bluuebunny/crossref_metadata_2025 huggingface dataset:
A decade post-HITECH: Critical access hospitals have electronic health records but struggle to keep up with other advanced functions
Authors: Apathy Nate C , Holmgren A Jay , Adler-Milstein Julia
Published: May 2021

Objective

Despite broad electronic health record (EHR) adoption in U.S. hospitals, there is concern that an “advanced use” digital divide exists between critical access hospitals (CAHs) and non-CAHs. We measured EHR adoption and advanced use over time to analyzed changes in the divide.

Materials and Methods

We used 2008 to 2018 American Hospital Association Information Technology survey data to update national EHR adoption statistics. We stratified EHR adoption by CAH status and measured advanced use for both patient engagement (PE) and clinical data analytics (CDA) domains. We used a linear probability regression for each domain with year-CAH interactions to measure temporal changes in the relationship between CAH status and advanced use.

Results

In 2018, 98.3% of hospitals had adopted EHRs; there were no differences by CAH status. A total of 58.7% and 55.6% of hospitals adopted advanced PE and CDA functions, respectively. In both domains, CAHs were less likely to be advanced users: 46.6% demonstrated advanced use for PE and 32.0% for CDA. Since 2015, the advanced use divide has persisted for PE and widened for CDA.

Discussion

EHR adoption among hospitals is essentially ubiquitous; however, CAHs still lag behind in advanced use functions critical to improving care quality. This may be rooted in different advanced use needs among CAH patients and lack of access to technical expertise.

Conclusions

The advanced use divide prevents CAH patients from benefitting from a fully digitized healthcare system. To close the widening gap in CDA, policymakers should consider partnering with vendors to develop implementation guides and standards for functions like dashboards and high-risk patient identification algorithms to better support CAH adoption.
Year 1 of the ZTF high-cadence Galactic plane survey: strategy, goals, and early results on new single-mode hot subdwarf B-star pulsators
Authors: Kupfer Thomas , Prince Thomas A , van Roestel Jan , Bellm Eric C , Bildsten Lars , Coughlin Michael W , Drake Andrew J , Graham Matthew J , Klein Courtney , Kulkarni Shrinivas R , Masci Frank J , Walters Richard , Andreoni Igor , Biswas Rahul , Bradshaw Corey , Duev Dmitry A , Dekany Richard , Guidry Joseph A , Hermes J J , Laher Russ R , Riddle Reed
Published: May 2021

We present the goals, strategy, and first results of the high-cadence Galactic plane survey using the Zwicky Transient Facility (ZTF). The goal of the survey is to unveil the Galactic population of short-period variable stars, including short-period binaries, and stellar pulsators with periods less than a few hours. Between 2018 June and 2019 January, we observed 64 ZTF fields resulting in 2990 deg2 of high stellar density in the ZTF-r band along the Galactic plane. Each field was observed continuously for 1.5 to 6 h with a cadence of 40 sec. Most fields have between 200 and 400 observations obtained over 2–3  continuous nights. As part of this survey, we extract a total of ≈230 million individual objects with at least 80 epochs obtained during the high-cadence Galactic plane survey reaching an average depth of ZTF–r ≈ 20.5 mag. For four selected fields with 2–10 million individual objects per field, we calculate different variability statistics and find that ≈1–2  per cent of the objects are astrophysically variable over the observed period. We present a progress report on recent discoveries, including a new class of compact pulsators, the first members of a new class of Roche lobe filling hot subdwarf binaries as well as new ultracompact double white dwarfs and flaring stars. Finally, we present a sample of 12 new single-mode hot subdwarf B-star pulsators with pulsation amplitudes between ZTF–r = 20–76 mmag and pulsation periods between P = 5.8–16 min with a strong cluster of systems with periods ≈6 min. All of the data have now been released in either ZTF Data Release 3 or Data Release 4.
The origin of metal-poor stars on prograde disc orbits in FIRE simulations of Milky Way-mass galaxies
Authors: Santistevan Isaiah B , Wetzel Andrew , Sanderson Robyn E , El-Badry Kareem , Samuel Jenna , Faucher-Giguère Claude-André
Published: May 2021

In hierarchical structure formation, metal-poor stars in and around the Milky Way (MW) originate primarily from mergers of lower mass galaxies. A common expectation is therefore that metal-poor stars should have isotropic, dispersion-dominated orbits that do not correlate strongly with the MW disc. However, recent observations of stars in the MW show that metal-poor ($\rm {[Fe/H]}\lesssim -2$) stars are preferentially on prograde orbits with respect to the disc. Using the Feedback In Realistic Environments 2 (FIRE-2) suite of cosmological zoom-in simulations of MW/M31-mass galaxies, we investigate the prevalence and origin of prograde metal-poor stars. Almost all (11 of 12) of our simulations have metal-poor stars on preferentially prograde orbits today and throughout most of their history: we thus predict that this is a generic feature of MW/M31-mass galaxies. The typical prograde-to-retrograde ratio is ∼2:1, which depends weakly on stellar metallicity at $\rm {[Fe/H]}\lesssim -1$. These trends predicted by our simulations agree well with MW observations. Prograde metal-poor stars originate largely from a single Large/Small Magellanic Cloud (LMC/SMC)-mass gas-rich merger $7\!-\!12.5\, \rm {Gyr}$ ago, which deposited existing metal-poor stars and significant gas on an orbital vector that sparked the formation of and/or shaped the orientation of a long-lived stellar disc, giving rise to a prograde bias for all low-metallicity stars. We find subdominant contributions from in situ stars formed in the host galaxy before this merger, and in some cases, additional massive mergers. We find few clear correlations between any properties of our MW/M31-mass galaxies at z = 0 and the degree of this prograde bias as a result of diverse merger scenarios.
STARFORGE: Towards a comprehensive numerical model of star cluster formation and feedback
Authors: Grudić Michael Y , Guszejnov Dávid , Hopkins Philip F , Offner Stella S R , Faucher-Giguère Claude-André
Published: May 2021

We present STARFORGE (STAR FORmation in Gaseous Environments): a new numerical framework for 3D radiation magnetohydrodynamic (MHD) simulations of star formation that simultaneously follow the formation, accretion, evolution, and dynamics of individual stars in massive giant molecular clouds (GMCs), while accounting for stellar feedback, including jets, radiative heating and momentum, stellar winds, and supernovae. We use the gizmo code with the MFM mesh-free Lagrangian MHD method, augmented with new algorithms for gravity, time-stepping, sink particle formation and accretion, stellar dynamics, and feedback coupling. We survey a wide range of numerical parameters/prescriptions for sink formation and accretion and find very small variations in star formation history and the IMF (except for intentionally unphysical variations). Modules for mass-injecting feedback (winds, SNe, and jets) inject new gas elements on the fly, eliminating the lack of resolution in diffuse feedback cavities otherwise inherent in Lagrangian methods. The treatment of radiation uses GIZMO’s radiative transfer solver to track five frequency bands (IR, optical, NUV, FUV, ionizing), coupling direct stellar emission and dust emission with gas heating and radiation pressure terms. We demonstrate accurate solutions for SNe, winds, and radiation in problems with known similarity solutions, and show that our jet module is robust to resolution and numerical details, and agrees well with previous AMR simulations. STARFORGE can scale up to massive (>105 M⊙) GMCs on current supercomputers while predicting the stellar (≳0.1 M⊙) range of the IMF, permitting simulations of both high- and low-mass cluster formation in a wide range of conditions.
What can be learned from a proto-neutron star’s mass and radius?
Authors: Préau E , Pascal A , Novak J , Oertel M
Published: May 2021

We make extensive numerical studies of masses and radii of proto-neutron stars during the first second after their birth in core-collapse supernova events. We use a quasi-static approach for the computation of proto-neutron star structure, built on parametrized entropy and electron fraction profiles, that are then evolved with neutrino cooling processes. We vary the equation of state of nuclear matter, the proto-neutron star mass, and the parameters of the initial profiles, to take into account our ignorance of the supernova progenitor properties. Our results suggest that if masses and radii of a proto-neutron star can be determined in the first second after the birth, e.g. from gravitational wave emission, no information could be obtained on the corresponding cold neutron star and therefore on the cold nuclear equation of state. Similarly, it seems unlikely that any property of the proto-neutron star equation of state (hot and not beta-equilibrated) could be determined either, mostly due to the lack of information on the entropy, or equivalently temperature, distribution in such objects.
Deep learning Blazar classification based on multifrequency spectral energy distribution data
Authors: Fraga Bernardo M O , Barres de Almeida Ulisses , Bom Clécio R , Brandt Carlos H , Giommi Paolo , Schubert Patrick , de Albuquerque Márcio P
Published: May 2021

Blazars are among the most studied sources in high-energy astrophysics as they form the largest fraction of extragalactic gamma-ray sources and are considered prime candidates for being the counterparts of high-energy astrophysical neutrinos. Their reliable identification amid the many faint radio sources is a crucial step for multimessenger counterpart associations. As the astronomical community prepares for the coming of a number of new facilities able to survey the non-thermal sky at unprecedented depths, from radio to gamma-rays, machine-learning techniques for fast and reliable source identification are ever more relevant. The purpose of this work was to develop a deep learning architecture to identify Blazar within a population of active galactic nucleus (AGN) based solely on non-contemporaneous spectral energy distribution information, collected from publicly available multifrequency catalogues. This study uses an unprecedented amount of data, with spectral energy distributions (SEDs) for ≈14 000 sources collected with the Open Universe VOU-Blazars tool. It uses a convolutional long short-term memory neural network purposefully built for the problem of SED classification, which we describe in detail and validate. The network was able to distinguish Blazars from other types of active galactic nuclei (AGNs) to a satisfying degree (achieving a receiver operating characteristic area under curve of 0.98), even when trained on a reduced subset of the whole sample. This initial study does not attempt to classify Blazars among their different sub-classes, or quantify the likelihood of any multifrequency or multimessenger association, but is presented as a step towards these more practically oriented applications.
Systematic search for long-term transit duration changes inKeplertransiting planets
Authors: Shahaf Sahar , Mazeh Tsevi , Zucker Shay , Fabrycky Daniel
Published: May 2021

Holczer, Mazeh, and collaborators (HM+16) used the Kepler 4-yr observations to derive a transit-timing catalog, identifying 260 Kepler objects of interest (KOI) with significant transit timing variations (TTV). For KOIs with high enough S/Ns, HM+16 also derived the duration and depth of their transits. In this work, we use the duration measurements of HM+16 to systematically study the duration changes of 561 KOIs and identify 15 KOIs with a significant long-term linear change of transit durations and another 16 KOIs with an intermediate significance. We show that the observed linear trend is probably caused by a precession of the orbital plane of the transiting planet, induced in most cases by another planet. The leading term of the precession rate depends on the mass and relative inclination of the perturber, and the period ratio between the two orbits, but not on the mass and period of the transiting planet itself. Interestingly, our findings indicate that, as a sample, the detected time derivatives of the durations get larger as a function of the planetary orbital period, probably because short-period planetary systems display small relative inclinations. The results might indicate that short-period planets reside in relatively flattened planetary systems, suggesting these systems experienced stronger dissipation either when formed or when migrated to short orbits. This should be used as a possible clue for the formation of such systems.
Melanotransferrin is efficiently sorted on the surface of exosomes secreted by melanoma cells
Authors: Bonhoure Anne , Henry Laurent , Morille Marie , Aissaoui Nesrine , Bellot Gaëtan , Stoebner Pierre-Emmanuel , Vidal Michel
Published: May 2021

Cutaneous melanoma is the most lethal type of skin cancer. Early detection is crucial to improve the outcome of melanoma patients. The identification of noninvasive prognostic biomarkers for the follow-up of melanoma patients is still in demand for clinical use. We show here that exosomal melanotransferrin fulfills the biomarker characteristics required to meet this demand. Melanotransferrin is typically overexpressed in melanoma cells compared to other cell types – including cancer cells – and is efficiently sorted and secreted with nanovesicles, or so-called exosomes, due to its membrane-anchoring by a glycosylphosphatidylinositol. Melanotransferrin is exposed on the surface of exosomes and is accessible for antibody recognition. An ELISA was set up to quantify melanotransferrin after immobilization of nanovesicles through the exosomal constituent tetraspanins CD63. Melanotransferrin was detected using a low number of exosomes purified from melanoma cell line cultures, and melanotransferrin detection was abolished by phosphatidylinositol-specific phospholipase C treatment. This exosomal melanotransferrin ELISA was able to discriminate an equal number of assayed exosomes purified from two different melanoma cell lines (A-375 vs. SK-MEL-28). Moreover, plasma samples from patients with melanoma and noncancer disease were assayed using this ELISA and elevated levels of exosomal melanotransferrin were seen in the plasma of patients with melanoma. We propose that exosomal melanotransferrin should be assessed as a potential melanoma biomarker.
Managing the first 120 min of cardiogenic shock: from resuscitation to diagnosis
Authors: Jentzer Jacob C. , Tabi Meir , Burstein Barry
Published: May 2021

Purpose of review

Cardiogenic shock continues to carry a high mortality, and recent randomized trials have not identified novel therapies that improve survival. Early optimization of patients with confirmed or suspected cardiogenic shock is crucial, as patients can quickly transition from a hemodynamic shock state to a treatment-resistant hemometabolic shock state, where accumulated metabolic derangements trigger a self-perpetuating cycle of worsening shock.

Recent findings

We describe a structured ABCDE approach involving stabilization of the airway, breathing and circulation, followed by damage control and etiologic assessment. Respiratory failure is common and many cardiogenic shock patients require invasive mechanical ventilation. Norepinephrine is titrated to restore mean arterial pressure and dobutamine is titrated to restore cardiac output and organ perfusion. Echocardiography is essential to identify potential causes and characterize the phenotype of cardiogenic shock. Coronary angiography is usually indicated, particularly when acute myocardial ischemia is suspected, followed by culprit-vessel revascularization if indicated. An invasive hemodynamic assessment can clarify whether temporary mechanical circulatory support is necessary.

Early stabilization of hemodynamics and end-organ function is necessary to achieve best outcomes in cardiogenic shock. Using a structured approach tailored to initial cardiogenic shock resuscitation may help to demonstrate benefit from novel therapies in the future.
Diurnal rhythms and obesity
Authors: Paschos Georgios K.
Published: May 2021

Purpose of review

This review will discuss the recent studies that implicate disturbed diurnal rhythms with the development of obesity. The second part of the review will discuss studies that use feeding time to restore diurnal rhythms and rescue obesity.

Recent findings

Studies in patients with obesity and diabetes reveal attenuated circadian and metabolic rhythms in adipose tissue. The use of animal models furthers our mechanistic insight on how environmental disturbances such as high-fat diet and shift work disturb circadian and metabolic rhythms. Studies in both animals and humans describe how disturbance of diurnal rhythms can lead to increased adiposity and obesity. The effects of time-restricted feeding in animals and the time of feeding in humans provide new evidence on how restoring diurnal rhythms can reverse adiposity and obesity.

Many more studies in humans were performed in recent years to confirm a number of findings from animal studies. It is becoming apparent that the time of feeding and maintaining a healthy daily schedule is important for metabolic health. Ongoing studies may soon improve current recommendations regarding the time of eating and time of day behavior.
Bone accrual in children and adolescents with type 1 diabetes: current knowledge and future directions
Authors: Weber David R.
Published: May 2021

Purpose of review

Skeletal fragility is now recognized as a significant complication of type 1 diabetes (T1D). Many patients with T1D develop the disease in childhood and prior to the attainment of peak bone mass and strength. This manuscript will review recent studies investigating the effects of T1D on skeletal development.

Recent findings

Mild-to-moderate deficits in bone density, structure, and mineral accrual were reported early in the course of T1D in some but not all studies. Childhood-onset disease was associated with a more severe skeletal phenotype in some adult studies. Lower than expected bone mass for muscle size was been described. Hemoglobin A1c was negatively associated with bone density and structure in several studies, though the mechanism was not clear.

The use of advanced imaging techniques has shown that the adverse effects of T1D on the developing skeleton extend beyond bone density to include abnormalities in bone size, shape, microarchitecture, and strength. Despite these gains, a uniform understanding of the pathophysiology underlying skeletal fragility in this disorder remains elusive. Longitudinal studies, especially in association with interventions to reduce hyperglycemia or improve muscle strength, are needed to inform bone healthcare in T1D.
The prognostic value of sarcopenia in patients with prostate cancer: a systematic review
Authors: Jahrreiss Victoria , Laukhtina Ekaterina , D’Andrea David , Shariat Shahrokh F.
Published: May 2021

Purpose of review

Sarcopenia is known to affect perioperative and oncologic outcomes in patients with different urological malignancies. Nevertheless, the use of pretreatment sarcopenia as a predictor of clinical outcomes in patients with prostate cancer is still poorly studied. Therefore, we aimed to conduct a systematic review summarizing the available evidence and identifying the prognostic value of sarcopenia in prostate cancer patients.

Recent findings

Sarcopenia was not predictive of biochemical recurrence in patients treated with radical prostatectomy. However, it was associated with worse long-term survival outcomes as well as the likelihood of developing postoperative complications after radical prostatectomy. In the context of radiotherapy, sarcopenia was a predictive factor for overall survival. In patients with hormone-sensitive prostate cancer treated with androgen deprivation, sarcopenia was associated with overall and cancer-specific survival. In patients with castration-resistant prostate cancer, sarcopenia was associated with poorer tolerance to docetaxel-based chemotherapy.

Most studies found sarcopenia to be a predictor for worse perioperative and oncologic outcomes in patients treated with radical surgery, radiotherapy, or systemic therapy for prostate cancer. However, there is significant heterogeneity across the studies in terms of sarcopenia definition. For a better understanding of the prognostic value of sarcopenia in patients with prostate cancer, large-scale prospective studies are needed.
Association between male infertility and prostate cancer: a systematic review and meta-analysis
Authors: Laukhtina Ekaterina , Mori Keiichiro , Pradere Benjamin , Shariat Shahrokh F.
Published: May 2021

Purpose of review

Male infertility has been shown to be associated with different maladies. The present systematic review and meta-analysis aimed to summarize the available evidence on the association between male infertility or childlessness and prostate cancer.

Recent findings

The PubMed, Web of Science, and Scopus databases were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they compared males with known infertility or childlessness to the control group including fertile males with regards to the diagnosis of prostate cancer. Overall, ten studies met our eligibility criteria. Three studies found that infertility was associated with higher risk of prostate cancer, four studies – with a reduced risk of prostate cancer, and three studies found no association. The forest plot revealed that infertility was not associated with prostate cancer (odds ratio [OR]: 1.26, 95% confidence interval [CI] 0.63–2.54; P = 0.5). Infertility was not associated with high (OR: 1.44, 95% CI 0.54–3.83; P = 0.5) or low (OR: 0.99, 95% CI 0.43–2.27; P = 0.9) grade prostate cancer.

Infertility or childlessness were not associated with the risk of prostate cancer. The significant heterogeneity between the included studies supports the need for more granular research to guide/fine tune early detection guidelines based on fertility.
COVID-19 crisis and minimally invasive surgery: a narrative review on intraoperative aerosol viral transmission and their impact on guidelines and clinical practice in Austria
Authors: Mun Dong-Ho , Pradere Benjamin , Shariat Shahrokh F. , Yurdakul Ozan , Remzi Mesut
Published: May 2021

Purpose of review

The purpose of this review is to evaluate the risk of intraoperative aerosol viral transmission and the impact of updated COVID-19 guidelines on minimally invasive surgery (MIS) in Austria.

Recent findings

The current literature does not support the risk of intraoperative viral transmission nor does it suggest a harm of minimally invasive procedures in the context of the COVID-19 pandemic. However, medical societies mostly adopted a precautionary approach with a focus on protective measures. Austrian surgeons considered MIS safe during the pandemic and Austria managed to keep the initial outbreak in control. Yet, MIS programs were still affected due to the postponements of elective procedures and switches to other methods by some surgeons.

The postponement and cancellation of MIS caused complexities in health-care delivery in Austria, whilst the evidence to substantiate this precautionary approach is missing. It must be noted, both the guidelines and our review are limited by the scarcity of evidence. In further consequence, regional factors should be considered while taking precautions. Specific studies on the severe acute respiratory syndrome coronavirus type 2 transmission risk during MIS are urgently needed.
Health-related quality of life in bladder cancer patients: general and cancer-specific instruments. Part 1
Authors: Zimmermann Kristin , Mostafaei Hadi , Heidenreich Axel , Schmelz Hans U. , Shariat Shahrokh F. , Mori Keiichiro
Published: May 2021

Purpose of review

Although survival outcomes are the primary outcomes to determine the effectiveness of treatment options, quality of life (QoL) is gaining in importance in addition to classic oncological outcomes. The present review aims to state and critically assess the challenges in health-related QoL (HRQoL) assessment especially in bladder cancer (BC) patients.

Recent findings

General QoL-instruments do not address concerns specific to cancer patients or BC patients. Domains, such as sexual functioning, embarrassment, self-consciousness, psychological distress, and urinary incontinence, are not adequately covered by any of the available instruments. With these QoL-instruments becoming increasingly specialized, the general aspects of QoL and possible unanticipated adverse effects are no longer likely to be accurately assessed. Sex-specific requirements have not been properly addressed by these QoL-instruments. HRQoL is reported to be lower in the elderly population, which may be due to their associated comorbidities and limitations, rather than treatment-related issues.

Due to their specifications, BC-specific instruments need to be used together with general QoL instruments to assess overall well being and disease- and treatment-specific QoL. Assessment of age-specific HRQoL is essential to understanding the QoL burden in each age group. QoL assessment calls for more detailed sex-specific questions to accurately address the HRQoL dimensions in men and women alike.
Artificial intelligence in stone disease
Authors: Ganesan Vishnu , Pearle Margaret S.
Published: May 2021

Purpose of review

Artificial intelligence (AI) is the ability of a machine, or computer, to simulate intelligent behavior. In medicine, the use of large datasets enables a computer to learn how to perform cognitive tasks, thereby facilitating medical decision-making. This review aims to describe advancements in AI in stone disease to improve diagnostic accuracy in determining stone composition, to predict outcomes of surgical procedures or watchful waiting and ultimately to optimize treatment choices for patients

Recent findings

AI algorithms show high accuracy in different realms including stone detection and in the prediction of surgical outcomes. There are machine learning algorithms for outcomes after percutaneous nephrolithotomy, extracorporeal shockwave lithotripsy, and for ureteral stone passage. Some of these algorithms show better predictive capabilities compared to existing scoring systems and nomograms.

The use of AI can facilitate the development of diagnostic and treatment algorithms in patients with stone disease. Although the generalizability and external validity of these algorithms remain uncertain, the development of highly accurate AI-based tools may enable the urologist to provide more customized patient care and superior outcomes.
Comparative Clinical and Neuropsychological Characteristics in Schizophrenia and Schizophrenia–Obsessive-Compulsive Disorder Patients
Authors: Temircan Zekeriya , Demirtaş Türev
Published: May 2021

The present study aimed to compare neuropsychological characteristics of patients with schizophrenia and patients with schizophrenia–obsessive-compulsive disorder (OCD). A total of 78 patients were included in the study, with 32 patients diagnosed with schizophrenia and 46 patients diagnosed with schizophrenia-OCD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Two groups of the patients were compared with each other in terms of demographic data, psychotic symptoms, and clinical and neuropsychological characteristics. In this study, the schizophrenia-OCD relationship was seen at a higher rate in male patients, and this group has worse clinical features. In addition, there was no significant difference among sociodemographics, clinical characteristics, and social and neuropsychological functionality between the two groups. According to our results, patients with schizophrenia-OCD experience more depression and anxiety that are related to poorer quality of life. Longitudinal and more homogeneous patient groups are needed for further studies to reveal whether schizophrenia accompanied by OCD is a comorbidity, a subtype of schizophrenia, or a different disorder.
Autistic Personality Traits and Treatment Outcome for Alcohol Use Disorders
Authors: Hildebrand Karlén Malin , Stålheim Jonas , Berglund Kristina , Wennberg Peter
Published: May 2021

The importance of personality traits for the outcome of psychiatric treatment, including treatment for alcohol use disorder (AUD), has been widely acknowledged. Also, research on autism spectrum disorders has evolved in recent years, emphasizing that the behavioral traits within these neuropsychiatric disorders exist on a dimension both within and outside the boundaries of psychopathology. In the present study, the relationship between personality traits associated with autistic functioning and level of alcohol use among patients before and after concluded AUD treatment was investigated. The participants (n = 165, diagnosed with AUD) were part of a longitudinal project on AUD treatment. Data from personality questionnaires (Structured Clinical Interview of Personality Disorders II and Temperament and Character Inventory) were used to assess autistic personality traits (APTs) based on behavior within Wing’s triad, which were related to background and treatment outcome. The chosen APT items illustrated a personality functioning with an emphasis on social interaction and rigidity. Only certain included questions were indicative of still having a problematic drinking pattern 2.5 years after treatment entry, which adhered to phobic, obsessive-compulsive, and schizoid personality traits, as well as rigidity/stubbornness. Albeit with modest influence, the degree of APTs was associated with heavier drinking at treatment entry, and symptoms relating to social interaction and rigidity were associated with still having a problematic drinking pattern 2.5 years after treatment entry. A higher degree of such traits may result in having problems taking advice from others and establishing treatment alliance, important parts of treatment efficacy, making assessment of such traits relevant to clinicians.
Cigarette Smoking in an Acute Partial Hospital Program
Authors: Guggenheim Frederick G. , Lieberman Paul B. , Farris Samantha G.
Published: May 2021

This study explored demographic and clinical features, plus clinical outcomes, in a smoke-free acute partial hospital (PH) among current smokers, former smokers, and those who had never smoked (nonsmokers). Compared with nonsmokers, current smokers were younger and more likely to be unmarried and unpartnered, unemployed, or receiving disability benefits. They had more prior inpatient (IP) and PH episodes. They also had more problems with interpersonal relationships, mood lability, psychosis, and substance use. Compared with nonsmokers, current smokers were more likely to miss PH treatment days and drop out. They also had longer time to readmission to PH or IP. Former smokers resembled nonsmokers, except that former smokers also had a high rate of dropout. Changes in symptoms and functioning for patients who completed PH were the same among all groups. In an acute PH setting, smoking is a marker for psychiatric and psychosocial impairment plus treatment interruption.
Current State of Evidence on Kidney Transplantation: How Fragile Are the Results?
Authors: Budhiraja Pooja , Kaplan Bruce , Kalot Mohamad , Alayli Abdallah El , Dimassi Ahmad , Chakkera Harini A. , Heilman Raymond , Edwards Audrene S. , Mustafa Reem A.
Published: May 2021

Background.

The study aims is to use the fragility index (FI) to examine the strength of evidence of randomized controlled trials (RCTs) published in the last decade on kidney transplantation.

Methods.

We searched MEDLINE for studies on kidney transplantation. We included the RCTs that compared 2 groups with 1:1 randomization and reported significant P values (<0.05) for a dichotomous outcome and were published in the top 10 transplant journals. We calculated the FI; a calculation used to determine the minimum number of subjects needed to change from a nonevent to an event to make the study results nonsignificant (P ≥ 0.05).

Results.

Fifty-seven RCTs met our inclusion criteria. The median sample size was 100 participants in each arm, the median number of events was 16 (interquartile range, 8–30) in the intervention group. Among the included trials, 79% were industry-funded, 93% involved medications, and the majority were open label. The median FI was 3 (interquartile range, 1–11). In 43% of the trials, the number of patients reported lost to follow-up was higher than or equal to the FI. Only 4% of the RCTs imputed a value for the missing dichotomous outcome. Furthermore, the median number of subjects who discontinued the trial because of adverse effects was 21, which was greater than the FI in 60% of the RCTs.

Conclusions.

The arbitrary classification of results into “significant” and “nonsignificant” based on P value <0.05 should perhaps be interpreted with the help of other statistical parameters and FI is one of them.
Whole exome sequencing in the UK Biobank reveals risk geneSLC2A1and biological insights for major depressive disorder
Authors: Tian Ruoyu , Ge Tian , Liu Jimmy Z. , Lam Max ,   Biogen Biobank team, Levey Daniel F. , Gelernter Joel , Stein Murray B. , Tsai Ellen A. , Huang Hailiang , Lencz Todd , Runz Heiko , Chen Chia-Yen
Published: May 2021

Nearly two hundred common-variant depression risk loci have been identified by genome-wide association studies (GWAS)1–4. However, the impact of rare coding variants on depression remains poorly understood. Here, we present the largest to date exome analysis of depression based on 320,356 UK Biobank participants. We show that the burden of rare disruptive coding variants in loss-of-function intolerant genes is significantly associated with depression risk. Among 30 genes with false discovery rate (FDR) <0.1,SLC2A1, a blood-brain barrier glucose transporter underlying GLUT1 deficiency syndrome5–7, reached exome-wide significance (P=2.96e-7). Gene-set enrichment supports neuron projection development and muscle activities2, 3as implicated in depression. Integrating exomes with polygenic risk revealed additive contributions from common and rare variants to depression risk. The burden of rare disruptive coding variants for depression overlapped with that of developmental disorder, autism and schizophrenia. Our study provides novel insight into the contribution of rare coding variants on depression and genetic relationships across developmental and psychiatric disorders.
Hypovitaminosis D is associated with sleep disorders in workers on alternating shifts with cardiovascular risk factors
Authors: de Menezes Júnior Luiz Antônio Alves , Fajardo Virgínia Capistrano , de Freitas Sílvia Nascimento , Pimenta Fausto Aloísio Pedrosa , de Oliveira Fernando Luiz Pereira , Machado-Coelho George Luiz Lins , Neto Raimundo Marques do Nascimento , Meireles Adriana Lúcia
Published: May 2021

Shift work has serious health impacts due to desynchronization of the circadian rhythm; consequently, the workers have increased sleep disturbances. Another impact is working hours, which can contribute to decreased sun exposure and lead to the development of hypovitaminosis D. Vitamin D has been implicated in extraskeletal functions in many physiological mechanisms, including sleep. Therefore, we aimed to verify the association between sleep parameters and hypovitaminosis D in shift workers with cardiovascular risk. We conducted a cross-sectional study of 82 male rotating shift workers (24-57 years old) with at least one cardiovascular risk factor (such as hyperglycemia, dyslipidemia, abdominal obesity, physical inactivity, hypertension, and smoking). Polysomnography was used to evaluate sleep parameters, while vitamin D levels were measured using a chemiluminescence method. Logistic regression was used to model the association between hypovitaminosis D and sleep parameters after adjustment for relevant covariates. Hypovitaminosis D (< 20 ng/mL) was seen in 30.5% of the workers. Shift workers with hypovitaminosis D had lower sleep efficiency, increased microarousal index, and lower arterial oxygen saturation after adjusting for seasonality, age, and body fat. Therefore, we suggest that hypovitaminosis D is associated with greater sleep disturbances in rotating shift workers with cardiovascular risk factors.
Importance of E484K and N501Y mutations in SARS-CoV-2 for genomic surveillance: rapid detection by restriction enzyme analysis
Authors: Jaspe Rossana C , Sulbaran Yoneira , Loureiro Carmen L , D Angelo Pierina , Rodriguez Lieska , Garzaro Domingo J , Rangel Hector R , Pujol Flor H
Published: May 2021

Introduction: Variants of Concern of SARS-CoV-2 (VOCs), the new coronavirus responsible for COVID-19, have emerged in several countries. Two mutations in the gene coding for the Spike protein of the viral genome are particularly important and associated with some of these variants: E484K and N501Y. Restriction enzyme analysis is proposed as a rapid method to detect these two mutations.
Methodology: A search on GISAID was performed in April 2021 to detect the frequency of these two mutations in the sequence available and their association with other lineages. A small amplicon from the Spike gene was digested with two enzymes: HpyAV, which allows detecting E484K mutation, and MseI, for detecting the N501Y one.
Results: The mutations E484K and N501Y, associated with VOCs, have emerged in several other lineages, particularly E484K. A 100% correlation was observed with sequencing results.
Conclusions: The proposed methodology, which allows screening a great number of samples, will probably help to provide more information on the prevalence and epidemiology of these mutations worldwide, to select the candidates for whole-genome sequencing.
Genomic and epidemiological analysis of SARS-CoV-2 viruses in Sri Lanka
Authors: Jeewandara Chandima , Jayathilaka Deshni , Ranasinghe Diyanath , Hsu Nienyun Sharon , Ariyaratne Dinuka , Jayadas Tibutius Thanesh , Madushanka Deshan , Lindsey Benjamin B. , Gomes Laksiri , Parker Matthew D. , Wijewickrama Ananda , Karunaratne Malika , Ogg Graham S. , de Silva Thushan I. , Malavige Gathsaurie Neelika
Published: May 2021

Background

In order to understand the molecular epidemiology of SARS-CoV-2 in Sri Lanka, since March 2020, we carried out genomic sequencing overlaid on available epidemiological data until April 2021.

Methods

Whole genome sequencing was carried out on diagnostic sputum or nasopharyngeal swabs from 373 patients with COVID-19. Molecular clock phylogenetic analysis was undertaken to further explore dominant lineages.

Results

The B.1.411 lineage was most prevalent, which was established in Sri Lanka and caused outbreaks throughout the country until March 2021. The estimated time of the most recent common ancestor of this lineage was 29th June 2020 (95% lower and upper bounds 23rd May to 30th July), suggesting cryptic transmission may have occurred, prior to a large epidemic starting in October 2020. Returning travellers were identified with infections caused by lineage B.1.258, as well as the more transmissible B.1.1.7 lineage, which has replaced B.1.411 to fuel the ongoing large outbreak in the country.

Conclusions

The large outbreak that started in early October, is due to spread of a single virus lineage, B.1.411 until the end of March 2021, when B.1.1.7 emerged and became the dominant lineage.
Diagnostic tests for Schistosomiasis for low prevalence settings: a systematic review and Meta-Analysis
Authors: Vaillant Michel T , Philippy Fred , Barré Jessica , Bulaev Dmitry , Garba Amadou T
Published: May 2021

Background

Tests for diagnosing schistosomiasis in areas where prevalence is low due to control programme of the disease should be suffiently sensitive to detect the residual disease. If they had sufficient diagnostic accuracy they could replace conventional microscopy as they provide a quicker answer and are easier to use.

Objectives

To compare sensitivity and specificity of new tests, especially rapid diagnostic tests (RDTs), with regard to a certain reference test.

Methods

We searched the electronic databases Pubmed, EMBASE, the Cochrane Library and LILACS up to February 2021. Furthermore we searched results from the previous meta-analyses.

We included studies that used microscopy as the reference standard: for S. haematobium, microscopy of urine prepared by filtration, centrifugation, or sedimentation methods; and for S. mansoni, microscopy of stool by Kato-Katz thick smear.

Two review authors independently extracted data, assessed quality of the data using QUADAS-2, and performed meta-analysis where appropriate. Grading of evidence was done with the GRADE methodology by using GradePro. Using the variability of test thresholds, we used a bayesian bivariate random-effects summary receiver operating characteristic model for all eligible tests. We investigated heterogeneity, and carried out sensitivity analyses where possible. Results for sensitivity and specificity are presented as percentages with 95% confidence intervals (CI).

Results

The review gathered 203 articles stating a diagnostic test for the diagnosis of S. haematobium and S. mansoni out of which 114 entered the analyses. Microscopy of Urine filtration or Kato-Katz smears were used as the reference standard.

Compared with Kato-Katz smears, AWE-SEA ELISA (Se=94%; Sp=64%) is comparable to CCA1 (Se=87%; Sp=60%). IgG ELISA (Se=93%; Sp=68%) has also a very good ability to detect true positive as well as CAA cassette (Se=73%; Sp=68%). For S. haematobium, proteinuria (Se=59%; Sp=83%) and haematuria (Se=74%; Sp=87%) reagent strips showed reasonably high specificities with a considerably better sensitivity for the haematuria test.

There are interesting promising new diagnostic tests that were tested in field studies. However prevalences of the locations where these studies took place are variable and there are no specific study with a high number of patients in areas with low level of schistosomiasis infection.
Characterizing cellular and molecular variabilities of peripheral immune cells in healthy inactivated SARS-CoV-2 vaccine recipients by single-cell RNA sequencing
Authors: Tong Renyang , Zhong Jianmei , Li Ronghong , Chen Yifan , Hu Liuhua , Li Zheng , Shi Jianfeng , Lin Guanqiao , Lyu Yuyan , Hu Li , Guo Xiao , Liu Qi , Shuang Tian , Zhang Chenjie , Yuan Ancai , Zhang Minchao , Lin Wei , Pu Jun
Published: May 2021

We systematically investigated the transcriptomes of the peripheral immune cells from 6 inactivated vaccine, BBIBP-CorV recipients at 4 pivotal time points using single-cell RNA-seq technique. First, the significant variation of the canonical immune-responsive signals of both humoral and cellular immunity, as well as other possible symptom-driver signals were evaluated in the specific cell types. Second, we described and compared the common and distinct variation trends across COVID-19 vaccination, disease progression, and flu vaccination to achieve in-depth understandings of the manifestation of immune response in peripheral blood under different stimuli. Third, the expanded T cell and B cell clones were correlated to the specific phenotypes which allowed us to characterize the antigen-specific ones much easier in the future. At last, other than the coagulopathy, the immunogenicity of megakaryocytes in vaccination were highlighted in this study. In brief, our study provided a rich data resource and the related methodology to explore the details of the classical immunity scenarios.
Rapid detection of neutralizing antibodies to SARS-CoV-2 variants in post-vaccination sera
Authors: Miyakawa Kei , Jeremiah Sundararaj Stanleyraj , Kato Hideaki , Yamaoka Yutaro , Go Hirofumi , Yamanaka Takeharu , Ryo Akihide
Published: May 2021

The uncontrolled spread of the COVID-19 pandemic has led to the emergence of different SARS-CoV-2 variants across the globe. The ongoing global vaccination strategy to curtail the COVID-19 juggernaut, is threatened by the rapidly spreading Variants of Concern (VOC) and other regional mutants, which are less responsive to neutralization by infection or vaccine derived antibodies. We have previously developed the hiVNT system which detects SARS-CoV-2 neutralizing antibodies in sera in less than three hours. In this study, we modify the hiVNT for rapid qualitative screening of neutralizing antibodies (nAb) to multiple variants of concern (VOC) of SARS-CoV-2, and assess the neutralizing efficacy of the BNT162b2 mRNA vaccine on seven epidemiologically relevant SARS-CoV-2 variants. Here we show that the BNT162b2 mRNA vaccine can activate humoral immunity against the major SARS-CoV-2 mutants that are currently in circulation. Albeit a small sample size, we observed that one dose of vaccine was sufficient to elicit a protective humoral response in previously infected people. Using a panel of seven SARS-CoV-2 variants and a single prototype virus, our modified hiVNT would be useful for large-scale community wide testing to detect protective immunity that may confer vaccine/immune passport in the ongoing COVID-19 pandemic.
SARS-CoV-2 antibody prevalence among homeless people, sex workers and shelter workers in Denmark: a nationwide cross-sectional study
Authors: Röthlin Eriksen Alexandra R , Fogh Kamille , Hasselbalch Rasmus B , Bundgaard Henning , Nielsen Susanne D , Jørgensen Charlotte S , Scharff Bibi FSS , Erikstrup Christian , Sækmose Susanne G. , Holm Dorte K , Aagaard Bitten , Kristensen Jonas H , Bødker Cecilie A , Norsk Jakob , Nielsen Pernille Brok , Østergaard Lars , Ellermann-Eriksen Svend , Andersen Berit , Nielsen Henrik , Johansen Isik S. , Wiese Lothar , Simonsen Lone , K.Fischer Thea , Folke Fredrik , Lippert Freddy , Ostrowski Sisse R , Ethelberg Steen , Koch Anders , Vangsted Anne-Marie , Krause Tyra , Fomsgaard Anders , Nielsen Claus , Ullum Henrik , Skov Robert , Iversen Kasper
Published: May 2021

Background

People experiencing homelessness (PEH) and associated shelter workers may be at higher risk of infection with “Severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). The aim of this study was to determine the prevalence of SARS-CoV-2 among PEH and shelter workers in Denmark.

Design and methods

In November 2020, we conducted a nationwide cross-sectional seroprevalence study among PEH and shelter workers at 21 recruitment sites in Denmark. The assessment included a point-of-care test for antibodies against SARS-CoV-2, followed by a questionnaire. The seroprevalence was compared to that of geographically matched blood donors considered as a proxy for the background population, tested using a total Ig ELISA assay.

Results

We included 827 participants in the study, of whom 819 provided their SARS-CoV-2 antibody results. Of those, 628 were PEH (median age 50.8 (IQR 40.9-59.1) years, 35.5% female) and 191 were shelter workers (median age 46.6 (IQR 36.1-55.0) years and 74.5% female). The overall seroprevalence was 6.7% and was similar among PEH and shelter workers (6.8% vs 6.3%, p=0.87); and 12.2% among all participants who engaged in sex work. The overall participant seroprevalence was significantly higher than that of the background population (2.9%, p <0.001). When combining all participants who reported sex work or were recruited at designated safe havens, we found a significantly increased risk of seropositivity compared to other participants (RR 2.1, 95% CI 1.16-3.75, p=0.02). Seropositive and seronegative participants reported a similar presence of at least one SARS-CoV-2 associated symptom (49% and 54%, respectively).

Interpretations

The prevalence of SARS-CoV-2 antibodies was more than twice as high among PEH and associated shelter workers, compared to the background population. The subset of the study participants who were also sex workers were at particularly high risk of COVID-19 infection.

Funding

TrygFonden and HelseFonden.