Antibody responses vary widely between individuals1, complicating the correct classification of low-titer measurements using conventional assay cut-offs. We found all participants in a clinically diverse cohort of SARS-CoV-2 PCR+ individuals (n=105) – and n=33 PCR+ hospital staff – to have detectable IgG specific for pre-fusion-stabilized spike (S) glycoprotein trimers, while 98% of persons had IgG specific for the receptor-binding domain (RBD). However, anti-viral IgG levels differed by several orders of magnitude between individuals and were associated with disease severity, with critically ill patients displaying the highest anti-viral antibody titers and strongest in vitro neutralizing responses. Parallel analysis of random healthy blood donors and pregnant women (n=1,000) of unknown serostatus, further demonstrated highly variable IgG titers amongst seroconverters, although these were generally lower than in hospitalized patients and included several measurements that scored between the classical 3 and 6SD assay cut-offs. Since the correct classification of seropositivity is critical for individual- and population-level metrics, we compared different probabilistic algorithms for their ability to assign likelihood of past infection. To do this, we used tandem anti-S and -RBD IgG responses from our PCR+ individuals (n=138) and a large cohort of historical negative controls (n=595) as training data, and generated an equal-weighted learner from the output of support vector machines and linear discriminant analysis. Applied to test samples, this approach provided a more quantitative way to interpret anti-viral titers over a large continuum, scrutinizing measurements overlapping the negative control background more closely and offering a probability-based diagnosis with potential clinical utility. Especially as most SARS-CoV-2 infections result in asymptomatic or mild disease, these platform-independent approaches improve individual and epidemiological estimates of seropositivity, critical for effective management of the pandemic and monitoring the response to vaccination.

Serological studies are critical for understanding pathogen-specific immune responses and informing public health measures (1,2). By developing highly sensitive and specific trimeric spike (S)-based antibody tests, we report IgM, IgG and IgA responses to SARS-CoV-2 in COVID-19 patients (n=105) representing different categories of disease severity. All patients surveyed were IgG positive against S. Elevated anti-SARS-CoV-2 antibody levels were associated with hospitalization, with IgA titers, increased circulating IL-6 and strong neutralizing responses indicative of intensive care status. Antibody-positive blood donors and pregnant women sampled during the pandemic in Stockholm, Sweden (weeks 14-25), displayed on average lower titers and weaker neutralizing responses compared to patients; however, inter-individual anti-viral IgG titers differed up to 1,000-fold. To provide more accurate estimates of seroprevalence, given the frequency of weak responders and the limitations associated with the dichotomization of a continuous variable (3,4), we used a Bayesian approach to assign likelihood of past infection without setting an assay cut-off. Analysis of blood donors (n=1,000) and pregnant women (n=900) sampled weekly demonstrated SARS-CoV-2-specific IgG in 7.2% (95% Bayesian CI [5.1-9.5]) of individuals two months after the peak of spring 2020 COVID-19 deaths. Seroprevalence in these otherwise healthy cohorts increased steeply before beginning to level-off, following the same trajectory as the Stockholm region deaths over this time period.

Laboratory-based cadaveric training is essential for the development and refinement of neurosurgical technical skills in the operating room and has become an integral training component around the world. Postresidency fellowship—the first pillar of skull base surgery training—includes both hands-on clinical care and surgery supervised by an experienced skull base surgeon. Time is spent in a skull base laboratory practicing approaches and developing anatomic mastery. The second pillar includes formal skull-base courses—institutional dissection laboratories provide continuous anatomic and surgical education while complementary annual or semiannual cadaver courses gather recognized experts to share their knowledge and experience in an essential 2- to 3-day setting. In this paper, we present the history of the longest running annual skull-base cadaver microsurgical course, which was started by Dr. Ossama Al-Mefty: Annual Surgical Approaches to the Skull Base Course. At the Microscopic and Endoscopic Hands-on Cadaver Workshop, held in St. Louis, Missouri, we celebrated its 30th anniversary in April 2019. We also present the impact this course has had on neurosurgery and skull base surgery and on the professional and scientific developments of its participants in particular.

Abstract Rationale: Circumcision like any other surgical procedure is not devoid of complications. Serious complications are rare and include iatrogenic hypospadias, glans ischemia/necrosis, and glans amputation, all of which require an emergent treatment. Patient concerns: We report here a case of 6 months-old-boy with a superficial glans ischemia following circumcision. Diagnosis: Physical examination revealed a severely cyanotic glans with the moderate edema of the dorsal penile skin. Plasma levels of D-dimer were 8.57 mg/L. Urine passage was unremarkable while color Doppler ultrasonography revealed a normal blood flow. Interventions: The patient was successfully treated with subcutaneous injection of enoxaparin (low-molecular-weight heparin) and topical 2.5% dihydrotestosterone. Outcomes: The appearance of the glans penis on the 5th day was close to normal while the control levels of D-dimer dropped to the reference range. The patient was discharged from the hospital on the 6th day. At 6-month follow-up, the appearance of the glans penis was normal. Lessons: Acute glans penis ischemia following circumcision is a rare complication. Its successful treatment with enoxaparin and topical dihydrotestosterone has not been previously reported in the literature.

SEIS, the seismometer of the InSight mission, which landed on Mars on 26 November 2018, is monitoring the seismic activity of the planet. The goal of the Mars Structure Service (MSS) is to provide, as a mission product, the first average 1‐D velocity model of Mars from the recorded InSight data. Prior to the mission, methodologies have been developed and tested to allow the location of the seismic events and estimation of the radial structure, using surface waves and body waves arrival times, and receiver functions. The paper describes these validation tests and compares the performance of the different algorithms to constrain the velocity model below the InSight station and estimate the 1‐D average model over the great circle path between source and receiver. These tests were performed in the frame of a blind test, during which synthetic data were inverted. In order to propagate the data uncertainties on the output model distribution, Bayesian inversion techniques are mainly used. The limitations and strengths of the methods are assessed. The results show the potential of the MSS approach to retrieve the structure of the crust and underlying mantle. However, at this time, large quakes with clear surface waves have not yet been recorded by SEIS, which makes the estimation of the 1‐D average seismic velocity model challenging. Additional locatable events, especially at large epicentral distances, and development of new techniques to fully investigate the data, will ultimately provide more constraints on the crust and mantle of Mars.

The aim of study was to examine the effect of the boar ejaculate collection frequency on the parameters of its quality. The research covered a three-year period, and four most common boar breeds in our area. A total of 1705 ejaculates were taken from Yorkshire boars, 1693 ejaculates from Landrace boars, 1106 ejaculates from Pietrain boars and 669 ejaculates from Duroc boars. Within each breed, groups were formed according to the frequency of ejaculate taking (once, twice, three, four, five, or six times a month). Evaluation of ejaculate quality was performed in a reprocentre laboratory, according to their quality standards. Quality parameters that have been determined were the volume of ejaculate, sperm concentration, progressive sperm motility, live sperm count, the number of doses per ejaculate and the overall assessment of ejaculate. Results of this study show that the volume and progressive motility increase with the increase of frequency in ejaculate taking, while the sperm concentration drops, except for the Pietrain boars. The best results were observed in ejaculates collected 5-6 times during the month. The highest mean volume of ejaculate was found in the Landrace boars (292.22 ml), in ejaculate taking frequency of five times per month. The highest average progressive sperm motility was 92% in the Yorkshire boars, on collection frequency of six times a month, while the highest concentration of spermatozoa was found in the Duroc boars in collection frequency of one taking per month (447.32 mil/ml). The results of this study indicate that the frequency of ejaculate taking affects the boar semen quality parameters.

Single-cell sequencing (SCS) data have great potential in reconstructing the evolutionary history of tumors. Rapid advances in SCS technology in the past decade were followed by the design of various computational methods for inferring trees of tumor evolution. Some of the earliest methods were based on the direct search in the space of trees with the goal of finding the maximum likelihood tree. However, it can be shown that instead of searching directly in the tree space, we can perform a search in the space of binary matrices and obtain maximum likelihood tree directly from the maximum likelihood matrix. The potential of the latter tree search strategy has recently been recognized by different research groups and several related methods were published in the past 2 years. Here we provide a review of the theoretical background of these methods and a detailed discussion, which are largely missing in the available publications, of the correlation between the two tree search strategies. We also discuss each of the existing methods based on the search in the space of binary matrices and summarize the best-known single-cell DNA sequencing data sets, which can be used in the future for assessing performance on real data of newly developed methods.

Metal chelators can be potentially employed in the treatment of various diseases, ranging from metal overload to neoplastic conditions. Some xanthene derivatives were previously reported to complex metals. Thus, in a search for a novel iron or copper chelator, a series of 9-(substituted phenyl)-2,6,7-trihydroxy-xanthene-3-ones was tested using a competitive spectrophotometric approach. The most promising compound was evaluated in biological models (breast adenocarcinoma cell lines and erythrocytes). In general, substitution of the benzene ring in position 9 had a relatively low effect on the chelation. Only the trifluoromethyl substitution resulted in stronger chelation, probably via a positive effect on solvation. All compounds chelated iron, but their copper-chelating effect was only minimal, since it was no longer observed under highly competitive conditions. Interestingly, all compounds reduced both iron and copper. Additional experiments showed that the trifluoromethyl derivative protected erythrocytes and even cancer cells against excess copper. In summary, the tested compounds are iron chelators, which are also capable of reducing iron/copper, but the copper-reducing effect is not associated with increased copper toxicity.