bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling the impact of HIV and hepatitis C virus prevention and treatment interventions among people who inject drugs in Kenya
Authors: Stone Jack , Fraser Hannah , Walker Josephine G. , Mafirakureva Nyashadzaishe , Mundia Bernard , Cleland Charles , Bartilol Kigen , Musyoki Helgar , Waruiru Wanjiru , Ragi Allan , Bhattacharjee Parinita , Chhun Nok , Lizcano John , Akiyama Matthew J. , Cherutich Peter , Wisse Ernst , Kurth Ann , Luhmann Niklas , Vickerman Peter 
Published: September 2022

Objectives:
People who inject drugs (PWID) in Kenya have high HIV (range across settings: 14–26%) and hepatitis C virus (HCV; 11–36%) prevalence. We evaluated the impact of existing and scaled-up interventions on HIV and HCV incidence among PWID in Kenya.

Design:
HIV and HCV transmission model among PWID, calibrated to Nairobi and Kenya's Coastal region.

Methods:
For each setting, we projected the impact (percent of HIV/HCV infections averted in 2020) of existing coverages of antiretroviral therapy (ART; 63–79%), opioid agonist therapy (OAT; 8–13%) and needle and syringe programmes (NSP; 45–61%). We then projected the impact (reduction in HIV/HCV incidence over 2021–2030), of scaling-up harm reduction [Full harm reduction (‘Full HR’): 50% OAT, 75% NSP] and/or HIV (UNAIDS 90–90–90) and HCV treatment (1000 PWID over 2021–2025) and reducing sexual risk (by 25/50/75%). We estimated HCV treatment levels needed to reduce HCV incidence by 90% by 2030.

Results:
In 2020, OAT and NSP averted 46.0–50.8% (range of medians) of HIV infections and 50.0–66.1% of HCV infections, mostly because of NSP. ART only averted 12.9–39.8% of HIV infections because of suboptimal viral suppression (28–48%). Full HR and ART could reduce HIV incidence by 51.5–64% and HCV incidence by 84.6–86.6% by 2030. Also halving sexual risk could reduce HIV incidence by 68.0–74.1%. Alongside full HR, treating 2244 PWID over 2021–2025 could reduce HCV incidence by 90% by 2030.

Conclusion:
Existing interventions are having substantial impact on HIV and HCV transmission in Kenya. However, to eliminate HIV and HCV, further scale-up is needed with reductions in sexual risk and HCV treatment.
Improved virologic outcomes in postpartum women living with HIV referred to differentiated models of care
Authors: Myer Landon , Odayar Jasantha , Malaba Thokozile R. , Allerton Joanna , Kabanda Siti , Hu Nai-Chung , Kalombo Cathy , Hsiao Nei-Yuan , Jacobs Shahieda , Nofemela Andile , Lesosky Maia 
Published: September 2022

Objectives:
Differentiated service delivery (DSD) models are used to deliver antiretroviral therapy (ART) but data are limited in postpartum women, who are at high risk of non-adherence and elevated viral load (VL) over the extended postpartum period.

Design:
Randomized controlled trial.

Methods:
We enrolled consecutive postpartum women who initiated ART during pregnancy and met local DSD eligibility (clinically stable, VL less than 400 copies/ml) at a large primary healthcare (PHC) clinic. Women were randomized to a community-based ‘adherence club’ (AC, the local DSD model: community health worker-led groups of 20–30 patients with ART dispensing at a community venue) or routine PHC clinics (local standard of care with nurse/doctor-led services). Follow-up visits with VL separate from routine care took place at 3, 6, 12, 18 and 24 months postpartum. Endpoints were time to VL of at least 1000 copies/ml (primary) and VL of at least 50 copies/ml (secondary) by intention-to-treat.

Results:
At enrolment (n = 409), the median duration postpartum was 10 days, all women had a VL less than 1000 copies/ml and 88% had a VL less than 50 copies/ml; baseline characteristics did not differ by arm. Twenty-four-month retention was 89%. Sixteen and 29% of women in AC experienced a VL of at least 1000 copies/ml by 12 and 24 months, compared to 23 and 37% in PHC, respectively (hazard ratio [HR] = 0.71; 95% confidence interval [CI] = 0.50–1.01). Thirty-two and 44% of women in ACs had a VL of at least 50 copies/ml by 12 and 24 months, compared to 42 and 56% in PHC, respectively (HR = 0.68; 95% CI = 0.51–0.91).

Conclusions:
Early DSD referral was associated with reduced viraemia through 24 months postpartum and may be an important strategy to improve maternal virologic outcomes.
Imaging, Clinical, and Demographic Differences in Patients With Type III Spinal Cerebrospinal Fluid Leak (Cerebrospinal Venous Fistulas) Compared With Patients With Types I and II Spinal Cerebrospinal Fluid Leak
Authors: Mehan William A. , Buch Karen 
Published: September 2022

Objective
Spinal cerebrospinal fluid (CSF) leaks are an underdiagnosed cause of neurologic symptoms. The most common types of spinal CSF leaks are from dural tears (type I) and meningeal diverticula (type II). Cerebrospinal fluid–venous fistulas (type III) are less common and underrecognized. The purpose of this study was to evaluate the intracranial and spinal imaging findings in patients with types I/II versus type III leaks.

Materials and Methods
This was a retrospective, institutional review board–approved study performed on adult patients between January 2020 to September 2021 with surgically confirmed type I/II/III spinal CSF leak. Patients had preoperative brain magnetic resonance imaging (MRI) with contrast and medical records detailing symptoms and clinical diagnoses. Patients were excluded for nondiagnostic brain MRIs. Demographic and clinical information were recorded. The presence of extra-axial collections, pachymeningeal thickening, brain sagging, and decreased pontomamillary distance were evaluated on MRI.

Results
Seven patients had type III leaks, and 16 had type I/II leaks. Patients with type III leaks were older (P = 0.0003) and had higher rates of initial misdiagnosis (100% vs 31%) and longer times to correct diagnosis (P = 0.03) compared with type I/II leaks. Intracranial extra-axial collections were never seen with type III leaks but were seen in 50% of type I/II leaks. Pachymeningeal thickening and brainstem sagging occurred in nearly equal frequency between groups. Smaller pontomamillary distances were seen in type III leaks versus type I/II leaks (P = 0.047).

Conclusions
When evaluating patients with suspected spinal CSF leak, findings of older age, absence of intracranial extra-axial collections, and small pontomamillary distances may raise suspicion for type III versus type I/II leak.
Preliminary Evaluation of a Novel Neural Network-Based Hybrid Simulator for Surgical Training and Performance Assessment of Neonatal Thoracentesis
Authors: Sheth Nihar N. , Srinivasan Nishant , Patel Saurabhkumar , Luciano Cristian J. 
Published: September 2022

Introduction
Tension pneumothorax is a rare and life-threatening situation in neonates requiring immediate intervention through thoracentesis. Significant complications can arise while performing thoracentesis in the case of inadequate skill level or exposure to the condition. Although simulation-based training (SBT) has proven to be effective in learning surgical skills, training sessions are long, subjective, and expensive, because of which they cannot be held regularly. This article attempts to improve traditional SBT for neonatal thoracentesis through an autonomous simulator that can provide real-time objective feedback during surgical training and assessment.

Methods
The simulator incorporates a custom manikin and virtual reality software interfaced through electromagnetic sensors that track the motion of surgical instruments. The software application reads and stores instrument motion information to replicate physical actions in the virtual environment, play back previously stored surgical performances and analyze data through a pretrained neural network. The simulator encapsulates the experience of SBT by allowing trainees to watch and replicate an ideal method of conducting the procedure, providing simplified, real-time autonomous guidance during practice and an objective taskwise assessment of the performance during testing.

Results
The preliminary trial held at the University of Illinois Hospital in the presence of 1 neonatologist and 4 fellows revealed that all the participants used the autonomous guidance more than once, and all found simulation experience to be accurate and overall effective in learning thoracentesis.

Conclusion
Although the sample size is small, the simulator shows potential in being a viable alternative approach for training and assessment for thoracentesis.
Disparity-Sensitive Measures in Surgical Care: A Delphi Panel Consensus
Authors: de Jager Elzerie , Osman Samia Y , Levine Adele A , Liu Charles , Maggard Gibbons Melinda A , Ko Clifford Y , Burstin Helen R , Haider Adil H , Hoyt David B , Schoenfeld Andrew J , Britt LD , Weissman Joel S 
Published: September 2022

BACKGROUND:
In the US, disparities in surgical care impede the delivery of uniformly high-quality care to all patients. There is a lack of disparity-sensitive measures related to surgical care. The American College of Surgeons Metrics for Equitable Access and Care in Surgery group, through research and expert consensus, aimed to identify disparity-sensitive measures in surgical care.

STUDY DESIGN:
An environmental scan, systematic literature review, and subspecialty society surveys were conducted to identify potential disparity-sensitive surgical measures. A modified Delphi process was conducted where panelists rated measures on both importance and validity. In addition, a novel literature-based disparity-sensitive scoring process was used.

RESULTS:
We identified 841 potential disparity-sensitive surgical measures. From these, our Delphi and literature-based approaches yielded a consensus list of 125 candidate disparity-sensitive measures. These measures were rated as both valid and important and were supported by the existing literature.

CONCLUSION:
There are profound disparities in surgical care within the US healthcare system. A multidisciplinary Delphi panel identified 125 potential disparity-sensitive surgical measures that could be used to track health disparities, evaluate the impact of focused interventions, and reduce healthcare inequity.
Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for critical COVID-19
Authors: Noureddine Sofia , Roux-Claudé Pauline , Laurent Lucie , Ritter Ophélie , Dolla Pauline , Karaer Sinan , Claudé Frédéric , Eberst Guillaume , Westeel Virginie , Barnig Cindy 
Published: September 2022

AbstractBackgroundCardiopulmonary exercise testing (CPET) is an important clinical tool that provides a global assessment of the respiratory, circulatory and metabolic responses to exercise which are not adequately reflected through the measurement of individual organ system function at rest. In the context of critical COVID-19, CPET is an ideal approach for assessing long term sequalae.MethodsIn this prospective single-center study, we performed CPET in 60 patients, 12 months after a critical COVID-19 infection that required intensive care unit (ICU) treatment. Lung function at rest and chest computed tomography (CT) scan were also performed.ResultsTwelve months after severe COVID-19 pneumonia, the majority of the patients had a peak O2 uptake (V’O2) considered within normal limits. However, length of ICU stay remained an independent predictor of V’O2. Surprisingly, more than half of the patients with a normal peak predicted V’O2 showed ventilatory inefficiency during exercise (high VE/VCO2 ratio and high VE/VCO2 slope) with increased physiological dead space (VD/Vt) and low end-tidal CO2 partial pressure (PETCO2) values. This impairment was even more pronounced in patients with persistent dyspnea. Notably, peak VD/Vt values were positively correlated with peak D-Dimer plasma concentrations from blood samples collected during ICU stay.ConclusionsEven if reduced exercise capacity was rare 12 months after critical COVID-19, more than half of the patients with normal exercise capacity showed ventilatory inefficiency.
Multiomic Approach Characterises the Neuroprotective Role of Retromer in Regulating Lysosomal Health
Authors: Daly James L. , Danson Chris M. , Lewis Philip A. , Riccardo Sara , Di Filippo Lucio , Cacchiarelli Davide , Cross Stephen J. , Heesom Kate J. , Ballabio Andrea , Edgar James R. , Cullen Peter J. 
Published: September 2022

ABSTRACTRetromer controls cellular homeostasis through regulating integral membrane protein sorting and transport and by controlling late-stage maturation of the endo-lysosomal network. Retromer dysfunction, which is linked to neurodegenerative disorders including Parkinson’s and Alzheimer’s diseases, manifests in complex cellular phenotypes, though the precise nature of this dysfunction, and its relation to neurodegeneration, remain unclear. Here, we perform the first integrated multiomics approach to provide precise insight into the impact of Retromer dysfunction on endo-lysosomal health and homeostasis within a human neuroglioma cell model. We quantify profound changes to the lysosomal proteome, indicative of broad lysosomal dysfunction and inefficient autophagic lysosome reformation, coupled with a reconfigured cell surface proteome and secretome reflective of increased lysosomal exocytosis. Through this global proteomic approach and parallel transcriptomic analysis, we provide an unprecedented integrated view of Retromer function in regulating lysosomal homeostasis and emphasise its role in neuroprotection.
Regenerative hallmarks of aging: Insights through the lens ofPleurodeles waltl
Authors: Tsissios Georgios , Theodoroudis-Rapp Gabriella , Chen Weihao , Sallese Anthony , Smucker Byran , Ernst Lake , Chen Junfan , Xu Yiqi , Ratvasky Sophia , Wang Hui , Del Rio-Tsonis Katia 
Published: September 2022

AbstractBackgroundAging and regeneration are heavily linked processes. While it is generally accepted that regenerative capacity declines with age, some vertebrates, such as newts, can bypass the deleterious effects of aging and successfully regenerate a lens throughout their lifetime.ResultsHere, we used Optical Coherence Tomography (OCT) to monitor the lens regeneration process of larvae, juvenile, and adult newts. While all three life stages were able to regenerate a lens through transdifferentiation of the dorsal iris pigment epithelial cells (iPECs), an age-related decline in the kinetics of the regeneration process was observed. Consistent with these findings, iPECs from older animals exhibited a delay in cell cycle re-entry. Furthermore, it was observed that clearance of the extracellular matrix (ECM) was delayed in older organisms.ConclusionsCollectively, our results suggest that although lens regeneration capacity does not decline throughout the lifespan of newts, the intrinsic and extrinsic cellular changes caused by aging alter the kinetics of this process. By understanding how aging affects lens regeneration in newts, we can gain important insights for restoring the age-related regeneration decline observed in most vertebrates.
TDP-43 safeguards the embryo genome from L1 retrotransposition
Authors: Li Ten D. , Murano Kensaku , Kitano Tomohiro , Guo Youjia , Negishi Lumi , Siomi Haruhiko 
Published: September 2022

AbstractTransposable elements (TEs) are genomic parasites that propagate within the host genome and introduce mutations. Long interspersed nuclear element-1 (LINE-1 or L1) is the major TE class, which occupies nearly 20% of the mouse genome. L1 is highly active in mammalian preimplantation embryos, posing a major threat to genome integrity, but the mechanism of stage-specific protection against L1 retrotransposition is unknown. Here, we show that TAR DNA binding protein 43 (TDP-43), mutations in which constitute a major risk factor for amyotrophic lateral sclerosis (ALS), inhibits L1 retrotransposition in mouse embryonic stem cells (mESCs) and preimplantation embryos. Knock-down of TDP-43 resulted in massive genomic L1 expansion and impaired cell growth in preimplantation embryos and ESCs. Functional analysis demonstrated that TDP-43 interacts with L1 open reading frame 1 protein (L1 ORF1p) to mediate genomic protection, and loss of this interaction led to de-repression of L1 retrotransposition. Our results identify TDP-43 as a guardian of the embryonic genome.TeaserKnocking-down of TDP-43 causes massive L1 retrotransposition in preimplantation embryos.
Viridiplantae-specific GLXI and GLXII isoforms co-evolved and detoxify glucosonein planta
Authors: Balparda Manuel , Schmitz Jessica , Duemmel Martin , Wuthenow Isabell C. , Schmidt Marc , Alseekh Saleh , Fernie Alisdair R. , Lercher Martin J. , Maurino Veronica G. 
Published: September 2022

AbstractReactive carbonyl species (RCS) such as methylglyoxal (MGO) and glyoxal (GO) are highly reactive, unwanted side-products of cellular metabolism maintained at harmless intracellular levels by specific scavenging mechanisms. MGO and GO are metabolized through the glyoxalase (GLX) system, which consists of two enzymes acting in sequence, GLXI and GLXII. While plant genomes encode a large number of different GLX isoforms, it is unclear what their specific functions are and how these arose in evolution. Here, we show that plants possess two GLX systems of different evolutionary origins and with distinct structural and functional properties. The first system is shared by all eukaryotes, scavenges MGO and GO especially during seedling establishment, and features Zn2+-type GLXI, a metal co-factor preference that arose already in the last eukaryotic common ancestor. The GLXI and GLXII of the second system can together metabolize KDG, a glucose-derived RCS, and were acquired by the last common ancestor of viridiplantae through horizontal gene transfer from proteobacteria. In contrast to bacterial GLXI homologs, which are active as dimers, plant Ni2+-type GLXI contain a domain duplication, are active as monomers, and have modified their second active site. The acquisition and neofunctionalization of a structurally, biochemically, and functionally distinct GLX systems indicate that viridiplantae are under strong selection to detoxify a diversity of RCS.
„APP family member dimeric complexes are formed predominantly in synaptic compartments“
Authors: Schilling S. , August A. , Meleux M. , Conradt C. , Tremmel L. , Teigler S. , Adam V. , Koo E.H. , Kins S. , Eggert S. 
Published: September 2022

AbstractThe amyloid precursor protein (APP), a key player in Alzheime’s disease (AD), is part of a larger gene family, including the APP like proteins APLP1 and APLP2. They share similar structures, form homo- and heterotypic dimers and exhibit overlapping functions. We investigated complex formation of the APP family members via two inducible dimerization systems, the FKBP-rapamycin based dimerization as well as cysteine induced dimerization, combined with coimmunoprecipitations and Blue Native (BN) gel analyses. Within the APP family, APLP1 shows the highest degree of dimerization and high molecular weight (HMW) complex formation. Interestingly, about 20% of APP is dimerized in cultured cells while about 50% of APP is dimerized in mouse brains, independent of age and splice forms. Furthermore, we could show that dimerized APP originates mostly from neurons and is enriched in synaptosomes. Finally, BN gel analysis of human cortex samples shows a significant decrease of APP dimers in AD patients compared to controls, suggesting that loss of dimers of full-length APP might correlate with loss of synapses in the process of AD.
No need for extensive artifact rejection for ICA - A multi-study evaluation on stationary and mobile EEG datasets
Authors: Klug M. , Berg T. , Gramann K. 
Published: September 2022

AbstractObjectiveElectroencephalography (EEG) studies increasingly make use of more ecologically valid experimental protocols involving mobile participants who actively engage with their environment (MoBI; Gramann et al., 2011). These mobile paradigms lead to increased artifacts in the recorded data that are often treated using Independent Component Analysis (ICA). When analyzing EEG data, especially in a mobile context, removing samples regarded as artifactual is a common approach before computing ICA. Automatic tools for this exist, such as the automatic sample rejection of the AMICA algorithm (Palmer et al., 2011), but the impact of the two factors movement intensity and the automatic sample rejection has not been systematically evaluated yet.ApproachWe computed AMICA decompositions on eight datasets from six open-access studies with varying degrees of movement intensities using increasingly conservative sample rejection criteria. We evaluated the subsequent decomposition quality in terms of the component mutual information, the amount of brain, muscle, and “other” components, the residual variance of the brain components, and an exemplary signal-to-noise ratio.Main resultsWe found that increasing movements of participants led to decreasing decomposition quality for individual datasets but not as a general trend across all movement intensities. The cleaning strength had less impact on decomposition results than anticipated, and moderate cleaning of the data resulted in the best decompositions.SignificanceOur results indicate that the AMICA algorithm is very robust even with limited data cleaning. Moderate amounts of cleaning such as 5 to 10 iterations of the AMICA sample rejection with 3 standard deviations as the threshold will likely improve the decomposition of most datasets, irrespective of the movement intensity.
Involvement of an IgE/Mast cell/B cell amplification loop in abdominal aortic aneurysm progression
Authors: Loste Alexia , Clément Marc , Delbosc Sandrine , Guedj Kevin , Sénémaud Jean , Gaston Anh-Thu , Morvan Marion , Even Guillaume , Gautier Grégory , Eggel Alexander , Arock Michel , Procopio Emanuele , Deschildre Catherine , Louedec Liliane , Michel Jean-Baptiste , Deschamps Lydia , Castier Yves , Coscas Raphaël , Alsac Jean-Marc , Launay Pierre , Caligiuri Giuseppina , Nicoletti Antonino , Borgne Marie Le 
Published: September 2022

AbstractAimsIgE type immunoglobulins and their specific effector cells, mast cells (MCs), are associated with abdominal aortic aneurysm (AAA) progression. In parallel, immunoglobulin-producing B cells, organised in tertiary lymphoid organs (TLOs) within the aortic wall, have also been linked to aneurysmal progression. We aimed at investigating the potential role and mechanism linking local MCs, TLO B cells, and IgE production in aneurysmal progression.Methods and ResultsThrough histological assays conducted on human surgical samples from AAA patients, we uncovered that activated MCs were enriched at sites of unhealed haematomas, due to subclinical aortic wall fissuring, in close proximity to adventitial IgE+ TLO B cells. Remarkably,in vitrothe IgEs deriving from these samples enhanced MC production of IL-4, a cytokine which favors IgE class-switching and production by B cells. Finally, the role of MCs in aneurysmal progression was further analysedin vivoin ApoE-/-mice subjected to angiotensin II infusion aneurysm model, through MC-specific depletion after the establishment of dissecting aneurysms. MC-specific depletion improved intramural haematoma healing and reduced aneurysmal progression.ConclusionsOur data suggest that MC located close to aortic wall fissures are activated by adventitial TLO B cell-produced IgEs and participate to their own activation by providing support for further IgE synthesis through IL-4 production. By preventing prompt repair of aortic subclinical fissures, such a runaway MC activation loop could precipitate aneurysmal progression, suggesting that MC-targeting treatments may represent an interesting adjunctive therapy for reducing AAA progression.