bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploitation of the host exocyst complex by bacterial pathogens
Authors: Ireton Keith , Gyanwali Gaurav Chandra , Herath Thilina U. B. , Lee Nicole
Published: January 2023

Intracellular bacterial pathogens remodel the plasma membrane of eukaryotic cells in order to establish infection. A common and well‐studied mechanism of plasma membrane remodelling involves bacterial stimulation of polymerization of the host actin cytoskeleton. Here, we discuss recent results showing that several bacterial pathogens also exploit the host vesicular trafficking pathway of ‘polarized exocytosis’ to expand and reshape specific regions in the plasma membrane during infection. Polarized exocytosis is mediated by an evolutionarily conserved octameric protein complex termed the exocyst. We describe examples in which the bacteria Listeria monocytogenes, Salmonella enterica serovar Typhimurium, and Shigella flexneri co‐opt the exocyst to promote internalization into human cells or intercellular spread within host tissues. We also discuss results showing that Legionella pneumophila or S. flexneri manipulate exocyst components to modify membrane vacuoles to favour intracellular replication or motility of bacteria. Finally, we propose potential ways that pathogens manipulate exocyst function, discuss how polarized exocytosis might promote infection and highlight the importance of future studies to determine how actin polymerization and polarized exocytosis are coordinated to achieve optimal bacterial infection.
Cell surface receptor kinase FERONIA linked to nutrient sensor TORC signaling controls root hair growth at low temperature linked to low nitrate in Arabidopsis thaliana
Authors: Pacheco Javier Martínez , Song Limei , Kuběnová Lenka , Ovečka Miroslav , Berdion Gabarain Victoria , Peralta Juan Manuel , Lehuedé Tomás Urzúa , Ibeas Miguel Angel , Ricardi Martiniano M. , Zhu Sirui , Shen Yanan , Schepetilnikov Mikhail , Ryabova Lyubov A. , Alvarez José M. , Gutierrez Rodrigo A. , Grossmann Guido , Šamaj Jozef , Yu Feng , Estevez José M.
Published: January 2023

Root hairs (RH) are excellent model systems for studying cell size and polarity since they elongate several hundred‐fold their original size. Their tip growth is determined both by intrinsic and environmental signals. Although nutrient availability and temperature are key factors for a sustained plant growth, the molecular mechanisms underlying their sensing and downstream signaling pathways remain unclear.

We use genetics to address the roles of the cell surface receptor kinase FERONIA (FER) and the nutrient sensing TOR Complex 1 (TORC) in RH growth.

We identified that low temperature (10°C) triggers a strong RH elongation response in Arabidopsis thaliana involving FER and TORC. We found that FER is required to perceive limited nutrient availability caused by low temperature. FERONIA interacts with and activates TORC‐downstream components to trigger RH growth. In addition, the small GTPase Rho of plants 2 (ROP2) is also involved in this RH growth response linking FER and TOR. We also found that limited nitrogen nutrient availability can mimic the RH growth response at 10°C in a NRT1.1‐dependent manner.

These results uncover a molecular mechanism by which a central hub composed by FER‐ROP2‐TORC is involved in the control of RH elongation under low temperature and nitrogen deficiency.
Foundationalism and empirical reason: On the rational significance of observation
Authors: Gupta Anil
Published: January 2023

A foundationalist account of our empirical thinking divides propositions we accept into two classes, basic and derivative, and sees the warrant of derivative propositions as accruing to them through their derivation from basic propositions. Such an account needs to answer two questions: which propositions are basic, and whence do basic propositions acquire their warrant? A natural and ancient answer to these questions is that basic propositions are observational and that these propositions gain their warrant from perceptions. I critically examine this view and also a variant view offered by Wilfrid Sellars. I put forward an alternative conception, dialectical foundationalism, that sees the distinction between the basic and the derivative as issuing from a distinction between two kinds of reasoning, derivational and dialectical. This type of foundationalism provides a more accurate account of our empirical thinking, I argue, than its traditional and Sellarsian counterparts.
Framing the climate crisis: Dread and fatalism in media and interest group responses to IPCC reports
Authors: Merry Melissa K. , Mattingly Hailey
Published: January 2023

While UN reports indicate increasingly dire consequences of climate change, the political will to initiate rapid decarbonization is lacking, as nations fail to meet targets set by international agreements. Given these developments, this paper investigates the role of climate dread and fatalism in the discourse about climate science. We examine the treatment of fatalism in major theories of the policy process, noting that climate policy represents a relatively novel situation—in which a problem once deemed solvable is being redefined as an issue outside the realm of human control. Using automated content analysis, we examine how journalists and interest groups framed reports issued by Intergovernmental Panel on Climate Change (IPCC) from 2013 to 2022. We find limited changes in the tone and content of news stories and environmental groups' statements, and we suggest that these findings reflect under‐reaction of the political system to new information.
Diagenesis, compaction strain and deformation associated with chert and carbonate concretions in organic‐rich marl and phosphorite; Upper Cretaceous to Eocene, Jordan
Authors: Abu‐Mahfouz Israa S. , Cartwright Joe A. , Powell John H. , Abu‐Mahfouz Mohammad S. , Podlaha Olaf G.
Published: January 2023

This paper presents an integrated petrographic–geochemical–geomechanical study of the growth mechanisms of carbonate and chert concretions observed at outcrop and core from the Upper Cretaceous to Eocene organic‐rich carbonate mudrocks, central Jordan. It provides evidence for displacive and replacive concretion growth from the analysis of primary lithological characteristics, compaction strain and deformation structures associated with concretion growth. Concretions were analysed to determine the primary lithological controls on their development and the measurement of strain in the host rock to develop a method for constraining the growth mode and their paragenesis. Concretions exhibit either a replacive or displacive growth mode largely dependent on the original host lithology. Displacive concretions exhibit irregular shapes and semi‐fibrous internal structures in contrast to regular shapes and microcrystalline textures observed for replacive concretions. Cement fraction is high in both carbonate concretion types, indicating early formation in high‐porosity sediments at shallow burial depths. The strain field around displacive concretions is vertically asymmetrical. Conversely, it is symmetrical with uniform differential compaction for the replacive concretions. Evidence for displacive growth comes from triangular areas of chert at the lateral margins of some carbonate concretions, interpreted as areas of reduced strain. Another indicator is the forced asymmetrical folding of heterolithic host rocks around displacive concretions, with displacive carbonate units separated by trace laminae of the original (chert) beds. Enveloping chert beds exhibit early‐formed radial silica fractures with increased aperture size in the areas of maximum curvature. Carbon isotopic signatures of carbonate concretions show a strong correlation between concretion centres and host rock, suggesting a relatively shallow depth (first few tens of metres) of initial growth. Carbonate concretions are interpreted to have formed at shallow depths in the presence of alkaline pore waters rich in dissolved organic carbon in the presence of Mg2+ ions, available organic matter and redox‐sensitive metals such as U and Mo. A paragenetic history for the different concretion types is presented.
The political and cultural inclusion of intra‐state ethnic minorities in Ethiopia: The case of the Qimant of Amhara state
Authors: Ayele Zemelak Ayitenew , Addisu Sisay Mengistie
Published: January 2023

Conflicts between the Qimant community – an intra‐state minority ethnic group endogenous to Amhara state in the Ethiopian federation – and the state’s special police forces have caused hundreds of deaths and the internal displacement of close to 50,000 people. Linked to these conflicts are the Qimants’ demands for recognition as a distinct ethnic community and the establishment of local government in the territories they inhabit; demands which have not received a satisfactory response from the federal or Amhara state government and which officials view with disdain. The situation raises several questions. Do the federal and regional‐state constitutions provide the necessary framework for accommodating intra‐state ethnic minorities such as the Qimant? If they do, why have the two levels of government failed to resolve the Qimant issue peacefully? What institutional mechanisms could they have used to satisfy the demands of the Qimant community? This article seeks to answer these and related questions.
Conditions for Use and Implementation of Globally-Aligned Versus Local Baseplate Coordinate Systems When Computing Migration Using Radiostereometric Analysis
Authors: Niesen Abigail E. , Kaptein Bart L. , Hull Maury L.
Published: January 2023

Radiostereometric analysis can be used for computing movement of a tibial baseplate relative to the tibia (termed migration) to determine stability of fixation. Quantifying migration in six degrees of freedom requires establishing a coordinate system in which to express the movement. Establishing consistent migration directions among patients and baseplate designs remains challenging. Deviations in imaging alignment (tibia/baseplate alignment during image acquisition) and surgical alignment (baseplate alignment on tibia) will affect computed migrations when using the conventional globally-aligned baseplate coordinate system (BCS) (defined by calibration box). Computing migration using a local BCS (defined by baseplate) may be preferrable. This paper (1) summarizes the migration equations when using a globally-aligned versus local BCS, (2) proposes a method for defining a local BCS, and (3) demonstrates differences in the two BCSs for an example patient whose baseplate has rotational deviations due to imaging or surgical alignments. Differences in migration for the two BCSs ranged from about ±0.5 mm in translations and −0.4 deg to 0.7 deg in rotations. Differences were largest for deviations in internal-external rotation and smallest for deviations in varus-valgus rotation. An example demonstrated that the globally-aligned BCS resulted in migration being quantified as subsidence instead of liftoff, thereby changing fundamental interpretations. Because migrations computed using a local BCS are independent of imaging and surgical alignments and instead characterize migration using baseplate features, a local BCS enhances consistency in migration directions among patients and baseplate designs relative to the interface in which fixation may be compromised.
Deciphering functional roles and interplay between Beclin1 and Beclin2 in autophagosome formation and mitophagy
Authors: Quiles Justin M. , Najor Rita H. , Gonzalez Eileen , Jeung Monica , Liang Wenjing , Burbach Sarah M. , Zumaya Erika A. , Diao Rachel Y. , Lampert Mark A. , Gustafsson Åsa B.
Published: January 2023

The degradation of macromolecules and organelles by the process of autophagy is critical for cellular homeostasis and is often compromised during aging and disease. Beclin1 and Beclin2 are implicated in autophagy induction, and these homologs share a high degree of amino acid sequence similarity but have divergent N-terminal regions. Here, we investigated the functions of the Beclin homologs in regulating autophagy and mitophagy, a specialized form of autophagy that targets mitochondria. Both Beclin homologs contributed to autophagosome formation, but a mechanism of autophagosome formation independent of either Beclin homolog occurred in response to starvation or mitochondrial damage. Mitophagy was compromised only in Beclin1-deficient HeLa cells and mouse embryonic fibroblasts because of defective autophagosomal engulfment of mitochondria, and the function of Beclin1 in mitophagy required the phosphorylation of the conserved Ser
15
residue by the kinase Ulk1. Mitochondria-ER–associated membranes (MAMs) are important sites of autophagosome formation during mitophagy, and Beclin1, but not Beclin2 or a Beclin1 mutant that could not be phosphorylated at Ser
15
, localized to MAMs during mitophagy. Our findings establish a regulatory role for Beclin1 in selective mitophagy by initiating autophagosome formation adjacent to mitochondria, a function facilitated by Ulk1-mediated phosphorylation of Ser
15
in its distinct N-terminal region.
Thermophilic Carboxylesterases from Hydrothermal Vents of the Volcanic Island of Ischia Active on Synthetic and Biobased Polymers and Mycotoxins
Authors: Distaso Marco A. , Chernikova Tatyana N. , Bargiela Rafael , Coscolín Cristina , Stogios Peter , Gonzalez-Alfonso Jose L. , Lemak Sofia , Khusnutdinova Anna N. , Plou Francisco J. , Evdokimova Elena , Savchenko Alexei , Lunev Evgenii A. , Yakimov Michail M. , Golyshina Olga V. , Ferrer Manuel , Yakunin Alexander F. , Golyshin Peter N.
Published: January 2023

High-temperature-active microbial enzymes are important biocatalysts for many industrial applications, including recycling of synthetic and biobased polyesters increasingly used in textiles, fibers, coatings and adhesives. Here, we identified three novel thermotolerant carboxylesterases (IS10, IS11, and IS12) from high-temperature enrichment cultures from Ischia hydrothermal vents and incubated with biobased polymers.
Visual Literacy of Molecular Biology Revealed through a Card-Sorting Task
Authors: Newman Dina L. , Spector Hannah , Neuenschwander Anna , Miller Anna J. , Trumpore Lauren , Wright L. Kate
Published: January 2023

Visual literacy, which is the ability to effectively identify, interpret, evaluate, use, and create images and visual media, is an important aspect of science literacy. As molecular processes are not directly observable, researchers and educators rely on visual representations (e.g., drawings) to communicate ideas in biology.
Retinoblastoma Protein Is Required for Epstein-Barr Virus Replication in Differentiated Epithelia
Authors: Myers Julia E. , Schaal Danielle L. , Nkadi Ebubechukwu H. , Ward B. J. H. , Bienkowska-Haba Malgorzata , Sapp Martin , Bodily Jason M. , Scott Rona S.
Published: January 2023

Terminally differentiated epithelium is known to support EBV genome amplification and virion morphogenesis following infection. The contribution of the cell cycle in differentiated tissues to efficient EBV replication is not understood.
A Camptothetin Analog, Topotecan, Promotes HIV Latency via Interference with HIV Transcription and RNA Splicing
Authors: Mukim Amey , Smith Davey M. , Deshmukh Savitha , Qazi Andrew A. , Beliakova-Bethell Nadejda
Published: January 2023

HIV survives in a state of very low activity, called latency, for long periods in persons with HIV on antiretroviral therapy. This low activity of HIV is linked to residual inflammation and associated diseases, such as heart disease and cancer.
Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related Neurological Dysfunction
Authors: Duran-Castells Clara , Llano Anuska , Kawana-Tachikawa Ai , Prats Anna , Martinez-Zalacain Ignacio , Kobayashi-Ishihara Mie , Oriol-Tordera Bruna , Peña Ruth , Gálvez Cristina , Silva-Arrieta Sandra , Clotet Bonaventura , Riveira-Muñoz Eva , Ballana Esther , Prado Julia G. , Martinez-Picado Javier , Sanchez Jorge , Mothe Beatriz , Hartigan-O’Connor Dennis , Wyss-Coray Tony , Meyerhans Andreas , Gisslén Magnus , Price Richard W. , Soriano-Mas Carles , Muñoz-Moreno José Antonio , Brander Christian , Ruiz-Riol Marta
Published: January 2023

Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control.
Selective and Cascade Reporting of Antimicrobial Susceptibility Testing Results and Its Impact on Antimicrobial Resistance Surveillance—National Healthcare Safety Network, April 2020 to March 2021
Authors: Wu Hsiu , Lutgring Joseph D. , McDonald L. Clifford , Webb Amy , Fields Virgie , Blum Laura , Mojica Malissa , Edwards Jonathan , Soe Minn Minn , Pollock Daniel A.
Published: January 2023

This study is the first to assess the extent of using selective and/or cascade antimicrobial susceptibility reporting for antimicrobial stewardship among U.S. hospitals and its impact on cumulative antibiograms in the context of electronic data exchange for national antimicrobial resistance surveillance.
Atorvastatin Potentially Reduces Mycobacterial Severity through Its Action on Lipoarabinomannan and Drug Permeability in Granulomas
Authors: Davuluri Kusuma Sai , Singh Amit Kumar , Singh Ajay Vir , Chaudhary Pooja , Raman Sunil Kumar , Kushwaha Shweta , Singh Shoor Vir , Chauhan Devendra Singh
Published: January 2023

Mycobacterium tuberculosis
binds to and enters the macrophage via the cell membrane cholesterol.
M. tuberculosis
limits phagosomal maturation and activation without engaging in phagocytosis. Aggregation of cholesterol in the cell wall of
M. tuberculosis
and an increase in the vascularity at the granuloma site reduce the permeability of rifampicin and isoniazid concentrations.
New Delhi Metallo-Beta-Lactamase (NDM)-5 in Uropathogenic Klebsiella pneumoniae in a Tertiary Care Hospital in Jamaica
Authors: Stone Steven , Thoms-Rodriguez Camille-Ann , Cameron Jenene , Seah Christine , Stephenson-Clarke Stacy , Melano Roberto G.
Published: January 2023

As the problem of antibiotic resistance continues to be a global problem, we hope to be able to shed further insight into what is happening within the Caribbean, from which there has been a paucity of data. The ability to appropriately tackle the problem of resistance requires surveillance from all territories, including resource limited settings.
Week-Old Chicks with High
Bacteroides
Abundance Have Increased Short-Chain Fatty Acids and Reduced Markers of Gut Inflammation
Authors: Fan Yi , Ju Tingting , Bhardwaj Tulika , Korver Douglas R. , Willing Benjamin P.
Published: January 2023

To date, limited information is available comparing distinct
Bacteroides
compositions in the chicken gut microbial communities, particularly in the context of microbial functional capacities and host responses. This study showed that possessing a microbiome with elevated
Bacteroides
in early life may confer beneficial effects to the chicken host, particularly in improving SCFA production and gut health.
Characterization of the Culturable Sporobiota of Spanish Olive Groves and Its Tolerance toward Environmental Challenges
Authors: Manetsberger Julia , Caballero Gómez Natacha , Benomar Nabil , Christie Graham , Abriouel Hikmate
Published: January 2023

Microbial communities are a key component of healthy soils. Spore-forming microorganisms represent a large fraction of this community—termed the “sporobiota”—and play a central role in creating a conducive environment for plant growth and food production.
Roles for Microglia in Cryptococcal Brain Dissemination in the Zebrafish Larva
Authors: Nielson Jacquelyn A. , Davis J. Muse
Published: January 2023

Cryptococcal meningitis is a fungal infection of the brain and a major cause of death in people with uncontrolled HIV. Infection begins in the lungs but can enter the bloodstream and disseminate to the brain.
Extraskeletal myxoid chondrosarcoma in the pelvis successfully treated with proton beam radiotherapy
Authors: Honda Yosuke , Katagiri Hirohisa , Onoe Tsuyoshi , Aramaki Takeshi
Published: January 2023

The standard treatment for extraskeletal myxoid chondrosarcoma is wide excision. However, extraskeletal myxoid chondrosarcoma is often located in the deep layers of the extremities and pelvis, so functional impairment due to wide resection is unavoidable in many cases. In addition, the efficacy of radiotherapy and chemotherapy has not been defined, so no treatment method is established for unresectable cases. Here we report a case involving a man in his late 60s with extraskeletal myxoid chondrosarcoma of the pelvis who responded to proton beam radiotherapy with intra-arterial chemotherapy and did not require surgery. The patient maintained a complete response for more than 7 years. The findings from this case suggest that definitive irradiation can be an alternative to wide resection for cases of extraskeletal myxoid chondrosarcoma in which severe disability cannot be avoided after resection or when the tumour is inoperable due to its size and location.
Ensemble of deep convolutional neural networks is more accurate and reliable than board-certified ophthalmologists at detecting multiple diseases in retinal fundus photographs
Authors: Pandey Prashant U , Ballios Brian G , Christakis Panos G , Kaplan Alexander J , Mathew David J , Ong Tone Stephan , Wan Michael J , Micieli Jonathan A , Wong Jovi C Y
Published: January 2023

Aims

To develop an algorithm to classify multiple retinal pathologies accurately and reliably from fundus photographs and to validate its performance against human experts.

Methods

We trained a deep convolutional ensemble (DCE), an ensemble of five convolutional neural networks (CNNs), to classify retinal fundus photographs into diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and normal eyes. The CNN architecture was based on the InceptionV3 model, and initial weights were pretrained on the ImageNet dataset. We used 43 055 fundus images from 12 public datasets. Five trained ensembles were then tested on an ‘unseen’ set of 100 images. Seven board-certified ophthalmologists were asked to classify these test images.

Results

Board-certified ophthalmologists achieved a mean accuracy of 72.7% over all classes, while the DCE achieved a mean accuracy of 79.2% (p=0.03). The DCE had a statistically significant higher mean F1-score for DR classification compared with the ophthalmologists (76.8% vs 57.5%; p=0.01) and greater but statistically non-significant mean F1-scores for glaucoma (83.9% vs 75.7%; p=0.10), AMD (85.9% vs 85.2%; p=0.69) and normal eyes (73.0% vs 70.5%; p=0.39). The DCE had a greater mean agreement between accuracy and confident of 81.6% vs 70.3% (p<0.001).

Discussion

We developed a deep learning model and found that it could more accurately and reliably classify four categories of fundus images compared with board-certified ophthalmologists. This work provides proof-of-principle that an algorithm is capable of accurate and reliable recognition of multiple retinal diseases using only fundus photographs.
Prevalence and correlates of depressive symptoms among prisoners in Kaliti Federal Prison in Ethiopia: a facility based cross-sectional study
Authors: Mengesha Tariku , Bedaso Asres , Berhanu Eyoel , Yesuf Aman , Duko Bereket
Published: January 2023

Objective

This study intended to examine the prevalence and correlates of depressive symptoms among inmates in Kaliti Prison Centre, Addis Ababa, Ethiopia.

Methods

A facility-based cross-sectional study was conducted among 694 randomly selected inmates in Kaliti Federal Prison in Ethiopia. The depressive symptom was examined using the Patient Health Questionnaire (PHQ-9). A binary logistic regression model was fitted to identify correlates of depressive symptoms. A p value <0.05 was considered to declare statistical significance, and an adjusted OR (AOR) with the corresponding 95% CI was computed to determine the strength of association. Data were analysed using SPSS V.20.

Result

The prevalence of depressive symptoms among prisoners in the current study was 56.6% (95% CI 53.2 to 60.8). Poor social support (AOR: 3.33, 95% CI 2.03 to 5.458), personal history of mental illness (AOR=3.16, 95% CI 1.62 to 6.14), physical abuse (AOR=2.31, 95% CI 1.41 to 3.78) and comorbid chronic medical illness (AOR=3.47, 95% CI 2.09 to 5.74) were independent correlates of depressive symptoms.

Conclusion

Our study shows that around one in two prisoners screened positive for depressive symptoms. There should be a regular screening of depressive symptoms for prisoners, and those screened positive should be linked to proper psychiatric service for early diagnosis and treatment.
Confronting ‘chaos’: a qualitative study assessing public health officials’ perceptions of the factors affecting Tanzania’s COVID-19 vaccine rollout
Authors: Yamanis Thespina , Carlitz Ruth , Gonyea Olivia , Skaff Sophia , Kisanga Nelson , Mollel Henry
Published: January 2023

Objectives

Mass COVID-19 vaccination in Africa is required to end the pandemic. In low-income settings, street-level bureaucrats (SLBs), or public officials who interact directly with citizens, are typically responsible for carrying out vaccination plans and earning community confidence in vaccines. The study interviewed SLBs to assess their perceptions of the factors affecting COVID-19 vaccination rollout in Tanzania.

Methods

We interviewed 50 SLBs (19 rural; 31 urban) responsible for implementing COVID-19 vaccination microplans across four diverse regions and districts of Tanzania in September 2021. Moreover, we conducted six in-depth interviews with non-governmental organisation representatives and seven focus group discussions with health facility governing committees. We asked for their perceptions of factors facilitating and challenging vaccine rollout according to three preidentified domains: political, health system and community. We analysed translated transcripts using a thematic analysis approach.

Results

Political factors facilitating mass vaccination included the executive leadership change from a denialist president to a president who accepted vaccines and promoted transparency. Global integration, commercially and politically, also motivated vaccine acceptance. Political challenges included community confusion that emerged from the consecutive presidents’ divergent communications and messaging by prominent religious antivaccination leaders. Health system factors facilitating vaccination included scaling up of immunisation sites and campaigns. Urban district officials reported greater access to vaccination sites, compared with rural officials. Limited financial resources for paying healthcare workers and for transport fuel and a lack of COVID-19 testing compromised mass vaccination. Furthermore, SLBs reported being inadequately trained on COVID-19 vaccine benefits and side effects. Having community sources of accurate information was critical to mass vaccination. Challenges at the community level included patriarchal gender dynamics, low risk perception, disinformation that the vaccine has satanic elements, and lack of trust in coronavirus vaccines.

Conclusion

Mass COVID-19 vaccination in Tanzania will require greater resources and investment in training SLBs to mitigate mistrust, overcome misinformation, and engage communities.
Capacity and quality of maternal and child health services delivery at the subnational primary healthcare level in relation to intermediate health outputs: a cross-sectional study of 12 low-income and middle-income countries
Authors: Ramadan Marwa , Gutierrez Jose Carlos , Feil Cameron , Bolongaita Sarah , Bernal Oscar , Villar Uribe Manuela
Published: January 2023

Objectives

To examine the capacity and quality of maternal and child health (MCH) services at the subnational primary healthcare (PHC) level in 12 low-income and middle-income countries (LMICs) and its association with intermediate health outputs such as coverage and access to care.

Design

Observational cross-sectional study using matched subnational data from service provision assessment surveys and demographic health surveys from 2007 to 2019.

Settings

138 subnational areas with available survey data in 12 LMICs (Afghanistan, Bangladesh, Democratic Republic of Congo, Haiti, Kenya, Malawi, Namibia, Nepal, Rwanda, Senegal, Tanzania and Uganda).

Outcomes

Eight intermediate MCH outcomes/outputs were explored: (1) met need for family planning by modern methods; (2) attendance of four or more antenatal care visits; (3) perceived financial barriers to care; (4) perceived geographical barriers to care; (5) diphtheria-pertussis-tetanus (DPT) third dose coverage; (6) DPT dropout-rate; (7) care-seeking for pneumonia; and (8) oral rehydration solutions coverage.

Results

Overall, moderate-to-poor PHC performance was observed across the 12 countries, with substantial heterogeneity between the different subnational areas in the same country as well as within the same subnational area across both capacity and quality subdomains. The analysis of the relationship between PHC service delivery and child health outcomes revealed that recent supervision (b=0.34, p<0.01) and supervisors’ feedback (b=0.28, p<0.05) were each associated with increased care-seeking for pneumonia. We also observed the associations of several measures of capacity and quality with DPT immunisation. The analysis of maternal health outcomes yielded only a few statistically significant results at p<0.05 level, however, none remained significant after adjusting for other covariates.

Conclusion

The results of this analysis illustrate the heterogeneity in the capacity and quality of PHC service delivery within LMICs. Countries seeking to strengthen their PHC systems could improve PHC monitoring at the subnational level to better understand subnational bottlenecks in service delivery.
Factors associated with COVID-19 vaccine uptake in people with kidney disease: an OpenSAFELY cohort study
Authors:   The OpenSAFELY Collaborative, Parker Edward PK , Tazare John , Hulme William J , Bates Christopher , Carr Edward J , Cockburn Jonathan , Curtis Helen J , Fisher Louis , Green Amelia CA , Harper Sam , Hester Frank , Horne Elsie MF , Loud Fiona , Lyon Susan , Mahalingasivam Viyaasan , Mehrkar Amir , Nab Linda , Parry John , Santhakumaran Shalini , Steenkamp Retha , Sterne Jonathan AC , Walker Alex J , Williamson Elizabeth J , Willicombe Michelle , Zheng Bang , Goldacre Ben , Nitsch Dorothea , Tomlinson Laurie A
Published: January 2023

Objective

To characterise factors associated with COVID-19 vaccine uptake among people with kidney disease in England.

Design

Retrospective cohort study using the OpenSAFELY-TPP platform, performed with the approval of NHS England.

Setting

Individual-level routine clinical data from 24 million people across GPs in England using TPP software. Primary care data were linked directly with COVID-19 vaccine records up to 31 August 2022 and with renal replacement therapy (RRT) status via the UK Renal Registry (UKRR).

Participants

A cohort of adults with stage 3–5 chronic kidney disease (CKD) or receiving RRT at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate (eGFR) or inclusion in the UKRR.

Main outcome measures

Dose-specific vaccine coverage over time was determined from 1 December 2020 to 31 August 2022. Individual-level factors associated with receipt of a 3-dose or 4-dose vaccine series were explored via Cox proportional hazards models.

Results

992 205 people with stage 3–5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 31 August 2022 was 97.5%, 97.0% and 93.9% for doses 1, 2 and 3, respectively, and 81.9% for dose 4 among individuals with one or more indications for eligibility. Delayed 3-dose vaccine uptake was associated with younger age, minority ethnicity, social deprivation and severe mental illness—associations that were consistent across CKD severity subgroups, dialysis patients and kidney transplant recipients. Similar associations were observed for 4-dose uptake.

Conclusion

Although high primary vaccine and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across clinical and demographic groups and 4-dose coverage is suboptimal. Targeted interventions are needed to identify barriers to vaccine uptake among under-vaccinated subgroups identified in the present study.
Practitioner-led, peer-group sports intervention combined with a context-focused intervention for children with cerebral palsy: a protocol of a feasibility randomised clinical trial
Authors: Souto Deisiane Oliveira , da Silva Luana Cristina , de Sousa Junior Ricardo Rodrigues , Clutterbuck Georgina , Anaby Dana , Longo Egmar , Magalhães Rafael Coelho , Camargos Ana Cristina Resende , Leite Hércules Ribeiro
Published: January 2023

Background

There is a need to investigate relevant, acceptable and feasible approaches that promote participation in leisure-time physical activity for children with cerebral palsy (CP). The aim of this study is to assess the feasibility of a randomised controlled trial comparing a peer-group intervention focused on improving physical literacy (Sports Stars) with the combination of Sports Stars and a context-focused intervention (Pathways and Resources for Engagement and Participation, PREP) for ambulant children with CP in Brazil.

Methods

In this feasibility trial, 18 ambulant children (aged 6–12 years) with CP will be randomised into two groups (nine per group): (1) Sports Stars and (2) Sports Stars plus PREP. The Sports Stars group will receive 8 weekly group sessions, focusing on developing the physical, social, cognitive and psychological skills required to participate in popular Brazilian sports. The combined Sports Stars and PREP group will receive Sports Stars in addition to eight individual PREP sessions focused on overcoming environmental barriers to participation. The primary outcome will include feasibility measures: willingness to participate in an RCT, eligibility and recruitment rates, maintenance of evaluator blinding, acceptability of screening procedures and random allocation, feasibility of evaluating outcomes, contamination between the groups, intervention adherence, treatment satisfaction, understanding of the intervention and implementation resources. Additional instruments will be applied to obtain data related to leisure-time physical activity participation goals, overall participation (home, school and community), physical literacy, level of physical activity and family empowerment. Outcomes will be assessed before, after and 12 weeks after intervention.

Ethics and dissemination

This feasibility trial has been approved by ethical Federal University of Minas Gerais’ Ethics Review Committee (CAAE: 33238520.5.0000.5149). All potential subjects will provide written informed consent. The results of this study will be published in peer-reviewed journals and be presented at academic conferences.

Trial registration numbers

RBR-4m3b4b6, U1111-1256-4998.
Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry)
Authors: Sass Marie Reeberg , Danielsen Andreas Aalkjær , Köhler-Forsberg Ole , Storgaard Heidi , Knop Filip K , Nielsen Mette Ødegaard , Sjödin Anders Mikael , Mors Ole , Correll Christoph U , Ekstrøm Claus , Vinberg Maj , Nielsen Jimmi , Vilsbøll Tina , Fink-Jensen Anders
Published: January 2023

Introduction

Clozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including pre-diabetes and diabetes. Non-pharmacological/behavioural interventions have had limited effects counteracting these adverse effects. Semaglutide, a glucagon-like peptide 1 receptor agonist, is approved for the treatment of type 2 diabetes and obesity. We will investigate the long-term effects of add-on treatment with semaglutide once a week versus placebo once a week on the metabolic status in pre-diabetic (glycated haemoglobin A1c (HbA1c) 35–47 mmol/mol (5.4%–6.4%) and diabetic (HbA1c 48–57 mmol/mol (6.5%–7.4%)) patients diagnosed with a schizophrenia spectrum disorder who initiated clozapine or olanzapine treatment within the last 60 months.

Methods and analysis

This is a 26-week, double-blinded, randomised, placebo-controlled trial. Altogether, 104 patients diagnosed with a schizophrenia spectrum disorder, aged 18–65 years, with pre-diabetes or diabetes will be randomised to injections of 1.0 mg semaglutide once a week or placebo for 26 weeks. The primary endpoint is change from baseline in HbA1c. Secondary endpoints include changes in body weight, hip and waist circumference and plasma levels of insulin, glucagon, glucose, and C-peptide, insulin sensitivity, beta cell function, hepatic function, fibrosis-4 score, lipid profile, incretin hormones, bone markers, body composition, bone density, proteomic analyses and oxidative stress markers. Together with alcohol, tobacco and drug use, potential effects on the reward value of a sweet–fat stimulus, psychopathology, level of activity and quality of life will also be assessed.

Ethics and dissemination

This study is approved by the Danish Medicines Agency and the regional scientific ethics committee of the Capital Region of Denmark (committee C, #H-20019008) and will be carried out in accordance with International Council for Harmonisation Good Clinical Practice guidelines and the Helsinki Declaration. The results will be disseminated through peer-review publications and conference presentations.

Trial registration number

NCT04892199.
Pharmacokinetics of a microdosed cocktail of three direct oral anticoagulants in children with congenital heart defects: study protocol for a single-centre clinical trial (DOAC-Child)
Authors: Hermann Simon A , Mikus Gerd , Chobanyan-Jürgens Kristine , Gorenflo Matthias , Ziesenitz Victoria C.
Published: January 2023

Introduction

Direct oral anticoagulants (DOACs) are direct inhibitors of coagulation factor Xa and are frequently used in adults for different indications such as deep vein thrombosis or non-valvular atrial fibrillation. Paediatric patients might benefit as well from DOACs because the simplicity and convenience of their use is likely to decrease physical and psychological stress related to invasive procedures associated with phenprocoumon and heparin therapy. Thus, it is expected that the future use of DOACs will ultimately improve compliance and overall safety of anticoagulant therapies in paediatric populations. To assure safe and effective use the clinical pharmacology and pharmacokinetics (PK) of these drugs need to be evaluated in children.

Methods and analysis

This study is a single-centre, open-label, clinical trial in a paediatric population with non-cyanotic congenital heart defects. After having obtained informed consent from the parents, each participant will receive a single oral administration of a drinkable solution of a microdose cocktail of three FXa inhibitors consisting of apixaban (12.5 µg), rivaroxaban (12.5 µg), edoxaban (50 µg), plus a microdose of the two probe drugs midazolam (10 µg) and yohimbine (25 µg). Serial blood samples (n=up to 20) will be collected at specified time points before and up to 25 hours after cocktail administration. The primary PK endpoint will be the area under the plasma concentration time curve of apixaban, rivaroxaban and edoxaban. Secondary PK outcomes will be Cmax, tmax, t1/2, Cl/F and Vss/F. Safety and tolerability of the microdose cocktail will be evaluated as well by a collection of adverse events.

Ethics

This study has been approved by the responsible Ethics Committee of the Medical Faculty of Heidelberg University.

Dissemination

Study results will be presented at international scientific meetings and published in peer-reviewed journals.

Trial registration number

EudraCT 2019-001759-38 16, DRKS00021455.
Sports-related traumatic brain injuries and acute care costs in children
Authors: Singh Sonia , Hoch Jeffrey S , Hearps Stephen , Dalziel Kim , Cheek John Alexander , Holmes James , Anderson Vicki , Kuppermann Nathan , Babl Franz E
Published: January 2023

Objective

To estimate traumatic brain injuries (TBIs) and acute care costs due to sports activities.

Methods

A planned secondary analysis of 7799 children from 5 years old to <18 years old with head injuries enrolled in a prospective multicentre study between 2011 and 2014. Sports-related TBIs were identified by the epidemiology codes for activity, place and injury mechanism. The sports cohort was stratified into two age groups (younger: 5–11 and older: 12–17 years). Acute care costs from the publicly funded Australian health system perspective are presented in 2018 pound sterling (£).

Results

There were 2903 children (37%) with sports-related TBIs. Mean age was 12.0 years (95% CI 11.9 to 12.1 years); 78% were male. Bicycle riding was associated with the most TBIs (14%), with mean per-patient costs of £802 (95% CI £644 to £960) and 17% of acute costs. The highest acute costs (21%) were from motorcycle-related TBIs (3.8% of injuries), with mean per-patient costs of £3795 (95% CI £1850 to £5739). For younger boys and girls, bicycle riding was associated with the highest TBIs and total costs; however, the mean per-patient costs were highest for motorcycle and horse riding, respectively. For older boys, rugby was associated with the most TBIs. However, motorcycle riding had the highest total and mean per-patient acute costs. For older girls, horse riding was associated with the most TBIs and highest total acute costs, and motorcycle riding was associated with the highest mean per-patient costs.

Conclusion

Injury prevention strategies should focus on age-related and sex-related sports activities to reduce the burden of TBIs in children.

Trial registration number

ACTRN12614000463673.
Early hearing detection and intervention (EHDI) programmes for infants and young children in low-income and middle-income countries in Asia: a systematic review
Authors: Joshi B Deepashree , Ramkumar Vidya , Nair Lekha S , Kuper Hannah
Published: January 2023

Background

Early hearing detection and intervention (EHDI) measures initiated in high-income countries (HICs) were attempted in low-income and middle-income countries (L&MICs). However, information regarding the models of EHDI, context-specific adaptations made to strategies and outcomes are not known.

Aims

The aims of this systematic review were to identify the various models of EHDI used in Asian L&MICs in the published scientific literature and to describe their efficacy and validity.

Methods

The studies were eligible if the programme was from Asian L&MICs, implemented for children below 6 years of age and published between 2010 and 2021. Google Scholar, PubMed, Web of Science, Scopus, EBSCOHost and EBSCO–CINAHL were used to find articles. Data were extracted from each selected article, and the risk of bias was assessed. The search results were summarised using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. For primary outcomes, narrative synthesis was used, and forest plots were generated for secondary outcomes.

Results

In all, 82 studies were included, and these studies were divided into two categories: newborn and infant screening programmes and screening programmes for older children. Predominantly, a two-stage objective otoacoustic emission (Distortion Product/Transient Evoked) or automated auditory brainstem response screening, followed by a detailed auditory brainstem response to confirm the hearing loss, was used in newborn and infant screening programmes. Audiologists were the most frequent screening personnel. Screening of older children was mostly done by otolaryngologists, school instructors and nurses. They performed a single-stage pure tone audiometry screening followed by a detailed examination.

Conclusion

The screening tools and protocols used were similar to those used in HICs. However, no uniform protocols were followed within each country. Long-term viability of EHDI programmes was not known as there was limited information on impact outcomes such as cost–benefit.

PROSPERO registration number

CRD42021240341.
Novel use of oral chloramphenicol for treatment-resistantMycoplasma genitalium
Authors: Goodfellow Jonathan Joseph , Hughes Stephen , Smith Jo , Jones Rachael , Moore Luke S P , Rayment Michael
Published: January 2023

We describe the novel use of oral chloramphenicol for treatment-resistantMycoplasma genitalium (M. genitalium) infection in a 20-year-old heterosexual cisgender male presenting with recurrent symptomatic non-gonococcal urethritis.M. genitaliumurethritis is an increasingly common clinical conundrum in sexual health clinics and in cases of second-line treatment failure (such as moxifloxacin), UK and international guidelines struggle to make recommendations for third-line treatments. As shown in our case, the evidence base for third-line treatments is lacking, with poor success rates, and may be poorly tolerated. Here we demonstrate the novel use of a well-tolerated oral antimicrobial, chloramphenicol, resulting in rapid microbiological and clinical cure in treatment-resistantM. genitaliumurethritis.
Tobacco endgame and priority populations: a scoping review
Authors: Puljević Cheneal , Feulner Leah , Hobbs Maria , Erku Daniel , Bonevski Billie , Segan Catherine , Baker Amanda , Hefler Marita , Cho Ara , Gartner Coral
Published: January 2023

Aim

To summarise the research literature on the impacts or perceptions of policies to end tobacco use at a population level (ie, tobacco endgame policies) among people from eight priority population groups (experiencing mental illness, substance use disorders, HIV, homelessness, unemployment or low incomes, who identify as lesbian, gay, bisexual, transgender, queer or intersex (LGBTQI+) or who have experienced incarceration).

Methods

Guided by JBI Scoping Review Methodology, we searched six databases for original research examining the impacts or perceptions of 12 tobacco endgame policies among eight priority populations published since 2000. We report the results according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist.

Results

Of the 18 included studies, one described perceptions of five endgame policies among people on low incomes in Aotearoa (New Zealand), and 17 focused on the effectiveness or impacts of a very low nicotine content (VLNC) cigarette standard among people experiencing mental illness (n=14), substance use disorders (n=8), low incomes (n=6), unemployment (n=1) or who identify as LGBTQI+ (n=1) in the USA. These studies provide evidence that VLNC cigarettes can reduce tobacco smoking, cigarette cravings, nicotine withdrawal and nicotine dependence among these populations.

Conclusions

Most of the tobacco endgame literature related to these priority populations focuses on VLNC cigarettes. Identified research gaps include the effectiveness of endgame policies for reducing smoking, impacts (both expected and unexpected) and policy perceptions among these priority populations.