bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring ultralarge scale effects in the presence of 21 cm intensity mapping foregrounds
Authors: Fonseca José , Liguori Michele
Published: March 2021

H i intensity mapping will provide maps of the large-scale distribution of neutral hydrogen (H i) in the universe. These are prime candidates to be used to constrain primordial non-Gaussianity using the large-scale structure of the Universe as well as to provide further tests of Einstein’s theory of Gravity (GR). But H i maps are contaminated by foregrounds, which can be several orders of magnitude above the cosmological signal. Here we quantify how degenerated are the large-scale effects (fNL and GR effects) with the residual foregrounds. We conclude that a joint analysis does not provide a catastrophic degradation of constraints and provides a framework to determine the marginal errors of large scale-effects in the presence of foregrounds. Similarly, we conclude that the macroscopical properties of the foregrounds can be measured with high precision. Notwithstanding, such results are highly dependent on accurate forward modelling of the foregrounds, which incorrectly done catastrophically bias the best-fitting values of cosmological parameters, foreground parametrizations, and large-scale effects.
Metals and a search for molecules in the distant Universe: Magellan mike observations of sub-DLAs at 2 < z < 3
Authors: Poudel Suraj , Kulkarni Varsha P , Som Debopam , Péroux Céline
Published: March 2021

We present abundance measurements of the elements Zn, S, O, C, Si, and Fe for four sub-DLAs at redshifts ranging from z = 2.173 to 2.635 using observations from the MIKE spectrograph on the Magellan telescope to constrain the chemical enrichment and star formation of gas-rich galaxies. Using weakly depleted elements O, S, and or Zn, we find the metallicities after the photoionization corrections to be [S/H] = −0.50 ± 0.11, [O/H] > −0.84, [O/H] = −1.27 ± 0.12, and [Zn/H]  = +0.40 ± 0.12 for the absorbers at z  = 2.173, 2.236, 2.539, and 2.635, respectively. Moreover, we are able to put constraints on the electron densities using the fine structure lines of C ii⋆ and Si ii⋆ for two of the sub-DLAs. We find that these values are much higher than the median values found in DLAs in the literature. Furthermore, we estimate the cooling rate lc = 1.20 × 10−26 erg s−1 per H atom for an absorber at z = 2.173, suggesting higher star formation rate density in this sub-DLA than the typical star formation rate density for DLAs at similar redshifts. We also study the metallicity versus velocity dispersion relation for our absorbers. Most of the absorbers follow the trend one can expect from the mass versus metallicity relation for sub-DLAs in the literature. Finally, we are able to put limits on the molecular column density from the non-detections of various strong lines of CO molecules. We estimate 3σ upper limits of logN(CO, J = 0) < 13.87, logN(CO, J = 0) < 13.17, and logN(CO, J = 0) < 13.08, respectively, from the non-detections of absorption from the J = 0 level in the CO AX 0–0, 1–0, and 2–0 bands near 1544, 1510, and 1478 Å.
Using Pantheon and DES supernova, baryon acoustic oscillation, and Hubble parameter data to constrain the Hubble constant, dark energy dynamics, and spatial curvature
Authors: Cao Shulei , Ryan Joseph , Ratra Bharat
Published: March 2021

We use Pantheon Type Ia supernova (SN Ia) apparent magnitude, DES-3 yr binned SN Ia apparent magnitude, Hubble parameter, and baryon acoustic oscillation measurements to constrain six spatially flat and non-flat cosmological models. These sets of data provide mutually consistent cosmological constraints in the six cosmological models we study. A joint analysis of these data sets provides model-independent estimates of the Hubble constant, $H_0=68.8\pm 1.8\ \rm {km \, s^{-1} \ Mpc^{-1}}$, and the non-relativistic matter density parameter, $\Omega _{\rm m_0}=0.294\pm 0.020$. Although the joint constraints prefer mild dark energy dynamics and a little spatial curvature, they do not rule out dark energy being a cosmological constant and flat spatial hypersurfaces. We also add quasar angular size and H ii starburst galaxy measurements to the combined data set and find more restrictive constraints.
Impact of high fat diet on the sterol regulatory element-binding protein 2 cholesterol pathway in the testicle
Authors: Funes Abi K , Simón Layla , Colombo Regina , Avena María Virginia , Monclús María , Crescitelli Julieta , Cabrillana María E , Conte María Inés , Cayado Niubys , Boarelli Paola , Fornés Miguel W , Saez Lancellotti Tania E
Published: March 2021

Male fertility has been shown to be dependent on cholesterol homeostasis. This lipid is essential for testosterone synthesis and spermatogenesis, but its levels must be maintained in an optimal range for proper testicular function. In particular, sperm cells’ development is very sensitive to high cholesterol levels, noticeably during acrosomal formation. The aim of this work was to study whether the molecular pathway that regulates intracellular cholesterol, the sterol regulatory element-binding protein (SREBP) pathway, is affected in the testicles of animals under a fat diet. To investigate this, we took advantage of the non-obese hypercholesterolemia (HC) model in New Zealand rabbits that displays poor sperm and seminal quality. The testicular expression of SREBP isoform 2 (SREBP2) and its target molecules 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and low-density lipoprotein receptor (LDLR) were studied under acute (6 months) and chronic (more than 12 months) fat intake by RT–PCR, western blot and immunofluorescence. Our findings showed that fat consumption promoted down-regulation of the SREBP2 pathway in the testicle at 6 months, but upregulation after a chronic period. This was consistent with load of testicular cholesterol, assessed by filipin staining. In conclusion, the intracellular pathway that regulates cholesterol levels in the testicle is sensitive to dietary fats, and behaves differently depending on the duration of consumption: it has a short-term protective effect, but became deregulated in the long term, ultimately leading to a detrimental situation. These results will contribute to the understanding of the basic mechanisms of the effect of fat consumption in humans with idiopathic infertility.
Water structure around a left-handed Z-DNA fragment analyzed by cryo neutron crystallography
Authors: Harp Joel M , Coates Leighton , Sullivan Brendan , Egli Martin
Published: March 2021

Even in high-quality X-ray crystal structures of oligonucleotides determined at a resolution of 1 Å or higher, the orientations of first-shell water molecules remain unclear. We used cryo neutron crystallography to gain insight into the H-bonding patterns of water molecules around the left-handed Z-DNA duplex [d(CGCGCG)]2. The neutron density visualized at 1.5 Å resolution for the first time allows us to pinpoint the orientations of most of the water molecules directly contacting the DNA and of many second-shell waters. In particular, H-bond acceptor and donor patterns for water participating in prominent hydration motifs inside the minor groove, on the convex surface or bridging nucleobase and phosphate oxygen atoms are finally revealed. Several water molecules display entirely unexpected orientations. For example, a water molecule located at H-bonding distance from O6 keto oxygen atoms of two adjacent guanines directs both its deuterium atoms away from the keto groups. Exocyclic amino groups of guanine (N2) and cytosine (N4) unexpectedly stabilize waters H-bonded to O2 keto oxygens from adjacent cytosines and O6 keto oxygens from adjacent guanines, respectively. Our structure offers the most detailed view to date of DNA solvation in the solid-state undistorted by metal ions or polyamines.
eIF4E3 forms an active eIF4F complex during stresses (eIF4FS) targeting mTOR and re-programs the translatome
Authors: Weiss Benjamin , Allen George Edward , Kloehn Joachim , Abid Karim , Jaquier-Gubler Pascale , Curran Joseph Alphonsus
Published: March 2021

The eIF4E are a family of initiation factors that bind the mRNA 5′ cap, regulating the proteome and the cellular phenotype. eIF4E1 mediates global translation and its activity is controlled via the PI3K/AKT/mTOR pathway. mTOR down-regulation results in eIF4E1 sequestration into an inactive complex with the 4E binding proteins (4EBPs). The second member, eIF4E2, regulates the translatome during hypoxia. However, the exact function of the third member, eIF4E3, has remained elusive. We have dissected its function using a range of techniques. Starting from the observation that it does not interact with 4EBP1, we demonstrate that eIF4E3 recruitment into an eIF4F complex occurs when Torin1 inhibits the mTOR pathway. Ribo-seq studies demonstrate that this complex (eIF4FS) is translationally active during stress and that it selects specific mRNA populations based on 5′ TL (UTR) length. The interactome reveals that it associates with cellular proteins beyond the cognate initiation factors, suggesting that it may have ‘moon-lighting’ functions. Finally, we provide evidence that cellular metabolism is altered in an eIF4E3 KO background but only upon Torin1 treatment. We propose that eIF4E3 acts as a second branch of the integrated stress response, re-programming the translatome to promote ‘stress resistance’ and adaptation.
Temozolomide-induced hypermutation is associated with distant recurrence and reduced survival after high-grade transformation of low-grade IDH-mutant gliomas
Authors: Yu Yao , Villanueva-Meyer Javier , Grimmer Matthew R , Hilz Stephanie , Solomon David A , Choi Serah , Wahl Michael , Mazor Tali , Hong Chibo , Shai Anny , Phillips Joanna J , Wainer Bruce H , McDermott Michael , Haas-Kogan Daphne , Taylor Jennie W , Butowski Nicholas , Clarke Jennifer L , Berger Mitchel S , Molinaro Annette M , Chang Susan M , Costello Joseph F , Oberheim Bush Nancy Ann
Published: March 2021

Background

Chemotherapy improves overall survival after surgery and radiotherapy for newly diagnosed high-risk IDH-mutant low-grade gliomas (LGGs), but a proportion of patients treated with temozolomide (TMZ) will develop recurrent tumors with TMZ-induced hypermutation. We aimed to determine the prevalence of TMZ-induced hypermutation at recurrence and prognostic implications.

Methods

We sequenced recurrent tumors from 82 patients with initially low-grade IDH-mutant gliomas who underwent reoperation and correlated hypermutation status with grade at recurrence and subsequent clinical outcomes.

Results

Hypermutation was associated with high-grade disease at the time of reoperation (OR 12.0 95% CI 2.5-115.5, P = .002) and was identified at transformation in 57% of recurrent LGGs previously exposed to TMZ. After anaplastic (grade III) transformation, hypermutation was associated with shorter survival on univariate and multivariate analysis (HR 3.4, 95% CI 1.2-9.9, P = .024), controlling for tumor grade, subtype, age, and prior radiotherapy. The effect of hypermutation on survival after transformation was validated in an independent, published dataset. Hypermutated (HM) tumors were more likely to develop discontiguous foci of disease in the brain and spine (P = .003). To estimate the overall incidence of high-grade transformation among low-grade IDH-mutant tumors, data from a phase II trial of TMZ for LGG were analyzed. Eight-year transformation-free survival was 53.8% (95% CI 42.8-69.2), and 61% of analyzed transformed cases were HM.

Conclusions

TMZ-induced hypermutation is a common event in transformed LGG previously treated with TMZ and is associated with worse prognosis and development of discontiguous disease after recurrence. These findings impact tumor classification at recurrence, prognostication, and clinical trial design.
The role of RB1 alteration and 4q12 amplification in IDH-WT glioblastoma
Authors: Dono Antonio , Ramesh Arvind V , Wang Emily , Shah Mauli , Tandon Nitin , Ballester Leomar Y , Esquenazi Yoshua
Published: March 2021

Background

Recent studies have identified that glioblastoma IDH-wildtype (GBM IDH-WT) might be comprised of molecular subgroups with distinct prognoses. Therefore, we investigated the correlation between genetic alterations and survival in 282 GBM IDH-WT patients, to identify subgroups with distinct outcomes.

Methods

We reviewed characteristics of GBM IDH-WT (2009–2019) patients analyzed by next-generation sequencing interrogating 205 genes and 26 rearrangements. Progression-free survival (PFS) and overall survival (OS) were evaluated with the log-rank test and Cox regression models. We validated our results utilizing data from cBioPortal (MSK-IMPACT dataset).

Results

Multivariable analysis of GBM IDH-WT revealed that treatment with chemoradiation and RB1-mutant status correlated with improved PFS (hazard ratio [HR] 0.25, P < .001 and HR 0.47, P = .002) and OS (HR 0.24, P < .001 and HR 0.49, P = .016). In addition, younger age (<55 years) was associated with improved OS. Karnofsky performance status less than 80 (HR 1.44, P = .024) and KDR amplification (HR 2.51, P = .008) were predictors of worse OS. KDR-amplified patients harbored coexisting PDGFRA and KIT amplification (P < .001) and TP53 mutations (P = .04). RB1-mutant patients had less frequent CDKN2A/B and EGFR alterations (P < .001). Conversely, RB1-mutant patients had more frequent TP53 (P < .001) and SETD2 (P = .006) mutations. Analysis of the MSK-IMPACT dataset (n = 551) validated the association between RB1 mutations and improved PFS (11.0 vs 8.7 months, P = .009) and OS (34.7 vs 21.7 months, P = .016).

Conclusions

RB1-mutant GBM IDH-WT is a molecular subgroup with improved PFS and OS. Meanwhile, 4q12 amplification (KDR/PDGFRA/KIT) denoted patients with worse OS. Identifying subgroups of GBM IDH-WT with distinct survival is important for optimal clinical trial design, incorporation of targeted therapies, and personalized neuro-oncological care.
Poppers, by Inducing HHV-8 Virion Production, Can Act as a Promoter for HHV-8 Transmission in Men Who Have Sex With Men
Authors: Jary Aude , Gothland Adélie , Palich Romain , Leducq Valentin , Monsel Gentiane , Imbert Sébastien , Schneider Luminita , Simon Anne , Spano Jean-Philippe , Katlama Christine , Larabi Islam Amine , Alvarez Jean-Claude , Calvez Vincent , Marcelin Anne-Geneviève
Published: March 2021

Environmental factors were reported to increase the risk of human herpesvirus 8 (HHV-8) transmission. In a population of men who have sex with men (MSM), we found evidence that chemsex was associated with human herpesvirus 8 seropositivity in vivo and that poppers induced HHV-8 virion production in vitro. Our finding may explain the higher HHV-8 transmission in MSM.
Drought affects the rate and duration of organ growth but not inter-organ growth coordination
Authors: Verbraeken Lennart , Wuyts Nathalie , Mertens Stien , Cannoot Bernard , Maleux Katrien , Demuynck Kirin , De Block Jolien , Merchie Julie , Dhondt Stijn , Bonaventure Gustavo , Crafts-Brandner Steven , Vogel Jonathan , Bruce Wesley , Inzé Dirk , Maere Steven , Nelissen Hilde
Published: March 2021

Drought at flowering and grain filling greatly reduces maize (Zea mays) yield. Climate change is causing earlier and longer-lasting periods of drought, which affect the growth of multiple maize organs throughout development. To study how long periods of water deficit impact the dynamic nature of growth, and to determine how these relate to reproductive drought, we employed a high-throughput phenotyping platform featuring precise irrigation, imaging systems, and image-based biomass estimations. Prolonged drought resulted in a reduction of growth rate of individual organs—though an extension of growth duration partially compensated for this—culminating in lower biomass and delayed flowering. However, long periods of drought did not affect the highly organized succession of maximal growth rates of the distinct organs, i.e. leaves, stems, and ears. Two drought treatments negatively affected distinct seed yield components: Prolonged drought mainly reduced the number of spikelets, and drought during the reproductive period increased the anthesis-silking interval. The identification of these divergent biomass and yield components, which were affected by the shift in duration and intensity of drought, will facilitate trait-specific breeding toward future climate-resilient crops.
Reliability of Quadriceps Femoris Muscle Strength Assessment Using a Portable Dynamometer and Protocol Tolerance in Patients With Chronic Obstructive Pulmonary Disease
Authors: Sentanin Anna Claudia , de Facio Carina Araujo , da Silva Marcela Maria Carvalho , Sousa Fernanda Cristina , Arcuri Juliano Ferreira , Mendes Renata Gonçalves , Di Lorenzo Valéria Amorim Pires
Published: March 2021

Objective

This study aimed to evaluate the intrarater and interrater reliability of isometric quadriceps strength (IQS) using a portable dynamometer in individuals with chronic obstructive pulmonary disease (COPD) and to verify their tolerance to the protocol.

Methods

A cross-sectional reliability study was conducted with 50 individuals with stable COPD (34 men and 16 women; mean age = 70 years [SD = 8]). The main outcome measure was obtained using a portable dynamometer (Microfet 2) to assess IQS. Two masked raters performed 2 assessments in the dominant lower limb on 2 nonconsecutive days. The intraclass correlation coefficient (ICC) was used to verify the intrarater and interrater reliability and was considered excellent when >0.90, with a 5% significance level.

Results

Rater 1 and 2 intrarater reliability was as follows: ICC = 0.96 (95% CI = 0.94 to 0.98) and ICC = 0.97 (95% CI = 0.95 to 0.98), respectively. The interrater reliability was as follows: ICC = 0.96 (95% CI = 0.93 to 0.98). The minimum detectable difference was 4 to 5 peak isometric strength, in mean, for intrarater and interrater reliability. Not all patients presented relevant changes in physiological responses, dyspnea, and lower limb fatigue.

Conclusion

There was an excellent intrarater and interrater reliability for IQS, and the participants tolerated the protocol.

Impact

This tool can be used to assess quadriceps strength in clinical practice in patients with COPD.
Pulmonary involvement in primary systemic vasculitides
Authors: Makhzoum Jean-Paul , Grayson Peter C , Ponte Cristina , Robson Joanna , Suppiah Ravi , Watts Richard A , Luqmani Raashid , Merkel Peter A , Pagnoux Christian ,   for the DCVAS Collaborators
Published: March 2021

Objectives

This study describes the spectrum and initial impact of pulmonary manifestations in the primary systemic vasculitides.

Methods

Description and comparison of pulmonary manifestations in adults with Takayasu’s arteritis (TAK), GCA, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic GPA (EGPA), polyarteritis nodosa (PAN) and IgA vasculitis (IgAV), using data collected within the Diagnostic and Classification Criteria in Vasculitis study.

Results

Data from 1952 patients with primary vasculitides were included: 170 TAK, 657 GCA, 555 GPA, 223 MPA, 146 EGPA, 153 IgAV and 48 PAN. Pulmonary manifestations were observed in patients with TAK (21.8%), GCA (15.8%), GPA (64.5%), MPA (65.9%), EGPA (89.0%), PAN (27.1%) and IgAV (5.9%). Dyspnoea occurred in patients with TAK (14.7%), GCA (7.8%), GPA (41.8%), MPA (43.5%), EGPA (65.8%), PAN (18.8%) and IgAV (2.6%). Cough was reported in TAK (7.6%), GCA (9.3%), GPA (34.8%), MPA (37.7%), EGPA (55.5%), PAN (16.7%) and IgAV (3.3%). Haemoptysis occurred mainly in patients with ANCA-associated vasculitis (AAV). Fibrosis on imaging at diagnosis was documented in GPA (1.9%), MPA (24.9%) and EGPA (6.3%). Only patients with AAV (GPA 2.7%, MPA 2.7% and EGPA 3.4%) required mechanical ventilation. At 6 months, the presence of at least one pulmonary item in the Vasculitis Damage Index was observed in TAK (4.1%), GCA (3.3%), GPA (15.4%), MPA (28.7%), EGPA (52.7%), PAN (6.2%) and IgAV (1.3%).

Conclusion

Pulmonary manifestations can occur in all primary systemic vasculitides, but are more frequent and more often associated with permanent damage in AAV.
High Efficacy and Low Risk of Phytotoxicity of Sulfur in the Suppression of Strawberry Powdery Mildew
Authors: Onofre Rodrigo B. , Gadoury David M. , Peres Natalia A.
Published: March 2021

Sulfur is a multisite inhibitor of strawberry powdery mildew (Podosphaera aphanis) recommended for fungicide resistance management, yet growers may refrain from its use due to purported phytotoxicity under conditions often qualitatively defined as “hot”, or “during periods of high temperature”. Our objectives were to (i) determine phytotoxicity of sulfur on three strawberry cultivars treated in controlled environments at temperatures of 30, 35, and 40°C for periods of 1, 2, 4, and 8 h after the sulfur application; and (ii) evaluate phytotoxicity and efficacy of sulfur on strawberry grown in open fields and high tunnels in Florida. Under controlled conditions, cultivars Florida127 and Florida Beauty exhibited minor phytotoxicity when exposed to sulfur at 30°C for 2 to 8 h. Cultivar Florida Radiance, however, was more sensitive, with greater phytotoxicity as exposure time increased. We found that weekly applications of sulfur on cultivar Florida127 significantly reduced P. aphanis foliar and fruit disease as well as or better than the standard fungicide treatment, and resulted in 80 to 300% higher yields (compared with nontreated controls) in open field and high tunnel trials, respectively. Ambient temperature did not exceed 35°C in open field trials, where no phytotoxicity was observed. In the high tunnel, where only mild leaf phytotoxicity was observed, temperatures exceeded 40°C for a total of 20 h across 9 days. Our results suggest that sulfur has benefits for disease suppression and fungicide resistance management that greatly surpass the minimal phytotoxicity observed only at temperatures above 35°C for a period of at least 2 h.
Therapeutic Potential of Digital Nerve Block in Rheumatoid Arthritis Patients
Authors: Elsaman Ahmed M. , Hamed Ahmed , Radwan Ahmed R.
Published: March 2021

Background:

This study attempted to test the effectiveness of digital nerve block (DNB) in active rheumatoid arthritis (RA) joints with respect to local disease control.

Methods:

The study included 83 RA patients aged 18 years or above and diagnosed, after American College of Rheumatology/European League Against Rheumatism criteria 2010, with bilateral proximal interphalangeal (PIP) arthritis. PIPs were examined by European League Against Rheumatism-outcome measures in rheumatoid arthritis clinical trials scoring system at 0, 2, and 8 weeks. Visual analog scales for each hand were also done at the same intervals. DNBs of the second and third PIPs were performed to the dominant hand in 50% of participants. The other hand was used as a control, and saline was injected in the same level at the control side.

Results:

At 2 weeks and 8 weeks intervals, the active side showed significantly less clinical and ultrasound scores when compared to the control side and the baseline values. The mean OMERACT score for the active hand dropped from 3.37±1.43 at 0 time to 2.31±1.66 after 2 weeks and 2.55±1.43 at 8 weeks (P<0.001). Also, visual analog scale decreased from 59 at 0 time to 41 at 2 weeks and 43 at 8 weeks (P<0.001). The amelioration was greater when the active side was the dominant one. The injected PIPs showed maximum improvement at 2 weeks. Improvement was more significant in the second PIP. Early patients achieved better outcomes.

Conclusion:

DNB is a new promising therapy for RA. It can control pain and inflammation of the PIPs. It has relatively short-term effect, yet it could limit escalation of systemic treatment plans.
Evidence-Based Facebook Recruitment of Study Participants
Authors: Stuart Wilma Powell , Moore Bridget
Published: March 2021

Traditional methods for research study recruitment such as snail mail lists and posting flyers may fail to reach the tech-savvy participants needed for today's healthcare studies. Word of mouth can be effective for recruiting a few participants but can rarely accomplish the numbers needed for a representative sample. Social media can be a viable avenue to reach increased numbers of sample participants; however, a good understanding of the risks and benefits of using social media is needed before embarking on active recruitment. A recent study developed an evidence-based participant recruitment plan for the use of Facebook. Potential participant misrepresentation was addressed with clear inclusion criteria, no incentives, and open-ended questions. The Facebook ads to recruit study participation targeted licensed nurses who worked in the prior 2-year period living in the United States based on information in Facebook user profiles. A total of 536 participants responded to all questions on the survey at a cost of $1.78 per completed survey. Daily activity and cost for ads were closely monitored and adjusted to maintain cost control. Facebook can be an effective tool for study participant recruitment across all age ranges for completion of online surveys.
Communicable and noncommunicable liver disease in HIV
Authors: Mauss Stefan , Boesecke Christoph
Published: March 2021

Purpose of review

The aim of this study was to highlight the profound changes in the cause in chronic liver disease in HIV-infected individuals.

Recent findings

Hepatitis C virus (HCV) has been transformed into a curable viral infection by highly effective treatments. This has resulted in elimination of chronic hepatitis C in HIV-coinfected individuals at least in resource-rich settings. Hepatitis B virus (HBV) has become a chronic infection, which is easily controlled by long-term therapy with HBV polymerase inhibitors. As a result, nonalcoholic steatohepatitis (NASH) has gained clinical importance. The obesity epidemic in the general population has also included people with HIV and weight gain has been associated with some newer antiretroviral drugs, such as HIV integrase inhibitors and tenofovir alafenamide fumarate. Medical treatment for obesity is a focus of intense research efforts, but currently, the only convincing therapeutic option in morbidly obese patients is bariatric surgery, which can also improve liver outcomes. The wider use of this approach has included HIV-infected individuals allowing to assess at least the safety aspects of bariatric surgery in this special population.

The shift from communicable to noncommunicable liver disease is changing the clinical practice in HIV-infected individuals. Research activities are focusing more on treatment of NASH and obesity, although a curative therapy for HBV infection would have a great clinical impact.
Major Prehospital Trauma and In-Hospital Emergencies
Authors: Estebaranz-Santamaría Cristina , Palmar-Santos Ana María , Pedraz-Marcos Azucena
Published: March 2021

Background

Massive transfusion (MT) in trauma is initiated on the basis of factors of different natures and depending on protocols and scales used both in prehospital and in-hospital care areas.

Objective

The main goal was to analyze and relate factors and predictive variables for MT requirements considering both health care areas.

Method

This was a retrospective cohort study that included patients who were treated either at the emergency department of a large hospital or through prehospital care before arrival at the hospital. The patients included were adults who received MT, defined as a blood bank request of 10 or more units of red cells in the first 24 hours or 5 or more within 4 hours of trauma, from January 1, 2009, to January 1, 2017. The variables included were individual characteristics and those associated with the trauma, clinical-analytical assessment, resuscitation, timing, and survival.

Results

A total of 52 patients who received MT were included. The average age of the patients was 41.23 ± 16.06 years, a mean of 19.56 ± 12.77 units was administered, and the mortality rate was 21.2%.

Discussion

Injury mechanism, clinical-analytical variables, and resuscitation strategies have a significant influence on the need for MT; therefore, early identification is fundamental for performing quality management and addressing avoidable factors during MT processes.
An analysis of prehospital critical care events and management patterns from 97 539 emergency helicopter medical service missions
Authors: Saviluoto Anssi , Laukkanen-Nevala Päivi , Raatiniemi Lasse , Jäntti Helena , Nurmi Jouni O.
Published: March 2021

BACKGROUND

It is largely unknown how often physicians in emergency helicopter medical services (HEMS) encounter various critical care events and if HEMS exposure is associated with particular practice patterns or outcomes.

OBJECTIVES

This study aimed: to describe the frequency and distribution of critical care events; to investigate whether HEMS exposure is associated with differences in practice patterns and determine if HEMS exposure factors are associated with mortality.

DESIGN

A retrospective registry-based study.

SETTING

Physician-staffed HEMS in Finland between January 2012 and August 2019.

PARTICIPANTS

Ninety-four physicians who worked at least 6 months in the HEMS during the study period. Physicians with undeterminable HEMS exposure were excluded from practice pattern comparisons and mortality analysis, leaving 80 physicians.

MAIN OUTCOME MEASURES

The primary outcome measure was a physician's average annual frequencies for operational events and clinical interventions. Our secondary outcomes were the proportion of missions cancelled or denied, time onsite (OST) and proportion of unconscious patients intubated. Our tertiary outcome was adjusted 30-day mortality of patients.

RESULTS

The physicians encountered 62 [33 to 98], escorted 31 [17 to 41] and transported by helicopter 2.1 [1.3 to 3.5] patients annually, given as median [interquartile range; IQR]. Rapid sequence intubation was performed 11 [6.2 to 16] times per year. Physicians were involved in out-of-hospital cardiac arrest (OHCA) 10 [5.9 to 14] and postresuscitation care 5.5 [3.1 to 8.1] times per year. Physicians with longer patient intervals had shorter times onsite. Proportionally, they cancelled more missions and intubated fewer unconscious patients. A short patient interval [odds ratio (OR); 95% confidence interval (CI)] was associated with decreased mortality (0.87; 95% CI, 0.76 to1.00), whereas no association was observed between mortality and HEMS career length.

CONCLUSION

Prehospital exposure is distributed unevenly, and some physicians receive limited exposure to prehospital critical care. This seems to be associated with differences in practice patterns. Rare HEMS patient contacts may be associated with increased mortality.
Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults
Authors: Wang Yang , Jia Hao , Gao Wei-Hua , Zou Ting , Yao Shi , Du Ming-Fei , Zhang Xiao-Yu , Chu Chao , Liao Yue-Yuan , Chen Chen , Wang Dan , Ma Qiong , Hu Jia-Wen , Wang Ke-Ke , Yan Yu , Sun Yue , Hu Gui-Lin , Niu Ze-Jiaxin , Zhou Hao-Wei , Zhang Xi , Wang Xin , Li Chun-Hua , Chen Fang-Yao , Gao Ke , Zhang Jie , Guan Yong-Juan , Chang John , Yang Tie-Lin , Mu Jian-Jun
Published: March 2021

Objective:

Pregnancy-associated plasma protein-A2 (PAPP-A2) is the homolog of PAPP-A in the vertebrate genome and its role in protecting against salt-induced hypertension in salt-sensitive rats has been confirmed. We sought to examine the associations of plasma PAPP-A2 levels and its genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in humans.

Methods:

Eighty participants (18–65 years old) sequentially consuming a usual diet, a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day). In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families in Northern China in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension over 14 years.

Results:

The plasma PAPPA2 levels significantly decreased with the change from baseline to a low-salt diet and decreased further when converting from the low-salt to high-salt diet. SNP rs12042763 in the PAPP-A2 gene was significantly associated with systolic BP responses to both low-salt and high-salt diet while SNP rs2861813 showed a significant association with the changes in SBP and pulse pressure at 14-year follow-up. Additionally, SNPs rs2294654 and rs718067 demonstrated a significant association with the incidence of hypertension over the 14-year follow-up. Finally, the gene-based analysis found that Pappa2 was significantly associated with longitudinal SBP changes and the incidence of hypertension over the 14-year follow-up.

Conclusions:

This study shows that dietary salt intake affects plasma PAPP-A2 levels and that PAPP-A2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations.
Personality Traits and Social Supports in Adolescents With Persistent Postconcussion Symptoms
Authors: Atif Hamna , Morgan Brianne , Tuohy Kyle , Zukowski Monica , Foster Zachary , Loeffert Andrea , Yeates Keith O. , Hicks Steven D.
Published: March 2021

Objectives:

To determine whether adolescents with persistent postconcussion symptoms (PPCS) differ from healthy peers in their personality traits and social supports.

Setting:

Specialty Concussion Clinic and Primary Care Clinic affiliated with an academic medical center.

Participants:

Ninety-seven adolescents (42 with PPCS, 55 healthy peers; age: 15 ± 2 years).

Design:

Participants completed a web-based survey that included medical and demographic characteristics, mechanisms of concussion, 10-item Big Five Inventory, and Child and Adolescent Social Support Scale. A Student's 2-tailed t test with multiple testing corrections was used to compare the youths with PPCS to healthy peers.

Main Measures:

The primary outcome was PPCS, defined by the presence of 2 or more concussion-related symptoms on the Post-Concussion Symptom Scale (PCSS), lasting for more than 4 weeks after initial injury. The secondary outcome was perceived personality traits and social support, based on the 10-item Big Five Inventory and the Child and Adolescent Social Support Scale, respectively.

Results:

The PPCS group had higher neuroticism scores on their Big Five Inventory than healthy peers. They also reported less social support from teachers and classmates than healthy peers.

Conclusion:

Youths with PPCS report specific personality and social support characteristics that differ from their peers. These findings suggest that individual personality and school-based social supports may influence concussion recovery.
EFFICACY AND SAFETY OF INTRAVITREAL AFLIBERCEPT USING A TREAT-AND-EXTEND REGIMEN FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Mitchell Paul , Holz Frank G. , Hykin Philip , Midena Edoardo , Souied Eric , Allmeier Helmut , Lambrou George , Schmelter Thomas , Wolf Sebastian ,   on behalf of the ARIES study investigators
Published: March 2021

Background/Purpose:

Treating neovascular age-related macular degeneration with intravitreal aflibercept treat-and-extend (T&E) can reduce treatment burden. ARIES assessed whether intravitreal aflibercept early-start T&E was noninferior to late-start T&E.

Methods:

A randomized, open-label, Phase 3b/4 study that included treatment-naïve patients aged ≥50 years with the best-corrected visual acuity 73–25 Early Treatment Diabetic Retinopathy Study letters and active choroidal neovascularization secondary to AMD. Patients received 2 mg intravitreal aflibercept at Week (W) 0, W4, W8, and W16. At W16, patients were randomized 1:1 to early-start (2W interval adjustments) or late-start T&E (8W intervals until W48 then 2W interval adjustments). Primary endpoint: the best-corrected visual acuity change from randomization to W104.

Results:

Two-hundred seventy-one patients were randomized. The mean (SD) best-corrected visual acuity at baseline was 60.2 (12.1; early-T&E) and 61.3 (10.8; late-T&E) letters. The mean (SD) best-corrected visual acuity change (W16–104) was −2.1 (11.4) versus −0.4 (8.4) letters (early-T&E vs. late-T&E; least-squares mean difference: −2.0; 95% confidence interval: −4.75 to 0.71; P = 0.0162 for noninferior); +4.3 (13.4) versus +7.9 (11.9) letters (W0–104). The mean (SD) number of injections was 12.0 (2.3) versus 13.0 (1.8). From baseline to W104, 93.4% and 96.2% maintained best-corrected visual acuity; the mean (SD) central retinal thickness change was −161.6 (135.6) µm and −158.6 (125.1) µm. The last injection interval (W104) was ≥12W for 47.2% and 51.9% of patients.

Conclusion:

Outcomes were similar between patients with neovascular age-related macular degeneration treated with an intravitreal aflibercept early-T&E or late-T&E regimen after initial dosing, with one injection difference over 2 years.

Trial Registration:

ClinicalTrials.gov Identifier: NCT02581891 https://clinicaltrials.gov/ct2/show/NCT02581891. Supplemental Digital Contents (files 1 http://links.lww.com/IAE/B419).
Anti-inflammatory and Antioxidant Effects of Selenium on Orbital Fibroblasts of Patients With Graves Ophthalmopathy
Authors: Kim Bo-Yeon , Jang Sun-Young , Choi Dug-Hyun , Jung Chan-Hee , Mok Ji-Oh , Kim Chul-Hee
Published: March 2021

Purpose:

In the present study, the authors investigated the effects of selenium on inflammation, hyaluronan production, and oxidative stress in primary cultured orbital fibroblasts of patients with Graves ophthalmopathy (GO).

Methods:

Orbital adipose/connective tissue specimens were obtained during the course of orbital surgery for patients with GO (n = 7) and other noninflammatory problems (n = 5). After incubation with various concentrations of sodium selenite for 48 hours, supernatants from primary cultures were collected. Hyaluronan and cytokine levels were measured using commercially available enzyme-linked immunosorbent assay kits. To determine the effect of selenium on reactive oxygen species (ROS) production stimulated by H2O2 (100 μM) for 30 minutes, the cells were pretreated with various concentrations of sodium selenite for 60 minutes.

Results:

Interleukin (IL)-6 and tumor necrosis factor-alpha levels were significantly higher in orbital fibroblasts of patients with GO than in orbital fibroblasts of control patients. Hyaluronan production was suppressed by selenium in cultured orbital fibroblasts of patients with GO. Inflammatory cytokines such as IL-1α, IL-8, and tumor necrosis factor-alpha were suppressed by selenium in cultured orbital fibroblasts of patients with GO. IL-1β and IL-6 were not suppressed by selenium in cultured orbital fibroblasts of patients with GO. Selenium pretreatment reduced intracellular ROS generation stimulated by H2O2 in cultured orbital fibroblasts of patients with GO.

Conclusions:

In conclusion, hyaluronan production, inflammatory cytokines, and intracellular ROS generation were suppressed by selenium in cultured orbital fibroblasts of patients with GO. Several inflammatory cytokines may be suppressed by selenium in cultured orbital fibroblasts of patients with GO. This study provide the basis for use of selenium in the treatment of GO.
Management of Pediatric Acute Dacryocystitis
Authors: Prat Daphna , Magoon Katie , Revere Karen E. , Katowitz James A. , Katowitz William R.
Published: March 2021

Purpose:

To analyze the clinical presentation, course, and management in a large cohort of pediatric acute dacryocystitis subjects and to examine whether hospitalization and urgent surgical intervention are indeed mandatory.

Methods:

A retrospective analysis of all pediatric subjects diagnosed with dacryocystitis at the Children’s Hospital of Philadelphia over a 12-year period (2009–2020).

Results:

One-hundred sixty-nine pediatric acute dacryocystitis patients were included in this study. Management included admission in 117 cases (69%). Sixty-eight patients (40%) were treated medically with no surgical intervention, 75 cases (44%) required urgent surgical intervention, and 26 additional cases (15%) required surgery due to persistent tearing symptoms after medical management. The urgent procedures included most commonly: 1) endonasal examination and microdebridement of intranasal cysts in 26 cases (35%); 2) probing and irrigation without examination and microdebridement, with or without stent intubation, in 30 cases (40%); and 3) dacryocystorhinostomy (13 endonasal and 4 external) in 17 cases (23%).

Conclusions:

Management of pediatric acute dacryocystitis should be tailored individually for each case. Hospital admission and early surgical intervention are not mandatory, as 31% of cases resolved without admission, and 56% without early surgical intervention. Although a specific age cutoff is not plausible, hospital admission for younger patients is more commonly advocated. When surgical intervention is indicated, endonasal examination and microdebridement of any associated intranasal cyst and probing with possible stenting are the initial procedures of choice. Dacryocystorhinostomy is reserved for more complex obstructions. Although pediatric acute dacryocystitis is an infection with serious potential problems, when managed appropriately, complications are rare.
Surgical Technique to Retrieve a Migrated Lester Jones Lacrimal Tube
Authors: Wirth Magdalena A. , Dolman Peter J.
Published: March 2021

Purpose:

To describe a technique for retrieving an inferomedially migrated Jones lacrimal tube.

Methods:

The distal end of the migrated Jones tube is visualized directly via the nose. The tip of an endoilluminator (23 Gauge Constellation Vision Systems) is bent to form a 45° to 60° angle using a mosquito forceps and inserted into the distal opening of the tube. The endoilluminator is used to push the tube upward toward the original medial canthal opening and limit downward displacement as the caruncular area is surgically explored. The light transilluminating the tube facilitates its visualization and retrieval in the caruncular area. A new tube may be threaded through the same passage, or if the ostium is traumatized, through a new passage.

Results:

This technique is time-efficient and has proven to be safe and successful in subsequent patients.

Conclusions:

The described technique aids in retrieving an inferomedially migrated Jones tube with minimal trauma to the surrounding structures.
Whole-milk consumption decreases the risk of inflammatory bowel disease: a two-sample Mendelian randomization analysis
Authors: Li Jiuling , Zhu Haoxue , Tian Aowen , Guo Ying , Zhao Xiaoxuan , Zhang Miaoran , Chen Lanlan , Wen Jianping , Yang Jianli , Qi Baiyu , Chen Peng
Published: March 2021

Objective:

The impact of dairy fat on inflammatory bowel disease remained inconclusive. We aimed to compare the effects of whole-milk and skimmed-milk consumption on the risk of inflammatory bowel disease using a Mendelian randomization analysis.

Methods:

We conducted a genome-wide association study of the preference for whole versus skimmed milk using data for 20,200 whole-milk consumers and 67,847 skimmed-milk consumers from the UK Biobank. The lead single nucleotide polymorphisms in the associated loci were identified at the genome-wide significance level, and were further employed as instrumental variables for whole-milk preference. We conducted a two-sample Mendelian randomization analysis with whole-milk preference as the exposure and inflammatory bowel disease as the outcome. The pleiotropic effects and heterogeneity of the instrumental variables were estimated using Mendelian randomization-Egger regression and Cochran
Q
test, respectively. This study was conducted using the UKB resources under the application "53536" . The UK Biobank was approved by the North West Multi-center Research Ethics Committee, the National Information Governance Board for Health and Social Care in England and Wales, and the Community Health Index Advisory Group in Scotland.

Results:

The genome-wide association study identified five lead nucleotide polymorphisms associated with whole-milk preference. Mendelian randomization indicated that whole-milk preference significantly decreased the risk of inflammatory bowel disease (
β
=-1.735,
P
=0.048). Of the two subtypes, whole-milk preference was associated with a lower risk of Crohn disease (
β
=-2.549,
P
=0.032), but had no significant effect on the risk of ulcerative colitis (
β
=-1.002,
P
=0.44).

Conclusion:

Consumption of whole-milk fat may protect against Crohn disease, compared with skimmed milk. This conclusion was based on causal inference in a cohort study, and further validation in randomized controlled trials is warranted.
Recent Changes in Durable Left Ventricular Assist Device Bridging to Heart Transplantation
Authors: Srinivasan Amudan J. , Seese Laura , Mathier Michael A. , Hickey Gavin , Lui Cecillia , Kilic Arman
Published: March 2021

This study evaluates the impact of the recent United Network for Organ Sharing (UNOS) allocation policy change on outcomes of patients bridged with durable left ventricular assist devices (LVADs) to orthotopic heart transplantation (OHT). Adults bridged to OHT with durable LVADs between 2010 and 2019 were included. Patients were stratified based on the temporal relationship of their OHT to the UNOS policy change on October 18, 2018. The primary outcome was early post-OHT survival. In total, 9,628 OHTs were bridged with durable LVADs, including 701 (7.3%) under the new policy. Of all OHTs performed during the study period, the proportion occurring following durable LVAD bridging decreased from 45% to 34% (p < 0.001). The more recent cohort was higher risk, including more extracorporeal membrane oxygenation bridging (2.6% vs. 0.3%, p < 0.001), more mechanical right ventricular support (9.7% vs. 1.4%, p < 0.001), greater pretransplant ICU admission (22.8% vs. 8.7%, p < 0.001) more need for total functional assistance (62.8% vs. 53.0%, p < 0.001), older donor age (33.3 vs. 31.7 years, p < 0.001), and longer ischemic times (3.38 vs. 3.13 hours, p < 0.001). Despite this, early post-OHT survival was comparable at 30 days (96.1% vs. 96.0%, p = 0.89), 90 days (93.7% vs. 94.0%, p = 0.76), and 6 months (91.0% vs. 93.0%, p = 0.96), findings that persisted after risk-adjustment. In this early analysis, OHT following bridging with durable LVADs is performed less frequently and in higher risk recipients under the new allocation policy. Despite this, short-term posttransplant outcomes appear to be unaffected in this patient cohort in the current era.
Impact of the COVID-19 pandemic on cardiac arrest systems of care
Authors: Kovach Christopher P. , Perman Sarah M.
Published: March 2021

Purpose of review

The emergence of severe acute respiratory syndrome coronavirus 2 virus, which causes coronavirus disease 2019 (COVID-19), led to the declaration of a global pandemic by the World Health Organization on March 11, 2020. As of February 6, 2021, over 105 million persons have been infected in 223 countries and there have been 2,290,488 deaths. As a result, emergency medical services and hospital systems have undergone unprecedented healthcare delivery reconfigurations. Here, we review the effects of the COVID-19 pandemic on out-of-hospital cardiac arrest (OHCA) epidemiology and systems of care.

Recent findings

Areas severely affected by the pandemic have reported increased incidence of OHCA, lower rates of successful resuscitation, and increased mortality. COVID-19 has significantly impacted patient outcomes through increased disease severity, decreased access to care, and the reshaping of emergency medical response and hospital-based healthcare systems and policies. The pandemic has negatively influenced attitudes toward resuscitation and challenged providers with novel ethical dilemmas provoked by the scarcity of healthcare resources.

The COVID-19 pandemic has had direct, indirect, psychosocial, and ethical impacts on the cardiac arrest chain of survival.