Miracle-dz/UniFAR-FTUs huggingface dataset:
Characteristics of Internet Use amongst Italian University Students.

BACKGROUND Problematic Internet use (PIU), that may be defined as the inability to control one's use of Internet with negative consequences in daily life, is an emerging problem involving primarily, but not only young generations. Different studies have shown that students are particularly vulnerable to PIU. Given the paucity of information on PIU in our country, the aim of this paper was at investigating the characteristics of PIU amongst Italian University students. SUBJECTS AND METHODS A self-assessment questionnaire, referred by the acronym QUNT ("Questionario sull'Utilizzo delle Nuove Tecnologie"), composed by 101 items grouped together to identify a series of factors, was developed and sent through e-mail invitation to several students from three Italian Universities. RESULTS The returned questionnaires were 3324, out of a total of 51,304 sent, with no difference between the two sexes. On the contrary, the distribution of the QUNT factors was different in the two sexes, in people living alone and in overweight subjects. Men resulted to be more involved in online recreational activities, whereas women seemed more attracted to instant messaging and generally to social networks. PIU was significantly more present in men than women. The comparisons of QUNT factor scores in the four BMI categories showed that the greater the BMI the greater the score of some factors. CONCLUSIONS The findings of the present study indicate that the use of Internet through new technologies may exceed its real utility amongst Italian university student, with some sex-related differences. Men seem more prone to use Internet for passing time and women for social relationships. Men are also at risk of developing PIU. Again, Internet use might be a basic vulnerability factor of increasing weight gain and obesity amongst young people.
Concordance between Tumor and Germline BRCA Status in High-Grade Ovarian Carcinoma Patients in the Phase III PAOLA-1/ENGOT-ov25 Trial.

BACKGROUND PAOLA1 is a phase III study assessing olaparib maintenance therapy in advanced high-grade ovarian carcinoma patients responding to first-line platinum-taxane-based chemotherapy plus bevacizumab as standard of care. Randomization was stratified by treatment outcome and tumor BRCA1/2 status (tBRCA) at screening. METHODS tBRCA was tested on FFPE tumor blocks on 5 French platforms using 2 Next-Generation Sequencing methods based either on hybrid capture or amplicon technology. One of the exploratory objectives was to assess the concordance between germline (gBRCA) and tBRCA testing in French patients. gBRCA testing was performed on blood samples on the same platforms. RESULTS From May 2015 to July 2017, tBRCA tests were performed for 1,176 screened patients. Only 52 (4.4%) tumor samples were non-contributive. The median interval between reception of the tumor sample and availability of the tBRCA status result was 37 days (range =8-260). A pathogenic variant (PV) was reported in 27.1% tumor samples (319 of 1,176 screened patients). tBRCA and gBRCA testing were both performed for 451 French patients with negative results for both tests in 306 patients (67.8%) and positive results for both tests in 85 patients (18.8%). Only one large genomic rearrangement of BRCA1 was detected, exclusively in the blood sample. Interestingly, tBRCA testing revealed 6.4% of PV (29 of 451) not detected by gBRCA testing. CONCLUSIONS tBRCA testing is an appropriate tool with an acceptable turnaround time for clinical practice and a low failure rate, ensuring reliable identification of patients likely to benefit from PARPi therapy.
Increased virulence of Puccinia coronata f. sp.avenae populations through allele frequency changes at multiple putative Avr loci

Pathogen populations are expected to evolve virulence traits in response to resistance deployed in agricultural settings. However, few temporal datasets have been available to characterize this process at the population level. Here, we examined two temporally separated populations of Puccinia coronata f. sp. avenae (Pca), which causes crown rust disease in oat (Avena sativa) sampled from 1990 to 2015. We show that a substantial increase in virulence occurred from 1990 to 2015 and this was associated with a genetic differentiation between populations detected by genome-wide sequencing. We found strong evidence for genetic recombination in these populations, showing the importance of the alternate host in generating genotypic variation through sexual reproduction. However, asexual expansion of some clonal lineages was also observed within years. Genome-wide association analysis identified seven Avr loci associated with virulence towards fifteen Pc resistance genes in oat and suggests that some groups of Pc genes recognize the same pathogen effectors. The temporal shift in virulence patterns in the Pca populations between 1990 and 2015 is associated with changes in allele frequency in these genomic regions. Nucleotide diversity patterns at a single Avr locus corresponding to Pc38, Pc39, Pc55, Pc63, Pc70, and Pc71 showed evidence of a selective sweep associated with the shift to virulence towards these resistance genes in all 2015 collected isolates.
Stress and Anxiety among Healthcare Workers Associated with COVID-19 Pandemic in Russia.

BACKGROUND Mental health of medical workers treating patients with COVID-19 is an issue of increasing concern worldwide. The available data on stress and anxiety symptoms among healthcare workers during the COVID-19 are relatively limited and have not been evaluated in Russia yet. SUBJECTS AND METHODS The cross-sectional anonymous survey included 1,090 healthcare workers. Stress and anxiety symptoms were assessed using Stress and Anxiety to Viral Epidemics - 9 (SAVE-9) and Generalized Anxiety Disorder - 7 (GAD-7) scales. Logistic regression, Kaiser-Meyer-Olkin two component factor model, Cronbach's alpha and ROC-analysis were performed to determine the influence of different variables, internal structure and consistency, sensitivity and specificity of SAVE-9 compared with GAD-7. RESULTS The median scores on the GAD-7 and SAVE-9 were 5 and 14, respectively. 535 (49.1%) respondents had moderate and 239 (21.9%) had severe anxiety according to SAVE-9. 134 participants (12.3%) had severe anxiety, 144 (13.2%) had moderate according to GAD-7. The component model revealed two-factor structure of SAVE-9: "anxiety and somatic concern" and "social stress". Female gender (OR - 0.98, p=0.04) and younger age (OR - 0.65, p=0.04) were associated with higher level of anxiety according to regression model. The total score of SAVE-9 with a high degree of confidence predicted the GAD-7 value in comparative ROC analysis. CONCLUSIONS Healthcare workers in Russia reported high rates of stress and anxiety. The Russian version of the SAVE-9 displayed a good ratio of sensitivity to specificity compared with GAD-7 and can be recommended as a screening instrument for detection of stress and anxiety in healthcare workers.
Mental Health of Psychiatrists and Physicians of Other Specialties in Early COVID-19 Pandemic: Risk ind Protective Factors.

BACKGROUND Many research has indicated that, during the COVID-19 pandemic, health care workers are under greatly increased pressure and at increased risk for the development of mental health problems. Furthermore, previous research has indicated that psychiatrists are exposed to a number of unique stressors that may increase their risk for poor mental health. The aims of the present study were to assess the level of COVID-19 related concerns, psychological distress and life satisfaction among psychiatrists and other physicians during the first period of the pandemic and to examine whether individual differences in COVID-19 concerns, psychological flexibility, psychological resilience and coping behaviors account for differences in mental health indicators. SUBJECTS AND METHODS The sample consisted of N=725 physicians, among whom 22.8% were psychiatrists. This study was conducted online during the first lockdown in Croatia and collected data regarding COVID-19 related concerns, coping behaviors and mental health indicators (Psychological Distress and Life Satisfaction). RESULTS Physicians of other specialties had higher scores on a measure of COVID-19 anxiety than psychiatrists (p=0.012). In addition, a number of differences in coping behaviors are evident. Specifically, psychiatrists were less likely than physicians of other specializations to believe that being informed about COVID-19 is an effective coping strategy (p=0.013), but more prone to using sedatives and drugs as a coping strategy (p=0.002; p=0.037). CONCLUSIONS Psychiatrists are at special risk for substance abuse. Younger age, psychological inflexibility, low resilience and greater COVID-19 concerns might act as specific risk factors for distress. Our findings highlight the need for promoting a healthy lifestyle and psychological flexibility as universal protective factors.
Anti‐cN1A antibodies do not correlate with specific clinical, electromyographic, or pathological findings in sporadic inclusion body myositis

Anti‐cytosolic 5′‐nucleotidase 1A (cN1A) antibodies are commonly detected in patients with sporadic inclusion body myositis (sIBM). However, their pathogenic role has not been established. Moreover, efforts toward identifying sIBM distinct clinicopathologic characteristics associated with these antibodies have yielded conflicting results.
Acute gastroenteritis due to Blastocystis hominis in an adolescent boy

Acute gastroenteritis with persistent vomiting, high degree fever and blood streaking stools often suggests bacterial aetiology in children. Authors report a 13-year-old boy presenting with acute watery diarrhoea with persistent vomiting, fever of 103°F, abdominal cramps and blood streaking stools who failed to show any response to parenteral third-generation cephalosporin for 72 hours. The stool examination revealed numerous cystic and amoeboid forms of Blastocystis hominis. Metronidazole was started and the boy promptly responded within 24 hours. There was no recurrence of symptoms then onwards. The case highlights the crucial stool examination in case of acute diarrhoeal disease for rare aetiology.
Clinical presentation and molecular characterization of a novel patient with variant POC1A‐related syndrome

Biallelic pathogenic variants in POC1A result in SOFT (Short‐stature, Onychodysplasia, Facial‐dysmorphism, and hypoTrichosis) and variant POC1A‐related (vPOC1A) syndromes. The latter, nowadays described in only two unrelated subjects, is associated with a restricted spectrum of variants falling in exon 10, which is naturally skipped in a specific POC1A mRNA. The synthesis of an amount of a POC1A isoform from this transcript in individuals with vPOC1A syndrome has been believed as the likely explanation for such a genotype–phenotype correlation. Here, we illustrate the clinical and molecular findings in a woman who resulted to be compound heterozygous for a recurrent frameshift variant in exon 10 and a novel variant in exon 9 of POC1A. Phenotypic characteristics of this woman included severe hyperinsulinemic dyslipidemia, acanthosis nigricans, moderate growth restriction, and dysmorphisms. These manifestations overlap the clinical features of the two previously published individuals with vPOC1A syndrome. RT‐PCR analysis on peripheral blood and subsequent sequencing of the obtained amplicons demonstrated a variety of POC1A alternative transcripts that resulted to be expressed in the proband, in the healthy mother, and in controls. We illustrate the possible consequences of the two POC1A identified variants in an attempt to explain pleiotropy in vPOC1A syndrome.
Influence of Window Function on Characterization of Materials in Terahertz Spectroscopy

ABSTRACT Terahertz spectroscopy is becoming a potential tool for characterizing various materials including biomaterial specimens, liquids, and semiconductors. Accuracy of the sample information is important for analysis. In this article, the influences of type and position of window functions on accuracy of extracting sample information are studied. Experimental results show that an appropriate type and position of window functions significantly improve the accuracy of the extracted sample information.
Sensitivity and specificity of increased pulse pressure as a diagnostic test for K/DOQI stage III-b CKD.

Background Increased pulse pressure (IPP) is associated with an estimated glomerular filtration ≤ 60/mL/min/1.73 m2; thus, it can be useful as a diagnostic test to identify people with K/DOQI stage III-b chronic kidney disease (CKD). Objective To determine the usefulness of IPP as a diagnostic test for K/DOQI stage III-b CKD. Method Diagnostic test study that included adult patients without comorbidities, registered in the Health Workers Cohort. The CKD-EPI formula was used to calculate glomerular filtration. Pulse pressure was determined by subtracting diastolic from systolic blood pressure. Sensitivity, specificity, positive predictive value, negative predictive value and prevalence were calculated using standard formulas. A ROC curve was generated to determine the area under the curve. Results A total of 6,215 patients were included. An IPP ≥ 50 mmHg was observed to have a sensitivity of 74 %, specificity of 70 %, positive predictive value of 1 %, negative predictive value of 100 % and a prevalence of 1 %. The inflection point in the ROC curve to identify K/DOQI III-b CKD was 0.71. Conclusion An IPP ≥ 50 mmHg is useful as a diagnostic test to identify people with K/DOQI stage III-b CKD.
Measuring Peripheral Chemoreflex Hypersensitivity in Heart Failure

Heart failure with reduced ejection fraction (HFrEF) induces chronic sympathetic activation. This disturbance is a consequence of both compensatory reflex disinhibition in response to lower cardiac output and patient-specific activation of one or more excitatory stimuli. The result is the net adrenergic output that exceeds homeostatic need, which compromises cardiac, renal, and vascular function and foreshortens lifespan. One such sympatho-excitatory mechanism, evident in ~40–45% of those with HFrEF, is the augmentation of carotid (peripheral) chemoreflex ventilatory and sympathetic responsiveness to reductions in arterial oxygen tension and acidosis. Recognition of the contribution of increased chemoreflex gain to the pathophysiology of HFrEF and to patients’ prognosis has focused attention on targeting the carotid body to attenuate sympathetic drive, alleviate heart failure symptoms, and prolong life. The current challenge is to identify those patients most likely to benefit from such interventions. Two assumptions underlying contemporary test protocols are that the ventilatory response to acute hypoxic exposure quantifies accurately peripheral chemoreflex sensitivity and that the unmeasured sympathetic response mirrors the determined ventilatory response. This Perspective questions both assumptions, illustrates the limitations of conventional transient hypoxic tests for assessing peripheral chemoreflex sensitivity and demonstrates how a modified rebreathing test capable of comprehensively quantifying both the ventilatory and sympathoneural efferent responses to peripheral chemoreflex perturbation, including their sensitivities and recruitment thresholds, can better identify individuals most likely to benefit from carotid body intervention.
Dendron‐Based Micelles for Topical Delivery of Endoxifen: A Potential Chemo‐Preventive Medicine for Breast Cancer

Endoxifen (EDX) is an active metabolite of tamoxifen that has been proven effective in the prevention and treatment of estrogen‐positive breast cancer; however, oral administration of tamoxifen often causes severe side effects. Here, the topical delivery of EDX is explored using polymeric micelles to achieve localized drug delivery with potentially minimal side effects. EDX is encapsulated into dendron micelles (DM) with various surface groups (‐NH2, ‐COOH, or ‐Ac) and into cationic liposomes as a control. End‐group modification significantly affects the drug loading, where the DM‐COOH micelles allow the most efficient encapsulation. Furthermore, unlike the burst release from the liposomes, all DMs show sustained release of EDX over 6 days. Each formulation is evaluated for its potential to deliver EDX across the skin layers. DMs substantially enhance the permeation of EDX through both mouse (up to 20‐fold) and human (up to 4‐fold) skin samples relative to ethanol, a chemical penetration enhancer. Franz diffusion cell experiments reveal that DM‐COOH induces the highest flux of EDX among all groups. The enhanced drug loading, controlled release profiles, and enhanced skin permeation all demonstrate that DMs are a useful platform for the topical delivery of EDX, offering a potential alternative administration route for chemoprevention.
Macrophage LC3-associated phagocytosis is an immune defense against Streptococcus pneumoniae that diminishes with host aging

Significance The elderly exhibit susceptibility to many infectious agents, including S. pneumoniae. A robust acute inflammatory response to S. pneumoniae is associated with severe disease. S. pneumoniae triggers canonical autophagy in nonprofessional phagocytes, but its role in macrophages is largely unexplored. We found that BMDMs utilize LAP, rather than canonical autophagy, to both eliminate S. pneumoniae and modulate inflammation. Notably, compared to young BMDMs, aged BMDMs were deficient in LAP, resulting in compromised bacterial killing and enhanced proinflammatory responses. Thus, S. pneumoniae triggers LAP in BMDMs, a process that controls both microbial numbers and tissue-damaging inflammation. Importantly, LAP diminishes with age and may contribute to the observed susceptibility of the elderly to many infectious diseases. Streptococcus pneumoniae is a leading cause of pneumonia and invasive disease, particularly, in the elderly. S. pneumoniae lung infection of aged mice is associated with high bacterial burdens and detrimental inflammatory responses. Macrophages can clear microorganisms and modulate inflammation through two distinct lysosomal trafficking pathways that involve 1A/1B-light chain 3 (LC3)-marked organelles, canonical autophagy, and LC3-associated phagocytosis (LAP). The S. pneumoniae pore-forming toxin pneumolysin (PLY) triggers an autophagic response in nonphagocytic cells, but the role of LAP in macrophage defense against S. pneumoniae or in age-related susceptibility to infection is unexplored. We found that infection of murine bone-marrow-derived macrophages (BMDMs) by PLY-producing S. pneumoniae triggered Atg5- and Atg7-dependent recruitment of LC3 to S. pneumoniae-containing vesicles. The association of LC3 with S. pneumoniae-containing phagosomes required components specific for LAP, such as Rubicon and the NADPH oxidase, but not factors, such as Ulk1, FIP200, or Atg14, required specifically for canonical autophagy. In addition, S. pneumoniae was sequestered within single-membrane compartments indicative of LAP. Importantly, compared to BMDMs from young (2-mo-old) mice, BMDMs from aged (20- to 22-mo-old) mice infected with S. pneumoniae were not only deficient in LAP and bacterial killing, but also produced higher levels of proinflammatory cytokines. Inhibition of LAP enhanced S. pneumoniae survival and cytokine responses in BMDMs from young but not aged mice. Thus, LAP is an important innate immune defense employed by BMDMs to control S. pneumoniae infection and concomitant inflammation, one that diminishes with age and may contribute to age-related susceptibility to this important pathogen.
Hidden proteome of synaptic vesicles in the mammalian brain

Significance Mammalian central synapses of diverse functions contribute to highly complex brain organization, but the molecular basis of synaptic diversity remains open. This is because current synapse proteomics are restricted to the “average” composition of abundant synaptic proteins. Here, we demonstrate a subcellular proteomic workflow that can identify and quantify the deep proteome of synaptic vesicles, including previously missing proteins present in a small percentage of central synapses. This synaptic vesicle proteome revealed many proteins of physiological and pathological relevance, particularly in the low-abundance range, thus providing a resource for future investigations on diversified synaptic functions and neuronal dysfunctions. Current proteomic studies clarified canonical synaptic proteins that are common to many types of synapses. However, proteins of diversified functions in a subset of synapses are largely hidden because of their low abundance or structural similarities to abundant proteins. To overcome this limitation, we have developed an “ultra-definition” (UD) subcellular proteomic workflow. Using purified synaptic vesicle (SV) fraction from rat brain, we identified 1,466 proteins, three times more than reported previously. This refined proteome includes all canonical SV proteins, as well as numerous proteins of low abundance, many of which were hitherto undetected. Comparison of UD quantifications between SV and synaptosomal fractions has enabled us to distinguish SV-resident proteins from potential SV-visitor proteins. We found 134 SV residents, of which 86 are present in an average copy number per SV of less than one, including vesicular transporters of nonubiquitous neurotransmitters in the brain. We provide a fully annotated resource of all categorized SV-resident and potential SV-visitor proteins, which can be utilized to drive novel functional studies, as we characterized here Aak1 as a regulator of synaptic transmission. Moreover, proteins in the SV fraction are associated with more than 200 distinct brain diseases. Remarkably, a majority of these proteins was found in the low-abundance proteome range, highlighting its pathological significance. Our deep SV proteome will provide a fundamental resource for a variety of future investigations on the function of synapses in health and disease.
Oral Administration of Salmon Cartilage Proteoglycan Attenuates Osteoarthritis in a Monosodium Iodoacetate-Induced Rat Model

Proteoglycan (PG) is a type of glycoprotein which forms an extracellular matrix with collagen and hyaluronic acid to maintain articular cartilage, synovial membrane, and synovial fluid. This study aimed to evaluate the antiosteoarthritis effects of salmon nasal cartilage-derived PG in alleviating knee osteoarthritis in an osteoarthritis rat model. Knee osteoarthritis was induced in rats by intra-articular injection of monosodium iodoacetate (MIA), 3 mg/knee, to the right knee. Animals were then administered either diclofenac (3 mg/kg body weight [b.w]/day) or proteoglycan F (PGF; 40 mg/kg and 120 mg/kg b.w/day) by oral gavage for 6 consecutive weeks. Knee diameters were measured throughout the experimental period; serum interleukin-1β and tumor necrosis factor-alpha (TNF-α) levels, and histological analysis of the ligament were carried out at the end of the experiment. Salmon cartilage PG considerably alleviated the osteoarthritis symptoms in the model and lowered the serum concentrations of interleukin-1β and TNF-α. Diclofenac 3 mg/kg/day and PGF at doses of 40 mg/kg/day and 120 mg/kg/day also improved articular cartilage structure on further histological studies. This study demonstrated the in vivo effect of salmon cartilage PG in attenuating symptoms in an MIA-induced rat model, including reduction of inflammatory markers and histological improvement of cartilage tissue.