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Pten germline haploinsufficient (Pten+/−) mice, which model macrocephaly/autism syndrome, show social and repetitive behavior deficits, early brain overgrowth, and cortical–subcortical hyperconnectivity. Previous work indicated that altered neuronal connectivity may be a substrate for behavioral deficits. We hypothesized that exposing Pten+/− mice to environmental enrichment after brain overgrowth has occurred may facilitate adaptation to abnormal “hard-wired” connectivity through enhancing synaptic plasticity. Thus, we reared Pten+/− mice and their wild-type littermates from weaning under either standard (4–5 mice per standard-sized cage, containing only bedding and nestlet) or enriched (9–10 mice per large-sized cage, containing objects for exploration and a running wheel, plus bedding and nestlet) conditions. Adult mice were tested on social and non-social assays in which Pten+/− mice display deficits. Environmental enrichment rescued sex-specific deficits in social behavior in Pten+/− mice and partially rescued increased repetitive behavior in Pten+/− males. We found that Pten+/− mice show increased excitatory and decreased inhibitory pre-synaptic proteins; this phenotype was also rescued by environmental enrichment. Together, our results indicate that environmental enrichment can rescue social behavioral deficits in Pten+/− mice, possibly through normalizing the excitatory synaptic protein abundance.

Haploinsufficiency for PTEN is a cause of autism spectrum disorder and brain overgrowth; however, it is not known if PTEN mutations disrupt scaling across brain areas during development. To address this question, we used magnetic resonance imaging to analyze brains of male Pten haploinsufficient (Pten+/−) mice and wild-type littermates during early postnatal development and adulthood. Adult Pten+/− mice display a consistent pattern of abnormal scaling across brain areas, with white matter (WM) areas being particularly affected. This regional and WM enlargement recapitulates structural abnormalities found in individuals with PTEN haploinsufficiency and autism. Early postnatal Pten+/− mice do not display the same pattern, instead exhibiting greater variability across mice and brain regions than controls. This suggests that Pten haploinsufficiency may desynchronize growth across brain regions during early development before stabilizing by maturity. Pten+/− cortical cultures display increased proliferation of glial cell populations, indicating a potential substrate of WM enlargement, and provide a platform for testing candidate therapeutics. Pten haploinsufficiency dysregulates coordinated growth across brain regions during development. This results in abnormally scaled brain areas and associated behavioral deficits, potentially explaining the relationship between PTEN mutations and neurodevelopmental disorders.

Modern language models capture a large body of factual knowledge. However, some facts can be incorrectly induced or become obsolete over time, resulting in factually incorrect generations. This has led to the development of various editing methods that allow updating facts encoded by the model. Evaluation of these methods has primarily focused on testing whether an individual fact has been successfully injected, and if similar predictions for other subjects have not changed. Here we argue that such evaluation is limited, since injecting one fact (e.g., ) introduces a “ripple effect” in the form of additional facts that the model needs to update (e.g., ). To address this, we propose novel evaluation criteria that consider the implications of an edit on related facts. Using these criteria, we then construct , a diagnostic benchmark of 5K factual edits, capturing various types of ripple effects. We evaluate prominent editing methods on , showing that they fail to introduce consistent changes in the model’s knowledge. In addition, we find that a simple in-context editing baseline obtains the best scores on our benchmark, suggesting a promising research direction for model editing.

Two doses of the BNT162b2 vaccine were associated mainly with low-grade local adverse effects that lasted 2 days or less and afforded nearly 50% protection against omicron infection and symptomatic illness, which was lower than that seen against delta. Greater protection in the youngest group was noted.

Additionally, many injured individuals arrived at hospitals simultaneously, which necessitated the cancellation of elective surgeries and the closure of outpatient services. 6 Subsequent rocket attacks, with direct hits on critical infrastructure such as the Child Development Institute at Barzilai Medical Center, exacerbated the situation and disrupted essential medical services, highlighting the indiscriminate nature of these attacks. 2 Moreover, testimonies from hostages revealed that they were treated without anaesthesia, a stark violation of medical ethics. 7 The Article by Alser and colleagues appears to be part of a broader narrative aimed at accusing Israel of war crimes, which is fundamentally at odds with the principles of medical neutrality and humanitarian law. According to a report by the Taub Center for Social Policy Studies in Israel, over 17 000 people were hospitalised in Israel due to the war between Oct 7, 2023, and Aug 22, 2024. OW reports consulting fees from Sanofi and AstraZeneca; reports honoraria from BI, GSK, AstraZeneca, Kamada, and Sanofi; and has participated on a data safety monitoring board for Sanofi and AstraZeneca.

Spatial modulation of electron beams is an essential tool for various applications such as nanolithography and imaging, yet its conventional implementations are severely limited and inherently non-tunable. Conversely, proposals of light-driven electron spatial modulation promise tunable electron wavefront shaping, for example, using the mechanism of photon-induced near-field electron microscopy. Here we present tunable photon-induced spatial modulation of electrons through their interaction with externally controlled surface plasmon polaritons (SPPs). Using recently developed methods of shaping SPP patterns, we demonstrate a dynamic control of the electron beam with a variety of electron distributions and verify their coherence through electron diffraction. Finally, the nonlinearity stemming from energy post-selection provides us with another avenue for controlling the electron shape, generating electron features far below the SPP wavelength. Our work paves the way to on-demand electron wavefront shaping at ultrafast timescales, with prospects for aberration correction, nanofabrication and material characterization.On-demand electron wavefront shaping is desirable for applications from nanolithography to imaging. Here, the authors present tunable photon-induced spatial modulation of electrons through their interaction with externally controlled surface plasmon polaritons.

IntroductionWhile there is evidence of the presence of the coronavirus in the kidneys and resultant acute kidney injury (AKI), information on the effect of chronic kidney disease (CKD) on COVID-19 outcomes and its pathogenesis is currently lacking.MethodsThis retrospective, observational study evaluated the outcomes of all consecutive patients hospitalized during COVID-19 outbreaks in Meir Medical Center. Serum creatinine level was assessed before hospitalization (“baseline serum creatinine”) and at admission, as well as minimum and maximum serum creatinine levels during hospitalization.ResultsAmong 658 patients, 152 had eGFR < 60 ml/min (termed the CKD group), 506 patients served as controls. Patients in the CKD group were older, with higher prevalence of hypertension, diabetes mellitus and atherosclerosis. Disease severity and clinical presentation of CKD group were comparable to that of control group. Odds ratio for AKI was 5.8 (95%CI 3.8–8.7; p < 0.001) in CKD group vs. control group and 3.4 (95%CI 1.1–10.8) for renal replacement therapy (p < 0.026). Among the CKD group, 32.2% died after COVID-19 infection versus 14.8% of the controls (p < 0.001). Mortality increased as CKD stage increased (14.8% in controls, 29.6% in CKD stage 3, and 39.3% in CKD stages 4 and 5, p < 0.001).ConclusionDespite comparable disease severity at presentation, patients with CKD had significantly more AKI events and required more renal replacement therapy during hospitalization than control patients did. Mortality increased as CKD stage increased.

Background We have developed the Suicide Crisis Inventory (SCI) to evaluate the intensity of the Suicidal Crisis Syndrome, an acute state hypothesized to precede suicide attempt. The psychometric properties of the SCI, including predictive validity for suicidal behavior (SB), were assessed. Methods Adult psychiatric patients (n = 201) hospitalized for high suicide risk were assessed. Logistic regression models assessed the SCI's predictive validity for SB in the 4–8 weeks following hospital discharge and its incremental predictive validity over traditional risk factors (n = 137, 64% f/u rate). Internal structure, reliability, convergent and discriminant validity, and state versus trait properties were also assessed. Results The SCI had excellent internal consistency (Cronbach's α 0.970). The SCI total score at discharge predicted short‐term SB with 64% sensitivity 88% specificity (OR = 13, P = .003) at its optimal cut score. In a test of its incremental predictive validity, SCI total score at discharge improved prediction of SB over traditional risk factors (Chi‐squared 5.597, P = .024, model P = .001), with AOR 2.02 (P = .030). The SCI admission versus discharge test–retest reliability and score distributions showed it to be an acute state measure. Conclusion The SCI was predictive of future SB in high‐risk psychiatric inpatients during the crucial weeks following their hospital discharge. Further validation in diverse patient populations is needed.

In the last few months the world has witnessed a global pandemic due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19). Obviously, this pandemic affected individuals differently, with a significant impact on populations considered to be at high-risk. One such population, was assumed to be patients with primary genetic defect involving components or pathways of the immune system. While human immunity against COVID-19 is not fully understood, it is, so far, well documented, that both adaptive and innate cells have a critical role in protection against SARS-CoV-2. Here, we aimed to summarize the clinical and laboratory data on primary immunodeficiency (PID) patients in Israel, who were tested positive for SARS-CoV-2, in order to estimate the impact of COVID-19 on such patients. Data was collected from mid-February to end-September. During this time Israel experienced two “waves” of COVID-19 diseases; the first, from mid-February to mid-May and the second from mid-June and still ongoing at the end of data collection. A total of 20 PID patients, aged 4 months to 60 years, were tested positive for SARS-CoV-2, all but one, were detected during the second wave. Fourteen of the patients were on routine monthly IVIG replacement therapy at the time of virus detection. None of the patients displayed severe illness and none required hospitalization; moreover, 7/20 patients were completely asymptomatic. Possible explanations for the minimal clinical impact of COVID-19 pandemic observed in our PID patients include high level of awareness, extra-precautions, and even self-isolation. It is also possible that only specific immune pathways (e.g. type I interferon signaling), may increase the risk for a more severe course of disease and these are not affected in many of the PID patients. In some cases, lack of an immune response actually may be a protective measure against the development of COVID-19 sequelae.

Chronic kidney disease is associated with an increased risk for cardiovascular and bleeding events. Data regarding the effectiveness and risks of aspirin therapy for primary prevention in the high-risk group of patients with chronic kidney disease are scant and controversial. This retrospective study included patients with chronic kidney disease. Participants were divided according to aspirin use. Outcomes included non-fatal cardiovascular events, major bleeding events and all-cause mortality. Among 10,303 patients, 2169 met the inclusion criteria and 1818 were included after 1:1 propensity-score matching. Our final cohort included patients with mean age of 73.4 ± 11.6 years, estimated glomerular filtration rate of 31.5 ± 10.5 ml/min/1.73m 2 with follow up of 4.9 ± 1.5 years. There were no significant differences in all-cause mortality and bleeding events (odds ratio = 1.03, confidence interval [0.62, 1.84], p  = .58 and odds ratio = 1.09, confidence interval [0.65, 1.72], p  = .87 respectively). The incidence of cardiovascular events was higher in aspirin users versus non-users on univariate analysis ( p  < 0.01) and was comparable after controlling for possible risk-factors (OR = 1.05, CI [0.61, 3.14], p  = .85). Chronic aspirin use for primary prevention of cardiovascular disease was not associated with lower mortality, cardiovascular events or increased bleeding among patients with chronic kidney disease. Those results were unexpected and should prompt further research in this field.