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The standard treatment approach for stage II/III rectal cancer is neoadjuvant chemoradiation therapy (nCRT) followed by surgery. In recent years, new treatment approaches have led to higher rates of complete tumor eradication combined with organ-preservation strategies. However, better tools are still needed to personalize therapy for the individual patient. In this prospective observational study, we analyzed colon-derived cell-free (cf)DNA (c-cfDNA) using a tissue-specific DNA methylation signature, and its association with therapy outcomes. Analyzing plasma samples (n = 303) collected during nCRT from 37 patients with locally advanced rectal cancer (LARC), we identified colon-specific methylation markers that discriminated healthy individuals from patients with untreated LARC (area under the curve, 0.81; 95% confidence interval, 0.70-0.92; P 0.0001). Baseline c-cfDNA predicted tumor response, with increased levels linked to larger residual cancer. c-cfDNA measured after the first week of therapy identified patients with maximal response and complete cancer eradication, who had significantly lower c-cfDNA compared with those who had residual disease (8.6 vs 57.7 average copies/mL, respectively; P = 0.013). Increased c-cfDNA after one week of therapy was also associated with disease recurrence. Methylation-based liquid biopsy can predict nCRT outcomes and facilitate patient selection for escalation and de-escalation strategies.

What is a creature within a creature, with no consanguinity or kinship between them? Upon what place did the sunshine once, but then never again? These and host of other Judeo-ʿ⁠Alīd brain-teasers are adduced by the seventeenth-century Shiʿite encyclopedist Muḥammad Bāqir al-Majlisī in order to shore up the most pristine and essential of Shiʿite claims: that ʿ⁠Alī should have been the successor to the Prophet Muḥammad. The material examined in this essay sheds light both upon aspects of the Sunni-Shiʿī polemic and on Shiʿism’s outlook on the previous monotheistic dispensations. This article analyzes the series of interlocutions adduced by Majlisī (and his sources) as part of the campaign to retroactively unseat the caliphs enshrined by Sunnism. As with Islamic tradition in general, Shiʿism displays in this material a penchant for drafting the exponents of surrounding creeds to shore up its political and religious claims.

Nitrate pollution is a global problem as it affects both the environment and human health. The objective of this research was to study the effect of electrode configuration on the electro-reduction of nitrate. Coaxial cylindrical (inner rod and outer tube copper cathodes) and vertical plate parallel copper cathodes paired with Ti/RuO2-IrO2 (rod, tube, and plate) configurations were studied under various current densities and initial nitrate concentrations. The efficiency of each configuration was determined based on the removal efficiency of nitrate, specific energy consumption, mass transfer coefficients, and first order rate constants. Additionally, the overall systems’ resistance and geometric factors are discussed. It was found that the performances of the inner rod and outer tube copper cathodes were similar. The vertical plate parallel configuration was superior to the coaxial cylindrical electrode setup, as evident from a higher maximum nitrate removal of 74 and 56% at a current density of 7 mA/cm2 and lower energy consumption of 46.7 × 10−3 and 54.3 × 10−3 kWh/mmol NO3− at 36.4 mA/cm2, respectively. In addition, the mass transfer coefficients and first order rate constants were higher in all conditions tested for the vertical plate parallel configuration.

This article deals with legal opinions (fatwās) for Muslims living in Israel as a minority under non-Muslim rule. A well-developed legal doctrine known as fiqh al-aqalliyyāt al-muslima (jurisprudence concerning Muslim minorities) applies to Muslim minorities living in the West. The innovators of fiqh al-aqalliyyāt, Yūsuf al-Qaraḍāwī and Ṭaha Jābir al-ʿAlwānī, did not issue legal opinions for the Muslim minority living in Israel, which, because of the Israeli-Palestinian conflict, is classified as The Abode of War (dār al-ḥarb). In this article, I examine developments in Islamic jurisprudence for the Muslim minority living in Israel, with a focus on the legal opinions of Sheikh Rāʾid Badīr, the senior religious authority of the southern branch of the Islamic Movement in Israel and the pioneer in issuing fatwās for the Muslim minority in Israel.

The use of cardiopulmonary bypass (CPB) is thought to cause delayed cardiac damage. DNA methylation-based liquid biopsies are novel biomarkers for monitoring acute cardiac cell death. We assessed cell-free DNA molecules as markers for cardiac damage after open-heart surgery. Novel cardiomyocyte-specific DNA methylation markers were applied to measure cardiac cfDNA in the plasma of 42 infants who underwent open-heart surgery. Cardiac cfDNA was elevated following surgery, reflecting direct surgery-related tissue damage, and declined thereafter in most patients. The concentration of cardiac cfDNA post-surgery correlated with the duration of CPB and aortic cross clamping. Strikingly, cardiac cfDNA at 6 h predicted duration of mechanical ventilation and maximal vasoactive-inotropic score better than did maximal troponin levels. Cardiac cfDNA reveals heart damage associated with CPB, and can be used to monitor cardiac cell death, to predict clinical outcome of surgery and to assess performance of cardioprotective interventions.

Reverse osmosis is used as a tertiary treatment for wastewater reclamation. However, sustainable management of the concentrate (ROC) is challenging, due to the need for treatment and/or disposal. The objective of this research was to investigate the efficiency of homogeneous and heterogeneous Fenton-like oxidation processes in removing propoxur (PR), a micro-pollutant compound, from synthetic ROC solution in a submerged ceramic membrane reactor operated in a continuous mode. A freshly prepared amorphous heterogeneous catalyst was synthesized and characterized, revealing a layered porous structure of 5–16 nm nanoparticles that formed aggregates (33–49 μm) known as ferrihydrite (Fh). The membrane exhibited a rejection of >99.6% for Fh. The homogeneous catalysis (Fe3+) exhibited better catalytic activity than the Fh in terms of PR removal efficiencies. However, by increasing the H2O2 and Fh concentrations at a constant molar ratio, the PR oxidation efficiencies were equal to those catalyzed by the Fe3+. The ionic composition of the ROC solution had an inhibitory effect on the PR oxidation, whereas increased residence time improved it up to 87% at a residence time of 88 min. Overall, the study highlights the potential of heterogeneous Fenton-like processes catalyzed by Fh in a continuous mode of operation.

How Israelis and Palestinians see the conflict between both groups and its eventual solution? Based on 38 in-depth interviews with Israeli and Palestinian political leaders, the article analyzes the Palestinian choice of the two-state solution as the best way to bring an end to the Israeli occupation of 1967. The article then explores the Israeli policy of annexation of the West Bank and the entrenchment of apartheid—a one-state reality of unequal rights from the river to the sea. While the Israeli interviewed attempt to normalize this one-state reality, the Palestinians oppose these attempts of normalization and perceive the emerging debate on the need to reconsider the two-state solution as part of Israel's efforts to normalize the facts on the ground. Finally, the article explores the particular position of the Palestinians in Israel, who were not part of the national project of Palestinian statehood and hence developed their own future vision, based on equal citizenship. The article concludes that more research is needed on this particular group.

The subject of this essay is the role Rabbi Menachem Froman played as a mediator in crises between Israelis and Palestinians against the background of his interreligious vision of peace and attempts to implement it. Rabbi Froman was very active in this matter and initiated various schemes to promote reconciliation between the Israelis and Palestinians, both in his discussions with religious leaders of the two peoples as well as with politicians in Israel and around the world. The network of contacts and the open discourse that the rabbi developed in order to promote his vision enabled him to serve as a mediator during numerous crises that arose in the Middle East, in general, and Israel in particular. This essay sheds light on Rabbi Froman’s attempts at mediation throughout the years, including the outline of a solution to the Israeli–Palestinian conflict he crafted with the other side. This essay is primarily based on archival materials and newspaper articles about the rabbi that were revealed after his death in 2013. The essay also chronologizes Rabbi Froman’s attempts to serve as mediator for the Israeli and Palestinian leadership and the “jihad for peace” he advocated.

Intrapartum transperineal ultrasound (ITU) is an accepted tool for assessing fetal head position and station prior to operative vaginal delivery attempt. However, the validity of intrapartum ultrasound in real-life obstetrics with operators at different proficiency level is yet to be established. We aimed to investigate the association between operator level of training and reliability of angle of progression (AOP) measurements in real-life obstetrics.This was a retrospective study in one university medical center. We included women who underwent ITU for the measurement of AOP, before vacuum assisted delivery from November 2017 to September 2020. AOP measurements performed by residents and their correlation to head station were compared to those performed by specialists.A total of 320 cases met the inclusion criteria. In 234 of them, AOP measurements were performed by specialists and in 86 by residents. Average AOP for each station was similar between the specialists and the residents groups, indicating similar accuracy. However, measurements in the residents group were more scattered (median deviation 11.4° vs. 8.9°, respectively,AOP measurements performed by obstetrics and gynecology (OBGYN) specialists are more precise than those performed by residents. Efforts should be taken to improve ITU training and to implement assessment of performance programs.

This paper focuses on new findings from Middle Paleolithic Geula Cave, Israel, located in the northern part of Mt. Carmel. The cave, consists of several small chambers that are remnants of a larger cave system, initially excavated between 1958 and 1964. The occupation at the cave was ascribed to Middle Paleolithic modern humans. In 2016, a salvage excavation was conducted in areas of the cave that were not previously explored. Analyses of the new excavation revealed a consistency in lithic technology throughout the new excavation areas, with an emphasis on Levallois production using mainly bidirectional and centripetal core preparation modes. The faunal study identified intensive hyena and porcupine activities in small chambers, probably at the back part of the cave, while fractured bones in association with flint artifacts were found at what appears as the living area in the cave. Luminescence ages indicated that Geula Cave was occupied as early as 175 ka, but that the major occupation was from 120 to 100 ka. The major occupation at Geula chronologically overlaps with the Skhul and Qafzeh Caves thus reinforcing the notion that Homo sapiens dominated the southern Levant during early MIS 5. This study demonstrates the importance of reinvestigating and reevaluating past excavated prehistoric sites and their contents to enhance our understanding of the regional, cultural and biological history.

Kerion is an inflammatory type of tinea capitis manifesting as boggy crusted nodules. Diagnosis of kerion is often challenging due to high rates of false-negative mycological samples.A retrospective study among children with kerion, prior to antifungal treatment, was conducted to assess rates of false-negative mycological samples. Specimens for direct microscopy and fungal culture were collected at baseline and after administration of an oral antibiotic course, with or without an oral steroid course. Kerion was categorized as highly inflammatory when a painful, moist scalp nodule with spontaneous purulent discharge or exuberant crust was present, or mildly inflammatory when an erythematous, dry scalp nodule was seen.Twenty-three children (mean age 7.9 ± 3.0 years) were included in the study. Trichophyton tonsurans was the most common species isolated (69.6%). Highly inflammatory kerions were significantly more likely to be culture negative before treatment than mildly inflammatory kerions (80% vs. 16.7%, p .01). Non-inflammatory tinea capitis lesions (n = 13) were culture positive in all cases. Following a combined oral antibiotic and steroid course given to most highly inflammatory kerions (n = 11/13), higher rates of positive fungal cultures were found compared to baseline (90.9% vs. 18.2%, p .01).High rates of negative fungal cultures were found only in highly inflammatory kerion. Sampling a highly inflammatory kerion after a combined oral antibiotic and steroid course improved rates of positive fungal cultures. In addition, sampling of non-inflammatory tinea capitis lesions (when present in addition to the kerion) had the highest culture sensitivity.

Data de publicació electrònica: 04-04-2022 Pathogenic variants in A Disintegrin And Metalloproteinase (ADAM) 22, the postsynaptic cell membrane receptor for the glycoprotein leucine-rich repeat glioma-inactivated protein 1 (LGI1), have been recently associated with recessive developmental and epileptic encephalopathy. However, so far, only two affected individuals have been described and many features of this disorder are unknown. We refine the phenotype and report 19 additional individuals harboring compound heterozygous or homozygous inactivating ADAM22 variants, of whom 18 had clinical data available. Additionally, we provide follow-up data from two previously reported cases. All affected individuals exhibited infantile-onset, treatment-resistant epilepsy. Additional clinical features included moderate to profound global developmental delay/intellectual disability (20/20), hypotonia (12/20), delayed motor development (19/20). Brain MRI findings included cerebral atrophy (13/20), supported by post-mortem histological examination in patient-derived brain tissue, cerebellar vermis atrophy (5/20), and callosal hypoplasia (4/20). Functional studies in transfected cell lines confirmed the deleteriousness of all identified variants and indicated at least three distinct pathological mechanisms: defective cell membrane expression (1), impaired LGI1-binding (2), and/or impaired interaction with the postsynaptic density protein PSD-95 (3). We reveal novel clinical and molecular hallmarks of ADAM22 deficiency and provide knowledge that might inform clinical management and early diagnostics. Funding: most families were collected as part of the SYNaPS Study Group collaboration funded by the Wellcome Trust and strategic award (Synaptopathies) funding (WT093205 MA and WT104033AIA). This study was also supported by JSPS/MEXT KAKENHI (Grants 19H03331, 19K22439 and 21K19390 to Y.F., Grant 19K16269 to Y.M., and Grants 20H00459 and 20H04915 to M.F.) and Japan Agency for Medical Research and Development (21wm0525022h0001 to Y.F.); intramural funding (fortüne) from the University of Tübingen (Grant 2545-1-0) and the Ministry of Science, Research and Art Baden-Württemberg to B.V. P.S. contributed to this work within the framework of the DINOGMI Department of Excellence of MIUR 2018-2022 (legge 232 del 2016). T.B.H. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 418081722, 433158657. I.S.P., V.Y.V. are supported by the Government Assignment of the Russian Ministry of Health (#121061500066-2). HL receives support from the Canadian Institutes of Health Research (Foundation Grant FDN-167281), the Canadian Institutes of Health Research and Muscular Dystrophy Canada (Network Catalyst Grant for NMD4C), the Canada Foundation for Innovation (CFI-JELF 38412), and the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950-232279). S.H. is funded by TUBITAK (Turkish Scientific and Technological Research Council) Project number 216S771. R.H. is a Wellcome Trust Investigator (109915/Z/15/Z), who received support from the Medical Research Council (UK) (MR/N025431/1 and MR/V009346/1), the European Research Council (309548), the Newton Fund (UK/Turkey, MR/N027302/1), the Addenbrookes Charitable Trust (G100142), the Evelyn Trust, the Stoneygate Trust, the Lily Foundation and an MRC strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) MR/S005021/1. This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014)

Purpose To investigate factors associated with pediatric feeding disorders (PFD) among children of parents that reported to have had feeding disorders during their own childhood compared to children with PFD with no history of parental PFD. Methods We retrospectively reviewed the medical records of children diagnosed with PFD according to the recent WHO-based definition. Demographic and clinical characteristics of children with PFD with a parental history of PFD were compared to those of children with a PFD with no history of parental PFD. Results Included were 231 children with PFD (median [interquartile range] age 10 (5.5–29) months at diagnosis, 58% boys) of whom 133 children had parents without PFD and 98 children had parents with PFD. Unexpectedly, children of parents without PFD had a higher rate of low birth weight (28% vs. 19%, respectively, p = 0.007), more delivery complications (10% vs. 2%, p = 0.006), more hospitalizations (33% vs. 17%, p = 0.004), more prescription medications (27% vs. 18%, p = 0.05), and a higher percent of gastrostomy tube use (6% vs. 0, p = 0.02). Moreover, more parents with PFD had an academic background compared with parents without PFD (72% vs. 59%, p = 0.05). There were no significant group differences in sex, history of breastfeeding, parental marital status, or type of the child's feeding disorder. Conclusions PFD among children with a parental history of PFD comprise a distinct group of patients with unique characteristics and outcomes. Since parental feeding history may explain their child's PFD in highly differing ways, treatment should be family-based and multidisciplinary.

Radiotherapy has an important role in the treatment of brain metastases (BrM) but carries risk of short and/or long-term toxicity, termed radiation-induced neurotoxicity (RIN). As the diagnosis of RIN is crucial for correct pa-tient management, there is an unmet need for reliable biomarkers for RIN. The aim of this proof-of concept study was to determine the utility of brain-derived circulating free DNA (BncfDNA), identified by specific methylation patterns for neurons, astrocytes, and oligodendrocytes, as RIN biomarkers. Twenty-four patients with BrM 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. During follow-up nine RIN events were detected, and all correlated with significant increase in BncfDNA levels compared to baseline. Additionally, resolution of RIN correlated with de-crease in BncfDNA. Changes in BncfDNA were independent of tumor response. Elevated BncfDNA levels reflects brain cell injury incurred by radiotherapy, further research is needed to establish BncfDNA as a novel plasma-based biomarker for RIN.

The SARS-CoV-2 pandemic led to unprecedented testing demands, causing significant testing delays globally. One strategy used for increasing testing capacity was pooled-testing, using a two-stage technique first introduced during WWII. Here we report the development, validation and clinical application of P-BEST - a single-stage pooled-testing strategy that was approved for clinical use in Israel. P-BEST was clinically evaluated using 3,636 side-by-side tests and was able to correctly detect all positive samples and accurately estimate their Ct value. P-BEST was then used to clinically test 837,138 samples using 270,095 PCR tests - a 3.1 fold reduction in the number of tests. Importantly, P-BEST was also used during the Alpha and Delta waves, when positivity rates exceeded 10%, rendering traditional pooling non-practical. We also describe a tablet-based solution that allows performing manual single-stage pooling in settings where liquid dispensing robots are not available. Our data provides a proof-of-concept for large-scale clinical implementation of single-stage pooled-testing for continuous surveillance of multiple pathogens with reduced test costs, and as an important tool for increasing testing efficiency during pandemic outbreaks.

SummaryChronological age prediction from DNA methylation sheds light on human aging, indicates poor health and predicts lifespan. Current clocks are mostly based on linear models from hundreds of methylation sites, and are not suitable for sequencing-based data.We present GP-age, an epigenetic clock for blood, that uses a non-linear cohort-based model of 11,910 blood methylomes. Using 30 CpG sites alone, GP-age outperforms state-of-the-art models, with a median accuracy of ~2 years on held-out blood samples, for both array and sequencing-based data. We show that aging-related changes occur at multiple neighboring CpGs, with far-reaching implications on aging research at the cellular level. By training three independent clocks, we show consistent deviations between predicted and actual age, suggesting individual rates of biological aging.Overall, we provide a compact yet accurate alternative to array-based clocks for blood, with future applications in longitudinal aging research, forensic profiling, and monitoring epigenetic processes in transplantation medicine and cancer.Graphical abstractMachine learning analysis of a large cohort (~12K) of DNA methylomes from bloodA 30-CpG regression model achieves a 2.1-year median error in predicting ageImproved accuracy (≥1.75 years) from sequencing data, using neighboring CpGsPaves the way for easy and accurate age prediction from blood, using NGS dataMotivationEpigenetic clocks that predict age from DNA methylation are a valuable tool in the research of human aging, with additional applications in forensic profiling, disease monitoring, and lifespan prediction. Most existing epigenetic clocks are based on linear models and require hundreds of methylation sites. Here, we present a compact epigenetic clock for blood, which outperforms state-of-the-art models using only 30 CpG sites. Finally, we demonstrate the applicability of our clock to sequencing-based data, with far reaching implications for a better understanding of epigenetic aging.

This article deals with the rulings of Sheikh Rāʾid Badīr, who served as a mediator between the Israeli government and the Muslim community over the course of the pandemic. As a senior leader and scholar of the southern branch of the Islamic Movement in Israel, Sheikh Rāʾid Badīr’s fatwās have historically addressed the unique circumstances and situational difficulties faced by Muslims living in Israel.

The application of myopia definition varies considerably within the literature. The purpose of this study was to examine the relationship between different myopia and high myopia definitions and resultant prevalence estimates. A population-based cross-sectional study of 1,588,508 Israeli adolescents assessed for medical fitness before mandatory military service at the age of 17 years between 1993 through 2015. Participants underwent non-cycloplegic autorefraction. Nine definitions of myopia and seven definitions of high myopia were examined. Prevalence estimates for each definition were calculated and compared with the reference definition (right eye spherical equivalent (SE)≤-0.50D and ≤-6.00D for myopia and high myopia, respectively), to yield a rate ratio (RR) across definitions. Applying the right eye SE≤-0.50D reference definition yielded 31.0% myopia prevalence. While some definitions resulted in similar prevalence estimates, using the right eye SE of ≤-0.75D; ≤-1.00D or least minus meridian of ≤-0.75D definitions yielded 28.8%, 26.3%, and 26.9% myopia prevalence, respectively, which corresponded to a 7.1%, 15.1% and 13.4% reduction in myopia RR, respectively. The prevalence of high myopia demonstrated considerable alternations, with a 1.7-fold increase in prevalence for the narrower threshold of SE≤-5.00D compared with SE≤-6.00D reference definition (4.2% and 2.4%, respectively). The prevalence of myopia and especially high myopia varies between frequently applied definitions, considering diverse thresholds, eye lateralization, and spherical vs. astigmatic refractive components. This variability highlights the pressing need for standardization of myopia definition in ophthalmic research. The results of this study provide crude estimates of a “conversion rate” across data, allowing comparisons between studies that utilize different myopia definitions.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease affecting approximately 25% of all people worldwide at some point during their lifetime. Although total serum immunoglobulin E (IgE) and blood eosinophil levels are not elevated in all patients with AD, they have been shown associated with AD severity. This study aimed to investigate whether IgE and blood eosinophil levels correlate with the response to phototherapy treatment, which is a second-line treatment for moderate-to-severe AD, and therefore could be considered a readily available and reliable biomarker that could guide patient management. Eighty-two patients with AD who received phototherapy at the Sheba Medical Center were retrospectively evaluated for the following: demographic characteristics, serum IgE levels, blood eosinophils count, hospitalization duration, response to phototherapy, and requirement for systemic treatment. Response to phototherapy treatment was assessed by comparing the pre- and post-treatment Investigator’s Global Assessment score for each patient in relation to the aforementioned factors. The total IgE and eosinophil levels were found to be significantly higher in patients who did not respond to phototherapy (p=0.018 and p=0.002, accordingly). Serum values of 1780 IU/mL for IgE and 225.0 cells/μL for eosinophils showed maximum sensitivity and specificity as predictive values for treatment response. In conclusion, this study found that high total serum IgE levels and eosinophilia were correlated with a low response to phototherapy. These results suggest that escalating treatment is recommended for patients presenting these clinical features.

A possible solution for the standoff detection of buried landmines is based on the use of microbial bioreporters, genetically engineered to emit a remotely detectable optical signal in response to trace amounts of explosives' signature chemicals, mostly 2,4-dinitrotoluene (DNT). Previously developed DNT sensor strains were based on the fusion of a DNT-inducible gene promoter to a reporting element, either a fluorescent protein gene or a bacterial bioluminescence gene cassette. In the present study, a different approach was used: the DNT-inducible promoter activates, in

Although it is known that the mutation rate varies across the genome, previous estimates were based on averaging across various numbers of positions. Here, we describe a method to measure the origination rates of target mutations at target base positions and apply it to a 6-bp region in the human hemoglobin subunit beta (HBB) gene and to the identical, paralogous hemoglobin subunit delta (HBD) region in sperm cells from both African and European donors. The HBB region of interest (ROI) includes the site of the hemoglobin S (HbS) mutation, which protects against malaria, is common in Africa, and has served as a classic example of adaptation by random mutation and natural selection. We found a significant correspondence between de novo mutation rates and past observations of alleles in carriers, showing that mutation rates vary substantially in a mutation-specific manner that contributes to the site frequency spectrum. We also found that the overall point mutation rate is significantly higher in Africans than in Europeans in the HBB region studied. Finally, the rate of the 20A→T mutation, called the “HbS mutation” when it appears in HBB, is significantly higher than expected from the genome-wide average for this mutation type. Nine instances were observed in the African HBB ROI, where it is of adaptive significance, representing at least three independent originations; no instances were observed elsewhere. Further studies will be needed to examine mutation rates at the single-mutation resolution across these and other loci and organisms and to uncover the molecular mechanisms responsible.

Background Methodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate early real-world VE in a closely monitored population. Methods We conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples – at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher’s exact test. Results Of the 1567 HCP enrolled between December 27, 2020 and February 15, 2021, 1250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR-confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant. Conclusions Our prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 infection in recently vaccinated HCP during a period of predominant alpha variant circulation. Funding Clalit Health Services.

This pilot study examines practices of community interpreting in Israel's social services, with a focus on two immigrant populations (Ethiopian Jews and French Jews) and the experience of the interpreters and the social workers who work with them. Twenty interviews were conducted, transcribed, and thematically analyzed. The analysis of the interviews highlights four major contexts in which the experience of interpreting within the social work services with immigrants are grounded: the cultural context of the interpreters, the community context of the interpreters, the organizational context of the agencies in which encounters between social workers and interpreters occur, and the context of the interpreters’ working conditions. The findings reflect contradictory messages regarding the importance of community interpreting in the social work services with immigrants. Despite the importance of having a triadic encounter attended by an interpreter, lack of awareness of the contexts that influence the practice of interpreting is evident in the professional encounter and its ramifications.

Background The incidence of invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from nonpharmaceutical interventions. We used multiple ongoing cohort surveillance projects in children Methods The first SARS-CoV-2 cases were detected in February 2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), nonalveolar lower respiratory infections necessitating chest X-rays (NA-LRIs), nasopharyngeal pneumococcal carriage in nonrespiratory visits, nasopharyngeal respiratory virus detection (by polymerase chain reaction), and nationwide IPD. Monthly rates (January 2020 through February 2021 vs mean monthly rates 2016–2019 [expected rates]) adjusted for age and ethnicity were compared. Results CAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios [IRRs]: .07 and .19, respectively); NA-LRIs and nonpneumonia IPD were also reduced by a lesser magnitude (IRRs: .46 and .42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced, and density of colonization and pneumococcal serotype distributions were similar to previous years. The decline in pneumococcus-associated disease was temporally associated with a full suppression of respiratory syncytial virus, influenza viruses, and human metapneumovirus, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels. Conclusions Reductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic in Israel were not predominantly related to reduced pneumococcal carriage and density but were strongly associated with the disappearance of specific respiratory viruses.

This article presents the position towards Jews, Judaism, and the State of Israel of Sheikh Dr. Ahmad al-Raysuni, the Moroccan scholar who is the current president of the International Union of Mus...

Microsporidia is a phylum of intracellular parasites that secrete spores and stay in water sources. These parasites can cause infection in humans by invading the digestive system, the urinary system, the muscular system and the eye. Recently, the Israeli Ministry of Health announced that dozens of people in Israel were suspected of being infected with microsporidial keratitis after bathing in the waters of the Kinneret (Sea of Galilee). Here we present a brief overview of this microsporidial keratitis as well as three case presentations.

Mono-Allelic germline disruptions of the transcription factor GATA2 result in a propensity for developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) affecting more than 85% of carriers. How a partial loss of GATA2 functionality enables leukemic transformation occurring years later in life, is unclear. This question is unsolved mainly due to lack of informative models, as Gata2 heterozygote mice do not develop hematologic malignancies. Here we show that two different germline Gata2 mutations (tgERG/GATA2het and tgERG/Gata2L359V) accelerate AML in mice expressing the human hematopoietic stem cell regulator ERG. Analysis of ERG/Gata2het fetal liver and bone marrow derived hematopoietic cells revealed a distinct pre-leukemic phenotype. This was characterized by enhanced transition from stem to progenitor state, increased proliferation, and a striking mitochondrial phenotype, consisting of highly expressed Oxidative- Phosphorylation related gene-sets, elevated oxygen consumption rates, and notably, markedly distorted mitochondrial morphology. Importantly, the same mitochondrial gene-expression signature was observed in human AMLs harboring GATA2 aberrations. Similar to the observations in mice, non-leukemic bone marrows from children with germline GATA2 mutation demonstrated marked mitochondrial abnormalities. Thus, we observed the tumor suppressive effects of GATA2 in two germline Gata2 genetic mouse models. As oncogenic mutations often accumulate with age, Gata2 deficiency mediated priming of hematopoietic cells for oncogenic transformation may explain the earlier occurrence of MDS/AML in patients with GATA2 germline mutation. The mitochondrial phenotype is a potential therapeutic opportunity for prevention of leukemic transformation in these patients.

Background During the early Covid-19 pandemic, we observed a close-to-full disappearance of the activity of 4 respiratory viruses (RSV, hMPV, influenza, and parainfluenza), followed by an off-season sequential re-emergence in 2021. Surprisingly, a striking similarity between the dynamics of pneumococcus-associated disease (PAD; namely community-acquired alveolar pneumonia [CAAP; often considered pneumococcal] and bacteremic-pneumococcal pneumonia [IPD-Pneumonia]), was also observed. In contrast, adenovirus and rhinovirus activities did not change during COVID-19. We examined the association between PAD and RSV, hMPV, influenza, and parainfluenza (PAD-viruses). Methods Surveillance of CAAP and IPD-Pneumonia incidences and viral activity in children < 5 years was described in detail previously [Danino D. et al. Clin Infect Dis. 2022, https://doi.org/10.1093/cid/ciab1014]. We extended the observations until December 2021, to capture the sequential re-emergence of the 4 PAD-viruses. A hierarchical linear regression model was used to quantify the association between PAD-viruses (each virus individually and combined), adenovirus and PAD. After fitting the models, the contribution of each virus was estimated. Results The Figure shows striking similarities in the dynamics of CAAP, IPD-Pneumonia, and PAD-viruses both before and during the COVID-19 pandemic. During the expected peak season (Oct 2020 – Apr 2021) PAD episodes were extremely low. However, off-season peaks were seen during May – Dec 2021. Overall, 78% and 25% of all CAAP and IPD-Pneumonia episodes, respectively, were attributable to these viruses in children < 5 (Table). In CAAP, cases were attributable to each of the 4 PAD-viruses individually throughout the first 5 years of life: RSV and hMPV combined contributed 80%, 63%, and 42% of all CAAP episodes in children aged < 1, 1, and 2-4 years, respectively. The respective figures for influenza and parainfluenza combined were 13%, 21%, and 22%. Only RSV significantly contributed to IPD-Pneumonia (19%). Adenovirus did not contribute to PAD episodes. Conclusion Our model suggests an important causative association between RSV, hMPV, influenza, and parainfluenza viruses and CAAP, and between RSV and IPD-Pneumonia. Disclosures All Authors: No reported disclosures.

Background Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) and to a lesser extent, parainfluenza and influenza viruses have been associated with pneumonia in young children. In contrast, adenovirus (AdV) and rhinovirus (RhV) are usually not associated with pneumonia. We aimed to evaluate the involvement of the four pneumonia associated viruses (grouped as PAV) in pediatric CAAP, before and during the COVID-19 pandemic. Methods CAAP incidence and viral activity surveillance in southern Israel in children < 5y and virological detection methods were described previously (Danino. CID 2022, https://doi.org/10.1093/cid/ciab1014). We reviewed the period of Jan 2016 - Mar 2022. Most cases of COVID-19 in children < 5y occurred during Dec 2021 - Mar 2022 (Figure 1); Over 95% of children admitted for respiratory disease were tested for COVID-19 (PCR). Since AdV and RhV activity was previously not associated with CAAP and tended to be equally involved in mixed and single infections, the current analysis was done for the four PAV only. Results CAAP incidence dynamics closely resembled the four PAV (grouped) activity dynamics (Figure 2A, 2B) with very low activity during the expected peak in winter 2020-2021, but with an off-season resurgence from spring 2021. Even though most CAAP episodes during the pandemic coincided with peak COVID-19 rates, only 9 CAAP episodes were COVID-19 positive (7 in 2022, of which 5 were RSV positive). Out of 3,430 CAAP episodes 55% were tested for PAV, of which 61% were positive, with similar rates before and during the pandemic. RSV was the most common involved virus, followed by hMPV. The virus distribution in CAAP during the entire period reflected their activity in the community (Figure 2C). Unlike pre-pandemic years where all four PAV appeared almost simultaneously, in 2021 PAV resurged sequentially, resulting in successive involvement in CAAP episodes, suggesting a causative association. Conclusion 1. SARS-CoV-2 was only rarely involved in CAAP in young children. 2. PAV were involved in 61% of CAAP episodes in children < 5y with predominance of RSV and hMPV. 3. The atypical dynamics imposed by the COVID-19 pandemic suggests a causative association between PAV and CAAP. Disclosures All Authors: No reported disclosures.

Forward Brillouin scattering interactions support the sensing and analysis of media outside the cladding boundaries of standard fibers, where light cannot reach. Quantitative point-sensing based on this principle has yet to be reported. In this work, we report a forward Brillouin scattering point-sensor in a commercially available, off-the-shelf multi-core fiber. Pump light at the inner, on-axis core of the fiber is used to stimulate a guided acoustic mode of the entire fiber cross-section. The acoustic wave, in turn, induces photoelastic perturbations to the reflectivity of a Bragg grating inscribed in an outer, off-axis core of the same fiber. The measurements successfully analyze refractive index perturbations on the tenth decimal point and distinguish between ethanol and water outside the centimeter-long grating. The measured forward Brillouin scattering linewidths agree with predictions. The acquired spectra are unaffected by forward Brillouin scattering outside the grating region. The results add point-analysis to the portfolio of forward Brillouin scattering optical fiber sensors.

Nitrate pollution is a global problem as it affects both the environment and human health. The objective of this research was to study the effect of electrode configuration on the electro-reduction of nitrate. Coaxial cylindrical (inner rod and outer tube copper cathodes) and vertical plate parallel copper cathodes paired with Ti/RuO

PURPOSE: To assess the refractive prediction error of four intraocular lens (IOL) calculation formulas in eyes that have undergone scleral fixation using the four-flanged technique. METHODS: This was a retrospective cohort analysis of patients who underwent scleral fixation using the four-flanged technique at the Shamir Medical Center between 2020 and 2021. Refractive prediction errors for four IOL prediction formulas (Barrett Universal II, Holladay 1, SRK/T, and Kane) were obtained by subtracting the predicted spherical equivalent from the postoperative spherical equivalent. Mean arithmetic refractive prediction error and mean absolute error were calculated and compared. RESULTS: Twenty-three eyes of 23 patients were included in the analysis. The Akreos AO60 IOL (Bausch & Lomb, Inc) was implanted in 9 eyes and the BunnyLens HP IOL (Hanita Lenses) in 14 eyes. Mean age was 72.84 ± 13.2 years. All formulas produced myopic mean arithmetic refractive prediction error. Mean arithmetic refractive error and mean absolute error were equal in absolute number. Mean arithmetic refractive prediction errors were −0.72 diopters (D) for Barrett Universal II, −0.61 D for Holladay 1, −0.77 D for SRK/T, and −0.94 D for Kane formulas. The refractive outcome differed significantly from the predicted refraction in all formulas. There were no statistically significant differences in prediction errors between the formulas. CONCLUSIONS: Refractive outcomes of the four-flanged fixation technique produced myopic results compared to the predicted refraction for all formulas tested. This suggests that the effective lens position is more anterior than in-the-bag IOL implantation. [ J Refract Surg . 2022;36(10):668–673.]

Circulating cell-free DNA (cfDNA) fragments are a biological analyte with extensive utility in diagnostic medicine. Understanding the source of cfDNA and mechanisms of release is crucial for designing and interpreting cfDNA-based liquid biopsy assays. Using cell type-specific methylation markers as well as genome-wide methylation analysis, we determined that megakaryocytes, the precursors of anuclear platelets, are major contributors to cfDNA (∼26%), while erythroblasts contribute 1-4% of cfDNA in healthy individuals. Surprisingly, we discovered that platelets contain genomic DNA fragments originating in megakaryocytes, contrary to the general understanding that platelets lack genomic DNA. Megakaryocyte-derived cfDNA is increased in pathologies involving increased platelet production (Essential Thrombocythemia, Idiopathic Thrombocytopenic Purpura) and decreased upon reduced platelet production due to chemotherapy-induced bone marrow suppression. Similarly, erythroblast cfDNA is reflective of erythrocyte production and is elevated in patients with Thalassemia. Megakaryocyte- and erythroblast-specific DNA methylation patterns can thus serve as novel biomarkers for pathologies involving increased or decreased thrombopoiesis and erythropoiesis, which can aid in determining the etiology of aberrant levels of erythrocytes and platelets.GRAPHICAL ABSTRACT

ObjectiveTo determine the yield of genetic diagnoses using chromosomal microarray (CMA) and trio whole exome sequencing (WES), separately and combined, among patients with cryptogenic cerebral palsy (CP).MethodsTrio WES of patients with prior CMA analysis for cryptogenic CP, defined as disabling, non-progressive motor symptoms beginning before the age of 3 years without known cause.ResultsGiven both CMA analysis and trio WES, clinically significant genetic findings were identified for 58% of patients (26 of 45). Diagnoses were eight large CNVs detected by CMA and 18 point mutations detected by trio WES. None had more than one severe mutation. Approximately half of events (14 of 26) were de novo. Yield was significantly higher in patients with CP with comorbidities (69%, 22 of 32) than in those with pure motor CP (31%, 4 of 13; p=0.02). Among patients with genetic diagnoses, CNVs were more frequent than point mutations among patients with congenital anomalies (OR 7.8, 95% CI 1.2 to 52.4) or major dysmorphic features (OR 10.5, 95% CI 1.4 to 73.7). Clinically significant mutations were identified in 18 different genes: 14 with known involvement in CP-related disorders and 4 responsible for other neurodevelopmental conditions. Three possible new candidate genes for CP were ARGEF10, RTF1 and TAOK3.ConclusionsCryptogenic CP is genetically highly heterogeneous. Genomic analysis has a high yield and is warranted in all these patients. Trio WES has higher yield than CMA, except in patients with congenital anomalies or major dysmorphic features, but these methods are complementary. Patients with negative results with one approach should also be tested by the other.

Trichophyton tonsurans tinea capitis has become a growing epidemiological concern. Yet, its clinical manifestations and treatment response, specifically among adults, have only been described among small sample size studies.To assess clinical manifestations and treatment outcome of T. tonsurans tinea capitis among adults.A retrospective cohort study was carried out among 111 adults with T. tonsurans tinea capitis. Diagnosis was confirmed by fungal culture or polymerase chain reaction. Examinees' demographics, disease characteristics and treatment response were measured. The risk factors for the treatment failure were evaluated.The mean age was 20.1 years (±3.1), with men (98.2%) outnumbering women. The follow-up lasted 12.2 months (±5.6). The majority of T. tonsurans tinea capitis was seen in the occipital area (87.6%). In 78.9% of the cases, the scalp manifestation was non-inflammatory (scaly plaques and papules:76.1% and seborrhoea-like: 2.8%). 21.1% of cases presented with inflammatory tinea capitis (21.1%; Kerion: 10.1% and pustular: 11%). Concomitant involvement of other than scalp areas was common: tinea corporis was seen in 38.7% of the cases; tinea faciei and barbae in 24.3%; nape and anterior neck in 76.6% and 2.7% of the cases, respectively. An adequate treatment course with oral terbinafine resulted in 83.2% clinical cure rate. Treatment failure was significantly associated with concomitant tinea corporis (odds ratio 3.9; 95% confidence interval 1.3-12.1, p-Value.02).The most common clinical presentation of T. tonsurans tinea capitis included occipital scaly plaques and papules with concomitant non-scalp lesions. Oral terbinafine was found to be highly effective. Concomitant tinea corporis increased the risk for treatment failure.

A growing number of familial Mediterranean fever (FMF) patients in Israel do not have a single country of origin for all four grandparents. We aimed to predict the Mediterranean fever gene (MEFV) variant most likely to be found for an individual FMF patient, by a machine learning approach. This study was conducted at the Sheba Medical Center, a referral center for FMF in Israel. All Jewish referrals included in this study carried an FMF associated variant in MEFV as shown by genetic testing performed between 2001 and 2017. We introduced the term ‘origin score’ to capture the dose and different combinations of the grandparents’ origin. A machine learning approach was used to analyze the data. In a total of 1781 referrals included in this study, the p.Met694Val variant was the most common, and the variants p.Glu148Gln and p.Val726Ala second and third most common, respectively. Of 26 countries of origin analyzed, those that increased the likelihood of a referral to carry specific variants were identified in North Africa for p.Met694Val, Europe for p.Val726Ala, and west Asia for p.Glu148Gln. Fourteen of the studied countries did not show a highly probable variant. Based on our results, it is possible to describe an association between modern day origins of the three most common MEFV variant types and a geographical region. A strong geographic association could arise from positive selection of a specific MEFV variant conferring resistance to endemic infectious agents.