bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infectious causes and mimickers of meniere's disease
Authors: Kurtzman Joey S. , Sioshansi Pedrom C. 
Published: June 2023

Purpose of review
To review the evidence of a possible viral etiology of Meniere's disease, the role of antiviral therapy, as well as other infectious disease processes that may mimic Meniere's disease. Better understanding of the etiology of Meniere's disease and the role of various infectious disease processes may allow for more effective diagnosis and management.

Recent findings
There is evidence that viral infections – to Herpes simplex virus, cytomegalovirus, Epstein Barr virus, influenza, adenovirus, Coxsackie virus B, and Varicella Zoster Virus – may be involved in the development of Meniere's disease, however the evidence is inconsistent and the underlying mechanism remains theoretical. Nevertheless, antiviral therapy may be effective for a subset of patients with Meniere's disease. Lastly, other infectious diseases including Lyme disease and syphilis can present with symptoms similar to Meniere's disease. It is important to discern these from Meniere's disease to determine the appropriate treatment.

Summary
There is a paucity of high-quality evidence to support a viral etiology of Meniere's disease, and the current evidence appears circumstantial and inconsistent. Additional research is necessary to establish the mechanism and causative pathogens. Antiviral therapy may provide therapeutic benefit for a subset of patients with Meniere's disease. Furthermore, clinicians should be aware of other infectious mimics of Meniere's disease and include them in the differential diagnosis of patients presenting with Meniere's-like symptoms. Research on this subject continues to evolve, and data from these studies represent a growing repository of evidence that can be used to guide clinical decision-making.
Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States – A Randomized Controlled Trial
Authors: Chapman William C. , Barbas Andrew S. , D’Alessandro Anthony M. , Vianna Rodrigo , Kubal Chandrashekhar A. , Abt Peter , Sonnenday Christopher , Barth Rolf , Alvarez-Casas Josue , Yersiz Hasan , Eckhoff Devin , Cannon Robert , Genyk Yuri , Sher Linda , Singer Andrew , Feng Sandy , Roll Garrett , Cohen Ari , Doyle Maria B. , Sudan Debra L. , Al-Adra David , Khan Adeel , Subramanian Vijay , Abraham Nader , Olthoff Kim , Tekin Akin , Berg Lynn , Coussios Constantin , Morris Chris , Randle Lucy , Friend Peter , Knechtle Stuart J. 
Published: June 2023

Objective:
A randomized controlled clinical trial comparison of conventional low temperature storage of transplant donor livers (static cold storage, SCS) with storage of the organs at physiological body temperature (normothermic machine preservation, NMP)

Background:
The high success rate of liver transplantation is constrained by the shortage of transplantable organs (e.g. waiting list mortality >20% in many centers). Normothermic machine perfusion maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age, comorbidities), and those from donors declared dead by cardiovascular criteria (DCD).

Methods:
383 donor organs were randomized by 15 US liver transplant centers to undergo NMP (n=192) or SCS (n=191). 266 donor livers proceeded to transplantation (NMP n=136; SCS n=130). The primary endpoint of the study was Early Allograft Dysfunction (EAD), a marker of early post-transplant liver injury and function.

Results:
The difference in incidence of EAD did not achieve significance, with 20.6% (NMP) vs. 23.7% (SCS). Using exploratory ‘as-treated’ rather than “intent to treat” sub-group analyses, there was a greater effect size in DCD donor livers (22.8% NMP vs. 44.6% SCS), and in organs in the highest risk quartile by donor risk (19.2% NMP vs. 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, ‘post-reperfusion syndrome’ as a secondary outcome was reduced in the NMP arm (5.9% vs. 14.6%).

Conclusions:
Normothermic machine perfusion did not lower EAD perhaps related to inclusion of lower risk liver donors, as higher risk donor livers appeared to benefit more The technology is safe in standard organ recovery, and appears to have greatest benefit in marginal donors.
The Evolution of Redo Liver Transplantation Over 35 years
Authors: Kaldas Fady M. , Horwitz Julian K. , Noguchi Daisuke , Korayem Islam M. , Markovic Daniela , Ebaid Samer , Agopian Vatche G. , Yersiz Hasan , Saab Sammy , Han Steven B. , El Kabany Mohamad M. , Choi Gina , Shetty Akshay , Singh Jasleen , Wray Christopher , Barjaktarvic Igor , Farmer Douglas G. , Busuttil Ronald W. 
Published: June 2023

Objective:
Despite the durability of liver transplantation (LT), graft failure affects up to 40% of LT recipients. We examined liver retransplantation (ReLT) over 35-years at a single center.

Methods:
All adult, ReLTs from 1984-2021 were analyzed. Comparisons were made between ReLTs in the pre- vs. post- model for end-stage liver disease (MELD) eras and between ReLTs and primary-LTs in the modern era. Multivariate analysis was used for prognostic modeling.

Results:
654 ReLTs were performed in 590 recipients. There were 372 pre-MELD ReLTs and 282 post-MELD ReLTs. 89% of ReLT recipients had one previous LT, while 11% had ≥2. Primary non-function was the most common indication in the pre-MELD era (33%) vs. recurrent disease (24%) in the post-MELD era. Post-MELD ReLT recipients were older (53 vs. 48, P=0.001), had higher MELD scores (35 vs. 31, P=0.01), and more comorbidities. However, post-MELD ReLT patients had superior 1-, 5-, and 10-year survival compared to pre-MELD ReLT (75%, 60%, and 43% vs. 53%, 43%, and 35% respectively, P<0.001) and lower in-hospital mortality and rejection rates. Notably, in the post-MELD era, MELD score did not affect survival. We identified the following risk factors for early mortality (≤12 months): coronary artery disease, obesity, ventilatory support, older recipient age, longer pre-ReLT hospital stay.

Conclusion:
This represents the largest single center ReLT report to date. Despite increased acuity and complexity of ReLT patients, post-MELD era outcomes have improved. With careful patient selection, these results support the efficacy and survival benefit of ReLT in an acuity-based allocation environment.
Integrating jigsaw puzzle thinking into practice: the assessment of cervical spine radiculopathy
Authors: Mansfield Michael , Thacker Mick 
Published: June 2023

Purpose of review
Cervical spine radiculopathy (CSR) presents a complex socioeconomic problem for patients, clinicians, families, employers and healthcare systems. Due to the heterogeneity of clinical presentation and underlying mechanisms, clinical assessment can be challenging. This review will examine the literature on the underlying pathophysiology and studies investigating the holistic assessment strategies for this disabling condition. The authors will focus particular attention on the psychological factors associated with CSR and the physical and imaging strategies to establish a diagnosis.

Recent findings
Contemporary CSR assessment should identify the underlying pathomechanisms and how this may impact the somatosensory nervous system integrity and function. No physical assessment test in isolation will establish CSR diagnosis; therefore, clinicians should utilise a cluster of tests and recognise the potential limitations as part of a clinical reasoning framework. The assessment of the somatosensory nervous system can provide insights into particular subgroups of CSR presentation, which may provide interesting opportunities to continue to enhance individualised assessment and management strategies for CSR. The interplay between psychological factors can influence the diagnosis and recovery times for a person with CSR, and clinicians should continue to explore how these factors may influence a person’s prognosis. The authors will discuss the opportunities for future research and limitations of contemporary approaches to assessment, underpinned by evidence, and how this supports a clinical assessment to establish CSR diagnosis.

Summary
Research should continue to investigate how clinicians assess the interplay between physical and psychological factors to inform the establishment of CSR. Specifically, there is a need to investigate the validity and reliability of combining somatosensory, motor and imaging assessment findings to reach a diagnosis and inform onward management plans.
Allogeneic Stem Cell Transplantation in Patients >40 Years of Age With Acute Lymphoblastic Leukemia: Reduced Intensity Versus Myeloablative Conditioning
Authors: Sijs-Szabo Aniko , Dinmohamed Avinash G. , Versluis Jurjen , van der Holt Bronno , Bellido Mar , Hazenberg Mette D. , van Gelder Michel , Schaap Nicolaas P.M. , Meijer Ellen , van der Wagen Lotte E , Halkes Constantijn J.M. , Rijneveld Anita W. , Cornelissen Jan J. 
Published: June 2023

Background.
The outcome in older patients with acute lymphoblastic leukemia (ALL) remains unsatisfactory due to high relapse and nonrelapse mortality (NRM) rates. Allogeneic stem cell transplantation (alloHSCT) as postremission therapy has an important role in reducing relapse rate, albeit its application is limited in older adult patients due to alloHSCT-related morbidity and mortality. Reduced-intensity conditioning (RIC) alloHSCT has been developed as a less toxic conditioning regimen, but comparative studies with myeloablative conditioning (MAC) are limited in patients with ALL.

Methods.
In this retrospective study, RIC-alloHSCT (n = 111) was compared with MAC-alloHSCT (n = 77) in patients aged 41 to 65 y with ALL in first complete remission. MAC was predominantly applied by combining high-dose total body irradiation and cyclophosphamide, whereas RIC mainly consisted of fludarabine and 2 Gy total body irradiation.

Results.
Unadjusted overall survival was 54% (95% confidence interval [CI], 42%-65%) at 5 y in MAC recipients compared with 39% (95% CI, 29%-49%) in RIC recipients. Overall survival and relapse-free survival were not significantly associated with type of conditioning after adjusted for the covariates age, leukemia risk status at diagnosis, donor type, and donor and recipient gender combination. NRM was significantly lower after RIC (subdistribution hazard ratio: 0.41, 95% CI, 0.22-0.78; P = 0.006), whereas relapse was significantly higher (subdistribution hazard ratio: 3.04, 95% CI, 1.71-5.40; P < 0.001).

Conclusions.
Collectively, RIC-alloHSCT has resulted in less NRM, but it was also found to be associated with a significantly higher relapse rate. These results suggest that MAC-alloHSCT may provide a more effective type of consolidation therapy for the reduction of relapse and that RIC-alloHSCT may be restricted to patients at higher risk for NRM.
Cortical hyperexcitability in amyotrophic lateral sclerosis: from pathogenesis to diagnosis
Authors: Timmins Hannah C. , Vucic Steve , Kiernan Matthew C. 
Published: June 2023

Purpose of review
Identification of upper motor neuron involvement remains a critical component of a diagnosis of amyotrophic lateral sclerosis (ALS), although supportive clinical signs are often not easily appreciated, particularly in the early symptomatic stages of the disease. Although diagnostic criteria have been developed to facilitate improved detection of lower motor neuron impairment through electrophysiological features that have improved diagnostic sensitivity, assessment of upper motor neuron involvement remains problematic.

Recent findings
Recent evidence has emerged about pathophysiological processes, particularly glutamate-mediated excitotoxicity, which has resulted in the development of novel diagnostic investigations and uncovered potential therapeutic targets. Advances in genetics, including the C9orf72 gene, have changed concepts of ALS, from being classified as a neuromuscular disease to a disease that forms a continuum with other primary neurodegenerative disorders, particularly frontotemporal dementia. Transcranial magnetic stimulation has been utilized to provide pathophysiological insights, leading to the development of diagnostic and therapeutic biomarkers, which are now being introduced into the clinical setting.

Summary
Specifically, the advent of cortical hyperexcitability has been consistently identified as an early and intrinsic feature of ALS. With greater accessibility of TMS techniques promoting clinical utilization, TMS measures of cortical function may develop as a diagnostic biomarker, with further potential utility in the clinical trial setting for monitoring of neuroprotective and genetic-based therapies.
EMBRACE: Explainable Multitask Burnout Prediction for Resident Physicians using Adaptive Deep Learning
Authors: Alam Saima , Alam Mohammad Arif Ul 
Published: June 2023

AbstractMedical residency is associated with long working hours, demanding schedules, and high stress levels, which can lead to burnout among resident physicians. Although wearable and machine learning-based interventions can be useful in predicting potential burnout, existing models fail to clinically explain their predictions, thereby undermining the trustworthiness of the research findings and rendering the intervention apparently useless to residents. This paper develops, EMBRACE,ExplainableMultitaskBurnout pRediction usingAdaptivEdeep learning, that employs a novel framework for predicting burnout that is clinically explainable. At first, we develop, a wearable sensor based improved workplace activity and stress detection algorithm, using deep multi-task learning. Next, we present a novel Adaptive Multi-Task Learning (MTL) framework built on top of our activity and stress detection algorithm, to automatically detect burnout. Additionally, this model also completes the resident burnout survey automatically such a way that it can clinically estimate the same burnout level i.e., clinically explainable and trustworthy estimation. We evaluated the efficacy and explainability of EMBRACE using a real-time data collected from 28 resident physicians (2-7 days each) with appropriate IRB approval (IRB# 2021-017).
Unbiased estimation of the population-level motor module
Authors: Matsui Yusuke , Uno Kohei , Nojima Ippei 
Published: June 2023

SummaryMotor module is a functional neurophysiological command for muscle coordination. In clinical settings, population-level characterization and comparison of motor modules are necessary to evaluate pathophysiological mechanisms and intervention effects. Previous studies have estimated individual motor modules and then compared them, but the validity of capturing the distribution of the latent population has not been fully understood. Our study aimed to address this issue by investigating the accuracy of estimating the population mean of motor modules. Through simulation experiments, we found that previous individual-based approach did not converge regardless of sample size and was vulnerable to noise. We developed an unbiased estimation algorithm using the framework of functional data analysis, which significantly improved estimation accuracy. Our findings highlight statistical challenges for motor module analysis and suggest the need for further research on new computational algorithms using large-scale clinical data.Graphical Abstract
nf-core/marsseq: systematic pre-processing pipeline for MARS-seq experiments
Authors: Proks Martin , Herrera Jose Alejandro Romero , Sedzinski Jakub , Brickman Joshua M. 
Published: June 2023

AbstractMotivationAs a result of advancing single sequencing technology (scRNA-seq), it has become possible to study gene regulatory mechanism(s) and their influence on evolving cell states in time at the level of individual cells. Since 2009, numerous scRNA-seq protocols have been developed, each with its own advantages, disadvantages and library preparation complexities (Ziegenhain et al. 2017). However, the interpretation of data arising from these techniques often shares similar limitations, such as the lack of a standardized pre-processing workflow and consistent data reproducibility. Here we focus on the standardization of the plate based Massively Parallel RNA Single cell Sequencing (MARS-seq, Jaitin et al. 2014) pre-processing pipeline as described in MARS-seq2.0 (Keren-Shaul et al. 2019), which was developed at the Weizmann Institute of Science.ResultsTo overcome the limitations mentioned above, we have taken the original MARS-seq2.0 pipeline and revised it to enable implementation using the nf-core framework (Ewels et al. 2020). By doing so, we have simplified pipeline execution enabling streamlined application, with increased transparency and scalability. Additionally, we have further improved the pipeline by implementing a custom workflow for RNA velocity estimation.Availability and implementationThe pipeline is part of the nf-core bioinformatics community and is freely available athttps://github.com/nf-core/marsseqwith data analysis athttps://github.com/brickmanlab/proks-et-al-2023.
Multi-omic lineage tracing predicts the transcriptional, epigenetic and genetic determinants of cancer evolution
Authors: Nadalin F. , Marzi M.J. , Pirra Piscazzi M. , Fuentes P. , Procaccia S. , Climent M. , Bonetti P. , Rubolino C. , Giuliani B. , Papatheodorou I. , Marioni J.C. , Nicassio F. 
Published: June 2023

ABSTRACTCancer is a highly heterogeneous disease, where phenotypically distinct subpopulations coexist and could be primed to different fates. Both genetic and epigenetic factors may drive cancer evolution, however little is known about whether and how such a process is pre-encoded in cancer clones. Using single-cell multi-omic lineage tracing and phenotypic assays, we investigate the predictive features of either tumour initiation or drug tolerance within the same cancer population. Clones primed to tumour initiationin vivodisplay two distinct transcriptional states at the baseline. Remarkably, these states share a distinctive DNA accessibility profile, highlighting an epigenetic basis for tumour initiation. The drug tolerant niche is also largely pre-encoded, but only partially overlaps the tumour-initiating one and evolves following two genetically and transcriptionally distinct trajectories. Our study highlights coexisting genetic, epigenetic and transcriptional determinants of cancer evolution, unravelling the molecular complexity of pre-encoded tumour phenotypes.
Risk of SARS-CoV-2 reinfection during multiple Omicron variant waves in the UK general population
Authors: Wei Jia , Stoesser Nicole , Matthews Philippa C. , Khera Tarnjit , Gethings Owen , Diamond Ian , Studley Ruth , Taylor Nick , Peto Tim E. A. , Walker A. Sarah , Pouwels Koen B. , Eyre David W. ,   COVID-19 Infection Survey team
Published: June 2023

AbstractSARS-CoV-2 reinfections increased substantially after Omicron variants emerged. Large-scale community-based comparisons across multiple Omicron waves of reinfection characteristics, risk factors, and protection afforded by previous infection and vaccination, are limited, especially after widespread national testing stopped. We studied 245,895 adults ≥18y in the UK’s national COVID-19 Infection Survey with at least one infection (identified from positive swab tests done within the study, linked from national testing programmes, or self-reported by participants, up to their last study assessment). We quantified the risk of reinfection in multiple infection waves, including those driven by BA.1, BA.2, BA.4/5, and most recently BQ.1/CH.1.1/XBB.1.5 variants, in which most reinfections occurred. Reinfections had higher cycle threshold (Ct) values (lower viral load) and lower percentages self-reporting symptoms compared with first infections. Across multiple Omicron waves, protection against reinfection was significantly higher in those previously infected with more recent than earlier variants, even at the same time from previous infection. Protection against Omicron reinfections decreased over time from the most recent infection if this was the previous or penultimate variant (generally within the preceding year), but did not change or even slightly increased over time if this was with an even earlier variant (generally >1 year previously). Those 14-180 days after receiving their most recent vaccination had a lower risk of reinfection with all Omicron variants except BA.2 than those >180 days from their most recent vaccination. Reinfection risk was independently higher in those aged 30-45 years, and with either low or high Ct values in their most recent previous infection. Overall, the risk of Omicron reinfection is high, but with lower severity than first infections; reinfection risk is likely driven as much by viral evolution as waning immunity.
Inflammatory Biomarkers and Physiomarkers of Late-Onset Sepsis and Necrotizing Enterocolitis in Premature Infants
Authors: Kumar Rupin , Kausch Sherry , Gummadi Angela K.S. , Fairchild Karen D. , Abhyankar Mayuresh , Petri William A. , Sullivan Brynne A. 
Published: June 2023

AbstractImpactLate-onset sepsis and necrotizing enterocolitis (NEC) in very low birth weight (VLBW, <1500g) premature infants can result in severe morbidity and mortality. Diagnosis is challenging due to overlap with non-infectious conditions, leading to a delayed or unnecessary antibiotic use.In a single-center cohort of VLBW infants, inflammatory biomarkers were elevated at the time of sepsis due to Gram-negative sepsis or NEC, but not other sepsis; compared to times without sepsis or NEC.Physiomarkers of sepsis correlate with some biomarkers of sepsis, and combining their information could help in the early diagnosis of sepsis.BackgroundEarly diagnosis of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in VLBW (<1500g) infants is challenging due to non-specific clinical signs. Inflammatory biomarkers increase in response to infection, but non-infectious conditions also cause inflammation in premature infants. Physiomarkers of sepsis exist in cardiorespiratory data and may be useful in combination with biomarkers for early diagnosis.ObjectivesTo determine whether inflammatory biomarkers at LOS or NEC diagnosis differ from times without infection, and whether biomarkers correlate with a cardiorespiratory physiomarker score.MethodsWe collected remnant plasma samples and clinical data from VLBW infants. Sample collection occurred with blood draws for routine laboratory testing and blood draws for suspected sepsis. We analyzed 11 inflammatory biomarkers and a continuous cardiorespiratory monitoring (POWS) score. We compared biomarkers at gram-negative (GN) bacteremia or NEC, gram-positive (GP) bacteremia, negative blood cultures, and routine samples.ResultsWe analyzed 188 samples in 54 VLBW infants. Biomarker levels varied widely, even at routine laboratory testing. Several biomarkers were increased at the time of GN LOS or NEC diagnosis compared with all other samples. POWS was higher in patients with LOS and correlated with five biomarkers. IL-6 had 78% specificity at 100% sensitivity to detect GN LOS or NEC and added information to POWS (AUC POWS = 0.610, POWS + IL-6 = 0.680).Conclusion(s)Inflammatory biomarkers discriminate sepsis due to GN bacteremia or NEC and correlate with cardiorespiratory physiomarkers. Baseline biomarkers did not differ from times of GP bacteremia diagnosis or negative blood cultures.