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The contribution of consonants and vowels in spoken word processing has been widely investigated, and studies have found a phenomenon of a Consonantal bias (C-bias), indicating that consonants carry more weight than vowels. However, across languages, various patterns have been documented, including that of no preference or a reverse pattern of Vowel bias. A central question is how the manifestation of the C-bias is modulated by language-specific factors. This question can be addressed by cross-linguistic studies. Comparing native Hebrew and native English speakers, this study examines the relative importance of transitional probabilities between non-adjacent consonants as opposed to vowels during auditory statistical learning (SL) of an artificial language. Hebrew is interesting because its complex Semitic morphological structure has been found to play a central role in lexical access, allowing us to examine whether morphological properties can modulate the C-bias in early phases of speech perception, namely, word segmentation. As predicted, we found a significant interaction between language and consonant/vowel manipulation, with a higher performance in the consonantal condition than in the vowel condition for Hebrew speakers, namely, C-bias, and no consonant/vowel asymmetry among English speakers. We suggest that the observed interaction is morphologically anchored, indicating that phonological and morphological processes interact during early phases of auditory word perception. [ABSTRACT FROM AUTHOR]

Traumatic injuries to the central nervous system (CNS) afflict millions of individuals worldwide1, yet an effective treatment remains elusive. Following such injuries, the site is populated by a multitude of peripheral immune cells, including T cells, but a comprehensive understanding of the roles and antigen specificity of these endogenous T cells at the injury site has been lacking. This gap has impeded the development of immune-mediated cellular therapies for CNS injuries. Here, using single-cell RNA sequencing, we demonstrated the clonal expansion of mouse and human spinal cord injury-associated T cells and identified that CD4+ T cell clones in mice exhibit antigen specificity towards self-peptides of myelin and neuronal proteins. Leveraging mRNA-based T cell receptor (TCR) reconstitution, a strategy aimed to minimize potential adverse effects from prolonged activation of self-reactive T cells, we generated engineered transiently autoimmune T cells. These cells demonstrated notable neuroprotective efficacy in CNS injury models, in part by modulating myeloid cells via IFNγ. Our findings elucidate mechanistic insight underlying the neuroprotective function of injury-responsive T cells and pave the way for the future development of T cell therapies for CNS injuries.This study presents a new T cell therapy targeting spinal cord injury, providing a potential new approach for injured CNS. [ABSTRACT FROM AUTHOR]

Background: Selective Immunoglobulin A Deficiency (SIgAD) is one of the most prevalent immunodeficiencies, characterized by an increased risk of mucosal infections. Attention deficit hyperactivity disorder (ADHD) is among the most common neurodevelopmental disorders and is associated with significantly higher rates of various infectious diseases, white blood cell abnormalities, and considerable morbidity. This study aimed to evaluate the prevalence of ADHD among patients with SIgAD. Methods: We conducted a retrospective, observational, population-based case–control study, within Leumit Health Services, by comparing individuals diagnosed with SIgAD to a matched control group. Data were extracted from electronic health records. Results: Of the >700,000 registered individuals, 772 aged ≥4 years with SIgAD were identified (mean age 22.0 ± 17.5 years; male/female ratio 1:1). The 5:1 matched control group consisted of 3860 subjects without SIgAD, with no significant differences between the groups regarding age, gender, ethnicity, and socioeconomic status. ADHD prevalence was significantly higher in the SIgAD group (16.2%) than in the control group (12.9%), with an odds ratio of 1.30 (95% confidence interval 1.05–1.61, p = 0.017), as was the use of methylphenidate (6.6% vs. 4%). Additionally, respiratory and intestinal infections were significantly more common in the SIgAD group (p < 0.001). Conclusion: A significantly higher prevalence of ADHD was observed in patients with SIgAD compared to strictly matched controls without SIgAD. These findings enhance our understanding of the pathophysiology of ADHD and its associated health complications. [ABSTRACT FROM AUTHOR]

We assessed the anti-inflammatory activity of the TSPO ligand 2-Cl-MGV-1. Lipopolysaccharide (LPS) was used to induce inflammatory response in a murine RAW264.7 macrophage model (LPS: 100 ng/mL) and a mouse model (C57BL/6) of lung inflammation (LPS: 5 mg/kg). In the macrophage model, the presence of 2-Cl-MGV-1 (25 µM) caused the LPS-induced elevation in nitrite levels to decrease by 70% (p < 0.0001) and interleukin (IL)-6 by 50% (p < 0.05). In the mouse model, 2-Cl-MGV-1, administered 30 min before, or co-administered with, an LPS injection, significantly inhibited the elevation in serum IL-5 levels (both by 65%; p < 0.001 and p < 0.01, respectively). 2-Cl-MGV-1 administration to mice 30 min before LPS injection and 1 h thereafter significantly inhibited the elevation in IL-1β serum levels (both by 63%, p < 0.005). IL-6 elevation was inhibited by 73% (p < 0.005) when 2-Cl-MGV-1 was administered 30 min before LPS, by 60% (p < 0.05) when co-administered with LPS, and by 64% (p < 0.05) when administered 1 h after LPS. All cytokine assessments were conducted 6 h post LPS injection. Histological analyses showed decreased leukocyte adherence in the lung tissue of the ligand-treated mice. 2-Cl-MGV-1 administration 30 min prior to exposure to LPS inhibited inflammation-induced open field immobility. The beneficial effect of 2-Cl-MGV-1 suggests its potential as a therapeutic option for inflammatory diseases. [ABSTRACT FROM AUTHOR]

This review reports on the use of sensors in wheelchair sports to monitor and analyze performance during match and training time. With rapid advancements in electronics and related technologies, understanding performance metrics in wheelchair sports is essential. We reviewed nine studies using various sensor types, including electric motors, inertial measurement units, miniaturized data loggers with magnetic reed switches, and smartphones with inbuilt accelerometers and gyroscopes, operating at frequencies from 8 Hz to 1200 Hz. These studies measured parameters such as angular and translational velocities, distance, number of starts/pushes, and other performance indicators in sports such as basketball, rugby, tennis, and racing. Despite differences in sport types and methodologies, most studies found sensor-derived data effective for assessment of performance. Future developments and research in this field should focus on multi-sensor systems that could provide real-time match analysis and deeper insights into performance metrics. Overall, sensor technologies show significant potential for improving wheelchair sport performance diagnostics, contributing to better athlete training and future wheelchair design, and enhancing competitive outcomes. This review emphasizes the need for continued innovation and standardization in applying sensor technologies in wheelchair sports. [ABSTRACT FROM AUTHOR]

The coefficient of friction (COF) is usually calculated from a force ratio or a translational velocity ratio. We developed a new method for calculating the COF between fingers and a thrown ball from the spin parameter (angular over translational velocity). We used triad data obtained from a motion analysis system. We rigidified the triad data with a new method by force-fitting a master triangle (obtained from average side lengths) to each triad, where the three distances between each pair of corresponding vertices are three virtual forces that are in force and moment equilibrium. We also applied a low-pass filter to the data. The following data were calculated: helical axis between two consecutive master triangles, angular velocity, translational velocity, and COF. We applied this method to cricket ball deliveries (finger-spin topspin Ft, finger-spin backspin Fb, wrist-spin topspin Wt, wrist-spin backspin Wb). The standard deviations of the triad side lengths were smaller without than with low-pass filter. The COF showed smaller interquartile and total ranges when force fitting the raw data than when force-fitting the filtered data; or filtered data without force fitting; or neither force-fitting nor filtering. The delivery finger-spin backspin exhibited the smallest COF, whereas wrist-spin backspin had the highest. Finger-spin deliveries had a smaller COF than wrist-spin ones. There was no significant difference between topspin and backspin in terms of the COF. Deliveries with the palm pointing medially (Ft, Wb) had a greater COF than deliveries with the palm pointing laterally (Fb, Wt). In conclusion, the force-fitting method was superior compared to low-pass filtering with the latter worsening the data because of filtering along the time axis rather than spatially. The COF imparted on cricket ball led to a new classification system of deliveries and to a proposal for a new bowling strategy. [ABSTRACT FROM AUTHOR]

Rationale: : Valproic acid (VPA) is commonly used as a second-line mood stabilizer or augmentative agent in severe mental illnesses. However, population pharmacokinetic studies specific to psychiatric populations are limited, and clinical predictors for the precision application of VPA remain undefined. Objectives: To identify steady-state serum VPA level predictors in pediatric/adolescent and adult psychiatric inpatients. Methods: We analyzed data from 634 patients and 1,068 steady-state therapeutic drug monitoring (TDM) data points recorded from 2015 to 2021. Steady-state VPA levels were obtained after tapering during each hospitalization episode. Electronic patient records were screened for routine clinical parameters and co-medication. Generalized additive mixed models were employed to identify independent predictors. Results: Most TDM episodes involved patients with psychotic disorders, including schizophrenia (29.2%) and schizoaffective disorder (17.3%). Polypharmacy was common, with the most frequent combinations being VPA + quetiapine and VPA + promethazine. Age was significantly associated with VPA levels, with pediatric/adolescent patients (< 18 years) demonstrating higher dose-adjusted serum levels of VPA (β = 7.6±2.34, p < 0.001) after accounting for BMI. Women tended to have higher adjusted VPA serum levels than men (β = 5.08±1.62, p < 0.001). The formulation of VPA (Immediate-release vs. extended-release) showed no association with VPA levels. Co-administration of diazepam exhibited a dose-dependent decrease in VPA levels (F = 15.7, p < 0.001), suggesting a potential pharmacokinetic interaction. Conclusions: This study highlights the utility of population-specific pharmacokinetic data for VPA in psychiatric populations. Age, gender, and co-administration of diazepam were identified as predictors of VPA levels. Further research is warranted to establish additional predictors and optimize the precision application of VPA in psychiatric patients. [ABSTRACT FROM AUTHOR]

This essay deals with perceptions of smoking among Haredi men in Israel. Though trends in smoking within the Haredi society have been quantitively examined, no qualitative research has ever focused on the motivations and mindsets stimulating individuals' choices to take health risks despite religious precepts to the contrary. Israeli Haredi men sometimes start smoking in their early childhood and are unmotivated to quit, and such circumstances should be examined. We interviewed 20 Israeli Haredi male smokers and overviewed the Haredi daily press and rabbinical attitudes toward smoking. Our findings indicate that Haredi men typically consider smoking as either permissible or, at worst, a minor sin. From childhood they view smoking as an expression of maturity, and moreover one which is associated with Jewish holidays and particular religious practices. Such perception relies on the Haredi establishment's normative exclusion of smoking from the Halachic commandments that aim to protect health. Finally, we illustrate key points to consider in paths leading to an intervention process to change these norms and practices. [ABSTRACT FROM AUTHOR]

Background: Diffusing alpha‐emitters radiation therapy ("Alpha‐DaRT") is a new method for treating solid tumors with alpha particles, relying on the release of the short‐lived alpha‐emitting daughter atoms of radium‐224 from interstitial sources inserted into the tumor. Alpha‐DaRT tumor dosimetry is governed by the spread of radium's progeny around the source, as described by an approximate framework called the "diffusion‐leakage model". The most important model parameters are the diffusion lengths of radon‐220 and lead‐212, and their estimation is therefore essential for treatment planning. Purpose: Previous works have provided initial estimates for the dominant diffusion length, by measuring the activity spread inside mice‐borne tumors several days after the insertion of an Alpha‐DaRT source. The measurements, taken when lead‐212 was in secular equilibrium with radium‐224, were interpreted as representing the lead‐212 diffusion length. The aim of this work is to provide first experimental estimates for the diffusion length of radon‐220, using a new methodology. Methods: The diffusion length of radon‐220 was estimated from autoradiography measurements of histological sections taken from 24 mice‐borne subcutaneous tumors of five different types. Unlike previous studies, the source dwell time inside the tumor was limited to 30 min, to prevent the buildup of lead‐212. To investigate the contribution of potential non‐diffusive processes, experiments were done in two sets: fourteen in vivo tumors, where during the treatment the tumors were still carried by the mice with active blood supply, and 10 ex‐vivo tumors, where the tumors were excised before source insertion and kept in a medium at 37∘C$37^\circ {\text{C}}$ with the source inside. Results: The measured diffusion lengths of radon‐220, extracted by fitting the recorded activity pattern up to 1.5 mm from the source, lie in the range 0.25−0.6mm${0.25-0.6}\nobreakspace {\text{mm}}$, with no significant difference between the average values measured in in‐vivo and ex‐vivo tumors: LRnin−vivo=0.40±0.08mm$L_{Rn}^{in-vivo}=0.40{\pm }0.08\nobreakspace {\text{mm}}$ versus LRnex−vivo=0.39±0.07mm$L_{Rn}^{ex-vivo}=0.39{\pm }0.07\nobreakspace {\text{mm}}$. However, in‐vivo tumors display an enhanced spread of activity 2–3 mm away from the source. This effect is not explained by the current model and is much less pronounced in ex‐vivo tumors. Conclusions: The average measured radon‐220 diffusion lengths in both in‐vivo and ex‐vivo tumors are consistent with published data on the diffusion length of radon in water and lie close to the upper limit of the previously estimated range of 0.2−0.4mm$0.2-0.4\nobreakspace {\text{mm}}$. The observation that close to the source there is no apparent difference between in‐vivo and ex‐vivo tumors, and the good agreement with the theoretical model in this region suggest that the spread of radon‐220 is predominantly diffusive in this region. The departure from the model prediction in in‐vivo tumors at large radial distances may hint at potential vascular contribution, which will be the subject of future works. [ABSTRACT FROM AUTHOR]

Microdosing ketamine is a novel antidepressant for treatment‐resistant depression. Traditional antidepressants, like selective serotonin reuptake inhibitors (SSRIs), inhibit serotonin reuptake, but it is not clear if ketamine shows a similar mechanism. Here, we tested the effects of feeding ketamine and SSRIs to Drosophila melanogaster larvae, which has a similar serotonin system to mammals and is a good model to track depressive behaviors, such as locomotion and feeding. Fast‐scan cyclic voltammetry (FSCV) was used to measure optogenetically stimulated serotonin changes, and locomotion tracking software and blue dye feeding to monitor behavior. We fed larvae various doses (1–100 mM) of antidepressants for 24 h and found that 1 mM ketamine did not affect serotonin, but increased locomotion and feeding. Low doses (≤10 mM) of escitalopram and fluoxetine inhibited dSERT and also increased feeding and locomotion behaviors. At 100 mM, ketamine inhibited dSERT and increased serotonin concentrations, but decreased locomotion and feeding because of its anesthetic properties. Since microdosing ketamine causes behavioral effects, we further investigated behavioral changes with a SERT16 mutant and low doses of other NMDA receptor antagonists and 5‐HT1A and 2 agonists. Feeding and locomotion changes were similar to ketamine in the mutant, and we found NMDA receptor antagonism increased feeding, while serotonin receptor agonism increased locomotion, which could explain these effects with ketamine. Ultimately, this work shows that Drosophila is a good model to discern antidepressant mechanisms, and that ketamine does not work on dSERT like SSRIs, but effects behavior with other mechanisms that should be investigated further. [ABSTRACT FROM AUTHOR]

Wheelchair propulsion and actuation are influenced by the moving masses of the wheelchair user; however, the extent of this effect is still unclear. The main evidence of this effect is that the speed of the wheelchair frame continues to increase after the end of the push phase. The wheelchair's speed was measured using IMUs and the duration of the push period was recorded using miniaturised pressure sensors attached to the driver's middle fingers. The velocity and acceleration were determined for various average stroke cycle speeds to determine the speed dependency of the acceleration. The wheelchair was then mounted on a force plate to measure the inertial forces of the hands moving back and forth. The aerodynamic drag and rolling resistance forces were determined from coast-down experiments. Based on the measured forces, the behaviour of the force and velocity profiles was finally modelled by gradually reducing the mass of the arms and thus their inertial force. The results showed that the wheelchair is accelerated throughout the push phase (except for a temporary deceleration in the middle of the push phase at higher velocities), and that this acceleration continues well after the push phase. In the second half of the recovery phase, the wheelchair decelerates. The horizontal inertial forces measured on the force plate are predominantly negative in the push phase and in the second half of the recovery phase, and positive in the first half of the push phase, and their impulse is zero due to the conservation of momentum. Modelling the wheelchair with moving masses showed that reducing the horizontal inertial forces has no effect on the driver's propulsive force but reduces the velocity fluctuations. The main conclusion of this research is that the wheelchair user's power should be calculated only from the pure propulsive force that is required in the push phase to overcome the dissipative forces and that enables the gain or loss in speed per stroke cycle, but not directly from the measured velocity. [ABSTRACT FROM AUTHOR]

Background: Disordered autonomic nervous system regulation and supraspinal pain inhibition have been repeatedly described in chronic pain. We aimed to explore the effects of δ-9-tetrahydrocannabinol (THC), an emerging treatment option, on autonomic nervous system and central pain modulation measures in patients with chronic pain. Methods: Twelve male patients with chronic radicular neuropathic pain participated in a randomized, double-blind, crossover, placebo-controlled, single-administration trial. Low/high frequency (LF/HF) heart rate variability (HRV) ratio and conditioned pain modulation (CPM) response were measured and resting-state functional magnetic resonance imaging (MRI) was performed at baseline and after sublingual administration of either 0.2 mg/kg oral THC or placebo. Results: THC significantly reduced the LF/HF ratio compared with placebo (interaction effect F(1,11) = 20.5; p < 0.005) and significantly improved CPM responses (interaction effect F(1,9) = 5.2; p = 0.048). The THC-induced reduction in LF/HF ratio correlated with increased functional connectivity between the rostral ventrolateral medulla and the dorsolateral prefrontal cortex [T(10) = 6.4, cluster p-FDR < 0.005]. Conclusions: THC shifts the autonomic balance towards increased parasympathetic tone and improves inhibitory pain mechanisms in chronic pain. The increase in vagal tone correlates with connectivity changes in higher-order regulatory brain regions, suggesting THC exerts top-down effects. These changes may reflect a normalizing effect of THC on multiple domains of supraspinal pain dysregulation. Clinical Trial Registry Number: NCT02560545. [ABSTRACT FROM AUTHOR]

Aims: To find clinical and immunological signatures of the SARS‐CoV‐2 and the COVID‐19 pandemic on children newly diagnosed with type 1 diabetes (T1D). Methods: A single‐centre, retrospective, observational study comparing the clinical and immunological characteristics of children diagnosed with T1D the year before and during the first 2 years of the COVID‐19 pandemic. Data extracted from the medical records included clinical and demographic parameters, COVID‐19 PCR results and the presence of anti‐islet, thyroid and celiac‐related antibodies. Also obtained from the medical records was a family history of T1D, celiac disease and autoimmune thyroid disease in a first‐degree family member. Results: A total of 376 children were diagnosed with T1D during the study period. A total of 132 in the pre‐COVID era and 246 in the first 2 years of the pandemic. At diagnosis, the pH in children with DKA was lower, and HbA1c tended to be higher in the COVID‐19 group compared to the pre‐COVID‐19 group (7.30 [7.18, 7.35] vs 7.33 [7.19, 7.36], p = 0.046) and (110.9 [86.9, 129.5] vs 100 [80.3, 129.5], p = 0.067]) respectively. Multiple islet antibodies (IA) were significantly more common among patients in the pre‐COVID‐19 group compared to the COVID‐19 group (72% vs 61%, p = 0.032). Tissue transglutaminase antibodies were more common among children diagnosed in the COVID‐19 compared to the pre‐COVID group (16.6% vs 7.9%, p = 0.022). Conclusions: Our findings suggest that SARS‐CoV‐2 and the environmental alterations caused by the pandemic affected the clinical characteristics and the immunological profile of children diagnosed with T1D. It is, therefore, plausible that the virus plays a role in the autoimmune process causing T1D. [ABSTRACT FROM AUTHOR]

Reducing production costs, known as scaling, is a significant obstacle in the advancement of cultivated meat. The cultivation process hinges on several key components, e.g., cells, media, scaffolds, and bioreactors. This study demonstrates an innovative approach, departing from traditional stainless steel or glass bioreactors, by integrating food-grade plant-based scaffolds and thermoplastic film bioreactors. While thermoplastic films are commonly used for constructing fluidic systems, conventional welding methods are cost-prohibitive and lack rapid prototyping capabilities, thus inflating research and development expenses. The developed laser welding technique facilitates contamination-free and leakproof sealing of polyethylene films, enabling the efficient fabrication of macrofluidic systems with various designs and dimensions. By incorporating food-grade plant-based scaffolds, such as rice seeded with bovine mesenchymal stem cells, into these bioreactors, this study demonstrates sterile cell proliferation on scaffolds within macrofluidic systems. This approach not only reduces bioreactor prototyping and construction costs but also addresses the need for scalable solutions in both research and industrial settings. Integrating single-use bioreactors with minimal shear forces and incorporating macro carriers such as puffed rice may further enhance biomass production in a scaled-out model. The use of food-grade plant-based scaffolds aligns with sustainable practices in tissue engineering and cultured-meat production, emphasizing its suitability for diverse applications. [ABSTRACT FROM AUTHOR]

Focusing on Israel/Palestine, this article explores the role of anticolonial settler-citizens, discussing how they may advance or impede struggles to dismantle the settler state. It shows how in settler states citizenship is founded on, and functions through, violence. It then analyses how the settler colonial condition imposes a set of paradoxes on those settler-citizens who wish to resist the colonial condition, thus limiting possibilities for settler solidarity and co-resistance. Overall, the article presents a critique of the role of citizenship in decolonisation struggles, including through the framework of 'acts of citizenship'. It shows that the role of violence and non-violence in the (anti)colonial project is key to unravelling the impossibility of bridging the inherent fault line of being anticolonial while remaining settlers. Lessons from other past and present decolonisation struggles teach us that settler solidarity and co-resistance must centre indigenous struggles and take leadership from them, in ways accepting the uncertainty of the settlers' future after decolonisation. Only such recognition can allow genuine allyship and solidarity and with it hope for such a future. [ABSTRACT FROM AUTHOR]

22q11.2 deletion is the most prominent risk factor for schizophrenia (SZ). The aim of the present study was to identify unique transcriptome profile for 22q11.2 deletion syndrome (DS)-related SZ-spectrum disorder (SZ-SD). We performed RNA-Seq screening in lymphoblasts collected from 20 individuals with 22q11.2DS (10 men and 10 women, four of each sex with SZ-SD and six with no psychotic disorders (Np)). Sex effect in RNA-Seq descriptive analysis led to separating the analyses between men and women. In women, only one differentially expressed gene (DEG), HLA-DQA2, was associated with SZ-SD. In men, 48 DEGs (adjp < 0.05) were found to be associated with SZ-SD. Ingenuity pathway analysis of top 85 DEGs (p < 4.66E − 04) indicated significant enrichment for immune-inflammatory response (IIR) and neuro-inflammatory signalling pathways. Additionally, NFATC2, IFNG, IFN-alpha, STAT1 and IL-4 were identified as upstream regulators. Co-expression network analysis revealed the contribution of endoplasmic reticulum protein processing and N-Glycan biosynthesis. These findings indicate dysregulation of IIR and post-translational protein modification processes in individuals with 22q11.2DS-related SZ-SD. Candidate pathways and upstream regulators may serve as novel biomarkers and treatment targets for SZ. Future transcriptome studies, including larger samples and proteomic analysis, are needed to substantiate our findings. [ABSTRACT FROM AUTHOR]

This article discusses a study on the use of daily intelligence-assisted online adaptive radiotherapy for the treatment of head and neck cancer. The study found that this treatment approach improved target coverage and reduced maximum dose to the tumor. The study also observed a reduction in certain side effects and a high local control rate. However, the study acknowledges the need for further research to determine which patients would benefit the most from this treatment approach. [Extracted from the article]

Introduction: Chloral hydrate (CH), a medication dating back to 1832, is tranquilizer and sleep promoter still used today. It remains an option for short-term insomnia therapy and sedation before medical procedures, despite its controversial safety profile. Methods: This study investigated the potential benefits of chloral hydrate addition for increasing sleep duration and reducing agitation and violence in inpatients with treatment-resistant schizophrenia (TRS). A retrospective, observational case series design was utilized, analyzing data from fourteen patients diagnosed with TRS disorders. Results: CH addition increased the rate of full night sleep and decreased the rates of agitation and verbal and physical violence events. Notably, no adverse events including falls were reported during CH addition. Discussion: CH shows some short-term benefits in improving sleep disorders and reducing violent and agitated behavior in patients with TRS. Our study has limitations due to its small sample size, retrospective design and lack of a control group. A large-scale, double-blind, randomized trial is needed to further explore the efficacy and safety of CH in psychiatric populations with TRS accompanied by agitation, violence and disturbed sleep. [ABSTRACT FROM AUTHOR]

Objective: We examined the association between the number, magnitude, and frequency of febrile episodes during the 0 to 4 years of life and subsequent diagnosis of ADHD. Methods: This population-based case-control study in an Israeli HMO, Leumit Health Services (LHS), uses a database for all LHS members aged 5 to 18 years between 1/1/2002 and 1/30/2022. The number and magnitude of measured fever episodes during the 0 to 4 years were recorded in individuals with ADHD (N = 18,558) and individually matched non-ADHD controls in a 1:2 ratio (N = 37,116). Results: A significant, independent association was found between the number and magnitude of febrile episodes during the 0 to 4 years and the probability of a later diagnosis of ADHD. Children who never had a measured temperature >37.5°C had a significantly lower rate of ADHD (OR = 0.834, 95% CI [0.802, 0.866], p <.0001). Conclusions: Febrile episodes during 0 to 4 years are associated with a significantly increased rate of a later diagnosis of ADHD in a doseresponse relationship. [ABSTRACT FROM AUTHOR]

Objective: There is growing evidence of involvement of inflammatory mechanisms in ADHD. Previous studies found significantly higher rates of ADHD among children with FMF. The present study examined the rate of exposure to FMF in children with a later (within a 5-year period) diagnosis of ADHD compared to non-ADHD children. Methods: A population-based case-control study of all children (<18 years) registered in Leumit Health Services during 01.01.2006 to 06.30.2021. All cases met ICD-9/10 criteria for ADHD. They were matched by age, sex, and socioeconomic status on a 1:2 rate to randomly selected non-ADHD controls. Results: Fifty-six (0.30%) children with ADHD (N = 18,756) were previously diagnosed with FMF compared to 65 of 37,512 controls (0.17%). A significant, independent association existed between a preceding FMF diagnosis and a later ADHD diagnosis [OR = 1.72 (95% CI 1.18–2.51); p =.003]. Conclusions: The mechanisms underlying the association w between FMF and later ADHD diagnosis merit further elucidation. [ABSTRACT FROM AUTHOR]

With the growing challenge of abandoned surplus embryos in the ART arena, and the limited traction of embryo donation as a viable embryo disposition choice, it is important to better understand barriers to wider adoption of this opportunity. We aim to learn about perspectives and experience of participants in directed and non-identified embryo donation programmes. This was a longitudinal cohort survey study, of all participants in an embryo donation programme in a single university affiliated clinic between 2016 and 2020. Clinical data were extracted from counselling reports. Based on these data, non-identified online questionnaires were constructed and refined via Delphi procedure for face and content validity. Sixty-five online questionnaires were emailed between March-April 2021. Descriptive statistics, cross-tabulation, Fisher's exact test and t-test were used for analyses. Source of patient awareness, factors influencing the decision-making process, patient perspective and satisfaction were explored. The response rate was 67.2%. Most participants in the non-identified programme learned of it through their treating physicians, whereas most participants in the directed programme learned of it online. The main driver to donate across both cohorts was wanting to give others the opportunity to experience the joy of parenthood. Overall, 45% described moderate to marked difficulty in decision making related to donating their embryos, and this did not differ between cohorts. Non-identified donors reported feeling highly attached to the donated embryos more often than directed donors. Level of satisfaction was higher in the directed donation programme. Participants were more satisfied following directed than non-identified donation, and some even consider their counterparts as extended family. Our findings should be validated in various settings, and on larger samples. [ABSTRACT FROM AUTHOR]

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, impacting 4.9% of the population and more prevalent in Mediterranean communities, is a common enzymopathy with potential relevance to Attention Deficit/Hyperactivity Disorder (ADHD). This study investigated this association. Methods: The clinical characteristics of 7473 G6PD-deficient patients and 29,892 matched case–controls (selected at a 1:4 ratio) from a cohort of 1,031,354 within the Leumit Health Services database were analyzed using Fisher's exact test for categorical variables and the Mann–Whitney U test for continuous variables. Results: In total, 68.7% were male. The mean duration of follow-up was 14.3 ± 6.2 years at a mean age of 29.2 ± 22.3 years. G6PD deficiency was associated with an increased risk of being diagnosed with ADHD (Odds Ratio (OR) = 1.16 [95% CI, 1.08–1.25], p < 0.001), seeking care from adult neurologists (OR = 1.30 [95% CI, 1.22–1.38], p < 0.001), and consulting adult psychiatrists (OR = 1.12 [95% CI, 1.01–1.24], p = 0.048). The use of stimulant medications among G6PD-deficient individuals was 17% higher for the methylphenidate class of drugs (OR = 1.17 [95% CI, 1.08, 1.27], p < 0.001), and there was a 16% elevated risk for amphetamine use (OR = 1.16 [95% CI, 1.03, 1.37], p = 0.047). Conclusions: G6PD deficiency signals an increased risk of ADHD diagnosis, more severe presentations of ADHD and a greater need for psychiatric medications to treat ADHD. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic resulted in approximately 7 million deaths and impacted 767 million individuals globally, primarily through infections. Acknowledging the impactful influence of sedentary behaviors, particularly exacerbated by COVID-19 restrictions, a substantial body of research has emerged, utilizing wearable sensor technologies to assess these behaviors. This comprehensive review aims to establish a framework encompassing recent studies concerning wearable sensor applications to measure sedentary behavior parameters during the COVID-19 pandemic, spanning December 2019 to December 2022. After examining 582 articles, 7 were selected for inclusion. While most studies displayed effective reporting standards and adept use of wearable device data for their specific research aims, our inquiry revealed deficiencies in apparatus accuracy documentation and study methodology harmonization. Despite methodological variations, diverse metrics, and the absence of thorough device accuracy assessments, integrating wearables within the pandemic context offers a promising avenue for objective measurements and strategies against sedentary behaviors. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy has an important role in the treatment of brain metastases but carries risk of short and/or long-term toxicity, termed radiation-induced brain injury (RBI). As the diagnosis of RBI is crucial for correct patient management, there is an unmet need for reliable biomarkers for RBI. The aim of this proof-of concept study is to determine the utility of brain-derived circulating free DNA (BncfDNA), identified by specific methylation patterns for neurons, astrocytes, and oligodendrocytes, as biomarkers brain injury induced by radiotherapy. Methods: Twenty-four patients with brain metastases were monitored clinically and radiologically before, during and after brain radiotherapy, and blood for BncfDNA analysis (98 samples) was concurrently collected. Sixteen patients were treated with whole brain radiotherapy and eight patients with stereotactic radiosurgery. Results: During follow-up nine RBI events were detected, and all correlated with significant increase in BncfDNA levels compared to baseline. Additionally, resolution of RBI correlated with a decrease in BncfDNA. Changes in BncfDNA were independent of tumor response. Conclusions: Elevated BncfDNA levels reflects brain cell injury incurred by radiotherapy. further research is needed to establish BncfDNA as a novel plasma-based biomarker for brain injury induced by radiotherapy. [ABSTRACT FROM AUTHOR]

The ability of immune cells to directly interact with transformed cells is an essential component of immune surveillance and critical for optimal tissue function. The tumor-immune interactome (the collective cellular interactions between oncogenic cells and immune cells) is distinct and varied based on the tissue location and immunogenicity of tumor subtypes. However, comprehensive landscape and the consequences of tumor-interacting immune cells in the tumor microenvironment are not well understood. Current tools are limited in their ability to identify and record interactors in vivo or be utilized for downstream analysis. Here, we describe the development and validation of a technology leveraging synthetic Notch receptors reporting physical tumor cell-immune cell contact in vivo in order to decipher the tumor-immune interactome. We call this approach, Tumor-Immune Interactome Non-biased Discovery Retroviral Reporter or TIINDRR. Using TIINDRR, we identify the tumor-immune interactomes that define immunological refractory and sensitive tumors and how different immunotherapies alter these interactions. Thus, TIINDRR provides a flexible and versatile tool for studying in-vivo tumor-immune cell interactions, aiding in the identification of biologically relevant information needed for the rational design of immune-based therapies. [ABSTRACT FROM AUTHOR]

The biological mechanisms linking sedentary lifestyles and metabolic derangements are incompletely understood. In this study, temporal muscle inactivation in Drosophila larvae carrying a temperature-sensitive mutation in the shibire (shi1) gene was induced to mimic sedentary behavior during early life and study its transcriptional outcome. Our findings indicated a significant change in the epigenetic profile, as well as the genomic profile, of RNA Pol II binding in the inactive muscles relative to control, within a relatively short time period. Whole-genome analysis of RNA-Pol II binding to DNA by muscle-specific targeted DamID (TaDa) protocol revealed that muscle inactivity altered Pol II binding in 121 out of 2010 genes (6%), with a three-fold enrichment of genes coding for lncRNAs. The suppressed protein-coding genes included genes associated with longevity, DNA repair, muscle function, and ubiquitin-dependent proteostasis. Moreover, inducing muscle inactivation exerted a multi-level impact upon chromatin modifications, triggering an altered epigenetic balance of active versus inactive marks. The downregulated genes in the inactive muscles included genes essential for muscle structure and function, carbohydrate metabolism, longevity, and others. Given the multiple analogous genes in Drosophila for many human genes, extrapolating our findings to humans may hold promise for establishing a molecular link between sedentary behavior and metabolic diseases. [ABSTRACT FROM AUTHOR]

Millions of dollars are spent annually in private litigation against jails. This article analyzes a novel dataset developed from dockets and reports of cases filed against jails by the estates of individuals who died in jail custody. The total amount of plaintiffs' awards represented in the sample was over $292,234,224. Cases attributing the cause of death to officer use of force had the highest average award ($2,243,079). Our findings suggest that suicide is still the most common cause of death for people in jail custody. Yet complications from a physical illness were not far behind, and nearly 20% of all cases in the sample were drug or alcohol related. In the first 24 hours of custody, people in jail were most at risk of drug-related deaths and suicide. [ABSTRACT FROM AUTHOR]

In evaluating the effectiveness of COVID-19 control measures, we propose a standardized approach to assess the impact of COVID-19 management on flattening the curve by analyzing the case data of Victoria, Australia. Its capital, Melbourne, is considered the most lock-downed city in the world. We used the daily case data from Victoria and their first time derivative and compared the dates when the six lockdowns were imposed with the start and end of the effective period, i.e., the period between the maximum and minimum acceleration. Lockdowns 1, 2 (Level 4 restrictions), 3, and 4 were found to be implemented too late, as they were expected to come into effect at the end or after the effective phase, and they were therefore ineffective. It was determined that Lockdown 2 (Level 3 restrictions) did not initiate the effective phase, and it was therefore ineffective, too. Lockdown 5 was expected to take effect in the second half of the effective phase, but showed no changes in the acceleration curve, and it was therefore also ineffective. Lockdown 6, implemented well before the effective period, did not flatten the curve, and was thus also found to be ineffective. The mask mandate between Lockdown 2 (Level 3 and 4 restrictions) initiated the effective phase (likely along with Lockdown 2, Level 3 restrictions), and was therefore found to effectively flatten the curve. The temporal relationship between the assumed cause (control measure) and the observed effect (flattening of the curve) is thus a crucial parameter for assessing the effect of control measures. [ABSTRACT FROM AUTHOR]

Objective: To develop novel fetal reference ranges for the characterization of the normal appearance of the Sylvian fissures (SF) along gestation and to apply them to fetuses with cortical abnormalities affecting the SF. Methods: In this cross‐sectional study, we used three‐dimensional sonographic multiplanar reformatting (3D‐MPR) to examine the fetal SF. Normal development was assessed in the second and third trimesters. SF parameters were evaluated in predefined axial and coronal planes: insular height and length, SF depth, and the extent of the coverage of the insula by the frontal and temporal lobes. Intra‐observer variability and inter‐rater reliability for the studied parameters were evaluated. The new reference charts were applied to 19 fetuses with cortical abnormalities involving the SF who had appropriate sonographic volumes for 3D‐MPR analysis. Their diagnoses were confirmed by autopsy, fetal or postnatal MRI, genetic findings related to cortical malformations, or an abnormal cortical imaging pattern with similar MRI findings in an affected sibling. We applied the two previously published references for the evaluation of fetal SF development to these cases and compared the ability of the references to correctly detect SF abnormalities. Results: The study included 189 fetuses of low‐risk singleton pregnancies between 24 and 34 gestational weeks. The insular length or height increased with gestational age in the axial and coronal planes with adjusted R2 = 0.621, p < 0.0001 and R2 = 0.384, p < 0.0001, respectively. The SF depth also increased with gestational age in the axial and coronal planes with adjusted R2 = 0.695, p < 0.0001 and R2 = 0.219, p = 0.008, respectively. The extent of the coverage of the insula by the frontal and temporal lobes in the coronal plane increased with gestational age (adjusted R2 = 0.627, p < 0.0001 and R2 = 0.589, p < 0.0001, respectively). The interclass correlation coefficients of the intra‐ and inter‐rater reliability of the studied parameters ranged between 0.71 and 0.97. The cortical anomalies in the 19 fetuses were polymicrogyria (7), simplified gyral pattern (3), dysgyria (3), lissencephaly (2), cortical malformation related to tubulinopathy (1), brain atrophy (1), cortical dysplasia (1), and cobblestone malformation (1). Three of the fetuses had multiple cortical anomalies. In 17 of 19 (89%) cases, at least one of our 6 SF parameters was found to be out of the normal range. In the coronal plane, SF height and depth were measured below 2SD in 9 (47%) and 4 (21%) cases, respectively. In the axial plane, SF length and depth were out of the normal ranges in six (31.5%) and four (21%), correspondingly. In the coronal plane, the opercular coverage by the frontal and temporal lobes was below 2 SD in 10 (52%) and 11 (57%), respectively. The scoring of the SF operculization by Quarello et al. was abnormal in 8 cases (42%). The measurement of the SF angle according to Poon et al. was abnormal in 14 cases (74%). Conclusions: The fetal SF is a complex developing structure that can be reliably characterized by sonographic parameters. One abnormal parameter is sufficient to raise the suspicion of SF malformation. Our new SF parameters might facilitate the detection of prenatal cortical abnormalities affecting the SF. Key points: What's already known about this topic? The fetal SF is a complex developing structure that can be characterized by sonographic parameters. Several studies have addressed the sonographic characterization of the SF during gestation using either qualitative criteria or measurable parameters. Although numerous studies provided normal references of SF biometry, only a few evaluated them in fetuses with MCD. What does this study add? We developed six new prenatal reference ranges for SF development assessing predefined axial and coronal planes using 3D multiplanar reformatting (MPR), of which one abnormal parameter is sufficient to raise the suspicion of an SF malformation. Our new SF parameters might facilitate the detection of prenatal cortical abnormalities affecting the SF. [ABSTRACT FROM AUTHOR]

This paper sets up to show how irony and reservations are explicitated in online media discourse, comparing their realizations in French and Hebrew online op-eds in leading journals. A corpus-based qualitative and quantitative analysis relies on two sets of big corpora for each language. The pragmatic analysis distinguishes between explicitating self- and other's presumed ironic intents, the target of irony, its locus and overall speaker's meanings. The findings indicate that the French data-set uses the verb ironiser , which has no comparable equivalent in Hebrew. More puzzling are the similarities between the two data-sets: both in French and in Hebrew journalists choose to explicitate irony and reservations, and they do so using similar discursive patterns. Conflicting forces are at play: interpretation paths are opened by irony, and are then narrowed down by the journalist's interpretations. The results are interpreted in terms of informativeness, accountability and commitment to speaker's meaning. [ABSTRACT FROM AUTHOR]

Physiological and psychological distress may accelerate cellular aging, manifested by shortening of telomere length (TL). The present study focused on TL shortening in anorexia nervosa (AN), an illness combining physiological and psychological distress. For that purpose, we measured TL in 44 female adolescents with AN at admission to inpatient treatment, in a subset of 18 patients also at discharge, and in 22 controls. No differences in TL were found between patients with AN and controls. At admission, patients with AN-binge/purge type (AN-B/P; n = 18) showed shorter TL compared with patients with AN-restricting type (AN-R; n = 26). No change in TL was found from admission to discharge, despite an improvement in body mass index standard deviation score (BMI-SDS) following inpatient treatment. Older age was the only parameter assessed to be correlated with greater TL shortening. Several methodological changes have to be undertaken to better understand the putative association of shorter TL with B/P behaviors, including increasing the sample size and the assessment of the relevant pathological eating disorder (ED) and non-ED psychological correlates in the two AN subtypes. [ABSTRACT FROM AUTHOR]

Aims The study aims to investigate the impact of direct oral anticoagulant (DOAC) management on the incidence of pocket haematoma in patients undergoing pacemaker or implantable cardioverter–defibrillator implantation. Methods and results All consecutive patients receiving DOAC and undergoing cardiac electronic device implantation were included in a large multicentre prospective observational study (NCT 03879473). The primary endpoint was clinically relevant haematoma within 30 days after implantation. Overall, 789 patients were enrolled [median age 80 (IQR 72–85) years old, 36.4% women, median CHA2DS2-VASc score 4 (IQR 0–8)], of which 632 (80.1%) received a pacemaker implantation. Antiplatelet therapy was combined with DOAC in 146 patients (18.5%). Direct oral anticoagulants (DOACs) were interrupted 52 (IQR 37–62) h before the procedure and resumed 31 (IQR 21–47) h later. Ninety-six percent of the patients had at least 12 h DOAC interruption before the procedure, and 78% had at least 12 h DOAC interruption after the procedure. Overall, anticoagulation was interrupted for 72 (IQR 48–96) h. Pre- or post-procedural heparin bridging was used in 8.2% and 3.9%, respectively. Timing of DOAC interruption of resumption was not associated with clinically relevant haematoma. Clinically relevant haematoma occurred in 26 patients (3.3%), and thromboembolic events occurred in 5 patients (0.6%). Conclusion In this large real-life registry where most patients had DOAC interruption, clinically relevant haematoma was rare. Despite DOAC interruption and high CHA2DS2-VASc score, thromboembolic events occurred seldomly, highlighting that bleeding exceeds thromboembolic risk in this peri-procedural period. Future research is needed to identify risk factors for clinically relevant haematoma and meaningfully guide clinicians in optimizing DOAC management. [ABSTRACT FROM AUTHOR]

Clinical observations suggest that girls suspected to have ASD manage to perform better in social and emotional tasks than boys, leading to a camouflage effect which results in the under-diagnosis of girls with ASD. We used the Social Attribution Task (SAT) in order to assess the performance of 12 girls who were previously diagnosed with ASD, and additionally to compare their performance in SAT to that of 12 boys who were previously diagnosed with ASD. No significant differences were found between girls and boys in all the indices of SAT except for the Person index; girls performed better than the boys in the Person index. The lack of significant differences between the boys and the girls in five out of the six SAT indices suggests that girls with ASD do not have a better social understanding than boys. They outperformed the boys only when the instructions included a clue that triggered them to name human traits, as they are instructed to do in the Person index. Implications of the usefulness of the Social Attribution Task (SAT) for diagnosing ASD in girls are discussed. [ABSTRACT FROM AUTHOR]

Aims Data on sports-related sudden cardiac arrest (SrSCA) among young adults in the general population are scarce. We aimed to determine the overall SrSCA incidence, characteristics, and outcomes in young adults. Methods and results Prospective cohort study of all cases of SrSCA between 2012 and 2019 in Germany and Paris area, France, involving subjects aged 18–35 years. Detection of SrSCA was achieved via multiple sources, including emergency medical services (EMS) reporting and web-based screening of media releases. Cases and aetiologies were centrally adjudicated. Overall, a total of 147 SrSCA (mean age 28.1 ± 4.8 years, 95.2% males) occurred, with an overall burden of 4.77 [95% confidence interval (CI) 2.85–6.68] cases per million-year, including 12 (8.2%) cases in young competitive athletes. While bystander cardiopulmonary resuscitation (CPR) was initiated in 114 (82.6%), automated external defibrillator (AED) use by bystanders occurred only in a minority (7.5%). Public AED use prior to EMS arrival (odds ratio 6.25, 95% CI 1.48–43.20, P = 0.02) was the strongest independent predictor of survival at hospital discharge (38.1%). Among cases that benefited from both immediate bystander CPR and AED use, survival rate was 90.9%. Coronary artery disease was the most frequent aetiology (25.8%), mainly through acute coronary syndrome (86.9%). Conclusion Sports-related sudden cardiac arrest in the young occurs mainly in recreational male sports participants. Public AED use remains disappointingly low, although survival may reach 90% among those who benefit from both bystander CPR and early defibrillation. Coronary artery disease is the most prevalent cause of SrSCA in young adults. [ABSTRACT FROM AUTHOR]