both locations indicated that only the highest (29.3 kg N ha-1) rate consistently reduced dollar spot severity relative to the non-treated control. Nitrogen source had minimal and inconsistent impacts on dollar spot severity based on location and year. While these results show that meaningful reductions in dollar spot severity can be achieved by manipulating N fertilizer application rate, the rate of N required for disease suppression may be impractical for most superintendents to apply and result in undesirable non-target impacts.
Availability Bias Causes Misdiagnoses by Physicians: Direct Evidence from a Randomized Controlled Trial

Objective Empirical evidence on the availability bias associated with diagnostic errors is still insufficient. We investigated whether or not recent experience with clinical problems can lead physicians to make diagnostic errors due to availability bias and whether or not reflection counteracts this bias. Methods Forty-six internal medicine residents were randomly divided into a control group (CG) and experimental group (EG). Among the eight clinical cases used in this study, three experimental cases were similar to the disease of dengue fever (DF) but exhibited different diagnoses, one was actually DF, and the other four filler cases were not associated with DF. First, only the EG received information on DF, while the CG knew nothing about this study. Then, six hours later, all participants were asked to diagnose eight clinical cases via nonanalytic reasoning. Finally, four cases were diagnosed again via reflective reasoning. Results In stage 2, the average score of the CG in the diagnosis of experimental cases was significantly higher than that of the filler cases (0.80 vs. 0.59, p<0.01), but the EG's average score in the two types of cases was not significantly different (0.66 vs. 0.64, p=0.756). The EG and CG had significantly different scores for each experimental case, while no difference was observed in the filler cases. The proportion of diseases incorrectly diagnosed as DF among experimental cases ranged from 71% to 100% in the EG. There were no significant differences between the mean diagnostic accuracy scores obtained by nonanalytic reasoning and those obtained by the reflective reasoning in any cases. Conclusion Availability bias led to diagnostic errors. Misdiagnoses cannot always be repaired solely by adopting a reflective approach.
Targeting TLR4 with ApTOLL Improves Heart Function in Response to Coronary Ischemia Reperfusion in Pigs Undergoing Acute Myocardial Infarction

Toll-like receptor 4 (TLR4) contributes to the pathogenesis of coronary ischemia/reperfusion (IR). To test whether the new TLR4 antagonist, ApTOLL, may prevent coronary IR damage, we administered 0.078 mg/kg ApTOLL or Placebo in pigs subjected to IR, analyzing the levels of cardiac troponins, matrix metalloproteinases, pro-, and anti-inflammatory cytokines, heart function, and tissue integrity over a period of 7 days after IR. Our results show that ApTOLL reduced cardiac troponin-1 24 h after administration, improving heart function, as detected by a significant recovery of the left ventricle ejection fraction (LVEF) and the shortening fraction (FS) cardiac parameters. The extension of necrotic and fibrotic areas was also reduced, as detected by Evans blue/2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxylin/Eosine, and Masson Trichrome staining of heart sections, together with a significant reduction in the expression of the extracellular matrix-degrading, matrix metalloproteinase 9. Finally, the expression of the following cytokines, CCL1, CCL2, MIP1-A-B, CCL5, CD40L, C5/C5A, CXCL1, CXCL10, CXCL11, CXCL12, G-CSF, GM-CSF, ICAM-1, INF-g, IL1-a, ILI-b, IL-1Ra, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, IL16, IL17-A, IL17- E, IL18, IL21, IL27, IL32, MIF, SERPIN-E1, TNF-a, and TREM-1, were also assayed, detecting a pronounced decrease of pro-inflammatory cytokines after 7 days of treatment with ApTOLL. Altogether, our results show that ApTOLL is a promising new tool for the treatment of acute myocardial infarction (AMI).
YRNAs and YRNA-Derived Fragments as New Players in Cancer Research and Their Potential Role in Diagnostics

YRNAs are a type of short, noncoding RNAs. A total of four different transcripts can be distinguished, which are YRNA1, YRNA3, YRNA4 and YRNA5. All YRNAs are relatively small, made up of about 100 nucleotides each. YRNAs are characterized by a stem-loop structure and each part of that structure carries a different function. YRNAs are transcribed in the nucleus by RNA polymerase III. Then, the YRNA molecule is bound to the polyuridine tail of the La protein responsible for both its nuclear retention and protection from degradation. They also bind to the Ro60 protein, making the molecule more stable. In turn, YRNA-derived small RNAs (YsRNAs) are a class of YRNAs produced in apoptotic cells as a result of YRNA degradation. This process is performed by caspase-3-dependent pathways that form two groups of YsRNAs, with lengths of either approximately 24 or 31 nucleotides. From all four YRNA transcripts, 75 well-described pseudogenes are generated as a result of the mutation. However, available data indicates the formation of up to 1000 pseudogenes. YRNAs and YRNA-derived small RNAs may play a role in carcinogenesis due to their altered expression in cancers and influence on cell proliferation and inflammation. Nevertheless, our knowledge is still limited, and more research is required. The main aim of this review is to describe the current state of knowledge about YRNAs, their function and contribution to carcinogenesis, as well as their potential role in cancer diagnostics. To confirm the promising potential of YRNAs and YRNA-derived fragments as biomarkers, their significant role in several tumor types was taken into consideration.
TERT Promoter Mutation as an Independent Prognostic Marker for Poor Prognosis MAPK Inhibitors-Treated Melanoma

Although the development of mitogen-activated protein kinase (MAPK) inhibitors has greatly improved the prognosis of BRAFV600 cutaneous melanomas, the identification of molecular indicators for mutated patients at risk of early progression remains a major issue. Using an amplicon-based next-generation-sequencing (NGS) assay that targets cancer-related genes, we investigated co-occurring alterations in 89 melanoma samples. We analyzed both their association with clinicopathological variables and clinical significance in terms of progression-free survival (PFS) and overall survival (OS) according to BRAF genotyping. Among co-occurring mutations, TERT promoter was the most frequently mutated gene. Although no significant difference in PFS was observed in the presence or absence of co-occurring alterations to BRAFV600, there was a trend of longer PFS for patients harboring TERT c. -124C>T mutation. Of most interest, this mutation is an independent marker of good prognosis in subgroups of patients with poor prognosis (presence of brain metastasis and elevated level of lactate dehydrogenase, LDH). Moreover, combination of elevated LDH level, presence of brain metastasis, and TERT c. -124C>T mutation was identified as the best fit model for predicting clinical outcome. Our work revealed the potential interest of c. -124C>T status determination in order to refine the prognosis of BRAFV600 melanoma under mitogen-activated protein kinase (MAPK) inhibitors.
Sequential Combination of Cognitive-Behavioral Treatment and Well-Being Therapy in Depressed Patients with Acute Coronary Syndromes: A Randomized Controlled Trial (TREATED-ACS Study)

Introduction: Randomized controlled trials (RCT) of psychotherapeutic interventions have addressed depression and demoralization associated with acute coronary syndromes (ACS). The present trial introduces psychological well-being, an increasingly recognized factor in cardiovascular health, as a therapeutic target. Objective: This study was designed to determine whether the sequential combination of cognitive-behavioral therapy (CBT) and well-being therapy (WBT) may yield more favorable outcomes than an active control group (clinical management; CM) and to identify subgroups of patients at greater risk for cardiac negative outcomes. Methods: This multicenter RCT comparedCBT/WBT sequential combination versus CM, with up to 30 months of follow-up. One hundred consecutive depressed and/or demoralized patients (out of 740 initially screened by cardiologists after a first episode of ACS) were randomized to CBT/WBT associated with lifestyle suggestions (n = 50) and CM (n = 50). The main outcome measures included: severity of depressive symptoms according to the Clinical Interview for Depression, changes in subclinical psychological distress, well-being, and biomarkers, and medical complications and events. Results: CBT/WBT sequential combination was associated with a significant improvement in depressive symptoms compared to CM. In both groups, the benefits persisted at follow-up, even though the differences faded. Treatment was also related to a significant amelioration of biomarkers (platelet count, HDL, and D-dimer), whereas the 2 groups showed similar frequencies of adverse cardiac events. Conclusions: Addressing psychological well-being in the psychotherapeutic approach to ACS patients with depressive symptoms was found to entail important clinical benefits. It is argued that lifestyle changes geared toward cardiovascular health may be facilitated by a personalized approach that targets well-being.
Evaluation of Nuclear Cataract with Smartphone-Attachable Slit-Lamp Device

Background: Visual impairments and age-related eye diseases need to be detected and treated in a timely manner. However, this is often hampered by lack of appropriate medical equipment. We have invented a portable, recordable, and smartphone-attachable slit-lamp device, called the Smart Eye Camera (SEC). The aim of this study was to compare evaluating nuclear cataract (NUC) between the SEC and the conventional, non-portable slit-lamp microscope. Methods: A total of 128 eyes of 64 Japanese patients (mean age: 73.95 ± 9.28 years; range: 51‒92 years; female: 34) were enrolled. The NUC was classified into four grades (grade 0 to 3) based on three standard photographs of nuclear opacities according to the WHO classification by ophthalmologists. An ophthalmic healthcare assistant (non-ophthalmologist) filmed the eyes in video mode by the SEC and an ophthalmologist graded the NUC. Grade correlation and inter-rater reproducibility were determined. Results: NUC grading by the two approaches correlated significantly (both eyes: r = 0.871 [95%CI: 0.821 to 0.907; p < 0.001]). Inter-rater agreement was high (weighted κ = 0.807 [95%CI: 0.798 to 0.816; p < 0.001]). Conclusions: This study suggests that the SEC is as reliable as the conventional non-portable slit-lamp microscope for evaluating NUC.
Intervention effects on professionals’ attitudes towards the participation of adults with visual and severe or profound intellectual disabilities

Abstract Background We investigated the effects of the “Care for Participation+” (CFP+) intervention on direct support professionals’ (DSPs’) attitudes regarding the participation of adults with visual and severe or profound intellectual disabilities (VSPID). Methods We implemented a pilot non‐randomized controlled trial with two control groups to compare DSPs’ attitudes towards CFP+ using the Attitudes towards Participation Questionnaire (APQ) and DSPs’ written profiles of adults with VSPID. Results CPP+ and the Participation Mind Map control group showed a positive trend for the “leisure/recreation,” “social relations,” and “ability to act” APQ domains compared to the usual care control group. The CFP+ group described significantly fewer disabilities at 6 months, reflecting a more positive attitude than controls. Conclusion CFP+ had positive effects on DSPs’ attitudes towards the participation of adults with VSPID. The small sample size, ceiling effects, measurement instruments used, and implementation difficulties may have hampered understanding the full potential of CFP+.