bluuebunny/crossref_metadata_2025 huggingface dataset:
Olfactory–Trigeminal Interactions in Patients with Parkinson’s Disease
Authors: Tremblay Cécilia , Frasnelli Johannes
Published: April 2021

Olfactory dysfunction (OD) is a highly frequent early non-motor symptom of Parkinson’s disease (PD). An important step to potentially use OD for the development of early diagnostic tools of PD is to differentiate PD-related OD from other forms of non-parkinsonian OD (NPOD: postviral, sinunasal, post-traumatic, and idiopathic OD). Measuring non-olfactory chemosensory modalities, especially the trigeminal system, may allow to characterize a PD-specific olfactory profile. We here review the literature on PD-specific chemosensory alteration patterns compared with NPOD. Specifically, we focused on the impact of PD on the trigeminal system and particularly on the interaction between olfactory and trigeminal systems. As this interaction is seemingly affected in a disease-specific manner, we propose a model of interaction between both chemosensory systems that is distinct for PD-related OD and NPOD. These patterns of chemosensory impairment still need to be confirmed in prodromal PD; nevertheless, appropriate chemosensory tests may eventually help to develop diagnostic tools to identify individuals at risks for PD.
Single-cell dual-omics reveals the transcriptomic and epigenomic diversity of cardiac non-myocytes
Authors: Wang Li , Yang Yuchen , Ma Hong , Xie Yifang , Xu Jun , Near David , Wang Haofei , Garbutt Tiffany , Li Yun , Liu Jiandong , Qian Li
Published: April 2021

Aims

The precise cellular identity and molecular features of non-myocytes (non-CMs) in a mammalian heart at a single-cell level remain elusive. Depiction of epigenetic landscape with transcriptomic signatures using the latest single-cell multi-omics has the potential to unravel the molecular programs underlying the cellular diversity of cardiac non-myocytes. Here, we characterized the molecular and cellular features of cardiac non-CM populations in the adult murine heart at the single-cell level.

Methods and results

Through single-cell dual omics analysis, we mapped the epigenetic landscapes, characterized the transcriptomic profiles and delineated the molecular signatures of cardiac non-CMs in the adult murine heart. Distinct cis-regulatory elements and trans-acting factors for the individual major non-CM cell types (endothelial cells, fibroblast, pericytes, and immune cells) were identified. In particular, unbiased sub-clustering and functional annotation of cardiac fibroblasts (FBs) revealed extensive FB heterogeneity and identified FB sub-types with functional states related to the cellular response to stimuli, cytoskeleton organization, and immune regulation, respectively. We further explored the function of marker genes Hsd11b1 and Gfpt2 that label major FB subpopulations and determined the distribution of Hsd11b1+ and Gfp2+ FBs in murine healthy and diseased hearts.

Conclusions

In summary, we characterized the non-CM cellular identity at the transcriptome and epigenome levels using single-cell omics approaches and discovered previously unrecognized cardiac fibroblast subpopulations with unique functional states.
Multiple percutaneous coronary interventions may negatively impact cardiac remodelling after bypass surgery
Authors: Nonaka Michihito , Komiya Tatsuhiko , Shimamoto Takeshi , Matsuo Takehiko
Published: April 2021

OBJECTIVES

Many patients undergo percutaneous coronary intervention (PCI) multiple times before being referred for coronary artery bypass grafting (CABG), in which bypass grafts are often anastomosed to small distal targets with higher risk of graft failure. We aimed to assess whether multiple PCIs adversely affect the long-term outcomes of patients who undergo CABG subsequently.

METHODS

A cohort of 368 patients with no history of PCI underwent initial isolated CABG between 2003 and 2013 (no PCI group). Ninety-seven patients who had undergone PCI 2 or more times preoperatively during the same period constituted the multiple PCI group. After propensity score matching, the group outcomes were compared.

RESULTS

There were no significant differences in the 10-year all-cause mortality and major adverse cardiac and cerebrovascular event rates in both groups. Although the left ventricular end-diastolic dimension in the multiple PCI group did not change markedly (from 48.0 ± 6.0 to 47.2 ± 7.9 mm; P = 0.25), it decreased significantly in the no PCI group (from 48.3 ± 6.1 to 44.9 ± 9.1 mm; P < 0.001). The left ventricular end-systolic dimension in the no PCI group decreased significantly (from 34.1 ± 8.7 to 31.4 ± 8.6 mm; P = 0.024), while it in the multiple PCI group did not (from 33.6 ± 8.3 to 32.7 ± 8.6 mm; P = 0.21).

CONCLUSIONS

For complex coronary artery disease, early surgical intervention could be considered with respect to postoperative left ventricular remodelling during the long-term follow-up.
Impact of sex on the management and outcome of aortic stenosis patients
Authors: Bienjonetti-Boudreau David , Fleury Marie-Ange , Voisine Martine , Paquin Amélie , Chouinard Isabelle , Tailleur Mathieu , Duval Raphael , Magnan Pierre-Olivier , Beaudoin Jonathan , Salaun Erwan , Clavel Marie-Annick
Published: April 2021

Objective

The aim of this study was to assess the impact of sex on the management and outcome of patients according to aortic stenosis (AS) severity.

Introduction

Sex differences in the management and outcome of AS are poorly understood.

Methods

Doppler echocardiography data of patients with at least mild-to-moderate AS [aortic valve area (AVA) ≤1.5 cm2 and peak jet velocity (VPeak) ≥2.5 m/s or mean gradient (MG) ≥25 mmHg] were prospectively collected between 2005 and 2015 and retrospectively analysed. Patients with reduced left ventricular ejection fraction (<50%), or mitral or aortic regurgitation >mild were excluded.

Results

Among 3632 patients, 42% were women. The mean indexed AVA (0.48 ± 0.17 cm2/m2), VPeak (3.74 ± 0.88 m/s), and MG (35.1 ± 18.2 mmHg) did not differ between sexes (all P ≥ 0.18). Women were older (72.9 ± 13.0 vs. 70.1 ± 11.8 years) and had more hypertension (75% vs. 70%; P = 0.0005) and less coronary artery disease (38% vs. 55%, P < 0.0001) compared to men. After inverse-propensity weighting (IPW), female sex was associated with higher mortality (IPW-HR: 1.91 [1.14–3.22]; P = 0.01) and less referral to valve intervention (competitive model IPW-HR: 0.88 [0.82–0.96]; P = 0.007) in the whole cohort. This excess mortality in women was blunted in concordant non-severe AS initially treated conservatively (IPW-HR = 1.03 [0.63–1.68]; P = 0.88) or in concordant severe AS initially treated by valve intervention (IPW-HR = 1.25 [0.71–2.21]; P = 0.43). Interestingly, the excess mortality in women was observed in discordant low-gradient AS patients (IPW-HR = 2.17 [1.19–3.95]; P = 0.01) where women were less referred to valve intervention (IPW-Sub-HR: 0.83 [0.73–0.95]; P = 0.009).

Conclusion

In this large series of patients, despite similar baseline hemodynamic AS severity, women were less referred to AVR and had higher mortality. This seemed mostly to occur in the patient subset with discordant markers of AS severity (i.e. low-gradient AS) where women were less referred to AVR.
Comprehensive catalogue of international measures aimed at preventing general practitioner shortages
Authors: Stigler Florian L , Zipp Carolin R , Jeitler Klaus , Semlitsch Thomas , Siebenhofer Andrea
Published: April 2021

Background

Many countries are facing a shortage and misallocation of general practitioners (GPs). The development of a policy response may benefit from the knowledge of worldwide policies that have been adopted and recommended to counteract such a development.

Aim

To identify measures proposed or taken internationally to prevent GP shortages.

Design and Setting

A literature review followed by an expert assessment focussed on sources from OECD countries.

Method

The literature search identified international policy documents and literature reviews in bibliographical databases, and examined institutional websites and references of included publications. The internet search engine Google was also used. The resulting measures were then assessed for completeness by three experts.

Results

Ten policy documents and 32 literature reviews provided information on 102 distinct measures aimed at preventing GP shortages. The measures attempt to influence GPs at all stages of their careers.

Conclusions

This catalogue of measures to prevent GP shortages is significantly more comprehensive than any of the policy documents it is based on. It may serve as a blueprint for effective reforms aimed at preventing GP shortages internationally.
The GBP1 microcapsule interferes with IcsA-dependent septin cage assembly around Shigella flexneri
Authors: Kutsch Miriam , González-Prieto Coral , Lesser Cammie F , Coers Jörn
Published: April 2021

Many cytosolic bacterial pathogens hijack the host actin polymerization machinery to form actin tails that promote direct cell-to-cell spread, enabling these pathogens to avoid extracellular immune defenses. However, these pathogens are still susceptible to intracellular cell-autonomous immune responses that restrict bacterial actin-based motility. Two classes of cytosolic antimotility factors, septins and guanylate-binding proteins (GBPs), have recently been established to block actin tail formation by the human-adapted bacterial pathogen Shigella flexneri. Both septin cages and GBP1 microcapsules restrict S. flexneri cell-to-cell spread by blocking S. flexneri actin-based motility. While septins assemble into cage-like structures around immobile S. flexneri, GBP1 forms microcapsules around both motile and immobile bacteria. The interplay between these two defense programs remains elusive. Here, we demonstrate that GBP1 microcapsules block septin cage assembly, likely by interfering with the function of S. flexneri IcsA, the outer membrane protein that promotes actin-based motility, as this protein is required for septin cage formation. However, S. flexneri that escape from GBP1 microcapsules via the activity of IpaH9.8, a type III secreted effector that promotes the degradation of GBPs, are often captured within septin cages. Thus, our studies reveal how septin cages and GBP1 microcapsules represent complementary host cell antimotility strategies.
Novel Approaches to Develop Critical Reference Materials for Noninvasive Prenatal Testing: A Pilot Study
Authors: Bianco Katherine , Sherwin Elizabeth B , Konigshofer Yves , Girsen Anna I , Sylvester Karl G , Garlick Russell K
Published: April 2021

Background

Highly characterized reference materials are required to expand noninvasive prenatal testing (NIPT) for low incidence aneuploidies and microdeletions. The goal of this study was to develop reference materials for the development of next generation circulating cell-free DNA (ccfDNA) assays.

Methods

This was a prospective study of pregnancies complicated by positive prenatal genetic screening. ccfDNA was isolated from maternal plasma and amplified. Lymphoblastoid cell lines were prepared from maternal peripheral blood mononuclear cells and fetal cord blood cells. Cells were Epstein-Barr virus immortalized and expanded. Amplified DNA and to a limited extent formulated lymphoblastoid-derived ccfDNA was tested in SNP-based and chromosome counting (CC) based massively parallel sequencing assays.

Results

Enrolled cases included fetuses with: T21 (2), T18 (1), T18-XXX (1), XYY (1), microdeletions (1), and euploid (2). Three lymphoblastoid cells lines were prepared. Genomic DNA was extracted from cell lines and fragmented to simulate ccfDNA. ccfDNA isolation yielded about 2000 usable genome equivalents of DNA for each case for amplification. Although the sonicated genomic DNA derived from lymphoblastoid cell lines did not yield results compatible with NIPT assays, when blinded, NIPT platforms correctly identified the amplified ccfDNA isolated from blood in the majority of cases.

Conclusions

This study showed that maternal blood samples from pregnancies complicated by common chromosomal abnormalities can be used to generate materials for the development and evaluation of NIPT assays.
ELISA Screens for Fentanyl in Urine Are Susceptible to False-Positives in High Concentration Methamphetamine Samples
Authors: Abbott Dustin L , Limoges Jennifer F , Virkler Kelly J , Tracy Seth J , Sarris Gregory G
Published: April 2021

Immunoassay techniques are commonly used for urine drug screening in forensic and clinical toxicology laboratories. While these techniques are excellent for the nonspecific detection of a wide variety of drug classes, their very nature renders them vulnerable to false negatives and false positives.The New York State Police Forensic Toxicology Laboratory investigated a trend of false-positive fentanyl urine drug screens and determined that urine methamphetamine levels greater than 40 μg/mL can cause a false-positive urine fentanyl screening result using the Neogen enzyme-linked immunosorbent assay kit at a 1 ng/mL fentanyl decision point.
Self-reported allergies correlate with a worse patient-reported outcome after hip arthroscopy: a matched control study
Authors: Swartwout Erica L , Feingold Jacob D , Wright-Chisem Joshua I , Apostolakos John M , Roberts Sacha A , Ranawat Anil S
Published: April 2021

Patient-reported outcome measures (PROMs) in patients with and without at least one self-reported allergy undergoing hip arthroscopy were compared. Data on 1434 cases were retrospectively reviewed, and 267 patients were identified with at least one self-reported allergy and randomly matched to a control group on a 1:2 ratio. Four PROMs [Modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), Hip Outcome Score-Sports (HOS-Sport) and 33-item International Hip Outcome Tool (iHOT-33)] were collected preoperatively, and at 5–11, 12–23 and 24–35 months postoperatively. Significant PROM differences were found 5–11 months postoperative on mHHS (P < 0.001), HOS-ADL (P = 0.002), HOS-Sport (P < 0.001) and iHOT-33 (P < 0.001). At 12–23 months postoperative, the allergy cohort had significantly worse scores on mHHS (P = 0.002), HOS-ADL (P = 0.001), HOS-Sport (P < 0.001) and iHOT-33 (P < 0.001). They also had significantly worse measures 24–35 months postoperative on mHHS (P = 0.019), HOS-Sport (P = 0.006) and iHOT-33 (P < 0.001). Multivariable logistic regression showed that each additional allergy reported significantly increased the risk of failing to meet the minimal clinically important difference 5–11 months after surgery on mHHS by 1.15 [OR (95% CI): 1.15 (1.03, 1.30), P = 0.014], on HOS-ADL by 1.16 [OR (95% CI): 1.16 (1.02, 1.31), P = 0.021] and on iHOT-33 by 1.20 [OR (95% CI): 1.20 (1.07, 1.36), P = 0.002]. Results suggest self-reported allergies increase the likelihood of a patient-perceived worse outcome after hip arthroscopy. An understanding of this association by the physician is essential during presurgical planning and in the management of postoperative care.
Coherence scale of magnetic fields generated in early-time forward shocks of GRBs
Authors: Jordana-Mitjans N , Mundell C G , Smith R J , Guidorzi C , Marongiu M , Kobayashi S , Gomboc A , Shrestha M , Steele I A
Published: April 2021

We report the earliest ever detection of optical polarization from a GRB forward shock (GRB 141220A), measured $129.5{-}204.3\,$s after the burst using the multicolour RINGO3 optical polarimeter on the 2-m fully autonomous robotic Liverpool Telescope. The temporal decay gradient of the optical light curves from $86\,$ to $\sim 2200\,$s post-burst is typical of classical forward shocks with α = 1.091 ± 0.008. The low-optical polarization $P_{ BV} = 2.8 _{- 1.6} ^{+ 2.0} \, {{\ \rm per\ cent}}$ (2σ) at mean time $\sim 168\,$s post-burst is compatible with being induced by the host galaxy dust ($A_{V, {\rm HG}}= 0.71 \pm 0.15 \,$mag), leaving low polarization intrinsic to the GRB emission itself – as theoretically predicted for forward shocks and consistent with previous detections of low degrees of optical polarization in GRB afterglows observed hours to days after the burst. The current sample of early-time polarization data from forward shocks suggests polarization from (a) the Galactic and host galaxy dust properties (i.e. $P \sim 1-3{{\ \rm per\ cent}}$), (b) contribution from a polarized reverse shock (GRB deceleration time, jet magnetization) or (c) forward shock intrinsic polarization (i.e. $P \le 2{{\ \rm per\ cent}}$), which depends on the magnetic field coherence length-scale and the size of the observable emitting region (burst energetics, circumburst density).
Building the Galilean moons system via pebble accretion and migration: a primordial resonant chain
Authors: Madeira Gustavo , Izidoro André , Giuliatti Winter Silvia M
Published: April 2021

The origins of the Galilean satellites – namely Io, Europa, Ganymede, and Callisto – is not fully understood yet. Here we use N-body numerical simulations to study the formation of Galilean satellites in a gaseous circumplanetary disc around Jupiter. Our model includes the effects of pebble accretion, gas-driven migration, and gas tidal damping and drag. Satellitesimals in our simulations first grow via pebble accretion and start to migrate inwards. When they reach the trap at the disc inner edge, scattering events and collisions take place promoting additional growth. Growing satellites eventually reach a multiresonant configuration anchored at the disc inner edge. Our results show that an integrated pebble flux of ≥2 × 10−3 MJ results in the formation of satellites with masses typically larger than those of the Galilean satellites. Our best match to the masses of the Galilean satellites is produced in simulations where the integrated pebble flux is ∼10−3 MJ. These simulations typically produce between three and five satellites. In our best analogues, adjacent satellite pairs are all locked in 2:1 mean motion resonances. However, they have also moderately eccentric orbits (∼0.1), unlike the current real satellites. We propose that the Galilean satellites system is a primordial resonant chain, similar to exoplanet systems as TRAPPIST-1, Kepler-223, and TOI-178. Callisto was probably in resonance with Ganymede in the past but left this configuration – without breaking the Laplacian resonance – via divergent migration due to tidal planet–satellite interactions. These same effects further damped the orbital eccentricities of these satellites down to their current values (∼0.001). Our results support the hypothesis that Io and Europa were born with water-ice rich compositions and lost all/most of their water afterwards. Firmer constraints on the primordial compositions of the Galilean satellites are crucial to distinguish formation models.
The AGNIFS survey: distribution and excitation of the hot molecular and ionized gas in the inner kpc of nearby AGN hosts
Authors: Riffel R A , Storchi-Bergmann T , Riffel R , Bianchin M , Zakamska N L , Ruschel-Dutra D , Schönell A J , Rosario D J , Rodriguez-Ardila A , Fischer T C , Davies R I , Dametto N Z , Dahmer-Hahn L G , Crenshaw D M , Burtscher L , Bentz M C
Published: April 2021

We use the Gemini NIFS instrument to map the H$_2\, 2.1218\, \mu$m and Brγ flux distributions in the inner 0.04–2 kpc of a sample of 36 nearby active galaxies (0.001 ≲ z ≲ 0.056) at spatial resolutions from 4 to 250 pc. We find extended emission in 34 galaxies. In ∼55 per cent of them, the emission in both lines is most extended along the galaxy major axis, while in the other 45 per cent the extent follows a distinct orientation. The emission of H2 is less concentrated than that of Brγ, presenting a radius that contains half of the flux 60 per cent greater, on average. The H2 emission is driven by thermal processes – X-ray heating and shocks – at most locations for all galaxies, where $0.4\lt \rm H_2/Br\gamma \lt 6$. For regions where H2/Brγ > 6 (seen in 40 per cent of the galaxies), shocks are the main H2 excitation mechanism, while in regions with H2/Brγ < 0.4 (25 per cent of the sample) the H2 emission is produced by fluorescence. The only difference we found between type 1 and type 2 active galactic nucleus (AGN) was in the nuclear emission-line equivalent widths that are smaller in type 1 than in type 2 due to a larger contribution to the continuum from the hot dusty torus in the former. The gas masses in the inner 125 pc radius are in the range 101−104 M⊙ for the hot H2 and 103−106 M⊙ for the ionized gas and would be enough to power the AGN in our sample for 105−108 yr at their current accretion rates.
Histone deacetylases control lysine acetylation of ribosomal proteins in rice
Authors: Xu Qiutao , Liu Qian , Chen Zhengting , Yue Yaping , Liu Yuan , Zhao Yu , Zhou Dao-Xiu
Published: April 2021

Lysine acetylation (Kac) is well known to occur in histones for chromatin function and epigenetic regulation. In addition to histones, Kac is also detected in a large number of proteins with diverse biological functions. However, Kac function and regulatory mechanism for most proteins are unclear. In this work, we studied mutation effects of rice genes encoding cytoplasm-localized histone deacetylases (HDAC) on protein acetylome and found that the HDAC protein HDA714 was a major deacetylase of the rice non-histone proteins including many ribosomal proteins (r-proteins) and translation factors that were extensively acetylated. HDA714 loss-of-function mutations increased Kac levels but reduced abundance of r-proteins. In vitro and in vivo experiments showed that HDA714 interacted with r-proteins and reduced their Kac. Substitutions of lysine by arginine (depleting Kac) in several r-proteins enhance, while mutations of lysine to glutamine (mimicking Kac) decrease their stability in transient expression system. Ribo-seq analysis revealed that the hda714 mutations resulted in increased ribosome stalling frequency. Collectively, the results uncover Kac as a functional posttranslational modification of r-proteins which is controlled by histone deacetylases, extending the role of Kac in gene expression to protein translational regulation.
Histone sumoylation and chromatin dynamics
Authors: Ryu Hong-Yeoul , Hochstrasser Mark
Published: April 2021

Chromatin structure and gene expression are dynamically controlled by post-translational modifications (PTMs) on histone proteins, including ubiquitylation, methylation, acetylation and small ubiquitin-like modifier (SUMO) conjugation. It was initially thought that histone sumoylation exclusively suppressed gene transcription, but recent advances in proteomics and genomics have uncovered its diverse functions in cotranscriptional processes, including chromatin remodeling, transcript elongation, and blocking cryptic initiation. Histone sumoylation is integral to complex signaling codes that prime additional histone PTMs as well as modifications of the RNA polymerase II carboxy-terminal domain (RNAPII-CTD) during transcription. In addition, sumoylation of histone variants is critical for the DNA double-strand break (DSB) response and for chromosome segregation during mitosis. This review describes recent findings on histone sumoylation and its coordination with other histone and RNAPII-CTD modifications in the regulation of chromatin dynamics.
An Analysis of Medicare Reimbursement for Neurosurgeon Office Visits: 2010 Compared to 2018
Authors: Harrington Maya T , Pollock Jordan R , Haglin Jack M , Richter Kent R , Patel Naresh P
Published: April 2021

BACKGROUND

Trends in Medicare billing and procedural reimbursement for outpatient office visits remain unclear within the field of neurosurgery.

OBJECTIVE

To analyze financial trends of neurosurgeon reimbursement for Medicare office visits in 2010 compared to 2018.

METHODS

The 2010 and 2018 physician/supplier files from the Centers for Medicare and Medicaid Services website were utilized. All payments submitted by neurosurgeons (provider ID 14) were included. Trends in office visit Current Procedural Terminology codes 99201 to 99205 and 99211 to 99215 were analyzed.

RESULTS

Neurosurgeons billed for 1 109 979 office visits (463 611 h) in 2010 and Medicare denied 63 704 payments (totaling $11 205 283). Neurosurgeons billed for 1 189 046 office visits (508 526 h) in 2018 and Medicare denied 57 048 payments (totaling $15 103 879). This is a 7.1% increase in total neurosurgery office visits billed to Medicare, 9.7% increase in total office hours, and 34.8% increase in the payment amounts denied over 8 yr. Furthermore, after adjusting for inflation, the average amount paid to physicians by Medicare decreased by 8.3% per office visit. Additionally, Medicare paid 36.1% of the total neurosurgeon submitted charge amount for all office visits in 2010 but paid only 27.8% in 2018 (−8.3%).

CONCLUSION

Neurosurgeons are performing more office visits and billing for more time with patients. Meanwhile, Medicare has been paying physicians less per office visit, denying higher amounts of payments and reimbursing a decreasing percentage of submitted charges for office visits. An understanding of these trends is necessary to ensure continued equity and quality access to neurosurgical care in the United States.
Clinical Features and Outcomes of Community-Acquired Pneumonia Caused by Haemophilus influenzae
Authors: Shoar Saeed , Centeno Fernando H , Musher Daniel M
Published: April 2021

Background

Long regarded as the second most common cause of community-acquired pneumonia (CAP), Haemophilus influenzae has recently been identified with almost equal frequency as pneumococcus in patients hospitalized for CAP. The literature lacks a detailed description of the presentation, clinical features, laboratory and radiologic findings, and outcomes in Haemophilus pneumonia.

Methods

During 2 prospective studies of patients hospitalized for CAP, we identified 33 patients with Haemophilus pneumonia. In order to provide context, we compared clinical findings in these patients with findings in 36 patients with pneumococcal pneumonia identified during the same period. We included and analyzed separately data from patients with viral coinfection. Patients with coinfection by other bacteria were excluded.

Results

Haemophilus pneumonia occurred in older adults who had underlying chronic lung disease, cardiac conditions, and alcohol use disorder, the same population at risk for pneumococcal pneumonia. However, in contrast to pneumococcal pneumonia, patients with Haemophilus pneumonia had less severe infection as shown by absence of septic shock on admission, less confusion, fewer cases of leukopenia or extreme leukocytosis, and no deaths at 30 days. Viral coinfection greatly increased the severity of Haemophilus, but not pneumococcal pneumonia.

Conclusions

We present the first thorough description of Haemophilus pneumonia, show that it is less severe than pneumococcal pneumonia, and document that viral coinfection greatly increases its severity. These distinctions are lost when the label CAP is liberally applied to all patients who come to the hospital from the community for pneumonia.
Striking Decrease of Enteroviral Meningitis in Children During the COVID-19 Pandemic
Authors: Stoffel Larissa , Agyeman Philipp K A , Keitel Kristina , Barbani Maria Teresa , Duppenthaler Andrea , Kopp Matthias V , Aebi Christoph
Published: April 2021

We report the unprecedented complete absence of pediatric enteroviral meningitis in 2020 in the area of Bern, Switzerland. Presumably an unintended effect of coronavirus disease 2019 public health measures, this finding highlights the potential of community-wide nonpharmaceutical interventions for controlling the circulation of a major pediatric pathogen, which is mainly transmitted by the fecal–oral route.
Prolonged SARS-CoV-2 Illness in a Patient Receiving Ocrelizumab for Multiple Sclerosis
Authors: Gibson Elena G , Pender Melissa , Angerbauer Michael , Cook Craig , Jones Barbara , Spivak Adam M , Spivak Emily S , Swaminathan Sankar
Published: April 2021

We describe a case of prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a patient receiving ocrelizumab for multiple sclerosis. Viral RNA shedding, signs, and symptoms persisted for 69 days with resolution after administration of convalescent plasma and antiviral therapy. This case suggests risk for persistent SARS-CoV-2 infection in patients treated with anti-CD-20 monoclonal antibodies and supports a role for humoral immunity in disease resolution.
E-learning to teach medical students about acute otitis media: A randomized controlled trial
Authors: Mousseau Sarah , Poitras Maude , Lapointe Annie , Nguyen Bich Hong , Hervouet-Zeiber Catherine , Gravel Jocelyn
Published: April 2021

Objectives

Acute otitis media (AOM) is extremely prevalent among children but its diagnosis remains challenging. Our primary objective was to measure the impact of an e-learning module on medical students’ accuracy in diagnosing paediatric AOM.

Methods

This randomized controlled trial was performed at a single tertiary care paediatric emergency department (ED). Medical students on their paediatric rotation were randomized to a locally developed e-learning module or a small-group lecture on AOM. They then had to examine at least 10 ears of patients at risk for AOM. The primary outcome was diagnostic accuracy and secondary outcomes included knowledge test scores and learning modality preference.

Results

Between May 2017 and September 2018, 201 medical students were randomized. Eighty-three evaluated at least 10 ears and were included in the primary analysis. Diagnostic accuracies (76.5% for the e-learning group versus 76.4% for the lecture group, difference of 0.1%; 95%CI: –6.2 to 6.4%) and post-test scores (difference of 0.5/20 points; 95%CI: –0.8 to 1.2/20 points) were similar between the groups. Sixty-two per cent of participants preferred the e-learning module to the lecture, while 15% had no preference.

Conclusions

Diagnostic accuracy for AOM was similar between students exposed to an e-learning module or a small-group lecture. E-learning was the preferred learning modality.
Genicular Nerve Radiofrequency Ablation for the Treatment of Painful Knee Osteoarthritis: Current Evidence and Future Directions
Authors: Conger Aaron , Gililland Jeremy , Anderson Lucas , Pelt Christopher E , Peters Christopher , McCormick Zachary L
Published: April 2021

Genicular nerve radiofrequency ablation (RFA) is increasingly being performed to treat chronic pain due to knee osteoarthritis (KOA). This narrative review provides a concise summary of the relevant neuroanatomy, randomized controlled trials, appropriate patient selection, and safety relating to genicular RFA. Cadaveric studies demonstrate significant variability in the location of the genicular nerves, which has stimulated debate about the ideal target locations for genicular RFA. Despite this, favorable outcomes have been observed in studies targeting only the superior medial genicular nerve, inferior medial genicular nerve, and superior lateral genicular nerve. Several randomized controlled trials demonstrate superiority of genicular RFA compared with intra-articular steroid, viscosupplementation, and oral analgesics. Genicular RFA of the superior medial genicular nerve, inferior medial genicular nerve, and superior lateral genicular nerve appears to be an effective treatment for painful KOA, but targeting additional sensory nerves may further improve treatment success. Although genicular RFA appears relatively safe on the basis of the available data, additional large-scale studies are needed to provide greater confidence.
Winding up the bloom clock—do sugar levels at senescence determine how trees respond to winter temperature?
Authors: Sperling Or , Zwieniecki Maciej A
Published: April 2021

Variable winter temperatures cause a year-to-year discrepancy in the phenology of deciduous trees. This implies that an intrinsic ‘winter clock’ synchronizes bloom with the progression of winter to spring. The carbohydrate–temperature (C–T) model established a mechanistic association between carbohydrate metabolism in dormant trees and hourly winter temperatures. Using historical winter temperature and bloom times of Prunus dulcis (Mill.) D. A. Webb (almond), Malus domestica L. (apple), Pistachia vera L. (pistachio) and Juglans regia L. (walnut) in California and Washington states, we parametrized species-specific metabolic parameters to the C–T model. There was a sound fit between actual and projected bloom dates with a deviation (root mean square error) of 4–7 days in all species. The parameterized model enabled us to study how the observed variability in soluble carbohydrate concentrations at senescence (SC0) could affect bloom time. The C–T model projected that low SC0 could advance, while high SC0 possibly delays, the bloom of the early blooming almond trees. In contrast, high SC0 would advance the bloom of apple, pistachio and walnut trees. These novel projections suggest that after experimental validation, SC0 could guide post-harvest farming applications that affect fall carbohydrate accumulation to mediate the effects of climate shifts.
Phylogenetics and phylogeography of red deer mtDNA lineages during the last 50 000 years in Eurasia
Authors: Doan Karolina , Niedziałkowska Magdalena , Stefaniak Krzysztof , Sykut Maciej , Jędrzejewska Bogumiła , Ratajczak-Skrzatek Urszula , Piotrowska Natalia , Ridush Bogdan , Zachos Frank E , Popović Danijela , Baca Mateusz , Mackiewicz Paweł , Kosintsev Pavel , Makowiecki Daniel , Charniauski Maxim , Boeskorov Gennady , Bondarev Alexey Anatolievich , Danila Gabriel , Kusak Josip , Rannamäe Eve , Saarma Urmas , Arakelyan Marine , Manaseryan Ninna , Krasnodębski Dariusz , Titov Vadim , Hulva Pavel , Bălășescu Adrian , Trantalidou Katerina , Dimitrijević Vesna , Shpansky Andrey , Kovalchuk Oleksandr , Klementiev Alexey M , Foronova Irina , Malikov Dmitriy G , Juras Anna , Nikolskiy Pavel , Grigoriev Semyon Egorovich , Cheprasov Maksim Yurievich , Novgorodov Gavril Petrovich , Sorokin Alexandr Dmitrievich , Wilczyński Jarosław , Protopopov Albert Vasilievich , Lipecki Grzegorz , Stanković Ana
Published: April 2021

The present phylogeographic pattern of red deer in Eurasia is not only a result of the contraction of their distribution range into glacial refugia and postglacial expansion, but probably also an effect of replacement of some red deer s.l. mtDNA lineages by others during the last 50 000 years. To better recognize this process, we analysed 501 sequences of mtDNA cytochrome b, including 194 ancient and 75 contemporary samples newly obtained for this study. The inclusion of 161 radiocarbon-dated samples enabled us to study the phylogeny in a temporal context and conduct divergence-time estimation and molecular dating. Depending on methodology, our estimate of divergence between Cervus elaphus and Cervus canadensis varied considerably (370 000 or 1.37 million years BP, respectively). The divergence times of genetic lineages and haplogroups corresponded to large environmental changes associated with stadials and interstadials of the Late Pleistocene. Due to the climatic oscillations, the distribution of C. elaphus and C. canadensis fluctuated in north–south and east–west directions. Some haplotypes dated to pre-Last Glacial Maximum periods were not detected afterwards, representing possibly extinct populations. We indicated with a high probability the presence of red deer sensu lato in south-eastern Europe and western Asia during the Last Glacial Maximum.
Assessment of Resistance to Cereal Cyst Nematode, Stripe Rust, and Powdery Mildew in Wheat-Thinopyrum intermedium Derivatives and Their Chromosome Composition
Authors: Cui Lei , Ren Yongkang , Bao Yinguang , Nan Hai , Tang Zhaohui , Guo Qing , Niu Yuqi , Yan Wenze , Sun Yu , Li Hongjie
Published: April 2021

Wide hybridization between wheat and wild relatives such as Thinopyrum intermedium is important for broadening genetic diversity and improving disease resistance in wheat. We developed 30 wheat-Th. intermedium derivatives. Here, we report assessments of their resistance to different pathogens including cereal cyst nematode (CCN; Heterodera spp.), Puccinia striiformis f. tritici Erikss. causing stripe rust, and Blumeria graminis f. tritici (DC.) Speer inciting powdery mildew. Under natural field infection, all the wheat-Th. intermedium lines were resistant to at least one of the pathogens, and four lines were resistant to multiple pathogens. Twenty-nine of 30 tested lines exhibited resistance to H. avenae, a dominant CCN species in wheat fields. Twenty-four lines were resistant to H. filipjevi, an emerging threat to wheat production. Tests of phenotypic responses in the naturally infected field nurseries identified six stripe rust-resistant lines and 13 powdery mildew-resistant lines. Mitotic observation demonstrated that these newly developed wheat-Th. intermedium derivatives included not only octoploid but also chromosome addition, substitution, and translocation lines. Chromosome compositions of the four lines resistant to multiple pathogens were analyzed by genomic in situ hybridization and fluorescence in situ hybridization. The octoploid lines Zhong 10-68 and Zhong 10-117 carried both intact Th. intermedium chromosomes and translocated chromosomes. Line Zhong 10-149 had 42 wheat chromosomes and two wheat ditelosomes plus a pair of T3BS·J translocated chromosomes. Line Zhong 10-160 carried 41 wheat chromosomes plus one pair of the J genome chromosomes of Th. intermedium. The multiple disease-resistant wheat-Th. intermedium derivatives, especially lines with chromosome counts close to that of common wheat, provide valuable materials for wheat resistance breeding programs.
Evaluation of the Prevalence of Psychiatric Readmission and Associated Factors in Shafa Psychiatric Hospital in Rasht During 2017-2019
Authors: Najafi Kiomars , Siahkoucheh Adel Yousefi , Siahkoucheh Adeleh Yousefi , Bayat Mohsen , Didar Fardad , Naeim Mahdi
Published: April 2021

Background:

Hospital readmission is one of the important priorities of health systems due to its impact on the cost and quality of hospital care and imposing an additional burden on the health system. Complications are much more severe in patients who are readmitted to the hospital, with high mortality, increased length of stay, and a 25% increase in medical costs.

Objective:

This study aimed to evaluate the prevalence of psychiatric readmission and associated factors in Shafa Psychiatric Hospital in Rasht during the years 2017-2019.

Methods:

The research method is descriptive-analytical and applied in terms of results. The statistical population of this study consisted of all patients admitted to Shafa Hospital of Rasht during 2017-2019. Sampling method: This study was a convenience sampling with a sample size of 196 people. Data were entered into SPSS 24 software. Descriptive data were expressed as mean, SD, frequency (percentage of frequency). Binomial and χ2 tests were also used to compare the frequency of the 2 groups in a population.

Results:

The results of this study showed that having a criminal record significantly increases the frequency of readmission, involuntary hospitalization, being single, and not having a readmission risk job.

Conclusion:

On the basis of the results, it is suggested that the follow-up of patients and providing hospitalization for emotional support and recommendation for appropriate medication can be helpful and reduce the rate of readmission.
Conversion to Resectability Using Transarterial Chemoembolization Combined With Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatocellular Carcinoma
Authors: Li Binkui , Qiu Jiliang , Zheng Yun , Shi Yunxing , Zou Ruhai , He Wei , Yuan Yichuang , Zhang Yuanping , Wang Chenwei , Qiu Zhiyu , Li Kai , Zhong Chengrui , Yuan Yunfei
Published: April 2021

Objective:

To evaluate whether this conversion rate to resectability could be increased when patients are treated with transarterial chemoembolization and hepatic arterial infusion chemotherapy (TACE-HAIC) using oxaliplatin plus fluorouracil/leucovorin.

Background:

Conventional TACE (c-TACE) is a common regimen for initially unresectable hepatocellular carcinoma (HCC), which converts to curative-intent resection in about 10% of those patients. It is urgent need to investigated better regimen for those patients.

Methods:

The data of 83 initially unresectable HCC patients were examined, including 41 patients in the TACE-HAIC group and 42 patients in the c-TACE group. Their response rate, conversion rate to resection, survival outcome, and adverse events were compared.

Results:

The conversion rate was significantly better in the TACE-HAIC group than in the c-TACE group (48.8% vs 9.5%; P < 0.001). The TACE-HAIC had marginal superiority in overall response rate as compared to c-TACE (14.6% vs 2.4%; P = 0.107 [RECIST]; 65.9% vs 16.7%; P < 0.001 [mRECIST], respectively). The median progression-free survival was not available and 9.2 months for the TACE-HAIC and cTACE groups, respectively (hazard rate [HR]: 0.38; 95% confidence interval [CI], 0.20–0.70; P = 0.003). The median overall survival was not available and 13.5 months for the TACE-HAIC and c-TACE groups, respectively (HR, 0.63; 95% CI, 0.34–1.17; P = 0.132). The 2 groups had similar rates of grade 3/4 adverse events (all P > 0.05).

Conclusions:

TACE-HAIC demonstrated a higher conversion rate and progression-free survival benefit than c-TACE and could be considered as a more effective regimen for patients with initially unresectable HCC. Future prospective randomized trials are needed to confirm it.
Percutaneous Dilational Tracheostomy for Coronavirus Disease 2019 Patients Requiring Mechanical Ventilation*
Authors: Angel Luis F. , Amoroso Nancy E. , Rafeq Samaan , Mitzman Brian , Goldenberg Ronald , Shekar Saketh Palasamudram , Troxel Andrea B. , Zhang Yan , Chang Stephanie H , Kwak Paul , Amin Milan R. , Sureau Kimberly , Nafday Heidi B. , Thomas Sarun , Kon Zachary , Sommer Philip M. , Segal Leopoldo N. , Moore William H. , Cerfolio Robert
Published: April 2021

OBJECTIVES:

To assess the impact of percutaneous dilational tracheostomy in coronavirus disease 2019 patients requiring mechanical ventilation and the risk for healthcare providers.

DESIGN:

Prospective cohort study; patients were enrolled between March 11, and April 29, 2020. The date of final follow-up was July 30, 2020. We used a propensity score matching approach to compare outcomes. Study outcomes were formulated before data collection and analysis.

SETTING:

Critical care units at two large metropolitan hospitals in New York City.

PATIENTS:

Five-hundred forty-one patients with confirmed severe coronavirus disease 2019 respiratory failure requiring mechanical ventilation.

INTERVENTIONS:

Bedside percutaneous dilational tracheostomy with modified visualization and ventilation.

MEASUREMENTS AND MAIN RESULTS:

Required time for discontinuation off mechanical ventilation, total length of hospitalization, and overall patient survival. Of the 541 patients, 394 patients were eligible for a tracheostomy. One-hundred sixteen were early percutaneous dilational tracheostomies with median time of 9 days after initiation of mechanical ventilation (interquartile range, 7–12 d), whereas 89 were late percutaneous dilational tracheostomies with a median time of 19 days after initiation of mechanical ventilation (interquartile range, 16–24 d). Compared with patients with no tracheostomy, patients with an early percutaneous dilational tracheostomy had a higher probability of discontinuation from mechanical ventilation (absolute difference, 30%; p < 0.001; hazard ratio for successful discontinuation, 2.8; 95% CI, 1.34–5.84; p = 0.006) and a lower mortality (absolute difference, 34%, p < 0.001; hazard ratio for death, 0.11; 95% CI, 0.06–0.22; p < 0.001). Compared with patients with late percutaneous dilational tracheostomy, patients with early percutaneous dilational tracheostomy had higher discontinuation rates from mechanical ventilation (absolute difference 7%; p < 0.35; hazard ratio for successful discontinuation, 1.53; 95% CI, 1.01–2.3; p = 0.04) and had a shorter median duration of mechanical ventilation in survivors (absolute difference, –15 d; p < 0.001). None of the healthcare providers who performed all the percutaneous dilational tracheostomies procedures had clinical symptoms or any positive laboratory test for severe acute respiratory syndrome coronavirus 2 infection.

CONCLUSIONS:

In coronavirus disease 2019 patients on mechanical ventilation, an early modified percutaneous dilational tracheostomy was safe for patients and healthcare providers and associated with improved clinical outcomes.
Wide-awake Surgery for Congenital Thumb Flexion Anomaly in a Child
Authors: Zukawa Mineyuki , Osada Ryusuke , Inagaki Miku , Hirokawa Tatsurou , Kwaguchi Yoshiharu
Published: April 2021

We report a rare case of absent thumb IP joint flexion in bilateral thumbs due to anomalous tendon slips of the flexor pollicis longus. Cutting the anomalous insertions failed to improve active flexion of the IP joints. Successful treatment was achieved by evaluating the musculotendinous units of the original flexor pollicis longus and the anomalous flexor pollicis longus tendon during a wide-awake surgery.
Application of FACE-Q and NOSE in Nasal Reconstruction with Paramedian Frontal Flap after Skin Cancer Resection
Authors: Pagotto Vitor Penteado Figueiredo , Tutihashi Rafael Mamoru Carneiro , Ribeiro Renan Diego Americo , Takahashi Giulia Godoy , Camargo Cristina Pires , Busnardo Fábio de Freitas , Gemperli Rolf
Published: April 2021

Introduction:

Nonmelanoma skin cancer (NMSC) is responsible for high morbidity and mortality, resulting in a high cost to the health system. The nose is the leading region affected by this type of tumor and may need reconstruction by tissue transfer. The paramedian forehead flap (PFF) is one of the main options used, and the factors that influence the result should be studied. The FACE-Q questionnaire allows the assessment of appearance, quality of life, and side effects related to the procedure, whereas the Nasal Obstruction Symptom Evaluation questionnaire enables the nose function evaluation.

Methods:

This study evaluates nasal reconstruction with a PFF after resection of NMSC with the FACE-Q questionnaire and Nasal Obstruction Symptom Evaluation. Spearman Rank correlation coefficient tests between the questionnaire results and patients' characteristics were performed.

Results:

The questionnaires were completely answered by 49 patients who underwent this reconstruction between 2011 and 2019 in a cancer center. The patients’ evaluations demonstrate high satisfaction with appearance, quality of life, side effects, and function. Completing reconstruction under 6 months was associated with a higher quality of life among patients (P = 0.002). Reconstruction of lining or scaffold, moment of flap division, complications, and number of operations did not show an association.

Conclusion:

This study suggests that the PFF is a reliable option for nasal reconstruction. Identifying the total reconstruction time as an impact factor on patients’ quality of life should be considered when planning treatment.