bluuebunny/crossref_metadata_2025 huggingface dataset:
Connecting the Dots: the Lava Domes' Perspective of Magmatism Related to an Ignimbrite Flare-Up
Authors: Smithies Sarah L , Gravley Darren M , Gualda Guilherme A R
Published: December 2023

Dome eruptions associated with rhyolitic calderas offer an important insight into how extremely large (> > 10 km3), rhyolitic magma systems are constructed through time. We focus on rhyolitic calderas in the central Taupō Volcanic Zone leading to, during, and immediately following the 350- to 240-ka ignimbrite flare-up. We identified 103 dome eruptions that are dated between ca. 650 and 150 ka and collated 239 literature whole-rock compositions from these domes. For each composition, we modelled the pressure of magma extraction from the magma mush and the mineral assemblage of the mush using the rhyolite-MELTS geobarometer. We calculated extraction temperatures using zircon saturation geothermometry. We show that magmas are extracted from typically quartz-bearing magma mush at a wide range of depths (~50–425 MPa, ~2–16 km) and temperatures (~750°C to ~850°C). Throughout the central TVZ, there are two dominant extraction pressure modes at 1) 150–175 MPa and 2) 250–325 MPa, consistent with 1) the depth of the brittle–ductile transition (~6 km) and just below typical pre-eruptive storage depths of other TVZ magmas (100–150 MPa, ~4–6 km); and 2) partial melt regions imaged below ~8 km by previous geophysical studies. In some regions, there is a clear correlation between crustal structures, the depth of magma extraction, and the composition of the magmas. In the Whakamaru caldera, the domes erupted inside the caldera following caldera collapse are extracted from ~225 to ~350 MPa at ~810°C and have orthopyroxene-bearing compositions dissimilar to the caldera-forming eruption. These domes are aligned along normal faults, suggesting that rifting creates pathways for magma extraction from a deeper mush rejuvenated by recharge. The domes erupted along the structural margins of the Whakamaru caldera have very evolved, hornblende-bearing compositions, similar to the caldera-forming eruption and shallow, colder extraction from ~100 to ~200 MPa at ~770°C, suggesting the mush feeding these domes is a remnant of the older caldera-forming magma system mobilized along the caldera-bounding faults. Two structural levels of magma extraction at ~6 km and 9 to 12 km are persistent throughout the flare-up period and across the central TVZ region, demonstrating the need for further investigation into the factors controlling the depth of mush development.
Xylan-directed cell wall assembly in grasses
Authors: Zhang Lanjun , Zhou Yihua , Zhang Baocai
Published: December 2023

Xylan is the most abundant hemicellulosic polysaccharide in the cell walls of grasses and is pivotal for the assembly of distinct cell wall structures that govern various cellular functions. Xylan also plays a crucial role in regulating biomass recalcitrance, ultimately affecting the utilization potential of lignocellulosic materials. Over the past decades, our understanding of the xylan biosynthetic machinery and cell wall organization has substantially improved due to the innovative application of multiple state-of-the-art techniques. Notably, novel xylan-based nanostructures have been revealed in the cell walls of xylem vessels, promoting a more extensive exploration of the role of xylan in the formation of cell wall structures. This Update summarizes recent achievements in understanding xylan biosynthesis, modification, modeling, and compartmentalization in grasses, providing a brief overview of cell wall assembly regarding xylan. We also discuss the potential for tailoring xylan to facilitate the breeding of elite energy and feed crops.
Altered microheterogeneity at several N‐glycosylation sites in OPSCC in constant protein expression conditions
Authors: Dickinson Amy , Joenväärä Sakari , Tohmola Tiialotta , Renkonen Jutta , Mattila Petri , Carpén Timo , Mäkitie Antti , Silén Suvi
Published: December 2023

Protein glycosylation responds sensitively to disease states. It is implicated in every hallmark of cancer and has recently started to be considered as a hallmark itself. Changes in N‐glycosylation microheterogeneity are more dramatic than those of protein expression due to the non‐template nature of protein glycosylation. This enables their potential use in serum‐based diagnostics. Here, we perform glycopeptidomics on serum from patients with oropharyngeal squamous cell carcinoma (OPSCC), compared to controls and comparing between cancers based on etiology (human papilloma virus‐ positive or negative). Using MS2, we then targeted glycoforms, significantly different between the groups, to identify their glycopeptide compositions. Simultaneously we investigate the same serum proteins, comparing whether N‐glycosylation changes reflect protein‐level changes. Significant glycoforms were identified from proteins such as alpha‐1‐antitrypsin (SERPINA1), haptoglobin, and different immunoglobulins. SERPINA1 had glycovariance at 2 N‐glycosylation sites, that were up to 35 times more abundant in even early‐stage OPSCCs, despite minimal differences between SERPINA1 protein levels between groups. Some identified glycoforms' fold changes (FCs) were in line with serum protein level FCs, others were less abundant in early‐stage cancers but with great variance in higher‐stage cancers, such as on immunoglobulin heavy constant gamma 2, despite no change in protein levels. Such findings indicate that glycovariant analysis might be more beneficial than proteomic analysis, which is yet to be fruitful in the search for biomarkers. Highly sensitive glycopeptide changes could potentially be used in the future for cancer screening. Additionally, characterizing the glycopeptide changes in OPSCC is valuable in the search for potential therapeutic targets.
Anakinra Removal by Continuous Renal Replacement Therapy: An Ex Vivo Analysis
Authors: Dubinsky Samuel D.J. , Watt Kevin M. , Imburgia Carina E. , Mcknite Autumn M. , Hunt J. Porter , Rice Cassandra , Rower Joseph E. , Edginton Andrea N.
Published: December 2023

OBJECTIVES:

Patients with sepsis are at significant risk for multiple organ dysfunction, including the lungs and kidneys. To manage the morbidity associated with kidney impairment, continuous renal replacement therapy (CRRT) may be required. The extent of anakinra pharmacokinetics in CRRT remains unknown. The objectives of this study were to investigate the anakinra–circuit interaction and quantify the rate of removal from plasma.

DESIGN:

The anakinra–circuit interaction was evaluated using a closed-loop ex vivo CRRT circuit. CRRT was performed in three phases based on the method of solute removal: 1) hemofiltration, 2) hemodialysis, and 3) hemodiafiltration. Standard control samples of anakinra were included to assess drug degradation.

SETTING:

University research laboratory.

PATIENTS:

None.

INTERVENTIONS:

Anakinra was administered to the CRRT circuit and serial prefilter blood samples were collected along with time-matched control and hemofiltrate samples. Each circuit was run in triplicate to assess inter-run variability. Concentrations of anakinra in each reference fluid were measured by enzyme-linked immunosorbent assay. Transmembrane filter clearance was estimated by the product of the sieving coefficient/dialysate saturation constant and circuit flow rates.

MEASUREMENTS AND MAIN RESULTS:

Removal of anakinra from plasma occurred within minutes for each CRRT modality. Average drug remaining (%) in plasma following anakinra administration was lowest with hemodiafiltration (34.9%). The average sieving coefficient was 0.34, 0.37, and 0.41 for hemodiafiltration, hemofiltration, and hemodialysis, respectively. Transmembrane clearance was fairly consistent across each modality with the highest during hemodialysis (5.53 mL/min), followed by hemodiafiltration (4.99 mL/min), and hemofiltration (3.94 mL/min). Percent drug remaining within the control samples (93.1%) remained consistent across each experiment, indicating negligible degradation within the blood.

CONCLUSIONS:

The results of this analysis are the first to demonstrate that large molecule therapeutic proteins such as anakinra, are removed from plasma with modern CRRT technology. Current dosing recommendations for patients with severe renal impairment may result in subtherapeutic anakinra concentrations in those receiving CRRT.
Deep Learning-Based Localization and Detection of Malpositioned Endotracheal Tube on Portable Supine Chest Radiographs in Intensive and Emergency Medicine: A Multicenter Retrospective Study*
Authors: Wang Chih-Hung , Hwang Tianyu , Huang Yu-Sen , Tay Joyce , Wu Cheng-Yi , Wu Meng-Che , Roth Holger R. , Yang Dong , Zhao Can , Wang Weichung , Huang Chien-Hua
Published: December 2023

OBJECTIVES:

We aimed to develop a computer-aided detection (CAD) system to localize and detect the malposition of endotracheal tubes (ETTs) on portable supine chest radiographs (CXRs).

DESIGN:

This was a retrospective diagnostic study. DeepLabv3+ with ResNeSt50 backbone and DenseNet121 served as the model architecture for segmentation and classification tasks, respectively.

SETTING:

Multicenter study.

PATIENTS:

For the training dataset, images meeting the following inclusion criteria were included: 1) patient age greater than or equal to 20 years; 2) portable supine CXR; 3) examination in emergency departments or ICUs; and 4) examination between 2015 and 2019 at National Taiwan University Hospital (NTUH) (NTUH-1519 dataset: 5,767 images). The derived CAD system was tested on images from chronologically (examination during 2020 at NTUH, NTUH-20 dataset: 955 images) or geographically (examination between 2015 and 2020 at NTUH Yunlin Branch [YB], NTUH-YB dataset: 656 images) different datasets. All CXRs were annotated with pixel-level labels of ETT and with image-level labels of ETT presence and malposition.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

For the segmentation model, the Dice coefficients indicated that ETT would be delineated accurately (NTUH-20: 0.854; 95% CI, 0.824–0.881 and NTUH-YB: 0.839; 95% CI, 0.820–0.857). For the classification model, the presence of ETT could be accurately detected with high accuracy (area under the receiver operating characteristic curve [AUC]: NTUH-20, 1.000; 95% CI, 0.999–1.000 and NTUH-YB: 0.994; 95% CI, 0.984–1.000). Furthermore, among those images with ETT, ETT malposition could be detected with high accuracy (AUC: NTUH-20, 0.847; 95% CI, 0.671–0.980 and NTUH-YB, 0.734; 95% CI, 0.630–0.833), especially for endobronchial intubation (AUC: NTUH-20, 0.991; 95% CI, 0.969–1.000 and NTUH-YB, 0.966; 95% CI, 0.933–0.991).

CONCLUSIONS:

The derived CAD system could localize ETT and detect ETT malposition with excellent performance, especially for endobronchial intubation, and with favorable potential for external generalizability.
Power outages and pediatric unintentional injury hospitalizations in New York State
Authors: Northrop Alexander J. , Flores Nina M. , Do Vivian , Sheffield Perry E. , Casey Joan A.
Published: December 2023

Background:

In the past decade, electrical power disruptions (outages) have increased in the United States, especially those attributable to weather events. These outages have a range of health impacts but are largely unstudied in children. Here, we investigated the association between outages and unintentional injury hospitalizations, a leading cause of childhood morbidity.

Methods:

The study setting was New York State (NYS) from 2017 to 2020. Outage exposure was defined as ≥10%, ≥20%, and ≥50% of customers from a power operating locality without power, ascertained from NYS Department of Public Service records and stratified by rural, urban non-New York City (NYC), and NYC regions. Outcome daily block group-level pediatric injury hospitalization data was from the Statewide Planning and Research Cooperative System (SPARCS). We leveraged a case-crossover study design with logistic conditional regression.

Results:

We identified 23,093 unintentional injury hospitalizations in children <18 years with complete block group and exposure data. Most hospitalizations occurred in urban regions (90%), whereas outages were more likely in rural than urban areas. In urban non-NYC regions, outages ≥4 hours were associated with 30% increased odds of all-cause unintentional injury hospitalizations when ≥50% of customers were without power. Analyses by injury subtype revealed increasing point estimates as the proportion of customers exposed increased. These results, however, had wide confidence intervals.

Conclusions:

Outage exposure differed significantly across rural, urban non-NYC, and NYC regions across New York. Especially at the highest outage threshold, we observed an increased risk of pediatric unintentional injury hospitalizations.
An Effective Approach to Collecting Lymph Vessels Using a Small Diameter Wire for Lymphaticovenous Anastomosis in Upper Limb Lymphedema
Authors: Sowa Yoshihiro , Nakayama Ichiro , Sunaga Ataru , Morishita Yuya , Toyohara Yoshihiro , Yoshimura Kotaro
Published: December 2023

Lymphaticovenous anastomosis (LVA), which involves connecting lymphatic vessels to veins under a microscope, is widely performed around the world as a surgical treatment for lymphedema due to its relatively low patient burden and consistent efficacy. One of the crucial points of LVA is identifying suitable lymphatic vessels from among many lymphatic vessels and connecting them at the most effective site, but in practice, this is not easy to do. To overcome this issue, we have been able to effectively drain lymph by connecting lymphatic vessels to veins just before the occluded site using a lymphatic wire that was just recently developed in Japan. The device guides the subcutaneous deep collecting lymphatic vessels from the peripheral relatively superficial lymphatic vessels. While this special wire is typically adapted in the lower limbs, we have confirmed its effectiveness in upper limb lymphedema as well. Overall, this approach shows promise for improving the accuracy and success rates of LVA procedures, which can have significant benefits for patients with upper limb lymphedema. In this article, we share our experience using lymphatic wire for upper limb lymphedema cases.
COVID-19 Infection Is Associated With Loss of Muscle Strength
Authors: Smith James M. , Arsenault Riley , Berry-Sullivan Sam , Lavier Shana , Longo Kayla , Petersen Benjamin , Tansley Taylor
Published: December 2023

Introduction:

Coronavirus disease 2019 (COVID-19) is a respiratory and multisystem infection accompanied by risk for multisystemic problems. Recent research proposed a risk for skeletal muscle weakness among those who experienced COVID-19 infection. The purpose of this systematic review is to identify if muscle strength impairment follows COVID-19 infection.

Methods:

This systematic review of the literature complied with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the design of the review was registered prospectively with International Prospective Register of Systematic Reviews (PROSPERO). To reveal appropriate studies, PubMed, CINAHL, and Cochrane Database of Systematic Reviews were searched. Risk of bias was measured through the Scottish Intercollegiate Guidelines Network, Methodology Checklist 3: Cohort studies.

Results:

Included were 6 studies with a total of 659 participants with COVID-19 infection (mean age: 59.8 years), all of whom were hospitalized or in a nursing facility. Risk of bias assessment revealed that 5 of the studies were of acceptable methodological quality and 1 was of high quality. Four of the studies measured strength using hand-grip dynamometry, 3 studies measured strength using handheld dynamometry, and 1 study measured performance on the 1-minute sit-to-stand test. Across all studies the results showed some degree of a decrease in skeletal muscle strength.

Discussion:

Those with more severe COVID-19 infections were at greater risk for weakness within skeletal muscles. Two studies measured performance by larger muscles (ie, those with greater cross-sectional size) and identified that larger muscles were at greater risk for weakness.

Conclusion:

People recovering from a COVID-19 infection are at risk for experiencing muscle weakness. Clinicians should measure strength among patients who have had COVID-19 infection, including the performance of larger muscles.
Mobility Checklist for Patients With Advanced Heart Failure and a Femoral Intra-aortic Balloon Pump
Authors: Skrzat Julie M. , Santhanam Gayathri Iyer , Olejer Molly S. , Sando Trisha A.
Published: December 2023

Background and Purpose:

Literature about early mobilization of patients with femoral intra-aortic balloon pumps (IABPs) is emerging. The purpose of our study is to describe the development and implementation of a mobility checklist for patients with advanced heart failure (HF) who had a femoral IABP and assess its safety and feasibility.

Case Description:

A description of the development and implementation of our institution's IABP Mobility Checklist is provided. A retrospective review was conducted for patients with advanced HF who had a femoral IABP to assess safety and feasibility of mobilization. Subjects' demographic, medical, and physical therapy data, as well as safety data, were analyzed.

Outcomes:

The IABP Mobility Checklist was designed to mirror our institution's practice patterns. It is unique in 2 ways. First, it uses a body systems review screening approach to assess a patient's readiness and tolerance to mobilization. Second, the checklist breaks the screening process into 4 broad but distinct mobility phases to encompass a spectrum of movement. Twenty subjects with advanced HF who had a femoral IABP received 49 physical therapy sessions. The highest level of mobility with a femoral IABP was ambulation (50%). There were no major safety events and 2 minor safety events. Subjects stabilized with termination of mobilization. No additional medical interventions were required.

Discussion and Conclusion:

The IABP Mobility Checklist was developed and successfully implemented in patients with advanced HF who had a femoral IABP. Through knowledge acquisition, education, and interprofessional collaboration, mobilization in this patient population was safe and feasible.
Onconephrology: mitigation of renal injury in chemotherapy administration
Authors: Selamet Umut , Ahdoot Rebecca S. , Salasnek Reed , Abdelnour Lama , Hanna Ramy M.
Published: December 2023

Purpose of review

Onconephrology was first coined as a name for the intersection of cancer medicine and nephrology in the early 2010s. It was recognized then that beyond and understanding of kidney physiology, a new generation of nephrologists skilled in both molecular biology and precision medicine were needed to deal with the challenges of emerging cancer therapies. Stem cell transplants, biologic agents, adjuvants blocking basic cellular signaling pathways, immunotherapy were found to promote novel anticancer outcomes, but also to pose new risks to the kidneys. The field rapidly overlapped with emerging expertise in vascular glomerular disease, glomerular disease, and the same biologic agents now applied to auto immune systemic and kidney diseases.

Recent findings

Many categories of chemotherapeutic agents have been discovered to have adverse renal side effects. In this review, we address classic chemotherapeutic nephrotoxicity and oncologic clinical situations leading to acute kidney injury. We also review the frontiers of nephrotoxicity reported with cell cycle inhibitors, diverse classes of tyrosine kinase inhibitors, immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy, anticancer vaccines, and thrombotic microangiopathies triggered by malignancy and chemotherapy. The aim will be to focus on published strategies to mitigate nephrotoxicity.

As onconephrology expands into its own field, it gives birth to new subdisciplines. An understanding that patient populations want the benefits of chemotherapy without the renal (and other) systemic toxicities is emerging. A need to develop a new class of molecular and genetic experts in onconephrology to mitigate nephrotoxicity from chemotherapy is apparent and urgent.
FGF2 promotes the chemotherapy resistance in colon cancer cells through activating PI3K/Akt signaling pathway
Authors: Jian Xiao-Lan , Zeng Pu-Hua , Li Ke-Xiong , Peng Wei
Published: December 2023

Background

To investigate the role of fibroblast growth factor 2 (FGF2) in chemotherapy resistance of colon cancer.

Methods

An HCT116/5-fluorouracil (5-FU)–resistant cell line was established, and FGF2 levels were detected in a sensitive cell group (HCT116) and a resistant cell group (HCT1116-R) using different methods. Fibroblast growth factor 2 levels in the medium were determined by enzyme-linked immunoassay. The protein expressions of FGF2, fibroblast growth factor receptor 1 (FGFR1), and phospho-FGFR1 were assessed by Western blotting, and FGF2 mRNA levels were detected by quantitative real-time polymerase chain reaction. Fibroblast growth factor 2 recombinant protein was added to sensitive cells, and FGFR inhibitor AZD4547 was added to resistant cells, and the cell survival rate was determined using the cell counting kit-8 method and the protein expressions of PI3K (phosphatidylinositol 3 kinase), p-PI3K (phospho-PI3K), Akt (protein kinase B), p-Akt (phospho-Akt), mammalian target of rapamycin (mTOR), p-mTOR (phospho-mTOR), Bad (Bcl-xL/Bcl-2–associated death promoter), NF-κB (nuclear factor κB), GSK-3 (glycogen synthase kinase-3), FKHR (forkhead box protein O1), and PTEN (phosphatase and tensin homolog deleted on chromosome ten) were detected by Western blotting.

Results

Fibroblast growth factor 2 protein and mRNA expression levels in the HCT116-R group were significantly higher than those in the HCT116 group. Fibroblast growth factor 2 increased the survival rate of HCT116 cells; improved tolerance to 5-FU; upregulated p-PI3K, p-Akt, and p-mTOR; and downregulated Bad. The FGFR inhibitor AZD4547 decreased cell survival rate and tolerance to 5-FU; downregulated p-PI3K, p-Akt, and p-mTOR expression; and upregulated Bad.

Conclusions

Fibroblast growth factor 2 promotes chemotherapy tolerance in colon cancer cells by activating the Akt/mTOR and Akt/Bad signaling pathways downstream of PI3K.
The impact of COVID-19 vaccines on patients with immune thrombocytopenic purpura: A protocol for a systematic review and meta-analysis
Authors: Li Yangyang , Kong Demin , Ding Yicheng , Wang Jinhuan
Published: December 2023

Introduction

Immune thrombocytopenic purpura (ITP) is characterized by a decrease in platelet counts and can be triggered by various factors, such as viral infections and vaccinations. Concerns have emerged regarding potential links between the vaccines for COVID-19 and the worsening of ITP. This systematic review aims to comprehensively assess the impact of COVID-19 vaccines on patients with ITP, including associated risks and outcomes.

Methods and Analysis

A thorough search will be conducted across multiple electronic databases, including PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, Wan Fang, VIP, and CBM, to identify pertinent studies. This study will encompass randomized controlled trials, cohort studies, case-control studies, and case series that assess the effects of COVID-19 vaccines on individuals with ITP. The primary outcome will center on alterations in platelet count, while secondary outcomes will encompass the occurrence of thromboembolic events, bleeding complications, recurrence rate of ITP, impact of ITP exacerbation, and adverse events. The data will be synthesized and subjected to meta-analysis using Review Manager Software (RevMan) V.5.3. Additionally, subgroup analyses will be conducted to investigate potential sources of heterogeneity.

Ethics and dissemination

Since this study involves the analysis of previously published data, ethical approval is not required. The findings will be disseminated through publication in a peer-reviewed journal and presentation at relevant scientific conferences.

PROSPERO registration numberCRD42023471315.

Strengths and limitations of this study

Assessing the overall impact of COVID-19 vaccines on patients with ITP

Incorporating a variety of study types to perform a thorough analysis

Implementing a standardized methodology to evaluate and mitigate bias in the studies included

Possible restrictions in data accessibility and variations in heterogeneity among the studies considered

The effects of different types of COVID-19 vaccines on patients with ITP may differ, leading to potential disparities in the outcomes.
Embedded deep-learning based sample-to-answer device for on-site malaria diagnosis
Authors: Bae Chae Yun , Shin Young Min , Kim Mijin , Song Younghoon , Lee Hong Jong , Kim Kyung Hwan , Lee Hong Woo , Kim Yong Jun , Kanyemba Creto , Lungu Douglas K , Kang Byeong-il , Han Seunghee , Beck Hans-Peter , Cho Shin-Hyeong , Woo Bo Mee , Lim Chan Yang , Choi Kyung-Hak
Published: December 2023

Improvements in digital microscopy are critical for the development of a malaria diagnosis method that is accurate at the cellular level and exhibits satisfactory clinical performance. Digital microscopy can be enhanced by improving deep learning algorithms and achieving consistent staining results. In this study, a novel miLabTMdevice incorporating the solid hydrogel staining method was proposed for consistent blood film preparation, eliminating the use of complex equipment and liquid reagent maintenance. By leveraging deformable staining patches, miLabTMensures consistent, high-quality, and reproducible blood films across various hematocrits. Embedded-deep-learning-enabled miLabTMwas used to detect and classify malarial parasites from the autofocused images of stained blood cells by using an internal optical system. The results of this method were consistent with manual microscopy images. This method not only minimizes human error but also facilitates remote assistance and review by experts through digital image transmission. This method can set new paradigm for on-site malaria diagnosis. The miLabTMalgorithm for malaria detection achieved a total accuracy of 98.86% for infected red blood cell (RBCs) classification. Clinical validation performed in Malawi demonstrated an overall percent agreement of 92.21%. Thus, miLabTMcan become a reliable and efficient tool for decentralized malaria diagnosis.
Development of the Individual Participant Data (IPD) Integrity Tool for assessing the integrity of randomised trials using individual participant data
Authors: Hunter KE , Aberoumand M , Libesman S , Sotiropoulos JX , Williams J , Li W , Aagerup J , Mol BW , Wang R , Barba A , Shrestha N , Webster AC , Seidler AL
Published: December 2023

Introduction

Increasing concerns about integrity in medical research have prompted the development of tools to detect untrustworthy studies. Existing tools focus on evaluating aggregate or published data, though some trustworthiness issues may only be detected upon scrutiny of individual participant data (IPD). To address this, we developed the IPD Integrity Tool for detecting integrity issues in randomised controlled trials with IPD available. This manuscript describes the development of this tool.

Methods

We conducted a literature review to collate and map existing integrity items. These were discussed with an expert advisory group, and agreed items were included in a standardised tool and automated where possible. We piloted this tool in two IPD meta-analyses, and conducted preliminary validation checks on 13 datasets with and without known integrity issues in a blinded manner.

Results

The literature review identified 120 integrity items: 54 could be conducted at the publication or aggregate data (AD) level, 48 required IPD, and 18 were possible with aggregate data, but more comprehensive with IPD. Based on these items, an initial reduced tool was developed in a consensus process involving 13 advisors with different backgrounds (countries, profession, education). This initial tool included 11 items across four domains for AD, and 12 items across 8 domains requiring IPD. The tool was iteratively refined throughout piloting on two IPD meta-analyses including a total of 116 trials (73 with IPD, and 43 with only AD available), and preliminary validation using an additional 13 datasets. All five studies with known integrity issues were accurately identified during validation. The final version of the tool included seven domains with 13 items for AD and eight domains with 18 items requiring IPD.

Conclusions

The quality of evidence informing health care relies on trustworthy data. This manuscript describes the development of a tool to enable researchers, editors, and other stakeholders to detect integrity issues in randomised trials using IPD. Detailed instructions on the application of this tool will be published subsequently.
Consuming less ultra-processed food is associated with inadequate protein intake among vegan dieters
Authors: Leitão Alice Erwig , Esteves Gabriel P. , Mazzolani Bruna Caruso , Smaira Fabiana Infante , Santini Martin Hindermann , Santo André Heloísa C. , Gualano Bruno , Roschel Hamilton
Published: December 2023

Importance

Major concerns regarding vegan dieters are whether they meet protein and essential amino acids (EAA) recommendations, and how reliant they are on ultra-processed foods (UPF).

Objectives

To investigate whether vegan dieters meet protein and EAA recommendations. As secondary objectives, to determine UPF intake and potential predictors of inadequate protein intake in this population.

Design

A survey conducted between September 2021 and January 2023.

Setting

Brazil.

Participants

Vegan dieters of both sexes, aged 18 years or older, following a vegan diet for at least 6 months.

Exposure

Adherence to a vegan diet, and unprocessed and minimally processed foods (UMPF) and UPF consumption.

Main outcome measures

Protein and EAA intake, and food consumption according to processing level (Nova classification).

Results

One thousand and fourteen participants completed the survey, and 774 confirmed vegan dieters with adequate food recalls were included in the analysis. Most participants (74%) met daily protein intake according to the Recommended Dietary Allowance (RDA) (median: 1.12 g·kg−1·day−1, 95%CI 1.05; 1.16). Median EAA intake was also above RDA (with 71–91% meeting recommendations). Median UMPF intake was 66.5% (95%CI 65.0; 67.9) of total energy intake (TEI), whereas UPF consumption was 13.2% TEI (95%CI 12.4; 14.4). Adjusted logistic regression models showed that consuming protein supplements or textured soy protein, higher caloric, and higher UPF intakes were associated with reduced odds of inadequate protein intake, and that higher UMPF intakes were associated with increased odds of inadequate protein intake.

Conclusions and Relevance

The majority of vegan dieters attained protein and EAA intake recommendations, largely based their diet on UMPF, and had a significantly lower proportion of UPF as compared to previous reports on vegans and overall Brazilian population. Importantly, participants consuming less UPF more likely exhibited inadequate protein intake, suggesting the importance of ultra-processed proteins for this population.

Key points

Question

Do vegan dieters meet protein needs, and how reliant are they on ultra-processed foods (UPF)?

Findings

In this large survey including 774 vegan dieters, 74% had adequate daily protein intake. Unprocessed and minimally processed foods and UPF consumption accounted for 66.5% and 13.2% of total energy intake. Consuming protein supplements and textured soy protein, and higher caloric and UPF intakes were associated with reduced odds of inadequate protein intake, whereas higher UMPF intakes were associated with increased odds of inadequate protein intake.

Meaning

Most vegan dieters attain protein recommendations, while being less likely to do so when consuming less UPF.
Outcomes of Antiplatelet Therapy Continuation in Older Hypertensive Adults With Peptic Ulcer Disease
Authors: Lan Yi-Tsang , Lim Kar-Chun , Ho Chung-Yu , Chao Ying-Ting , Yen Tsung-Yi , Shih Ming-Feng , Chiang Chien-Hsieh
Published: December 2023

Background

The appropriateness of continuation of antiplatelet therapy in older hypertensive aspirin users with documented peptic ulcer disease (PUD) is uncertain.

Methods

This multicenter cohort study screened adults aged 65 years or older, using aspirin for primary and secondary cardiovascular disease prevention between January 2014 and December 2018. Patients with panendoscopy-proven PUD and hypertension were identified. Subsequent antiplatelet strategies were categorized as aspirin discontinuation (AD), aspirin continuation (AC), and switch to clopidogrel (SC) groups. Inverse probability of treatment weighting was applied to balance baseline characteristics. The main outcomes were incident major adverse cardiac events (MACEs) and hospitalizations for upper gastrointestinal bleeding (UGIB), followed through 31 December 2020.

Results

735 eligible patients were analyzed. During a median follow-up of 39.7 months, 178 MACEs occurred. Compared with AD, SC was not related to the risk of incident MACEs, but AC increased the risk of incident MACEs (adjusted HR, 1.58; 95% CI, 1.04-2.38) in secondary prevention patients. On the other hand, 102 hospitalizations for UGIB occurred during a median follow-up of 43.4 months. Compared with AD, neither AC nor SC affected the risk of hospitalization for UGIB in secondary prevention patients. However, secondary prevention patients with chronic kidney disease were at increased risk of hospitalizations for UGIB (adjusted HR, 2.41; 95% CI, 1.30-4.47).

Conclusions

AC may increase the risk of incident MACEs in older hypertensive adults with PUD previously taking aspirin for secondary cardiovascular disease prevention. The appropriateness of antiplatelet therapy continuation after PUD is diagnosed in older hypertensive adults warrants rigorous considerations.
Regional changes in cellular and molecular pathology in children with end-stage dilated cardiomyopathy: Correlation with regional and global cardiac performance
Authors: Pisesky Andrea , Chen Ching Kit , Sun Mei , Duaz John , Stephenson Elizabeth , Coles John , Friedberg Mark K.
Published: December 2023

Background

Paediatric dilated cardiomyopathy (DCM) carries a poor prognosis. We previously identified regional heterogeneity and patterns of left ventricular (LV) dysfunction that correlated with outcomes. In this project, we aimed to describe associations of regional myocardial performance with fibrosis and molecular signalling.

Methods

We prospectively studied children undergoing heart transplantation for DCM. Pre-transplant clinical and echocardiographic features were correlated with regional histological and molecular findings from explanted hearts. Ten LV and one right ventricular (RV) regions were assessed for fibrosis, myocyte area, and protein expression related to hypertrophy and fibrosis signalling (p38, ERK, phospho-JNK, phospho-GSK3β, SMA, cadherin, ILK), contractile function (myosin heavy chain), and calcium handling (SERCA2a, phospho-CamKII, phospholamban [PLN], and phospho-PLN).

Results

Eight children were included [median age 2.0years (0.3–15.1years)], of whom six required mechanical circulatory support. There was no difference in fibrosis burden or myocyte area between LV segments, and between ventricles. LV dimensions, ejection fraction and diastolic parameters were not related to fibrosis, myocyte area or molecular signalling. Tricuspid annular systolic plane excursion was related to myocyte volume (r=0.89, p<0.01). There was an inverse relationship between fibrosis and segmental longitudinal strain for LV basal and mid-posterior segments (basal posterior, r=0.96, p<0.01; mid-posterior, r=0.74, p=0.05). Global longitudinal strain was related to expression of ILK (r=0.78, p=0.02) and SERCA2a (r=0.71, p=0.04).

Conclusion

In paediatric end-stage DCM, regional cardiac function is associated with interstitial fibrosis and expression of calcium-cycling and contractile proteins. Phenotypic and molecular expression is variable. The RV shows similar injury and protein expression to the LV despite better myocardial function. These findings suggest that even with severely reduced LV function, paediatric DCM is a highly heterogeneous disease involving both ventricles.
Comparative transcriptomic analyses of peripheral blood mononuclear cells of patients with non-pneumonia and severe pneumonia at 1 year-Long-COVID-19
Authors: Kayalar Ozgecan , Cetinkaya Pelin Duru , Eldem Vahap , Baris Serap Argun , Koktürk Nurdan , Kuralay Selim Can , Rajabi Hadi , Konyalilar Nur , Mortazavi Deniz , Korkunc Seval Kubra , Erkan Sinem , Aksoy Gizem Tuşe , Eyikudamaci Gul , Deniz Pelin Pinar , Toprak Oya Baydar , Gulhan Pinar Yildiz , Sagcan Gulseren , Kose Neslihan , Erdem Aysegul Tomruk , Fakili Fusun , Ozturk Onder , Basyigit Ilknur , Boyaci Hasim , Azak Emel , Ciftci Tansu Ulukavak , Oguzulgen Ipek Kivilcim , Ozger Hasan Selcuk , Yildiz Pinar Aysert , Hanta Ismail , Ataoglu Ozlem , Ercelik Merve , Cuhadaroglu Caglar , Okur Hacer Kuzu , Tor Muge Meltem , Temel Esra Nurlu , Kul Seval , Tutuncu Yıldız , Itil Oya , Bayram Hasan
Published: December 2023

Long-COVID-19 manifests as a multisystemic condition with varied symptoms lingering beyond three weeks of acute SARS-CoV-2 infection, though its underlying mechanisms remain elusive. Aiming to decipher the long-term molecular impacts of COVID-19, we conducted a transcriptomic analysis on PBMCs from 1-year post-covid patients, including individuals without pneumonia (NP, n=10), those with severe pneumonia (SP, n=11), and healthy controls (C, n=13). Our extensive RNA sequencing revealed 4843 differentially expressed genes (DEGs) and 1056 differentially expressed long non-coding RNAs (DElncRNAs) in “C vs NP,” 1651 DEGs and 577 DElncRNAs in “C vs SP,” 954 DEGs and 148 DElncRNAs in “NP vs SP,” with 291 DEGs and 70 DElncRNAs shared across all groups. We identified 14 hub genes from 291 DEGs, with functional enrichment analysis showing upregulated DEGs mainly linked to inflammation and osteoclast differentiation, and downregulated DEGs to viral infections and immune responses. These hub genes play central roles in inflammatory and immune processes and are significantly associated with pneumonitis and diverse lung diseases. Investigations revealed unique immune cell signatures across DEG categories, associating upregulated DEGs with neutrophils and monocytes, and downregulated DEGs with CD4 memory effector T cells. Analysis of 14 hub genes showed notable upregulation in the no pneumonia group versus healthy controls, displaying complex patterns in the severe pneumonia group. Our study uncovered potential idiopathic pulmonary fibrosis signals in Long-COVID-19 patients’ PBMC transcriptome, highlighting the urgency for thorough monitoring and extended research to understand COVID-19’s lasting effects. This study sheds light on COVID-19’s transcriptomic changes and potential lasting effects, guiding future research and therapeutic approaches for Long-COVID-19.
Elevated plasma matrix metalloproteinases associate withMycobacterium tuberculosisblood stream infection and mortality in HIV-associated tuberculosis
Authors: Walker NF , Schutz C , Ward A , Barr D , Opondo C , Shey M , Elkington PT , Wilkinson KA , Wilkinson RJ , Meintjes G
Published: December 2023

Mortality from HIV-associated tuberculosis (HIV-TB) is high, particularly among hospitalised patients. In 433 people living with HIV admitted to hospital with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality andMycobacterium tuberculosis(Mtb)blood stream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and inMtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP- 3, -7, -8, -10 and procollagen III N-terminal propeptide (PIIINP) associated withMtb-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV- TB.
Late start of antenatal care in Burundi: Effect of socio-demographic, socio-cultural, and health system-related factors
Authors: Butoyi Jean M. , Sagam Caleb K. , Munezero Belyse , Nkeshimana Anatole , Coppieters Yves
Published: December 2023

Despite intensive international efforts to extend the coverage of primary healthcare services for women, pregnancy and childbirth still represent a high-risk period for both mother and child, particularly in low- and middle-income countries. Lack of access to antenatal care and its inadequate use during pregnancy contribute to maternal mortality. This study aimed to establish the factors associated with late start of antenatal care (ANC) in Muramvya health district, Burundi. A cross– sectional study was carried out in six randomly selected health facilities of the Muramvya district. The study population consisted of pregnant women who attended antenatal clinics. A total of 280 women were included in the study. Data were collected through face-to-face interviews. Descriptive statistics, bivariate and multivariate logistic regression models were used to measure the determinants of the late start of ANC after 12 weeks of gestation. ANC was initiated after 12 weeks of pregnancy in 72.50% of women, 58.6% and 13.9% respectively in the second and last trimester. Based on Multivariate logistic regression: Women between 20 and 35 years of age have a lower risk of starting ANC late than adolescents (AOR = 0.18; 95%CI:0.03-0.83). Lack of knowledge about the interventions offered during ANC (AOR = 2.37; 95%CI:1.32-4.25), late recognition of pregnancy status (AOR= 6.7; 95%CI:2.41-18.66), unplanned pregnancy (AOR = 1.85 95%CI:1.01-3.40) and the time for women to reach the health facility: between 30minutes to 1 hour (AOR = 2.40 95%CI:1.25-4.59) and more than 1 hour of walking (AOR = 2.15; 95%CI:1.01-4.60) are associated with the late start of ANC. The results of the study show that most women start ANC late. There is a need for effective behavioral interventions and public awareness and education targeting adolescents and women to improve early initiation of ANC
A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines
Authors: Lee Jimin , Stewart Cameron , Schaefer Alexandra , Leaf Elizabeth M. , Park Young-Jun , Asarnow Daniel , Powers John M. , Treichel Catherine , Corti Davide , Baric Ralph , King Neil P. , Veesler David
Published: December 2023

Continuous evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and monoclonal antibody therapies. To overcome this challenge, we set out to develop a vaccine focusing antibody responses on the highly conserved but metastable S2subunit, which folds as a spring-loaded fusion machinery. Here, we describe a protein design strategy enabling prefusion-stabilization of the SARS-CoV-2 S2subunit and high yield recombinant expression of trimers with native structure and antigenicity. We demonstrate that our design strategy is broadly generalizable to all sarbecoviruses, as exemplified with the SARS-CoV-1 (clade 1a) and PRD-0038 (clade 3) S2fusion machineries. Immunization of mice with a prefusion-stabilized SARS-CoV-2 S2trimer vaccine elicits broadly reactive sarbecovirus antibody responses and neutralizing antibody titers of comparable magnitude against Wuhan-Hu-1 and the immune evasive XBB.1.5 variant. Vaccinated mice were protected from weight loss and disease upon challenge with SARS-CoV-2 XBB.1.5, providing proof-of-principle for fusion machinery sarbecovirus vaccines motivating future development.
Detecting Features of Protein Structure through their Mediator-Accessible Redox Activities
Authors: Motabar Dana , Kim Eunkyoung , Li Jinyang , Zhao Zhiling , Mouchahoir Trina , Gallagher D. Travis , Schiel John E. , Garige Mamatha , Sourbier Carole , Payne Gregory F. , Bentley William E.
Published: December 2023

Protein function relies on sequence, folding, and post-translational modification, and molecular measurements are commonly used to reveal these structural features. Here, we report an alternative approach that represents these molecular features as readily measurable electronic patterns and validate this experimental approach by detecting structural perturbations commonly encountered during protein biomanufacturing. Specifically, we studied a monoclonal antibody standard (NISTmAb) and focused on the electronic detection of variants that have undergone interchain-disulfide bond reduction and methionine oxidation. Electronic detection of these structural perturbations is based on mediated electrochemical probing (MEP) that discerns patterns associated with the antibody’s mediator-accessible redox activity. We demonstrate that MEP can rapidly (within minutes) and quantitatively transduce the protein’s structural features into robust electronic signals that can enable bioprocess monitoring and control. More broadly, the ability to transduce information of a protein’s molecular structure into a more convenient electronic domain offers fundamentally new opportunities to apply the power of microelectronics and real-time data analytics to chemical and biological analysis.
Multistability driven by cooperative growth in microbial communities
Authors: Lopes William , Amor Daniel R. , Gore Jeff
Published: December 2023

Microbial communities often exhibit more than one possible stable composition for the same set of external conditions1-7. In the human microbiome, persistent changes in species composition and abundance are associated with health and disease states8. The main drivers of these alternative stable states remain relatively unknown9. Here we experimentally demonstrate that a cross-kingdom community, composed of six species relevant to the respiratory tract, displays four alternative stable states each dominated by a different species. In pairwise coculture, we observe widespread bistability among species pairs, providing a natural origin for the multistability of the full community. In contrast with the common association between bistability and antagonism, experiments reveal many positive interactions within and between community members. We find that multiple species display self-facilitation, or cooperative growth, and modeling predicts that this could drive the observed multistability within the community as well as non-canonical pairwise outcomes. A tailored biochemical screening assay reveals that glutamate supplementation either reduces or eliminates cooperativity in the growth of several species, and we confirm that such supplementation reduces the extent of bistability across pairs and reduces multistability in the full community. Our findings provide a mechanistic explanation of how cooperative growth rather than competitive interactions can underlie multistability in microbial communities.