bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation and Its Enforcement
Authors: Braga Anthony A. , Cook Philip J.
Published: January 2023

Gun regulations can only be effective to the extent that they are enforced. The goal of regulation is to keep guns away from dangerous people while allowing the vast majority of law-abiding adults to purchase and possess firearms. Federal regulations place restrictions on firearm design, transactions, and possession. Some states have more stringent controls that do not infringe on Second Amendment rights allowing people to keep guns in their home. Convicted felons and other prohibited persons generally do not acquire firearms from licensed retail dealers. Rather, proscribed people get their guns from unregulated transactions with friends and family or from the street. Increasing the time, effort, and expense of illegally acquiring guns can reduce gun use in violent crime. The Bureau of Alcohol, Tobacco, Firearms and Explosives, local police, and other law enforcement agencies can increase transaction costs for prohibited possessors by policing underground gun markets. Police can also enforce regulations against illegal carrying of guns in public places.
Reducing Shootings by the Police
Authors: Braga Anthony A. , Cook Philip J.
Published: January 2023

Police officers shoot roughly 1,000 people each year in the line of duty. Police killings typically occur in the context of fraught encounters with people carrying guns or other weapons, who in many cases are intoxicated or impaired due to mental illness, and who pose an imminent threat to the officer or others. Most police shootings are legally justifiable but are still problematic and preventable. Police departments need to improve their internal accountability mechanisms in order to launch a powerful response to officer-involved shootings. Nonlethal means of responding to tense situations must receive priority attention in training and departmental policy. Other reforms include better training for dealing with mental health crises, and strategies to prevent people from dying after being shot. Many police departments fail to provide sufficient training, guidance, and options to the great majority of officers who want to do the right thing in challenging circumstances.
Management of Diabetic Ketoacidosis in Pregnancy
Authors: Spencer Nicholas R. , Clark Shannon M. , Harirah Hassan M.
Published: January 2023

Diabetic ketoacidosis (DKA) is a rare, but potentially life-threatening complication of diabetes. Certain physiological changes during pregnancy predispose pregnant individuals to developing DKA. Early recognition and aggressive treatment are essential to avoid maternal and fetal morbidity and mortality. Although laboratory values can help to support, pregnant patients with DKA may not meet the usual criteria and the diagnosis can be made clinically. The key components to treatment include volume replacement, insulin infusion, correction of serum potassium, and fetal monitoring. With appropriate treatment, maternal mortality is low. After recovery, steps should be taken to avoid recurrence.
Acute Respiratory Distress Syndrome in Pregnancy: Updates in Principles and Practice
Authors: Watts Abigail , Duarte Alexander G.
Published: January 2023

Acute respiratory failure occurs in 0.05% to 0.3% of pregnancies and is precipitated by pulmonary and nonpulmonary insults. Acute respiratory distress syndrome (ARDS) is the rapid onset of hypoxemic respiratory failure associated with bilateral pulmonary opacities on chest imaging attributed to noncardiogenic pulmonary edema. The pathophysiological features of ARDS include hypoxemia, diminished lung volumes, and decreased lung compliance. While there is a paucity of data concerning ARDS in the pregnant individual, management principles do not vary significantly between pregnant and nonpregnant patients. The following review will discuss the diagnosis and management of the pregnant patient with ARDS.
Engaging medical students in cardiac surgery: a focus on equity, diversity, and inclusion
Authors: Elfaki Lina , Nwakoby Akachukwu , Lia Hillary , Zhao George , Sicila Amanda , Yoshida Nao , Yanagawa Bobby
Published: January 2023

Purpose of review

The Coronavirus Disease 2019 pandemic prohibited Canadian medical students from in-person observerships. This may be particularly detrimental to under-represented groups that may consider surgical subspecialties. To address the unprecedented need for alternative surgical career exploration and diversity within the profession, The University of Toronto Cardiac Surgery Interest Group and Division of Cardiac Surgery collaborated on virtual experiential programming.

Recent findings

Medical students were invited to virtual (1) observerships of a cardiac bypass case, (2) mentorship sessions with surgeons, (3) resident teaching sessions, (4) multidisciplinary case-based Heart Team discussions to further their understanding of the scope of Cardiac surgery, and (5) a virtual coronary anastomosis training program. Additionally, a comprehensive virtual program was spearheaded to increase interest in Cardiac surgery among low-income Black high school students.

Trainee response to the virtual education, mentorship, and skill acquisition was positive. Trainees reported high levels of interest in the profession, particularly among females and under-represented minorities, supporting the principles of equity diversity, and inclusion in Cardiac surgery.
RETRACTABLE UROLOGY THREE-PRONGED GRASPING FORCEPS FOR REMOVAL OF LARGE, NONMAGNETIC INTRAOCULAR FOREIGN BODIES
Authors: Brown Jaime E. , Fowler Benjamin J. , Channa Roomasa
Published: January 2023

Purpose:

To demonstrate the use of urology retractable three-pronged grasping forceps in the removal of a large, round, and nonmagnetic intraocular foreign body (IOFB) that was difficult to remove with other surgical instruments.

Methods:

Extraction of a 3.0 mm lead shot pellet embedded in vitreous hemorrhage was attempted with multiple surgical instruments including an intraocular magnet, IOFB forceps, and two tools designed for urology stone removal: a three-pronged grasping forceps and a nitinol basket extractor.

Results:

Owing to the round and smooth surface, large size, and nonmagnetic nature of the IOFB, extraction was challenging and failed with multiple other surgical instruments. The wide and secure grasp of the grasping forceps allowed for swift IOFB extraction without iatrogenic injury to the retina.

Conclusion:

The grasping forceps offer an effective and safe method for removal of large, round, and nonmagnetic IOFBs.
Factors Influencing the Acceptability of Nominal, Non-nominal, and Anonymous HIV Testing Options Among Young Men Living in Vancouver, Canada: A Qualitative Study
Authors: Lowik A.J. , Prangnell Amy , Carson Anna , Wong Jason , Knight Rod
Published: January 2023

Individuals unaware of their HIV seropositive status continue to represent a key “driver” of the HIV epidemic. Strategies to improve initiation into the HIV treatment cascade, including among young men, are required. This study assesses the acceptability of three HIV testing options among young cisgender men living in Vancouver, British Columbia. Using a modified grounded theory approach, we conducted semi-structured interviews with 45 young cisgender men ages 18–30 years to identify the factors influencing the acceptability of diverse HIV testing approaches. Participants ascribed value to non-nominal testing as a means of providing a secure pathway to HIV-related care for those who test positive while also safeguarding privacy. Anonymous HIV testing was problematized by participants as potentially creating difficulty in accessing ongoing HIV-related care. Most participants preferred non-nominal testing. Nevertheless, based on principles of equity, we argue that anonymous access to one's serostatus should be available, especially within a criminalized context.
Automated Coronary Artery Calcium and Quantitative Emphysema in Lung Cancer Screening
Authors: Balbi Maurizio , Sabia Federica , Ledda Roberta E. , Milanese Gianluca , Ruggirello Margherita , Silva Mario , Marchianò Alfonso V. , Sverzellati Nicola , Pastorino Ugo
Published: January 2023

Purpose:

To assess automated coronary artery calcium (CAC) and quantitative emphysema (percentage of low attenuation areas [%LAA]) for predicting mortality and lung cancer (LC) incidence in LC screening. To explore correlations between %LAA, CAC, and forced expiratory value in 1 second (FEV1) and the discriminative ability of %LAA for airflow obstruction.

Materials and Methods:

Baseline low-dose computed tomography scans of the BioMILD trial were analyzed using an artificial intelligence software. Univariate and multivariate analyses were performed to estimate the predictive value of %LAA and CAC. Harrell C-statistic and time-dependent area under the curve (AUC) were reported for 3 nested models (Modelsurvey: age, sex, pack-years; Modelsurvey-LDCT: Modelsurvey plus %LAA plus CAC; Modelfinal: Modelsurvey-LDCT plus selected confounders). The correlations between %LAA, CAC, and FEV1 and the discriminative ability of %LAA for airflow obstruction were tested using the Pearson correlation coefficient and AUC-receiver operating characteristic curve, respectively.

Results:

A total of 4098 volunteers were enrolled. %LAA and CAC independently predicted 6-year all-cause (Modelfinal hazard ratio [HR], 1.14 per %LAA interquartile range [IQR] increase [95% CI, 1.05-1.23], 2.13 for CAC ≥400 [95% CI, 1.36-3.28]), noncancer (Modelfinal HR, 1.25 per %LAA IQR increase [95% CI, 1.11-1.37], 3.22 for CAC ≥400 [95%CI, 1.62-6.39]), and cardiovascular (Modelfinal HR, 1.25 per %LAA IQR increase [95% CI, 1.00-1.46], 4.66 for CAC ≥400, [95% CI, 1.80-12.58]) mortality, with an increase in concordance probability in Modelsurvey-LDCT compared with Modelsurvey (P<0.05). No significant association with LC incidence was found after adjustments. Both biomarkers negatively correlated with FEV1 (P<0.01). %LAA identified airflow obstruction with a moderate discriminative ability (AUC, 0.738).

Conclusions:

Automated CAC and %LAA added prognostic information to age, sex, and pack-years for predicting mortality but not LC incidence in an LC screening setting. Both biomarkers negatively correlated with FEV1, with %LAA enabling the identification of airflow obstruction with moderate discriminative ability.
A review of online learning strategies for biological NMR techniques a survey of educators
Authors: Phelan Marie M
Published: January 2023

Disruption to teaching over the pandemic has led to a range of online and digital solutions. Given the utility of software and remote platforms for NMR teaching a UK-based survey for NMR educators in undergraduate and postgraduate teaching was rolled out Spring 2022 in order to establish what online tools and techniques are employed to teach NMR to biological sciences and appraise their relative efficacy. Based on the survey outcomes an overview of the breadth of methods employed as well as their perceived effectiveness is presented with a list of recommendations for common and successful strategies for online (and hybrid) teaching of NMR to the life sciences.
CRISPR/Cas9-mediated disruption ofCjACOS5confers no-pollen formation on sugi trees (Cryptomeria japonicaD. Don)
Authors: Nishiguchi Mitsuru , Futamura Norihiro , Endo Masaki , Mikami Masafumi , Toki Seiichi , Katahata Shin-Ichiro , Ohmiya Yasunori , Konagaya Ken-ichi , Nanasato Yoshihiko , Taniguchi Toru , Maruyama Tsuyoshi Emilio
Published: January 2023

Sugi (Cryptomeria japonicaD. Don) is an economically important coniferous tree in Japan. However, abundant sugi pollen grains are dispersed and transported by the wind each spring and cause a severe pollen allergy syndrome (Japanese cedar pollinosis). The use of pollen-free sugi that cannot produce pollen has been thought as a countermeasure to Japanese cedar pollinosis. The sugiCjACOS5gene is an ortholog ofArabidopsis ACOS5and riceOsACOS12, which encode an acyl-CoA synthetase that is involved in the synthesis of sporopollenin in pollen walls. To generate pollen-free sugi, we mutatedCjACOS5using the CRISPR/Cas9 system. As a result of sugi transformation mediated byAgrobacterium tumefaciensharboring theCjACOS5-targetedCRISPR/Cas9 vector, 1 bp-deleted homo biallelic mutant lines were obtained. Chimeric mutant lines harboring both mutant and wild-typeCjACOS5genes were also generated. The homo biallelic mutant lines had no-pollen in male strobili, whereas chimeric mutant lines had male strobili with or without pollen grains. Our results suggest thatCjACOS5is essential for the production of pollen in sugi and that its disruption is useful for the generation of pollen-free sugi. In addition to conventional transgenic technology, genome editing technology, including CRISPR/Cas9, can confer new traits on sugi.
Extensive and Persistent Extravascular Dermal Fibrin Deposition Characterizes Systemic Sclerosis
Authors: Browning Jeffrey L. , Bhawan Jag , Tseng Anna , Crossland Nicholas , Bujor Andreea M , Akassoglou Katerina , Assassi Shervin , Skaug Brian , Ho Jonathan
Published: January 2023

Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive multiorgan fibrosis. While the cause of SSc remains unknown, a perturbed vasculature is considered a critical early step in the pathogenesis. Using fibrinogen as a marker of vascular leakage, we found extensive extravascular fibrinogen deposition in the dermis of both limited and diffuse systemic sclerosis disease, and it was present in both early and late-stage patients. Based on a timed series of excision wounds, retention on the fibrin deposit of the splice variant domain, fibrinogen αEC, indicated a recent event, while fibrin networks lacking the αEC domain were older. Application of this timing tool to SSc revealed considerable heterogeneity in αEC domain distribution providing unique insight into disease activity. Intriguingly, the fibrinogen-αEC domain also accumulated in macrophages. These observations indicate that systemic sclerosis is characterized by ongoing vascular leakage resulting in extensive interstitial fibrin deposition that is either continually replenished and/or there is impaired fibrin clearance. Unresolved fibrin deposition might then incite chronic tissue remodeling.
Efficient chemical and enzymatic syntheses of FAD nucleobase analogues and their analysis as enzyme cofactors
Authors: Shah Ateek , Kumar Yashwant , Rohan S. , Hazra Amrita B.
Published: January 2023

Flavin adenine dinucleotide (FAD), an essential cofactor in cellular metabolism, catalyses a wide range of redox reactions. The organic synthesis of FAD is typically conducted by coupling flavin mononucleotide (FMN) and adenosine monophosphate. The reported synthesis routes have certain limitations such as multiple reaction steps, low yields, and/or difficult-to-obtain starting materials. In this study, we report the synthesis of FAD nucleobase analogues using chemical and enzymatic methods with readily available starting materials achieved in 1-3 steps with moderate yields (10-51%). Further, we demonstrate thatEscherichia coliglutathione reductase can use these analogues to catalyse the reduction of glutathione. Finally, we show that FAD nucleobase analogues can also be synthesized inside a cell from cellular substrates FMN and nucleoside triphosphates. This lays the foundation for their use in studying the molecular role of FAD in cellular metabolism and as biorthogonal reagents in biotechnology and synthetic biology applications.
Estimating the energy requirements for long term memory formation
Authors: Girard Maxime , Jiang Jiamu , van Rossum Mark CW
Published: January 2023

Brains consume metabolic energy to process information, but also to store memories. The energy required for memory formation can be substantial, for instance in fruit flies memory formation leads to a shorter lifespan upon subsequent starvation (Mery and Kawecki, 2005). Here we estimate that the energy required corresponds to about 10mJ/bit and compare this to biophysical estimates as well as energy requirements in computer hardware. We conclude that while the reason behind it is not known, biological memory storage is metabolically expensive,
A partially shared joint clustering framework for detecting protein complexes from multiple state-specific signed interaction networks
Authors: Zhan Youlin , Liu Jiahan , Wu Min , Heng Tan Chris Soon , Li Xiaoli , Ou-Yang Le
Published: January 2023

Detecting protein complexes is critical for studying cellular organizations and functions. The accumulation of protein-protein interaction (PPI) data enables the identification of protein complexes computationally. Although various computational approaches have been proposed to detect protein complexes from PPI networks, most of them ignore the signs of PPIs that reflect the ways proteins interact (activation or inhibition). As not all PPIs imply cocomplex relationships, taking into account the signs of PPIs can benefit the detection of protein complexes. Moreover, PPI networks are not static, but vary with the change of cell states or environments. However, existing protein complex identification algorithms are primarily designed for single-network clustering, and rarely consider joint clustering of multiple PPI networks. In this study, we propose a novel partially shared signed network clustering model (PS-SNC) for detecting protein complexes from multiple state-specific signed PPI networks jointly. PS-SNC can not only consider the signs of PPIs, but also identify the common and unique protein complexes in different states. Experimental results on synthetic and real datasets show that PS-SNC outperforms other state-of-the-art protein complex detection methods. Extensive analysis on real datasets demonstrate the effectiveness of PS-SNC in revealing novel insights about the underlying patterns of different cell lines.
COL7A1 expression improves prognosis prediction for patients with clear cell renal cell carcinoma atop of stage
Authors: Koca Dzenis , Séraudie Irinka , Jardiller Rémy , Cochet Claude , Filhol Odile , Guyon Laurent
Published: January 2023

Clear cell renal cell carcinoma (ccRCC) accounts for 75% of kidney cancers. Due to the high recurrence rate, and treatment options that come with high costs and potential side effects correct prognosis of patient survival is essential for the successful and effective treatment of patients. Novel biomarkers could play an important role in the assessment of the overall survival of patients. COL7A1 encodes for collagen type VII, a constituent of the basal membrane. COL7A1 is associated with survival in many cancers; however, the prognostic value of COL7A1 expression as a standalone biomarker in ccRCC has not been investigated. We used Kaplan-Meier curves and Cox proportional hazards model to investigate the prognostic value of COL7A1, as well as Gene Set Enrichment Analysis to investigate genes that are co-expressed with COL7A1. COL7A1 expression was used to stratify patients into four groups of expression, where the 5-year survival probability of each group was 72.4%, 59.1%, 34.15%, and 8.6% in order of increasing expression. Additionally, COL7A1 expression was successfully used to further divide patients of each stage and histological grade into groups of high and low risk. Similar results were obtained in independent cohorts.In-vitroknockdown of COL7A1 expression significantly impacted ccRCC cells’ ability to migrate and proliferate. To conclude, we identified COL7A1 as a new prognosis marker that can stratify ccRCC patients.
Osteoblast-intrinsic defect in glucose metabolism impairs bone formation in type II diabetic mice
Authors: Song Fangfang , Lee Won Dong , Marmo Tyler , Ji Xing , Song Chao , Liao Xueyang , Seeley Rebbeca , Yao Lutian , Liu Haoran , Long Fanxin
Published: January 2023

Skeletal fragility is associated with type 2 diabetes mellitus (T2D), but the underlying mechanism is not well understood. Here, in a mouse model for youth-onset T2D, we show that both trabecular and cortical bone mass are reduced due to diminished osteoblast activity. Stable isotope tracing in vivo with13C-glucose demonstrates that both glycolysis and glucose fueling of the TCA cycle are impaired in diabetic bones. Similarly, Seahorse assays show suppression of both glycolysis and oxidative phosphorylation by diabetes in bone marrow mesenchymal cells as a whole, whereas single-cell RNA sequencing reveals distinct modes of metabolic dysregulation among the subpopulations. Metformin not only promotes glycolysis and osteoblast differentiation in vitro, but also improves bone mass in diabetic mice. Finally, targeted overexpression of Hif1a or Pfkfb3 in osteoblasts of T2D mice averts bone loss. The study identifies osteoblast-intrinsic defects in glucose metabolism as an underlying cause of diabetic osteopenia, which may be targeted therapeutically.
A single amino acid polymorphism in natural Metchnikowin alleles ofDrosophilaresults in systemic immunity and life history tradeoffs
Authors: Perlmutter Jessamyn I. , Chapman Joanne R. , Wilkinson Mason C. , Nevarez-Saenz Isaac , Unckless Robert L.
Published: January 2023

Antimicrobial peptides (AMPs) are at the interface of interactions between hosts and microbes and are therefore expected to be fast evolving in a coevolutionary arms race with pathogens. In contrast, previous work demonstrated that one AMP, Metchikowin (Mtk), has a single residue that segregates as either proline (P) or arginine (R) in populations of four differentDrosophilaspecies, some of which diverged more than 10 million years ago. The recurrent finding of this polymorphism regardless of geography or host species, coupled with evidence of balancing selection inDrosophilaAMPs, suggest there is a distinct functional importance to each allele. The most likely hypotheses involve alleles having specificity to different pathogens or the more potent allele conferring a cost on the host. To assess their functional differences, we createdD. melanogasterlines with the P allele, R allele, orMtknull mutation using CRISPR/Cas9 genome editing. Here, we report results from experiments assessing the two hypotheses using these lines. In males, testing of systemic immune responses to a repertoire of bacteria and fungi demonstrated that the R allele performs as well or better than the P and null alleles with most infections. With some pathogens, however, females show results in contrast with males whereMtkalleles either do not contribute to survival or where the P allele outperforms the R allele. In addition, measurements of life history traits demonstrate that the R allele is more costly in the absence of infection for both sexes. These results provide strongin vivoevidence that differential fitness with or without infection and sex-based functional differences in alleles may be adaptive mechanisms of maintaining immune gene polymorphisms in contrast with expectations of rapid evolution. Therefore, a complex interplay of forces including pathogen species and host sex may lead to balancing selection for immune genotypes. Strikingly, this selection may act on even a single amino acid polymorphism in an AMP.
CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway
Authors: Green Luke R. , Issa Rahaf , Albaldi Fawzyah , Urwin Lucy , Khalid Henna , Turner Claire E. , Ciani Barbara , Partridge Lynda J. , Monk Peter N.
Published: January 2023

Objectives

Epithelial colonisation is a critical first step in bacterial pathogenesis.Staphylococcus aureuscan utilise several host factors to associate with cells, including α5βl integrin and heparan sulphate proteoglycans, such as the syndecans. Here, we demonstrate that a partner protein of both integrins and syndecans, the host membrane adapter protein tetraspanin CD9, is essential for syndecan-mediated staphylococcal adhesion. Fibronectin is also essential in this process while integrins are only critical for post-adhesion entry into human epithelial cells.

Methods and Results

Treatment of epithelial cells with CD9-derived peptide or heparin caused significant reductions in staphylococcal adherence, dependent on both CD9 and syndecan-1. Exogenous fibronectin caused a CD9-dependent increase in staphylococcal adhesion whereas blockade of β1 integrins did not affect adhesion but did reduce the subsequent internalisation of adhered bacteria. CD9 disruption or deletion increased β1 integrin-mediated internalisation, suggesting that CD9 coordinates sequential staphylococcal adhesion and internalisation.

Conclusions

CD9 controls staphylococcal adhesion through syndecan-1, using a mechanism that likely requires CD9-mediated syndecan organisation to correctly display fibronectin at the host cell surface. We propose that CD9-derived peptides or heparin analogues could be developed as anti-adhesion treatments to inhibit the initial stages of staphylococcal pathogenesis.
Proline catabolism is key to facilitatingCandida albicanspathogenicity
Authors: Silao Fitz Gerald S. , Jiang Tong , Bereczky-Veress Biborka , Kühbacher Andreas , Ryman Kicki , Uwamohoro Nathalie , Jenull Sabrina , Nogueira Filomena , Ward Meliza , Lion Thomas , Urban Constantin F. , Rupp Steffen , Kuchler Karl , Chen Changbin , Peuckert Christiane , Ljungdahl Per O.
Published: January 2023

Candida albicans, the primary etiology of human mycoses, is well-adapted to catabolize proline to obtain energy to initiate morphological switching (yeast to hyphal) and for growth. We report thatput1-/-andput2-/- strains, carrying defectiveProlineUTilization genes, display remarkable proline sensitivity withput2-/- mutants being hypersensitive due to the accumulation of the toxic intermediate P5C, which inhibits mitochondrial respiration. Theput1-/- andput2-/-mutations attenuate virulence inDrosophilaand murine candidemia models. Using intravital 2-photon microscopy and label-free non-linear imaging, we visualized the initial stages ofC. albicanscells colonizing a kidney in real-time, directly deep in the tissue of a living mouse, and observed morphological switching of wildtype but not ofput2-/-cells. Multiple members of theCandidaspecies complex, includingC. auris, are capable of using proline as a sole energy source. Our results indicate that a tailored proline metabolic network tuned to the mammalian host environment is a key feature of opportunistic fungal pathogens.
Obesity Modifies Clinical Outcomes of Right Ventricular Dysfunction
Authors: Ma Janet I. , Zern Emily , Jiang Nona , Wang Dongyu , Rambarat Paula , Pomerantsev Eugene , Picard Michael H. , Ho Jennifer E.
Published: January 2023

Introduction

Right ventricular (RV) dysfunction is associated with increased mortality across a spectrum of cardiovascular diseases. The role of obesity in RV dysfunction and adverse outcomes is unclear.

Methods

We examined patients undergoing right heart catheterization between 2005-2016 in a hospital-based cohort. Linear regression was used to examine the association of obesity with hemodynamic indices of RV dysfunction [pulmonary artery pulsatility index (PAPi), right atrial pressure: pulmonary capillary wedge pressure ratio (RAP:PCWP), RV stroke work index (RVSWI)]. Cox models were used to examine the association of RV function measures with clinical outcomes.

Results

Among 8285 patients (mean age 63 years, 40% women), higher BMI was associated with worse indices of RV dysfunction, including lower PAPi (β -0.26, SE 0.01, p <0.001), higher RA:PCWP ratio (β 0.25, SE 0.01, p-value <0.001), and lower RVSWI (β -0.05, SE 0.01, p-value <0.001). Over 7.3 years of follow-up, we observed 3006 mortality and 2004 heart failure (HF) hospitalization events. RV dysfunction was associated with greater risk of mortality (eg PAPi: HR 1.11 per 1-SD increase, 95% CI 1.04-1.18), with similar associations with risk of HF hospitalization. BMI modified the effect of RV dysfunction on outcomes (P-interaction <=0.005 for both), such that the effect of RV dysfunction was more pronounced at higher BMI.

Conclusions

Patients with obesity had worse hemodynamic measured indices of RV function across a broad hospital-based sample. While RV dysfunction was associated with worse clinical outcomes including mortality and HF hospitalization, this association was especially pronounced among individuals with higher BMI.
Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated cell response toListeriainfection
Authors: Corre Morgane , Boehm Volker , Besic Vinko , Kurowska Anna , Viry Anouk , Mohammad Ammara , Sénamaud-Beaufort Catherine , Thomas-Chollier Morgane , Lebreton Alice
Published: January 2023

Cell autonomous responses to intracellular bacteria largely depend on gene expression reorganization. To gain isoform-level resolution into these regulations, we combined long- and short-read transcriptomic analyses of the response of intestinal epithelial cells to infection by the foodborne pathogenListeria monocytogenes. Among the most striking isoform-based regulations, expression of the cellular stress response regulator CIRBP (cold-inducible RNA-binding protein) and of several SRSFs (serine/arginine-rich splicing factors) switched from canonical transcripts to nonsense-mediated decay-sensitive isoforms by inclusion of “poison exons”. We showed that damage to host cell membranes caused by bacterial pore-forming toxins (listeriolysin O, perfringolysin, streptolysin, or aerolysin) led to the dephosphorylation of SRSF proteinsviathe inhibition of the kinase activity of CLK1, thereby driving CIRBP alternative splicing. CIRBP isoform usage was found to have consequences on infection, since selective repression of canonical CIRBP reduced intracellular bacterial load while that of the poison exon-containing isoform exacerbated it. Consistently, CIRBP-bound mRNAs were shifted towards stress-relevant transcripts in infected cells, with increased mRNA levels or reduced translation efficiency for some targets. Our results thus generalize the alternative splicing of CIRBP and SRSFs as a common response to biotic or abiotic stresses by extending its relevance to the context of bacterial infection.
Multiomics study ofCHCHD10S59L-related disease reveals energy metabolism downregulation: OXPHOS and β-oxidation deficiencies associated with lipids alterations
Authors: Hounoum Blandine Madji , Bellon Rachel , Genin Emmanuelle C , Bannwarth Sylvie , Lefevre Antoine , Fleuriol Lucile , Debayle Delphine , Gay Anne-Sophie , Petit-Paitel Agnès , Lacas-Gervais Sandra , Blasco Hélène , Emond Patrick , Paquis-Flucklinger Veronique , Ricci Jean-Ehrland
Published: January 2023

Mutations in the coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) gene have been associated with a large clinical spectrum including myopathy, cardiomyopathy and amyotrophic lateral sclerosis (ALS). Herein, we analyzed the metabolic changes induced by the p.S59LCHCHD10mutation to identify new therapeutic opportunities. Using metabolomic, lipidomic and proteomic analysis we observed a strong alteration of metabolism in plasma and heart ofChchd10S59L/+mice compared to their wild type littermates at pre-symptomatic and symptomatic stages. In plasma, levels of phospholipids were decreased while those of carnitine derivatives and most of amino acids were increased. The cardiac tissue fromChchd10S59L/+mice showed a decreased Oxidative Phosphorylation (OXPHOS) and β-oxidation proteins levels as well as tricarboxylic acid cycle (TCA) intermediates and carnitine pathway metabolism. In parallel, lipidomics analysis reveals a drastic change in the lipidome, including triglycerides, cardiolipin and phospholipids. Consistent with this energetic deficiency in cardiac tissue, we show that L-acetylcarnitine supplementation improves the mitochondrial network length in IPS-derived cardiomyocytes from a patient carrying theCHCHD10S59L/+mutation. These data indicate that a bioenergetic intermediate such as L-acetylcarnitine may restore mitochondrial function inCHCHD10-related disease, due to the reduction in energy deficit that could be compensated by carnitine metabolic pathways.
Remittances, institutional quality and investment in Sub-Saharan Africa
Authors: Mohammed Umar , Karagöl Erdal Tanas
Published: January 2023

Purpose

This paper investigates the relationship between remittances, institutional quality and investment in Sub-Saharan African (SSA) countries using data from 2004 to 2018.

Design/methodology/approach

The two-stage least squares (2SLS) estimator is the main methodology used, while the system generalized method of moments (Sys-GMM) technique is employed to test the robustness of the results.

Findings

The results show a positive and significant impact of remittances on investment in SSA. The findings further reveal a substitutional linkage between remittances and institutions in promoting investment. In essence, remittances serve as investment capital in countries with poor institutions. The results also show that the marginal significance of remittances as a source of funds for investment decreases in countries with well-developed institutions.

Research limitations/implications

The sample excludes some of the SSA countries due to the unavailability of data.

Practical implications

In the face of current institutional weaknesses, there is a need for SSA countries to prioritize policies that encourage the effective use of remittances for business activities. Furthermore, SSA countries must improve their economic freedom and democratic practices by reducing government size, protecting property rights, and promoting respect for political and civil rights.

Originality/value

This is the first study to analyze the relationship between remittances, institutional quality and investment in SSA. It also provides a novel framework for future research on the remittance–investment nexus.
Expatriate bubbles in Dubai: expatriates from West and East cohabitating with locals
Authors: Primecz Henriett
Published: January 2023

Purpose

Focussing on the stratification of expatriates and the boundaries between different types of expatriates and locals, this study investigates the lived experiences and testimonies of Eastern European expatriates and their relationships in Dubai. The purpose of this article to develop the current knowledge on expatriates cohabiting in a cosmopolitan city by providing empirical evidence on expatriate bubbles in Dubai.

Design/methodology/approach

Explorative qualitative research was conducted using online and face-to-face interviews, along with a week-long intensive ethnography with observations, interviews and informal discussions.

Findings

Three distinct groups of people live in Dubai, namely, Westerners, expatriates from the East and Emiratis. They hardly mingle with each other on equal terms, but they do work in a complementary fashion. In Dubai, the status of East European experts, a subgroup of Westerners, is similar to their Western counterparts and in that they are considered European. Consequently, they experience a slight status development in comparison to when they work in the West. The research provides evidence on social stratification of expatriate bubbles.

Research limitations/implications

This very short ethnography with a relatively small number of qualitative interviews could be complemented by a further in-depth study.

Originality/value

Expatriate bubbles have not previously been empirically investigated from an Eastern European perspective, nor has the unique case of Dubai been analysed extensively. Distinct expatriate bubbles with their stratified hierarchies have been identified in this study.
Similarities and differences in motivation in cross-disciplinary biomedical, policy, and education health science teams: a mixed methods comparative case study using the MATRICx
Authors: Lotrecchiano Gaetano Romano , Balog Emily , Brundage Shelley , Deyo Patricia , Conlon Leocadia , Bugin Kevin , Sheffey Landria , Cook Ellen , Gentry Melissa
Published: January 2023

Purpose

This study aims to investigate individual motivations for participating in collaborative health knowledge producing teams (KPTs), as well as satisfaction gained by participation in science teams. The authors focus on understanding motivators across team types, levels of engagement and alignment within and across teams and need satisfaction in a total of six science teams. Areas of strong congruence and divergence of motivating factors can be aligned across (i) learning and professional growth satisfaction, (ii) respect, collegiality and enjoyment satisfaction and (iii) accomplishment and discovery satisfaction. Levels of satisfaction are hierarchically mapped showing their relation to more external and communal foci to motivations that seek satisfaction of individual needs.

Design/methodology/approach

This mixed method comparative study uses data from the motivation assessment for team readiness integration and collaboration (MATRICx) tool and themes generated from semi-structured interviews. This methodology provided a means to compare a hierarchy of motivations against levels of collaborative engagement, as well as individual needs satisfaction and ultimately the identification of higher and lower-level motivations related to self and external foci.

Findings

The findings indicate that there are both similarities and differences in motivations in different health science teams when one compares biomedical, education and policy teams. A comparison of MATRICx data from across team types and teams suggests areas of strong congruence as well as areas of divergence in motivation factors.

Originality/value

The paper and its findings use a novel tool along with qualitative research techniques to identify motivation in KPTs and uses these data to understand what type of needs satisfaction are important across three areas of health science teaming. Our research informs team leaders, facilitators and consultants about the important motivations team members have entering teams and has the potential to provide a blueprint to ensure peak performance as individual team members seek to address their ever-growing professional needs.
All together now: Geographically coordinated miticide treatment benefits honey bee health
Authors: Woodford Luke , Sharpe Graeme , Highet Fiona , Evans David J.
Published: January 2023

Deformed wing virus (DWV) is a pathogenic virus of honey bees transmitted by the ectoparasitic mite Varroa destructor. Annual overwintering colony losses, accounting for ~25% of all colonies, are associated with high levels of Varroa‐DWV infestation. Effective miticide treatments are available to control Varroa. However, the absence of coordinated treatment means environmental transmission of mites continues unchecked. We aimed to determine whether rational, coordinated treatment is beneficial, and characterized the DWV population as an indicator of colony health.

This study uses coordinated treatment of Varroa in a geographically isolated environment (Isle of Arran, Scotland) over 3 years. The study area contained 50–84 colonies managed by ~20 amateur beekeepers. Sampling and virus analysis to assess strain diversity and viral loads were conducted before and after treatments, and changes in population diversity were quantified by sequence analysis.

Over the 3 years analysis of the virus population revealed that the dominant DWV variant shifted from Type A to Type B in all apiaries, regardless of mite levels or proximity to other colonies. During this period the number of managed colonies increased by 47% (57–84 colonies), but despite this, we estimate total mite numbers decreased by 58%.

Synthesis and applications. In this study, the beekeepers in Arran significantly improved the number of colonies they managed, without importing any bees onto the island, indicating that an improved focus on management techniques, through the combination of a coordinated miticide programme and an improved understanding of bee diseases, could yield positive results for bee health and sustainability.
Challenges and directions for open ecosystems biodiversity restoration: An overview of the techniques applied for Cerrado
Authors: Pilon Natashi A. L. , Campos Bruna H. , Durigan Giselda , Cava Mário G. B. , Rowland Lucy , Schmidt Isabel , Sampaio Alexandre , Oliveira Rafael S.
Published: January 2023

Ecological restoration of tropical open ecosystems remains challenging for both science and practice. Over the last decade, innovative techniques have been developed, but whether they have been successful or not remains to be demonstrated. Assessing the outcomes of these initiatives is crucial to drive the following steps to improve tropical grasslands and savanna restoration.

Analysing 82 data sets from the literature and primary data collection, we assessed the effectiveness of passive and active restoration techniques applied in Cerrado open ecosystems. We used plant diversity variables (species and growth forms) as indicators, considering ruderals and exotics as non‐target species. Specifically, we aimed to answer: (i) How does the diversity of target species change through time in areas subject to passive restoration? (ii) Are active and passive restoration techniques effective in restoring the proportion of target species found in old‐growth reference ecosystems? (iii) Have the current techniques been successful in recovering the proportions of growth forms of reference ecosystems?

We found that target species proportions do not increase with time, suggesting limitations of typical species to colonise degraded sites. Hence, passive restoration will promote the conservation of a limited and constant number of target species. This number will depend on the magnitude of degradation and previous land use.

The restoration techniques currently applied to restore the biodiversity of Cerrado open ecosystems are not reaching the reference standards, with distinct techniques driving plant communities to different sets of growth forms. Active restoration based on propagules obtained from pristine donor sites (topsoil translocation, plant material transplant, and seeding) performed better than passive restoration for most of the growth forms analysed.

Synthesis and applications: Different growth forms have different roles in determining the structure and functioning of Cerrado vegetation. A mix of techniques can better approximate plant diversity and the proportionality of target species of pristine ecosystems. Singular restoration approaches are insufficient for restoring Cerrado open ecosystem biodiversity. Mixed efforts encompassing various techniques are required instead. Furthermore, it is likely restoration success can be improved with greater investment in improving our understanding of, and developing existing restoration techniques.
Early adulthood and current physical activity and their association with symptoms of pelvic floor disorders in middle‐aged women: An observational study with retrospective physical activity assessment
Authors: Kuutti Mari A. , Hyvärinen Matti , Kauppinen Markku , Sipilä Sarianna , Aukee Pauliina , Laakkonen Eija K.
Published: January 2023

Objective

To investigate associations of early and middle adulthood physical activity (PA) with symptoms of pelvic floor disorders (PFDs), i.e. stress urinary incontinence (SUI), urge urinary incontinence (UUI), faecal incontinence (FI), constipation or defecation difficulties (CDDs) and feeling of pelvic organ prolapse (POP) among middle‐aged women.

Design

A cross‐sectional, observational study with retrospective PA assessment.

Setting

University Research Laboratory.

Sample

A random population sample of 1098 Finnish women aged 47–55 years.

Methods

Early adulthood PA, current PA, and demographic and gynaecological variables were assessed using self‐report questionnaires. Logistic regression analyses were applied to study associations of PA variables with symptoms of PFDs. Potential confounding effects of demographic and gynaecological variables were controlled in multiple logistic regression models.

Main Outcome Measures

Structured questionnaire‐assessed retrospective PA assessment at the age of 17–29 years, current PA at middle age, and prevalence of symptoms of CDD, FI, POP, SUI and UUI.

Results

Current PA was not independently associated with the occurrence of the symptoms of PFDs. Middle‐aged women with an early adulthood history of competitive sports were more likely to experience symptoms of UUI (OR 2.16, 95% CI 1.10–4.24, p = 0.025) but not symptoms of SUI, FI, CDD or POP, whereas women with a history of regular PA were more likely to experience symptoms of FI (OR 4.41, 95% CI 1.05–18.49, p = 0.043) but no other symptoms of PFDs.

Conclusions

Competitive sports during early adulthood may increase the risk of UUI in middle age. Regular PA during early adulthood may increase the risk of FI.
Diagnostic testing for evaluation of brief resolved unexplained events
Authors: Mittal Manoj K. , Tieder Joel S. , Westphal Kathryn , Sullivan Erin , Hall Matt , Bochner Risa , Cohen Adam , Colgan Jennifer Y. , Delaney Atima C. , DeLaroche Amy M. , Graf Thomas , Harper Beth , Kaplan Ron L. , Neubauer Hannah C. , Neuman Mark I. , Shastri Nirav , Wilkins Victoria , Stephans Allayne
Published: January 2023

Background

Since the publication of the American Academy of Pediatrics (AAP) clinical practice guideline for brief resolved unexplained events (BRUEs), a few small, single‐center studies have suggested low yield of diagnostic testing in infants presenting with such an event. We conducted this large retrospective multicenter study to determine the role of diagnostic testing in leading to a confirmatory diagnosis in BRUE patients.

Methods

Secondary analysis from a large multicenter cohort derived from 15 hospitals participating in the BRUE Quality Improvement and Research Collaborative. The study subjects were infants < 1 year of age presenting with a BRUE to the emergency departments (EDs) of these hospitals between October 1, 2015, and September 30, 2018. Potential BRUE cases were identified using a validated algorithm that relies on administrative data. Chart review was conducted to confirm study inclusion/exclusion, AAP risk criteria, final diagnosis, and contribution of test results. Findings were stratified by ED or hospital discharge and AAP risk criteria. For each patient, we identified whether any diagnostic test contributed to the final diagnosis. We distinguished true (contributory) results from false‐positive results.

Results

Of 2036 patients meeting study criteria, 63.2% were hospitalized, 87.1% qualified as AAP higher risk, and 45.3% received an explanatory diagnosis. Overall, a laboratory test, imaging, or an ancillary test supported the final diagnosis in 3.2% (65/2036, 95% confidence interval [CI] 2.7%–4.4%) of patients. Out of 5163 diagnostic tests overall, 1.1% (33/2897, 95% CI 0.8%–1.5%) laboratory tests and 1.5% (33/2266, 95% CI 1.0%–1.9%) of imaging and ancillary studies contributed to a diagnosis. Although 861 electrocardiograms were performed, no new cardiac diagnoses were identified during the index visit.

Conclusions

Diagnostic testing to explain BRUE including for those with AAP higher risk criteria is low yield and rarely contributes to an explanation. Future research is needed to evaluate the role of testing in more specific, at‐risk populations.