Predicting autism from young Infants' empathic responding: A prospective study.

Difficulties in empathy are frequent among children with autism spectrum disorder (ASD), and often considered a core feature of autism. Reduced empathy during the second year of life has been shown to predict subsequent ASD diagnosis. However, links between empathy in the first year and ASD have not yet been investigated. Moreover, prior work focused on empathy for others' distress but not for others' joy. To address these gaps, this prospective longitudinal study followed 60 infants (33% girls), 39 at high genetic risk of ASD (siblings of children with ASD) and a matching control group. Infants' empathic responses to others' distress and happiness were assessed at ages 6, 9, and 12 months, using simulations by the mother/experimenter and videos of crying and laughing infants. Diagnosis was determined between 18 and 36 months. Infants later diagnosed with ASD showed a reduced empathic response toward a person simulating distress, but not toward a video of a crying peer, and not in response to others' joy (either in simulation or video). Overall, reduced empathic concern during the first year of life appears to be an early prodromal marker of subsequent ASD. Implications for theory, research, and practice are discussed.

Deep learning method for pinhole array color image reconstruction.

The following paper proposes a combination of a supervised encoder-decoder neural network with coded apertures. Coded apertures provide improved sensitivity and signal-to-noise ratio (SNR) in planar images. The unique array design of this method overcomes the spatial frequency cutoff found in standard multi-pinhole arrays. In this design, the pinholes were positioned to minimize loss in spatial frequencies. The large number of pinholes results in significant overlapping on the detector. To overcome the overlapping issue, reconstruction of the object from the obtained image is done using inverse filtering methods. However, traces of duplications remain leading to a decline in SNR, contrast, and resolution. The proposed technique addresses the challenge of image distortion caused by the lack of accuracy in the inverse filter methods, by using a deep neural network. In this work, the coded aperture is combined with a deep convolutional neural network (CNN) to remove noise caused by pinhole imaging and inverse filter limitations. Compared to only using Wiener filtering, the proposed method delivers higher SNR, contrast, and resolution. The imaging system is presented in detail with experimental results that illustrate its efficiency.

Sense of mastery among older adults and its relation to invalidating childhood experiences.

ObjectivesSense of mastery, a well-recognized resource for older adults, has been shown to be related to early life experiences, especially parent-child interactions. Yet while there are indications that a reduced sense of mastery is related to early experiences of child maltreatment, this association has not been studied among older adults. The aim of this study was to examine the relation between experiences of childhood parental invalidation and sense of mastery among older adults, through the mediation of self-objectification and perceived disrupted body boundaries.Methods: Three-hundred-and-sixteen older adults (Mean = 72.24; SD = 8.12 years; range: 60-94) filled out a battery of questionnaires assessing their levels of exposure to childhood parental invalidation experiences, sense of self-objectification, disrupted body boundaries, and sense of masteryResults: A structural equation modeling (SEM) analysis supported the hypothesized research model. More specifically, two significant indirect effects were observed, according to which the association between invalidating childhood experiences and sense of mastery was mediated by both self-objectification and by disrupted body boundaries.Conclusion: As these results suggest that early life experiences continue to affect individuals' sense of self in older age, they should be considered an important factor for evaluation and intervention.

Feasibility and preliminary effectiveness of mobile cognitive control training during basic combat training in the military.

Periods of stressful events, such as those experienced during combat training in the military, may lead to psychological distress and reduced quality of life (QoL). Mental resilience, the capacity to overcome negative effects of setbacks on performance, may help protect one from the adversities associated with basic combat training. Among the factors contributing to mental resilience is cognitive control, the mechanism which helps maintain our goal directed behavior. Here we examined the feasibility of a mobile cognitive control training (CCT) app to engage young adults during their basic military training with the intention of improving resilience, mental health and QoL. 153 participants were randomly assigned to complete 2-3 weeks of either mobile CCT (n = 74) or active control training (ACT, mobile games; n = 79). Resilience, QoL, mood and self-efficacy were assessed at baseline and post-intervention. Participants completed, on average, 7.28 ± 3.03 training sessions (out of the planned 14), indicating relatively low feasibility of CCT during basic combat training period and inconsistent engagement with training. In addition, there was lack of improvement in the training tasks ('target engagement'). Accordingly, no significant time by group interactions were found on any of the outcome measures, potentially due to the limited feasibility. We conclude that short-term mobile CCT has low feasibility during basic combat training and discuss the results of this study considering factors that might have contributed to the lack of feasibility of the training protocol.

Assessing predictions of the impact of variants on splicing in CAGI5.

Precision medicine and sequence-based clinical diagnostics seek to predict disease risk or to identify causative variants from sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. In the past, few CAGI challenges have addressed the impact of sequence variants on splicing. In CAGI5, two challenges (Vex-seq and MaPSY) involved prediction of the effect of variants, primarily single-nucleotide changes, on splicing. Although there are significant differences between these two challenges, both involved prediction of results from high-throughput exon inclusion assays. Here, we discuss the methods used to predict the impact of these variants on splicing, their performance, strengths, and weaknesses, and prospects for predicting the impact of sequence variation on splicing and disease phenotypes.

Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial.

BACKGROUND: We aimed to assess whether distinct lifestyle strategies can differentially affect specific body adipose depots. METHODS: We performed an 18-month randomized controlled trial among 278 sedentary adults with abdominal obesity (75%) or dyslipidemia in an isolated workplace with a monitored provided lunch. Participants were randomized to isocaloric low-fat or Mediterranean/low-carbohydrate (MED/LC) diet+28 g walnuts/day with/without added moderate physical activity (PA; 80% aerobic; supervised/free gym membership). Overall primary outcome was body fat redistribution, and the main specific end point was visceral adipose tissue (VAT). We further followed the dynamics of different fat depots (deep and superficial subcutaneous, liver, pericardial, muscle, pancreas, and renal sinus) by magnetic resonance imaging. RESULTS: Of 278 participants (age, 48 years, 89% men, body mass index, 30.8 kg/m2), 86% completed the trial with good adherence. The low-fat group preferentially decreased reported fat intake (-21.0% versus -11.5% for the MED/LC; P<0.001), and the MED/LC group decreased reported carbohydrates intake (-39.5% versus -21.3% for the low-fat group; P<0.001). The PA+ groups significantly increased the metabolic equivalents per week versus the PA- groups (19.0 versus 2.1; P=0.009). Whereas final moderate weight loss was indifferent, exercise attenuated the waist circumference rebound with the greatest effect in the MED/LCPA+ group (P<0.05). VAT (-22%), intrahepatic (-29%), and intrapericardial (-11%) fats declines were higher than pancreatic and femur intermuscular fats (1% to 2%) loss. Independent of weight loss, PA+ with either diet had a significantly greater effect on decreasing VAT (mean of difference, -6.67cm2; 95% confidence interval, -14.8 to -0.45) compared with PA-. The MED/LC diet was superior to the low-fat diet in decreasing intrahepatic, intrapericardial, and pancreatic fats (P<0.05 for all). In contrast, renal sinus and femoral intermuscular fats were not differentially altered by lifestyle interventions but by weight loss per se. In multivariate models further adjusted for weight loss, losing VAT or intrahepatic fat was independently associated with improved lipid profile, losing deep subcutaneous adipose tissue with improved insulin sensitivity, and losing superficial subcutaneous adipose tissue remained neutral except for an association with decreased leptin. CONCLUSIONS: Moderate weight loss alone inadequately reflects the significant lifestyle effects on atherogenic and diabetogenic fat depots. The MED/LC diet mobilizes specific ectopic fat depots, and exercise has an independent contribution to VAT loss. Fat depots exhibit diverse responsiveness and are differentially related to cardiometabolic markers. Distinct lifestyle protocols may uniquely induce fat mobilization from specific anatomic sites. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01530724.

The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content.

BACKGROUND & AIM: It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes. METHODS: In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months. RESULTS: Of 278 participants (mean HFC 10.2% [range: 0.01%-50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (-6.6% absolute units [-41% relatively]) and 18 months (-4.0% absolute units [-29% relatively]; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes. CONCLUSIONS: %HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss. LAY SUMMARY: High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. ClinicalTrials.gov Identifier: NCT01530724.

Subretinal Fluid Optical Density and Spectral-Domain Optical Coherence Tomography Characteristics for the Diagnosis of Circumscribed Choroidal Hemangioma.

PURPOSE: To investigate spectral domain-optical coherence tomography (SD-OCT) features of untreated circumscribed choroidal hemangioma (CCH), and the optical density (OD) of the associated subretinal fluid (SRF). PROCEDURES: This international retrospective multicenter study conducted at 5 tertiary retina referral centers included 34 patients with symptomatic CCH imaged on SD-OCT. CCH surface, size, and overlying retinal changes and OD ratio (ODR) were evaluated. RESULTS: The mean ODR of the SRF was 0.808 ± 0.287. Tumor base measured on ultrasound correlated significantly with the ODR (p = 0.012). ODR values in cases of CCH were similar to those of choroidal metastasis, but significantly lower than those of choroidal melanoma (p = 0.006). Thirty-two out of 34 cases (94%) presented with a regular smooth choroidal surface. OCT demonstrated SRF overlying the CCH in 29 eyes (85%). The presence of SRF correlated significantly with a larger basal tumor diameter (p = 0.035). OCT displayed sub- and intraretinal hyperreflective foci, correlating with both larger maximal retinal thickness overlying the tumor (p = 0.031) and the amount of SRF (p = 0.016) in 29 eyes (85%). CONCLUSION: CCH displays typical findings on SD-OCT. ODR is a new important tool in the differential diagnosis of choroidal tumors and should be considered for enhancing the accuracy of diagnosing CCH. This benefit is especially relevant for cases in which the presentation of CCH is atypical.

Total serum cholinesterase activity predicts hemodynamic changes during exercise and associates with cardiac troponin detection in a sex-dependent manner.

BACKGROUND: Imbalanced autonomic nervous system (ANS) activity is associated with poor cardiovascular outcome. However, clinically validated biomarkers to assess parasympathetic function are not yet available. We sought to evaluate parasympathetic dysfunction by measuring serum cholinesterase activity and to determine its relationship to high sensitive cardiac troponin T (hs-cTnT) as well as traditional non-invasive parameters of ANS function during exercise in apparently healthy individuals. METHODS: We enrolled 1526 individuals (mean age 49 ± 11 yr., 75% men) from the Tel Aviv Medical Center Inflammation Survey (TAMCIS). We used the acetylcholine (ACh) analog acetylthiocholine (ATCh) as a substrate that is hydrolyzed by both ACh degrading enzymes and reflects the total serum capacity for acetylcholine hydrolysis, referred to as cholinergic status (CS). All subjects performed a cardiac stress test reviewed on the spot by a cardiologist and multiple physiological and metabolic parameters including hs-cTnT were measured. RESULTS: CS values at rest predicted multiple exercise-hemodynamic changes. Heart rate recovery after exercise was inversely correlated to CS values (p < 0.01 and p = 0.03 for women and men respectively), and a hypertensive reaction during exercise was associated with elevated CS levels in women. Most importantly, women with detectable hs-cTnT (> 5 ng/L) presented with elevated CS levels compared to women with undetectable levels; 1423 ± 272.5 vs 1347 ± 297.9 (p = 0.02). An opposite trend was observed in men. Metabolic dysfunction parameters were also associated with CS elevation in both men and women. CONCLUSIONS: Parasympathetic dysfunction assessed by total serum cholinesterase activity predicts hemodynamic changes during exercise. CS is also associated with hs-cTnT detection in women and inversely so in men. Future studies to assess the potential clinical use of this new sex-specific biomarker in cardiovascular disease risk stratification are warranted.

Comparison of Children With and Without ADHD on a New Pictorial Self-Assessment of Executive Functions.

OBJECTIVE: We examined the Pictorial Interview of Children's Metacognition and Executive Functions' (PIC-ME's) reliability and validity, targeting children's appraisal of their executive function (EF) in daily life. METHOD: One hundred children with attention deficit hyperactivity disorder (ADHD) and 44 typically developing children (ages 5-10 yr) completed the PIC-ME. Parents completed the PIC-ME and Behavior Rating Inventory of Executive Function (BRIEF). RESULTS: Cronbach's α for the child PIC-ME was .914. A high correlation was found between the parent PIC-ME total and the BRIEF (r = .724). Comparisons between groups revealed significant differences on the parent PIC-ME (p < .0001) but none on the child PIC-ME. Children with ADHD identified a median of eight EF challenges they wanted to set as treatment goals. CONCLUSION: Results support the PIC-ME's initial reliability and validity among children with ADHD. Children were able to identify several EF challenges and engage in goal setting.

Innovative Tools and Technology for Analysis of Single Cells and Cell-Cell Interaction.

Heterogeneity in single-cell responses and intercellular interactions results from complex regulation of cell-intrinsic and environmental factors. Single-cell analysis allows not only detection of individual cellular characteristics but also correlation of genetic content with phenotypic traits in the same cell. Technological advances in micro- and nanofabrication have benefited single-cell analysis by allowing precise control of the localized microenvironment, cell manipulation, and sensitive detection capabilities. Additionally, microscale techniques permit rapid, high-throughput, multiparametric screening that has become essential for -omics research. This review highlights innovative applications of microscale platforms in genetic, proteomic, and metabolic detection in single cells; cell sorting strategies; and heterotypic cell-cell interaction. We discuss key design aspects of single-cell localization and isolation in microfluidic systems, dynamic and endpoint analyses, and approaches that integrate highly multiplexed detection of various intracellular species.

Intrahepatic fat, abdominal adipose tissues, and metabolic state: magnetic resonance imaging study.

BACKGROUND: Intrahepatic fat (IHF) is best known to associate with waist circumference (WC) and visceral adipose tissue (VAT), but its relation to abdominal subcutaneous adipose tissue is controversial. While IHF ≥ 5% dichotomously defines fatty liver, %IHF is rarely considered as a continuous variable that includes the normal range. In this study, we aimed to evaluate %IHF association with abdominal fat subdepots, pancreatic, and renal-sinus fats. METHODS: We evaluated %IHF, abdominal fat subdepots, %pancreatic, and renal-sinus fats, among individuals with moderate abdominal obesity, using 3-Tesla magnetic resonance imaging. RESULTS: Among 275 participants, %IHF widely ranged (0.01%-50.4%) and was lower in women (1.6%) than men (7.3%; P < .001). In an age, sex, and WC-adjusted models, VAT area (P < .006) was directly associated with %IHF, while superficial-subcutaneous adipose tissue proportion was inversely associated with %IHF (P < .006). In these models, renal-sinus fat was positively associated with %IHF (P = .005). In an age, sex, WC, and VAT-adjusted models, elevated liver enzymes, glycemic, lipid, and inflammatory biomarkers were associated with increased %IHF (P < .003 for all). In these models, the associations remained robust even within the normal range strata of IHF < 5% for triglycerides and chemerin (P ≤ .004 for all). For the diagnosis of fatty liver, the joint area under the curve of WC, alanine-aminotransferase, triglycerides/high-density lipoprotein cholesterol, and homeostasis model assessment of insulin resistance was 0.84(95% CI, 0.79-0.89). CONCLUSIONS: Intrahepatic fat is differentially associated with abdominal fat subdepots. Intrahepatic-fat as a continuous variable could be predicted by specific traditional parameters, even within the current normal range, and partially independent of VAT.

A droplet-merging platform for comparative functional analysis of m1 and m2 macrophages in response to e. coli-induced stimuli.

Microfluidic droplets are used to isolate cell pairs and prevent crosstalk with neighboring cells, while permitting free motility and interaction within the confined space. Dynamic analysis of cellular heterogeneity in droplets has provided insights in various biological processes. Droplet manipulation methods such as fusion and fission make it possible to precisely regulate the localized environment of a cell in a droplet and deliver reagents as required. Droplet fusion strategies achieved by passive mechanisms preserve cell viability and are easier to fabricate and operate. Here, we present a simple and effective method for the co-encapsulation of polarized M1 and M2 macrophages with Escherichia coli (E. coli) by passive merging in an integrated droplet generation, merging, and docking platform. This approach facilitated live cell profiling of effector immune functions in situ and quantitative functional analysis of macrophage heterogeneity. Biotechnol. Bioeng. 2017;114: 705-709. © 2016 Wiley Periodicals, Inc.

Effects of initiating moderate wine intake on abdominal adipose tissue in adults with type 2 diabetes: a 2-year randomized controlled trial.

OBJECTIVE: To generate evidence-based conclusions about the effect of wine consumption on weight gain and abdominal fat accumulation and distribution in patients with type 2 diabetes. DESIGN: In the 2-year randomized controlled CASCADE (CArdiovaSCulAr Diabetes & Ethanol) trial, patients following a Mediterranean diet were randomly assigned to drink 150 ml of mineral water, white wine or red wine with dinner for 2 years. Visceral adiposity and abdominal fat distribution were measured in a subgroup of sixty-five participants, using abdominal MRI. SETTING: Ben-Gurion University of the Negev, Soroka-Medical Center and the Nuclear Research Center Negev, Israel. SUBJECTS: Alcohol-abstaining adults with well-controlled type 2 diabetes. RESULTS: Forty-eight participants (red wine, n 27; mineral water, n 21) who completed a second MRI measurement were included in the 2-year analysis. Similar weight losses (sd) were observed: red wine 1·3 (3·9) kg; water 1·0 (4·2) kg (P=0·8 between groups). Changes (95 % CI) in abdominal adipose-tissue distribution were similar: red wine, visceral adipose tissue (VAT) -3·0 (-8·0, 2·0) %, deep subcutaneous adipose tissue (DSAT) +5·2 (-1·1, 11·6) %, superficial subcutaneous adipose tissue (SSAT) -1·9 (-5·0, 1·2) %; water, VAT -3·2 (-8·9, 2·5) %, DSAT +2·9 (-2·8, 8·6) %, SSAT -0·15 (-3·3, 2·9) %. No changes in antidiabetic medication and no substantial changes in energy intake (+126 (sd 2889) kJ/d (+30·2 (sd 690) kcal/d), P=0·8) were recorded. A 2-year decrease in glycated Hb (ß=0·28, P=0·05) was associated with a decrease in VAT. CONCLUSIONS: Moderate wine consumption, as part of a Mediterranean diet, in persons with controlled diabetes did not promote weight gain or abdominal adiposity.

DNA-methylation effect on cotranscriptional splicing is dependent on GC architecture of the exon-intron structure.

DNA methylation is known to regulate transcription and was recently found to be involved in exon recognition via cotranscriptional splicing. We recently observed that exon-intron architectures can be grouped into two classes: one with higher GC content in exons compared to the flanking introns, and the other with similar GC content in exons and introns. The first group has higher nucleosome occupancy on exons than introns, whereas the second group exhibits weak nucleosome marking of exons, suggesting another type of epigenetic marker distinguishes exons from introns when GC content is similar. We find different and specific patterns of DNA methylation in each of the GC architectures; yet in both groups, DNA methylation clearly marks the exons. Exons of the leveled GC architecture exhibit a significantly stronger DNA methylation signal in relation to their flanking introns compared to exons of the differential GC architecture. This is accentuated by a reduction of the DNA methylation level in the intronic sequences in proximity to the splice sites and shows that different epigenetic modifications mark the location of exons already at the DNA level. Also, lower levels of methylated CpGs on alternative exons can successfully distinguish alternative exons from constitutive ones. Three positions at the splice sites show high CpG abundance and accompany elevated nucleosome occupancy in a leveled GC architecture. Overall, these results suggest that DNA methylation affects exon recognition and is influenced by the GC architecture of the exon and flanking introns.

Drugs that reverse disease transcriptomic signatures are more effective in a mouse model of dyslipidemia.

High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the physiological manifestations of the disease, especially in response to treatment, has not been investigated in a systematic manner. To this end, we studied a mouse model of diet-induced dyslipidemia and atherosclerosis that was subject to various drug treatments relevant to the disease in question. Both physiological data and gene expression data (from the liver and white adipose) were analyzed and compared. We find that treatments that restore gene expression patterns to their norm are associated with the successful restoration of physiological markers to their baselines. This holds in a tissue-specific manner­treatments that reverse the transcriptomic signatures of the disease in a particular tissue are associated with positive physiological effects in that tissue. Further, treatments that introduce large non-restorative gene expression alterations are associated with unfavorable physiological outcomes. These results provide a sound basis to in silico methods that rely on omic metrics for drug repurposing and drug discovery by searching for compounds that reverse a disease's omic signatures. Moreover, they highlight the need to develop drugs that restore the global cellular state to its healthy norm rather than rectify particular disease phenotypes.

Similar Rates of Symptomatic Marginal Ulcers After One-Anastomosis-Gastric Bypass Compared to Roux-en-Y Gastric Bypass.

PURPOSE: One-anastomosis-gastric-bypass (OAGB) has become a common bariatric procedure worldwide. Marginal ulcers (MU) are a significant non-immediate complication of gastric bypass surgeries. There seems to be concern among surgeons that MU are more common after OAGB compared with Roux-en-Y gastric bypass (RYGB) due to the constant and extensive exposure of the anastomosis to bile. The aim of this study was to compare the incidence, presentation, and management of MU between the two surgeries. MATERIALS AND METHODS: A retrospective study of prospectively collected data was performed to include all consecutive patients between 2010 and 2020, who underwent elective OAGB or RYGB at our institution. Patients diagnosed with symptomatic MU were identified. Factors associated with this complication were assessed and compared between the two surgeries. RESULTS: Symptomatic MU were identified in 23/372 OAGB patients (6.2%) and 35/491 RYGB patients (7.1%) (p = 0.58). Time to ulcer diagnosis was shorter in OAGB patients (12 ± 11 vs. 22 ± 17 months, p < 0.01). Epigastric pain was the common symptom (78% OAGB vs. 88.5% RYGB, p = 0.7) and approximately 15% of ulcers presented with perforation upon admission (17% vs.11.4%, p = 0.7). Re-operation was required in 5/23 OAGB (21.7%) and 6/36 RYGB (17%) patients (p = 0.11) while the rest of the patients were managed non-operatively. CONCLUSIONS: The risk of developing a marginal ulcer is similar between patients who underwent OAGB and RYGB. Patients diagnosed with MU following OAGB tend to present earlier; however, the clinical presentation is similar to RYGB patients. The management of this serious complication seems to be associated with acceptable outcomes with comparable operative and non-operative approaches.

The remote work of child protection professionals during COVID-19: A scoping review and thematic analysis.

BACKGROUND: The COVID-19 pandemic created new challenges and barriers for the work of child protection professionals (CPPs) and intensified existing hardships for families and children, increasing the risk of child maltreatment. As new restrictions and precautions were implemented by governments worldwide to stop the virus from spreading, CPPs had to adapt to a new reality of working remotely. However, limited research has investigated how remote work impacted CPPs and child protection work and how CPPs handled this alternative work style. OBJECTIVE: This review aims to address gaps in the research to reveal the creative and effective approaches CPPs developed to overcome the challenges presented by COVID-19, defined as the 'positive legacy' of CPPs, particularly in adapting to remote work challenges. METHOD: This review was conducted using a scoping review, followed by two rounds of thematic analysis. The scoping review was conducted in six languages: Hebrew, Arabic, French, Portuguese, Spanish, and English. RESULTS: The first round of thematic analysis found 18 articles relevant to this review. The second round extracted two main themes: 1) the challenges of remote work and 2) overcoming the challenges of no contact. CONCLUSIONS: The findings of this review may be used to inform future strategies for child protection during a pandemic. They also provide an opportunity to rethink the relationship child protection work has with technology to systematically reform current and future protection policies and practices, including outside of a pandemic.

Enhanced production yields of rVSV-SARS-CoV-2 vaccine using Fibra-Cel® macrocarriers.

The COVID-19 pandemic has led to high global demand for vaccines to safeguard public health. To that end, our institute has developed a recombinant viral vector vaccine utilizing a modified vesicular stomatitis virus (VSV) construct, wherein the G protein of VSV is replaced with the spike protein of SARS-CoV-2 (rVSV-ΔG-spike). Previous studies have demonstrated the production of a VSV-based vaccine in Vero cells adsorbed on Cytodex 1 microcarriers or in suspension. However, the titers were limited by both the carrier surface area and shear forces. Here, we describe the development of a bioprocess for rVSV-ΔG-spike production in serum-free Vero cells using porous Fibra-Cel® macrocarriers in fixed-bed BioBLU®320 5p bioreactors, leading to high-end titers. We identified core factors that significantly improved virus production, such as the kinetics of virus production, the use of macrospargers for oxygen supply, and medium replenishment. Implementing these parameters, among others, in a series of GMP production processes improved the titer yields by at least two orders of magnitude (2e9 PFU/mL) over previously reported values. The developed process was highly effective, repeatable, and robust, creating potent and genetically stable vaccine viruses and introducing new opportunities for application in other viral vaccine platforms.

The role of reverse transcriptase in intron gain and loss mechanisms.

Intron density is highly variable across eukaryotic species. It seems that different lineages have experienced considerably different levels of intron gain and loss events, but the reasons for this are not well known. A large number of mechanisms for intron loss and gain have been suggested, and most of them have at least some level of indirect support. We therefore figured out that the variability in intron density can be a reflection of the fact that different mechanisms are active in different lineages. Quite a number of these putative mechanisms, both for intron loss and for intron gain, postulate that the enzyme reverse transcriptase (RT) has a key role in the process. In this paper, we lay out three predictions whose approval or falsification gives indication for the involvement of RT in intron gain and loss processes. Testing these predictions requires data on the intron gain and loss rates of individual genes along different branches of the eukaryotic phylogenetic tree. So far, such rates could not be computed, and hence, these predictions could not be rigorously evaluated. Here, we use a maximum likelihood algorithm that we have devised in the past, Evolutionary Reconstruction by Expectation Maximization, which allows the estimation of such rates. Using this algorithm, we computed the intron loss and gain rates of more than 300 genes in each branch of the phylogenetic tree of 19 eukaryotic species. Based on that we found only little support for RT activity in intron gain. In contrast, we suggest that RT-mediated intron loss is a mechanism that is very efficient in removing introns, and thus, its levels of activity may be a major determinant of intron number. Moreover, we found that intron gain and loss rates are negatively correlated in intron-poor species but are positively correlated for intron-rich species. One explanation to this is that intron gain and loss mechanisms in intron-rich species (like metazoans) share a common mechanistic component, albeit not a RT.