bluuebunny/crossref_metadata_2025_split huggingface dataset:
GGGCTA repeats can fold into hairpins poorly unfolded by replication protein A: a possible origin of the length-dependent instability of GGGCTA variant repeats in human telomeres
Authors: Chatain Jean , Blond Alain , Phan Anh Tuân , Saintomé Carole , Alberti Patrizia 
Published: June 2021

Abstract
Human telomeres are composed of GGGTTA repeats and interspersed with variant repeats. The GGGCTA variant motif was identified in the proximal regions of human telomeres about 10 years ago and was shown to display a length-dependent instability. In parallel, a structural study showed that four GGGCTA repeats folded into a non-canonical G-quadruplex (G4) comprising a Watson–Crick GCGC tetrad. It was proposed that this non-canonical G4 might be an additional obstacle for telomere replication. In the present study, we demonstrate that longer GGGCTA arrays fold into G4 and into hairpins. We also demonstrate that replication protein A (RPA) efficiently binds to GGGCTA repeats structured into G4 but poorly binds to GGGCTA repeats structured into hairpins. Our results (along with results obtained with a more stable variant motif) suggest that GGGCTA hairpins are at the origin of GGGCTA length-dependent instability. They also suggest, as working hypothesis, that failure of efficient binding of RPA to GGGCTA structured into hairpins might be involved in the mechanism of GGGCTA array instability. On the basis of our present and past studies about telomeric G4 and their interaction with RPA, we propose an original point of view about telomeric G4 and the evolution of telomeric motifs.
Does Variceal Drainage Affect Arteriovenous Malformation Obliteration and Hemorrhage Rates After Stereotactic Radiosurgery? A Case-Matched Analysis
Authors: Faramand Andrew , Alan Nima , Kano Hideuyki , Niranjan Ajay , Agarwal Nitin , Ozpinar Alp , Flickinger John , Lunsford L Dade 
Published: June 2021

Abstract

BACKGROUND
Stereotactic radiosurgery (SRS) is widely accepted as a minimally invasive alternative to surgery in the management of arteriovenous malformations (AVMs). Dilated AVM outflow veins or varices may be caused by high-flow or partial outflow obstruction, which may increase the risk of a hemorrhage before or after SRS.

OBJECTIVE
To compare the obliteration and hemorrhage risks in patients with and without AVM varices (AVMv).

METHODS
From our prospective database of 1012 AVM patients who underwent Gamma Knife® (Elekta) SRS, we identified 103 patients with AVMv, and 847 patients without varices. The median follow-up was 52 mo. Balancing variable score matching was performed to compare obliteration and hemorrhage rates between the 2 groups.

RESULTS
Obliteration rates in the AVMv group were 38% at 3 yr, 65% at 4 yr, and 70% at 5 yr. Patients with an AVMv had no difference in the final obliteration rate compared to patients who did not have variceal drainage (P = .35). Actuarial hemorrhage after SRS in the matched patients with AVMv was 4.9%, 13%, and 13.7%, at 1, 3, and 5 yr, respectively. The rate of hemorrhage in the group with no varix was 2.9%, 5.4%, and 9.1% at 1, 3, and 5 yr, respectively (P = .14).

CONCLUSION
The presence of AVM variceal venous drainage did not affect the obliteration rate and did not confer a higher risk of a subsequent hemorrhage both before and after SRS.
Hospital-Acquired Bloodstream Infections in Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 Infection (Coronavirus Disease 2019): Association With Immunosuppressive Therapies
Authors: Khatri Akshay , Malhotra Prashant , Izard Stephanie , Kim Angela , Oppenheim Michael , Gautam-Goyal Pranisha , Chen Thomas , Doan Thien-ly , Berlinrut Ilan , Niknam Negin , Flannery Sarah , Hirschwerk David , Epstein Marcia , Farber Bruce 
Published: June 2021

Abstract

Background
Immunosuppressive therapies proposed for Coronavirus disease 2019 (COVID-19) management may predispose to secondary infections. We evaluated the association of immunosuppressive therapies with bloodstream-infections (BSIs) in hospitalized COVID-19 patients.

Methods
This was an institutional review board-approved retrospective, multicenter, cohort study of adults hospitalized with COVID-19 over a 5-month period. We obtained clinical, microbiologic and laboratory data from electronic medical records. Propensity-score-matching helped create balanced exposure groups. Demographic characteristics were compared across outcome groups (BSI/no BSI) using two-sample t-test and Chi-Square test for continuous and categorical variables respectively, while immunosuppressive therapy use was compared using McNemar’s test. Conditional logistic regression helped assess the association between immunosuppressive therapies and BSIs.

Results
13,007 patients were originally included, with propensity-score-matching producing a sample of 6,520 patients. 3.74% and 3.97% were diagnosed with clinically significant BSIs in the original and propensity-score-matched populations respectively. COVID-19 patients with BSIs had significantly longer hospitalizations, higher intensive care unit admission and mortality rates compared to those without BSIs. On univariable analysis, combinations of corticosteroids/anakinra [odds-ratio (OR) 2.00, 95% confidence intervals (C.I.) 1.05-3.80, P value.0342] and corticosteroids/tocilizumab [OR 2.13, 95% C.I. 1.16–3.94, P value .0155] were significantly associated with BSIs. On multivariable analysis (adjusting for confounders), combination corticosteroids/tocilizumab were significantly associated with any BSI [OR 1.97, 95% C.I. 1.04–3.73, P value.0386] and with bacterial BSIs [OR 2.13, 95% C.I. 1.12–4.05, p-value 0.0217].

Conclusions
Combination immunosuppressive therapies were significantly associated with BSI occurrence in COVID-19 patients; their use warrants increased BSI surveillance. Further studies are needed to establish their causative role.
Quantifying the Impact of Lifting Community Nonpharmaceutical Interventions for COVID-19 During Vaccination Rollout in the United States
Authors: Matrajt Laura , Janes Holly , Schiffer Joshua T , Dimitrov Dobromir 
Published: June 2021

AbstractUsing a mathematical model, we estimated the potential impact on mortality and total infections of completely lifting community nonpharmaceutical interventions when only a small proportion of the population has been fully vaccinated in 2 states in the United States. Lifting all community nonpharmaceutical interventions immediately is predicted to result in twice as many deaths over the next 6 months as a more moderate reopening allowing 70% of prepandemic contacts.
On the nature of the anomalous event in 2021 in the dwarf nova SS Cygni and its multi-wavelength transition
Authors: Kimura Mariko , Yamada Shinya , Nakaniwa Nozomi , Makita Yoshihiro , Negoro Hitoshi , Shidatsu Megumi , Kato Taichi , Enoto Teruaki , Isogai Keisuke , Mihara Tatehiro , Akazawa Hidehiko , Gendreau Keith C , Hambsch Franz-Josef , Dubovsky Pavol A , Kudzej Igor , Kasai Kiyoshi , Tordai Tamás , Pavlenko Elena , Sosnovskij Aleksei A , Babina Julia V , Antonyuk Oksana I , Itoh Hiroshi , Maehara Hiroyuki 
Published: June 2021

AbstractSS Cyg has long been recognized as the prototype of a group of dwarf novae that show only outbursts. However, this object has entered a quite anomalous event in 2021, which at first appeared to be standstill, i.e., an almost constant luminosity state observed in Z Cam-type dwarf novae. This unexpected event gives us a great opportunity to reconsider the nature of standstill in cataclysmic variables. We have observed this anomalous event and its forerunner, a gradual and simultaneous increase in the optical and X-ray flux during quiescence, through many optical telescopes and the X-ray telescopes NICER and NuSTAR. We have not found any amplification of the orbital hump during quiescence before the anomalous event, which suggests that the mass transfer rate did not significantly fluctuate on average. The estimated X-ray flux was not enough to explain the increment of the optical flux during quiescence via X-ray irradiation of the disk and the secondary star. It would be natural to consider that viscosity in the quiescent disk was enhanced before the anomalous event, which increased mass accretion rates in the disk and raised not only the optical flux but also the X-ray flux. We suggest that enhanced viscosity also triggered the standstill-like phenomenon in SS Cyg, which is considered to be a series of small outbursts. The inner part of the disk would always stay in the outburst state and only its outer part would be unstable against the thermal–viscous instability during this phenomenon, which is consistent with the observed optical color variations. This scenario is in line with our X-ray spectral analyses which imply that the X-ray-emitting inner accretion flow became hotter than usual and vertically expanded, and that it became denser and was cooled down after the onset of the standstill-like state.
Biocompatible and antibacterial soy protein isolate/quaternized chitosan composite sponges for acute upper gastrointestinal hemostasis
Authors: Wang Zijian , Ke MeiFang , He Liu , Dong Qi , Liang Xiao , Rao Jun , Ai Junjie , Tian Chuan , Han Xinwei , Zhao Yanan 
Published: June 2021

Abstract
Innovative biomedical applications have high requirements for biomedical materials. Herein, a series of biocompatible, antibacterial and hemostatic sponges were successfully fabricated for the treatment of acute upper gastrointestinal bleeding (AUGB). Quaternized chitosan (QC) and soy protein isolate (SPI) were chemically cross-linked to obtain porous SPI/QC sponges (named SQS-n, with n = 30, 40, 50 or 60 corresponding to the weight percentage of the QC content). The chemical composition, physical properties and biological activity of SQS-n were investigated. SQS-n could support the adhesion and proliferation of L929 cells while triggering no obvious blood toxicity. Meanwhile, SQS-n exhibited good broad-spectrum antibacterial activity against both gram-positive bacteria (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli). The in vivo hemostatic effect of SQS-n was evaluated using three different bleeding models. The results revealed that SQS-50 performed best in reducing blood loss and hemostatic time. The overall hemostatic effect of SQS-50 was comparable to that of a commercial gelatin sponge. The enhanced antibacterial and hemostatic activities of SQS-n were mainly attributed to the QC component. In conclusion, this work developed a QC-functionalized hemostatic sponge that is highly desirable for innovative biomedical applications, such as AUGB.
Recognition of foreign family foundations in Switzerland
Authors: Peter Natalie 
Published: June 2021

Abstract
Swiss Family Foundations are not commonly used for asset protection or estate planning purposes due to a de facto prohibition of family maintenance foundation. Since families are often spread over different countries and continents and assets are located in various jurisdictions, contributions of assets to a foundation may very well be an optimal solution, also because these assets no longer fall within the scope of the estate. For this purpose, foundations are set up in jurisdictions like Liechtenstein.
Caffeine consumption attenuates ethanol-induced inflammation through the regulation of adenosinergic receptors in the UChB rats cerebellum
Authors: Rossetto Isabela Maria Urra , Cagnon Valéria Helena Alves , Kido Larissa Akemi , Lizarte Neto Fermino Sanches , Tirapelli Luís Fernando , Tirapelli Daniela Pretti da Cunha , de Almeida Chuffa Luiz Gustavo , Martinez Francisco Eduardo , Martinez Marcelo 
Published: June 2021

Abstract
Caffeine consumption is able to interfere in cellular processes related to inflammatory mechanisms by acting through the adenosinergic system. This study aimed to recognize alterations related to adenosinergic system and inflammatory process in the cerebellum of University of Chile Bibulous (UChB) rats after the consumption of ethanol and caffeine. UChB and Wistar rats, males at 5 months old, were divided into the groups (n = 15/group): (i) Control (Wistar rats receiving water); (ii) Ethanol group (UChB rats receiving ethanol solution at 10%) and (iii) Ethanol+caffeine group (UChB rats receiving ethanol solution at 10% added of 3 g/L of caffeine). The cerebellar tissue was collected and processed for immunohistochemistry, Reverse transcription polymerase chain reaction (RT-PCR) and western blotting techniques for the adenosinergic receptors A1 and A2a and inflammatory markers, including Nuclear factor kappa B (NFkB), TLR4, TLR2, MyD88, TNF-α, COX-2, iNOS and microglial marker Iba-1. Results showed ethanol and caffeine consumption differentially altering the immunolocalization of adenosinergic receptors and inflammatory markers in the cerebellar tissue. The A2a receptor was overexpressed in the Ethanol group and was evident in the glial cells. The Ethanol group had increased protein levels for NFκB and TLR4, expressively in Bergmann glia and Purkinje cells. Caffeine reduced the expression of these markers to levels similar to those found in the Control group. The A1 gene was upregulated the Ethanol group, but not its protein levels, suggesting post-transcriptional interference. In conclusion, caffeine seems to attenuate ethanol-induced inflammation in the cerebellum of UChB rats through the A1 and A2a modulation, playing a neuroprotective role in the chronic context of ethanol consumption.
EdTech in Developing Countries: A Review of the Evidence
Authors: Rodriguez-Segura Daniel 
Published: June 2021

Abstract
The emergence of educational technology (“EdTech”) in developing countries has been received as a promising avenue to address some of the most challenging policy questions within educational systems. In this paper, I review and synthesize all existing studies with credible causal identification frameworks of EdTech interventions in developing countries. While other studies review the evidence for EdTech interventions in developed countries, there is currently no equivalent study for developing contexts, in spite of the rising number of studies being produced. I classify studies into four thematic categories based on the type of EdTech intervention analyzed: Access to technology; technology-enabled behavioral interventions; improvements to instruction; and self-led learning. I find that EdTech interventions centered around self-led learning and improvements to instruction are the most effective forms of EdTech at raising learning outcomes. Similarly, technology-enabled behavioral interventions are less promising for generating large effects but highly cost-effective given their typically low marginal costs. Although expanding access to technology alone is not sufficient to improve learning, it is a necessary first step for some other types of interventions. More broadly, the overall success of interventions rests on the thoughtful customization of the EdTech solution to the policy constraints at hand. Finally, EdTech interventions across all thematic areas can and should act as complements by leveraging their respective comparative advantages to address deficiencies within educational systems in developing countries.
An Empirical Investigation Into Milestones Factor Structure Using National Data Derived From Clinical Competency Committees
Authors: Yamazaki Kenji , Holmboe Eric S. , Hamstra Stanley J. 
Published: June 2021

Purpose
To investigate whether milestone data obtained from clinical competency committee (CCC) ratings in a single specialty reflected the 6 general competency domains framework.

Method
The authors examined milestone ratings from all 275 U.S. Accreditation Council for Graduate Medical Education–accredited categorical obstetrics and gynecology (OBGYN) programs from July 1, 2018, to June 30, 2019. The sample size ranged from 1,371 to 1,438 residents from 275 programs across 4 postgraduate years (PGYs), each with 2 assessment periods. The OBGYN milestones reporting form consisted of 28 subcompetencies under the 6 general competency domains. Milestone ratings were determined by each program’s CCC. Intraclass correlations (ICCs) and design effects were calculated for each subcompetency by PGY and assessment period. A multilevel confirmatory factor analysis (CFA) perspective was used, and the pooled within-program covariance matrix was obtained to compare the fit of the 6-domain factor model against 3 other plausible models.

Results
Milestone ratings from 5,618 OBGYN residents were examined. Moderate to high ICCs and design effects greater than 2.0 were prevalent among all subcompetencies for both assessment periods, warranting the use of the multilevel approach in applying CFA to the milestone data. The theory-aided split-patient care (PC) factor model, which used the 6 general competency domains but also included 3 factors within the PC domain (obstetric technical skills, gynecology technical skills, and ambulatory care), was consistently shown as the best-fitting model across all PGYs by assessment period conditions, except for one.

Conclusions
The findings indicate that in addition to using the 6 general competency domains framework in their rating process, CCCs may have further distinguished the PC competency domain into 3 meaningful factors. This study provides internal structure validity evidence for the milestones within a single specialty and may shed light on CCCs’ understanding of the distinctive content embedded within the milestones.
Cost Effectiveness of Cochlear Implantation in Single-Sided Deafness
Authors: Dreyfuss Michael , Giat Yahel , Veraguth Dorothe , Röösli Christof , Huber Alexander M. , Laske Roman D. 
Published: June 2021

Objective:
To analyze the cost effectiveness of cochlear implantation (CI) for the treatment of single-sided deafness (SSD).

Study Design:
Cost-utility analysis in an adapted Markov model.

Setting:
Adults with single-sided deafness in a high-income country.

Intervention:
Unilateral CI was compared with no intervention.

Main Outcome Measure:
Incremental cost-effectiveness ratios were compared with different cost-effectiveness thresholds ($10,000 to $150,000) for different age, sex, and cost combinations. The calculations were based on the quality-adjusted life year (QALY), national life expectancy tables, and different cost settings. The health utility values for the QALY were either directly collected from published data, or, derived from published data using a regression model of multiple utility indices (regression estimate).

Results:
The regression estimate showed an increase of the health utility value from 0.62 to 0.74 for SSD patients who underwent CI. CI for SSD was cost effective for women up to 64 years ($50,000 per-QALY threshold), 80 years ($100,000 per-QALY threshold), and 86 years ($150,000 per-QALY threshold). For men, these values were 58, 77, and 84, respectively. Changing the discount rate by up to 5% further increased the cutoff ages up to 5 years. A detailed cost and age sensitivity analysis is presented and allows testing for cost effectiveness in local settings worldwide.

Conclusions:
CI is a cost-effective option to treat patients with SSD.
A Clinical Evaluation of Minimally Invasive Ponto Surgery With a Modified Drill System for Inserting Bone-Anchored Hearing Implants
Authors: Caspers Coosje Jacoba Isabella , Kruyt Ivo Joachim , Mylanus Emmanuel Antonius Maria , Hol Myrthe Karianne Sophie 
Published: June 2021

Objective:
To compare 6-months outcomes of the modified minimally invasive Ponto surgery (m-MIPS) to both the linear incision technique with soft tissue preservation (LIT-TP), and original MIPS (o-MIPS) for inserting bone-anchored hearing implants (BAHIs).

Study design:
Exploratory pilot study with one test group and two historical control groups.

Setting:
Tertiary referral center.

Patients:
In the test group, 24 patients (25 implants) were prospectively included. Each control group comprised 25 patients (25 implants) who participated in previously conducted clinical trials.

Interventions:
The test group received a BAHI using m-MIPS. The two control groups underwent surgery using the LIT-TP and o-MIPS, respectively.

Main outcome measures:
Implant survival, implant stability, and surgery-related variables were compared between the test and control groups. Soft tissue status, skin sensibility, and subjective numbness were compared between m-MIPS and LIT-TP only.

Results:
Implant survival was comparable between m-MIPS and LIT-TP, whereas implant stability measurements were slightly lower for m-MIPS. M-MIPS resulted in comparable adverse skin reactions and skin sensibility, significantly reduced surgical time and slightly improved subjective numbness, compared with LIT-TP. Between m-MIPS and o-MIPS, no statistically significant differences in implant survival, implant stability and surgical time were observed.

Conclusions:
A trend toward lower implant loss rates after m-MIPS was observed, when compared with o-MIPS. M-MIPS seems to be a good alternative to LIT-TP for inserting BAHIs, since most clinical outcomes were either comparable or slightly better for m-MIPS. Upon deciding on which technique to use, larger studies on implant survival should be performed. Furthermore, other aspects such as costs, training aspects and surgical experience should be evaluated.
Contralesional High-Acceleration Vestibulo-Ocular Reflex Function in Vestibular Schwannoma
Authors: Lee Jennifer Wing Yee , Hassannia Fatemeh , Rutka John Alexander 
Published: June 2021

Impairment of ipsilesional vestibulo-ocular reflex (VOR) function is well described in vestibular schwannoma (VS) and a correlation between gain of the VOR and tumor size has been suggested. Bilateral VOR impairment may also occur in VS patients, but its mechanisms are poorly understood. We sought to explore the effect of unilateral VS on ipsilesional and contralesional high-acceleration VOR function using video head impulse testing, and evaluate potential factors responsible for contralesional VOR impairment.

Materials and Methods:
Chart review in tertiary referral center of patients with unilateral VS, who completed neurotological examination and vestibular function testing.

Results:
One hundred one patients (mean age 57.4 yrs) were included. Maximal tumor diameter ranged from 0.3 to 5.0 cm. Forty one patients had evidence of brainstem compression from VS on magnetic resonance imaging (MRI). Ipsilesional and contralesional VOR impairment was present in 81 (80%) and 44 (43%) patients, respectively. Bilateral VOR impairment was seen in 42 (42%) patients. Bilateral VOR impairment correlated with tumor size. Presence of brainstem compression was associated with reduced ipsilesional VOR gain, but not contralesional VOR gain.