bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspergillosis in free-ranging Magellanic penguins
Authors: Melo Aryse Martins , Poester Vanice Rodrigues , Trápaga Mariana Rodrigues , Stevens David A , Canabarro Paula Lima , Adornes Andréa Corrado , da Silva Andrine Paiva , Estima Sérgio Curi , Frere Esteban , Sabino Raquel , Xavier Melissa Orzechowski
Published: February 2023

We evaluated the mortality due to aspergillosis in free-ranging Magellanic penguins during their migration and the reproductive season. A total of 98 carcasses of penguins were collected along 370 km of coastline in Southern Brazil, between June 2017 and October 2019, and from reproductive colonies in Patagonian Argentina, in January 2019. All animals were necropsied, and only proven cases were computed. Aspergillosis was diagnosed in 2.5% of the penguins evaluated during their migration route. Our study, of the Southern coast of Brazil, is the first to demonstrate that aspergillosis is an important cause of mortality in free-ranging penguins. The implications of these findings in the One Health context are discussed.
Line luminosities of Galactic and Magellanic Cloud Wolf–Rayet stars
Authors: Crowther Paul A , Rate G , Bestenlehner Joachim M
Published: February 2023

We provide line luminosities and spectroscopic templates of prominent optical emission lines of 133 Galactic Wolf–Rayet (WR) stars by exploiting Gaia DR3 parallaxes and optical spectrophotometry, and provide comparisons with 112 counterparts in the Magellanic Clouds. Average line luminosities of the broad blue (He ii λ4686, C iii λλ4647,51, N iii λλ4634,41, and N v λλ4603,20) and yellow (C iv λλ5801,12) emission features for WN, WN/C, WC, and WO stars have application in characterizing the WR populations of star-forming regions of distant, unresolved galaxies. Early-type WN stars reveal lower line luminosities in more metal-poor environments, but the situation is less clear for late-type WN stars. LMC WC4–5 line luminosities are higher than their Milky Way counterparts, with line luminosities of Magellanic Cloud WO stars higher than Galactic stars. We highlight other prominent optical emission lines, N iv λλ3478,85 for WN and WN/C stars, O iv λλ3403,13 for WC and WO stars, and O vi λλ3811,34 for WO stars. We apply our calibrations to representative metal-poor and metal-rich WR galaxies, IC 4870 and NGC 3049, respectively, with spectral templates also applied based on a realistic mix of subtypes. Finally, the global blue and C iv λλ5801,12 line luminosities of the Large Magellanic Clouds or LMCs (Small Magellanic Clouds) are 2.6 × 1038 erg s−1 (9 × 1036 erg s−1) and 8.8 × 1037 erg s−1 (4 × 1036 erg s−1), respectively, with the cumulative WR line luminosity of the Milky Way estimated to be an order of magnitude higher than the LMC.
The Predominant Six-Four in the Late Music of Richard Strauss
Authors: Hutchinson Kyle
Published: February 2023

This article examines a unique family of six-four sonorities in the works of Richard Strauss. These six-fours typically sound with 6^, 4^, or 2^ (or modal variants thereof) in the bass but occur immediately prior to a cadential dominant, and thus impart a sense of predominant function despite their unstable inversion. In examining how the sixth and fourth behave, I suggest that rather than hearing these chords as consonant inversions of a triad, they can instead be interpreted as accented six-fours; in other words, reading the sixth and fourth as dissonances, whose resolution to a fifth and third is deferred to occur over a subsequent harmony. I suggest that the sense of fragmentation that coalesces through the process of suspension creates a conflict between phenomenological and analytic hearings of this music, which reflects a type of modernism typically overlooked in Strauss’s late music.
Preschool-Aged Household Contacts as a Risk Factor for Viral Respiratory Infections in Healthcare Personnel
Authors: Most Zachary M , Nyquist Ann-Christine , Radonovich Lewis J , Rodriguez-Barradas Maria C , Price Connie Savor , Simberkoff Michael S , Bessesen Mary T , Cummings Derek A T , Rattigan Susan M , Warren-Gash Charlotte , Gaydos Charlotte A , Gibert Cynthia L , Gorse Geoffrey J , Perl Trish M
Published: February 2023

Background

Viral respiratory infections (VRIs) are common and are occupational risks for healthcare personnel (HCP). VRIs can also be acquired at home and other settings among HCPs. We sought to determine if preschool-aged household contacts are a risk factor for VRIs among HCPs working in outpatient settings.

Methods

We conducted a secondary analysis of data from a cluster randomized trial at 7 medical centers in the United States over 4 influenza seasons from 2011–2012 to 2014–2015. Adult HCPs who routinely came within 6 feet of patients with respiratory infections were included. Participants were tested for respiratory viruses whenever symptomatic and at 2 random times each season when asymptomatic. The exposure of interest was the number of household contacts 0–5 years old (preschool-aged) at the beginning of each HCP-season. The primary outcome was the rate of polymerase chain reaction–detected VRIs, regardless of symptoms. The VRI incidence rate ratio (IRR) was calculated using a mixed-effects Poisson regression model that accounted for clustering at the clinic level.

Results

Among the 4476 HCP-seasons, most HCPs were female (85.4%) and between 30 and 49 years of age (54.6%). The overall VRI rate was 2.04 per 100 person-weeks. In the adjusted analysis, HCPs having 1 (IRR, 1.22 [95% confidence interval {CI}, 1.05–1.43]) and ≥2 (IRR, 1.35 [95% CI, 1.09–1.67]) preschool-aged household contacts had higher VRI rates than those with zero preschool-aged household contacts.

Conclusions

Preschool-aged household contacts are a risk factor for developing VRIs among HCPs working in outpatient settings.
The institutional design of agri-environmental contracts—How stakeholder attitudes can inform policy making
Authors: Schulze Christoph , Matzdorf Bettina
Published: February 2023

Agri-environmental climate measures (AECM) are considered a promising tool to achieve environmental policy goals. Not only farmers but also policy administrators and intermediaries are important actors whose attitudes and actions drive the success of these measures. To follow the idea of better stakeholder participation in the design of policy instruments, we analyse stakeholder viewpoints on the contract design of the AECM. We apply the Q methodology to 25 individuals from Brandenburg, Germany, who are from the farmer, policy administrator, and intermediary domains. We identify three distinct attitudinal profiles: the ‘planners’, the ‘cooperators’, and the ‘individualists’, which do not correspond to the three individual stakeholder groups. The results provide evidence that general differences in the viewpoints of policy designers and implementers on the one hand and farmers on the other hand are not a source of potential institutional mismatch. We further use the attitudinal profiles to develop three types of policy programmes with slightly different underlying rationalities. Policymakers could use such an approach to better develop target group-specific (sub)programmes in parallel. Our research strengthens the argument that multiple stakeholders should be involved in co-designing conservation measures. Moreover, behavioural factors should be considered in policy making processes.
Die hard: cell death mechanisms and their implications in nanotoxicology
Authors: Lomphithak Thanpisit , Fadeel Bengt
Published: February 2023

Cell death is a fundamental biological process, and its fine-tuned regulation is required for life. However, the complexity of regulated cell death is often reduced to a matter of live-dead discrimination. Here, we provide a perspective on programmed or regulated cell death, focusing on apoptosis, pyroptosis, necroptosis, and ferroptosis (the latter three cell death modalities are examples of regulated necrosis). We also touch on other, recently described manifestations of (pathological) cell death including cuproptosis. Furthermore, we address how engineered nanomaterials impact on regulated cell death. We posit that an improved understanding of nanomaterial-induced perturbations of cell death may allow for a better prediction of the consequences of human exposure to these materials and could also yield novel approaches by which to mitigate their effects. Finally, we provide examples of the harnessing of nanomaterials to achieve cancer cell killing through the induction of regulated cell death.
Dried Blood Spot Sampling in the Monitoring of Anticancer Therapy for Solid Tumors: A Systematic Review
Authors: Shafiei Mohsen , Mahmood Alina , Beale Philip , Galettis Peter , Martin Jennifer , McLachlan Andrew J. , Blinman Prunella
Published: February 2023

Background:

Dried blood spot (DBS) sampling is a convenient alternative to whole-blood sampling for therapeutic drug monitoring (TDM) in clinical practice. The aim of this study was to systematically review studies that have examined and used DBS sampling for the TDM of chemotherapy and targeted therapy agents for the treatment of patients with solid cancers.

Methods:

Using the PRISMA guidelines, a systematic literature search of EMBASE and PUBMED was performed to identify eligible clinical studies that used DBS sampling to monitor chemotherapy or targeted therapy for the treatment of solid cancers.

Results:

Of the 23 eligible studies, 3 measured concordance between drug concentrations determined by DBS and whole-blood, 7 developed analytical methods of DBS, and 13 performed both. DBS was employed for the TDM of everolimus (3 studies), vemurafenib (2 studies), pazopanib (2 studies), abiraterone (2 studies), mitotane, imatinib, adavosertib, capecitabine, 5-fluorouracil, gemcitabine, cyclophosphamide, ifosfamide, etoposide, irinotecan, docetaxel, gefitinib, palbociclib/ribociclib, and paclitaxel (one study each). The studies included a median of 14 participants (range: 6–34), with 10–50 μL of blood dispensed on DBS cards (20) and Mitra devices (3). Seventeen of the 20 studies that used DBS found no significant impact of the hematocrit on the accuracy and precision of the developed method in the normal hematocrit ranges (eg, 29.0%–59.0%). DBS and plasma or venous concentrations were highly correlated (correlation coefficient, 0.872–0.999) for all drugs, except mitotane, which did not meet a predefined level of significance (r > 0.872; correlation coefficient, r = 0.87, P < 0.0001).

Conclusions:

DBS provides an alternative sampling strategy for the TDM of many anticancer drugs. Further research is required to establish a standardized approach for sampling and processing DBS samples to allow future implementation.
Nursing Workforce Optimization Study: A Multi-method Evaluation and Process Improvement Intervention for HIV Service Delivery in Tanzania and Zambia
Authors: Coe Megan , Kawakyu Nami , Gimbel Sarah , Nyakuya Baraka , Gabriel Neema , Leonard Devotha , Chale Stella , Masiye Felix , Banda Charles M. , Manangwa Saturini , Moyo Gustav , Boyle Gabriela , Freistadt Fernanda , Kohler Pamela
Published: February 2023

Nurses are often suboptimally used in HIV care, due to misalignment of training and practice, workflow inefficiencies, and management challenges. We sought to understand nursing workforce capacity and support implementation of process improvement strategies to improve efficiency of HIV service delivery in Tanzania and Zambia. We conducted time and motion observations and task analyses at 16 facilities followed by process improvement workshops. On average, each nurse cared for 45 clients per day in Tanzania and 29 in Zambia. Administrative tasks and documentation occupied large proportions of nurse time. Self-reported competency was low at baseline and higher at follow-up for identifying and managing treatment failure and prescribing antiretroviral therapy. After workshops, facilities changed care processes, provided additional training and mentorship, and changed staffing and supervision. Efficiency outcomes were stable despite staffing increases. Collaborative approaches to use workforce data to engage providers in improvement strategies can support roll-out of nurse-managed HIV treatment.
Comparison of Right Colon Flat Polyp Detection Rate by Water Exchange Versus Water Immersion-pooled Results of Data File of 3 Published Reports
Authors: Leung Felix W. , Koo Malcolm , Jia Hui , Cadoni Sergio , Hsieh Yu-Hsi , Leung Joseph W
Published: February 2023

Goals:

We tested the hypothesis that water exchange (WE) achieved a significantly higher right colon flat polyp detection rate (rFPDR) than water immersion (WI).

Background:

Current endoscopy methods provide real-time morphology but not histopathology. Flat serrated polyps are difficult to find during colonoscopy. In 2022 2 studies reported that the serrated polyp detection rate (SPDR) significantly inversely predicted the development of interval cancers. In 2021 1 systemic review with meta-analysis showed that WE, but not WI increased SPDR. The relative contributions of WE and WI on rFPDR are unknown.

Study:

Individual patient data from 3 reports comparing air insufflation, WI, and WE were pooled. Multiple logistic regression analysis was used to assess the factors associated with a higher rFPDR.

Results:

The pooled data showed that the rFPDR of air insufflation, WI, and WE were 15.4%, 14.1%, and 19.4% (P=0.009), respectively. After adjusting for age and withdrawal time, multiple logistic regression analysis revealed that WE, when compared with WI, was significantly associated with a higher rFPDR (adjusted odds ratio[aOR]=1.53, P=0.002). Analysis of data on pathology and size were omitted to avoid duplicating our earlier publications.

Conclusions:

Significantly higher rFPDR was achieved by WE. Water exchange rather than WI merits consideration for use to maximize rFPDR. Removal of flat polyps, and by inference serrated polyps, ensures their optimal management to minimize the occurrence of interval cancers. The potential benefit of WE in maximizing SPDR and minimizing interval cancers deserves evaluation in long-term randomized controlled studies focused on flat polyps detection.
Using organ perfusion to optimize donor livers
Authors: Lee-Riddle Grace S. , Panayotova Guergana G. , Guarrera James V.
Published: February 2023

Purpose of review

The shortage of donor organs has led to the use of marginal extended criteria donor (ECD) livers to increase access to liver transplant. Ex-vivo machine perfusion allows for treatment and assessment of organs during preservation, potentially facilitating safe use of ECD livers at risk for worse clinical outcomes. This article reviews the latest published literature on the application of ex-vivo machine perfusion technologies in liver transplantation.

Recent findings

Multiple randomized controlled trials on the use of hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) have been published in the past 5 years demonstrating improved graft function and decreased biliary complications after machine perfusion. Novel applications of machine perfusion include pretransplant organ viability testing, expansion to pediatric transplant, and prolonged preservation.

There is now a body of evidence that HMP and NMP treatment improves clinical outcomes in ECD livers. There is a wide horizon for future applications of these preservation techniques to further optimize donor livers and to facilitate more liver transplants for those on the waitlist.
A Scoping Review of Nurse Educator Competencies
Authors: Wells-Beede Elizabeth , Sharpnack Patricia , Gruben Darla , Klenke-Borgmann Laura , Goliat Laura , Yeager Caitlin
Published: February 2023

Background:

Unclear guidance continues faculty role preparation for promoting students' successful transition to practice.

Objectives:

To examine nurse educator competencies and their role in students' transition to practice.

Design:

This study utilized Arksey and O'Malley's methodological framework for conducting a scoping review. The review is reported using the Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews (PRISMA-ScR), including the PRISMA-ScR checklist.

Methods:

A comprehensive systematic search of MEDLINE, EMBASE, PsycINFO, ERIC, and CINAHL was performed for nurse educator competency. For the original search, no limitations were placed on dates. Two authors independently assessed eligibility via abstract review. The reference lists of the included studies were also examined.

Results:

Eleven articles were included in the review dating from 1992 to 2021. Three themes in the literature were identified by the authors: (1) the need for appropriate mentorship, (2) lack of preparation of educators who transition directly from clinical practice, and (3) lack of use and/or vague operationalization of the National League for Nursing nurse educator competencies.

Conclusion:

Evidence regarding requisite competencies of nurse educators is limited. Further research on the competencies required for nurse educators to facilitate successful student transitions to practice is needed.
Prehospital Tranexamic Acid Administration in Pediatric Trauma Patients: A Propensity-Matched Analysis of the Israeli Defense Forces Registry
Authors: Gendler Sami , Gelikas Shaul , Talmy Tomer , Lipsky Ari M. , Avital Guy , Nadler Roy , Radomislensky Irina , Ahimor Alon , Glassberg Elon , Mozer Glassberg Yael , Almog Ofer , Yazer Mark H. , Benov Avi
Published: February 2023

OBJECTIVES:

Tranexamic acid (TXA) administration confers a survival benefit in bleeding trauma patients; however, data regarding its use in pediatric patients are limited. This study evaluates the prehospital treatment with TXA in pediatric trauma patients treated by the Israel Defense Forces Medical Corps (IDF-MC).

DESIGN:

Retrospective, cohort study using the Israel Defense Forces registry, 2011–2021.

PATIENTS:

Pediatric trauma patients less than 18 years old. We excluded patients pronounced dead at the scene.

INTERVENTIONS:

None.

SETTING:

All cases of pediatric trauma in the registry were assessed for treatment with TXA. Propensity score matching was used to assess the association between prehospital TXA administration and mortality.

MEASUREMENTS AND MAIN RESULTS:

Overall, 911 pediatric trauma patients were treated with TXA by the IDF-MC teams; the median (interquartile) age was 10 years (5–15 yr), and 72.8% were male. Seventy patients (7.6%) received TXA, with 52 of 70 (74%) receiving a 1,000 mg dose (range 200–1,000 mg). There were no prehospital adverse events associated with the use of TXA (upper limit of 95% CI for 0/70 is 4.3%). Compared with pediatric patients who did not receive TXA, patients receiving TXA were more likely to suffer from shock (40% vs 10.7%;p< 0.001), sustain more penetrating injuries (72.9% vs 31.7%;p< 0.001), be treated with plasma or crystalloids (62.9% vs 11.4%;p< 0.001), and undergo more lifesaving interventions (24.3% vs 6.2%;p< 0.001). The propensity score matching failed to identify an association between TXA and lesser odds of mortality, although a lack of effect (or even adverse effect) could not be excluded (non-TXA: 7.1% vs TXA: 4.3%, odds ratio = 0.584; 95% CI 0.084–3.143;p= 0.718).

CONCLUSIONS:

Although prehospital TXA administration in the pediatric population is feasible with adverse event rate under 5%, more research is needed to determine the appropriate approach to pediatric hemostatic resuscitation and the role of TXA in this population.
Strength-based rehabilitation on clinical outcomes in patients post-partial meniscectomy: a systematic review and meta-analysis
Authors: Vivekanantha Prushoth , Diao David , Cohen Dan , Murphy Ben , de SA Darren
Published: February 2023

Objective

To determine the effect of strength-based rehabilitation programs on patients who underwent partial meniscectomy procedures

Design

Three databases MEDLINE, PubMed and EMBASE were searched from inception to May 9th, 2022. Data on functional outcomes such as quadriceps and hamstring strengths, as well as patient-reported outcomes such as Knee Osteoarthritis and Outcome Score (KOOS) and Visual-Analogue Scale (VAS) were recorded.

Results

A total of nine studies comprising 417 patients were included in this review. There were no significant differences in quadriceps or hamstring strength measures between pre and post-intervention for both groups. KOOS scores significantly increased from pre and post-intervention in both control and exercise groups. VAS scores changed from 5.0 cm to 1.4 cm in the exercise arm and 3.1 cm to 1.9 cm in the control arm.

Conclusion

Strength-based exercise programs for patients post-partial meniscectomy did not result in significantly different improvements in quadriceps or hamstring strength compared to control programs. However, strength-based exercise programs resulted in significantly higher KOOS scores and a greater decrease in VAS scores. Further studies, specifically well-designed systematic randomized controlled trials are necessary in order to elucidate the specifics behind what type of exercises to use in addition to load progression and frequency of training.
Changes in mild neurocognitive disorder status in mobility limited older primary care patients— implications for rehabilitative care
Authors: Ogawa Elisa F. , Ward Rachel E. , Milberg William P. , Dufour Alyssa B. , Moye Jennifer , Driver Jane A. , Bean Jonathan F.
Published: February 2023

Objective

To identify potential rehabilitative treatment targets associated with participants’ annual cognitive status.

Design

A cohort study patients with self-reported mobility limitation who completed neuropsychological, physical performance testing, and questionnaires at baseline to 2-year follow-up were categorized into three groups (persistently cognitively normal (mNCD-), non-persistent mild neurocognitive disorder (mNCD) and persistently mNCD+) based on their annual cognitive status using baseline, years 1 and 2 performance on Hopkins Verbal Learning, Trail Making, and Digit Symbol Substitution Tests. Repeated measures multinomial regression analysis was used to examine the differences between groups and associated characteristics.

Results

Study included 349 participants (mean age 76 ± 7) with 57% of participants were persistently mNCD-, 16% persistently mNCD+, and 27% non-persistent mNCD over 2 years of follow-up. Faster gait speed (Relative Risk Reduction (RRR):0.64-0.89) was associated with risk reduction and increase in depressive symptoms (RRR:1.09-1.12) was associated with greater risk of being classified into the non-persistent or persistently mNCD+ compared to persistently mNCD-.

Conclusion

Variability across cognitive status over time was observed. Gait speed and depressive symptoms were modifiable risk factors associated with non-persistent and persistent mNCD status. This study reinforces the potential benefit of multifaceted rehabilitation for preventing and treating older adults with mobility and/or cognitive problems.
Antiviral therapies for influenza
Authors: Chan Ken K.P. , Hui David S.C.
Published: February 2023

Purpose of review

The heavily suppressed global influenza activity during the coronavirus disease 2019 (COVID-19) pandemic is expected to return upon relaxation of travel restriction and nonpharmaceutical interventions (NPI). We reviewed the four marketed neuraminidase inhibitors (NAI e.g., oseltamivir, zanamivir, peramivir, laninamivir) and the only endonuclease inhibitor (baloxavir) on their clinical therapeutic effects and the ability of viral suppression in various groups of patients of different clinical settings based on the latest evidence.

Recent findings

Early initiation, preferably within 48 h of symptom onsets, of antiviral treatments with NAI and baloxavir, is crucial to produce favourable outcomes in patients with influenza infection. Updated evidence does not suggest routine use of combined antiviral agents in patients with influenza infection. Treatment-emergent resistant influenza variants may occur during NAI and baloxavir use, but it has no major impact on subsequent recovery. Early treatment of index patients with influenza infection and post-exposure prophylaxis in specific populations is crucial in preventing influenza transmission.

Antiviral therapy is the major defence therapeutically in the community and hospital settings to expedite early recovery and reduce influenza-related complications. Early treatment of index patients and post-exposure prophylaxis in susceptible close contacts may mitigate the spread of infection.
Malignant Peripheral Nerve Sheath Tumors of the Brachial Plexus
Authors: Donaldson Elsa K. , Winter Jessica M. , Chandler Rowan M. , Clark Tod A. , Giuffre Jennifer L.
Published: February 2023

Introduction

The incidence of malignant peripheral nerve sheath tumors (MPNSTs) is 0.001%. Commonly, MPNST arise in neurofibromatosis; however, they can occur sporadically, de novo or from a preexisting neurofibroma. Malignant peripheral nerve sheath tumors are aggressive tumors with high rates of local recurrence and metastasis. The prognosis is poor with 5-year survival rates of 15% to 50%. Unfortunately, given the rarity of these tumors, it is not clear how to best manage these patients. The purposes of this study were (1) to discuss our experience with MPNST and particularly our difficulties with diagnosis and management, and (2) to review the literature.

Materials and Methods

We report on all tumors of the brachial plexus excised between 2013 and 2019. We report 3 cases of MPNST, their treatment, and their outcomes.

Results

Thirteen patients underwent surgical excision of an intrinsic brachial plexus mass. Three of these patients (2 male, 1 female; average age, 36 years) were diagnosed with an MPNST. Two patients with an MPNST had neurofibromatosis type 1. All patients with an MPNST had a tumor >8 cm, motor and sensory deficits, and pain. All 3 patients with MPNST underwent a magnetic resonance imaging (MRI) before diagnosis. The average time from initial symptom onset to MRI was 12.3 months. Only 1 of the MRIs suggested a malignant tumor, with no MRI identifying an MPNST. One patient underwent an excisional biopsy, and 2 had incisional biopsies. Because of the lack of diagnosis preoperatively, all patients had positive margins given the limited extent of surgery. Returning for excision in an attempt to achieve negative margins in a large oncologically contaminated field was not possible because defining the boundaries of the initial surgical field was unachievable; therefore, the initial surgery was their definitive surgical management. All patients were referred to oncology and received radiation therapy.

Conclusions

Malignant peripheral nerve sheath tumors must be suspected in enlarging masses (>5 cm) with the constellation of pain, motor, and sensory deficits. Computed tomography– or ultrasound-guided core needle biopsy under brachial plexus block or sedation is required for definitive diagnosis to allow for a comprehensive approach to the patient's tumor with a higher likelihood of disease-free survival.
Polycomb protein RYBP activates transcription factor
Plagl1
during
in vitro
cardiac differentiation of mouse embryonic stem cells
Authors: Henry Surya , Kokity Lilla , Pirity Melinda Katalin
Published: February 2023

RING1 and YY1 binding protein (RYBP) is primarily known to function as a repressor being a core component of the non-canonical polycomb repressive complexes 1 (ncPRC1s). However, several ncPRC1-independent functions of RYBP have also been described. We previously reported that RYBP is essential for mouse embryonic development and that
Rybp
null mutant embryonic stem cells cannot form contractile cardiomyocytes (CMCs)
in vitro
. We also showed that PLAGL1, a cardiac transcription factor, which is often mutated in congenital heart diseases (CHDs), is not expressed in
Rybp
-null mutant CMCs. However, the underlying mechanism of how RYBP regulates
Plagl1
expression was not revealed. Here, we demonstrate that RYBP cooperated with NKX2-5 to transcriptionally activate the
P1
and
P3
promoters of the
Plagl1
gene and that this activation is ncPRC1-independent. We also show that two non-coding RNAs residing in the
Plagl1
locus can also regulate the
Plagl1
promoters. Finally, PLAGL1 was able to activate
Tnnt2
, a gene important for contractility of CMCs in transfected HEK293 cells. Our study shows that the activation of
Plagl1
by RYBP is important for sarcomere development and contractility, and suggests that RYBP, via its regulatory functions, may contribute to the development of CHDs.
Departure, routing and landing decisions of long-distance migratory songbirds in relation to weather
Authors: Rüppel Georg , Hüppop Ommo , Lagerveld Sander , Schmaljohann Heiko , Brust Vera
Published: February 2023

Migrating birds flexibly adjust their individual migratory decisions, i.e. departing, routing and landing, based on intrinsic (e.g. energy stores) and extrinsic (e.g. landscape features and weather) factors modulating the endogenous stimuli. So far, these decisions have mostly been studied separately. Notably, we lack information on which factors landing decisions during active flight are based on. Therefore, we simultaneously recorded all three decisions in free-flying long-distance migratory songbirds in a coastal stopover area via regional-scale radio-telemetry and related them to the prevailing weather. Birds departed under favourable weather conditions resulting in specific nights with increased departure probability. Once departed, birds could either fly offshore or take a route along the coast, which was predicted by wind support. Radio-tracking revealed that departed individuals more likely interrupted their migratory endurance flight under overcast or headwind conditions. Studying departure, routing and landing decisions in concert, we highlight the importance of weather as a common driver across all migratory decisions. By radio-tracking individuals between stopovers, we provide evidence that avoidance of adverse weather conditions is an important function of stopover. Understanding how birds adjust migratory decisions and how they affect the timing of migration and survival is key to link migration performance to individual fitness.
The impact of age-related increase in passive muscle stiffness on simulated upper limb reaching
Authors: Murtola Tiina , Richards Christopher
Published: February 2023

Ageing changes the musculoskeletal and neural systems, potentially affecting a person’s ability to perform daily living activities. One of these changes is increased passive stiffness of muscles, but its contribution to performance is difficult to separate experimentally from other ageing effects such as loss of muscle strength or cognitive function. A computational upper limb model was used to study the effects of increasing passive muscle stiffness on reaching performance across the model’s workspace (all points reachable with a given model geometry). The simulations indicated that increased muscle stiffness alone caused deterioration of reaching accuracy, starting from the edges of the workspace. Re-tuning the model’s control parameters to match the ageing muscle properties does not fully reverse ageing effects but can improve accuracy in selected regions of the workspace. The results suggest that age-related muscle stiffening, isolated from other ageing effects, impairs reaching performance. The model also exhibited oscillatory instability in a few simulations when the controller was tuned to the presence of passive muscle stiffness. This instability is not observed in humans, implying the presence of natural stabilizing strategies, thus pointing to the adaptive capacity of neural control systems as a potential area of future investigation in age-related muscle stiffening.
Metabolomic signatures of corals thriving across extreme reef habitats reveal strategies of heat stress tolerance
Authors: Haydon Trent D. , Matthews Jennifer L. , Seymour Justin R. , Raina Jean-Baptiste , Seymour Jamie E. , Chartrand Kathryn , Camp Emma F. , Suggett David J.
Published: February 2023

Anthropogenic stressors continue to escalate worldwide, driving unprecedented declines in reef environmental conditions and coral health. One approach to better understand how corals can function in the future is to examine coral populations that thrive within present day naturally extreme habitats. We applied untargeted metabolomics (gas chromatography–mass spectrometry (GC–MS)) to contrast metabolite profiles of
Pocillopora acuta
colonies from hot, acidic and deoxygenated mangrove environments versus those from adjacent reefs. Under ambient temperatures,
P. acuta
predominantly associated with endosymbionts of the genera
Cladocopium
(reef) or
Durusdinium
(mangrove), exhibiting elevated metabolism in mangrove through energy-generating and biosynthesis pathways compared to reef populations. Under transient heat stress,
P. acuta
endosymbiont associations were unchanged. Reef corals bleached and exhibited extensive shifts in symbiont metabolic profiles (whereas host metabolite profiles were unchanged). By contrast, mangrove populations did not bleach and solely the host metabolite profiles were altered, including cellular responses in inter-partner signalling, antioxidant capacity and energy storage. Thus mangrove
P. acuta
populations resist periodically high-temperature exposure via association with thermally tolerant endosymbionts coupled with host metabolic plasticity. Our findings highlight specific metabolites that may be biomarkers of heat tolerance, providing novel insight into adaptive coral resilience to elevated temperatures.
Convergence and contingency in the evolution of a specialized mode of life: multiple origins and high disparity of rock-boring bivalves
Authors: Collins Katie S. , Edie Stewart M. , Jablonski David
Published: February 2023

Evolutionary adaptation to novel, specialized modes of life is often associated with a close mapping of form to the new function, resulting in narrow morphological disparity. For bivalve molluscs, endolithy (rock-boring) has biomechanical requirements thought to diverge strongly from those of ancestral functions. However, endolithy in bivalves has originated at least eight times. Three-dimensional morphometric data representing 75 species from approximately 94% of extant endolithic genera and families, along with 310 non-endolithic species in those families, show that endolithy is evolutionarily accessible from many different morphological starting points. Although some endoliths appear to converge on certain shell morphologies, the range of endolith shell form is as broad as that belonging to any other bivalve substrate use. Nevertheless, endolithy is a taxon-poor function in Bivalvia today. This limited richness does not derive from origination within source clades having significantly low origination or high extinction rates, and today's endoliths are not confined to low-diversity biogeographic regions. Instead, endolithy may be limited by habitat availability. Both determinism (as reflected by convergence among distantly related taxa) and contingency (as reflected by the endoliths that remain close to the disparate morphologies of their source clades) underlie the occupation of endolith morphospace.
Declines in body size of sockeye salmon associated with increased competition in the ocean
Authors: Ohlberger Jan , Cline Timothy J. , Schindler Daniel E. , Lewis Bert
Published: February 2023

Declining body sizes have been documented for several species of Pacific salmon; however, whether size declines are caused mainly by ocean warming or other ecological factors, and whether they result primarily from trends in age at maturation or changing growth rates remain poorly understood. We quantified changes in mean body size and contributions from shifting size-at-age and age structure of mature sockeye salmon returning to Bristol Bay, Alaska, over the past 60 years. Mean length declined by 3%, corresponding to a 10% decline in mean body mass, since the early 1960s, though much of this decline occurred since the early 2000s. Changes in size-at-age were the dominant cause of body size declines and were more consistent than trends in age structure among the major rivers that flow into Bristol Bay. Annual variation in size-at-age was largely explained by competition among Bristol Bay sockeye salmon and interspecific competition with other salmon in the North Pacific Ocean. Warm winters were associated with better growth of sockeye salmon, whereas warm summers were associated with reduced growth. Our findings point to competition at sea as the main driver of sockeye salmon size declines, and emphasize the trade-off between fish abundance and body size.
Surveillance of invasive meningococcal disease in southern Brazil: considerations of an immunization programme
Authors: Silveira Marcelle Moura , Crespo da Silva Pedro Augusto , Conrad Neida Lucia , Oliveira Thaís Larré , Hartwig Daiane Drawanz , Trotter Caroline
Published: February 2023

Invasive meningococcal disease (IMD) is a major cause of meningitis and septicaemia worldwide. Changes in serogroup predominance contribute to the unpredictable nature of the disease, with significant health impact. This study aimed to determine the epidemiological profile of IMD in Rio Grande do Sul, Santa Catarina and Paraná, three states in southern Brazil. We analysed 1024 IMD cases that had been confirmed by clinical and/or laboratory criteria and reported to the national information system for notifiable diseases between 2015 and 2019. Additionally, we calculated the proportions of serogroup and incidence by age. Of 1024 cases, 562 (55 %) were caused by serogroup C. Furthermore, serogroup W was responsible for almost half of the cases among children younger than 5 years between 2017 and 2018, with an overall incidence of 1.5 cases/100 000 infants. IMD remains a significant healthcare issue in southern Brazil despite reduced serogroup C incidence after the introduction of the meningococcal C conjugate vaccine into the childhood immunization programme. Changes in disease epidemiology were observed, and serogroup W was the most common serogroup among children younger than 5 years in 2017 and 2018. Although future cost-effectiveness studies are necessary, our results could have future implications for meningococcal vaccination programmes.
Addressing a climate emergency amidst the COVID-19 pandemic: A mixed-methods study on a hospital evacuation during the 2021 European floods
Authors: Wal Willemijn vd , Barten Dennis G. , Ketelings Linsay , Osch Frits v , Rao Madhura , Mortelmans Luc , Bierens Joost
Published: February 2023

Introduction

In July 2021, several European countries were affected by severe floods with water levels of the river Meuse reaching a record high. VieCuri Medical Center (Venlo, the Netherlands) is a hospital located directly adjacent to this river, and in response to the flood threat it was decided to completely evacuate the hospital. The aim of this study was to explore the decision-making process of this emergent evacuation.

Methods

A mixed-method approach was used. Qualitative data were collected through semi-structured interviews with 11 key participants closely involved in the evacuation. Quantitative data on the patients that were admitted at the time of the evacuation decision were collected, and included 30-day mortality, 7-day readmission rates and Charlson Comorbidity Index.

Results

Three themes were constructed from the interviews: risk-assessment, COVID-19 experience and collaboration. Participants highlighted the role of previous experiences from the COVID-19 pandemic. The use of a national patient coordination center enabled to rapidly assess capacity of potential destination hospitals. Furthermore, the hospital’s preparedness for evacuation could be improved by a thorough analysis of locoregional hazards and preparing for loss of regional healthcare capacity. Findings unrelated to decision-making included the inefficiency of large-scale ambulance dispatches and the expansion of business continuity plans. No patients died unanticipated during this hospital evacuation or within 30 days.

Conclusion

Experiences of the COVID-19 pandemic and the availability of a national patient coordination center were found to be decisive in performing this evacuation. This allowed for the swift identification of available capacity in appropriate destination hospitals.
IVUS Improves Outcomes with SUPERA Stents for the Treatment of Superficial Femoral-popliteal Artery Disease
Authors: Krishnan Prakash , Sharma Raman , Avadhani Sriya , Tarricone Arthur , Gee Allen , Farhan Serdar , Kamran Haroon , Kini Annapoorna , Sharma Samin
Published: February 2023

Objectives

To determine the effect of intravenous ultrasound (IVUS) when used adjunctively with nitinol interwoven bare metal stents in the management of femoropopliteal lesions.

Background

Nitinol interwoven bare metal stents represent an advancement in stent technology; however nominal deployment remains an area of focus. Intravascular Ultrasound (IVUS) has been shown to improve outcomes in both the coronary and peripheral vasculature by providing the operator with greater vessel detail. The use of adjunctive IVUS with Nitinol bare metal stents has not been widely studied.

Methods

This study included a cohort of 200 consecutive patients with peripheral artery disease. All patients were treated with ≥1 Supera bare metal stent, and 91 received adjunctive IVUS imaging prior to stent deployment. Deployment conditions of nominal, compressed, and elongated were measured and the primary clinical outcomes included target lesion reintervention, major and minor, below the knee amputation, and mortality.

Results

The patients who received IVUS had a significantly greater number of nominally deployed stents (p<0.001). Patients who had IVUS imaging also had significantly lower reintervention rates compared to those who did not receive IVUS imaging (p=0.047).

Conclusion

IVUS and angiography decreases clinically driven target lesion reintervention and increases nominal deployment compared to angiography alone in femoropopliteal lesions treated with interwoven bare metal nitinol stents.

Condensed Abstract

This retrospective study was done to examine the utility of intravenous ultrasound when used adjunctively for visualization in the management of femoropopliteal lesions in peripheral artery disease patients. There was total of 200 subjects and all were treated using the Supera nitinol self-expanding stent. By the end of the study, the group of subjects treated with intravenous ultrasound had significantly fewer reinterventions and had a greater rate of nominally deployed stents. These findings suggest the beneficial role intravenous ultrasound has compared to angiography alone in the management of femoropopliteal lesions with Supera stents.
Impact of Immune Evasion, Waning and Boosting on Dynamics of Population Mixing Between a Vaccinated Majority and Unvaccinated Minority
Authors: Fisman David N. , Amoako Afia , Simmons Allison , Tuite Ashleigh R.
Published: February 2023

Background

We previously demonstrated that when vaccines prevent infection, the dynamics of mixing between vaccinated and unvaccinated sub-populations is such that use of imperfect vaccines markedly decreases risk for vaccinated people, and for the population overall. Risks to vaccinated people accrue disproportionately from contact with unvaccinated people. In the context of the emergence of Omicron SARS-CoV-2 and evolving understanding of SARS-CoV-2 epidemiology, we updated our analysis to evaluate whether our earlier conclusions remained valid.

Methods

We modified a previously published Susceptible-Infectious-Recovered (SIR) compartmental model of SARS-CoV-2 with two connected sub-populations: vaccinated and unvaccinated, with non-random mixing between groups. Our expanded model incorporates diminished vaccine efficacy for preventing infection with the emergence of Omicron SARS-CoV-2 variants, waning immunity, the impact of prior immune experience on infectivity, “hybrid” effects of infection in previously vaccinated individuals, and booster vaccination. We evaluated the dynamics of an epidemic within each subgroup and in the overall population over a 10-year time horizon.

Results

Even with vaccine efficacy as low as 20%, and in the presence of waning immunity, the incidence of COVID-19 in the vaccinated subpopulation was lower than that among the unvaccinated population across the full 10-year time horizon. The cumulative risk of infection was 3-4 fold higher among unvaccinated people than among vaccinated people, and unvaccinated people contributed to infection risk among vaccinated individuals at twice the rate that would have been expected based on the frequency of contacts. These findings were robust across a range of assumptions around the rate of waning immunity, the impact of “hybrid immunity”, frequency of boosting, and the impact of prior infection on infectivity in unvaccinated people.

Interpretation

Although the emergence of the Omicron variants of SARS-CoV-2 has diminished the protective effects of vaccination against infection with SARS-CoV-2, updating our earlier model to incorporate loss of immunity, diminished vaccine efficacy and a longer time horizon, does not qualitatively change our earlier conclusions. Vaccination against SARS-CoV-2 continues to diminish the risk of infection among vaccinated people and in the population as a whole. By contrast, the risk of infection among vaccinated people accrues disproportionately from contact with unvaccinated people.
EphrinA4/EphA4 controls blood pressure via arterial sympathetic innervation
Authors: Simonnet Emilie , Martin Sabrina , Vilar José , Vessieres Emilie , Taib Sonia , Monceau Virginie , Pardanaud Luc , Bouby Nadine , Eichmann Anne , Silvestre Jean-Sébastien , Henrion Daniel , Brunet Isabelle
Published: February 2023

The autonomic sympathetic nervous system innervates peripheral resistance arteries, thereby controlling arterial diameter and modulating blood supply to organs and arterial tone. Despite its fundamental role in blood flow regulation and adaptive response of the cardiovascular system to challenging situations, how sympathetic arterial innervation develops remains poorly understood.

We here show that sympathetic arterial innervation is regulated by the axonal guidance molecule EphrinA4 in arterial Smooth Muscle Cells (SMCs), which repels sympathetic axons via the EphA4 receptor. Specific inactivation of EphA4 in sympathetic axons induced a loss of repulsion and increased sympathetic innervation of peripheral arteries throughout life. Functional consequences were a significant increase in arterial tone (resistivity and vasoconstriction), leading to an elevated systemic arterial blood pressure that reached to hypertension under stressful circumstances. These findings identify a novel pathway that negatively regulates sympathetic arterial innervation, and could participate to the appearance of idiopathic resistant hypertension.