Miracle-dz/UniFAR-FTUs huggingface dataset:
Stonewall prevents expression of ectopic genes in the ovary and accumulates at insulator elements in D. melanogaster

Germline stem cells (GSCs) are the progenitor cells of the germline for the lifetime of an animal. In Drosophila, these cells reside in a cellular niche that is required for both their maintenance (self-renewal) and differentiation (asymmetric division resulting in a daughter cell that differs from the GSC). The stem cell—daughter cell transition is tightly regulated by a number of processes, including an array of proteins required for genome stability. The germline stem-cell maintenance factor Stonewall (Stwl) associates with heterochromatin, but its molecular function is poorly understood. We performed RNA-Seq on stwl mutant ovaries and found significant derepression of many transposon families but not heterochromatic genes. We also discovered inappropriate expression of multiple classes of genes. Most prominent are testis-enriched genes, including the male germline sex-determination switch Phf7, the differentiation factor bgcn, and a large testis-specific gene cluster on chromosome 2, all of which are upregulated or ectopically expressed in stwl mutant ovaries. Surprisingly, we also found that RNAi knockdown of stwl in somatic S2 cells results in ectopic expression of these testis genes. Using parallel ChIP-Seq and RNA-Seq experiments in S2 cells, we discovered that Stwl localizes upstream of transcription start sites and at heterochromatic sequences including repetitive sequences associated with telomeres. Stwl is also enriched at bgcn, suggesting that it directly regulates this essential differentiation factor. Finally, we identify Stwl binding motifs that are shared with known insulator binding proteins. We propose that Stwl affects gene regulation, including repression of male transcripts in the female germline, by binding insulators and establishing chromatin boundaries.
Keep it SIMPL: Improved Feedback After Implementation of an App-Based Feedback Tool

Background Data defining the utility of the system for improving and measuring procedural learning (SIMPL) in surgical education is limited. The aim of this pilot study is to describe the impact of SIMPL on resident and faculty perspectives regarding operative feedback. Methods Residents and faculty were surveyed prior to and 6 months after SIMPL implementation. Associations were analyzed using χ 2 for categorical and Student’s t-test for continuous variables. Statistical significance was defined as P-value < . 05. Results The proportion of residents receiving intraoperative feedback at least once/day increased significantly (35% to 73%, P = .025); there was a trend toward increased postoperative feedback (15% to 33%, P = .201). Faculty reported an increase in intraoperative (55% to 91%, P = .041) and postoperative feedback (21% to 64%, P = .020). Satisfaction with intraoperative feedback improved from a score of 3.50 ± 1.05 to 3.93 ± . 62, although not statistically significant (P = .181). Satisfaction with postoperative feedback improved significantly from 2.85 ± . 93 to 3.50 ± . 65 (P = .032). The proportion of faculty who felt they were providing effective feedback increased (53% to 91%, P = .032). The proportion of residents who perceived that feedback enhanced their surgical skill increased as well (65% to 93%, P = .048). Discussion Despite a modest increase in frequency of postoperative feedback, perceived quality of feedback improved substantially after implementation of SIMPL. Introduction of SIMPL also increased the amount of feedback provided by faculty intraoperatively. SIMPL, via direct and indirect effects, has a positive impact on the resident operative learning environment. Further work is necessary to examine the influence this may have on resident operative skill and patient outcomes.
The Impact of Healthcare 4.0 on the Healthcare Service Quality: A Systematic Literature Review

Abstract Healthcare 4.0 is inspired by Industry 4.0 and its application has resulted in a paradigmatic shift in the field of healthcare. However, the impact of this digital revolution in the healthcare system on healthcare service quality is not known. The purpose of this study is to examine the impact of healthcare 4.0 on healthcare service quality. This study used the systematic literature review methodology suggested by Transfield et al. to critically examine 67 articles. The impact of healthcare 4.0 is analyzed in-depth in terms of the interpersonal, technical, environmental, and administrative aspect of healthcare service quality. This study will be useful to hospitals and other stakeholders to understand the impact of healthcare 4.0 on the service quality of health systems. Besides, this study critically analyses the existing literature and identifies research areas in this field and hence will be beneficial to researchers. Though there are few literature reviews in healthcare 4.0, this is the first study to examine the impact of Healthcare 4.0 on healthcare service quality.
A Comparison between Conventional and Extracorporeal Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis

There is limited evidence comparing the use of extracorporeal cardiopulmonary resuscitation (ECPR) to CPR in the management of refractory out-of-hospital cardiac arrest (OHCA). We conducted a systematic review and meta-analysis to compare survival and neurologic outcomes associated with ECPR versus CPR in the management of OHCA. We searched PubMed, EMBASE, and Scopus to identify observational studies and randomized controlled trials comparing ECPR and CPR. We used the Newcastle–Ottawa Scale and Cochrane’s risk-of-bias tool to assess studies’ quality. We used random-effects models to compare outcomes between the pooled populations and moderator analysis to identify sources of heterogeneity and perform subgroup analysis. We identified 2088 articles and included 13, with 18,620 patients with OHCA. A total of 16,701 received CPR and 1919 received ECPR. Compared with CPR, ECPR was associated with higher odds of achieving favorable neurologic outcomes at 3 (OR 5, 95% CI 1.90–13.1, p < 0.01) and 6 months (OR 4.44, 95% CI 2.3–8.5, p < 0.01). We did not find a significant survival benefit or impact on neurologic outcomes at hospital discharge or 1 month following arrest. ECPR is a promising but resource-intensive intervention with the potential to improve long-term outcomes among patients with OHCA.
Phenytoin and damage to the cerebellum – a systematic review of published cases

ABSTRACT Introduction The antiseizure medication phenytoin has been associated with changes in the cerebellum, cerebellar signs, and permanent cerebellar damage. We have systematically reviewed the clinical and radiological features, and their correlation. Areas covered We identified sixty case reports and case series of the effects of phenytoin on the cerebellum by searching Medline and Embase and relevant reference lists. The reports described 92 [median 1, range 1–5] cases, documented median age 28 [2.7–78] years. Eighty-one cases described one or more clinical sign of ataxia (present in 96%), dysarthria (63%), and nystagmus (70%). The neurological outcome (in 76 cases): 10 (13%) recovered by 12 months; 55 (72%) suffered residual disability; and 11 (14%) died. Median serum phenytoin concentration (48 cases) was 50 (interquartile range 31–66) mg/L; only three values were below 20 mg/L. The radiological findings included cerebellar atrophy in 41 of 61 patients (67%) with at least one scan. Expert opinion Evidence mainly comes from case reports, and is inevitably biased. Most patients with cerebellar dysfunction have phenytoin concentrations above the reference range. Clinical signs of ataxia can persist without radiological evidence of cerebellar atrophy, and cerebellar atrophy is seen without any clinical evidence of cerebellar dysfunction.
A cluster randomized non‑inferiority field trial of gestational diabetes mellitus screening.

CONTEXT Although it is well-acknowledged that gestational diabetes mellitus (GDM) is associated with the increased risks of adverse pregnancy outcomes, the optimal strategy for screening and diagnosis of GDM are still a matter of debate. OBJECTIVE This study was conducted to demonstrate the non-inferiority of less strict GDM-screening criteria compared to the strict International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria with respect to maternal and neonatal outcomes. METHODS A cluster randomized non-inferiority field-trial was conducted on 35528 pregnant women; they were scheduled to have two phases of GDM-screening, based on five different pre-specified protocols including fasting plasma glucose in the first trimester with threshold of 5.1 mmol/L (92 mg/dL) (protocols A, D) or 5.6 mmol/L (100 mg/dL) (protocols B, C, E) and either a one-step (GDM is defined if one of the plasma glucose values is exceeded ( protocol A and C) or two or more exceeded values are needed (protocol B)) or two-step approach (protocol D, E) in the second trimester. Guidelines for treatment of GDM were consistent with all protocols. Primary outcomes of the study were the prevalence of macrosomia and primary cesarean-section (C-S). The null hypothesis that less strict protocols are inferior to protocol A (IADPSG) was tested with a non-inferiority margin effect (OR) of 1.7. RESULTS The percentages of pregnant women diagnosed with GDM and assigned to protocols A, B, C, D and E were 21.9%, 10.5%, 12.1%, 19.4%, and 8.1%, respectively. Intention to treat (ITT) analyses satisfying the non-inferiority of the less strict protocols of B, C, D and E compared to protocol A. However, non-inferiority was not shown for primary C-section comparing protocol E vs A. The ORs (95% CI) for macrosomia and C-S were: B (1.01(0.95-1.08); 0.85(0.56- 1.28), C (1.03, (0.73-1.47); 1.16, (0.88-1.51)), D (0.89(0.68-1.17); 0.94, (0.61-1.44)) and E (1.05, (0.65-1.69); 1.33, (0.82-2.00)) versus A. There were no statistically significant differences in the adjusted odds of adverse pregnancy outcomes in the two-step compared to one-step screening approaches, considering multiplicity adjustment. CONCLUSIONS The IADPSG GDM-definition significantly increased the prevalence of GDM diagnosis. However, the less strict approaches were not inferior to other criteria in terms of adverse maternal and neonatal outcomes.
Comparative analyses of small molecule and antibody inhibition on glycoprotein‐mediated entry of Měnglà virus with other filoviruses

The ability of viruses in the Filoviridae family (Ebola virus [EBOV] and Marburg virus [MARV]) to cause severe human disease and their pandemic potential makes all emerging filoviral pathogens a concern to humanity. Měnglà virus (MLAV) belonging to the new genus Dianlovirus was recently discovered in the liver of bats from Měnglà County, Yunnan Province, China. The capacity of MLAV to utilize NPC1 as an endosomal receptor, to transduce mammalian cells, and suppress IFN response suggests that this potential pathogen could cause human illness. Despite great effort by researchers, only the viral genome has been recovered and isolation of live MLAV had been unsuccessful. Here using a pseudovirus model baring the MLAV glycoprotein (GP), we studied the protease dependence of the MLAV‐GP, and the ability of small molecules and antibodies to inhibit MLAV viral entry. Like EBOV and MARV, the MLAV‐GP requires proteolytic processing but like MARV it does not depend on cathepsin B activity for viral entry. Furthermore, previously discovered small‐molecule inhibitors and antibodies are MLAV inhibitors and show the possibility of developing these inhibitors as broad‐spectrum filovirus antivirals. Overall, the findings in the study confirmed that MLAV viral entry is biologically distinct but has similarities to MARV.
The contribution of extra‐pair paternity to the variation in lifetime and age‐specific male reproductive success in a socially monogamous species

In socially monogamous species, extra‐pair paternity (EPP) is predicted to increase variance in male reproductive success (RS) beyond that resulting from genetic monogamy, thus, increasing the “opportunity for selection” (maximum strength of selection that can act on traits). This prediction is challenging to investigate in wild populations because lifetime reproduction data are often incomplete. Moreover, age‐specific variances in reproduction have been rarely quantified. We analyzed 21 years of near‐complete social and genetic reproduction data from an insular population of Seychelles warblers (Acrocephalus sechellensis). We quantified EPP's contribution to lifetime and age‐specific opportunities for selection in males. We compared the variance in male genetic RS vs social (“apparent”) RS (RSap) to assess if EPP increased the opportunity for selection over that resulting from genetic monogamy. Despite not causing a statistically significant excess (19%) of the former over the latter, EPP contributed substantially (27%) to the variance in lifetime RS, similarly to within‐pair paternity (WPP, 39%) and to the positive WPP‐EPP covariance (34%). Partitioning the opportunity for selection into age‐specific (co)variance components, showed that EPP also provided a substantial contribution at most ages, varying with age. Therefore, despite possibly not playing the main role in shaping sexual selection in Seychelles warblers, EPP provided a substantial contribution to the lifetime and age‐specific opportunity for selection, which can influence evolutionary processes in age‐structured populations.
Childhood perspectives of parental young onset dementia: A qualitative data synthesis

Background While it is less common, young onset dementia manifests at a significantly younger age (< 65). Many people with young onset dementia are parents; however, little is known about impact of the condition on children and young adults. A qualitative thematic analysis was conducted to synthesise the literature on the perspectives of children and young adults with a parent living with young onset dementia. Methods Electronic databases were searched in order to identify all peer-reviewed literature in relation to the perspectives of children and young adults with a parent living with young onset dementia. A thematic analysis was conducted on the relevant literature. Results The electronic database search resulted in 15 full texts articles. Four main themes with related subthemes emerged from the thematic analysis. The four main themes were: changing family dynamics; psychological and physical strain; stigma and coping strategies. Conclusion The current synthesis outlines the perspectives of children and young adults with a parent living with young onset dementia. There is a significant lack of research in this area which adds to the stereotypical view of dementia as an older person’s disease. This can lead to children and young adults being impacted by lack of awareness and stigma resulting in significant psychosocial problems. As the number of people living with dementia (including young onset) is set to increase, future research with children and young adults with a parent with young onset dementia is important in order to better support this cohort.
Newly designed foraminifera primers identify habitat‐specific lineages through metabarcoding analyses

Foraminifera include diverse shell‐building lineages found in a wide array of aquatic habitats from the deep‐sea to intertidal zones to brackish and freshwater ecosystems. Recent estimates of morphological and molecular foraminifera diversity have increased the knowledge of foraminiferal diversity, which is critical as these lineages are used as bioindicators of past and present environmental perturbation. However, a comparative analysis of foraminiferal biodiversity between their major habitats (freshwater, brackish, intertidal, and marine) is underexplored, particularly using molecular tools. Here, we present a metabarcoding survey of foraminiferal diversity across different ecosystems using newly designed foraminifera‐specific primers that target the hypervariable regions of the foraminifera SSU‐rRNA gene (~250–300 bp long). We tested these primer sets on four foraminifera species and then across several environments: the intertidal zone, coastal ecosystems, and freshwater vernal pools. We retrieved 655 operational taxonomic units (OTUs); the majority of which are undetermined taxa that have no closely matching sequences in the reference database. Furthermore, we identified 163 OTUs with distinct habitat preferences. Most of the observed OTUs belonged to lineages of single‐chambered foraminifera, including poorly explored freshwater foraminifera which encompass a clade of Reticulomyxa‐like forms. Our pilot study provides the community with an additional set of newly designed and taxon‐specific primers to elucidate foraminiferal diversity across different habitats.
Neural Stem/Progenitor Cell Transplantation in Parkinson’s Rodent Animals: A Meta-Analysis and Systematic Review

Abstract The effects of neural stem/progenitor cells (NSPCs) have been extensively evaluated by multiple studies in animal models of Parkinson’s disease (PD), but the therapeutic efficacy was inconsistent. Here, we searched 4 databases (PubMed, Embase, Scopus, and Web of Science) and performed a meta-analysis to estimate the therapeutic effects of unmodified NSPCs on neurological deficits in rodent animal models of PD. Data on study quality score, behavioral outcomes (apomorphine or amphetamine-induced rotation and limb function), histological outcome (densitometry of TH+ staining in the SNpc), and cell therapy-related severe adverse events were extracted for meta-analysis and systematic review. Twenty-one studies with a median quality score of 6 (range from 4 to 9) in 11 were examined. Significant improvement was observed in the overall pooled standardized mean difference (SMD) between animals transplanted with NSPCs and with control medium (1.22 for apomorphine-induced rotation, P < .001; 1.50 for amphetamine-induced rotation, P < .001; 0.86 for limb function, P < .001; and –1.96 for the densitometry of TH+ staining, P < .001). Further subgroup analysis, animal gender, NSPCs source, NSPCs dosage, and pretreatment behavioral assessment were closely correlated with apomorphine-induced rotation and amphetamine-induced rotation. In conclusion, unmodified NSPCs therapy attenuated behavioral deficits and increased dopaminergic neurons in rodent PD models, supporting the consideration of early-stage clinical trial of NSPCs in patients with PD.
Low volume proximal suprascapular nerve block after arthroscopic shoulder surgery – A randomised, controlled trial

A proximal suprascapular nerve block has been suggested as an alternative to an interscalene brachial plexus block after arthroscopic shoulder surgery. The aim of this randomised controlled trial was to compare the analgesic and opioid‐sparing effect of a low volume proximal suprascapular nerve block with placebo in patients with moderate‐to‐severe pain after arthroscopic shoulder surgery.
A molecular interpretation of the toughness of multiple network elastomers at high temperature

Significance Soft materials can be toughened by creating dissipative mechanisms in stretchy matrixes. Yet using them over a wide range of temperatures requires dissipative mechanisms independent of stretch rate or temperature. We show that sacrificial covalent bonds in multiple network elastomers are most useful in toughening elastomers at high temperature and act synergistically with viscoelasticity at lower temperature. We do not attribute this toughening mechanism only to the scission of bonds during crack propagation but propose that the highly stretched network diluted in a stretchy matrix acts by simultaneously stiffening the elastomer and delaying the localization of bond scission and the propagation of a crack. Such a toughening mechanism has never been proposed for elastomers and should guide network design.
Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe

The conventional targeted delivery of chemotherapeutic and diagnostic agents utilizing nanocarriers is a promising approach for cancer theranostics. Unfortunately, this approach often faces hindered tumor access that decreases the therapeutic index and limits the further clinical translation of a developing drug. Here, we demonstrated a strategy of simultaneously double-targeting the drug to two distinct cites of tumor tissue: the tumor endothelium and cell surface receptors. We used fourth-generation polyamideamine dendrimers modified with a chelated Gd and functionalized with selectin ligand and alpha-fetoprotein receptor-binding peptide. According to the proposed strategy, IELLQAR peptide promotes the conjugate recruitment to the tumor inflammatory microenvironment and enhances extravasation through the interaction of nanodevice with P- and E-selectins expressed by endothelial cells. The second target moiety—alpha-fetoprotein receptor-binding peptide—enhances drug internalization into cancer cells and the intratumoral retention of the conjugate. The final conjugate contained 18 chelated Gd ions per dendrimer, characterized with a 32 nm size and a negative surface charge of around 18 mV. In vitro contrasting properties were comparable with commercially available Gd-chelate: r1 relaxivity was 3.39 for Magnevist and 3.11 for conjugate; r2 relaxivity was 5.12 for Magnevist and 4.81 for conjugate. By utilizing this dual targeting strategy, we demonstrated the increment of intratumoral accumulation, and a remarkable enhancement of antitumor effect, resulting in high-level synergy compared to monotargeted conjugates. In summary, the proposed strategy utilizing tumor tissue double-targeting may contribute to an enhancement in drug and diagnostic accumulation in aggressive tumors.
An shRNA kinase screen identifies regulators of UHRF1 stability and activity in mouse embryonic stem cells

ABSTRACT Propagation of DNA methylation through cell division relies on the recognition of methylated cytosines by UHRF1. In reprogramming of mouse embryonic stem cells to naive pluripotency (also known as ground state), despite high levels of Uhrf1 transcript, the protein is targeted for degradation by the proteasome, leading to DNA methylation loss. We have undertaken an shRNA screen to identify the signalling pathways that converge upon UHRF1 and control its degradation, using UHRF1-GFP fluorescence as readout. Many candidates we identified are key enzymes in regulation of glucose metabolism, nucleotide metabolism and Pi3K/AKT/mTOR pathway. Unexpectedly, while downregulation of all candidates we selected for validation rescued UHRF1 protein levels, we found that in some of the cases this was not sufficient to maintain DNA methylation. This has implications for development, ageing and diseased conditions. Our study demonstrates two separate processes that regulate UHRF1 protein abundance and activity.
Implementation of a telehealth videoconference to improve hospital‐to‐skilled nursing care transitions: Preliminary data

Transition‐related patient safety errors are high among patients discharged from hospitals to skilled nursing facilities (SNFs), and interventions are needed to improve communication between hospitals and SNF providers. Our objective was to describe the implementation of a pilot telehealth videoconference program modeled after Extension for Community Health Outcomes‐Care Transitions and examine patient safety errors and readmissions.