bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacteriophage and antibiotic combination therapy for recurrent
Enterococcus faecium
bacteremia
Authors: Stellfox Madison E. , Fernandes Carolyn , Shields Ryan K. , Haidar Ghady , Hughes Kramer Kailey , Dembinski Emily , Mangalea Mihnea R. , Arya Garima , Canfield Gregory S. , Duerkop Breck A. , Van Tyne Daria 
Published: February 2024

ABSTRACT

Enterococcus faecium
is a member of the human gastrointestinal (GI) microbiota but can also cause invasive infections, especially in immunocompromised hosts. Enterococci display intrinsic resistance to many antibiotics, and most clinical
E. faecium
isolates have acquired vancomycin resistance, leaving clinicians with a limited repertoire of effective antibiotics. As such, vancomycin-resistant
E. faecium
(VREfm) has become an increasingly difficult to treat nosocomial pathogen that is often associated with treatment failure and recurrent infections. We followed a patient with recurrent
E. faecium
bloodstream infections (BSIs) of increasing severity, which ultimately became unresponsive to antibiotic combination therapy over the course of 7 years. Whole-genome sequencing (WGS) showed that the patient was colonized with closely related
E. faecium
strains for at least 2 years and that invasive isolates likely emerged from a large
E. faecium
population in the patient’s gastrointestinal (GI) tract. The addition of bacteriophage (phage) therapy to the patient’s antimicrobial regimen was associated with several months of clinical improvement and reduced intestinal burden of VRE and
E. faecium. In vitro
analysis showed that antibiotic and phage combination therapy improved bacterial growth suppression compared to therapy with either alone. Eventual
E. faecium
BSI recurrence was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage-neutralizing antibody response occurred that coincided with an increased relative abundance of VRE in the GI tract, both of which may have contributed to clinical failure. Taken together, these findings highlight the potential utility and limitations of phage therapy to treat antibiotic-resistant enterococcal infections.

IMPORTANCE

Phage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent
E. faecium
infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced
E. faecium
and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.
Humoral and cellular immune responses against SARS-CoV-2 post-vaccination in immunocompetent and immunocompromised cancer populations
Authors: Titova Elizabeth , Kan Veronica W. , Lozy Tara , Ip Andrew , Shier Kileen , Prakash Vittal P. , Starolis Meghan , Ansari Sara , Goldgirsh Kira , Kim Seoyeon , Pelliccia Michael C. , Mccutchen Aamirah , Megalla Martinus , Gunning Thomas S. , Kaufman Harvey W. , Meyer William A. , Perlin David S. 
Published: February 2024

ABSTRACT

Cancer patients are at risk for severe coronavirus disease 2019 (COVID-19) outcomes due to impaired immune responses. However, the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is inadequately characterized in this population. We hypothesized that cancer vs non-cancer individuals would mount less robust humoral and/or cellular vaccine-induced immune SARS-CoV-2 responses. Receptor binding domain (RBD) and SARS-CoV-2 spike protein antibody levels and T-cell responses were assessed in immunocompetent individuals with no underlying disorders (
n
= 479) and immunocompromised individuals (
n
= 115). All 594 individuals were vaccinated and of varying COVID-19 statuses (i.e., not known to have been infected, previously infected, or “Long-COVID”). Among immunocompromised individuals, 59% (
n
= 68) had an underlying hematologic malignancy; of those, 46% (
n
= 31) of individuals received cancer treatment <30 days prior to study blood collection. Ninety-eight percentage (
n
= 469) of immunocompetent and 81% (
n
= 93) of immunocompromised individuals had elevated RBD antibody titers (>1,000 U/mL), and of these, 60% (
n
= 281) and 44% (
n
= 41), respectively, also had elevated T-cell responses. Composite T-cell responses were higher in individuals previously infected with SARS-CoV-2 or those diagnosed with Long-COVID compared to uninfected individuals. T-cell responses varied between immunocompetent vs carcinoma (
n
= 12) cohorts (
P
< 0.01) but not in immunocompetent vs hematologic malignancy cohorts. Most SARS-CoV-2 vaccinated individuals mounted robust cellular and/or humoral responses, though higher immunogenicity was observed among the immunocompetent compared to cancer populations. The study suggests B-cell targeted therapies suppress antibody responses, but not T-cell responses, to SARS-CoV-2 vaccination. Thus, vaccination continues to be an effective way to induce humoral and cellular immune responses as a likely key preventive measure against infection and/or subsequent more severe adverse outcomes.

IMPORTANCE
The study was prompted by a desire to better assess the immune status of patients among our cancer host cohort, one of the largest in the New York metropolitan region. Hackensack Meridian Health is the largest healthcare system in New Jersey and cared for more than 75,000 coronavirus disease 2019 patients in its hospitals. The John Theurer Cancer Center sees more than 35,000 new cancer patients a year and performs more than 500 hematopoietic stem cell transplants. As a result, the work was undertaken to assess the effectiveness of vaccination in inducing humoral and cellular responses within this demographic.
Are web-based stress management interventions effective as an indirect treatment for depression? An individual participant data meta-analysis of six randomised trials
Authors: Harrer Mathias , Nixon Patricia , Sprenger Antonia A , Heber Elena , Boß Leif , Heckendorf Hanna , Buntrock Claudia , Ebert David Daniel , Lehr Dirk 
Published: February 2024

QuestionDepression is highly prevalent and associated with numerous adverse consequences for both individuals and society. Due to low uptake of direct treatment, interventions that target related, but less stigmatising problems, such as perceived stress, have emerged as a new research paradigm.This individual participant data (IPD) meta-analysis examines if a web-based stress management intervention can be used as an ‘indirect’ treatment of depression.Study selection and analysisBayesian one-stage models were used to estimate pooled effects on depressive symptom severity, minimally important improvement and reliable deterioration. The dose–response relationship was examined using multilevel additive models, and IPD network meta-analysis was employed to estimate the effect of guidance.FindingsIn total, N=1235 patients suffering from clinical-level depression from K=6 randomised trials were included. Moderate-to-large effects were found on depressive symptom severity at 7 weeks post-intervention (d=−0.65; 95% credibility interval (CrI): −0.84 to −0.48) as measured with the Center for Epidemiological Studies’ Depression Scale. Effects were sustained at 3-month follow-up (d=−0.74; 95% CrI: −1.01 to −0.48). Post-intervention symptom severity was linearly related to the number of completed sessions. The incremental impact of guidance was estimated at d=−0.25 (95% CrI: −1.30 to 0.82), with a 35% posterior probability that guided and unguided formats produce equivalent effects.ConclusionsOur results indicate that web-based stress management can serve as an indirect treatment, yielding effects comparable with direct interventions for depression. Further research is needed to determine if such formats can indeed increase the utilisation of evidence-based treatment, and to corroborate the favourable effects for human guidance.Study registrationOpen material repository: osf.io/dbjc8, osf.io/3qtbe.Trial registration numberGerman Clinical Trial Registration (DRKS): DRKS00004749, DRKS00005112, DRKS00005384, DRKS00005687, DRKS00005699, DRKS00005990.
Non-invasive neuromodulation of the right temporoparietal junction using theta-burst stimulation in functional neurological disorder
Authors: Bühler Janine , Weber Samantha , Loukas Serafeim , Walther Sebastian , Aybek Selma 
Published: February 2024

BackgroundDisrupted sense of agency (SoA)—the sense of being the agent of one’s own actions—has been demonstrated in patients with functional neurological disorder (FND), and a key area of the corresponding neuronal network is the right temporoparietal junction (rTPJ). Several functional MRI (fMRI) studies have found hypoactivation as well as hyperactivation of the rTPJ in FND. In a proof-of-concept study, we tested whether repetitive transcranial magnetic stimulation (rTMS) over the rTPJ could restore this aberrant activity.MethodsIn a randomised, crossover, single-blinded, sham-controlled study design, theta-burst stimulation (tb-rTMS) was applied over the rTPJ in 23 patients with FND and 19 healthy controls (HC), with each participant undergoing three stimulatory visits (inhibitory continuous TBS (cTBS), excitatory intermittent TBS (iTBS) and sham). During fMRI, participants played a visuomotor task artificially reducing their SoA (manipulated agency, MA), repeated after each neurostimulation. We compared brain activity and behavioural SoA as primary outcomes before and after tb-rTMS and investigated the feasibility of tb-rTMS over the rTPJ in FND as secondary outcome.ResultsAt baseline, patients showed decreased accuracy in detecting reduced agency compared with controls (p<0.001), paralleled by lower brain activation in the rTPJ during MA (p=0.037, volume of interest). A region of interest analysis on the rTPJ showed no effect of the sham condition in FND or HC (p=0.917; p=0.375) but revealed a significant effect of stimulation protocol (cTBS/iTBS, p=0.037) in patients with FND, with the excitatory protocol increasing the blood-oxygen-level-dependent (BOLD) signal, whereas this effect was not found in HC. In neither group, a behavioural effect of tb-rTMS was observed.ConclusionAberrant processing of agency in FND was confirmed at baseline, reflected in behavioural outcome and reduced activity in the rTPJ. Tb-rTMS over this key region elicited neuronal changes in patients, paving ways for future studies exploring TMS as neurobiologically informed intervention to restore SoA in FND. We critically discuss methodological intricacies and outline further steps in this research line.
Is there a role for fibreoptic bronchoscopy in patients presenting with haemoptysis and negative CT? A systematic review and meta-analysis
Authors: Mohammad Syed , Wijayaratne Thisarana , Mavilakandy Akash , Karim Nawazish , Theaker Margaret , Reddy Raja , Tsaknis George 
Published: February 2024

IntroductionHaemoptysis can be a feature of lung cancer and patients are typically fast-tracked for evaluation with chest radiography, contrast-enhanced CT and fibreoptic bronchoscopy (FOB).ObjectiveWe aim to explore whether FOB should be conducted as a component of the routine evaluation of non-massive haemoptysis, especially in the context of suspected lung cancer.MethodsMEDLINE, EMBASE and Cochrane Library were searched for studies comparing FOB with CT in the evaluation of non-massive haemoptysis while reporting at least one of the listed primary outcomes. Primary outcomes include sensitivity of diagnostic modality with respect to lung cancer. Secondary outcomes include detection of other aetiologies such as infection. Results were synthesised using a random effects meta-analysis. Sensitivity analysis was performed for patient age group and year of study. Risk of bias assessment was carried out with the Quality Assessment of Diagnostic Accuracy Studies-2 tool.ResultsA total of 2273 citations were screened and 11 studies were included, comprising a total sample size of 2015 patients with 226 confirmed cases of lung cancer. A total of 1816 and 1734 patients received a CT scan and FOB, respectively. The pooled sensitivities for detection of lung cancer using CT scan and bronchoscopy were 98% (95% CI 93.0% to 99.0%) and 86% (95% CI 63.0% to 95.0%), respectively. The sensitivity of CT was higher than that of FOB for both primary and secondary outcomes.ConclusionThis study suggests that bronchoscopy does not offer significant additional diagnostic benefit in the evaluation of patients presenting with non-massive haemoptysis and a negative CT scan.
Diagnostic accuracy of venous system ultrasound for subtypes of acute kidney injury
Authors: Aslaner Mehmet Ali , Helvacı Özant , Haycock Korbin , Kılıçaslan İsa , Yaşar Emre , Cerit Mahi Nur , Şendur Halit Nahit , Güz Galip , Demircan Ahmet 
Published: February 2024

BackgroundManagement of acute kidney injury (AKI) in the ED can be difficult due to uncertainty regarding the aetiology. This study investigated the diagnostic value of venous system ultrasound for determining the aetiological subtypes of AKI in the ED.MethodsThis multidisciplinary prospective cohort study was conducted in a single academic ED over the course of a year. Adult patients with AKI were evaluated using the venous excess ultrasound (VExUS) score, which is a four-step ultrasound protocol. The protocol begins with the inferior vena cava (IVC) measurement and examines organ flow patterns, including portal, hepatic and renal veins in the presence of dilated IVC. The AKI subtypes (hypovolaemia, cardiorenal, systemic vasodilatation and renal) were adjudicated by nephrologists and emergency physicians, considering data that became available during the hospitalisation. We determined the diagnostic test characteristics of VExUS for identifying each of the four AKI aetiological subtypes.Results150 patients with AKI were included in the study. Hypovolaemia was the most frequent finally adjudicated cause of AKI (66%), followed by cardiorenal (18%), systemic vasodilatation (8.7%) and renal (7.3%). In diagnosing the cardiorenal subtype, the area under the curve (AUC) for VExUS grade >0 was 0.819, with 77.8% sensitivity and 80.5% specificity, and the AUC for IVC maximum diameter >20.4 mm was 0.865, with 74.1% sensitivity and 86.2% specificity. For the hypovolaemia subtype, the AUC for VExUS grade ≤0 was 0.711, with 83.8% sensitivity and 56.9% specificity, and the AUC for IVC maximum diameter ≤16.8 mm was 0.736, with 73.7% sensitivity and 68.6% specificity. None of the parameters achieved adequate test characteristics for renal and systemic vasodilatation subtypes.ConclusionThe VExUS score has good diagnostic accuracy for cardiorenal AKI and fair accuracy for hypovolaemic AKI but cannot identify renal and systemic vasodilatation subtypes. It should not therefore be used in isolation to determine the cause of AKI in the ED.Trial registration numberNCT04948710.
Circumstances of unintentional fall-related adult deaths: Utah, 2010–2020
Authors: Shi Yanling , Bennion Erica , Ward Chuck , Nolen Leisha D. 
Published: February 2024

ObjectiveFall-related deaths have been on the rise nationwide. Our objective was to characterise the trend in unintentional fall-related adult deaths in Utah and evaluate the underlying and contributing causes associated with these deaths.MethodsWe used 2010–2020 Utah death certificate data and included all Utah deaths aged 18 and older with a fall listed on their death records as the underlying or contributing cause of death in the analysis.ResultsFrom 2010 to 2020, the overall age-adjusted unintentional fall death rate increased 70% from 15.7 to 26.8 per 100 000 person-years, while the overall age-adjusted death rate increase was 12% at the time. On average, the group with falls as one of the contributing causes had 4.9 other contributing causes, while the group with falls as an underlying cause had 3.3; the two averages were statistically different. Incidence of death increased 60% (12.1–19.4 per 100 000) for falls classified as the underlying cause of death and 103% (3.6–7.3 per 100 000) for those with fall as a contributing cause. Coding for the type of fall became more specific with a 30% decrease in unspecified fall (International Classification of Diseases, 10th revision code W19) (5.9–4.1 per 100 000).ConclusionThere was an increasing trend of unintentional fall-related adult deaths in Utah from 2010 to 2020. This increase is consistent with national trends. Our data supports there is more specific reporting of fall deaths, but better reporting alone cannot explain the uptrend. Furthermore, the deaths with falls as contributing causes increased the most, and these individuals have more comorbidities.
Inadequate prophylaxis in patients with trauma: anti-Xa-guided enoxaparin dosing management in critically ill patients with trauma
Authors: Niziolek Grace Martin , Mangan Lauren , Weaver Cassidi , Prendergast Vanessa , Lamore Raymond , Zielke Megan , Martin Niels D 
Published: February 2024

IntroductionVenous thromboembolism (VTE) causes significant morbidity in patients with trauma despite advances in pharmacologic therapy. Prior literature suggests standard enoxaparin dosing may not achieve target prophylactic anti-Xa levels. We hypothesize that a new weight-based enoxaparin protocol with anti-Xa monitoring for dose titration in critically injured patients is safe and easily implemented.MethodsThis prospective observational study included patients with trauma admitted to the trauma intensive care unit (ICU) from January 2021 to September 2022. Enoxaparin dosing was adjusted based on anti-Xa levels as standard of care via a performance improvement initiative. The primary outcome was the proportion of subtarget anti-Xa levels (<0.2 IU/mL) on 30 mg two times per day dosing of enoxaparin. Secondary outcomes included the dosing modifications to attain goal anti-Xa levels, VTE and bleeding events, and hospital and ICU lengths of stay.ResultsA total of 282 consecutive patients were included. Baseline demographics revealed a median age of 36 (26–55) years, and 44.7% with penetrating injuries. Of these, 119 (42.7%) achieved a target anti-Xa level on a starting dose of 30 mg two times per day. Dose modifications for subtarget anti-Xa levels were required in 163 patients (57.8%). Of those, 120 underwent at least one dose modification, which resulted in 78 patients (47.8%) who achieved a target level prior to hospital discharge on a higher dose of enoxaparin. Overall, only 69.1% of patients achieved goal anti-Xa level prior to hospital discharge. VTE occurred in 25 patients (8.8%) and major bleeding in 3 (1.1%) patients.ConclusionA majority of critically injured patients do not meet target anti-Xa levels with 30 mg two times per day enoxaparin dosing. This study highlights the need for anti-Xa-based dose modification and efficacy of a pharmacy-driven protocol. Further optimization is warranted to mitigate VTE events.Level of evidenceTherapeutic/care management, level III
Do we still need Illumina sequencing data? Evaluating Oxford Nanopore Technologies R10.4.1 flow cells and the Rapid v14 library prep kit for Gram negative bacteria whole genome assemblies
Authors: Lerminiaux Nicole , Fakharuddin Ken , Mulvey Michael R. , Mataseje Laura 
Published: February 2024

The best whole genome assemblies are currently built from a combination of highly accurate short-read sequencing data and long-read sequencing data that can bridge repetitive and problematic regions. Oxford Nanopore Technologies (ONT) produce long-read sequencing platforms and they are continually improving their technology to obtain higher quality read data that is approaching the quality obtained from short-read platforms such as Illumina. As these innovations continue, we evaluated how much ONT read coverage produced by the Rapid Barcoding Kit v14 (SQK-RBK114) is necessary to generate high-quality hybrid and long-read-only genome assemblies for a panel of carbapenemase-producing Enterobacterales bacterial isolates. We found that 30× long-read coverage is sufficient if Illumina data are available, and that more (at least 100× long-read coverage is recommended for long-read-only assemblies. Illumina polishing is still improving single nucleotide variants (SNVs) and INDELs in long-read-only assemblies. We also examined if antimicrobial resistance genes could be accurately identified in long-read-only data, and found that Flye assemblies regardless of ONT coverage detected >96% of resistance genes at 100% identity and length. Overall, the Rapid Barcoding Kit v14 and long-read-only assemblies can be an optimal sequencing strategy (i.e., plasmid characterization and AMR detection) but finer-scale analyses (i.e., SNV) still benefit from short-read data.
ParticleNet and its application on CEPC jet flavor tagging
Authors: Zhu Yongfeng , Liang Hao , Wang Yuexin , Qu Huilin , Zhou Chen , Ruan Manqi 
Published: February 2024

AbstractQuarks (except top quarks) and gluons produced in collider experiments hadronize and fragment into sprays of stable particles, called jets. Identification of quark flavor is desired for collider experiments in high-energy physics, relying on flavor tagging algorithms. In this study, using a full simulation of the Circular Electron Positron Collider (CEPC), we investigate the flavor tagging performance of two different algorithms: ParticleNet, based on a Graph Neural Network, and LCFIPlus, based on the Gradient Booted Decision Tree. Compared to LCFIPlus, ParticleNet significantly enhances flavor tagging performance, resulting in a significant improvement in benchmark measurement accuracy, i.e., a 36% improvement for $$\sigma (ZH)\cdot Br(Z\rightarrow \nu \bar{\nu }, H\rightarrow c\bar{c})$$

σ
(
Z
H
)
·
B
r
(
Z
→
ν

ν

¯

,
H
→
c

c

¯

)

measurement and a 75% improvement for $$|V_{cb}|$$

|

V

cb

|

measurement via W boson decay, respectively, when the CEPC operates as a Higgs factory at the center-of-mass energy of 240 GeV and collects an integrated luminosity of 5.6 ab$$^{-1}$$

-
1

. We compare the performance of ParticleNet and LCFIPlus at different vertex detector configurations, observing that the inner radius is the most sensitive parameter, followed by material budget and spatial resolution.