bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of CFTR in diabetes‐induced pancreatic ductal fluid and HCO3− secretion
Authors: Ébert Attila , Gál Eleonóra , Tóth Emese , Szögi Titanilla , Hegyi Péter , Venglovecz Viktória
Published: February 2024

Type 1 diabetes is a disease of the endocrine pancreas; however, it also affects exocrine function. Although most studies have examined the effects of diabetes on acinar cells, much less is known regarding ductal cells, despite their important protective function in the pancreas. Therefore, we investigated the effect of diabetes on ductal function. Diabetes was induced in wild‐type and cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice following an i.p. administration of streptozotocin. Pancreatic ductal fluid and HCO3− secretion were determined using fluid secretion measurements and fluorescence microscopy, respectively. The expression of ion transporters was measured by real‐time PCR and immunohistochemistry. Transmission electron microscopy was used for the morphological characterization of the pancreas. Serum secretin and cholecystokinin levels were measured by an enzyme‐linked immunosorbent assay. Ductal fluid and HCO3− secretion, CFTR activity, and the expression of CFTR, Na+/H+ exchanger‐1, anoctamine‐1 and aquaporin‐1 were significantly elevated in diabetic mice. Acute or chronic glucose treatment did not affect HCO3− secretion, but increased alkalizing transporter activity. Inhibition of CFTR significantly reduced HCO3− secretion in both normal and diabetic mice. Serum levels of secretin and cholecystokinin were unchanged, but the expression of secretin receptors significantly increased in diabetic mice. Diabetes increases fluid and HCO3− secretion in pancreatic ductal cells, which is associated with the increased function of ion and water transporters, particularly CFTR.

image

Key points

There is a lively interaction between the exocrine and endocrine pancreas not only under physiological conditions, but also under pathophysiological conditions

The most common disease affecting the endocrine part is type‐1 diabetes mellitus (T1DM), which is often associated with pancreatic exocrine insufficiency

Compared with acinar cells, there is considerably less information regarding the effect of diabetes on pancreatic ductal epithelial cells, despite the fact that the large amount of fluid and HCO3− produced by ductal cells is essential for maintaining normal pancreatic functions

Ductal fluid and HCO3− secretion increase in T1DM, in which increased cystic fibrosis transmembrane conductance regulator activation plays a central role.

We have identified a novel interaction between T1DM and ductal cells. Presumably, the increased ductal secretion represents a defence mechanism in the prevention of diabetes, but further studies are needed to clarify this issue.
The Effects of Trade Participation on Labor Productivity, Wages and Female Employment: Evidence from Egyptian Manufacturing Firms
Authors: Kamal Yasmine
Published: February 2024

The study examines the effects of firm trade participation on labor productivity, wages, and female employment using recent manufacturing enterprise survey data for Egypt. It finds positive labor productivity premium for both exporting and importing firms, being the highest for small-sized exporting firms reflecting their greater benefits from learning-by-exporting. Importing intermediate inputs enhances productivity the most for firms in medium-high and high technology intensive sectors. Moreover, both exporting and importing firms pay higher average wages than non-exporters and non-importers, where economies of scale and higher productivity of trading firms-rather than the skill characteristics or composition of labor force- work as the explanatory channels. Also, firm trade participation enhances gender labor outcomes through reducing the gender wage gap and employing a higher share of female workers especially in low technology export sectors. To translate these favorable impacts into an economywide labor market improvements in Egypt, more efforts should be done in reforming the business environment to enable a greater participation of small firms into export markets and an easier access of firms-especially those operating in technologically advanced sectors- to essential imported inputs that embody advanced foreign knowledge and/or are of higher quality than domestic alternatives.
Numerical and Experimental Study on the Influence of Honeycomb Bushing Wear on the Leakage Flow Characteristics of Labyrinth Seal
Authors: Xu Wenfeng , Wang Zeming , Sun Dan , Ren Guozhe , Li Yu , Lu Dezheng
Published: February 2024

Honeycomb bushing wear has a significant effect on the leakage characteristics of the labyrinth seal. In this paper, four kinds of honeycomb bushing labyrinth seals was designed and processed. The leakage characteristics of honeycomb bushing labyrinth seal were studied experimentally under different inlet and outlet pressure ratios and sealing clearance conditions. At the same time, the numerical model of honeycomb bushing labyrinth seals were established, and the influence of honeycomb bushing wear on the flow field characteristics of labyrinth seals was analyzed by numerical simulation. The existing leakage formula was modified by the correction coefficient method. The results show that with the increase in wear depth, the leakage of the honeycomb bushing labyrinth seal increases, and the maximum leakage can be increased by 59.59%. The wear groove weakens the throttling effect of the labyrinth, causing the leakage of the seal to increase. The increase of the depth of the wear groove changes the flow area and the direction of the jet so that the leakage increases slightly. The influence of the wear groove on the leakage characteristics of the honeycomb bushing labyrinth seal is gradually reduced under the condition of large clearance. The theoretical formula of leakage is corrected by the correction coefficient method. The value calculated by the corrected theoretical formula of leakage is in good agreement with the experiment, and the error is within 10%. It meets the practical application of the project.
Multidisciplinary Design Methodology for Micro-Gas-Turbines—Part II: System Analysis and Optimization
Authors: Badum Lukas , Cukurel Beni
Published: February 2024

Owing to their high specific energy capabilities, ultramicrogas turbines (UMGT) are a high-potential technology to provide portable electric power supply for applications with demand of less than 1 kW. UMGT conceptual design is challenged by small-scale effects augmenting interdisciplinary dependencies leading to highly coupled, nonlinear component interactions. This work provides a novel approach to conceptual UMGT design by combining reduced order component and system modeling with constrained multi-objective optimization. Hereby, Part I presents integrated design and performance modeling of compressor, turbine, combustor, and generator. In Part II, the heat engine and generator modules are merged into a system framework by establishing conceptual UMGT rotor geometry and engine design. Following bearing selection and lifetime assessment, experimentally validated reduced order models are developed for heat transfer and rotordynamic analysis. Using the elaborated framework, a constrained multi-objective system optimization of a 300 W engine is performed based on ten design parameters and comparing SiAlON and Inconel 718 as potential rotor materials available for additive manufacturing. Hereby, bearing lifetime, system efficiency, and specific power are maximized while meeting rotordynamic, structural, and thermal requirements. Evaluating the results, interdisciplinary effects are highlighted, and two optimum engine configurations are suggested.
Effect of the Key Geometry and Flow Parameters on Discharge Coefficient of Laidback Fan-Shaped Hole Under Coolant Crossflow Condition
Authors: Haoyang Liu , Qiang Du , Qingzong Xu , Guangyao Xu , Hongye Li , Dawei Chen , Song Liu , Siyi Wang
Published: February 2024

A laidback fan-shaped hole is commonly used due to its superior lateral film coverage. Its discharge coefficient is significantly influenced by internal crossflow owing to its complex geometrical structure. In this paper, the authors numerically investigate the flow mechanisms of the laidback fan-shaped hole under the influence of internal crossflow. The numerical simulations utilize the validated SST k–ω turbulence model, with the Reynolds number of internal crossflow ranging from 20,000 to 160,000 and the ratio of pressure ranging from 1 to 1.6. The results show that the different orientations of internal crossflow cause varying degrees of in-hole separation that led to a discrepancy in the discharge coefficient. The larger the Reynolds number of the crossflow is, the more drastic the change in the discharge coefficient. Furthermore, a comparison between the results obtained with and without internal crossflow has shown that the length of the cylindrical section is the primary factor determining the discharge coefficient of the laidback fan-shaped hole. The magnitude of the discharge coefficient depended on the extent of flow separation within the cylindrical section. Additionally, the numerical simulations obtained the discharge coefficient under a high internal crossflow Reynolds number of internal crossflow and a wall with a constant thickness and compared it with the predictions of a low-dimensional model of the discharge coefficient (based on our previous experimental data). The discrepancy between the results is within 10%, thus verifying the scalability of the low-dimensional model.
Evaluating OpenAI's Whisper ASR: Performance analysis across diverse accents and speaker traits
Authors: Graham Calbert , Roll Nathan
Published: February 2024

This study investigates Whisper's automatic speech recognition (ASR) system performance across diverse native and non-native English accents. Results reveal superior recognition in American compared to British and Australian English accents with similar performance in Canadian English. Overall, native English accents demonstrate higher accuracy than non-native accents. Exploring connections between speaker traits [sex, native language (L1) typology, and second language (L2) proficiency] and word error rate uncovers notable associations. Furthermore, Whisper exhibits enhanced performance in read speech over conversational speech with modifications based on speaker gender. The implications of these findings are discussed.
Social Media and Sport Research: Empirical Examinations Showcasing Diversity in Methods and Topics
Authors: Sanderson Jimmy , Abeza Gashaw
Published: February 2024

This commentary introduces the second of two special issues in the International Journal of Sport Communication centered on social media and sport. The empirical studies presented in this issue illustrate both the diversity of topics and methodological approaches utilized by researchers working at the intersection of social media and sport. Research articles in this issue analyze topics ranging from sport consumer behavior to online fan communities to coaches’ perceptions of activism-related content posted on team social media accounts. The research presented here also employs a variety of methodological approaches including experimental design, critical discourse analysis, rhetorical analysis, and applications of artificial intelligence and machine learning. Collectively, these studies offer a foundation on which future research in social media and sport can build to continue to enhance our understanding of social media’s impact on the sport world.
The incredible bulk: Human cytomegalovirus tegument architectures uncovered by AI-empowered cryo-EM
Authors: Jih Jonathan , Liu Yun-Tao , Liu Wei , Zhou Z. Hong
Published: February 2024

The compartmentalization of eukaryotic cells presents considerable challenges to the herpesvirus life cycle. The herpesvirus tegument, a bulky proteinaceous aggregate sandwiched between herpesviruses’ capsid and envelope, is uniquely evolved to address these challenges, yet tegument structure and organization remain poorly characterized. We use deep-learning–enhanced cryogenic electron microscopy to investigate the tegument of human cytomegalovirus virions and noninfectious enveloped particles (NIEPs; a genome packaging-aborted state), revealing a portal-biased tegumentation scheme. We resolve atomic structures of portal vertex-associated tegument (PVAT) and identify multiple configurations of PVAT arising from layered reorganization of pUL77, pUL48 (large tegument protein), and pUL47 (inner tegument protein) assemblies. Analyses show that pUL77 seals the last-packaged viral genome end through electrostatic interactions, pUL77 and pUL48 harbor a head–linker–capsid-binding motif conducive to PVAT reconfiguration, and pUL47/48 dimers form 45-nm-long filaments extending from the portal vertex. These results provide a structural framework for understanding how herpesvirus tegument facilitates and evolves during processes spanning viral genome packaging to delivery.
Intensification of daily tropical precipitation extremes from more organized convection
Authors: Bao Jiawei , Stevens Bjorn , Kluft Lukas , Muller Caroline
Published: February 2024

Tropical precipitation extremes and their changes with surface warming are investigated using global storm resolving simulations and high-resolution observations. The simulations demonstrate that the mesoscale organization of convection, a process that cannot be physically represented by conventional global climate models, is important for the variations of tropical daily accumulated precipitation extremes. In both the simulations and observations, daily precipitation extremes increase in a more organized state, in association with larger, but less frequent, storms. Repeating the simulations for a warmer climate results in a robust increase in monthly-mean daily precipitation extremes. Higher precipitation percentiles have a greater sensitivity to convective organization, which is predicted to increase with warming. Without changes in organization, the strongest daily precipitation extremes over the tropical oceans increase at a rate close to Clausius-Clapeyron (CC) scaling. Thus, in a future warmer state with increased organization, the strongest daily precipitation extremes over oceans increase at a faster rate than CC scaling.
The gene regulatory basis of bystander activation in CD8
+
T cells
Authors: Watson Neva B. , Patel Ravi K. , Kean Connor , Veazey Janelle , Oyesola Oyebola O. , Laniewski Nathan , Grenier Jennifer K. , Wang Jocelyn , Tabilas Cybelle , Yee Mon Kristel J. , McNairn Adrian J. , Peng Seth A. , Wesnak Samantha P. , Nzingha Kito , Davenport Miles P. , Tait Wojno Elia D. , Scheible Kristin M. , Smith Norah L. , Grimson Andrew , Rudd Brian D.
Published: February 2024

CD8
+
T cells are classically recognized as adaptive lymphocytes based on their ability to recognize specific foreign antigens and mount memory responses. However, recent studies indicate that some antigen-inexperienced CD8
+
T cells can respond to innate cytokines alone in the absence of cognate T cell receptor stimulation, a phenomenon referred to as bystander activation. Here, we demonstrate that neonatal CD8
+
T cells undergo a robust and diverse program of bystander activation, which corresponds to enhanced innate-like protection against unrelated pathogens. Using a multi-omics approach, we found that the ability of neonatal CD8
+
T cells to respond to innate cytokines derives from their capacity to undergo rapid chromatin remodeling, resulting in the usage of a distinct set of enhancers and transcription factors typically found in innate-like T cells. We observed that the switch between innate and adaptive functions in the CD8
+
T cell compartment is mediated by changes in the abundance of distinct subsets of cells. The innate CD8
+
T cell subset that predominates in early life was also present in adult mice and humans. Our findings provide support for the layered immune hypothesis and indicate that the CD8
+
T cell compartment is more functionally diverse than previously thought.
Contribution of Hfq to gene regulation and virulence in
Histophilus somni
Authors: Cao Dianjun , Subhadra Bindu , Lee Yue-Jia , Thoresen Merrilee , Cornejo Santiago , Olivier Alicia , Woolums Amelia , Inzana Thomas J.
Published: February 2024

Histophilus somni
is one of the predominant bacterial pathogens responsible for bovine respiratory and systemic diseases in cattle. Despite the identification of numerous
H. somni
virulence factors, little is known about the regulation of such factors. The post-transcriptional regulatory protein Hfq may play a crucial role in regulation of components that affect bacterial virulence. The contribution of Hfq to
H. somni
phenotype and virulence was investigated following creation of an
hfq
deletion mutant of
H. somni
strain 2336 (designated
H. somni
2336Δ
hfq
). A comparative analysis of the mutant to the wild-type strain was carried out by examining protein and carbohydrate phenotype, RNA sequence, intracellular survival in bovine monocytes, serum susceptibility, and virulence studies in mouse and calf models.
H. somni
2336Δ
hfq
exhibited a truncated lipooligosaccharide (LOS) structure, with loss of sialylation. The mutant demonstrated increased susceptibility to intracellular and serum-mediated killing compared to the wild-type strain. Transcriptomic analysis displayed significant differential expression of 832 upregulated genes and 809 downregulated genes in
H. somni
2336Δ
hfq
compared to
H. somni
strain 2336, including significant downregulation of
lsgB
and
licA
, which contribute to LOS oligosaccharide synthesis and sialylation. A substantial number of differentially expressed genes were associated with polysaccharide synthesis and other proteins that could influence virulence. The
H. somni
2336Δ
hfq
mutant strain was attenuated in a mouse septicemia model and somewhat attenuated in a calf intrabronchial challenge model.
H. somni
was recovered less frequently from nasopharyngeal swabs, endotracheal aspirates, and lung tissues of calves challenged with
H. somni
2336Δ
hfq
compared to the wild-type strain, and the percentage of abnormal lung tissue in calves challenged with
H. somni
2336Δ
hfq
was lower than in calves challenged with the wild-type strain. In conclusion, our results support that Hfq accounts for the regulation of
H. somni
virulence factors.
Cytotoxic rhamnolipid micelles drive acute virulence in
Pseudomonas aeruginosa
Authors: Xu Qi , Kang Donghoon , Meyer Matthew D. , Pennington Christopher L. , Gopal Citrupa , Schertzer Jeffrey W. , Kirienko Natalia V.
Published: February 2024

Pseudomonas aeruginosa
is an opportunistic human pathogen that has developed multi- or even pan-drug resistance toward most frontline and last resort antibiotics, leading to increasing frequency of infections and deaths among hospitalized patients, especially those with compromised immune systems. Further complicating treatment,
P. aeruginosa
produces numerous virulence factors that contribute to host tissue damage and immune evasion, promoting bacterial colonization and pathogenesis. In this study, we demonstrate the importance of rhamnolipid production in host-pathogen interactions. Secreted rhamnolipids form micelles that exhibited highly acute toxicity toward murine macrophages, rupturing the plasma membrane and causing organellar membrane damage within minutes of exposure. While rhamnolipid micelles (RMs) were particularly toxic to macrophages, they also caused membrane damage in human lung epithelial cells, red blood cells, Gram-positive bacteria, and even noncellular models like giant plasma membrane vesicles. Most importantly, rhamnolipid production strongly correlated with
P. aeruginosa
virulence against murine macrophages in various panels of clinical isolates. Altogether, our findings suggest that rhamnolipid micelles are highly cytotoxic virulence factors that drive acute cellular damage and immune evasion during
P. aeruginosa
infections.
AHL-differential quorum sensing regulation of amino acid metabolism in
Hafnia alvei
H4
Authors: Yan Congyang , Li Xue , Zhang Gongliang , Bi Jingran , Hao Hongshun , Hou Hongman
Published: February 2024

Quorum sensing (QS) regulation of functional metabolites is rarely reported but a common trait of some bacteria. In this study, we found that QS promoted the extracellular accumulation of glycine and serine while inhibiting the extracellular accumulation of methionine in
Hafnia alvei
H4. The correlation analysis of five QS signals with the above three QS-regulated amino acids suggested that these QS signals may have functional differences in amino acid regulation. The exogenous AHL add-back studies on genes involved in glycine, serine, and methionine metabolic pathway highlighted that
N
-octanoyl-
l
-homoserine lactone (C8-HSL) downregulated the expression of
sdhC
/
fumA
genes involved in the succinate to malate pathway, thereby reducing the metabolic flux of the tricarboxylic acid (TCA) cycle as an amino acid metabolism platform. Further in-depth research revealed that the QS system promoted the conversion of folate to tetrahydrofolate (THF) by positively regulating the expression of
folA
and
folM
, thus impairing the ability of folate to promote methionine accumulation. Moreover, folate positively regulated the expression of the QS signal synthesis gene
luxI
, promoting the synthesis of QS signals, which may further enhance the influence of the QS system on amino acid metabolism. These findings contribute to the understanding of amino acid metabolism regulated by QS and provide new perspectives for accurate control of metabolic regulation caused by QS.

IMPORTANCE

As one of the important regulatory mechanisms of microorganisms, quorum sensing (QS) is involved in the regulation of various physiological activities. However, few studies on the regulation of amino acid metabolism by QS are available. This study demonstrated that the LuxI-type QS system of
Hafnia alvei
H4 was involved in the regulation of multiple amino acid metabolism, and different types of QS signals exhibited different roles in regulating amino acid metabolism. Additionally, the regulatory effects of the QS system on amino acid metabolism were investigated from two important cycles that influence the conversion of amino acids, including the TCA cycle and the folate cycle. These findings provide new ideas on the role of QS system in the regulation of amino acid metabolism in organisms.
Zea mays
cultivation, biochar, and arbuscular mycorrhizal fungal inoculation influenced lead immobilization
Authors: Jia Qiong , Sun Jiahua , Gan Qiuyu , Shi Nan-Nan , Fu Shenglei
Published: February 2024

Plant cultivation can influence the immobilization of heavy metals in soil. However, the roles of soil amendments and microorganisms in crop-based phytoremediation require further exploration. In this study, we evaluated the impact of
Zea mays
L. cultivation, biochar application, and arbuscular mycorrhizal fungi (AMF) inoculation on soil lead (Pb) immobilization. Our results indicated that biochar addition resulted in a significant, 42.00%, reduction in AMF colonization. Plant cultivation, AMF inoculation, and biochar addition all contributed to enhanced Pb immobilization, as evidenced by decreased levels of diethylenetriaminepentaacetic acid- and CaCl
2
-extractable Pb in the soil. Furthermore, soil subjected to plant cultivation with AMF and biochar displayed reduced concentrations of bioavailable Pb. Biochar addition altered the distribution of Pb fractions in the soil, transforming the acid-soluble form into the relatively inert reducible and oxidizable forms. Additionally, biochar, AMF, and their combined use promoted maize growth parameters, including height, stem diameter, shoot and root biomass, and phosphorus uptake, while simultaneously reducing the shoot Pb concentration. These findings suggest a synergistic effect in Pb phytostabilization. In summary, despite the adverse impact of biochar on mycorrhizal growth, cultivating maize with the concurrent use of biochar and AMF emerges as a recommended and effective strategy for Pb phytoremediation.

IMPORTANCE

Heavy metal contamination in soil is a pressing environmental issue, and phytoremediation has emerged as a sustainable approach for mitigating this problem. This study sheds light on the potential of maize cultivation, biochar application, and arbuscular mycorrhizal fungi (AMF) inoculation to enhance the immobilization of Pb in contaminated soil. The findings demonstrate that the combined use of biochar and AMF during maize cultivation can significantly improve Pb immobilization and simultaneously enhance maize growth, offering a promising strategy for sustainable and effective Pb phytoremediation practices. This research contributes valuable insights into the field of phytoremediation and its potential to address heavy metal pollution in agricultural soils.
Risk factors and provider awareness of sexually transmitted enteric pathogens among men who have sex with men
Authors: Miller Timothy Isaac , Banning Stephanie , Lieberman Joshua A.
Published: February 2024

Sexual transmission of enteric pathogens among men who have sex with men (MSM) is well documented, although whether providers are cognizant of this risk when MSM patients present with gastrointestinal symptoms has not been studied. Over 34 months at a major tertiary metropolitan medical system, this study retrospectively analyzed 436 BioFire FilmArray Gastrointestinal results from 361 patients documented as MSM. An extensive chart review was performed, including specific sexual behaviors, socioeconomic risk factors, and whether providers charted a sexual history when a patient presented for care. Overall BioFire positivity rate was 62% with no significant difference in positivity between persons living with HIV and those without. Patients charted as sexually active had a significantly increased odds ratio (OR) of a positive result compared to those who were not. Anilingus had the highest OR. Providers charted any type of sexual history in 40.6% of cases, and HIV/infectious disease providers were significantly more likely to do this compared to other subspecialties. Sexual transmission of enteric pathogens within MSM is ongoing, and patients are at risk regardless of living with HIV. Not all sexual behaviors have the same associated risk, highlighting opportunities to decrease transmission. Increased provider vigilance and better patient education on sexual transmission of enteric pathogens are needed to reduce the disease burden.

IMPORTANCE

Our work adds several key findings to the growing body of literature describing the epidemiology of enteric pathogens as sexually transmitted infections among men who have sex with men (MSM). We analyzed clinical test results, housing status, provider awareness, sexual behaviors, and symptoms for 361 patients. We found that any sexual activity was associated with an increased risk of diarrheal pathogen detection, whereas being unhoused was not a risk factor. These findings suggest separate transmission networks between unhoused persons, who are also at risk of infectious diarrhea, and MSM. Moreover, our study suggested low awareness among patient-facing clinicians that diarrheal pathogens can be sexually transmitted. Together, our findings indicate an important opportunity to disrupt transmission cycles by educating clinicians on how to assess and counsel MSM patients.
Orally available nucleoside analog UMM-766 provides protection in a murine model of orthopox disease
Authors: Mudhasani Rajini R. , Golden Joseph W. , Adam Gregory C. , Hartingh Timothy J. , Kota Krishna P. , Ordonez David , Quackenbush Corey R. , Tran Julie P. , Cline Curtis , Williams Janice A. , Zeng Xiankun , Olsen David B. , Lieberman Linda A. , Boyce Christopher , Ginnetti Anthony , Meinig J. Matthew , Panchal Rekha G. , Mucker Eric M.
Published: February 2024

Although smallpox has been eradicated, other orthopoxviruses continue to be a public health concern as exemplified by the ongoing Mpox (formerly monkeypox) global outbreak. While medical countermeasures (MCMs) previously approved by the Food and Drug Administration for the treatment of smallpox have been adopted for Mpox, previously described vulnerabilities coupled with the questionable benefit of at least one of the therapeutics during the 2022 Mpox outbreak reinforce the need for identifying and developing other MCMs against orthopoxviruses. Here, we screened a panel of Merck proprietary small molecules and identified a novel nucleoside inhibitor with potent broad-spectrum antiviral activity against multiple orthopoxviruses. Efficacy testing of a 7-day dosing regimen of the orally administered nucleoside in a murine model of severe orthopoxvirus infection yielded a dose-dependent increase in survival. Treated animals had greatly reduced lesions in the lung and nasal cavity, particularly in the 10 µg/mL dosing group. Viral levels were also markedly lower in the UMM-766-treated animals. This work demonstrates that this nucleoside analog has anti-orthopoxvirus efficacy and can protect against severe disease in a murine orthopox model.

IMPORTANCE

The recent monkeypox virus pandemic demonstrates that members of the orthopoxvirus, which also includes variola virus, which causes smallpox, remain a public health issue. While currently FDA-approved treatment options exist, risks that resistant strains of orthopoxviruses may arise are a great concern. Thus, continued exploration of anti-poxvirus treatments is warranted. Here, we developed a template for a high-throughput screening assay to identify anti-poxvirus small-molecule drugs. By screening available drug libraries, we identified a compound that inhibited orthopoxvirus replication in cell culture. We then showed that this drug can protect animals against severe disease. Our findings here support the use of existing drug libraries to identify orthopoxvirus-targeting drugs that may serve as human-safe products to thwart future outbreaks.
True mesothelial cyst of the adrenal gland: its clinical profile and management
Authors: Saini Vikram , Garg Richa , Kataria Kamal , Nelson Thirugnanasambandam
Published: February 2024

The incidence of adrenal cysts is 0.06% and only 9% of these are true mesothelial cysts. Here, we present a case of a true mesothelial cyst together with a review of the literature. A female in her 30s presented to the surgical outpatient department complaining of right flank pain. Her contrast-enhanced CT scan revealed a 7.5×6.5×4.5 cm right adrenal gland cyst. The patient underwent a laparoscopic right adrenalectomy. Immunohistopathology revealed the cyst to be mesothelial in nature. The majority of true mesothelial adrenal cysts are benign, unilateral and more common in women. Any adrenal cyst diagnosed as a functional lesion or one that may be malignant or with a diameter of 5 cm or greater requires surgical care whereas smaller lesions can be managed conservatively. Laparoscopic adrenalectomy for an adrenal cyst of diameter greater than 6 cm is a safe and feasible procedure in expert hands if there is no invasion of surrounding tissue.
Looking back to see forward: multidirectional learning between the US Ryan White HIV/AIDS Program and the US President’s Emergency Plan for AIDS Relief
Authors: Patel-Larson Alpa , Ledikwe Jenny H , West Tanchica , Cheever Laura , Hauck Heather , Andrews Gail , Lipita Faless , Gugsa Salem , Life Tola , Perlman Jaclyn , Wilson Amber , Phillips Harold J , Haddad Carla
Published: February 2024

To end the HIV epidemic as a public health threat, there is urgent need to increase the frequency, depth and intentionality of bidirectional and mutually beneficial collaboration and coordination between the USA and global HIV/AIDS response. The US Health Resources and Services Administration (HRSA) is uniquely positioned to showcase bidirectional learning between high-income and low-income and middle-income countries (LMICs) in the fight against HIV. For 30 years, HRSA has successfully administered the Ryan White HIV/AIDS Program (RWHAP), the largest federal programme designed specifically for people with HIV in the USA. Further, HRSA has developed and delivered innovative, cost-effective, impactful HIV programmes in over 30 countries as an implementing agency for the US President’s Emergency Plan for AIDS Relief (PEPFAR). When PEPFAR was authorised in 2003, HRSA rapidly developed systems and infrastructures to deliver life-saving treatment, initiated workforce development programmes to mitigate health worker shortages, and laid the path for transitioning PEPFAR activities from US-based organisations to sustainable, country-led entities. As global programmes matured, lessons learnt within LMICs gradually began strengthening health services in the USA. To fully optimise synergies between RWHAP and PEPFAR, there is a critical need to build on successful initiatives, harness innovation and technology, and inculcate the spirt of multidirectional learning into global health. HRSA is promoting bidirectional learning between domestic and international HIV programming through documenting, sharing and implementing strategies, lessons learnt, best practices and effective models of care to accelerate achievement of HIV epidemic control and support country-led, sustained responses to public health threats.
Socioeconomic inequalities in underweight children: a cross-sectional analysis of trends in West Africa over two decades
Authors: Adamou Habila , Naba Gregoire , Koné Hamidou
Published: February 2024

Objective

To study trends in socioeconomic inequalities in underweight children in West Africa, and specifically to analyse the concentration index of underweight inequalities and measure inequalities in the risk of being malnourished by household wealth index.

Design

Cross-sectional study.

Setting

The study used 50 Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys conducted between 1999 and 2020 across 14 countries by the DHS and UNICEF.

Participants

The study included 481 349 children under the age of 5 years.

Primary and secondary outcome measures

The analysis used three variables: weight-for-age index, household wealth index and household residence. The inequality concentration index for underweight children and the relative risk of being underweight between 2000 and 2020 were calculated.

Results

The prevalence of underweight in West Africa showed a downward trend from 2000 to 2020. Nonetheless, the prevalence of underweight children under 5 years of age is still very high in West Africa compared with other sub-Saharan African countries, and the sustainable development objective is yet to be achieved. There was a wide disparity among countries and significant socioeconomic inequalities in underweight children within countries. The proportions of underweight children were concentrated in poor households in all countries in West Africa and over all periods. Socioeconomic inequalities in underweight children were more significant in countries where the prevalence of underweight was low. These inequalities were more pronounced in urban areas in West Africa from 2000 to 2020.

Conclusions and relevance

There is a high concentration of socioeconomic inequalities in underweight children in disadvantaged households in West Africa.
Guidelines and recommendations about virtual mental health services from high-income countries: a rapid review
Authors: Ekeleme Ngozichukwuka , Yusuf Abban , Kastner Monika , Waite Karen , Montesanti Stephanie , Atherton Helen , Salvalaggio Ginetta , Langford Lucie , Sediqzadah Saadia , Ziegler Carolyn , Do Amaral Tamara , Melamed Osnat C , Selby Peter , Kelly Martina , Anderson Elizabeth , O'Neill Braden
Published: February 2024

Objectives

This study reviewed existing recommendations for virtual mental healthcare services through the quadruple aim framework to create a set of recommendations on virtual healthcare delivery to guide the development of Canadian policies on virtual mental health services.

Design

We conducted a systematic rapid review with qualitative content analysis of data from included manuscripts. The quadruple aim framework, consisting of improving patient experience and provider satisfaction, reducing costs and enhancing population health, was used to analyse and organise findings.

Methods

Searches were conducted using seven databases from 1 January 2010 to 22 July 2022. We used qualitative content analysis to generate themes.

Results

The search yielded 40 articles. Most articles (85%) discussed enhancing patient experiences, 55% addressed provider experiences and population health, and 25% focused on cost reduction. Identified themes included: screen patients for appropriateness of virtual care; obtain emergency contact details; communicate transparently with patients; improve marginalised patients’ access to care; support health equity for all patients; determine the cost-effectiveness of virtual care; inform patients of insurance coverage for virtual care services; increase provider training for virtual care and set professional boundaries between providers and patients.

Conclusions

This rapid review identified important considerations that can be used to advance virtual care policy to support people living with mental health conditions in a high-income country.
Association of non-obstructive dyspnoea with all-cause mortality and incident chronic obstructive pulmonary disease: a systematic literature review and meta-analysis
Authors: Hou Yuyan , Wu Fan , Fan Huanhuan , Li Haiqing , Hao Binwei , Deng Zhishan , Lu Xiaoyan , Zhou Yumin , Ran Pixin
Published: February 2024

Background

Controversy exists regarding the association between non-obstructive dyspnoea and the future development of chronic obstructive pulmonary disease (COPD) and mortality. Therefore, we aimed to evaluate the association of non-obstructive dyspnoea with mortality and incident COPD in adults.

Methods

We searched PubMed, Embase, and Web of Science to identify studies published from inception to 13 May 2023. Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted independently by two reviewers. Studies were included if they were original articles comparing incident COPD and all-cause mortality between individuals with normal lung function with and without dyspnoea. The primary outcomes were incident COPD and all-cause mortality. The secondary outcome was respiratory disease-related mortality. We used the random-effects model to calculate pooled estimates and corresponding 95% confidence interval (CI). Heterogeneity was determined using the I² statistic.

Results

Of 6486 studies, 8 studies involving 100 758 individuals fulfilled the inclusion and exclusion criteria and were included in the study. Compared with individuals without non-obstructive dyspnoea, individuals with non-obstructive dyspnoea had an increased risk of incident COPD (relative risk: 1.41, 95% CI: 1.08 to 1.83), and moderate heterogeneity was found (p=0.079, I2=52.2%). Individuals with non-obstructive dyspnoea had a higher risk of all-cause mortality (hazard ratio: 1.21, 95% CI: 1.14 to 1.28, I2=0.0%) and respiratory disease-related mortality (hazard ratio: 1.52, 95% CI: 1.14 to 2.02, I2=0.0%) than those without.

Conclusions

Individuals with non-obstructive dyspnoea are at a higher risk of incident COPD and all-cause mortality than individuals without dyspnoea. Further research should investigate whether these high-risk adults may benefit from risk management and early therapeutic intervention.

PROSPERO registration number

CRD42023395192.
Top 10 needs of Ukraine’s Olympic sports in hostile conditions: a Delphi study
Authors: Kuvaldina Olga , Sarkauskiene Asta , Rybak Oleh , Taran Larysa , Derkach Viktor , Biryuk Svitlana , Agostinis-Sobrinho Cesar
Published: February 2024

Following the tragic events surrounding the war in Ukraine, which started on 24 February 2022, Russian troops have been destroying many Olympic sports infrastructures and athletes and Olympic sports professionals are suffering serious consequences, and sports talents are being lost. Therefore, this Delphi study aimed to identify the most important needs of Ukraine’s Olympic sports in hostile conditions. It sought to formulate priority areas crucial for support during and after the war period, aimed at safeguarding the career prospects of Ukrainian athletes. The study further aimed to identify well-informed priorities for developing Ukraine’s Olympic sports. These priorities, once discerned, can be advocated for promotion and prioritisation in present and future agendas, thereby shaping the course of international support and ensuring the preservation of Ukrainian athletes’ career prospects. A three-round Delphi study was conducted with 42 participants who had expertise as coaches, athletes and researchers (PhD, professor) in sports science. There was a strong panellist agreement on the needs of Ukraine’s Olympic sports in the identified hostile conditions. The list of the final top 10 needs included: (1) ‘Develop and maintain the athlete’s fitness level’; (2) ‘Implementation of a better recovery system for athletes’; and (3) ‘To ensure a safe training place for athletes’. The needs identified in this study are of tremendous value and guide efforts to Ukraine’s sports talents during wartime and, as a result, will guide the international institutions to direct appropriate aid and international support.
Bimekizumab treatment in patients with active psoriatic arthritis and prior inadequate response to tumour necrosis factor inhibitors: 52-week safety and efficacy from the phase III BE COMPLETE study and its open-label extension BE VITAL
Authors: Coates Laura C , Landewé Robert , McInnes Iain B , Mease Philip J , Ritchlin Christopher T , Tanaka Yoshiya , Asahina Akihiko , Behrens Frank , Gladman Dafna D , Gossec Laure , Orbai Ana-Maria , Gottlieb Alice B , Warren Richard B , Ink Barbara , Bajracharya Rajan , Shende Vishvesh , Coarse Jason , Merola Joseph F
Published: February 2024

Objectives

To assess 52-week safety and efficacy of bimekizumab in patients with active psoriatic arthritis (PsA) and prior inadequate response/intolerance to tumour necrosis factor inhibitors.

Methods

Patients completing the 16-week phase III double-blind, placebo-controlled BE COMPLETE (NCT03896581) study entered the open-label extension, BE VITAL (NCT04009499). All patients in BE VITAL received 160 mg bimekizumab every 4 weeks. Safety and efficacy are reported to week 52.

Results

A total of 347/400 (86.8%) patients completed week 52. To week 52, the exposure-adjusted incidence rate/100 patient-years for ≥1 treatment-emergent adverse event (TEAE) was 126.0, and was 7.0 for serious TEAEs. The most frequent TEAEs were SARS-CoV-2 (COVID-19), oral candidiasis, nasopharyngitis and urinary tract infection. All fungal infections were mild or moderate in severity and localised; two patients discontinued the study due to oral candidiasis. No cases of active tuberculosis, uveitis or inflammatory bowel disease were reported. One sudden death occurred. Sustained efficacy was observed with bimekizumab from week 16 to ‍52 across clinical and patient-reported outcomes. At week 52, 51.7% bimekizumab-randomised and 40.6% placebo/bimekizumab patients (receiving bimekizumab from week 16 to 52) had ≥50% improvement in the American College of Rheumatology criteria. Complete skin clearance (Psoriasis Area and Severity Index 100) was achieved by 65.9% bimekizumab and 60.2% placebo/bimekizumab patients at week 52. Minimal disease activity was achieved by 47.2% bimekizumab and 33.1% placebo/bimekizumab patients at week 52.

Conclusions

Bimekizumab demonstrated a safety profile consistent with previous reports; no new safety signals were identified. Sustained efficacy was observed from week 16 to 52.
Crossing the line: access to trauma care across state borders
Authors: Kumar Satvika , Song Jamie , Reilly Patrick M , Dickinson Edward T , Buckler David G , Haddad Diane N , Kaufman Elinore
Published: February 2024

Objective

This study investigates the challenge posed by state borders by identifying the population, injury, and geographic scope of areas of the country where the closest trauma center is out-of-state, and by collating state emergency medical services (EMS) policies relevant to cross-border trauma transport.

Methods

We identified designated levels I, II, and III trauma centers using data from American Trauma Society. ArcGIS was used to map the distance between US census block groups and trauma centers to identify the geographic areas for which cross-border transport may be most expedient. National Highway Traffic Safety Administration data were queried to quantify the proportion of fatal crashes occurring in the areas of interest. State EMS protocols were categorized by stance on cross-border transport.

Results

Of 237 596 included US census block groups, 18 499 (7.8%) were closest to an out-of-state designated level I or II trauma center. These census block groups accounted for 6.9% of the US population and 9.5% of all motor vehicle fatalities. With the inclusion of level III trauma centers, the number of US census block groups closest to an out-of-state designated level I, II, or III trauma center decreased to 13 690 (5.8%). These census block groups accounted for 5.1% of the US population and 7.1% of all motor vehicle fatalities. Of the 48 contiguous states, 30 encourage cross-border transport, 2 discourage it, 12 are neutral, and 4 leave it to local discretion.

Conclusion

Cross-border transport can expedite access to care in at least 5% of US census block groups. While few states discourage this practice, more robust policy guidance could reduce delays and enhance care.

Level of Evidence

III, Epidemiological.
Outcomes of patients with traumatic brain injury after stress ulcer prophylaxis: a retrospective multicenter study
Authors: McGraw Constance , Briscoe Abigale , Reynolds Cassandra , Carrick Matthew , Palacio Carlos H , Waswick William , Miller April , Trujillo Laura , Bar-Or David
Published: February 2024

Background

Stress ulcers in patients with traumatic brain injury (TBI) and spinal cord injury (SCI) present significant morbidity and mortality risks. Despite the low reported stress ulcer rates, stress ulcer prophylaxis (SUP) is widely administered in neurocritical care. It was hypothesized that universal SUP administration may not be associated with reduced rates of complications across all neurocritical care patients.

Methods

This retrospective study encompassed neurocritical care patients aged ≥18 with moderate or severe TBI or SCI, admitted to the intensive care unit (ICU) between October 2020 and September 2021, across six level I trauma centers. Exclusions included patients with an ICU stay <2 days, prior SUP medication use, and pre-existing SUP diagnoses. The primary exposure was SUP, with the primary outcome being clinically significant gastrointestinal bleeds (CSGIBs). Secondary outcomes included pneumonia and in-hospital mortality. Patients were stratified by admission Glasgow Coma Scale (GCS) groups.

Results

Among 407 patients, 83% received SUP, primarily H2 receptor antagonists (88%) and proton pump inhibitors (12%). Patients on SUP were significantly younger, had lower admission GCS scores, higher Injury Severity Scores, longer ICU stays, and higher rates of mechanical ventilation than non-SUP patients. Overall, CSGIBs were rare (1%) and not significantly different between the SUP and non-SUP groups (p=0.06). However, CSGIBs exclusively occurred in patients with GCS scores of 3–8, and SUP was associated with a significantly lower rate of CSGIBs in this subgroup (p=0.03). SUP was also linked to significantly higher pneumonia rates in both GCS 3–8 and GCS 9–12 patients.

Conclusions

This study highlights the low incidence of CSGIBs in neurocritical trauma patients and suggests potential benefits of SUP, particularly for those with severe neurological impairment. Nevertheless, the increased risk of pneumonia associated with SUP in these patients warrants caution. Further research is crucial to refine SUP guidelines for neurocritical care patients and inform optimal strategies.

Level of evidence

Level III, retrospective.