Cross polarization from dipolar-order under magic angle spinning: The ADRF-CPMAS NMR experiment.

Techniques for enhancing the signals arising from low-γ, insensitive (I) nuclei are central to solid-state nuclear magnetic resonance. One of the leading and best-established methods to sensitize these unreceptive species is Hartmann-Hahn cross polarization (HH-CP), a polarization transfer mechanism often executed under MAS. Herein, we explore the possibility of utilizing the 1H dipolar order created via adiabatic demagnetization in the rotating frame (ADRF), to enhance the unreceptive spins under MAS. It is found that an efficient polarization transfer via ADRF-CPMAS is not only possible but can exceed, at least in some instances involving plastic crystals, the efficiency of an optimized HH-CPMAS transfer. The experiment requires low radiofrequency nutation fields on both the 1H- and the I-spin channels, and displays unusual matching conditions that are reminiscent of the zero- and double-quantum matching conditions arising under CPMAS, albeit centered at zero frequency and demanding the simultaneous involvement of several spins. The origin of these multi-spin transfer processes is analytically derived and numerically simulated in predictions that compare well with experimental 13C and 15N results collected on model compounds at different spinning speeds. These derivations start from descriptions that depart from traditional thermodynamic arguments, and treat instead the ADRF processes in static and spinning solids on the basis of coherent evolutions. The predictions of these analytical derivations are corroborated by numerical simulations. The effects of additional factors, including chemical shift anisotropies, J-couplings, and radiofrequency inhomogeneities, are also theoretically and experimentally explored.

Trends in the Epidemiology of Non-Typhoidal Salmonellosis in Israel between 2010 and 2021.

Non-typhoidal salmonellosis (NTS) is one of the most common foodborne diseases worldwide. In this study, we aimed to analyze trends in the epidemiology of NTS in the last decade in Israel. Laboratory-confirmed cases of NTS at eight sentinel laboratories were reported to the Israel Sentinel Laboratory-Based Surveillance Network, integrated with the serotype identification performed at the Salmonella National Reference Laboratory of the Ministry of Health. The decrease in NTS incidence since 1999 continued between 2010 and 2014 (16.1 per 100,000 in 2014) and was interrupted by a rise between 2015 and 2017 (39.1 per 100,000 in 2017) associated with outbreaks of Salmonella Enteritidis. The incidence of NTS dropped again thereafter (21.4 per 100,000 in 2021). The 0-4 age group was the most affected by NTS (55.5% of the cases) throughout the surveillance period. The age-adjusted incidence rates were consistently high in the summer months (June-September) and low in the winter months (December-February). The overall decrease in the incidence of NTS in Israel since 1999 was temporarily interrupted in the last decade by country-wide outbreaks involving emerging or re-emerging Salmonella serotypes. Control measures should be enhanced for all risk points of food chain transmission of Salmonella spp. to further reduce the NTS morbidity in Israel.

Indirectly detected satellite-transition quadrupolar NMR via progressive saturation of the proton reservoir.

Static satellite-transitions (ST) NMR line shapes from half-integer quadrupolar nuclei could be very informative: they can deliver insight about local motions over a wide range of timescales, and can report on small changes in the local electronic environments as reflected by variations in the quadrupolar parameters. Satellite transitions, however, are typically "invisible" for half-integer quadrupolar nuclei due to their sheer breadth, leading to low signal-to-noise ratio -especially for unreceptive low-gamma or dilute quadrupolar nuclei. Very recently we have introduced a method for enhancing the NMR sensitivity of unreceptive X nuclei in static solids dubbed PROgressive Saturation of the Proton Reservoir (PROSPR), which opens the possibility of magnifying the signals from such spins by repeatedly imprinting frequency-selective X-driven depolarizations on the much more sensitive 1H NMR signal. Here, we show that PROSPR's efficacy is high enough for enabling the detection of static ST NMR for challenging species like 35Cl, 33S and even 17O -all at natural-abundance. The ensuing ST-PROSPR NMR experiment thus opens new approaches to probe ultra-wideline (6-8 MHz wide) spectra. These highly pronounced anisotropies can in turn deliver new vistas about dynamic changes in solids, as here illustrated by tracking ST line shapes as a function of temperature during thermally-driven events.

Quadrupolar Isotope-Correlation Spectroscopy in Solid-State NMR.

Quadrupolar solid-state NMR carries a wealth of structural information, including insights about chemical environments arising through the determination of local coupling parameters. Current methods can successfully resolve these parameters for individual sites using sample-spinning methods techniques applicable to quadrupolar I ≥ 1 nuclei, provided second-order central transition broadenings do not exceed by much the spinning rate. For large quadrupolar coupling (C Q) values, however, static acquisitions are often preferable, leading to challenges in extracting local structural information. This study explores the use of two-dimensional QUadrupolar Isotope Correlation SpectroscopY (QUICSY) experiments as a means to increase the NMR spectral resolution and enrich the characterization of quadrupolar NMR patterns under static conditions. QUICSY seeks to correlate the solid-state NMR powder line shapes for two quadrupolar isotopes belonging to the same element via a 2D experiment. In general, two isotopes of the same element will have different nuclear quadrupole moments, gyromagnetic ratios, and spin numbers but essentially identical chemical environments. The possibility then arises of obtaining sharp "ridges" in these 2D correlations, even in static samples showing large quadrupolar effects, which lead to second-order line shapes that are several kilohertz wide. Moreover, pairs of quadrupolar isotopes are recurrent in the periodic table and include important elements such as 35,37Cl, 69,71Ga, 79,81Br, and 85,87Rb. The potential of this approach is explored theoretically and experimentally on two rubidium-containing salts: RbClO4 and Rb2SO4. We find that each compound gives rise to distinctive 2D QUICSY line shapes, depending on the quadrupolar and chemical shift anisotropy (CSA) parameters of its sites. These experimental line shapes show good agreement with analytically derived 2D spectra relying on literature values of the quadrupolar and CSA tensors of these compounds. The approach underlined here paves the way toward better characterization of wideline NMR spectra of quadrupolar nuclei possessing different nuclear isotopes.

Minimizing treatment-induced emergence of antibiotic resistance in bacterial infections.

Treatment of bacterial infections currently focuses on choosing an antibiotic that matches a pathogen's susceptibility, with less attention paid to the risk that even susceptibility-matched treatments can fail as a result of resistance emerging in response to treatment. Combining whole-genome sequencing of 1113 pre- and posttreatment bacterial isolates with machine-learning analysis of 140,349 urinary tract infections and 7365 wound infections, we found that treatment-induced emergence of resistance could be predicted and minimized at the individual-patient level. Emergence of resistance was common and driven not by de novo resistance evolution but by rapid reinfection with a different strain resistant to the prescribed antibiotic. As most infections are seeded from a patient's own microbiota, these resistance-gaining recurrences can be predicted using the patient's past infection history and minimized by machine learning-personalized antibiotic recommendations, offering a means to reduce the emergence and spread of resistant pathogens.

Mpox Infection in a Developed Country: A Case Report.

This is the first Israeli case report of mpox (monkeypox) disease, as it is manifested in the current outbreak. This manuscript depicts two detailed patient journeys of Israeli men in their 30s who were diagnosed in recent months, depicting their symptoms, presumed exposure, and outcomes. The two cases were atypical compared to the clinical presentation prior to the current outbreak but were similar to other recent reported cases; they differed in their prodromal presentation. Importantly, both patients described that significant anxiety around the diagnosis dominated their journey while sharing that a concern is rising in the GBMSM community, a concern that should be addressed by healthcare providers.

HPV Screening Test for the Detection of Precancerous Cervical Lesions and Cervical Cancer in Israeli Women.

OBJECTIVES: This work is aimed to summarize the first year of the high-risk human papillomavirus (hrHPV) screening test and compare it to the cytology screening test, regarding positivity rates and premalignant lesions diagnosed in the Israeli population. A specific consideration is for the age group 25-30 that is not considered mandatory for the HPV primary screening testing. METHODS: A retrospective study was performed in women who were screened for prevention of cervical cancer in Maccabi HealthCare HMO from March 2017 to March 2019. Screening methods included hrHPV typing for types 16, 18, and the other 12 hrHPV types and the PAP LBC test. RESULTS: A total of 115,807 cervical samples were tested for HPV presence and 91% (105,225) were found negative for hrHPV. The other 9% (10,582) were positive for one or more of the 14 hrHPV types tested, and 37% (3,916) of them showed abnormal PAP LBC results. In the age group of 25-30, 3,104 (17.5%) women were found positive for hr-HPV (825 had hrHPV types 16 and/or 18), of which 42% (1,293) of them showed abnormal PAP LBC results. During the hrHPV versus PAP LBC screening era, 258 more women were diagnosed with precancerous cervical lesions (CIN2/3), 70% increased detection versus cytology screening. CONCLUSIONS: The hrHPV screening test is currently the best method for the detection of precancerous cervical lesions and cervical cancer, and it is better started at age 25.

Kinetics of SARS-CoV-2 anti-S IgG after BNT162b2 vaccination.

Deployment of the BNT162b2 mRNA Covid-19 Vaccine in Israel began in December 2020. This is a retrospective analysis of serological data, showing SARS-CoV-2 anti-S IgG kinetics in 116 Israeli health care workers receiving BNT162b2. Sero-conversion occurred in 14 days in all study participants, with IgG levels peaking approximately 30 days after initiation of the vaccination series. A statistically significant difference was observed in IgG levels between subjects younger than 50 years and older participants, although in all cases, IgG levels were well above the level considered reactive by the test's manufacturer. The importance of this difference needs to be studied further, but a potential difference in vaccine efficacy and vaccine effect length could possibly be present between these two groups.

Initial report of decreased SARS-CoV-2 viral load after inoculation with the BNT162b2 vaccine.

Beyond their substantial protection of individual vaccinees, coronavirus disease 2019 (COVID-19) vaccines might reduce viral load in breakthrough infection and thereby further suppress onward transmission. In this analysis of a real-world dataset of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results after inoculation with the BNT162b2 messenger RNA vaccine, we found that the viral load was substantially reduced for infections occurring 12-37 d after the first dose of vaccine. These reduced viral loads hint at a potentially lower infectiousness, further contributing to vaccine effect on virus spread.

Multi-center nationwide comparison of seven serology assays reveals a SARS-CoV-2 non-responding seronegative subpopulation.

BACKGROUND: An Israeli national taskforce performed a multi-center clinical and analytical validation of seven serology assays to determine their utility and limitations for SARS-CoV-2 diagnosis. METHODS: Serology assays from Roche, Abbott, Diasorin, BioMerieux, Beckman-Coulter, Siemens, and an in-house RBD ELISA were included. Negative samples from 2391 individuals representative of the Israeli population, and 698 SARS-CoV-2 PCR positive patients, collected between March and May 2020, were analyzed. FINDINGS: Immunoassays sensitivities between 81.5%-89.4% and specificities between 97.7%-100% resulted in a profound impact on the expected Positive Predictive Value (PPV) in low (<15%) prevalence scenarios. No meaningful increase was detected in the false positive rate in children compared to adults. A positive correlation between disease severity and antibody titers, and no decrease in antibody titers in the first 8 weeks after PCR positivity was observed. We identified a subgroup of symptomatic SARS-CoV-2 positive patients (~5% of patients), who remained seronegative across a wide range of antigens, isotypes, and technologies. INTERPRETATION: The commercially available automated immunoassays exhibit significant differences in performance and expected PPV in low prevalence scenarios. The low false-positivity rate in under 20's suggests that cross-reactive immunity from previous CoV strains is unlikely to explain the milder disease course in children. Finding no decrease in antibody titers in the first 8 weeks is in contrast to some reports of short half-life for SARS-CoV-2 antibodies. The ~5% who were seronegative non-responders, using multiple assays in a population-wide manner, represents the proportion of patients that may be at risk for re-infection. FUNDING: Israel Ministry of Health.

Endogenous Dynamic Nuclear Polarization for Natural Abundance 17O and Lithium NMR in the Bulk of Inorganic Solids.

In recent years magic angle spinning-dynamic nuclear polarization (MAS-DNP) has developed as an excellent approach for boosting the sensitivity of solid-state NMR (ssNMR) spectroscopy, thereby enabling the characterization of challenging systems in biology and chemistry. Most commonly, MAS-DNP is based on the use of nitroxide biradicals as polarizing agents. In materials science, since the use of nitroxides often limits the signal enhancement to the materials' surface and subsurface layers, there is need for hyperpolarization approaches which will provide sensitivity in the bulk of micron sized particles. Recently, an alternative in the form of paramagnetic metal ions has emerged. Here we demonstrate the remarkable efficacy of Mn(II) dopants, used as endogenous polarization agents for MAS-DNP, in enabling the detection of 17O at a natural abundance of only 0.038%. Distinct oxygen sites are identified in the bulk of micron-sized crystals, including battery anode materials Li4Ti5O12 (LTO) and Li2ZnTi3O8, as well as the phosphor materials NaCaPO4 and MgAl2O4, all doped with Mn(II) ions. Density functional theory calculations are used to assign the resonances to specific oxygen environments in these phases. Depending on the Mn(II) dopant concentration, we obtain significant signal enhancement factors, 142 and 24, for 6Li and 7Li nuclei in LTO, respectively. We furthermore follow the changes in the 6,7Li LTO resonances and determine their enhancement factors as a function of Mn(II) concentration. The results presented show that MAS-DNP from paramagnetic metal ion dopants provides an efficient approach for probing informative nuclei such as 17O, despite their low gyromagnetic ratio and negligible abundance, without isotope enrichment.

Free-Standing Nanocrystalline Materials Assembled from Small Molecules.

We demonstrate a solution-based fabrication of centimeter-size free-standing films assembled from organic nanocrystals based on common organic dyes (perylene diimides, PDIs). These nanostructured films exhibit good mechanical stability, and thermal robustness superior to most plastics, retaining the crystalline microstructure and macroscopic shape upon heating up to 250-300 °C. The films show nonlinear optical response and can be used as ultrafiltration membranes. The macroscopic functional materials based on small molecules can be alternative or complementary to materials based on macromolecules.

Identification of dopant site and its effect on electrochemical activity in Mn-doped lithium titanate.

Doped metal oxide materials are commonly used for applications in energy storage and conversion, such as batteries and solid oxide fuel cells. The knowledge of the electronic properties of dopants and their local environment is essential for understanding the effects of doping on the electrochemical properties. Using a combination of X-ray absorption near-edge structure spectroscopy (XANES) experiment and theoretical modeling we demonstrate that in the dilute (1 at. %) Mn-doped lithium titanate (Li4/3Ti5/3O4, or LTO) the dopant Mn2+ ions reside on tetrahedral (8a) sites. First-principles Mn K-edge XANES calculations revealed the spectral signature of the tetrahedrally coordinated Mn as a sharp peak in the middle of the absorption edge rise, caused by the 1s → 4p transition, and it is important to include the effective electron-core hole Coulomb interaction in order to calculate the intenisty of this peak accurately. This dopant location explains the impedance of Li migration through the LTO lattice during the charge-discharge process, and, as a result - the observed remarkable 20% decrease in electrochemical rate performance of the 1% Mn-doped LTO compared to the pristine LTO.

First Israeli National Iodine Survey Demonstrates Iodine Deficiency Among School-Aged Children and Pregnant Women.

BACKGROUND: National data on iodine status in Israel are lacking. Reliance on iodine-depleted desalinated water, the absence of a salt iodization program, and reports of increased use of thyroid medication in Israel suggest that the population's iodine intake is likely inadequate. The aims of this study were therefore to determine the iodine status of Israeli school-age children (SAC) and pregnant women (PW) in a nationally representative sample obtained by a novel approach of using pre-discard urinalysis samples collected from a centralized national laboratory. METHODS: Spot urine samples from 1023 SAC and 1074 PW, representing all regions and major sectors in Israel, were collected during 2016 at the Maccabi Healthcare Services central laboratory. Urinary iodine concentration (UIC) was measured, and the results were analyzed by trimester, sex, region, and sector. RESULTS: SAC were iodine deficient, with a median (interquartile range [IQR]) UIC of 83 µg/L (52-127 µg/L); 62% of SAC UICs were below the World Health Organization adequacy range for SAC (100-199 µg/L). PW were also iodine deficient, with a median (IQR) UIC of 61 µg/L (36-97 µg/L); 85% of PW UICs were below the adequacy range for PW (150-249 µg/L). For both SAC and PW, the median UIC was below the World Health Organization's adequacy range across all sectors, sexes, and districts. Among SAC, the median (IQR) UIC was lower among females (75 µg/L; 48-119 µg/L) than males (92 µg/L; 59-133 µg/L; p < 0.05). Median UIC values of PW correlated significantly with the median UIC for SAC by sub-district (R2 = 0.3, p < 0.05). CONCLUSIONS: Urine sampling via a centralized national laboratory was efficient and cost-saving. Iodine deficiency in Israeli SAC and PW is a serious public-health concern. A national program of salt iodization and iodine supplementation of PW should be urgently considered.

Effect of temperature on the structure of charged membranes.

Interactions between charged and neutral self-assembled phospholipid membranes are well understood and take into account temperature dependence. Yet, the manner in which the structure of the membrane is affected by temperature was hardly studied. Here we study the effect of temperature on the thickness, area per lipid, and volume per lipid of charged membranes. Two types of membranes were studied: membranes composed of charged lipids and dipolar (neutral) membranes that adsorbed divalent cations and became charged. Small-angle X-ray scattering data demonstrate that the thickness of charged membranes decreases with temperature. Wide-angle X-ray scattering data show that the area per headgroup increases with temperature. Intrinsically charged membranes linearly thin with temperature, whereas neutral membranes that adsorb divalent ions and become charged show an exponential decrease of their thickness. The data indicate that, on average, the tails shorten as the temperature rises. We attribute this behavior to higher lipid tail entropy and to the weaker electrostatic screening of the charged headgroups, by their counterions, at elevated temperatures. The latter effect leads to stronger electrostatic repulsion between the charged headgroups that increases the area per headgroup and decreases the bilayer thickness.