Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Effects from a School-Based Trial Comparing Interpersonal Psychotherapy-Adolescent Skills Training to Group Counseling

Adolescence represents a vulnerable developmental period for depression and an opportune time for prevention efforts. In this study, 186 adolescents with elevated depressive symptoms (M age = 14.01, SD = 1.22; 66.7% female; 32.2% racial minority) were randomized to receive either Interpersonal Psychotherapy–Adolescent Skills Training (IPT-AST; n = 95) delivered by research clinicians or group counseling (GC; n = 91) delivered by school counselors. We previously reported the short-term outcomes of this school-based randomized controlled trial: IPT-AST youth experienced significantly greater improvements in depressive symptoms and overall functioning through 6-month follow-up. Here, we present the long-term outcomes through 24 months postintervention. We examined differences in rates of change in depressive symptoms and overall functioning and differences in rates of depression diagnoses. Youth in both conditions showed significant improvements in depressive symptoms and overall functioning from baseline to 24-month follow-up, demonstrating the efficacy of school-based depression prevention programs. However, the two groups did not differ in overall rates of change or in rates of depression diagnoses from baseline to 24-month follow-up. Although IPT-AST demonstrated advantages over GC in the short term, these effects dissipated over long-term follow-up. Specifically, from 6- to 24-month follow-up, GC youth showed continued decreases in depressive symptoms, whereas IPT-AST youth showed a nonsignificant increase in symptoms. GC youth remained relatively stable in overall functioning, whereas IPT-AST youth experienced a small but statistically significant worsening in functioning. This study highlights the potential of school-based depression prevention efforts and the need for further research.
Improved vasculogenesis and bone matrix formation through coculture of endothelial cells and stem cells in tissue‐specific methacryloyl gelatin‐based hydrogels

The coculture of osteogenic and angiogenic cells and the resulting paracrine signaling via soluble factors are supposed to be crucial for successfully engineering vascularized bone tissue equivalents. In this study, a coculture system combining primary human adipose‐derived stem cells (hASCs) and primary human dermal microvascular endothelial cells (HDMECs) within two types of hydrogels based on methacryloyl‐modified gelatin (GM) as three‐dimensional scaffolds was examined for its support of tissue specific cell functions. HDMECs, together with hASCs as supporting cells, were encapsulated in soft GM gels and were indirectly cocultured with hASCs encapsulated in stiffer GM hydrogels additionally containing methacrylate‐modified hyaluronic acid and hydroxyapatite particles. After 14 days, the hASC in the stiffer gels (constituting the “bone gels”) expressed matrix proteins like collagen type I and fibronectin, as well as bone‐specific proteins osteopontin and alkaline phosphatase. After 14 days of coculture with HDMEC‐laden hydrogels, the viscoelastic properties of the bone gels were significantly higher compared with the gels in monoculture. Within the soft vascularization gels, the formed capillary‐like networks were significantly longer after 14 days of coculture than the structures in the control gels. In addition, the stability as well as the complexity of the vascular networks was significantly increased by coculture. We discussed and concluded that osteogenic and angiogenic signals from the culture media as well as from cocultured cell types, and tissue‐specific hydrogel composition all contribute to stimulate the interplay between osteogenesis and angiogenesis in vitro and are a basis for engineering vascularized bone.
HappyTools: A software for high-throughput HPLC data processing and quantitation

High-performance liquid chromatography (HPLC) is widely used for absolute quantitation. The advent of new columns and HPLC technology has enabled higher sample throughput, and hence, larger scale studies that perform quantitation on different sample types (e.g. healthy controls vs. patients with rheumatoid arthritis) using HPLC are becoming feasible. However, there remains a lack of methods that can analyse the increased number of HPLC samples. To address this in part, the modular toolkit HappyTools has been developed for the high-throughput targeted quantitation of HPLC measurements. HappyTools enables the user to create an automated workflow that includes retention time (tr) calibration, data extraction and the calculation of several quality criteria for data curation. HappyTools has been tested on a biopharmaceutical standard and previously published clinical samples. The results show comparable accuracy between HappyTools, Waters Empower and ThermoFisher Chromeleon. However, HappyTools offered superior precision and throughput when compared with Waters Empower and ThermoFisher Chromeleon. HappyTools is released under the Apache 2.0 license, both the source code and a Windows binary can be freely downloaded from https://github.com/Tarskin/HappyTools.
Financial Reporting in XBRL on the SEC's EDGAR System: A Critique and Evaluation

This paper evaluates the implications of the proposed Securities and Exchange Commission (SEC) Rule (33‐8496) which encourages companies to file reports in the eXtensible Business Reporting Language (XBRL) format. We examine the impact of the proposed rule in three domains: (1) the role of XBRL in financial reporting, (2) concerns with XBRL taxonomies, and (3) the impact of XBRL on the SEC's filing program. The paper adopts a descriptive approach to generate normative and prescriptive propositions with implications for research that will guide preparers, users, and regulators of XBRL‐tagged information.
Protocol of the randomised placebo controlled pilot trial of the management of acute sciatica (SCIATICA): a feasibility study

Introduction Acute sciatica (symptom duration less than 4 weeks), a major cause of pain and disability, is a common presentation to medical practices and hospital emergency departments. Selective CT fluoroscopy transforaminal epidural steroid injection is often used with the hope of reducing pain and improving function. Recently, there has been interest in using systemic corticosteroids in acute sciatica. However, there is limited evidence to inform management of selective CT fluoroscopy transforaminal epidural steroid in subacute and chronic sciatica and there is no evidence in acute sciatica, even though the practice is widespread. There is also limited evidence for the use of systemic corticosteroids in acute sciatica. Furthermore, the management of selective CT fluoroscopy transforaminal epidural steroid versus systemic steroids has never been directly studied. Methods and analysis SCIATICA is a pilot/feasibility study of patients with acute sciatica designed to evaluate the feasibility of undertaking a blinded four-arm randomised controlled intervention study of (1) selective CT fluoroscopy transforaminal epidural steroid (arm 1), (2) selective CT fluoroscopy transforaminal epidural saline (arm 2), (3) 15 days tapering dose of oral steroids (arm 3) and (4) a sham epidural and oral placebo control (arm 4). This feasibility study is designed to evaluate head-to-head, route versus pharmacology of interventions. The primary outcome measure is the Oswestry Disability Index (ODI) at 3 weeks. Secondary outcome is the ODI at 48 weeks. Other outcomes include numerical rating scale for leg pain, Pain DETECT Questionnaire, quality of life, medication use, rescue procedures or surgery, and adverse events. Results of outcomes from this randomised controlled trial will be used to determine the feasibility, sample size and power calculations for a large multicentre study. Ethics and dissemination The study has been approved by South Eastern Sydney Local Health District Human Research Ethics Committee (HREC/15/331/POHW/586). Trial registration number NCT03240783; Pre-results.
Branched rolling circle amplification method for measuring serum circulating microRNA levels for early breast cancer detection

Serum circulating microRNAs (c‐miRNAs) are serving as useful biomarkers for cancer diagnosis. Here, we describe the development of a one‐step branched rolling circle amplification (BRCA) method to measure serum c‐miRNAs levels for early diagnosis of breast cancer. Four c‐miRNAs, c‐miRNA16 (c‐miR‐16), c‐miRNA21 (c‐miR‐21), c‐miRNA155 (c‐miR‐155), and c‐miRNA195 (c‐miR‐195) were isolated from the serum of 49 breast cancer patients (stages I‐IV) and 19 healthy controls, and analyzed using one‐step BRCA. The serum levels of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 were higher (P < 0.0001) in stage I breast cancer patients than healthy controls. These levels were also higher in several breast cancer molecular subtypes (HER‐2 over‐expression, Luminal A, Luminal B, and triple negative breast cancer) than in healthy control subjects. The diagnostic accuracy of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 for early diagnosis of breast cancer was confirmed by receiver operating characteristic (ROC) curve assay. These results show that the BRCA method can be used to measure serum c‐miRNAs levels, and that this method has high accuracy, sensitivity, and specificity. Moreover, both BRCA approach and quantitative real‐time PCR (qRT‐PCR) method show that the serum levels of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 could be used as biomarkers to improve the early diagnosis of breast cancer, and distinguish different breast cancer molecular subtypes.
The interaction between DNA methylation and long non‐coding RNA during the onset of puberty in goats

Epigenetics plays an important role in controlling female puberty. Both DNA methylation and long non-coding RNAs (lncRNA) regulate the initiation of puberty by affecting the expression of genes related to puberty. While recent studies have indicated that DNA methylation of lncRNA represses the expression of lncRNA, its role in regulating puberty remains unclear. To explore the mechanism between DNA methylation and lncRNAs during puberty onset, we performed whole-genome bisulphite sequencing (WGBS) and RNA-sequencing (RNA-seq). We found that DNA methylation was inversely correlated to gene expression levels during puberty. Methylation levels gradually decreased near the transcription initiation site and were present at high levels in the exon, intron and 3' untranslated regions. In the promoter, lncRNA expression was negatively related to DNA methylation. We reported hypermethylation in the gene body and downstream of the lncRNA compared with upstream regions. In GO and KEGG analyses, we found enriched target genes of lncRNA, XLOC_960044 and XLOC_767346. During puberty, methylation of these genes increased while expression decreased. Our study indicates that DNA methylation of the promoter is negatively correlated with lncRNA during puberty onset, and methylation regulates the initiation of puberty via lncRNA, which provides new insight into the epigenetic mechanism of puberty onset.
Age‐associated changes in waking hippocampal sharp‐wave ripples

Hippocampal sharp‐wave ripples are brief high‐frequency (120–250 Hz) oscillatory events that support mnemonic processes during sleep and awake behavior. Although ripples occurring during sleep are believed to facilitate memory consolidation, waking ripples may also be involved in planning and memory retrieval. Recent work from our group determined that normal aging results in a significant reduction in the peak oscillatory frequency and rate‐of‐occurrence of ripples during sleep that may contribute to age‐associated memory decline. It is unknown, however, how aging alters waking ripples. We investigated whether characteristics of waking ripples undergo age‐dependent changes. Sharp‐wave ripple events were recorded from the CA1 region of the hippocampus in old (n = 5) and young (n = 6) F344 male rats as they performed a place‐dependent eyeblink conditioning task. Several novel observations emerged from this analysis. First, although aged rats expressed more waking ripples than young rats during track running and reward consumption, this effect was eliminated, and, in the case of track‐running, reversed when time spent in each location was accounted for. Thus, aged rats emit more ripples, but young rats express a higher ripple rate. This likely results from reduced locomotor activity in aged animals. Furthermore, although ripple rates increased as young rats approached rewards, rates did not increase in aged rats, and rates in aged and young animals were not affected by eyeblink conditioning. Finally, although the oscillatory frequency of ripples was lower in aged animals during rest, frequencies in aged rats increased during behavior to levels indistinguishable from young rats. Given the involvement of waking ripples in memory retrieval, a possible consequence of slower movement speeds of aged animals is to provide more opportunity to replay task‐relevant information and compensate for age‐related declines in ripple rate during task performance.
A characterization of postzygotic mutations identified in monozygotic twins

Postzygotic mutations are DNA changes acquired from the zygote stage onwards throughout the lifespan. These changes lead to differences in DNA sequence among cells of an individual, potentially contributing to the etiology of complex disorders. Here we compared whole genome DNA sequence data of two monozygotic twin pairs, 40 and 100 years old, to detect somatic mosaicism. DNA samples were sequenced twice on two Illumina platforms (13X and 40X read depth) for increased specificity. Using differences in allelic ratios resulted in sets of 1,720 and 1,739 putative postzygotic mutations in the 40‐year‐old twin pair and 100‐year‐old twin pair, respectively, for subsequent enrichment analysis. This set of putative mutations was strongly (p < 4.37e–91) enriched in both twin pairs for regulatory elements. The corresponding genes were significantly enriched for genes that are alternatively spliced, and for genes involved in GTPase activity. This research shows that somatic mosaicism can be detected in monozygotic twin pairs by using allelic ratios calculated from DNA sequence data and that the mutations which are found by this approach are not randomly distributed throughout the genome.
Intergenerational effects on mouse sperm quality after in utero exposure to acetaminophen and ibuprofen

Nonsteroidal antiinflammatory drugs and analgesic drugs, such as N‐acetyl‐p‐aminophenol (APAP; acetaminophen, paracetamol), are widely used by pregnant women. Accumulating evidence has indicated that these molecules can favor genital malformations in newborn boys and reproductive disorders in adults. However, the consequences on postnatal testis development and adult reproductive health after exposure during early embryo‐genesis are still unknown. Using the mouse model, we show that in utero exposure to therapeutic doses of the widely used APAP‐ibuprofen combination during the sex determination period leads to early differentiation and decreased proliferation of male embryonic germ cells, and early 5‐mefhylcytosine and extracellular matrix protein deposition in 13.5 d postcoitum exposed testes. Consequently, in postnatal testes, Sertoli‐cell maturation is delayed, the Leydig‐cell compartment is hyperplasia and the spermatogonia A pool is decreased. This results in a reduced production of testosterone and in epididymal sperm parameter defects. We observed a reduced sperm count (19%) in utero–exposed (FO) adult males and also a reduced sperm motility (40%) in their offspring (Fl) when both parents were exposed, which leads to subfertility among the 6 mo old Fl animals. Our study suggests that the use of these drugs during the critical period of sex determination affects the germ‐line development and leads to adverse effects that could be passed to the offspring. —Rossitto, M. , Marchive, C. , Pruvost, A. , Sellem, E. , Ghettas, A. , Badiou, S. , Sutra, T. , Poulat, F. , Philibert, P., Boizet‐Bonhoure, B. Intergenerational effects on mouse sperm quality after in utero exposure to acetaminophen and ibuprofen. FASEB J. 33, 339–357 (2019). www.fasebj. org
Policy-Level Specifications in REA Enterprise Information Systems

The Resource‐Event‐Agent (REA) enterprise model is a widely accepted framework for the design of the accountability infrastructure of enterprise information systems. Policy‐level specifications define constraints and guidelines under which an enterprise operates, and they are an extension to the REA enterprise model, adding the “what should, could, or must be” to the “what is. ” This paper aims both at comprehensive understanding of policy‐level definitions as part of REA enterprise systems and at understanding of the semantic constructs that enable such definitions. We first explore two distinctive semantic abstractions essential to policy‐level specifications: typification and grouping. The typification abstraction links instances of an object class to concepts for which they are concrete realizations, while the grouping abstraction aggregates objects into collections. We next present a number of patterns for the semantic modeling of policies. Following, we look at policy‐level applications for REA enter.
The N terminus of α-ENaC mediates ENaC cleavage and activation by furin

Epithelial Na+ channels comprise three homologous subunits (&agr;, &bgr;, and &ggr;) that are regulated by alternative splicing and proteolytic cleavage. Here, we determine the basis of the reduced Na+ current (INa) that results from expression of a previously identified, naturally occurring splice variant of the &agr; subunit (&agr;-ENaC), in which residues 34–82 are deleted (&agr;&Dgr;34–82). &agr;&Dgr;34–82-ENaC expression with WT &bgr; and &ggr; subunits in Xenopus oocytes produces reduced basal INa, which can largely be recovered by exogenous trypsin. With this &agr;&Dgr;34–82-containing ENaC, both &agr; and &ggr; subunits display decreased cleavage fragments, consistent with reduced processing by furin or furin-like convertases. Data using MTSET modification of a cysteine, introduced into the degenerin locus in &bgr;-ENaC, suggest that the reduced INa of &agr;&Dgr;34–82-ENaC arises from an increased population of uncleaved, near-silent ENaC, rather than from a reduced open probability spread uniformly across all channels. After treatment with brefeldin A to disrupt anterograde trafficking of channel subunits, INa in oocytes expressing &agr;&Dgr;34–82-ENaC is reestablished more slowly than that in oocytes expressing WT ENaC. Overnight or acute incubation of oocytes expressing WT ENaC in the pore blocker amiloride increases basal ENaC proteolytic stimulation, consistent with relief of Na+ feedback inhibition. These responses are reduced in oocytes expressing &agr;&Dgr;34–82-ENaC. We conclude that the &agr;-ENaC N terminus mediates interactions that govern the delivery of cleaved and uncleaved ENaC populations to the oocyte membrane.
Influenza A Virus Induces Autophagosomal Targeting of Ribosomal Proteins

Seasonal epidemics of influenza A virus are a major cause of severe illness and are of high socio-economic relevance. For the design of effective antiviral therapies, a detailed knowledge of pathways perturbed by virus infection is critical. We performed comprehensive expression and organellar proteomics experiments to study the cellular consequences of influenza A virus infection using three human epithelial cell lines derived from human lung carcinomas: A549, Calu-1 and NCI-H1299. As a common response, the type I interferon pathway was up-regulated upon infection. Interestingly, influenza A virus infection led to numerous cell line-specific responses affecting both protein abundance as well as subcellular localization. In A549 cells, the vesicular compartment appeared expanded after virus infection. The composition of autophagsomes was altered by targeting of ribosomes, viral mRNA and proteins to these double membrane vesicles. Thus, autophagy may support viral protein translation by promoting the clustering of the respective molecular machinery in autophagosomes in a cell line-dependent manner.
Siglec-6 on Chronic Lymphocytic Leukemia Cells Is a Target for Post-Allogeneic Hematopoietic Stem Cell Transplantation Antibodies

Mining the antibody repertoire of patients responding well to allogeneic hematopoietic stem cell transplantation (alloHST) can unveil targets with therapeutic potential. Through the use of phage display, Siglec-6 was identified as a major antigenic target of such antibodies. Although the 5-year survival rate of chronic lymphocytic leukemia (CLL) patients has risen to >80%, the only potentially curative treatment is allogeneic hematopoietic stem cell transplantation (alloHSCT). To identify possible new monoclonal antibody (mAb) drugs and targets for CLL, we previously developed a phage display–based human mAb platform to mine the antibody repertoire of patients who responded to alloHSCT. We had selected a group of highly homologous post-alloHSCT mAbs that bound to an unknown CLL cell surface antigen. Here, we show through next-generation sequencing of cDNAs encoding variable heavy-chain domains that these mAbs had a relative abundance of ∼0.1% in the post-alloHSCT antibody repertoire and were enriched ∼1,000-fold after three rounds of selection on primary CLL cells. Based on differential RNA-seq and a cell microarray screening technology for discovering human cell surface antigens, we now identify their antigen as Siglec-6. We verified this finding by flow cytometry, ELISA, siRNA knockdown, and surface plasmon resonance. Siglec-6 was broadly expressed in CLL and could be a potential target for antibody-based therapeutic interventions. Our study reaffirms the utility of post-alloHSCT antibody drug and target discovery. Cancer Immunol Res; 6(9); 1008–13. ©2018 AACR.
Effect of diverse physical rehabilitative interventions on static postural control in diabetic peripheral neuropathy: a systematic review

ABSTRACT Background and Purpose There are diverse forms of rehabilitative techniques available to improve postural control in diabetic peripheral neuropathy but little is known about the efficacy of these techniques. The primary focus of this review is to find out the effectiveness of diverse rehabilitative interventions in improving postural control in type 2 induced diabetic peripheral neuropathy. Methods: Two reviewers independently scrutinized the included studies. The selected studies underwent quality assessment by PEDro scale. Randomized Controlled Trial (RCT) having a score of 4 or more were included in the review. A search was conducted in PUBMED, MEDLINE, CINAHL, EMBASE, PROQUEST, Science Direct, Cochrane Library, Physiotherapy Evidence Database (PEDro) and Google Scholar. The Medical Subject Headings (MeSH) related to the interventions were also taken into account. Results: A total of 563 studies were identified and finally 8 studies were included in the review process. The included studies were 3 in task-specific balance training, 1 in treadmill, 1 in strengthening, 2 in whole body vibration, and 1 study in pilates analyzing posture using static posturography. No RCTs were reportedly found under tai chi and yoga. Conclusions: Interventions related to task-specific approach in balance training, treadmill, strengthening, WBV showed improvement in static postural control. Intervention with pilates did not show any beneficial effects. However, there still remains a need for quality trials as the results of these studies were ambivalent in interpretation and quality of the studies were limited by small sample size and higher attrition rates.