bluuebunny/crossref_metadata_2025_split huggingface dataset:
Removal of common antimicrobial agents by sustained low-efficiency dialysis
Authors: Hudson Joanna Q. , Hilgers Madelyn N. , Gosmanova Elvira O. 
Published: February 2024

ABSTRACT

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin–tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for 8 hours during SLED (on-SLED). Arterial samples were collected every 2 hours for up to 6 hours while not receiving SLED (off-SLED) for the calculation of SLED clearance, half-life (
t
1/2
) on-SLED and off-SLED, and the fraction of removal by SLED (
f
D
). Twenty-one patients completed the study: 52% male, mean age (±SD) 53 ± 13 years, and mean weight of 98 ± 30 kg. Eighty-six percent had AKI, and 4 patients were receiving cefepime, 3 daptomycin, 10 meropenem, 6 piperacillin–tazobactam, and 13 vancomycin. The average SLED time was 7.3 ± 1.1 hours, and the mean ultrafiltration rate was 95 ± 52 mL/hour (range 10–211). The
t
1/2
on-SLED was substantially lower than the off-SLED
t
1/2
for all antimicrobials, and the SLED
f
D
varied between 44% and 77%. An 8-hour SLED session led to significant elimination of most antimicrobials evaluated. If SLED is performed, modification of the dosing regimen is warranted to avoid subtherapeutic concentrations.
Population-level transposable element expression dynamics influence trait evolution in a fungal crop pathogen
Authors: Abraham Leen Nanchira , Oggenfuss Ursula , Croll Daniel 
Published: February 2024

ABSTRACT

The rapid adaptive evolution of microbes is driven by strong selection pressure acting on genetic variation. How adaptive genetic variation is generated within species and how such variation influences phenotypic trait expression is often not well understood though. We focused on the recent activity of transposable elements (TEs) using deep population genomics and transcriptomics analyses of a fungal plant pathogen with a highly active content of TEs in the genome.
Zymoseptoria tritici
causes one of the most damaging diseases on wheat, with recent adaptation to the host and environment being facilitated by TE-associated mutations. We obtained genomic and RNA-sequencing data from 146 isolates collected from a single wheat field. We established a genome-wide map of TE insertion polymorphisms in the population by analyzing recent TE insertions among individuals. We quantified the locus-specific transcription of individual TE copies and found considerable population variation at individual TE loci in the population. About 20% of all TE copies show transcription in the genome suggesting that genomic defenses such as repressive epigenetic marks and repeat-induced polymorphisms are at least partially ineffective at preventing the proliferation of TEs in the genome. A quarter of recent TE insertions are associated with expression variation of neighboring genes providing broad potential to influence trait expression. We indeed found that TE insertions are likely responsible for variation in virulence on the host and potentially diverse components of secondary metabolite production. Our large-scale transcriptomics study emphasizes how TE-derived polymorphisms segregate even in individual microbial populations and can broadly underpin trait variation in pathogens.

IMPORTANCE

Pathogens can rapidly adapt to new hosts, antimicrobials, or changes in the environment. Adaptation arises often from mutations in the genome; however, how such variation is generated remains poorly understood. We investigated the most dynamic regions of the genome of
Zymoseptoria tritici,
a major fungal pathogen of wheat. We focused on the transcription of transposable elements. A large proportion of the transposable elements not only show signatures of potential activity but are also variable within a single population of the pathogen. We find that this variation in activity is likely influencing many important traits of the pathogen. Hence, our work provides insights into how a microbial species can adapt over the shortest time periods based on the activity of transposable elements.
Complete coding genome sequence of a
Teschovirus A
genotype strain
Authors: Ding Yanbin , Xie Xiaofang , Huang Jiefeng , Yin Can , Yang Taotao 
Published: February 2024

ABSTRACT

This study reports the complete coding genome sequence of a novel
Teschovirus A
genotype strain, SG2, isolated from the fecal sample of an infected indigenous pig in western Jiangxi, China.
Self-administered versus clinician-performed BinaxNOW COVID rapid test: a comparison of accuracy
Authors: Vaeth Mary Jane E. , Cheema Minahil , Omer Sarah , Gupta Ishaan , Sun Kristie J. , Mitchell Asia , Elhabashy Maryam , Foyez Maisha , Cheema Aamna , Javed Binish , Purekal Sophia , Rahat Resham , Michtalik Henry , Locke Charles , Kantsiper Melinda , Campbell James D. , Hammershaimb E. Adrianne , Manabe Yukari C. , Robinson Matthew L. , Johnson J. Kristie , Wilson Lucy E. , Callahan Charles W. ,   CONQUER COVID Consortium, Siddiqui Zishan K. 
Published: February 2024

ABSTRACT

We conducted a single-center study at a free community testing site in Baltimore City to assess the accuracy of self-performed rapid antigen tests (RATs) for COVID-19. Self-administered BinaxNOW RATs were compared with clinician-performed RATs and against a reference lab molecular testing as the gold standard. Of the 953 participants, 14.9% were positive for SARS- CoV-2 as determined by RT-PCR. The sensitivity and specificity were similar for both self- and clinician-performed RATs (sensitivity: 83.9% vs 88.2%,
P
= 0.40; specificity: 99.8% vs 99.6%,
P
= 0.6). Subgroup comparisons based on age and race yielded similar results. Notably, 5.2% (95% CI: 1.5% to 9.5%) of positive results were potentially missed due to participant misinterpretation of the self-test card. However, the false-positive rate for RATs was reassuringly comparable in accuracy to clinician-administered tests. These findings hold significant implications for physicians prescribing treatment based on patient-reported, self-administered positive test results. Our study provides robust evidence supporting the reliability and utility of patient-performed RATs, underscoring their comparable accuracy to clinician-performed RATs, and endorsing their continued use in managing COVID-19. Further studies using other rapid antigen test brands are warranted.

IMPORTANCE
Accurate and accessible COVID-19 testing is crucial for effective disease control and management. A recent single-center study conducted in Baltimore City examined the reliability of self-performed rapid antigen tests (RATs) for COVID-19. The study found that self-administered RATs yielded similar sensitivity and specificity to clinician-performed tests, demonstrating their comparable accuracy. These findings hold significant implications for physicians relying on patient-reported positive test results for treatment decisions. The study provides robust evidence supporting the reliability and utility of patient-performed RATs, endorsing their continued use in managing COVID-19. Furthermore, the study highlights the need for further research using different rapid antigen test brands to enhance generalizability. Ensuring affordable and widespread access to self-tests is crucial, particularly in preparation for future respiratory virus seasons and potential waves of reinfection of SARS-CoV-2 variants such as the Omicron variant.
Patient and public involvement in abortion research: reflections from the Shaping Abortion for Change (SACHA) Study
Authors: Blaylock Rebecca , Lewandowska Maria , Kelly Charlotte , Gunn Becky , Meiksin Rebecca , Scott Rachel H , Palmer Melissa J , Wellings Kaye , Lohr Patricia A , French Rebecca S , N/A The SACHA Study Team 
Published: February 2024

Patient and public involvement (PPI) is limited within abortion-related research. Possible reasons for this include concerns about engaging with a stigmatised patient group who value confidentiality and may be reluctant to re-engage with services. Structural barriers, including limited funding for abortion-related research, also prevent researchers from creating meaningful PPI opportunities. Here, we describe lessons learnt on undertaking PPI as part of the Shaping Abortion for Change (SACHA) Study, which sought to create an evidence base to guide new directions in abortion care in Britain.Two approaches to PPI were used: involving patients and the public in the oversight of the research and its dissemination as lay advisors, and group meetings to obtain patients’ views on interpretation of findings and recommendations. All participants observed the SACHA findings aligned with their own experiences of having an abortion in Britain. These priorities aligned closely with those identified in a separate expert stakeholder consultation undertaken as part of the SACHA Study. One additional priority which had not been identified during the research was identified by the PPI participants.We found abortion patients to be highly motivated to engage in the group meetings, and participation in them actively contributed to the destigmatisation of abortion by giving them a space to share their experiences. This may alleviate any ethical concerns about conducting research and PPI on abortion, including the assumption that revisiting an abortion experience will cause distress. We hope that our reflections are useful to others considering PPI in abortion-related research and service improvement.
Non-invasive biomarkers of disease activity and organ damage in ANCA-associated vasculitis: a systematic review
Authors: Renson Thomas , Kelly Margaret M , Benediktsson Hallgrimur , Grundhoefer Nele , Luca Nadia , Miettunen Paivi , Twilt Marinka , Grisaru Silviu , Wade Andrew , Banks Anke , Fifi-Mah Aurore , Hamiwka Lorraine , Benseler Susanne 
Published: February 2024

BackgroundIn anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), histopathological assessment of affected tissue is often necessary for diagnosis and assessment of disease extent. There is a requirement for validated non-invasive biomarkers to avoid the need for serial tissue biopsies.MethodsA systematic review of scientific databases from 2012 until present was performed to identify studies fulfilling the inclusion criteria. Studies were assessed for quality using the Strengthening the Reporting of Observational Studies in Epidemiology checklist for cohort, case–control and cross-sectional studies and the Risk of Bias Assessment tool for Non-randomised Studies, or the Cochrane Risk of Bias tool 2.0 for randomised controlled trials. A descriptive synthesis of the data for non-invasive (blood-based or urinary) biomarkers of AAV-related disease activity and organ damage was performed.ResultsTwenty-two high quality studies were included. These articles reported the value of blood-based and urinary biomarkers including anti-neutrophil cytoplasmic antibodies, immune cells, complement factors, gene expression profiles, cytokines, chemokines and other proteins in the assessment of disease activity and/or organ damage in patients with AAV. Many of these biomarkers involve the alternative complement pathway, neutrophil activation and macrophage activation.ConclusionThis is the first contemporary systematic review synthesising the value of non-invasive biomarkers of AAV-related disease activity and organ damage. The incorporation of individual markers in combined biomarker profiles might enhance clinical decision-making. Many unmet needs were identified; few studies involve oeosinophilic granulomatosis with polyangiitis and patients with childhood-onset AAV. Further validation of the candidate biomarkers is warranted in large prospective studies to bridge the existing knowledge gaps and apply precision health to systemic vasculitis.
Metabolic and molecular imaging in inflammatory arthritis
Authors: Noversa de Sousa Rita , Tascilar Koray , Corte Giulia , Atzinger Armin , Minopoulou Ioanna , Ohrndorf Sarah , Waldner Maximilian , Schmidkonz Christian , Kuwert Torsten , Knieling Ferdinand , Kleyer Arnd , Ramming Andreas , Schett Georg , Simon David , Fagni Filippo 
Published: February 2024

It is known that metabolic shifts and tissue remodelling precede the development of visible inflammation and structural organ damage in inflammatory rheumatic diseases such as the inflammatory arthritides. As such, visualising and measuring metabolic tissue activity could be useful to identify biomarkers of disease activity already in a very early phase. Recent advances in imaging have led to the development of so-called ‘metabolic imaging’ tools that can detect these changes in metabolism in an increasingly accurate manner and non-invasively.Nuclear imaging techniques such as18F-D-glucose and fibroblast activation protein inhibitor-labelled positron emission tomography are increasingly used and have yielded impressing results in the visualisation (including whole-body staging) of inflammatory changes in both early and established arthritis. Furthermore, optical imaging-based bedside techniques such as multispectral optoacoustic tomography and fluorescence optical imaging are advancing our understanding of arthritis by identifying intra-articular metabolic changes that correlate with the onset of inflammation with high precision and without the need of ionising radiation.Metabolic imaging holds great potential for improving the management of patients with inflammatory arthritis by contributing to early disease interception and improving diagnostic accuracy, thereby paving the way for a more personalised approach to therapy strategies including preventive strategies. In this narrative review, we discuss state-of-the-art metabolic imaging methods used in the assessment of arthritis and inflammation, and we advocate for more extensive research endeavours to elucidate their full field of application in rheumatology.
Consequences of anemia in geriatric hip fractures: how low is too low?
Authors: Bruce Kimberli , Mangram Alicia , Sucher Joseph F , Blake Nuria , Balcome Charles D , Prokuski Laura , Dzandu James , Barletta Jeffrey F , Shirah Gina R 
Published: February 2024

BackgroundThe transfusion threshold for low hemoglobin (Hgb) in geriatric patients with hip fractures is widely debated. In certain populations, low Hgb is associated with poor outcomes. Our objective was to evaluate the relationship between lowest Hgb and outcome to identify the Hgb threshold where poor outcomes were more prevalent.MethodsThis retrospective cohort study included consecutive patients with hip fractures, aged ≥60 years, evaluated at two level 1 trauma centers from 2018 to 2021. Patients who did not undergo operative fixation or had a length of stay <1 day were excluded. The primary endpoint was adverse outcome defined as the composite of myocardial infarction, stroke, new-onset arrhythmia or death. We compared lowest Hgb and possible confounders between patients with and without adverse outcomes. Classification and regression tree (CART) analysis was performed to identify the threshold for Hgb where adverse outcomes were more prevalent. Multivariate analysis was performed.ResultsWe evaluated 935 patients. Mean age was 80±10 years; admission Hgb was 12.5±1.7 g/dL. Diabetes was present in 20%, and 20% had coronary artery disease. Adverse outcomes were noted in 57 patients (6.1%). CART identified ≤7.1 g/dL as the Hgb threshold where adverse outcomes were more prevalent (15% vs. 4.1%, p<0.001). Additionally, a greater number of adverse outcomes were noted in the subgroup of patients having both a hemoglobin ≤7.1 g/dL and advanced age (age >79 years (22%)). After controlling for age, American Society of Anesthesiologist Physical Status Classification (ASA), antiplatelet medication, admission Hgb, time to operation and blood transfusions, lowest Hgb ≤7.1 g/dL remained a risk factor for adverse outcomes.ConclusionsIn geriatric patients with isolated hip fractures, Hgb ≤7.1 g/dL is associated with a significantly higher rate of adverse outcomes. This risk was most pronounced in patients older than 79 years; particular care should be taken in this demographic.Level of evidence/study typeLevel III/prognostic and epidemiological.
Heavy neutral lepton corrections to SM boson decays: lepton flavour universality violation in low-scale seesaw realisations
Authors: Abada A. , Kriewald J. , Pinsard E. , Rosauro-Alcaraz S. , Teixeira A. M. 
Published: February 2024

AbstractWe study lepton flavour universality violation in SM boson decays in low-scale seesaw models of neutrino mass generation, also addressing other electroweak precision observables. We compute the electroweak next-to-leading order corrections, which turn out to be important – notably in the case of the invisible decay width of theZboson, for which the corrections can be as large as the current experimental uncertainty. As a well-motivated illustrative study case, we choose a realisation of the Inverse Seesaw mechanism, and discuss the complementary role of lepton flavour conserving, lepton flavour violating and precision observables, both in constraining and in probing such models of neutrino mass generation. Our findings suggest that invisibleZdecays are especially important, potentially at the origin of the most stringent constraints for certain regimes of the Inverse Seesaw (while complying with charge lepton flavour violation and other electroweak precision tests). We also discuss the probing power of the considered observables in view of the expected improvement in experimental precision at FCC-ee.
Neutrino mass models at $$\mu $$TRISTAN
Authors: Dev P. S. Bhupal , Heeck Julian , Thapa Anil 
Published: February 2024

AbstractWe study the prospects of probing neutrino mass models at the newly proposed antimuon collider $$\mu $$
μ
TRISTAN, involving $$\mu ^+e^-$$

μ
+

e
-

scattering at $$\sqrt{s}= 346~\text {GeV}$$

s

=
346

GeV

and $$\mu ^+\mu ^+$$

μ
+

μ
+

scattering at $$\sqrt{s}= 2~\text {TeV}.$$

s

=
2

TeV
.

We show that $$\mu $$
μ
TRISTAN is uniquely sensitive to leptophilic neutral and doubly-charged scalars naturally occurring in various neutrino mass models, such as Zee, Zee–Babu, cocktail, and type-II seesaw models, over a wide range of mass and coupling values, well beyond the current experimental constraints. It also allows for the possibility to correlate the collider signals with neutrino mixing parameters and charged lepton flavor violating observables.
Differential Responses to Immune Checkpoint Inhibitors are Governed by Diverse Mismatch Repair Gene Alterations
Authors: Khushman Moh'd M. , Toboni Michael D. , Xiu Joanne , Manne Upender , Farrell Alex , Lou Emil , Shields Anthony F. , Philip Philip A. , Salem Mohamed E. , Abraham Jim , Spetzler David , Marshall John , Jayachandran Priya , Hall Michael J. , Lenz Heinz-Josef , Sahin Ibrahim Halil , Seeber Andreas , Powell Mathew A. 
Published: February 2024

Abstract

Purpose:
The response to immune checkpoint inhibitors (ICI) in deficient mismatch repair (dMMR) colorectal cancer and endometrial cancer is variable. Here, we explored the differential response to ICIs according to different mismatch repair alterations

Experimental Design:
Colorectal cancer (N = 13,701) and endometrial cancer (N = 3,315) specimens were tested at Caris Life Sciences. Median overall survival (mOS) was estimated using Kaplan–Meier. The prediction of high-, intermediate-, and low-affinity epitopes by tumor mutation burden (TMB) values was conducted using R-squared (R2).

Results:
Compared with mutL (MLH1 and PMS2) co-loss, the mOS was longer in mutS (MSH2 and MSH6) co-loss in all colorectal cancer (54.6 vs. 36 months; P = 0.0.025) and endometrial cancer (81.5 vs. 48.2 months; P &lt; 0.001) patients. In ICI-treated patients, the mOS was longer in mutS co-loss in colorectal cancer [not reached (NR) vs. 36 months; P = 0.011). In endometrial cancer, the mOS was NR vs. 42.2 months; P = 0.711]. The neoantigen load (NAL) in mutS co-loss compared with mutL co-loss was higher in colorectal cancer (high-affinity epitopes: 25.5 vs. 19; q = 0.017, intermediate: 39 vs. 32; q = 0.004, low: 87.5 vs. 73; q &lt; 0.001) and endometrial cancer (high-affinity epitopes: 15 vs. 11; q = 0.002, intermediate: 27.5 vs. 19; q &lt; 0.001, low: 59 vs. 41; q &lt; 0.001), respectively. R2 ranged from 0.25 in mutS co-loss colorectal cancer to 0.95 in mutL co-loss endometrial cancer.

Conclusions:
Patients with mutS co-loss experienced longer mOS in colorectal cancer and endometrial cancer and better response to ICIs in colorectal cancer. Among all explored biomarkers, NAL was higher in mutS co-loss and may be a potential driving factor for the observed better outcomes. TMB did not reliably predict NAL.
Evaluating for Correlations between Specific Metabolites in Patients Receiving First-Line or Second-Line Immunotherapy for Metastatic or Recurrent NSCLC: An Exploratory Study Based on Two Cohorts
Authors: Xu Yanjun , Ding Kaibo , Peng Zhongsheng , Ding Ling , Li Hui , Fan Yun 
Published: February 2024

Abstract
Immune checkpoint inhibitors (ICI) have displayed impressive clinical efficacy in the context of non–small cell lung cancer (NSCLC). However, most patients do not achieve long-term survival. Minimally invasive collected samples are attracting significant interest as new fields of biomarker study, and metabolomics is one of these growing fields. We concentrated on the augmented value of the metabolomic profile in differentiating long-term survival from short-term survival in patients with NSCLC subjected to ICIs. We prospectively recruited 97 patients with stage IV NSCLC who were treated with anti–PD-1 inhibitor, including patients treated with monoimmunotherapy as second-line treatment (Cohort 1), and patients treated with combination immunotherapy as first-line treatment (Cohort 2). Each cohort was divided into long-term and short-term survival groups. All blood samples were collected before beginning immunotherapy. Serum metabolomic profiling was performed by UHPLC-Q-TOF MS analysis. Pareto-scaled principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis were performed. In Cohort 1, the mPFS and mOS of long-survival patients are 27.05 and NR months, respectively, and those of short-survival patients are 2.79 and 10.59 months. In Cohort 2, the mPFS and mOS of long-survival patients are 27.35 and NR months, respectively, and those of short-survival patients are 3.77 and 12.17 months. A total of 41 unique metabolites in Cohort 1 and 47 in Cohort 2 were screened. In Cohorts 1 and 2, there are 6 differential metabolites each that are significantly associated with both progression-free survival and overall survival. The AUC values for all groups ranged from 0.73 to 0.95. In cohort 1, the top 3 enriched KEGG pathways, as determined through significant different metabolic pathway analysis, were primary bile acid biosynthesis, African trypanosomiasis, and choline metabolism in cancer. In Cohort 2, the top 3 enriched KEGG pathways were the citrate cycle (TCA cycle), PPAR signaling pathway, and primary bile acid biosynthesis. The primary bile acid synthesis pathway had significant differences in the long-term and short-term survival groups in both Cohorts 1 and 2. Our study suggests that peripheral blood metabolomic analysis is critical for identifying metabolic biomarkers and pathways responsible for the patients with NSCLC treated with ICIs.