Miracle-dz/UniFAR-FTUs huggingface dataset:
Covariation between spontaneous neural activity in the insula and affective temperaments is related to sleep disturbance in individuals with major depressive disorder

Abstract Background Affective temperaments have been considered antecedents of major depressive disorder (MDD). However, little is known about how the covariation between alterations in brain activity and distinct affective temperaments work collaboratively to contribute to MDD. Here, we focus on the insular cortex, a critical hub for the integration of subjective feelings, emotions, and motivations, to examine the neural correlates of affective temperaments and their relationship to depressive symptom dimensions. Methods Twenty-nine medication-free patients with MDD and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Patients also received assessments of the Hamilton Depression Rating Scale (HDRS). We used multivariate analyses of partial least squares regression and partial correlation analyses to explore the associations among the insular activity, affective temperaments, and depressive symptom dimensions. Results A profile (linear combination) of increased fractional amplitude of low-frequency fluctuations (fALFF) of the anterior insular subregions (left dorsal agranular–dysgranular insula and right ventral agranuar insula) was positively associated with an affective-temperament (depressive, irritable, anxious, and less hyperthymic) profile. The covariation between the insula-fALFF profile and the affective-temperament profile was significantly correlated with the sleep disturbance dimension (especially the middle and late insomnia scores) in the medication-free MDD patients. Conclusions The resting-state spontaneous activity of the anterior insula and affective temperaments collaboratively contribute to sleep disturbances in medication-free MDD patients. The approach used in this study provides a practical way to explore the relationship of multivariate measures in investigating the etiology of mental disorders.
Direct observation of damage clustering in irradiated DNA with atomic force microscopy

Abstract Ionizing radiation produces clustered DNA damage that contains two or more lesions in 10–20 bp. It is believed that the complexity of clustered damage (i.e., the number of lesions per damage site) is related to the biological severity of ionizing radiation. However, only simple clustered damage containing two vicinal lesions has been demonstrated experimentally. Here we developed a novel method to analyze the complexity of clustered DNA damage. Plasmid DNA was irradiated with densely and sparsely ionizing Fe-ion beams and X-rays, respectively. Then, the resulting DNA lesions were labeled with biotin/streptavidin and observed with atomic force microscopy. Fe-ion beams produced complex clustered damage containing 2–4 lesions. Furthermore, they generated two or three clustered damage sites in a single plasmid molecule that resulted from the hit of a single track of Fe-ion beams. Conversely, X-rays produced relatively simple clustered damage. The present results provide the first experimental evidence for complex cluster damage.
An Overview of Systematic Reviews of Randomized-Controlled Trials for Preventing Necrotizing Enterocolitis in Preterm Infants

Necrotizing enterocolitis (NEC) remains a major cause for neonatal mortality and morbidity in preterm infants. The purpose of this review was to summarize evidence from systematic reviews of randomized-controlled trials (RCTs) regarding antenatal and postnatal interventions for preventing NEC. PubMed, EMBASE, the Cochrane Library Databases, Database of Abstracts of Reviews of Effects, and Campbell Library were searched for meta-analyses in which NEC was reported as an outcome after antenatal or postnatal strategies. The AMSTAR instrument was used to evaluate quality of included reviews. Grading of Recommendations, Assessment, Development and Evaluation assessment was used to evaluate certainty of evidence. We identified 98 meta-analyses of RCTs. The quality of included reviews was adequate, whereas the certainty of evidence was moderate to very low. Moderate certainty evidence showed a reduction in NEC following administration of a combination of species of probiotics, probiotics (any), antenatal corticosteroids in pregnant women at risk of preterm birth, and ibuprofen versus indomethacin for treatment of patent ductus arteriosus (PDA). For surgical NEC, moderate certainty evidence showed an increased risk with lower (85–89%) oxygen saturation target levels, compared with higher (91–95%) oxygen saturation target levels. In conclusion, decreased risk of NEC is observed with probiotics, antenatal corticosteroids for women at risk of preterm birth, and ibuprofen versus indomethacin for treatment of PDA. Targeting lower oxygen saturations may increase the risk of surgical NEC, compared to targeting higher saturations.
Epidemiology and outcome of idiopathic generalized epilepsy in adults

Drug‐resistant idiopathic generalized epilepsy (IGE) remains challenging despite a favourable overall prognosis of IGE, and little is known about basic epidemiology and long‐term outcome of drug‐resistant IGE. The aim of the study was to describe the incidence, prevalence and outcome of IGE in an unbiased, population‐based cohort.
Emergence of West Nile virus lineage 2 in Europe: Characteristics of the first seven cases of West Nile neuroinvasive disease in horses in Austria

Abstract We report details of the first seven equine cases of confirmed West Nile neuroinvasive disease in Austria. The cases presented during summer and autumn of 2016 (n = 2), 2017 (n = 3) and 2018 (n = 2). All horses showed gait abnormalities and 6 of 7 horses exhibited fasciculations and/or tremors, and we provide video recordings of these. Three horses also showed cranial nerve involvement. Following rapid improvement, three horses were discharged. Four horses were euthanized due to the severity of clinical signs and subjected to neuropathological examination. West Nile virus (WNV) lineage 2 nucleic acid was detected in 5 of 7 horses, and WNV‐specific neutralizing antibodies in all 7 horses. In addition, serologic evidence of WNV infection was found in two out of fourteen in‐contact horses. Horses may be considered a sentinel species for human WNV infections, integrating human and veterinary medicine and thus contributing to the one health concept.
Metabolic compounds within the porcine uterine environment are unique to the type of conceptus present during the early stages of blastocyst elongation

The objective of this study was to identify metabolites within the porcine uterine milieu during the early stages of blastocyst elongation. At Days 9, 10, or 11 of gestation, reproductive tracts of White cross‐bred gilts (n = 38) were collected immediately following harvest and flushed with Roswell Park Memorial Institute‐1640 medium. Conceptus morphologies were assessed from each pregnancy and corresponding uterine flushings were assigned to one of five treatment groups based on these morphologies: (a) uniform spherical (n = 8); (b) heterogeneous spherical and ovoid (n = 8); (c) uniform ovoid (n = 8); (d) heterogeneous ovoid and tubular (n = 8); and (e) uniform tubular (n = 6). Uterine flushings from these pregnancies were submitted for nontargeted profiling by gas chromatography–mass spectrometry (GC–MS) and ultra performance liquid chromatography (UPLC)–MS techniques. Unsupervised multivariate principal component analysis (PCA) was performed using pcaMethods and univariate analysis of variance was performed in R with false discovery rate (FDR) adjustment. PCA analysis of the GC–MS and UPLC–MS data identified 153 and 104 metabolites, respectively. After FDR adjustment of the GC–MS and UPLC–MS data, 38 and 59 metabolites, respectively, differed (p < .05) in uterine flushings from pregnancies across the five conceptus stages. Some metabolites were greater (p < .05) in abundance for uterine flushings containing earlier stage conceptuses (i.e., spherical), such as uric acid, tryptophan, and tyrosine. In contrast, some metabolites were greater (p < .05) in abundance for uterine flushings containing later stage conceptuses (i.e., tubular), such as creatinine, serine, and urea. These data illustrate several putative metabolites that change within the uterine milieu during early porcine blastocyst elongation.
PIWI Proteins and piRNAs in the Nervous System

PIWI Argonaute proteins and Piwi-interacting RNAs (piRNAs) are expressed in all animal species and play a critical role in cellular defense by inhibiting the activation of transposable elements in the germline. Recently, new evidence suggests that PIWI proteins and piRNAs also play important roles in various somatic tissues, including neurons. This review summarizes the neuronal functions of the PIWI-piRNA pathway in multiple animal species, including their involvement in axon regeneration, behavior, memory formation, and transgenerational epigenetic inheritance of adaptive memory. This review also discusses the consequences of dysregulation of neuronal PIWI-piRNA pathways in certain neurological disorders, including neurodevelopmental and neurodegenerative diseases. A full understanding of neuronal PIWI-piRNA pathways will ultimately provide novel insights into small RNA biology and could potentially provide precise targets for therapeutic applications.
PLF‐1 (Proliferin‐1) Modulates Smooth Muscle Cell Proliferation and Development of Experimental Intimal Hyperplasia

Background Although apoptosis and cell proliferation have been extensively investigated in atherosclerosis and restenosis postinjury, the communication between these 2 cellular events has not been evaluated. Here, we report an inextricable communicative link between apoptosis and smooth muscle cell proliferation in the promotion of vascular remodeling postinjury. Methods and Results Cathepsin K–mediated caspase‐8 maturation is a key initial step for oxidative stress–induced smooth muscle cell apoptosis. Apoptotic cells generate a potential growth‐stimulating signal to facilitate cellular mass changes in response to injury. One downstream mediator that cathepsin K regulates is PLF‐1 (proliferin‐1), which can potently stimulate growth of surviving neighboring smooth muscle cells through activation of PI3K/Akt/p38MAPK (phosphatidylinositol 3‐kinase/protein kinase B/p38 mitogen‐activated protein kinase)‐dependent and ‐independent mTOR (mammalian target of rapamycin) signaling cascades. We observed that cathepsin K deficiency substantially mitigated neointimal hyperplasia by reduction of Toll‐like receptor‐2/caspase‐8–mediated PLF‐1 expression. Interestingly, PLF‐1 blocking, with its neutralizing antibody, suppressed neointima formation and remodeling in response to injury in wild‐type mice. Contrarily, administration of recombinant mouse PLF‐1 accelerated injury‐induced vascular actions. Conclusions This is the first study detailing PLF‐1 as a communicator between apoptosis and proliferation during injury‐related vascular remodeling and neointimal hyperplasia. These data suggested that apoptosis‐driven expression of PLF‐1 is thus a novel target for treatment of apoptosis‐based hyperproliferative disorders.
CDH1 on multigene panel testing: Look before you leap.

Multigene panel testing (MGPT) has become a critical component of cancer risk assessment in clinical practice. As technology and access improves, and costs decrease, more individuals than ever are undergoing MGPT for genetic evaluation. One gene that deserves special consideration when included on MGPT is CDH1, which codes for the cell-cell adhesion protein E-cadherin. Pathogenic germline variants in CDH1 have been associated with hereditary diffuse gastric cancer syndrome, and in highly penetrant families, testing for these variants is critical for proper risk management. However, recent data demonstrated that gastric cancer penetrance in unselected CDH1 carriers may be lower than expected. Further complicating matters are the lack of effective screening strategies for gastric cancer and recommendation for risk-reducing total gastrectomy in CDH1 carriers. Therefore, the discovery of an unexpected pathogenic CDH1 variant on multigene panel testing, when testing for CDH1 would not normally be considered based on personal or family history alone, creates dilemmas for both patients and providers. In this commentary, we highlight the potential for unexpected CDH1 variants on MGPT, outline the uncertainties associated with these variants, and emphasize the importance of pre-test counseling regarding the potential for an unexpected CDH1 variant. While CDH1 testing is often important for clinical decision making, individuals and providers need to be aware of the potential for an unexpected CDH1 variant when CDH1 is included on MGPT for cancer risk assessment.
High ctDNA molecule numbers relate with poor outcome in advanced ER+, HER2− postmenopausal breast cancer patients treated with everolimus and exemestane

We determined whether progression‐free survival (PFS) in metastatic breast cancer (MBC) patients receiving everolimus plus exemestane (EVE/EXE) varies depending on circulating tumour DNA (ctDNA) characteristics. Baseline plasma cell‐free DNA (cfDNA) from 164 postmenopausal women with ER‐positive, HER2‐negative MBC refractory to a nonsteroidal aromatase inhibitor and treated with standard EVE/EXE (Everolimus Biomarker Study, Eudract 2013‐004120‐11) was characterised for 10 relevant breast cancer genes by next‐generation sequencing with molecular barcoding. ctDNA molecule numbers, number of mutations and specific variants were related with PFS and overall survival (OS). Missense hotspot mutations in cfDNA were detected in 125 patients. The median of 54 ctDNA molecules per mL plasma distinguished patients with high and low/no ctDNA load. Patients with low/no ctDNA load (N = 102) showed longer median PFS of 5.7 months (P = 0.006) and OS of 124.8 months (P = 0.008) than patients with high ctDNA load (N = 62; 4.4 months and 107.7 months, respectively) in multivariate analyses. Patients with < 3 specific mutations (N = 135) had longer median PFS of 5.4 months compared to those with ≥ 3 mutations (3.4 months; P < 0.001). In conclusion, MBC patients with low/no ctDNA load or < 3 hotspot mutations experience longer PFS while treated with EVE/EXE.
Refining genome-wide associated loci for serum uric acid in individuals with African ancestry.

OBJECTIVE Serum uric acid is the end-product of purine metabolism and at high levels is a risk factor for several human diseases including gout and cardiovascular disease. Heritability estimates range from 0.32 to 0.63. Genome-wide association studies (GWAS) provide an unbiased approach to identify loci influencing serum uric acid. Here, we performed the first GWAS for serum uric acid in continental Africans, with replication in African Americans. METHODS Africans (n = 4126) and African Americans (n = 5007) were genotyped on high density GWAS arrays. Efficient mixed model association, a variance components approach, was used to perform association testing for a total of ~ 18 million autosomal genotyped and imputed variants. CAVIARBF was used to fine map significant regions. RESULTS We identified two genome-wide significant loci: 4p16.1 (SLC2A9) and 11q13.1 (SLC22A12). At SLC2A9, the most strongly associated SNP was rs7683856 (p = 1.60 × 10-44). Conditional analysis revealed a second signal indexed by rs6838021 (p = 5.75 × 10-17). Gene expression and regulatory motif data prioritized a single candidate causal variant for each signal. At SLC22A12, the most strongly associated SNP was rs147647315 (p = 6.65 × 10-25). Conditional analysis and functional annotation prioritized the missense variant rs147647315 (R (Arg) > H (His))as the sole causal variant. Functional annotation of these three signals implicated processes in skeletal muscle, subcutaneous adipose tissue, and the kidneys, respectively. CONCLUSIONS This first GWAS of serum uric acid in continental Africans identified three associations at two loci, SLC2A9 and SLC22A12. The combination of weak linkage disequilibrium in Africans and functional annotation led to the identification of candidate causal SNPs for all three signals. Each candidate causal variant implicated a different cell type. Collectively, the three associations accounted for 4.3% of the variance of serum uric acid.
Peripartum management of hypertension. A position paper of the ESC Council on Hypertension and the European Society of Hypertension.

Hypertensive disorders are the most common medical complications in the peripartum period associated with a substantial increase in morbidity and mortality. Hypertension in the peripartum period may be due to the continuation of pre-existing or gestational hypertension, de novo development of pre-eclampsia or it may be also induced by some drugs used for analgesia or suppression of postpartum haemorrhage. Women with severe hypertension and hypertensive emergencies are at high risk of life threatening complications, therefore, despite the lack of evidence-based data, based on expert opinion, antihypertensive treatment is recommended. Labetalol intravenously and metyldopa orally are then the two most frequently used drugs. Short-acting oral nifedipine is suggested to be used only if other drugs or iv access are not available. Induction of labour is associated with improved maternal outcome and should be advised for women with gestational hypertension or mild pre-eclampsia at 37 weeks᾽ gestation. This position paper provides the first interdisciplinary approach to the management of hypertension in the peripartum period based on the best available evidence and expert consensus.
Comparison of Various Abdominal Obesity Measures for Predicting Metabolic Syndrome, Diabetes, Nephropathy, and Dyslipidemia.

OBJECTIVE To evaluate abdominal volume index (AVI), body roundness index (BRI), body adiposity index (BAI), a body shape index (ABSI) and conicity index (C-Index) for differences in subjects with or without metabolic syndrome, diabetes, nephropathy, and dyslipidemia; and secondly, to evaluate the diagnostic performance through measuring area under curve (AUC) by ROC curve analysis for new and conventional obesity measures in diagnosing metabolic syndrome. STUDY DESIGN Cross-sectional analytical study. PLACE AND DURATION OF STUDY PNS Hafeez Hospital, Islamabad, from January 2016 to December 2018. METHODOLOGY Baseline anthropometric measures including BMI, WHpR, WHtR, AVI, BRI, BAI, ABSI and C-Index were measured for 232 subjects along with measurement of various biochemical parameters. Differences among subjects with and without metabolic syndrome, diabetes, nephropathy, and groups based upon insulin resistance were noted. ROC curve analysis was utilised to measure AUC for all anthropometric measures for diagnosing metabolic syndrome. RESULTS Pearson's correlation between obesity measures and lipid indices suggested highest correlation for AVI for most lipid indices followed by WHpR and WHtR. Mean AUC for obesity measures were greater than 0.80 for WHtR and AVI, followed by other parameters. The least AUC i.e. 0.320, was observed for ABSI. The differences between various anthropometric measures for groups based upon metabolic syndrome, diabetes, nephropathy, and insulin resistance remain variable indicating that each anthropometric index may depict a different aspect of the metabolic risk. CONCLUSION WHtR and AVI showed the highest AUC to diagnose metabolic syndrome and were better associated with metabolic diseases.
Concomitant Sacral Neuromodulation and Gynecologic Surgery: A Single‐Institution Experience

Sacral Neuromodulation (SNM) is a safe and minimally invasive treatment for urinary and fecal pelvic floor disorders (PFDs). With a high prevalence of women reporting multiple PFDs, knowledge regarding concomitant surgery may inform optimal patient care. Our literature search did not identify any published data on this topic, thus we sought to report our experience with concomitant SNM and gynecologic surgery. Our primary objective was to identify the rate of adverse events among cases. Secondarily, we reviewed the anesthetics used to identify potential associations when performing combined surgery.
Differential Impact of a Cardiac Rehabilitation Program on Functional Parameters in Elderly versus Non-Elderly Myocardial Infarction Survivors

Background: Exercise-based cardiac rehabilitation (EBCR) plays a pivotal role in the management of acute myocardial infarction (AMI). Studies have shown that older individuals have a worse prognosis after an AMI, attesting to the importance of risk reduction strategies. We aimed at assessing the impact of age (patients dichotomized as ≥65 years old or <65 years old) on the functional benefits of an EBCR program among AMI survivors. Design: Observational, retrospective cohort study. Participants: All patients admitted due to an AMI who completed a phase II EBCR program after discharge, between November 2012 and April 2017. Intervention: EBCR program. Measurements: Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test. Results: A total of 379 patients were included (30% aged ≥65 years). After the EBCR program, peak oxygen uptake (pVO2) and exercise duration increased significantly. Patients aged ≥65 years presented with more comorbidities and a lower functional capacity. Those aged ≥65 years presented significantly smaller improvements in pVO2 (0.79 ± 2.61 vs. 1.60 ± 3.11 mL/kg/min, p = 0.016) and exercise duration [75 (59–120) vs. 120 s (60–180), p = 0.002]. This was maintained after adjusting for several potential confounders. Conclusion: Older patients have a worse functional capacity than their younger counterparts. Still, a contemporary EBCR program was associated with significant functional improvements among those aged ≥65 years. The smaller improvements even after adjustments for potential confounders suggest that physiological differences may contribute to this finding. These results highlight the relevance of EBCR among this higher-risk subgroup.
Personality and prosocial behavior: A theoretical framework and meta-analysis.

Decades of research document individual differences in prosocial behavior using controlled experiments that model social interactions in situations of interdependence. However, theoretical and empirical integration of the vast literature on the predictive validity of personality traits to account for these individual differences is missing. Here, we present a theoretical framework that identifies 4 broad situational affordances across interdependent situations (i.e., exploitation, reciprocity, temporal conflict, and dependence under uncertainty) and more specific subaffordances within certain types of interdependent situations (e.g., possibility to increase equality in outcomes) that can determine when, which, and how personality traits should be expressed in prosocial behavior. To test this framework, we meta-analyzed 770 studies reporting on 3,523 effects of 8 broad and 43 narrow personality traits on prosocial behavior in interdependent situations modeled in 6 commonly studied economic games (Dictator Game, Ultimatum Game, Trust Game, Prisoner's Dilemma, Public Goods Game, and Commons Dilemma). Overall, meta-analytic correlations ranged between -. 18 ≤ ρ̂ ≤ . 26, and most traits yielding a significant relation to prosocial behavior had conceptual links to the affordances provided in interdependent situations, most prominently the possibility for exploitation. Moreover, for several traits, correlations within games followed the predicted pattern derived from a theoretical analysis of affordances. On the level of traits, we found that narrow and broad traits alike can account for prosocial behavior, informing the bandwidth-fidelity problem. In sum, the meta-analysis provides a theoretical foundation that can guide future research on prosocial behavior and advance our understanding of individual differences in human prosociality. (PsycINFO Database Record (c) 2019 APA, all rights reserved).