Miracle-dz/UniFAR-FTUs huggingface dataset:
High-achieving schools connote risks for adolescents: Problems documented, processes implicated, and directions for interventions.

Excessive pressures to excel, generally in affluent contexts, are now listed among the top 4 "high risk" factors for adolescents' mental health, along with exposure to poverty, trauma, and discrimination. Multiple studies of high-achieving school (HAS) cohorts have shown elevated rates of serious symptoms relative to norms, with corroborating evidence from other research using diverse designs. Grounded in theories on resilience and ecological influences in development, a conceptual model is presented here on major risk and protective processes implicated in unrelenting achievement pressures facing HAS youth. These include forces at the macrolevel, including economic and technological changes that have led to the "middle class squeeze," and proximal influences involving the family, peers, schools, and communities. Also considered are potential directions for future interventions, with precautions about some practices that are currently widespread in HAS contexts. In the years ahead, any meaningful reductions in the high distress of HAS youth will require collaborations among all stakeholders, with parents and educators targeting the specific areas that must be prioritized in their own communities. Leaders in higher education and social policy could also help in beginning to curtail this problem, which is truly becoming an epidemic among today's youth. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Does Maternal Reflective Functioning Mediate Associations Between Representations of Caregiving With Maternal Sensitivity in a High-Risk Sample?

Although it is known that mothers with substance-use disorders struggle to provide adequate parenting to their children, little is understood about the mechanisms behind this. This cross-sectional study uses an attachment perspective to examine whether reflective functioning mediates the relationship between mental representations of caregiving and maternal sensitivity, in an ethnically diverse sample of 142 substance-dependent mothers (M = 29.81, SD = 5.85 years of age) and their toddlers (M = 24.04, SD = 15.15 months of age). Data were baseline measures from 2 randomized controlled trials. The 3 variables of primary interest were positively correlated. As expected, there was a significant relationship between mental representations of caregiving and maternal sensitivity that was largely explained by reflective functioning. Confounding and alternate explanations were not supported by secondary data analyses. The findings underscore the importance of reflective functioning in positive parenting within this high-risk population of mothers, and they provide support for the development of attachment-based interventions.
The Proteome of the Dentate Terminal Zone of the Perforant Path Indicates Presynaptic Impairment in Alzheimer Disease*

Synaptic dysfunction is an early pathogenic event in Alzheimer disease (AD). Hence the maintenance of healthy neurotransmission becomes crucial to slow or halt cognitive decline. In search of identifying proteins that could play a role in synaptic dysfunction, we studied the proteome of a highly vulnerable hippocampal region that is enriched in excitatory synapses. Our in-depth proteomic analysis suggests an impaired presynaptic signaling in AD. Using immunohistochemistry, we verified significantly reduced levels of complexin-1, complexin-2, and synaptogyrin-1 in AD. Graphical Abstract Highlights Laser microdissection of highly vulnerable hippocampal region. Proteomic analysis of postmortem human brain tissue of AD and control cases. Decreased levels of presynaptic proteins, but not postsynaptic proteins, in AD. Immunohistochemistry verifies decreased levels of selected presynaptic proteins. Synaptic dysfunction is an early pathogenic event in Alzheimer disease (AD) that contributes to network disturbances and cognitive decline. Some synapses are more vulnerable than others, including the synapses of the perforant path, which provides the main excitatory input to the hippocampus. To elucidate the molecular mechanisms underlying the dysfunction of these synapses, we performed an explorative proteomic study of the dentate terminal zone of the perforant path. The outer two-thirds of the molecular layer of the dentate gyrus, where the perforant path synapses are located, was microdissected from five subjects with AD and five controls. The microdissected tissues were dissolved and digested by trypsin. Peptides from each sample were labeled with different isobaric tags, pooled together and pre-fractionated into 72 fractions by high-resolution isoelectric focusing. Each fraction was then analyzed by liquid chromatography-mass spectrometry. We quantified the relative expression levels of 7322 proteins, whereof 724 showed significantly altered levels in AD. Our comprehensive data analysis using enrichment and pathway analyses strongly indicated that presynaptic signaling, such as exocytosis and synaptic vesicle cycle processes, is severely disturbed in this area in AD, whereas postsynaptic proteins remained unchanged. Among the significantly altered proteins, we selected three of the most downregulated synaptic proteins; complexin-1, complexin-2 and synaptogyrin-1, for further validation, using a new cohort consisting of six AD and eight control cases. Semi-quantitative analysis of immunohistochemical staining confirmed decreased levels of complexin-1, complexin-2 and synaptogyrin-1 in the outer two-thirds of the molecular layer of the dentate gyrus in AD. Our in-depth proteomic analysis provides extensive knowledge on the potential molecular mechanism underlying synaptic dysfunction related to AD and supports that presynaptic alterations are more important than postsynaptic changes in early stages of the disease. The specific synaptic proteins identified could potentially be targeted to halt synaptic dysfunction in AD.
Do vacations alter the connection between stress and cardiovascular activity? The effects of a planned vacation on the relationship between weekly stress and ambulatory heart rate

Abstract Objective: To examine how the association between psychological stress and ambulatory heart rate varies in the weeks before and after a planned vacation. We hypothesized that the impact of stress on heart rate would weaken in the weeks leading up to the vacation and return to normal levels in the weeks following the vacation. Method: Fifty-four workers eligible for paid vacation time were recruited; stress ratings obtained via weekly surveys and ambulatory heart rate readings obtained via a wrist-worn consumer device were collected before and after the vacation. Results: A statistically significant interaction was observed between weekly stress and the time period leading up to the vacation on ambulatory heart rate (b = −0.51, SE = 0.21, 95% CI = −0.91, −0.10, p = 0.01). A plot of predicted values demonstrated that the relationship between weekly stress and heart rate was stronger when the vacation was further away in the future and imparted less of an effect as the vacation approached. Conclusions: Vacations may have physical health benefits that extend beyond the vacation experience by reducing the association between stress and ambulatory heart rate in the weeks leading up to a planned vacation.
Elderly-onset Still's Disease Complicated by Macrophage Activation Syndrome: A Case Report and Review of the Literature

Adult-onset Still's disease (AOSD) usually affects young adults. Some cases of elderly-onset Still's disease (EOSD) have been reported, but its clinical features are unclear. We herein report a 74-year-old woman who developed AOSD with macrophage activation syndrome (MAS). We also reviewed 24 previous EOSD cases in patients over 70 years old and compared the findings with overall AOSD. While the clinical features were similar between the two, including the presence of MAS, disseminated intravascular coagulation was more frequent in EOSD than in AOSD. Furthermore, despite a similar frequency of glucocorticoid use, immunosuppressants and biologics were less frequently administered in EOSD than in AOSD. This report highlights the fact that typical AOSD can develop in elderly patients with some characteristic features.
Loss of Tiparp Results in Aberrant Layering of the Cerebral Cortex

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose polymerase (TIPARP) is an enzyme that adds a single ADP-ribose moiety to itself or other proteins. Tiparp is highly expressed in the brain; however, its function in this organ is unknown. Here, we used Tiparp–/– mice to determine Tiparp’s role in the development of the prefrontal cortex. Abstract 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose polymerase (TIPARP) is an enzyme that adds a single ADP-ribose moiety to itself or other proteins. Tiparp is highly expressed in the brain; however, its function in this organ is unknown. Here, we used Tiparp–/– mice to determine Tiparp’s role in the development of the prefrontal cortex. Loss of Tiparp resulted in an aberrant organization of the mouse cortex, where the upper layers presented increased cell density in the knock-out mice compared with wild type. Tiparp loss predominantly affected the correct distribution and number of GABAergic neurons. Furthermore, neural progenitor cell proliferation was significantly reduced. Neural stem cells (NSCs) derived from Tiparp–/– mice showed a slower rate of migration. Cytoskeletal components, such as α-tubulin are key regulators of neuronal differentiation and cortical development. α-tubulin mono-ADP ribosylation (MAR) levels were reduced in Tiparp–/– cells, suggesting that Tiparp plays a role in the MAR of α-tubulin. Despite the mild phenotype presented by Tiparp–/– mice, our findings reveal an important function for Tiparp and MAR in the correct development of the cortex. Unravelling Tiparp’s role in the cortex, could pave the way to a better understanding of a wide spectrum of neurological diseases which are known to have increased expression of TIPARP.
WEE1 Inhibition Enhances Anti-Apoptotic Dependency as a Result of Premature Mitotic Entry and DNA Damage

Genomically unstable cancers are dependent on specific cell cycle checkpoints to maintain viability and prevent apoptosis. The cell cycle checkpoint protein WEE1 is highly expressed in genomically unstable cancers, including diffuse large B-cell lymphoma (DLBCL). Although WEE1 inhibition effectively induces apoptosis in cancer cells, the effect of WEE1 inhibition on anti-apoptotic dependency is not well understood. We show that inhibition of WEE1 by AZD1775 induces DNA damage and pre-mitotic entry in DLBCL, thereby enhancing dependency on BCL-2 and/or MCL-1. Combining AZD1775 with anti-apoptotic inhibitors such as venetoclax (BCL-2i) or S63845 (MCL-1i) enhanced sensitivity in a cell-specific manner. In addition, we demonstrate that both G2/M cell cycle arrest and DNA damage induction put a similar stress on DLBCL cells, thereby enhancing anti-apoptotic dependency. Therefore, genotoxic or cell cycle disrupting agents combined with specific anti-apoptotic inhibitors may be very effective in genomic unstable cancers such as DLBCL and therefore warrants further clinical evaluation.
SPISE and other fasting indexes of insulin resistance: risks of coronary heart disease or type 2 diabetes. Comparative cross-sectional and longitudinal aspects

Abstract Background: Fasting insulin resistance indexes are used extensively nowadays. We intended to analyze a new recently presented fasting index, SPISE (sensitivity formula: 600 × HDL-cholesterol0.185/triglycerides0.2/BMI1.338), in comparison with three previously known fasting indexes, regarding correlation with the insulin clamp index, and for the predictive effects of future long-term risks of coronary heart disease (CHD) or manifest type 2 diabetes. Methods: A total of 1049 71-year-old male subjects from the Swedish ULSAM study, median follow-up 8 years, were included. All subjects performed the euglycemic insulin clamp, and analyses of four fasting insulin resistance indexes: SPISE-IR (= 10/SPISE), QUICKI-IR, Log HOMA-IR, and Revised QUICKI-IR. Results: Spearman correlation coefficients with the insulin clamp were 0.60–0.62 for all indexes. Area under curve at ROC analysis was 0.80 for SPISE-IR, and 0.84 for QUICKI-IR, Log HOMA-IR, and Rev QUICKI-IR. Adjusted hazard ratios per 1 SD index increase for long-term risk CHD were similar in all patients: 1.20–1.24 (p = 0.02–0.03). However, comparing the highest quartile (recommended to define insulin resistance) with the lower quartiles, SPISE-IR was the strongest and the only statistically significant insulin resistance index: HR 1.53 (p = 0.02). Adjusted odds ratios per 1 SD index increase for long-term risk of type 2 diabetes were fairly similar (p < 0.001) in all patients: 1.62 for SPISE-IR, 1.97 for QUICKI-IR and Log HOMA-IR, and 2.04 for Rev QUICKI-IR, and also when comparing the highest versus the lower quartiles: 2.8–3.1 (p < 0.001). Conclusion: SPISE, easily applicable, performed equally well as other fasting insulin indexes previously recommended for clinical use, regarding correlation with the insulin clamp, and as predictor for future long-term risks of CHD or type 2 diabetes.
Cell-Penetrating And Antibacterial BUF-II Nanobioconjugates: Enhanced Potency Via Immobilization On Polyetheramine-Modified Magnetite Nanoparticles

Introduction Controlled delivery of therapeutic molecules in a localized manner has become an area of interest due to its potential to reduce drug exposure to healthy tissues and consequently to minimize undesirable side effects. We have recently introduced novel cell-penetrating vehicles by immobilizing the antimicrobial peptide Buforin II (BUF-II) on magnetite nanoparticles (MPNPs). Despite the potent translocating abilities of such nanobioconjugates, they failed to preserve the antimicrobial activity of native BUF-II. In this work, we explored immobilization on MNPs with the aid of polymer surface spacers, which has been considered as an attractive alternative for the highly efficient conjugation of various biomolecules. Methods Here, we immobilized BUF-II on polyetheramine-modified magnetite nanoparticles to preserve its structural integrity. As a result, for the obtained nanobioconjugates the lost antimicrobial activity against gram-positive and gram-negative bacteria was only 50% with respect to the native BUF-II. The nanobioconjugates were also characterized via FTIR, DLS, TEM, and TGA. Delivery on THP-1, HaCaT, HFF, and Escherichia coli cells was conducted to confirm capability for cell membrane translocation. Results Colocalization with Lysotracker showed an endosomal escape efficiency of about 73∓12% in THP-1 cells. Avoidance of endocytic pathways of internalization was qualitatively confirmed by a delivery assay at low temperature. Nuclear penetration of the nanobioconjugates was corroborated via confocal microscopy and showed high biocompatibility as demonstrated by hemolysis levels below 5% and acute cytotoxicity of around 15%. Conclusion The obtained nanobioconjugates were capable of translocating the cell membrane and nuclei of different normal and cancerous cell lines without significantly decreasing viability. This makes the vehicle addressable for a number of applications ranging from antimicrobial topical treatments to the delivery of nucleotides and therapeutic molecules with difficulties to bypass cell membranes.
Physical Map of FISH 5S rDNA and (AG3T3)3 Signals Displays Chimonanthus campanulatus R.H. Chang & C.S. Ding Chromosomes, Reproduces its Metaphase Dynamics and Distinguishes Its Chromosomes

Chimonanthus campanulatus R.H. Chang & C.S. Ding is a good horticultural tree because of its beautiful yellow flowers and evergreen leaves. In this study, fluorescence in situ hybridization (FISH) was used to analyse mitotic metaphase chromosomes of Ch. campanulatus with 5S rDNA and (AG3T3)3 oligonucleotides. Twenty-two small chromosomes were observed. Weak 5S rDNA signals were observed only in proximal regions of two chromosomes, which were adjacent to the (AG3T3)3 proximal signals. Weak (AG3T3)3 signals were observed on both chromosome ends, which enabled accurate chromosome counts. A pair of satellite bodies was observed. (AG3T3)3 signals displayed quite high diversity, changing in intensity from weak to very strong as follows: far away from the chromosome ends (satellites), ends, subtelomeric regions, and proximal regions. Ten high-quality spreads revealed metaphase dynamics from the beginning to the end and the transition to anaphase. Chromosomes gradually grew larger and thicker into linked chromatids, which grew more significantly in width than in length. Based on the combination of 5S rDNA and (AG3T3)3 signal patterns, ten chromosomes were exclusively distinguished, and the remaining twelve chromosomes were divided into two distinct groups. Our physical map, which can reproduce dynamic metaphase progression and distinguish chromosomes, will powerfully guide cytogenetic research on Chimonanthus and other trees.
Large Undifferentiated Pleomorphic Sarcoma of the Posterior Thigh

Patient: Female, 62 Final Diagnosis: Undifferentiated pleomorphic sarcoma Symptoms: Pain in the leg Medication: — Clinical Procedure: Surgical excision Specialty: Oncology Objective: Rare disease Background: Sarcomas account for less than 1% of all cancers. Undifferentiated Pleomorphic Sarcoma, formerly called Malignant Fibrous Histiocytoma, is a rare subtype identified by a lack specific immunohistochemical markers for a specific lineage of differentiation. These soft tissue tumors are aggressive and rapidly enlarge. Risk for metastasis increases almost linearly as the tumor increases in size, emphasizing the importance of early detection, treatment, and post-resection monitoring. Case Report: This article reports a case of a large undifferentiated pleomorphic sarcoma of the posterior thigh in a 62-year-old female. Given the patient’s history of thrombotic thrombocytopenic purpure, her initial mass was thought to be a hematoma following a hernia repair surgery. After diagnosis of undifferentiated pleomorphic sarcoma, she underwent radical excision revealing a 24×9.5×7cm lesion – one of the largest reported in the literature. Conclusions: Sarcomas are very rare soft tissue neoplasms, but they should not be excluded in a physician’s differentials when a patient presents with an enlarging soft tissue mass. Because sarcomas enlarge rapidly, delay in evaluation and management should be avoided and these patients should be quickly referred to a center specializing in sarcoma treatment. Magnetic Resonance Imaging (MRI) is the recommended initial imaging for all soft tissue masses of the extremities, trunk, and head and neck while Computed Tomography (CT) is the recommended imaging choice for retroperitoneal and visceral masses. After successful surgical excision with clean margins, patients should undergo serial monitoring by CT or MRI for surveillance of recurrence or late pulmonary metastases.
Guideline on the Use of Iodinated Contrast Media in Patients With Kidney Disease 2018.

J-STAGE Advance Publication released online November 11, 2019 This guideline was developed in collaboration with JSN, JRS, and JCS. This book, which was published in Tokyo Igakusya, was approved by JSN, JRS and JCS Science Advisory and Coordinating Committee in 2018. This is the English version of that Japanese book. Mailing address: Scientific Committee of the Japanese Circulation Society, 18F Imperial Hotel Tower, 1-1-1 Uchisaiwai-cho, Chiyoda-ku, Tokyo 100-0011, Japan. E-mail: meeting@j-circ.or. jp Joint Working Groups: Japanese Society of Nephrology, Japan Radiological Society, the Japanese Circulation Society ISSN-1346-9843 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or. jp Guideline on the Use of Iodinated Contrast Media in Patients With Kidney Disease 2018
Beliefs, practices and knowledge of community pharmacists regarding complementary and alternative medicine: national cross-sectional study in Lebanon

Introduction Pharmacists are uniquely positioned to provide patients with evidence-based information in order to ensure effective and safe use of Complementary and alternative medicine (CAM) products. Objective Assess beliefs, practices and knowledge related to CAM products among community pharmacists in Lebanon. Design, methods and setting Using stratified random sampling, a nationally representative survey was conducted among community pharmacists in Lebanon. Through face-to-face interviews, pharmacists completed a multicomponent questionnaire consisting of four sections: (1) sociodemographic characteristics; (2) beliefs related to regulation of CAM products, role of media in promoting their safe use, availability of resources and continuing education; (3) practices including selling CAM products, providing advice for patients and reporting adverse effects and (4) knowledge about specific CAM products, their uses, side effects and interactions. Results A total of 341 pharmacists agreed to participate (response rate: 86%). Only pharmacists with complete data were included in this study (n=310). Pharmacists agreed that CAM products are effective (63.8%) and that they should be exclusively sold in pharmacies (80.3%), but disagreed that commercially marketed CAM products are well regulated (63.5%) and that media plays a positive role in educating users about these products (55.8%). As for practices, 64.5% of pharmacists were always or often advising patients on safe use; however, 74.2% of participants rarely or never reported adverse effects. Regarding knowledge, although the majority of pharmacists were aware of the uses of CAM products, fewer knew about their side effects and their interactions with drugs. After adjustment for covariates, receiving education/training on CAM products during university was the sole predictor of higher knowledge score (ß=0.68, 95% CI 0.29 to 1.07). Conclusions This study revealed positive beliefs of pharmacists in Lebanon towards CAM products and indicated important gaps in their practice and knowledge. Deliberate efforts to enhance the education of pharmacists are warranted to ensure the safe integration and use of CAM products in Lebanon.