Miracle-dz/UniFAR-FTUs huggingface dataset:
Parenting stress in caregivers of children with chronic physical condition—A meta‐analysis

On the basis of the parenting stress model we compared levels of parenting stress in families with and without a child with a chronic physical condition and analysed correlates of parenting stress in families with a child with a chronic condition. A systematic search through electronic databases identified 547 relevant studies that were included in a random-effects meta-analysis. Parents of children with a chronic condition showed small to moderate elevations of general parenting stress and stress related to the parent-child relationship in particular. They showed moderate to large elevations in health-related parenting stress. Parents of children with cancer, cerebral palsy, HIV infection or AIDS, and spina bifida showed the highest levels of parenting stress. Stress levels also varied by illness severity and duration, child age, parental gender and mental health, marital status, marital quality, and levels of perceived support. Behaviour problems of the child and low parental mental health were the strongest correlates of parenting stress. The present results assist with identifying parents at highest needs for interventions aimed at reducing parenting stress. These interventions should address the reduction of child behaviour problems, the promotion of parental mental health, the increase in marital quality and social support in general, and skills for dealing with stressors.
How Constraints Affect Content: The Case of Twitter's Switch from 140 to 280 Characters

It is often said that constraints affect creative production, both in terms of form and quality. Online social media platforms frequently impose constraints on the content that users can produce, limiting the range of possible contributions. Do these restrictions tend to push creators towards producing more or less successful content? How do creators adapt their contributions to fit the limits imposed by social media platforms? To answer these questions, we conduct an observational study of a recent event: on November 7, 2017, Twitter changed the maximum allowable length of a tweet from 140 to 280 characters, thereby significantly altering its signature constraint. In the first study of this switch, we compare tweets with nearly or exactly 140 characters before the change to tweets of the same length posted after the change. This setup enables us to characterize how users alter their tweets to fit the constraint and how this affects their tweets' success. We find that in response to a length constraint, users write more tersely, use more abbreviations and contracted forms, and use fewer definite articles. Also, although in general tweet success increases with length, we find initial evidence that tweets made to fit the 140-character constraint tend to be more successful than similar-length tweets written when the constraint was removed, suggesting that the length constraint improved tweet quality.
Binary System Exhibiting the Nematic to Twist-Bend Nematic Transition: Behavior of Permittivity and Elastic Constants.

We describe measurements of the permittivity and Frank elastic constant in the nematic phase of a binary system displaying a transition between the nematic (N) and the recently discovered twist-bend nematic (NTB) phase. Among the salient features observed are (i) the existence of the NTB phase even when the system is loaded with a high concentration (∼64 mol %) of a rodlike component; (ii) a clear signature in permittivity of the N–NTB transition; and (iii) a lower value of the bend elastic constant compared to the splay over a large phase space, with the difference between the two becoming a maximum for an intermediate mixture. These studies further support the surprising idea that the elastic features associated with bent molecules can be further augmented by suitable rodlike additives.
Factors associated with online victimisation among Malaysian adolescents who use social networking sites: a cross-sectional study

Objective To determine the prevalence of online interpersonal victimisation and its association with patterns of social networking site (SNS) use, offline victimisation, offline perpetration and parental conflict among Malaysian adolescents using SNS. Methods A cross-sectional study of students from randomly selected public secondary schools in the state of Negeri Sembilan was conducted using an anonymous self-administered questionnaire. The questionnaire examined patterns of SNS use and included measures of online victimisation, online perpetration, offline victimisation and parental conflict. A response rate of 91% from a total of 1634 yielded a sample of 1487 students between 15 years and 16 years of age. Results Ninety-two per cent of respondents had used at least one SNS. More than half of SNS users (52.2%) reported experiences of online victimisation over the past 12 months. Boys were significantly more likely to experience online harassment compared with girls (52.2% vs 43.3%, p<0.001). There were no significant gender differences in experiences of unwanted sexual solicitation. Adolescents who engaged in perpetration behaviours online had almost six times higher odds of reporting frequent online victimisation compared with online behaviours involving personal disclosure. There was a significant dose-response relationship between engagement in multiple types of online behaviour and the risk of frequent online victimisation. Both online and offline perpetrations were associated with an increased risk of victimisation. Those who were victimised offline or experienced parental conflict were twice as likely to report online victimisation. Conclusion Interventions to prevent online electronic aggression should target perpetration behaviour both online and offline. Youth should be equipped with skills in communication and decision-making in relationships that can be applied across a spectrum of contexts both online and offline.
Cholinergic signaling mediates the effects of xenin-25 on secretion of pancreatic polypeptide but not insulin or glucagon in humans with impaired glucose tolerance

We previously demonstrated that infusion of an intestinal peptide called xenin-25 (Xen) amplifies the effects of glucose-dependent insulinotropic polypeptide (GIP) on insulin secretion rates (ISRs) and plasma glucagon levels in humans. However, these effects of Xen, but not GIP, were blunted in humans with type 2 diabetes. Thus, Xen rather than GIP signaling to islets fails early during development of type 2 diabetes. The current crossover study determines if cholinergic signaling relays the effects of Xen on insulin and glucagon release in humans as in mice. Fasted subjects with impaired glucose tolerance were studied. On eight separate occasions, each person underwent a single graded glucose infusion- two each with infusion of albumin, Xen, GIP, and GIP plus Xen. Each infusate was administered ± atropine. Heart rate and plasma glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide (PP) levels were measured. ISRs were calculated from C-peptide levels. All peptides profoundly increased PP responses. From 0 to 40 min, peptide(s) infusions had little effect on plasma glucose concentrations. However, GIP, but not Xen, rapidly and transiently increased ISRs and glucagon levels. Both responses were further amplified when Xen was co-administered with GIP. From 40 to 240 min, glucose levels and ISRs continually increased while glucagon concentrations declined, regardless of infusate. Atropine increased resting heart rate and blocked all PP responses but did not affect ISRs or plasma glucagon levels during any of the peptide infusions. Thus, cholinergic signaling mediates the effects of Xen on insulin and glucagon release in mice but not humans.
The REAnimation Low Immune Status Markers (REALISM) project: a protocol for broad characterisation and follow-up of injury-induced immunosuppression in intensive care unit (ICU) critically ill patients

Introduction The host response to septic shock is dynamic and complex. A sepsis-induced immunosuppression phase has recently been acknowledged and linked to bad outcomes and increased healthcare costs. Moreover, a marked suppression of the immune response has also been partially described in patients hospitalized in intensive care unit (ICU) for severe trauma or burns. It has been hypothesized that immune monitoring could enable identification of patients who might most benefit from novel, adjunctive immune-stimulating therapies. However, there is currently neither a clear definition for such injury-induced immunosuppression nor a stratification biomarker compatible with clinical constraints. Methods and analysis We set up a prospective, longitudinal single-centre clinical study to determine the incidence, severity and persistency of innate and adaptive immune alterations in ICU patients. We optimized a workflow to describe and follow the immunoinflammatory status of 550 patients (septic shock, severe trauma/burn and major surgery) during the first 2 months after their initial injury. On each time point, two immune functional tests will be performed to determine whole-blood TNF-α production in response to ex vivo lipopolysaccharide stimulation and the T lymphocyte proliferation in response to phytohaemagglutinin. In addition, a complete immunophenotyping using flow cytometry including monocyte HLA-DR expression and lymphocyte subsets will be obtained. New markers (ie, levels of expression of host mRNA and viral reactivation) will be also evaluated. Reference intervals will be determined from a cohort of 150 age-matched healthy volunteers. This clinical study will provide, for the first time, data describing the immune status of severe ICU patients over time. Ethics and dissemination Ethical approval has been obtained from the institutional review board (no 69HCL15_0379) and the French National Security agency for drugs and health-related products. Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals. Trial registration number Clinicaltrials.gov Registration number: NCT02638779. Pre-results.
Distinct Growth and Secretome Strategies for Two Taxonomically Divergent Brown Rot Fungi

ABSTRACT Brown rot fungi are wood-degrading fungi that employ both oxidative and hydrolytic mechanisms to degrade wood. Hydroxyl radicals that facilitate the oxidative component are powerful nonselective oxidants and are incompatible with hydrolytic enzymes unless they are spatially segregated in wood. Differential gene expression has been implicated in the segregation of these reactions in Postia placenta, but it is unclear if this two-step mechanism varies in other brown rot fungi with different traits and life history strategies that occupy different niches in nature. We employed proteomics to analyze a progression of wood decay on thin wafers, using brown rot fungi with significant taxonomic and niche distances: Serpula lacrymans (Boletales; “dry rot” lumber decay) and Gloeophyllum trabeum (order Gloeophyllales; slash, downed wood). Both fungi produced greater oxidoreductase diversity upon wood colonization and greater glycoside hydrolase activity later, consistent with a two-step mechanism. The two fungi invested very differently, however, in terms of growth (infrastructure) versus protein secretion (resource capture), with the ergosterol/extracted protein ratio being 7-fold higher with S. lacrymans than with G. trabeum. In line with the native substrate associations of these fungi, hemicellulase-specific activities were dominated by mannanase in S. lacrymans and by xylanase in G. trabeum. Consistent with previous observations, S. lacrymans did not produce glycoside hydrolase 6 (GH6) cellobiohydrolases (CBHs) in this study, despite taxonomically belonging to the order Boletales, which is distinguished among brown rot fungi by having CBH genes. This work suggests that distantly related brown rot fungi employ staggered mechanisms to degrade wood, but the underlying strategies vary among taxa. IMPORTANCE Wood-degrading fungi are important in forest nutrient cycling and offer promise in biotechnological applications. Brown rot fungi are unique among these fungi in that they use a nonenzymatic oxidative pretreatment before enzymatic carbohydrate hydrolysis, enabling selective removal of carbohydrates from lignin. This capacity has independently evolved multiple times, but it is unclear if different mechanisms underpin similar outcomes. Here, we grew fungi directionally on wood wafers and we found similar two-step mechanisms in taxonomically divergent brown rot fungi. The results, however, revealed strikingly different growth strategies, with S. lacrymans investing more in biomass production than secretion of proteins and G. trabeum showing the opposite pattern, with a high diversity of uncharacterized proteins. The “simplified” S. lacrymans secretomic system could help narrow gene targets central to oxidative brown rot pretreatments, and a comparison of its distinctions with G. trabeum and other brown rot fungi (e.g., Postia placenta) might offer similar traction in noncatabolic genes.
Molecular dynamics simulation and binding free energy studies of novel leads belonging to the benzofuran class inhibitors of Mycobacterium tuberculosis Polyketide Synthase 13

In this work, the binding mechanism of new Polyketide Synthase 13 (Pks13) inhibitors has been studied through molecular dynamics simulation and free energy calculations. The drug Tam1 and its analogs, belonging to the benzofuran class, were submitted to 100 ns simulations, and according to the results obtained for root mean square deviation, all the simulations converged from approximately 30 ns. For the analysis of backbone flotation, the root mean square fluctuations were plotted for the Cα atoms; analysis revealed that the greatest fluctuation occurred in the residues that are part of the protein lid domain. The binding free energy value (ΔGbind) obtained for the Tam16 lead molecule was of −51.43 kcal/mol. When comparing this result with the ΔGbind values for the remaining analogs, the drug Tam16 was found to be the highest ranked: this result is in agreement with the experimental results obtained by Aggarwal and collaborators, where it was verified that the IC50 for Tam16 is the smallest necessary to inhibit the Pks13 (IC50 = 0.19 μM). The energy decomposition analysis suggested that the residues which most interact with inhibitors are: Ser1636, Tyr1637, Asn1640, Ala1667, Phe1670, and Tyr1674, from which the greatest energy contribution to Phe1670 was particularly notable. For the lead molecule Tam16, a hydrogen bond with the hydroxyl of the phenol not observed in the other analogs induced a more stable molecular structure. Aggarwal and colleagues reported this hydrogen bonding as being responsible for the stability of the molecule, optimizing its physic-chemical, toxicological, and pharmacokinetic properties.
The Landscape of Somatic Genetic Alterations in Metaplastic Breast Carcinomas

Purpose: Metaplastic breast carcinoma (MBC) is a rare and aggressive histologic type of breast cancer, predominantly of triple-negative phenotype, and characterized by the presence of malignant cells showing squamous and/or mesenchymal differentiation. We sought to define the repertoire of somatic genetic alterations and the mutational signatures of MBCs. Experimental Design: Whole-exome sequencing was performed in 35 MBCs, with 16, 10, and 9 classified as harboring chondroid, spindle, and squamous metaplasia as the predominant metaplastic component. The genomic landscape of MBCs was compared with that of triple-negative invasive ductal carcinomas of no special type (IDC-NST) from The Cancer Genome Atlas. Wnt and PI3K/AKT/mTOR pathway activity was assessed using a qPCR assay. Results: MBCs harbored complex genomes with frequent TP53 (69%) mutations. In contrast to triple-negative IDC-NSTs, MBCs more frequently harbored mutations in PIK3CA (29%), PIK3R1 (11%), ARID1A (11%), FAT1 (11%), and PTEN (11%). PIK3CA mutations were not found in MBCs with chondroid metaplasia. Compared with triple-negative IDC-NSTs, MBCs significantly more frequently harbored mutations in PI3K/AKT/mTOR pathway–related (57% vs. 22%) and canonical Wnt pathway–related (51% vs. 28%) genes. MBCs with somatic mutations in PI3K/AKT/mTOR or Wnt pathway–related genes displayed increased activity of the respective pathway. Conclusions: MBCs are genetically complex and heterogeneous, and are driven by a repertoire of somatic mutations distinct from that of triple-negative IDC-NSTs. Our study highlights the genetic basis and the importance of PI3K/AKT/mTOR and Wnt pathway dysregulation in MBCs and provides a rationale for the metaplastic phenotype and the reported responses to PI3K/AKT/mTOR inhibitors in these tumors. Clin Cancer Res; 23(14); 3859–70. ©2017 AACR.
Dyadic resources in the return to work of cancer survivors: exploring supervisor–employee perspectives

Abstract Purpose: The number of working-age people recovering from cancer is gradually on the rise; yet, cancer survivors have higher rates of unemployment compared to other employees. Cancer survivors returning to work cope with symptoms of fatigue, distress, cognitive difficulties and physical limitations. The present article addresses the supervisor–cancer survivor dyad as the unit of analysis, in an attempt to identify the dyadic resources that underlie the coping of the supervisor–employee unit with return to work. Materials and methods: In-depth, semi-structured individual interviews were conducted with 12 dyads of cancer survivors and their supervisors, representing successful return to work, followed by comparative content analysis of the data. Results: Four themes were revealed: (1) Congruent supervisor–cancer survivor views regarding personalized/standard management of cancer survivors’ returning to work; (2) Return to work as a team work approach; (3) Commitment and persistence in the face of obstacles, and (4) Supervisor and cancer survivor mutual appreciation. Conclusions: Joint coping of supervisors and cancer survivors with the difficulties of the return to work process is perceived to contribute significantly to the success of return to work. Training of cancer survivors and supervisors conducted by rehabilitation professionals regarding aspects of the orientation toward return to work is suggested. Implication for rehabilitation Cancer survivors have different preferences regarding standard versus exceptional organizational treatment following return to work. Organizational acknowledgment of the cancer survivor’s value for the organizations supports cancer survivors’ return to work. Cancer survivors can benefit from a sense of responsibility and involvement in decision making regarding the process of return to work.
Home-based versus centre-based cardiac rehabilitation.

BACKGROUND The burden of cardiovascular disease world-wide is one of great concern to patients and health care agencies alike. Traditionally centre-based cardiac rehabilitation (CR) programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. OBJECTIVES To determine the effectiveness of home-based cardiac rehabilitation programmes compared with supervised centre-based cardiac rehabilitation on mortality and morbidity, health-related quality of life and modifiable cardiac risk factors in patients with coronary heart disease. SEARCH STRATEGY We updated the search of a previous review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2007, Issue 4), MEDLINE, EMBASE and CINAHL from 2001 to January 2008. We checked reference lists and sought advice from experts. No language restrictions were applied. SELECTION CRITERIA Randomised controlled trials (RCTs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes, in adults with myocardial infarction, angina, heart failure or who had undergone revascularisation. DATA COLLECTION AND ANALYSIS Studies were selected independently by two reviewers, and data extracted by a single reviewer and checked by a second one. Authors were contacted where possible to obtain missing information. MAIN RESULTS Twelve studies (1,938 participants) met the inclusion criteria. The majority of studies recruited a lower risk patient following an acute myocardial infarction (MI) and revascularisation. There was no difference in outcomes of home- versus centre-based cardiac rehabilitation in mortality risk ratio (RR) was1.31 (95% confidence interval (C) 0.65 to 2.66), cardiac events, exercise capacity standardised mean difference (SMD) -0.11 (95% CI -0.35 to 0.13), as well as in modifiable risk factors (systolic blood pressure; diastolic blood pressure; total cholesterol; HDL-cholesterol; LDL-cholesterol) or proportion of smokers at follow up or health-related quality of life. There was no consistent difference in the healthcare costs of the two forms of cardiac rehabilitation. AUTHORS' CONCLUSIONS Home- and centre-based cardiac rehabilitation appear to be equally effective in improving the clinical and health-related quality of life outcomes in acute MI and revascularisation patients. This finding, together with an absence of evidence of difference in healthcare costs between the two approaches, would support the extension of home-based cardiac rehabilitation programmes such as the Heart Manual to give patients a choice in line with their preferences, which may have an impact on uptake of cardiac rehabilitation in the individual case.
Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation

Significance Recent success of T cell-based cancer immunotherapies highlights the importance of further understanding molecular mechanisms in the regulation of T cell responsiveness. Here, we performed a genome-wide CRISPR screen to identify genes that regulate T cell activation upon anti-T cell receptor (TCR) stimulation. Our screen confirmed many of the known regulators in proximal T cell signaling. Moreover, we identified a previously uncharacterized gene named FAM49B, which acts as a negative regulator in T cell activation. Our study suggests that genome-wide CRISPR screening is a powerful means to identify key regulators of TCR signaling. The same strategy could be applied to CD28-mediated costimulatory signaling or PD-1–mediated coinhibitory signaling. The unbiased approach presented here may allow us to identify new therapeutic targets for cancer immunotherapy. Despite decades of research, mechanisms controlling T cell activation remain only partially understood, which hampers T cell-based immune cancer therapies. Here, we performed a genome-wide CRISPR screen to search for genes that regulate T cell activation. Our screen confirmed many of the known regulators in proximal T cell receptor signaling and, importantly, also uncovered a previously uncharacterized regulator, FAM49B (family with sequence similarity 49 member B). FAM49B deficiency led to hyperactivation of Jurkat T cells following T cell receptor stimulation, as indicated by enhancement of CD69 induction, PAK phosphorylation, and actin assembly. FAM49B directly interacted with the active form of the small GTPase Rac, and genetic disruption of the FAM49B–Rac interaction compromised FAM49B function. Thus, FAM49B inhibits T cell activation by repressing Rac activity and modulating cytoskeleton reorganization.