Miracle-dz/UniFAR-FTUs huggingface dataset:
Morocco as a possible source for acquisition of Rhinocladiella mackenziei

Rhinocladiella mackenziei cerebral phaeohyphomycosis is a rare severe disease that has been typically described in the Middle East. Here, we report 2 cases of R. mackenziei cerebral phaeohyphomycosis in patients from Morocco, diagnosed and treated in France, and raise a concern about the ever-going extension of the area at risk for this devastating invasive fungal infection.
Naringin and Hesperidin Counteract Diclofenac-Induced Hepatotoxicity in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities

This study is aimed at evaluating the preventive effect and at suggesting the mode of actions of naringin and hesperidin and their combination in diclofenac-induced hepatotoxicity. Male Wistar rats, intraperitoneally injected with diclofenac sodium (3 mg/kg b.wt/day), were orally treated with naringin (20 mg/kg b.wt/day) and hesperidin (20 mg/kg b.wt/day) and their combination for 4 weeks. The administrations of naringin and hesperidin to diclofenac-injected rats led to a significant decrease in the elevated serum ALT, AST, LDH, ALP, GGT, total bilirubin, TNF-α, and IL-17 levels as well as liver lipid peroxidation and liver p53 and caspase-3 mRNA expressions. In contrast, serum IL-4 level, liver GSH content, and liver GPx and SOD activities increased. In association, diclofenac-induced deleterious histological alterations including hydropic degeneration, cytoplasmic vacuolization, apoptosis, and focal hepatic necrosis of hepatocytes associated with inflammatory cells' infiltration were remarkably improved by treatments with naringin and hesperidin. In conclusion, naringin, hesperidin, and their combination, which was the most potent, counteract diclofenac-induced liver injury via antioxidant, anti-inflammatory, and antiapoptotic actions. Thus, this study recommends the use of naringin and hesperidin or their combination to resolve the side effects of drugs like diclofenac on the liver.
Primary Laparoscopic Surgery Does Not Affect the Prognosis of Early-Stage Ovarian Clear Cell Cancer

Purpose Minimally invasive surgery (MIS) is performed frequently in early-stage ovarian cancer patients, especially in ovarian clear cell carcinoma (OCCC). The aim of this study was to investigate whether primary laparoscopic surgery influences prognosis in patients with early-stage OCCC. Patients and Methods Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I OCCC were retrospectively reviewed in two hospitals between April 2010 and August 2020. Clinical data were abstracted, and patients were followed up until February 2021. Patients were divided into open surgery (laparotomy) and laparoscopy groups, and the Kaplan–Meier method was applied to compare progression-free survival (PFS) and overall survival (OS) between the groups. Statistical differences were determined by the Log rank test. Results Eighty-nine patients were included in the study; 20 (22.5%) and 69 (77.5%) patients underwent laparoscopic and open surgery, respectively. The patients’ characteristics were well-balanced except that patients in the laparoscopy group tended to have smaller tumors and lower frequency of omentectomy and lymphadenectomy compared with the open surgery group. The median follow-up duration was 42.6 and 36.5 months in the laparoscopy and open surgery groups, respectively. Nine (10.1%) patients developed recurrence, and 4 (4.5%) died of the disease; all in the open surgery group. The estimated 2-year PFS rates were 100.0% and 90.1%, and the estimated 5-year OS rates were 100.0% and 91.9% in the laparoscopy and open surgery groups, respectively. No significant survival differences were found between the groups. Conclusion Survival was not compromised when primary laparoscopic surgery was performed in early-stage OCCC patients. A well-designed randomized controlled trial is warranted.
SEC23A Inhibit Melanoma Metastatic through Secretory PF4 Cooperation with SPARC to Inhibit MAPK Signaling Pathway

Metastasis of melanoma to the distant organs is a multistep process in which the tumor microenvironment (TME) may play an important role. However, the relationship between metastatic progression and TME is intricate. In the present study, using melanoma derivative cell lines OL (oligometastatic) and POL (polymetastatic) that differ in their metastatic colonization capability, we have elucidated a new mechanism involving “SEC23A-PF4-MAPK/ERK axis” in which PF4 transported by COPII hinders metastasis through inhibition of MAPK/ERK signaling pathway. Furthermore, SPARC can act cooperatively to enhance the inhibition of Pf4 on ERK phosphorylation and melanoma cell metastasis. Our findings show the possibility of targeting cancer cell secretome for therapeutic development.
Changes in leisure-time physical activity during the adult life span and relations to cardiovascular risk factors—Results from multiple Swedish studies

Objective To evaluate how self-reported leisure-time physical activity (PA) changes during the adult life span, and to study how PA is related to cardiovascular risk factors using longitudinal studies. Methods Several Swedish population-based longitudinal studies were used in the present study (PIVUS, ULSAM, SHE, and SHM, ranging from hundreds to 30,000 participants) to represent information across the adult life span in both sexes. Also, two cross-sectional studies were used as comparison (EpiHealth, LifeGene). PA was assessed by questionnaires on a four or five-level scale. Results Taking results from several samples into account, an increase in PA from middle-age up to 70 years was found in males, but not in females. Following age 70, a decline in PA was seen. Young adults reported both a higher proportion of sedentary behavior and a higher proportion high PA than the elderly. Females generally reported a lower PA at all ages. PA was mainly associated with serum triglycerides and HDL-cholesterol, but also weaker relationships with fasting glucose, blood pressure and BMI were found. These relationships were generally less strong in elderly subjects. Conclusion Using data from multiple longitudinal samples the development of PA over the adult life span could be described in detail and the relationships between PA and cardiovascular risk factors were portrayed. In general, a higher or increased physical activity over time was associated with a more beneficial cardiovascular risk factor profile, especially lipid levels.
Cardiac Ultrasound under Speckle Tracking Technology Based Analysis of Efficacy of Respiratory Rehabilitation on Chronic Obstructive Pulmonary Disease

The study shined spotlight on the effect of respiratory rehabilitation training on chronic obstructive pulmonary disease (COPD), which was evaluated using speckle ultrasound algorithm-based cardiac ultrasound. Then, 90 patients with stable COPD, who were admitted to the hospital from January 2018 to December 2019, were randomly rolled into three groups, namely, the fast inhalation and slow exhalation (A) group, abdominal breathing (B) group, and control (C) group. For group A, on the basis of the conventional treatment, the method of rapid inhalation and slow exhalation was adopted. The group B (n = 30) adopted the abdominal breathing method besides the conventional treatment. In addition, the group C (n = 30) received only conventional treatment. Finally, the efficacy and parameters of the three treatment methods were compared. The echocardiographic parameters and echocardiographic images were calculated and processed by the speckle tracking method. Three kinds of operators were used to track the myocardial spots successfully, and the corresponding points in the image were obtained and calculated. It was found that there was no significant difference in the degree of dyspnea, exercise endurance, lung function, respiratory muscle function, and quality of life (QOL) before treatment (P > 0.05). After treatment, in contrast with group C, the previously mentioned indicators in groups A and B were obviously better (P < 0.05). Further, both the echocardiographic images and echocardiographic parameters of groups A and B were obviously improved, and there was no obvious difference between groups A and B. Hence, some degree of respiratory rehabilitation was very effective in the diagnosis of patients with chronic pulmonary obstruction. In conclusion, the speckle tracking algorithm-based cardiac ultrasound improves the image quality. At the same time, respiratory rehabilitation training is effective on COPD and worthy of clinical promotion.
Short-term transport stress and supplementation alter immune function in aged horses

Long-distance transport is associated with stress-related changes in equine immune function, and shipping-associated illnesses are often reported. Horses are frequently transported short distances, yet the effects of short-term transport on immune function remain largely unknown. Twelve horses, aged 15–30 yr, were assigned to either the control (n = 6) or treatment (n = 6) groups; treatment horses received a daily antioxidant supplement 3 weeks before and after transport. All horses were transported for approximately 1.5–2 hr on Day 0. Blood was collected via jugular venipuncture at 15-min pre- and post-transport and on Days –21, 1, 3, 7, 14, and 21. Body temperature, heart rate, body weight, total cortisol, and gene expression of IFNγ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12α, IL-17α, SAA1, and TNFα in whole blood were measured. Peripheral blood mononuclear cells were isolated, stimulated with PMA/ionomycin, and stained for IFNγ and TNFα before analysis via flow cytometry. Statistical analyses were performed with significance set at P < 0.05 (SAS 9.4). Transport and supplementation did not appear to affect body weight, heart rate, IL-4, IL-8, IL-12α, IL-17α, change (Δ) in the % and mean fluorescence intensity (MFI) of IFNγ+ lymphocytes after stimulation, or Δ in the % and MFI of TNFα+ lymphocytes after stimulation. Supplementation decreased IL-1β and SAA1 expression. Transport increased total cortisol concentration, body temperature, and IL-2, IL-6, and IL-10 expression but decreased IL-1β, TNFα, and IFNγ expression. Short-term transportation affected physiological, endocrine, and immune responses; supplementation may ameliorate inflammation in aged horses. Immune responses were most altered at 15-min post-transport and typically recovered by Day 1, suggesting that horses may be vulnerable to disease during and almost immediately after short-term transport.
Whose Product Is Essential for Bacterial Viability above 33°C in Rich Media

We have identified and studied the htrB gene of Escherichia coli. Insertional inactivation of the htrB gene leads to bacterial death at temperatures above 33°C. The mutant bacterial phenotype at nonpermissive temperatures includes an arrest of cell division followed by the formation of bulges or filaments. The htrB + gene has been cloned by complementation and shown to reside at 23.4 min on the E. coli genetic map, the relative order of the neighboring loci being mboA-htrB-pyrC. The htrB gene is transcribed in a counterclockwise fashion, relative to the E. coli genetic map, and its product has been identified as a membrane-associated protein of 35,000 Da. Growth experiments in minimal media indicate that the HtrB function becomes dispensable at low growth rates.
Influence of Contingent and Noncontingent Drug Histories on the Development of High Levels of MDPV Self-Administration

A subset of rats that self-administer 3,4-methylenedioxypyrovalerone (MDPV) develop unusually high levels of drug taking. A history of responding maintained by cocaine, but not food, prevents the development of this high-responder phenotype; however, it is unclear how histories of noncontingent cocaine exposure or self-administering drugs from other pharmacological classes would affect its development. In the current studies, 5 groups of male Sprague-Dawley rats were used to determine whether histories of responding maintained by drugs from different pharmacological classes (e.g., MDPV, cocaine, fentanyl, nicotine, or ketamine) would differentially impact the development of the high-responder phenotype when MDPV was available for self-administration. Two additional groups were used to determine whether noncontingent exposure to cocaine would prevent the development of the high-responder phenotype when MDPV was available for self-administration, and whether noncontingent exposure to MDPV would facilitate the development of the high-responder phenotype when cocaine was available for self-administration. Consistent with previous reports, a history of response-contingent cocaine, and to a lesser extent noncontingent cocaine, prevented the MDPV high-responder phenotype; however, when responding was initially maintained by fentanyl, nicotine, or ketamine, the MDPV high-responder phenotype developed in ∼45% of rats. By manipulating behavioral and pharmacological histories prior to evaluating MDPV self-administration, the current studies provide additional evidence that a history of response-contingent (or noncontingent) cocaine can prevent the transition from well regulated to aberrant drug-taking when responding is maintained by MDPV. Although the mechanism(s) that underlies this novel high-responder phenotype are unknown, elucidation may provide insight into individual differences relating to substance use disorder. SIGNIFICANCE STATEMENT A subset of outbred Sprague-Dawley rats self-administer high levels of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV). Understanding the behavioral and/or pharmacological factors that can prevent the development of dysregulated MDPV self-administration may provide insight into individual differences in vulnerability to develop a substance use disorder.
How Compassionate Abilities Influence the Experience of Loneliness and Quality of Life of People with and without Chronic Physical Disease?

Abstract The current study aimed to test whether individuals with and without a chronic physical disease differ in levels of compassionate abilities, loneliness and quality of life (QoL); and to examine whether loneliness mediated the impact of self-compassion and of receiving compassion from others in physical, psychological, and social QoL. In this cross-sectional study, individuals with (n = 278) and without (n = 455) physical chronic disease were recruited through an online self-report protocol. The Compassionate Attributes and Engagement Scale, the UCLA Loneliness Scale, and the World Health Organization’s QoL-BREF were used. Individuals with a chronic physical disease diagnosis reported lower compassionate abilities and QoL, as well as higher levels of loneliness, when compared to participants without a diagnosis. For both samples, compassionate abilities were negatively linked to loneliness, and positively linked to QoL. Path analysis results indicated that compassionate abilities have a direct effect on loneliness, which explains individuals’ perceived QoL. Results highlight the crucial role of self-compassion skills and the ability to perceive others as compassionate, in loneliness and QoL, both in individuals with and without a chronic physical disease. These findings seem to have important research and clinical implications.
Repurposing of tamoxifen ameliorates CLN3 and CLN7 disease phenotype

Batten diseases (BDs) are a group of lysosomal storage disorders characterized by seizure, visual loss, and cognitive and motor deterioration. We discovered increased levels of globotriaosylceramide (Gb3) in cellular and murine models of CLN3 and CLN7 diseases and used fluorescent‐conjugated bacterial toxins to label Gb3 to develop a cell‐based high content imaging (HCI) screening assay for the repurposing of FDA‐approved compounds able to reduce this accumulation within BD cells. We found that tamoxifen reduced the lysosomal accumulation of Gb3 in CLN3 and CLN7 cell models, including neuronal progenitor cells (NPCs) from CLN7 patient‐derived induced pluripotent stem cells (iPSC). Here, tamoxifen exerts its action through a mechanism that involves activation of the transcription factor EB (TFEB), a master gene of lysosomal function and autophagy. In vivo administration of tamoxifen to the CLN7Δex2 mouse model reduced the accumulation of Gb3 and SCMAS, decreased neuroinflammation, and improved motor coordination. These data strongly suggest that tamoxifen may be a suitable drug to treat some types of Batten disease.
Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review

Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.
Systemic thrombolysis in ischaemic stroke patients with COVID‐19

Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is the core medical therapy of acute ischaemic stroke (AIS). COVID‐19 infection negatively modifies acute stroke procedures and, due to its pro‐coagulative effect, may potentially impact on IVT outcome. Thus, short‐term efficacy and safety of IVT were compared in patients with and without evidence of SARS‐CoV‐2.
Inhibition of NOD1 Attenuates Neonatal Hypoxia-Ischemia Induced Long-Term Cognitive Impairments in Mice Through Modulation of Autophagy-Related Proteins

Background Autophagy is implicated in neonatal hypoxia-ischemia (HI) induced cognitive impairment. The nucleotide-oligomerizing domain-1 (NOD1), a protein involved in inflammatory responses, has been shown to activate autophagy to promote progression of other diseases. We aimed to investigate whether and how NOD1 is involved in HI-induced brain injury using an HI mouse model. Methods We induced HI in neonatal mice and examined levels of NOD1 and genes associated with autophagy. We then inhibited NOD1 by intracerebroventricular injection of si-NOD1 following HI induction and tested the effects on autophagy, inflammatory responses and long-term behavioral outcomes through Morris water maze and open field tests. Results We found that HI induction significantly elevated mRNA levels of NOD1 (3.54 folds change) and autophagy-related genes including Atg5 (3.89 folds change) and Beclin-1 (3.34 folds change). NOD1 inhibition following HI induction suppressed autophagy signaling as well as HI induced proinflammatory cytokine production. Importantly, NOD1 inhibition after HI improved long-term cognitive function, without impacting exploratory and locomotor activities. Conclusion We show here that NOD1 is involved in the pathogenesis of HI-induced brain injury through modulation of autophagy-related proteins and inflammatory responses. Our findings suggest that NOD1 may be a potent target for developing therapeutic strategies for treating HI-induced brain injury.
Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.
Acute hepatic porphyria and maternal health: Clinical and biochemical follow‐up of 44 pregnancies

Pregnancy in women with acute hepatic porphyria (AHP) has historically been associated with significant morbidity. Clinical outcomes have been the focus of previous reports on porphyria and maternal health, with little data available on the levels of heme precursors during pregnancy. We present the results of a follow‐up program for women with AHP in the Swedish cohort who were pregnant between 2001 and 2020.
Short-Term Outcomes following “Switching” to Monthly Ranibizumab in Neovascular Age-Related Macular Degeneration Showing Insufficient Response to Bimonthly Aflibercept

Results CRT and logMAR VA were 349.62 ± 223.51 μm and 0.50 ± 0.23 at the baseline and 274.69 ± 148.77 μm and 0.46 ± 0.24, 311.54 ± 192.90 μm and 0.45 ± 0.20 at 1 month after the first and third ranibizumab injections, respectively. The CRT decrease during three ranibizumab injections was statistically significant (38.08 ± 69.52 μm, p=0.033). Change in VA was not statistically significant. The percentage of eyes with SRF was 100% at baseline and 53.8%, 76.9%, and 69.2% one month after each ranibizumab injections. The percentage of eyes with IRF was 38.5% at baseline and 23.1%, 23.1%, and 15.4%, respectively, after switching. Conclusion Switching to monthly ranibizumab in nAMD showing an insufficient response to bimonthly aflibercept led to immediate anatomical improvement. It can be considered in countries where the healthcare insurance system limits the minimum injection interval of aflibercept.