bluuebunny/crossref_metadata_2025_split huggingface dataset:
TLR2 and TLR4 activity in monocytes and macrophages after exposure to amoxicillin, ciprofloxacin, doxycycline and erythromycin
Authors: Silva Lagos Luis , Luu Thy Viet , De Haan Bart , Faas Marijke , De Vos Paul 
Published: July 2022

Abstract

Background
Antibiotics are used to treat bacterial infections but also impact immunity. This is usually attributed to antibiotic-induced dysbiosis of the microbiota, but antibiotics may have a direct effect on immune cells and immunity-associated receptors, such as Toll-like receptors (TLRs).

Objectives
To investigate whether antibiotics alter TLR2/1, TLR2/6 and TLR4 activity in immune cells.

Methods
We evaluated the effects of amoxicillin, ciprofloxacin, doxycycline and erythromycin on TLR2/1-, TLR2/6- and TLR4-induced NF-κB activation in THP1-XBlue™-MD2-CD14 cells. Furthermore, we studied TNF-α and IL-6 levels in THP-1-derived macrophages after exposure to these antibiotics and TLR ligands.

Results
Amoxicillin had no effect on any of the TLRs studied. However, ciprofloxacin reduced TLR2/1, TLR2/6 and TLR4 activity in THP1-XBlue™-MD2-CD14 cells and decreased TLR2/1-induced TNF-α and IL-6 in macrophages. Doxycycline reduced TLR2/6 and TLR4 activity in THP1-XBlue™-MD2-CD14 cells and TNF-α and IL-6 levels in response to TLR2/6 stimulation in macrophages. Erythromycin decreased TLR2/1 and TLR4 activity in THP1-XBlue™-MD2-CD14 cells without changes in TNF-α and IL-6 levels in macrophages. In addition, ciprofloxacin decreased the expression of TLR2 mRNA.

Conclusions
These results suggest that some antibiotics may attenuate TLR-dependent monocyte/macrophage responses and likely reduce bacterial clearance. The latter is particularly important in infections with AMR bacteria, where misprescribed antibiotics not only fail in control of AMR infections but might also weaken host defence mechanisms by limiting innate immune responses. Our data suggest that efforts should be made to prevent the deterioration of the immune response during and after antibiotic treatment.
Comprehensive Diabetes Autoantibody Laboratory-Based Clinical Service Testing in 6044 Consecutive Patients: Analysis of Age and Sex Effects
Authors: Dahl Amanda , Jenkins Sarah , Pittock Sean J , Mills John , Foster Jesica , McKeon Andrew , Pittock Siobhan 
Published: July 2022

Abstract

Background
In 2017, Mayo Clinic Laboratories commenced offering a comprehensive type 1 diabetes mellitus (T1DM) autoantibody (Ab) evaluation including 4 known Abs targeting glutamic acid decarboxylase (GAD65), protein tyrosine phosphatase-like islet antigen 2 (IA2), insulin (IAA), and zinc transporter 8 protein (ZnT8) antigens.

Methods
The objective of this study was to evaluate real-time data on the frequency and patterns of all 4 Abs stratified by age and sex from 6044 unique consecutive adult and pediatric patients undergoing evaluation for suspected diabetes.

Results
At least one Ab was found in 3370 (56%) of all samples: 67% of children (aged 0–17), 49% of young adults (aged 18–35), and 41% for both middle-aged (aged 36–55) and older (aged &gt;55) adults (P ≤ 0.0001). GAD65-Abs were the most common in all age groups, followed by ZnT8-Ab in those &lt;36 years, or IAA-Ab in those ≥36. Frequencies of IA2- and ZnT8-Abs drop significantly with increasing age. Clusters of 3 or 4 Abs were more frequently encountered in younger patients (41% of children vs 12% in middle- and 13% in older age groups, P ≤ 0.0001).

Conclusions
Children undergoing serological evaluation for T1DM were more commonly positive for autoantibodies than older age groups. The frequency of ZnT8- and IA2-Abs decreases, and IAA-Ab frequency increases with increasing age, and clusters of 2 to 4 autoantibodies are more common in children. In clinical practice, comprehensive testing for diabetes autoantibodies resulted in a switch in diagnosis to T1DM for patients previously classified as type 2 diabetes mellitus.
Reevaluating the Icterus Index Cutoff of a Jaffé Creatinine Method
Authors: Alvarez Yasel F , Kelliher Michael T , Hubbard Jacqueline A , Nerenz Robert D , Cervinski Mark A 
Published: July 2022

Abstract

Background
The aim of this study was to redefine the icterus index cutoff for the Roche Jaffé creatinine method using both conjugated and unconjugated bilirubin on 3 Roche cobas modules (c311, c501, and c701/c702) at laboratories across our hospital network.

Methods
Interference was evaluated by adding conjugated bilirubin (as bilirubin conjugate, ditaurate) and unconjugated bilirubin to pooled remnant plasma. The effects of conjugated and unconjugated bilirubin were tested separately to assess the contribution of each species. The magnitude of interference was calculated as both absolute and percentage error with total allowable error limits set at 0.1 mg/dL (8 µmol/L or 8%).

Results
Analysis of interference data across the 3 Roche modules did not show bias exceeding our total allowable error limits for plasma creatinine up to a conjugated bilirubin icterus index of 16.2 (approximately 16.2 mg/dL or 277 μmol/L) or an unconjugated bilirubin icterus index of 18.5 (approximately 18.5 mg/dL or 316 μmol/L), the highest concentrations tested.

Conclusions
Our results demonstrate that the Roche Jaffé method exhibits acceptable performance in the presence of icterus at icterus indexes above the manufacturer’s current recommendations of 5 (approximately 5 mg/dL or 86 μmol/L) and 10 (approximately 10 mg/dL or 171 μmol/L) for conjugated and unconjugated bilirubin, respectively. We have updated the icterus index in our hospital system to 16 for conjugated bilirubin and 18 for unconjugated bilirubin.
Digital interventions for antimicrobial prescribing and monitoring: a qualitative meta-synthesis of factors influencing user acceptance
Authors: Van Dort Bethany A , Carland Jane E , Penm Jonathan , Ritchie Angus , Baysari Melissa T 
Published: July 2022

Abstract

Objective
To understand and synthesize factors influencing user acceptance of digital interventions used for antimicrobial prescribing and monitoring in hospitals.

Materials and Methods
A meta-synthesis was conducted to identify qualitative studies that explored user acceptance of digital interventions for antimicrobial prescribing and/or monitoring in hospitals. Databases were searched and qualitative data were extracted and systematically classified using the unified theory of acceptance and use of technology (UTAUT) model.

Results
Fifteen qualitative studies met the inclusion criteria. Eleven papers used interviews and four used focus groups. Most digital interventions evaluated in studies were decision support for prescribing (n = 13). Majority of perceptions were classified in the UTAUT performance expectancy domain in perceived usefulness and relative advantage constructs. Key facilitators in this domain included systems being trusted and credible sources of information, improving performance of tasks and increasing efficiency. Reported barriers were that interventions were not considered useful for all settings or patient conditions. Facilitating conditions was the second largest domain, which highlights the importance of users having infrastructure to support system use. Digital interventions were viewed positively if they were compatible with values, needs, and experiences of users.

Conclusions
User perceptions that drive users to accept and utilize digital interventions for antimicrobial prescribing and monitoring were predominantly related to performance expectations and facilitating conditions. To ensure digital interventions for antimicrobial prescribing are accepted and used, we recommend organizations ensure systems are evaluated and benefits are conveyed to users, that utility meets expectations, and that appropriate infrastructure is in place to support use.
Consent Builder: an innovative tool for creating research informed consent documents
Authors: Sward Katherine A , Enriquez Rene , Burr Jeri , Ozier Julie , Roebuck Megan , Elliott Carrie , Dean J Michael 
Published: July 2022

Abstract

Objective
To describe process innovations related to research informed consent documents, and development and formative evaluation of Consent Builder, a platform for generating consent documents for multicenter studies.

Materials and Methods
Analysis of Institutional Review Board workflows and documents, followed by process redesign, document redesign, and software development. Locally developed software leverages REDCap and LaTeX. A small-scale usability study was conducted.

Results
Process innovations were combining document types, and conceptualizing 2-part informed consent documents: part 1 standardizing the study description and part 2 with local site verbiage. Consent Builder was implemented in the Trial Innovation Network. User survey scores were acceptable; but areas for improvement were noted. LaTeX coding was the biggest challenge for users.

Discussion
The process changes were generally well accepted. The software implementation uncovered un-accounted for assumptions, and variability in IRB review workflow across centers. Technical modifications may be needed before widespread implementation.

Conclusion
We demonstrated proof-of-concept of an approach to generate research consent documents that are consistent across sites in study description, but which allow for customization of local site verbiage. The Consent Builder tool is an example of an operational innovation, helping meet a need that arose in part due to regulations around use of Single IRB for multicenter trials.
Leadership Diversity and Development in the Nation’s Cancer Centers
Authors: Lerman Caryn , Hughes-Halbert Chanita , Falcone Mary , Gosky David M , Jensen Roy A , Lee Kelvin P , Mitchell Edith , Odunsi Kunle , Pegher Jennifer W , Rodriguez Elisa , Sanchez Yolanda , Shaw Reuben , Weiner George , Willman Cheryl L 
Published: July 2022

Abstract
The capacity and diversity of the oncology leadership workforce has not kept pace with the emerging needs of our increasingly complex cancer centers and the spectrum of challenges our institutions face in reducing the cancer burden in diverse catchment areas. Recognizing the importance of a diverse workforce to reduce cancer inequities, the Association of American Cancer Institutes conducted a survey of its 103 cancer centers to examine diversity in leadership roles from research program leaders to cancer center directors. A total of 82 (80%) centers responded, including 64 National Cancer Institute–designated and 18 emerging centers. Among these 82 respondents, non-Hispanic White individuals comprised 79% of center directors, 82% of deputy directors, 72% of associate directors, and 72% of program leaders. Women are underrepresented in all leadership roles (ranging from 16% for center directors to 45% for associate directors). Although the limited gender, ethnic, and racial diversity of center directors and perhaps deputy directors is less surprising, the demographics of current research program leaders and associate directors exposes a substantial lack of diversity in the traditional cancer center senior leadership pipeline. Sole reliance on the cohort of current center leaders and leadership pipeline is unlikely to produce the diversity in cancer center leadership needed to facilitate the ability of those centers to address the needs of the diverse populations they serve. Informed by these data, this commentary describes some best practices to build a pipeline of emerging leaders who are representative of the diverse populations served by these institutions and who are well positioned to succeed.
Inactivated COVID-19 vaccines: durability of Covaxin/BBV152 induced immunity against variants of concern
Authors: Kumar Nathella Pavan , Banurekha V V , Kumar C P Girish , Nancy Arul , Padmapriyadarsini Chandrasekaran , Shankar Sakila , Hanna Luke Elizabeth , Murhekar Manoj , Devi K R Uma , Babu Subash 
Published: July 2022

Abstract

Background
Covaxin/BBV152 is one of the most widely used vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and one of the few vaccines used extensively in low- and middle-income countries (LMIC).

Methods
We investigated the effect of Covaxin on the SARS-CoV-2 specific IgG and IgA and neutralizing antibody (NAb) levels at baseline (M0) and at Months 1 (M1), 2 (M2), 3 (M3), 4 (M4), 6 (M6) and 12 (M12) following vaccination in healthcare workers. In addition, we also examined the NAb levels against variant lineages of B.1.617.2 (Delta, India), B.1.617.2.1 (Delta Plus, India), B.1.351 (Beta, SA), B.1.1.7 (Alpha, UK) and B.1.1.529 (Omicron).

Results
Covaxin induces enhanced SARS-CoV-2 binding antibodies of IgG and IgA responses against both spike (S) and nucleocapsid (N) antigens at M1, M2, M3, M4, M6 and M12 in comparison with M0. Our data also reveal that NAb levels against the ancestral strain (Wuhan, wild type) are elevated and sustained at M1, M2, M3, M4, M6 and M12 in comparison with M0 and against variant lineages of B.1.617.2 (Delta, India), B.1.617.2.1 (Delta Plus, India), B.1.351 (Beta, SA) and B.1.1.7 (Alpha, UK) are elevated at M3, M6 and M12 in comparison with M0. However, NAb levels against B.1.1.529 (Omicron) was consistently below the limit of detection except at M12.

Conclusion
Thus, Covaxin induces an enhanced humoral immune response, with persistence till at least 12 months post-vaccination against most SARS-CoV-2 variants.
An Experimental Study on Kinetics-Controlled Ca-Carbonate Aqueous Reduction into CH4 (1 and 2 GPa, 550°C): Implications for C Mobility in Subduction Zones
Authors: Peng Weigang , Tumiati Simone , Zhang Lifei , Tiraboschi Carla , Vitale Brovarone Alberto , Toffolo Luca , Poli Stefano 
Published: July 2022

Abstract
Abiotic methane (CH4) generation under subduction zone conditions has been experimentally investigated through aqueous reduction of pure C-bearing materials (e.g. carbonate minerals and organic matter). However, quantitative assessments of CH4 production in these experiments, as well as the potential effects of other components such as SiO2 on the reduction processes, have not yet been well established. Here, we performed experiments to quantitatively evaluate the time-resolved Ca-carbonate aqueous reduction into CH4 at P = 1 and 2 GPa and T = 550°C in the CaO + COH, CaO + SiO2 + COH, and CaO + SiO2 + MgO + COH systems, employing calcite + water ± quartz ± serpentine (synthetic chlorine (Cl)-bearing chrysotile and natural Fe−Al-bearing antigorite) as starting materials. Redox conditions of the experiments were buffered by iron−wüstite (IW) using a double capsule setting, corresponding to oxygen fugacity (fO2) values (expressed as log units relative to the fayalite–magnetite–quartz buffer, ΔFMQ) in the inner capsule of ΔFMQ ≈ −5.5 at 1 GPa and ΔFMQ ≈ −6.0 at 2 GPa. The solid products are mainly composed of portlandite ± larnite ± wollastonite ± brucite, while Ca-carbonate and/or silicate reactants commonly occur as relicts. Quadrupole mass spectrometric analysis shows that CH4 and H2O are the major COH molecular species in the fluid products, with molar ratios between CH4 and starting calcite representing the reaction progress ranging from ~0.13 to ~1.00. Comparisons of experimental run products with thermodynamically predicted phase assemblages, together with time-series experiments, indicate that the reduction processes are primarily controlled by reaction kinetics. At 1 GPa and 550°C, rate constants of 4.0 × 10−6 s−1, 7.4 × 10−6 s−1, and 2.6 × 10−6 s−1 were retrieved for reactions starting with calcite + quartz + water, calcite + synthetic Cl-bearing chrysotile + water, and calcite + natural Fe−Al-bearing antigorite + water, respectively, significantly higher than the constant of 0.8 × 10−6 s−1 for the silicate-absent reaction. Besides, an increase in pressures can also enhance the reduction efficiency of Ca-carbonates until reaching equilibrium with the fluids. Our data provide experimental evidence for kinetics-controlled Ca-carbonate aqueous reduction into CH4 in subduction zones, indicating that silicate involvement and/or pressure increase can accelerate the reaction rates through short-lived fluid–rock interactions, which may have important implications for deep C mobility.
Arabidopsis ERdj3B coordinates with ERECTA-family receptor kinases to regulate ovule development and the heat stress response
Authors: Leng Ya-Jun , Yao Ya-Sen , Yang Ke-Zhen , Wu Pei-Xiang , Xia Yu-Xin , Zuo Chao-Ran , Luo Jing-Hong , Wang Pu , Liu Yang-Yang , Zhang Xue-Qin , Ye De , Le Jie , Chen Li-Qun 
Published: July 2022

Abstract
The endoplasmic reticulum-localized DnaJ family 3B (ERdj3B), is a component of the stromal cell-derived factor 2 (SDF2)–ERdj3B–binding immunoglobulin protein (BiP) chaperone complex, which functions in protein folding, translocation, and quality control. We found that ERdj3B mutations affected integument development in the Ler ecotype but not in the Col-0 ecotype of Arabidopsis (Arabidopsis thaliana). Map-based cloning identified the ERECTA (ER) gene as a natural modifier of ERdj3B. The double mutation of ERdj3B and ER caused a major defect in the inner integument under heat stress. Additional mutation of the ER paralog ERECTA-LIKE 1 (ERL1) or ERL2 to the erdj3b er double mutant exacerbated the defective integument phenotype. The double mutation of ER and SDF2, the other component of the SDF2–ERdj3B–BiP complex, resulted in similar defects in the inner integument. Furthermore, both the protein abundance and plasma membrane partitioning of ER, ERL1, and ERL2 were markedly reduced in erdj3b plants, indicating that the SDF2–ERdj3B–BiP chaperone complex might control the translocation of ERECTA-family proteins from the endoplasmic reticulum to the plasma membrane. Our results suggest that the SDF2–ERdj3B–BiP complex functions in ovule development and the heat stress response in coordination with ERECTA-family receptor kinases.
Argonaute 2 modulates EGFR–RAS signaling to promote mutantHRASandNRAS-driven malignancies
Authors: Siebenaler Ronald F , Chugh Seema , Waninger Jessica J , Dommeti Vijaya L , Kenum Carson , Mody Malay , Gautam Anudeeta , Patel Nidhi , Chu Alec , Bawa Pushpinder , Hon Jennifer , Smith Richard D , Carlson Heather , Cao Xuhong , Tesmer John J G , Shankar Sunita , Chinnaiyan Arul M 
Published: July 2022

AbstractActivating mutations in RAS GTPases drive nearly 30% of all human cancers. Our prior work described an essential role for Argonaute 2 (AGO2), of the RNA-induced silencing complex, in mutant KRAS-driven cancers. Here, we identified a novel endogenous interaction between AGO2 and RAS in both wild-type (WT) and mutant HRAS/NRAS cells. This interaction was regulated through EGFR-mediated phosphorylation of Y393-AGO2, and utilizing molecular dynamic simulation, we identified a conformational change in pY393-AGO2 protein structure leading to disruption of the RAS binding site. Knockdown of AGO2 led to a profound decrease in proliferation of mutant HRAS/NRAS-driven cell lines but not WT RAS cells. These cells demonstrated oncogene-induced senescence (OIS) as evidenced by β-galactosidase staining and induction of multiple downstream senescence effectors. Mechanistically, we discovered that the senescent phenotype was mediated via induction of reactive oxygen species. Intriguingly, we further identified that loss of AGO2 promoted a novel feed forward pathway leading to inhibition of the PTP1B phosphatase and activation of EGFR–MAPK signaling, consequently resulting in OIS. Taken together, our study demonstrates that the EGFR–AGO2–RAS signaling axis is essential for maintaining mutant HRAS and NRAS-driven malignancies.
Persistent Exertional Dyspnea and Perceived Exercise Intolerance After Mild COVID-19: A Critical Role for Breathing Dysregulation?
Authors: van Voorthuizen Esther L , van Helvoort Hanneke A C , Peters Jeanette B , van den Heuvel Michel M , van den Borst Bram 
Published: July 2022

Abstract

Objective
After mild COVID-19, a subgroup of patients reported post–acute-phase sequelae of COVID-19 (PASC) in which exertional dyspnea and perceived exercise intolerance were common. Underlying pathophysiological mechanisms remain incompletely understood. The purpose of this study was to examine outcomes from cardiopulmonary exercise testing (CPET) in these patients.

Methods
In this observational study, participants were patients who were referred for the analysis of PASC after mild COVID-19 and in whom CPET was performed after standard clinical workup turned out unremarkable. Cardiocirculatory, ventilatory, and metabolic responses to and breathing patterns during exercise at physiological limits were analyzed.

Results
Twenty-one patients (76% women; mean age = 40 years) who reported severe disability in physical functioning underwent CPET at 32 weeks (interquartile range = 22–52) after COVID-19. Mean peak O2 uptake was 99% of predicted with normal anaerobic thresholds. No cardiovascular or gas exchange abnormalities were detected. Twenty of the 21 patients (95%) demonstrated breathing dysregulation (ventilatory inefficiency [29%], abnormal course of breathing frequency and tidal volume [57%], absent increase of end-tidal Pco2 [57%], and abnormal resting blood gases [67%]).

Conclusion
Breathing dysregulation may explain exertional dyspnea and perceived exercise intolerance in patients with PASC after mild COVID-19 and can be present in the absence of deconditioning. This finding warrants further study on the levels of neural control of breathing and muscle function, and simultaneously provides a potential treatment opportunity.

Impact
This study contributes to the understanding of persistent exertional dyspnea and perceived exercise intolerance following mild COVID-19, which is vital for the development of effective rehabilitation strategies.
Factors associated with depression in residents in the post-epidemic era
Authors: Li S , Guo B , Yang Q , Yin J , Jiang Y , Tian L , Ji Y , Zhu H 
Published: July 2022

Summary

Objective
To explore the factors associated with depression in residents in the post-epidemic era of COVID-19.

Methods
A multi-stage stratified random sampling method was used to conduct a questionnaire survey among community residents through self-designed questionnaires and self-rating depression scale (SDS). Multivariate logistic regression analysis was performed on the influencing factors of depressive symptoms.

Results
A total of 1993 residues completed the survey of depression status. The incidence of depressive symptoms was 27.04%. The multivariate logistic regression analysis showed that female (odds ratio (OR): 6.239, 95% confidence interval (CI): 2.743–10.698), body mass index (BMI) &gt; 24 (OR: 2.684, 95% CI: 1.059–3.759) and drinking (OR: 1.730, 95% CI: 1.480–3.153) were the risk factors for developing depressive symptoms. Married (OR: 0.417, 95% CI: 0.240–0.652), monthly income (3001–5000 yuan, OR: 0.624, 95% CI: 0.280–0.756; &gt;5000 yuan, OR: 0.348, 95% CI: 0.117–0.625), ordinary residents (OR: 0.722, 95% CI: 0.248–0.924) and urban residents (OR: 0.655, 95% CI: 0.394–0.829) were the protective factors of depressive symptoms.

Conclusions
Under the post-epidemic era of COVID-19, depressive symptoms are still common among community residents in China. Gender, BMI, drinking, marriage, monthly income and nature of personnel and residential area are associated with the incidence of depressive symptoms.