Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial proteomics alterations in rat hearts following ischemia/reperfusion and diazoxide post-conditioning

Diazoxide post-conditioning (D-Post) has been shown to be effective in alleviating myocardial ischemia/reperfusion (I/R) injury; however, the specific mechanisms are not fully understood. In the present study, isolated rat hearts were subjected to I/R injury and D-Post. The mitochondria were extracted, and mitochondrial protein expression was detected in normal, I/R and D-Post hearts using two-dimensional electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Differentially expressed proteins were then identified using comparative proteomics. In total, five differentially expressed proteins were identified between the I/R and D-Post hearts. Compared with the I/R hearts, the expression of NADH dehydrogenase (ubiquinone) flavoprotein 1 (NDUFV1), NADH-ubiquinone oxidoreductase 75 kDa subunit (NDUFS1), 2-oxoglutarate dehydrogenase (OGDH) and ATP synthase α subunit (isoform CRA_b, gi|149029482) was increased in D-Post hearts. In addition, the expression of another isoform of ATP synthase α subunit (isoform CRA_c, gi|149029480) was decreased in the D-Post group compared with the I/R group. The expression profiles of NDUFV1, NDUFS1 and OGDH in the two groups were further validated via western blotting. The five differentially expressed proteins may be protective effectors in D-Post, as well as potential targets for the treatment of cardiac I/R injury.
Antimicrobial effect of insect chitosan on Salmonella Typhimurium, Escherichia coli O157:H7 and Listeria monocytogenes survival

The antimicrobial capability of chitosan from Tenebrio molitor as compared with chitosan from crustacean (Penaeus monodon) on different pathogenic microorganisms of concern in food safety was studied. The antimicrobial effect was tested at pH 5 and pH 6.2 and at two different initial concentrations (103 or 106 CFU/mL). Results indicated that chitosan from both sources have antimicrobial activity, although the effect depended on the microorganism considered (Salmonella Typhimurium, Listeria monocytogenes and Escherichia coli O157:H7). Our results indicated that Salmonella was the most resistant bacteria, and that chitosan from insect was less active than chitosan from crustacean, especially against Salmonella. Another important factor on antimicrobial activity was the pH of the sample. When chitosan was added to a solution with a pH of 6.2 it was more active against Listeria and Escherichia coli, than at pH 5.00. Besides, the effect of chitosan appears to decrease with the incubation time, since some increases in counts were observed on E. coli and Salmonella after the 24 and 49 hours of incubation.
Heterogeneity in Genomic Risk Assessment From Tissue Based Prognostic Signatures Used in the Biopsy Setting and the Impact of MRI Targeted Biopsy.

PURPOSE Genomic prognostic signatures are used on prostate biopsy tissue for cancer risk assessment, but tumor heterogeneity and multi-focality may be an issue. We evaluated the variability in genomic risk assessment from different biopsy cores within the prostate using three prognostic signatures (Decipher, CCP, GPS). MATERIALS AND METHODS Men in this study came from two prospective prostate cancer trials of patients undergoing mpMRI and MRI targeted biopsy with genomic profiling of positive biopsy cores. We explored the relationship between tumor grade, MRI risk, and genomic risk for each signature. We evaluated the variability in genomic risk assessment between different biopsy cores, and assessed how often MRI targeted biopsy or the current standard of care (profiling the core with the highest grade) resulted in the highest genomic risk level. RESULTS 224 positive biopsy cores from 78 men with prostate cancer were profiled. For each signature, higher biopsy grade (p <0.001) and MRI risk level (p <0.001) were associated with higher genomic scores. Genomic scores from different biopsy cores varied with risk categories changing by 21-62% depending on which core or signature was used. MRI targeted biopsy and profiling the core with the highest grade resulted in the highest genomic risk level in 72-84% and 75-87% of cases, respectively, depending on the signature used. CONCLUSIONS There is variation in genomic risk assessment from different biopsy cores regardless of the signature used. MRI directed biopsy or profiling the highest grade core resulted in the highest genomic risk level in most cases.
Impact of Feature Choice on Machine Learning Classification of Fractional Anomalous Diffusion

The growing interest in machine learning methods has raised the need for a careful study of their application to the experimental single-particle tracking data. In this paper, we present the differences in the classification of the fractional anomalous diffusion trajectories that arise from the selection of the features used in random forest and gradient boosting algorithms. Comparing two recently used sets of human-engineered attributes with a new one, which was tailor-made for the problem, we show the importance of a thoughtful choice of the features and parameters. We also analyse the influence of alterations of synthetic training data set on the classification results. The trained classifiers are tested on real trajectories of G proteins and their receptors on a plasma membrane.
Protective effect of Feijoa sellowianan fruit on testicular toxicity‐induced by cadmium chloride

The purpose of the present study was to investigate the protective potential of Feijoa fruit extract on cadmium chloride (CdCl2)‐induced testicular injury and pituitary–gonadal axis. Adult male Wistar rats were randomly divided into four groups: (a) control (normal saline, orally), (b) cadmium chloride (0.1 mg/kg, single dose, intraperitoneally), (c) Feijoa fruit extract (400 mg/kg, orally for 30 consecutive days) and (d) CdCl2 + Feijoa fruit extract. One day after receiving the last medicine, the LH, FSH, prolactin and testosterone concentration were assayed. Also, sperm parameters and tissue structure of the testis were evaluated. Administration of Feijoa fruit extract after CdCl2 injection in rats ameliorated sperm parameters such as sperm count, morphology, motility and sperm viability, increased levels of LH, FSH, prolactin and testosterone and improved testicular histology. According to the results of this study, it was shown that Feijoa can reduce the destructive side effects of CdCl2 on testicular tissue and sex hormones of the pituitary–gonadal pathway.
Re-expression of SMARCA4/BRG1 in small cell carcinoma of ovary, hypercalcemic type (SCCOHT) promotes an epithelial-like gene signature through an AP-1-dependent mechanism

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive form of ovarian cancer. SCCOHT tumors have inactivating mutations in SMARCA4 (BRG1), one of the two mutually exclusive ATPases of the SWI/SNF chromatin remodeling complex. To address the role that BRG1 loss plays in SCCOHT tumorigenesis, we performed integrative multi-omic analyses in SCCOHT cell lines +/- BRG1 reexpression. BRG1 reexpression induced a gene and protein signature similar to an epithelial cell and gained chromatin accessibility sites correlated with other epithelial originating TCGA tumors. Gained chromatin accessibility and BRG1 recruited sites were strongly enriched for transcription-factor-binding motifs of AP-1 family members. Furthermore, AP-1 motifs were enriched at the promoters of highly upregulated epithelial genes. Using a dominant-negative AP-1 cell line, we found that both AP-1 DNA-binding activity and BRG1 reexpression are necessary for the gene and protein expression of epithelial genes. Our study demonstrates that BRG1 reexpression drives an epithelial-like gene and protein signature in SCCOHT cells that depends upon by AP-1 activity.
The prevalence of problematic internet use among a sample of Egyptian adolescents and its psychiatric comorbidities

Background: Problematic internet use has been identified in the last decade as a rising problem due to growing availability and impact of Internet use through social media, mobiles, and laptops are now a must in life, adolescents are most vulnerable for the misuse and its impacts. Aim: To assess the prevalence of problematic internet use, Facebook, and gaming addiction among Egyptian adolescents and its impact. Methods: The study assessed 700 adolescents aged from 14 to 18 years, both sexes, using Young internet addiction test, Internet gaming disorder scale, the Bergen Facebook addiction scale, the MINI international neuropsychiatry interview for children and adolescents and the socioeconomic status scale. Results: A total of 584 students continued the study to the end with response rate more than 75%, the mean age was 16.1 = 1.2, 65.6% were having internet addiction, 61.3% were gaming addicts, and 92.8% Facebook addicts. Depression, dysthymia, suicide, social anxiety panic, and phobias were common comorbidities in addicted adolescents. Conclusion: This study shows that a significant percentage of adolescents are having different patterns of problematic internet use which is negatively impacting their mental health.
Modelling the variability of UK sugar beet yields under climate change and husbandry adaptations

In the future, UK summers are likely to be warmer and drier. Modelling differential water redistribution and uptake, we assessed the impact of future drier climates on sugar beet yields. Weather was generated for 1961–1990 (BASE) and predictions based on low‐ and high‐emission scenarios (LO, HI) described in the most recent global climate simulations by the Hadley Centre, UK. Distributions and variability of relative soil moisture deficit (rSMD) and yield gap (drought‐related yield loss, YGdr = 1−actual yield/potential yield), and sugar yield were calculated for different time‐lines using regional weather, soil texture and management inputs. The rSMD is estimated to exceed the senescence threshold with a probability of 75% (2050sLO) to 95% (2080sHI) compared with 65% (BASE). The potential yield loss, YGdr, is likely to increase from 17% (BASE) to 22% (2050sLO) to 35% (2080sHI). However, increasing potential growth rates (CO2 × temperature) cause average sugar yields to rise by between 1.4 and 2 t ha−1 (2050sLO and 2050sHI respectively). Yield variation (CV%) may increase from 15–18% (BASE) to 18–23% (2050s) and 19–25% (2080s). Differences are small between regions but large within regions because of soil variability. In future, sugar yields on sands (8 t ha−1) are likely to increase by little (0.5–1.5 t ha−1), but on loams yields are likely to increase from 11 to 13 t ha−1 (2050sHI) and 15 t ha−1 (2080sHI). Earlier sowing and later harvest are potential tools to compensate for drought‐related losses on sandy soils.
Shear wave elastography of the submandibular gland in healthy individuals

Objectives Shear wave elastography is a rapidly evolving new technique. The purpose of the present study was to determine the sonoelastographic features of the submandibular glands in healthy individuals. Methods We conducted a cross-sectional study of 45 healthy individuals, whose submandibular glands were studied using shear wave elastography. The stiffness of both submandibular glands was measured and its relationships with the age, sex, body mass, body mass index (BMI), and height of the participants were assessed. Results The participants had a mean age of 31.82 ± 5.53 years, a mean height of 158.30 ± 7.16 cm, a mean body mass of 57.83 ± 8.84 kg, and a mean BMI of 22.99 ± 2.72 kg/m2. The mean shear elastic modulus of the right and left submandibular glands were 18.02 kPa and 19.09 kPa, respectively. Positive correlations were found between the elasticity of the right submandibular gland and the anthropometric parameters. Conclusion The elastic modulus of the submandibular glands has been determined in healthy individuals and the data generated can serve as a reference for future studies of pathological conditions of these structures.
Views on Early Diagnosis of Alzheimer’s Disease Among Dutch Physicians: A Qualitative Interview Study

Background: Hope for future treatments to prevent or slow down dementia motivates researchers to strive for ever-earlier diagnoses of Alzheimer’s disease (AD) based on biomarkers, even before symptoms occur. But is a biomarker-based early diagnosis desirable in clinical practice? Objective: This study explores the ethical considerations that shape current clinical practice regarding early AD diagnostics and the use of biomarkers. Methods: In this qualitative study, Dutch physicians were interviewed. Topics included physicians’ views concerning early AD diagnosis in persons with no or mild cognitive impairment, physicians’ considerations regarding current and expected future practices of early AD diagnosis, the use of biomarkers, and the use of the concepts preclinical and prodromal AD. We analyzed the transcripts using directed content analysis. Results: 15 general practitioners, neurologists, and geriatricians in the Netherlands were interviewed. Most of them interpreted an early AD diagnosis with an early diagnosis of dementia. We identified six clusters of considerations sometimes in favor but most often against pursuing an early AD diagnosis in people with no or mild cognitive impairment that influence physicians’ diagnostic decision-making: preferences and characteristics of persons, test characteristics, impact on care, type of setting, disease concepts, and issues on a societal level. Conclusion: The discussion concerning an early AD diagnosis based on biomarkers which is widely held in the scientific field, has not entered clinical practice structurally. A biomarker-based early diagnosis does not fit within Dutch physicians’ views on what good care for people with no, subjective, or mild cognitive impairment should entail.
Availability of point-of-care culture and microscopy in general practice - does it lead to more appropriate use of antibiotics in patients with suspected urinary tract infection?

Abstract Background Urinary tract infection (UTI) is a common condition in general practice, and urine culture can help reduce inappropriate antibiotic prescriptions. In case of delay of the result, antibiotic treatment can be guided by one or more point-of-care (POC) tests. In Denmark, POC microscopy and POC urine culture are widely used for this purpose. Objectives To investigate if availability of POC microscopy or POC culture in general practice was associated with a more appropriate treatment decision in patients with suspected UTI while waiting for the result from the microbiological laboratory. Methods This prospective observational study was conducted in 2016 in general practice in the Copenhagen area, Denmark. Data on all patients presenting in general practice with symptoms of UTI were registered anonymously and a urine sample was sent for culture at the microbiological laboratory. The association between the availability of POC tests and the appropriateness of antibiotic prescribing was assessed with multivariable logistic regression. Results Seventy-six general practices included 1545 patients (83% female); 71% received appropriate treatment in practices with POC culture available and 65% in practices without POC culture available (p = 0.042). Having a microscope available was not associated with more appropriate treatment (70% vs. 69%, p = 0.54). Conclusion Availability of POC culture marginally increased appropriate treatment while waiting for the result from the microbiological laboratory. Practices should adopt a strategy where they either perform culture within the practice or send urine for culture at the microbiological laboratory. Trial registration number ClinicalTrials.gov NCT02698332.
Effect of combined home-based, overground robotic-assisted gait training and usual physiotherapy on clinical functional outcomes in people with chronic stroke: A randomized controlled trial

Objectives: To assess the effect of a home-based over-ground robotic-assisted gait training program using the AlterG Bionic Leg orthosis on clinical functional outcomes in people with chronic stroke. Design: Randomized controlled trial. Setting: Home. Participants: Thirty-four ambulatory chronic stroke patients who recieve usual physiotherapy. Intervention: Usual physiotherapy plus either (1)10-week over-ground robotic-assisted gait training program (n = 16), using the device for ⩾30 minutes per day, or (2) control group (n = 18), 30 minutes of physical activity per day. Measurements: The primary outcome was the Six-Minute Walk Test. Secondary outcomes included: Timed-Up-and-Go, Functional Ambulation Categories, Dynamic Gait Index and Berg Balance Scale. Physical activity and sedentary time were assessed using accelerometry. All measurements were completed at baseline, 10 and 22 weeks after baseline. Results: Significant increases in walking distance were observed for the Six-Minute Walk Test between baseline and 10 weeks for over-ground robotic-assisted gait training (135 ± 81 m vs 158 ± 93 m, respectively; P ⩽ 0.001) but not for control (122 ± 92 m vs 119 ± 84 m, respectively). Findings were similar for Functional Ambulation Categories, Dynamic Gait Index and Berg Balance Scale (all P ⩽ 0.01). For over-ground robotic-assisted gait training, there were increases in time spent stepping, number of steps taken, number of sit-to-stand transitions, and reductions in time spent sitting/supine between baseline and 10 weeks (all P < 0.05). The differences observed in all of the aforementioned outcome measures were maintained at 22 weeks, 12 weeks after completing the intervention (all P > 0.05). Conclusion: Over-ground robotic-assisted gait training combined with physiotherapy in chronic stroke patients led to significant improvements in clinical functional outcomes and physical activity compared to the control group. Improvements were maintained at 22 weeks.
Icaritin inhibits PD‐L1 expression by Targeting Protein IκB Kinase α

Icaritin, a small molecule currently being investigated in phase III clinical trials in China (NCT03236636 and NCT03236649) for treatment of advanced hepatocellular carcinoma (HCC), is a prenylflavonoid derivative obtained from the Epimedium genus. Previously, it was found that Icaritin decreased the expression of PD‐L1, but its direct molecular targets and the underlying mechanisms have not been identified. In this study, we report the identification of IKK‐α as the protein target of Icaritin by biotin‐based affinity binding assay. The further mutagenesis assay has provided evidence that C46 and C178 in IKK‐α were essential amino acids for Icaritin binding to IKK‐α, revealing the binding sites of Icaritin to IKK‐α for the first time. Functionally, Icaritin inhibited the NF‐κB signalling pathway by blocking IKK complex formation, which led to decreased nuclear translocation of NF‐κB p65, and subsequent downregulation of PD‐L1 expression in a dose–dependent manner. More importantly, PD‐L1‐positive patients exhibited longer overall survival upon Icaritin therapy. Finally, Icaritin in combination with checkpoints antibodies, such as α‐PD‐1, has demonstrated much better efficacy than any single therapy in animal models. This is the first report that anticancer effects of Icaritin are mediated, at least in part, by impairing functions of IKK‐α.
LRP1 regulates food intake and energy balance in GABAergic neurons independently of leptin action.

Low-density lipoprotein receptor-related protein 1 (LRP1) is a member of LDL receptor family that plays a key role in systemic glucose and lipid homeostasis. LRP1 also regulates energy balance in the hypothalamus by mediating leptin's anorexigenic action, although the underlying neurocircuitry involved is still unclear. Because GABAergic neurons are a major mediator of hypothalamic leptin action, we studied the role of GABAergic LRP1 in energy balance and leptin action using mice lacking LRP1 in Vgat- or AgRP-expressing neurons (Vgat-Cre; LRP1loxP/loxP or AgRP-Cre; LRP1loxP/loxP). Here we show that LRP1 deficiency in GABAergic neurons results in severe obesity in male and female mice fed a normal chow diet. This effect is most likely due to increased food intake and decreased energy expenditure and locomotor activity. Increased adiposity in GABAergic neuron-specific LRP1-deficient mice is accompanied by hyperleptinemia and hyperinsulinemia. Insulin resistance and glucose intolerance in these mice are occurred without change in body weight. Importantly, LRP1 in GABAergic neurons is not required for leptin action, as evidenced by normal leptin's anorexigenic action and leptin-induced hypothalamic Stat3 phosphorylation. In contrast, LRP1 deficiency in AgRP neurons has no effect on adiposity and caloric intake. In conclusion, our data identify GABAergic neurons as a key neurocircuitry that underpins LRP1-dependent regulation of systemic energy balance and body-weight homeostasis. We further find that the GABAergic LRP1 signaling pathway modulates food intake and energy expenditure independently of leptin signaling and AgRP neurons.
The Perfect Storm: Hidden Risk of Child Maltreatment During the Covid-19 Pandemic

The Covid-19 pandemic upended the country, with enormous economic and social shifts. Given the increased contact from families living in virtual confinement coupled with massive economic disarray, the Covid-19 pandemic may have created the ideal conditions to witness a rise in children’s experience of abuse and neglect. Yet such a rise will be difficult to calculate given the drop in official mechanisms to track its incidence. The current investigation utilized two studies conducted early in the pandemic to evaluate maltreatment risk. In the first cross-sectional study, parents (n = 405) reported increased physical and verbal conflict and neglect which were associated with their perceived stress and loneliness. In the second study, parents (n = 106) enrolled in a longitudinal study reported increased parent-child conflict, which was associated with concurrent child abuse risk, with several links to employment loss, food insecurity, and loneliness; findings also demonstrated increases in abuse risk and psychological aggression relative to pre-pandemic levels. Findings are discussed in the context of a reactive welfare system rather than a pro-active public-health oriented approach to child maltreatment, connecting with families through multiple avenues. Innovative approaches will be needed to reach children faced with maltreatment to gauge its scope and impact in the pandemic’s aftermath.