Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidemiologic Analysis of Chilblains Cohorts Before and During the COVID-19 Pandemic.

Importance Beginning in March 2020, case reports and case series linked the COVID-19 pandemic with an increased occurrence of chilblains, but this association has not been evaluated in an epidemiologic study. Objective To assess whether a correlation exists between COVID-19 incidence and chilblains incidence. Design, Setting, and Participants A retrospective cohort study was conducted within the Kaiser Permanente Northern California system from January 1, 2016, to December 31, 2020; health plan members of all ages were included. Exposure COVID-19 incidence in 207 location-months, representing 23 geographic locations in northern California across 9 months. Main Outcome and Measures Chilblains incidence was the main outcome. The association of chilblains incidence with COVID-19 incidence across the 207 location-months was measured using the Spearman rank correlation coefficient. Results Of 780 patients with chilblains reported during the pandemic, 464 were female (59.5%); mean (SD) age was 36.8 (21.8) years. COVID-19 incidence was correlated with chilblains incidence at 207 location-months (Spearman coefficient 0.18; P = .01). However, only 17 of 456 (3.7%) patients with chilblains tested during the pandemic were positive for SARS-CoV-2, and only 9 of 456 (2.0%) were positive for SARS-CoV-2 within 6 weeks of the chilblains diagnosis. Test results of 1 of 97 (1.0%) patients were positive for SARS-CoV-2 IgG antibodies. Latinx patients were disproportionately affected by COVID-19 but not by chilblains. Conclusions and Relevance This cohort study found that in northern California, the incidence of chilblains increased during the pandemic but was correlated weakly with the incidence of COVID-19 across 207 location-months. These findings may have resulted from a causal role of COVID-19, increased care-seeking by patients with chilblains during the pandemic, or changes in behavior during shelter in place.
Kinase inhibitor screening reveals aurora‐a kinase is a potential therapeutic and prognostic biomarker of gastric cancer

Gastric cancer is one of the most common and deadly types of cancer in the world, and poor prognosis with treatment failure is widely reported in the literature. In this context, kinases have been considered a relevant choice for targeted therapy in gastric cancer. Here, we explore the antiproliferative and antimigratory effects of the AURKA inhibitor and the prognostic and therapeutic value as a biomarker of gastric cancer. A total of 145 kinase inhibitors were screened to evaluate the cytotoxic or cytostatic effects in the gastric cancer cell line. Using the Alamar Blue assay, flow cytometry, quantitative polymerase chain reaction, and observation of caspase 3/7 activity and cell migration, we investigated the antiproliferative, proapoptotic, and antimigratory effects of the AURKA inhibitor. Moreover, AURKA overexpression was evaluated in the gastric cell lines and the gastric tumor tissue. Out of the 145 inhibitors, two presented the highest antiproliferative effect. Both molecules can induce apoptosis by the caspases 3/7 pathway in addition to inhibiting cancer cell migration, mainly the AURKA inhibitor. Moreover, molecular docking analysis revealed that GW779439X interacts in the active site of the AURKA enzyme with similar energy as a well‐described inhibitor. Our study identified AURKA overexpression in the gastric cancer cell line and gastric tumor tissue, revealing that its overexpression in patients with cancer is correlated with low survival. Therefore, it is feasible to suggest AURKA as a potential marker of gastric cancer, besides providing robust information for diagnosis and estimated survival of patients. AURKA can be considered a new molecular target used in the prognosis and therapy of gastric cancer.
Theory of Mind and Suicidality: A Meta-Analysis

Abstract Objective Disturbances in interpersonal functioning are prevalent in individuals with suicidality. Foundational for interpersonal functioning is theory of mind (ToM), a social-cognitive ability that allows individuals to understand the thoughts and feelings of others. Recent work has begun to investigate ToM performance in individuals with suicidality, though no review has quantitatively aggregated findings from these varied studies. The current study investigated the relations between ToM and suicidality with meta-analysis. Method We identified and meta-analyzed 15 studies that presented data for 2,895 participants (617 of whom had reported at least one suicide attempt). Results Results indicated a significant, negative relation between ToM and suicidality with a medium overall effect size (g = −.475). Moderator analyses revealed that this effect was consistent across age, sex, ToM content, and suicidal outcome. Conclusion Deficits in ToM associated with suicidality hold promise for risk-identification, treatment, and prevention work. Highlights Theory of mind (ToM) abilities are critical for effective interpersonal functioning. Meta-analytics results indicate that ToM deficits are associated with suicidality. Identifying such suicidality-related ToM deficits may inform risk-identification, treatment, and prevention work.
Ganciclovir therapeutic drug monitoring in transplant recipients

Abstract Background The use of (val)ganciclovir is complicated by toxicity, slow response to treatment and acquired resistance. Objectives To evaluate a routine therapeutic drug monitoring (TDM) programme for ganciclovir in a transplant patient population. Methods An observational study was performed in transplant recipients from June 2018 to February 2020. Dose adjustments were advised by the TDM pharmacist as part of clinical care. For prophylaxis, a trough concentration (Cmin) of 1–2 mg/L and an AUC24h of >50 mg·h/L were aimed for. For treatment, a Cmin of 2–4 mg/L and an AUC24h of 80–120 mg·h/L were aimed for. Results Ninety-five solid organ and stem cell transplant patients were enrolled. Overall, 450 serum concentrations were measured; with a median of 3 (IQR = 2–6) per patient. The median Cmin and AUC24h in the treatment and prophylaxis groups were 2.0 mg/L and 90 mg·h/L and 0.9 mg/L and 67 mg·h/L, respectively. Significant intra- and inter-patient patient variability was observed. The majority of patients with an estimated glomerular filtration rate of more than 120 mL/min/1.73 m2 and patients on continuous veno-venous haemofiltration showed underexposure. The highest Cmin and AUC24h values were associated with the increase in liver function markers and decline in WBC count as compared with baseline. Conclusions This study revealed that a standard weight and kidney function-based dosing regimen resulted in highly variable ganciclovir Cmin and under- and over-exposure were observed in patients on dialysis and in patients with increased renal function. Clearly there is a need to explore the impact of concentration-guided dose adjustments in a prospective study.
INTEGRIN-MEDIATED INTERACTIONS WITH A LAMININ-PRESENTING SUBSTRATE MODULATE BIOSYNTHESIS AND PHENOTYPIC EXPRESSION FOR CELLS OF THE HUMAN NUCLEUS PULPOSUS

With aging and pathology, cells of the nucleus pulposus (NP) de-differentiate towards a fibroblast-like phenotype, a change that contributes to degeneration of the intervertebral disc (IVD). Laminin isoforms are a component of the NP extracellular matrix during development but largely disappear in the adult NP tissue. Exposing human adult NP cells to hydrogels made from PEGylated-laminin-111 (PEGLM) has been shown to regulate NP cell behaviors and promote cells to assume a biosynthetically active state with gene/protein expression and morphology consistent with those observed in juvenile NP cells. However, the mechanism regulating this effect has remained unknown. In the present study, the integrin subunits that promote adult degenerative NP cell interactions with laminin-111 are identified by performing integrin blocking studies along with assays of intracellular signaling and cell phenotype. The findings indicate that integrin α3 is a primary regulator of cell attachment to laminin and is associated with phosphorylation of signaling molecules downstream of integrin engagement (ERK 1/2 and GSK3β). Sustained effects of blocking integrin α3 were also demonstrated including decreased expression of phenotypic markers, reduced biosynthesis, and altered cytoskeletal organization. Furthermore, blocking both integrin α3 and additional integrin subunits elicited changes in cell clustering, but did not alter the phenotype of single cells. These findings reveal that integrin-mediated interactions through integrin α3 are critical in the process by which NP cells sense and alter phenotype in response to culture upon laminin and further suggest that targeting integrin α3 has potential for reversing or slowing degenerative changes to the NP cell.
Proven COVID‐19—associated pulmonary aspergillosis in patients with severe respiratory failure

An increasing number of reports have described the COVID‐19–associated pulmonary aspergillosis (CAPA) as being a further contributing factor to mortality. Based on a recent consensus statement supported by international medical mycology societies, it has been proposed to define CAPA as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Considering current challenges associated with proven diagnoses, there is pressing need to study the epidemiology of proven CAPA.
Anti-microbial and anti-cancer activities of Mn0.5Zn0.5DyxFe2-xO4 (x ≤ 0.1) nanoparticles

Abstract Combining two or more nanoparticles is a promising approach. Previously we have reported synthesis of nanoparticles Dysprosium (Dy) substituted with manganese (Mn) zinc (Zn) by using ultrasonication method. The five different nanoparticles (NPs) Mn0.5Zn0. 5DyxFe2-xO4 (x ≤ 0.1) have been structurally and morphologically characterized but there is no report on the biological application of these NPs. In the present study, we have examined the anti-cancer, anti-bacterial, and anti-fungal activities of Mn0.5Zn0. 5DyxFe2-xO4 (x ≤ 0.1) NPs. Human colorectal carcinoma cells (HCT-116) were tested with different concentrations of NPs by using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. In addition, the impact of NPs was also examined on normal cells such as human embryonic kidney cells, HEK-293. After 48 h of treatment, Mn0.5Zn0. 5DyxFe2-xO4 NPs (x = 0.02, 0.04 and 0.06) showed no inhibitory action on cancer cell’s growth and proliferation, whereas Mn0.5Zn0. 5DyxFe2-xO4 NPs (x = 0.08 and 0.1) showed profound inhibitory action on cancer cell’s growth and proliferation. However, the treatment of Mn0.5Zn0. 5DyxFe2-xO4 NPs on the normal cells (HEK-293) did not show cytotoxic or inhibitory action on HEK-293 cells. The treatment of Mn0.5Zn0. 5DyxFe2-xO4 NPs (x ≤ 0.1) also inhibited both the bacteria (Escherichia coli ATCC35218 and Staphylococcus aureus) with lowest MIC and MBC values of 4 and 8 mg/mL and fungus (Candida albicans) with MIC and MFC values of 4 and 8 mg/mL on treatment with x = 0.08 and 0. 1.
Deoxyribonuclease 1-like 3 may be a potential prognostic biomarker associated with immune infiltration in colon cancer

Colon adenocarcinoma (COAD) is a common cancer of the digestive system. It’s high morbidity and mortality make it one of the leading causes of cancer deaths. In this study, we studied the microenvironment of colon cancer to find new diagnostic markers and immunotherapy targets for colon cancer. Tumor purity of colon cancer samples in TCGA database were obtained by ESTIMATE algorithm. Then, we analyzed the association of Immune, Stromal, and Estimate scores with tumor prognosis and clinicopathological features. By comparing the gene expression profiles between tumor and normal samples, the high and low immune score groups, 117 intersecting differentially expressed genes (DEGs) were obtained. The function, molecular pathway, and prognostic value of these 117 DEGs pointed toward the importance of deoxyribonuclease 1-like 3 (DNASE1L3). Validation results from multiple databases showed low expression of DNASE1L3 in colon cancer. A single GSEA and correlation analysis of immune cells indicated that DNASE1L3 was closely related to immunity. The low expression of DNASE1L3 in colon cancer samples was measured with qRT-PCR. The scratch and cell proliferation experiments suggested that DNASE1L3 may affect cell migration. Therefore, we concluded that DNASE1L3 might be a biomarker associated with prognosis and immune infiltration in colon cancer.
Alcohol unleashes homo economicus by inhibiting cooperation

Human behavior lies somewhere between purely self-interested homo economicus and socially-motivated homo reciprocans. The factors that cause people to choose self-interest over costly cooperation can provide insights into human nature and are essential when designing institutions and policies that are meant to influence behavior. Alcohol consumption can shed light on the inflection point between selfish and selfless because it is commonly consumed and has global effects on the brain. The present study administered alcohol or placebo (N = 128), titrated to sex and weight, to examine its effect on cooperation in a standard task in experimental economics, the public goods game (PGG). Alcohol, compared to placebo, doubled the number of free-riders who contributed nothing to the public good and reduced average PGG contributions by 32% (p = .005). This generated 64% higher average profits in the PGG for those who consumed alcohol. The degree of intoxication, measured by blood alcohol concentration, linearly reduced PGG contributions (r = -0.18, p = .05). The reduction in cooperation was traced to a deterioration in mood and an increase in physiologic stress as measured by adrenocorticotropic hormone. Our findings indicate that moderate alcohol consumption inhibits the motivation to cooperate and that homo economicus is stressed and unhappy.
Role of miRNA-324-5p-Modified Adipose-Derived Stem Cells in Post-Myocardial Infarction Repair

Background and Objectives To seek out the role of mircoRNA (miR)-324-5p-modified adipose-derived stem cells (ADSCs) in post-myocardial infarction (MI) myocardial repair. Methods and Results Rat ADSCs were cultivated and then identified by morphologic observation, osteogenesis and adipogenesis induction assays and flow cytometry. Afterwards, ADSCs were modified by miR-324-5p lentiviral vector, with ADSC proliferation and migration measured. Then, rat MI model was established, which was treated by ADSCs or miR-324-5p-modified ADSCs. Subsequently, the function of miR-324-5p-modified ADSCs in myocardial repair of MI rats was assessed through functional assays. Next, the binding relation of miR-324-5p and Toll-interacting protein (TOLLIP) was validated. Eventually, functional rescue assay of TOLLIP was performed to verify the role of TOLLIP in MI. First, rat ADSCs were harvested. Overexpressed miR-324-5p improved ADSC viability. ADSC transplantation moderately enhanced cardiac function of MI rats, reduced enzyme levels and decreased infarct size and apoptosis; while miR-324-5p-modified ADSCs could better promote post-MI repair. Mechanically, miR-324-5p targeted TOLLIP in myocardial tissues. Moreover, TOLLIP overexpression debilitated the promotive role of miR-324-5p-modified ADSCs in post-MI repair in rats. Conclusions miR-324-5p-modified ADSCs evidently strengthened post-MI myocardial repair by targeting TOLLIP in myocardial tissues.
Adaptation of a Mailed-FIT Kit and Patient Navigation Intervention to Increase Colorectal Cancer (CRC) Screening Among Spanish-Speaking Hispanic/Latino Patients

Background: Hispanic/Latino populations experience significant barriers to colorectal cancer (CRC) screening. ProCRCScreen is a multicomponent CRC screening program that can help primary care clinics improve CRC screening rates, but it needs adaptation to better meet the health care needs of Spanish-speaking Hispanic/Latino populations. Methods: We conducted four focus groups with 22 Spanish-speaking Latino patients and used inductive qualitative content analysis to identify potential program adaptations. Results: We identified lack of social support for CRC screening and confusion about completing stool-based testing as important barriers to CRC screening. Participants recommended increased specificity of the fecal immunochemical test (FIT) instructions to increase the likelihood of successful test completion, especially for first-time screening. They also endorsed patient navigation for support in completing CRC screening. Discussion: We adapted the informational materials and workflows for the ProCRCScreen program. Future research to test the adapted program is needed.
Advances in the discovery and development of melanoma drug therapies

ABSTRACT Introduction Therapeutic strategies for melanoma have evolved significantly over the last decade shifting from cytotoxic chemotherapies like dacarbazine to targeted therapies and immunotherapies including immune checkpoint inhibitors. These new drug therapies have improved overall as well as progression-free survival, lowering the mortality of this cancer for melanoma patients with advanced disease. Newer strategies incorporate combination therapies that harness synergies between mechanisms of anticancer efficacy as well as help overcome resistance issues of monotherapies, which remain a challenge. Areas covered This review looks at each class of drug therapy for melanoma and provides an overview of the preclinical mechanism of action, the clinical efficacy data, and their applications in combination therapy regimens. NCCN treatment guidelines, safety, toxicity, and immune-related adverse events are also described as well as a note on cost. Expert opinion Numerous ongoing trials continue to evaluate the role of novel therapies and combinations for this challenging disease and understanding their mechanism of action, risks, benefits, and treatment guidelines can help care providers and patients have a more comprehensive and tailored discussion of treatment options and expectations.
Platelet activation and aggregation response to dengue virus nonstructural protein 1 and domains

Platelets are now recognized as immunological sentries in the first line of defense that participate in the detection and response to pathogens. This frequently results in a decrease in the number of circulating platelets. Different mechanisms have been hypothesized to explain the thrombocytopenia in patients with severe dengue, one of them is the participation of the non‐structural protein 1 (NS1) of dengue virus (DENV), which can be secreted into circulation during DENV infection and promotes a more efficient infection.
Extravasation Injuries of the Limbs in Neonates and Children-Development of a Treatment Algorithm.

BACKGROUND Hospitalized children and neonates very often receive intravenous treatment. There has not yet been any systematic study of the incidence of extravasation injuries in this age group. In a few studies of neonates in intensive care receiving intravenous treatment, incidence figures in the range of 18-46% have been reported; 2.4-4% sustain serious complications, such as necrosis and ulceration, that can lead over the long term to contractures, deformities, and impaired limb function due to unfavorable scarring. No guidelines currently exist for the care of pediatric extravasation injuries. METHODS This review is based on pertinent publications (from 1979 to June 2020) retrieved by a selective search in PubMed, as well as on experience from the authors' own institution. RESULTS In the absence of randomized controlled trials on the care of pediatric extravasation injuries, the available evidence is limited to small-scale comparative studies and case series. Conservative, medical, or surgical treatment can be used, depending on the volume of the extravasate, the nature of the substrate, and individual patient-related factors. It should first be determined whether the extravasated substance has no primary toxic properties or is a tissue irritant or a necrosis-inducing substance (vesicant). The skin and subcutaneous tissue should be examined for injury, coloration, swelling, capillary refill time, and pulses distal to the injury. Depending on the volume of the extravasate, the substrate, and the degree of tissue damage, the injury can be treated conservatively; medically, with the administration of an antidote, hyaluronidase, or a vasodilator such as phentolamine; or surgically, with multiple puncture procedures, washouts, or liposuction. CONCLUSION As there is no clear evidence that one form of treatment is superior to any other, the treatment of pediatric extravasation injuries remains an individual decision, with the known attendant risks of off-label treatment.
Circulating miR‐19a‐3p and miR‐19b‐3p characterize the human aging process and their isomiRs associate with healthy status at extreme ages

Blood circulating microRNAs (c‐miRs) are potential biomarkers to trace aging and longevity trajectories to identify molecular targets for anti‐aging therapies. Based on a cross‐sectional study, a discovery phase was performed on 12 donors divided into four groups: young, old, healthy, and unhealthy centenarians. The identification of healthy and unhealthy phenotype was based on cognitive performance and capabilities to perform daily activities. Small RNA sequencing identified 79 differentially expressed c‐miRs when comparing young, old, healthy centenarians, and unhealthy centenarians. Two miRs, that is, miR‐19a‐3p and miR‐19b‐3p, were found increased at old age but decreased at extreme age, as confirmed by RT‐qPCR in 49 donors of validation phase. The significant decrease of those miR levels in healthy compared to unhealthy centenarians appears to be due to the presence of isomiRs, not detectable with RT‐qPCR, but only with a high‐resolution technique such as deep sequencing. Bioinformatically, three main common targets of miR‐19a/b‐3p were identified, that is, SMAD4, PTEN, and BCL2L11, converging into the FoxO signaling pathway, known to have a significant role in aging mechanisms. For the first time, this study shows the age‐related increase of plasma miR‐19a/b‐3p in old subjects but a decrease in centenarians. This decrease is more pronounced in healthy centenarians and was confirmed by the modified pattern of isomiRs comparing healthy and unhealthy centenarians. Thus, our study paves the way for functional studies using c‐miRs and isomiRs as additional parameter to track the onset of aging and age‐related diseases using new potential biomarkers.