bluuebunny/crossref_metadata_2025 huggingface dataset:
Care pathways in older patients seen in a multidisciplinary same day emergency care (SDEC) unit
Authors: Elias Tania C N , Jacklin Chloe , Bowen Jordan , Lasserson Daniel S , Pendlebury Sarah T
Published: January 2024

Background

Same day emergency care (SDEC) services are being advocated in the UK for frail, older patients in whom hospitalisation may be associated with harm but there are few data on the ‘ambulatory pathway’. We therefore determined the patient pathways pre- and post-first assessment in a SDEC unit focussed on older people.

Methods

In consecutive patients, we prospectively recorded follow-up SDEC service reviews (face-to-face, telephone, Hospital-at-Home domiciliary visits), outpatient referrals (e.g. to specialist clinics, imaging, and community/voluntary/social services), and hospital admissions <30 days. In the first 67 patients, we also recorded healthcare interactions (except GP attendances) in the 180 days pre- and post-first assessment.

Results

Among 533 patients (mean/SD age = 75.0/17.5 years, 246, 46% deemed frail) assessed in an SDEC unit, 210 were admitted within 30 days (152 immediately). In the 381(71%) remaining initially ambulatory, there were 587 SDEC follow-up reviews and 747 other outpatient referrals (mean = 3.5 per patient) with only 34 (9%) patients being discharged with no further follow-up. In the subset (n = 67), the number of ‘healthcare days’ was greater in the 180 days post- versus pre-SDEC assessment (mean/SD = 26/27 versus 13/22 days, P = 0.003) even after excluding hospital admission days, with greater healthcare days in frail versus non-frail patients.

Discussion and Conclusion

SDEC assessment in older, frail patients was associated with a 2-fold increase in frequency of healthcare interactions with complex care pathways involving multiple services. Our findings have implications for the development of admission-avoidance models including cost-effectiveness and optimal delivery of the multi-dimensional aspects of acute geriatric care in the ambulatory setting.
Minimal Detectable Change for the ImPACT Subtests at Baseline
Authors: Quigley Kristen G , Fenner Madison , Pavilionis Philip , Constantino Nora L , Moran Ryan N , Murray Nicholas G
Published: January 2024

Objective

To establish the minimal detectable change (MDC) of the subtests that comprise the composite scores from remotely administered Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) baselines.

Method

Remote ImPACT baseline data from 172 (male = 45, female = 127) National Collegiate Athletic Association Division I student-athletes from the 2020 and 2021 athletic preseasons were used to calculate the MDC at the 95%, 90%, and 80% confidence intervals (CIs) for all subtest scores used to generate the four core composite scores and the impulse control composite.

Results

The MDCs for the verbal memory subtests at the 95% CI were 10.31 for word memory percent correct, 4.68 for symbol match total correct hidden, and 18.25 for three letters percentage correct. Visual memory subtest MDCs were 19.03 for design memory total percent correct and 4.90 for XO total correct memory. Visual motor speed subtest MDCs were 18.89 for XO total correct interference and 5.40 for three letters average counted correctly. Reaction time (RT) MDCs were 0.12 for XO average correct, 0.95 for symbol match average correct RT, and 0.28 for color match average correct. Impulse control MDCs were 5.97 for XO total incorrect and 1.15 for color match total commissions. One-way repeated measures MANOVA, repeated measures ANOVAs, and Wilcoxon signed-ranks test all suggested no significant difference between any subtests across two remote ImPACT baselines.

Conclusions

The ImPACT subtest scores did not significantly change between athletic seasons. Our study suggests the subtests be evaluated in conjunction with the composite scores to provide additional metrics for clinical interpretation.
RAMZIS: a bioinformatic toolkit for rigorous assessment of the alterations to glycoprotein composition that occur during biological processes
Authors: Hackett William Edwin , Chang Deborah , Carvalho Luis , Zaia Joseph
Published: January 2024

Motivation

Glycosylation elaborates the structures and functions of glycoproteins; glycoproteins are common post-translationally modified proteins and are heterogeneous and non-deterministically synthesized as an evolutionarily driven mechanism that elaborates the functions of glycosylated gene products. Glycoproteins, accounting for approximately half of all proteins, require specialized proteomics data analysis methods due to micro- and macro-heterogeneities as a given glycosite can be divided into several glycosylated forms, each of which must be quantified. Sampling of heterogeneous glycopeptides is limited by mass spectrometer speed and sensitivity, resulting in missing values. In conjunction with the low sample size inherent to glycoproteomics, a specialized toolset is needed to determine if observed changes in glycopeptide abundances are biologically significant or due to data quality limitations.

Results

We developed an R package, Relative Assessment of m/z Identifications by Similarity (RAMZIS), that uses similarity metrics to guide researchers to a more rigorous interpretation of glycoproteomics data. RAMZIS uses a permutation test to generate contextual similarity, which assesses the quality of mass spectral data and outputs a graphical demonstration of the likelihood of finding biologically significant differences in glycosylation abundance datasets. Investigators can assess dataset quality, holistically differentiate glycosites, and identify which glycopeptides are responsible for glycosylation pattern change. RAMZIS is validated by theoretical cases and a proof-of-concept application. RAMZIS enables comparison between datasets too stochastic, small, or sparse for interpolation while acknowledging these issues in its assessment. Using this tool, researchers will be able to rigorously define the role of glycosylation and the changes that occur during biological processes.

Availability and implementation

https://github.com/WillHackett22/RAMZIS.
DIRECTEUR: transcriptome-based prediction of small molecules that replace transcription factors for direct cell conversion
Authors: Hamano Momoko , Nakamura Toru , Ito Ryoku , Shimada Yuki , Iwata Michio , Takeshita Jun-ichi , Eguchi Ryohei , Yamanishi Yoshihiro
Published: January 2024

Motivation

Direct reprogramming (DR) is a process that directly converts somatic cells to target cells. Although DR via small molecules is safer than using transcription factors (TFs) in terms of avoidance of tumorigenic risk, the determination of DR-inducing small molecules is challenging.

Results

Here we present a novel in silico method, DIRECTEUR, to predict small molecules that replace TFs for DR. We extracted DR-characteristic genes using transcriptome profiles of cells in which DR was induced by TFs, and performed a variant of simulated annealing to explore small molecule combinations with similar gene expression patterns with DR-inducing TFs. We applied DIRECTEUR to predicting combinations of small molecules that convert fibroblasts into neurons or cardiomyocytes, and were able to reproduce experimentally verified and functionally related molecules inducing the corresponding conversions. The proposed method is expected to be useful for practical applications in regenerative medicine.

Availability and implementation

The code and data are available at the following link: https://github.com/HamanoLaboratory/DIRECTEUR.git.
vcfpp: a C++ API for rapid processing of the variant call format
Authors: Li Zilong
Published: January 2024

Motivation

Given the widespread use of the variant call format (VCF/BCF) coupled with continuous surge in big data, there remains a perpetual demand for fast and flexible methods to manipulate these comprehensive formats across various programming languages.

Results

This work presents vcfpp, a C++ API of HTSlib in a single file, providing an intuitive interface to manipulate VCF/BCF files rapidly and safely, in addition to being portable. Moreover, this work introduces the vcfppR package to demonstrate the development of a high-performance R package with vcfpp, allowing for rapid and straightforward variants analyses.

Availability and implementation

vcfpp is available from https://github.com/Zilong-Li/vcfpp under MIT license. vcfppR is available from https://cran.r-project.org/web/packages/vcfppR.
Interpreting protein abundance in Saccharomyces cerevisiae through relational learning
Authors: Brunnsåker Daniel , Kronström Filip , Tiukova Ievgeniia A , King Ross D
Published: January 2024

Motivation

Proteomic profiles reflect the functional readout of the physiological state of an organism. An increased understanding of what controls and defines protein abundances is of high scientific interest. Saccharomyces cerevisiae is a well-studied model organism, and there is a large amount of structured knowledge on yeast systems biology in databases such as the Saccharomyces Genome Database, and highly curated genome-scale metabolic models like Yeast8. These datasets, the result of decades of experiments, are abundant in information, and adhere to semantically meaningful ontologies.

Results

By representing this knowledge in an expressive Datalog database we generated data descriptors using relational learning that, when combined with supervised machine learning, enables us to predict protein abundances in an explainable manner. We learnt predictive relationships between protein abundances, function and phenotype; such as α-amino acid accumulations and deviations in chronological lifespan. We further demonstrate the power of this methodology on the proteins His4 and Ilv2, connecting qualitative biological concepts to quantified abundances.

Availability and implementation

All data and processing scripts are available at the following Github repository: https://github.com/DanielBrunnsaker/ProtPredict.
TKSM: highly modular, user-customizable, and scalable transcriptomic sequencing long-read simulator
Authors: Karaoğlanoğlu Fatih , Orabi Baraa , Flannigan Ryan , Chauve Cedric , Hach Faraz
Published: January 2024

Motivation

Transcriptomic long-read (LR) sequencing is an increasingly cost-effective technology for probing various RNA features. Numerous tools have been developed to tackle various transcriptomic sequencing tasks (e.g. isoform and gene fusion detection). However, the lack of abundant gold-standard datasets hinders the benchmarking of such tools. Therefore, the simulation of LR sequencing is an important and practical alternative. While the existing LR simulators aim to imitate the sequencing machine noise and to target specific library protocols, they lack some important library preparation steps (e.g. PCR) and are difficult to modify to new and changing library preparation techniques (e.g. single-cell LRs).

Results

We present TKSM, a modular and scalable LR simulator, designed so that each RNA modification step is targeted explicitly by a specific module. This allows the user to assemble a simulation pipeline as a combination of TKSM modules to emulate a specific sequencing design. Additionally, the input/output of all the core modules of TKSM follows the same simple format (Molecule Description Format) allowing the user to easily extend TKSM with new modules targeting new library preparation steps.

Availability and implementation

TKSM is available as an open source software at https://github.com/vpc-ccg/tksm.
Optimized protocol for shotgun label-free proteomic analysis of pancreatic islets
Authors: SanchesTrevizol Juliana , Dionizio Aline , Delgado Aislan Quintiliano , Ventura Talita Mendes Oliveira , da Silva Ribeiro Caroline Fernanda , Rabelo Buzalaf Nathalia , Bosqueiro José Roberto , Buzalaf Marília Afonso Rabelo
Published: January 2024

Pancreatic islets are crucial in diabetes research. Consequently, this protocol aims at optimizing both the protein-extraction process and the proteomic analysis via shotgun methods for pancreatic islets. Six protocols were tested, combining three types of chemical extraction with two mechanical extraction methods. Furthermore, two protocols incorporated a surfactant to enhance enzymatic cleavage. The steps involved extraction and concentration of protein, protein quantification, reduction, alkylation, digestion, purification and desalination, sample concentration to ∼1 µl, and proteomic analysis using the mass spectrometer. The most effective protocol involves either a milder chemical extraction paired with a more intensive mechanical process, or a more robust chemical extraction paired with a gentle mechanical process, tailored to the sample’s characteristics. Additionally, it was observed that the use of a surfactant proved ineffective for these types of samples. Protocol 5 was recently used with success to examine metabolic changes in pancreatic islets of non-obese diabetic mice exposed to low doses of fluoride ions (F−) and the primary pathways altered by the treatment.
Panoramic imaging errors in machine learning model development: a systematic review
Authors: Delamare Eduardo , Fu Xingyue , Huang Zimo , Kim Jinman
Published: January 2024

Objectives

To investigate the management of imaging errors from panoramic radiography (PAN) datasets used in the development of machine learning (ML) models.

Methods

This systematic literature followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and used three databases. Keywords were selected from relevant literature.

Eligibility criteria

PAN studies that used ML models and mentioned image quality concerns.

Results

Out of 400 articles, 41 papers satisfied the inclusion criteria. All the studies used ML models, with 35 papers using deep learning (DL) models. PAN quality assessment was approached in 3 ways: acknowledgement and acceptance of imaging errors in the ML model, removal of low-quality radiographs from the dataset before building the model, and application of image enhancement methods prior to model development. The criteria for determining PAN image quality varied widely across studies and were prone to bias.

Conclusions

This study revealed significant inconsistencies in the management of PAN imaging errors in ML research. However, most studies agree that such errors are detrimental when building ML models. More research is needed to understand the impact of low-quality inputs on model performance. Prospective studies may streamline image quality assessment by leveraging DL models, which excel at pattern recognition tasks.
Statin treatment after surgical aortic valve replacement for aortic stenosis is associated with better long-term outcome
Authors: Pan Emily , Nielsen Susanne J , Landenhed-Smith Maya , Törngren Charlotta , Björklund Erik , Hansson Emma C , Jeppsson Anders , Martinsson Andreas
Published: January 2024

OBJECTIVES

The aim of this study was to evaluate the association between statin use after surgical aortic valve replacement for aortic stenosis and long-term risk for major adverse cardiovascular events (MACEs) in a large population-based, nationwide cohort.

METHODS

All patients who underwent isolated surgical aortic valve replacement due to aortic stenosis in Sweden 2006–2020 and survived 6 months after discharge were included. Individual patient data from 5 nationwide registries were merged. Primary outcome is MACE (defined as all-cause mortality, myocardial infarction or stroke). Multivariable Cox regression model adjusted for age, sex, comorbidities, valve type, operation year and secondary prevention medications is used to evaluate the association between time-updated dispense of statins and long-term outcome in the entire study population and in subgroups based on age, sex and comorbidities.

RESULTS

A total of 11 894 patients were included. Statins were dispensed to 49.8% (5918/11894) of patients at baseline, and 51.0% (874/1713) after 10 years. At baseline, 3.6% of patients were dispensed low dose, 69.4% medium dose and 27.0% high-dose statins. After adjustments, ongoing statin treatment was associated with a reduced risk for MACE [adjusted hazard ratio 0.77 (95% confidence interval 0.71–0.83). P < 0.001], mainly driven by a reduction in all-cause mortality [adjusted hazard ratio, 0.70 (0.64–0.76)], P < 0.001. The results were consistent in all subgroups.

CONCLUSIONS

The results suggest that statin therapy might be beneficial for patients undergoing surgical aortic valve replacement for aortic stenosis. Randomized controlled trials are warranted to establish causality between statin treatment and improved outcome.
Removal of pomt1 in zebrafish leads to loss of α-dystroglycan glycosylation and dystroglycanopathy phenotypes
Authors: Karas Brittany F , Terez Kristin R , Mowla Shorbon , Battula Namarata , Flannery Kyle P , Gural Brian M , Aboussleman Grace , Mubin Numa , Manzini M Chiara
Published: January 2024

Biallelic mutations in Protein O-mannosyltransferase 1 (POMT1) are among the most common causes of a severe group of congenital muscular dystrophies (CMDs) known as dystroglycanopathies. POMT1 is a glycosyltransferase responsible for the attachment of a functional glycan mediating interactions between the transmembrane glycoprotein dystroglycan and its binding partners in the extracellular matrix (ECM). Disruptions in these cell-ECM interactions lead to multiple developmental defects causing brain and eye malformations in addition to CMD. Removing Pomt1 in the mouse leads to early embryonic death due to the essential role of dystroglycan during placental formation in rodents. Here, we characterized and validated a model of pomt1 loss of function in the zebrafish showing that developmental defects found in individuals affected by dystroglycanopathies can be recapitulated in the fish. We also discovered that pomt1 mRNA provided by the mother in the oocyte supports dystroglycan glycosylation during the first few weeks of development. Muscle disease, retinal synapse formation deficits, and axon guidance defects can only be uncovered during the first week post fertilization by generating knock-out embryos from knock-out mothers. Conversely, maternal pomt1 from heterozygous mothers was sufficient to sustain muscle, eye, and brain development only leading to loss of photoreceptor synapses at 30 days post fertilization. Our findings show that it is important to define the contribution of maternal mRNA while developing zebrafish models of dystroglycanopathies and that offspring generated from heterozygous and knock-out mothers can be used to differentiate the role of dystroglycan glycosylation in tissue formation and maintenance.
Developing the next-generation cancer research workforce in the National Institutes of Health Intramural Research Program
Authors: Schor Nina F
Published: January 2024

Although the National Institutes of Health is renowned for being the largest funder of biomedical research in the world, the research and associated career development programs on its own campuses are relatively unknown. These intramural programs provide many outstanding and programmatically unique opportunities for research-intensive careers and training in cancer biology, prevention, diagnosis, and therapeutics. Their complementary foci, structures, and review mechanisms make the extramural and intramural cancer research contributions of the National Institutes of Health the perfect partners in the quest to rid the world of cancer as we know it.
Localized pseudomembranous gastritis associated with hepatic cirrhosis and portal hypertensive gastropathy: a case report
Authors: Tran Pierre , Sai P Rama , Prasad Chaya , Parsa Cyrus
Published: January 2024

Pseudomembranes in the large and small intestines are common in hospitalized patients that are immunosuppressed or on certain oral antibiotics. Pseudomembranous enterocolitis, histologically characterized by volcanic-like eruption of inflammatory cellular exudate from the mucosal surface, is mainly attributed to Clostridium difficile toxins and often presents with symptomatic diarrhea. Rarely, there are case reports of similar pseudomembranous lesions limited to the stomach in the absence of intestinal involvement. In this paper, we present a case of localized pseudomembranous gastritis in a 76-year-old patient with personal history limited to prior gastrointestinal bleed, liver cirrhosis, alcohol dependence, diabetes mellitus, and hypertension who was referred to the emergency department from his primary care physician’s office due to low hemoglobin.
Post-craniotomy coronal suture diastases in a transformed lower grade glioma
Authors: Pinheiro Teresa Morais , Awan Mariam , Wroe-Wright Oliver , Ghimire Prajwal , Marchi Francesco , Elhag Ali , Lavrador José Pedro
Published: January 2024

Cranial suture diastases are an uncommon clinical entity, with post craniotomy diastases being a previously undescribed finding in literature to our best knowledge. Herein, we report a case of a 28-year-old adult who underwent a second-stage low-grade glioma surgery 7 months after initial surgery. This study presents coronal suture diastases adjacent to the previously performed craniotomy. After literature and pathophysiology review, we found it to be unique and that the craniotomy can resemble the mechanical stress of trauma.
Lower limb preservation in pediatric trauma: a case study of Gustilo grade IIIC fracture in a 7-year-old
Authors: Ataya Jamal , Daaboul Rawan , Alhomsi Hassan , Issa Hassan , Elewee Ahmad
Published: January 2024

This case report describes the intricate aspects of managing pediatric lower limb trauma. A 7-year-old patient had a severe compound fracture and significant soft tissue damage in the left lower limb, classified as Gustilo Grade IIIC. This necessitated the use of scoring systems such as the Mangled Extremity Severity Score and limb salvage index to assess the likelihood of limb preservation. Despite these high amputation risk indicators, a multidisciplinary approach has led to limb salvage surgery with internal fixation. Detailed postoperative monitoring revealed progressive recovery culminating in restored sensation, bone healing, and functional recovery. The discussion emphasizes the difficulties in deciding between limb salvage and amputation, stressing the importance of tailored care and cautious scoring system interpretation in pediatric cases. This conclusion advocates the prioritization of limb salvage in children owing to their unique healing capabilities while highlighting the need for further research to refine treatment protocols for pediatric lower limb trauma.
On the incidence of episodic accretion in Class I YSOs from VVV
Authors: Contreras Peña Carlos , Lucas Philip W , Guo Zhen , Smith Leigh
Published: January 2024

Episodic accretion is one of the competing models to explain the observed luminosity spread in young stellar clusters. These short-lived high accretion events could also have a strong impact on planet formation. Observations of high-amplitude variability in young stellar objects (YSOs) due to large changes in the accretion rate provide direct observational evidence for episodic accretion. However, there are still uncertainties in the frequency of these events and if episodic accretion is universal among YSOs. To determine the frequency of outbursts in Class I YSOs, we built a large and robust sample of objects at this evolutionary stage, and searched for high-amplitude near-infrared (ΔKS > 2 mag) variability in the VIRAC2 database of the Vista Variables in the Via Lactea survey. By complementing with near-IR (2MASS and DENIS) and mid-IR (WISE/Neo-WISE) data, we find that from ∼7000 Class I YSOs, 97 objects can be classified as eruptive variable YSOs. The duration of the outbursts vary from a few months to longer than 9 yr, and cover a similar range of amplitudes. Values of ΔKS > 5 mag, however, are only observed in outbursts with duration longer than 9 yr. When considering different effects of completeness and contamination, we estimate that the incidence of episodic accretion in Class I YSOs is between 2 and 3 per cent. Finally, we determine a recurrence time-scale of long-term outbursts (a.k.a FUors) of $\tau =1.75^{+1.12}_{-0.87}$ kyr. The latter value agrees with previous estimates and is in line with the expectations of higher frequency of FUor outbursts during younger stages of evolution.
Association between P1NP value and increases in bone mineral density in patients with postmenopausal osteoporosis treated with romosozumab
Authors: Hattori Kyosuke , Kanayama Yasuhide
Published: January 2024

Objectives

The present study aimed to investigate the effectiveness of treatment with romosozumab for 1 year and association between bone turnover markers and changes in bone mineral density (BMD) in patients with postmenopausal osteoporosis.

Methods

Participants were 53 treatment-naïve postmenopausal osteoporosis patients. Correlations of per cent changes (Δ) in lumbar (L) and total hip (TH) BMD 12 months after initiating romosozumab with baseline demographic factors and parameters of N-terminal propeptide of Type 1 collagen (P1NP) and tartrate-resistant acid phosphatase-5b at baseline and Months 1, 3, and 6 were assessed. Multiple regression analysis was performed on factors significantly correlated with ΔL-BMD and ΔTH-BMD at Month 12.

Results

ΔL-BMD and ΔTH-BMD at Month 12 were 17.5% and 8.1%, respectively. Multiple regression analysis revealed that a high P1NP value at Month 3 predicted large increases in L-BMD and TH-BMD at Month 12. High total amount of P1NP values from baseline to Month 6 was associated with large increases in L-BMD and TH-BMD at Month 12 and was most strongly correlated with the P1NP value at Month 3.

Conclusions

A high P1NP value at Month 3 predicted large increases in both L-BMD and TH-BMD at Month 12 in postmenopausal osteoporosis patients treated with romosozumab.
Firm-level financial frictions and aggregate allocative efficiency
Authors: Maurin Laurent , Wolski Marcin
Published: January 2024

Capitalizing on the productivity decomposition proposed by Olley and Pakes, we analyse the role of financial factors behind the relatively muted post-crisis rebound in productivity compared to previous upturns in Europe. First, we provide an Ordinary Least Squares framework to decompose the index of sector-level productivity into trend and allocative efficiency components. We then extend our approach to estimate the contribution of firm-level confounders to the sector-level allocative component. Secondly, we find that financial leverage played an important role in explaining the change in aggregate productivity growth in Europe between 2004 and 2017. Thirdly, focusing on Northern and Western Europe, we show that the productivity potential could not be fully exploited due to access to credit conditions. Specifically, reducing collateral bottlenecks could more than double the effectiveness of financial leverage in spurring productivity growth in this region between 2014 and 2017.
Providing family updates: a primer for the medical trainee
Authors: Ng Isaac K S , Tan Li Feng , Kumarakulasinghe Nesaretnam Barr , Goh Wilson G W , Ngiam Nicola , Teo Desmond B
Published: January 2024

Providing family updates is a common clinical task for medical trainees and practitioners working in hospital settings. Good clinical communication skills are essential in clinical care as it is associated with improved patient satisfaction, understanding of condition, treatment adherence, and better overall clinical outcomes. Moreover, poor communications are often the source of medical complaints. However, while patient-centred communication skills training has generally been incorporated into clinical education, there hitherto remains inadequate training on clinical communications with patients’ families, which carry different nuances. In recent years, it is increasingly recognized that familial involvement in the care of hospitalized patients leads to better clinical and psychological outcomes. In fact, in Asian populations with more collectivistic cultures, families are generally highly involved in patient care and decision-making. Therefore, effective clinical communications and regular provision of family updates are essential to build therapeutic rapport, facilitate familial involvement in patient care, and also provide a more holistic understanding of the patient’s background and psychosocial set-up. In this article, we herein describe a seven-step understand the clinical context, gather perspectives, deliver medical information, address questions, concerns and expectations, provide tentative plans, demonstrate empathy, postcommunication reflections model as a practical guide for medical trainees and practitioners in provision of structured and effective family updates in their clinical practice.
IgA vasculitis nephritis—outcomes in adult-onset disease
Authors: Stanway James , Brown Nina , Pervez Afeera , Van de Perre Els , Tollitt James , Marketos Nikolaos , Wong Nikki , Dhaygude Ajay , Ponnusamy Arvind , O'Riordan Ed , Venning Michael , Segelmark Mårten , Morgan Matthew , Jayne David , Hamilton Patrick , Pusey Charles D , Oni Louise , Salama Alan D
Published: January 2024

Objectives

IgA vasculitis (IgAV) in adults has been relatively under-investigated. Since outcomes are worse in other forms of vasculitis with increasing age, we investigated the outcomes of IgAV comparing younger adults (18–34), middle-aged adults (35–64) and elderly patients (≥64 years) focusing on kidney outcomes.

Methods

We identified patients with renal biopsy-confirmed IgAV nephritis and collected data regarding clinical features and progression to end stage kidney disease (ESKD). The relationship between patient factors and ESKD was analysed by regression.

Results

We identified 202 cases, 34% aged 18–34, 43% aged 35–64 and 23% elderly (>64 years). Median follow-up was 44 months. Elderly patients were more likely to present with ESKD (23.9%) compared with middle-aged (13.7%) and younger adults (2.9%) (χ2 11.6, P = 0.002). In patients with independent kidney function at biopsy, there was no difference in outcomes between age groups. Male gender, Black ethnicity, diabetes, histological evidence of chronic renal damage and estimated glomerular filtration rate < 30 ml/min were risk factors for development of ESKD. In this observational study 68.3% of patients received glucocorticoids and 56.9% additional immunosuppression.

Conclusion

Elderly patients with IgAV are more likely to have ESKD at presentation, but there is no difference in renal survival between age groups, among those presenting with independent renal function. Renal impairment at biopsy is an independent risk factor for subsequent development of ESKD. There is significant variability in the timing of kidney biopsy and management of these patients among specialist centres. Young adults have outcomes more in keeping with childhood IgAV.
Thresholds for unacceptable work state in radiographic axial spondyloarthritis of four presenteeism and two clinical outcome measurement instruments
Authors: Capelusnik Dafne , Ramiro Sofia , Nikiphorou Elena , Maksymowych Walter P , Magrey Marina Nighat , Marzo-Ortega Helena , Boonen Annelies
Published: January 2024

Objectives

To (i) identify threshold values of presenteeism measurement instruments that reflect unacceptable work state in employed r-axSpA patients; (ii) determine whether those thresholds accurately predict future adverse work outcomes (AWO) (sick leave or short/long-term disability); (iii) evaluate the performance of traditional health-outcomes for r-axSpA; and (iv) explore whether thresholds are stable across contextual factors.

Methods

Data from the multinational AS-PROSE study was used. Thresholds to determine whether patients consider themselves in an ‘unacceptable work state’ were calculated at baseline for four instruments assessing presenteeism and two health outcomes specific for r-axSpA. Different approaches derived from the receiver operating characteristic methodology were used. Validity of the optimal thresholds was tested across contextual factors and for predicting future AWO over 12 months.

Results

Of 366 working patients, 15% reported an unacceptable work state; 6% experienced at least one AWO in 12 months. Optimal thresholds were: WPAI-presenteeism ≥40 (AUC 0.85), QQ-method <97 (0.76), WALS ≥0.75 (AUC 0.87), WLQ-25 ≥ 29 (AUC 0.85). BASDAI and BASFI performed similarly to the presenteeism instruments: ≥4.7 (AUC 0.82) and ≥3.5 (AUC 0.79), respectively. Thresholds for WALS and WLQ-25 were stable across contextual factors, while for all other instruments they overestimated unacceptable work state in lower educated persons. Proposed thresholds could also predict future AWO, although with lower performance, especially for QQ-method, BASDAI and BASFI.

Conclusions

Thresholds of measurement instruments for presenteeism and health status to identify unacceptable work state have been established. These thresholds can help in daily clinical practice to provide work-related support to r-axSpA patients at risk for AWO.
Aberrant mitochondrial aggregation of TDP-43 activated mitochondrial unfolded protein response and contributed to recovery of acetaminophen induced acute liver injury
Authors: Liu Zhaoxiong , Qiang Yalong , Shan Shulin , Wang Shuai , Liu Zhidan , Yang Yiyu , Huang Zhengcheng , Song Mingxue , Zhao Xiulan , Song Fuyong
Published: January 2024

Mitochondrial dysfunction is a key pathological event in the acute liver injury following the overdose of acetaminophen (APAP). Calpain is the calcium-dependent protease, recent studies demonstrate that it is involved in the impairment of mitochondrial dynamics. The mitochondrial unfolded protein response (UPRmt) is commonly activated in the context of mitochondrial damage following pathological insults and contributes to the maintenance of the mitochondrial quality control through regulating a wide range of gene expression. More importantly, it is reported that abnormal aggregation of TDP-43 in mitochondria induced the activation of UPRmt. However, whether it is involved in APAP induced-hepatotoxicity remains unclear. In the present study, C57/BL6 mice were given 300 mg/kg APAP to establish a time-course model of acute liver injury. Furthermore, Calpeptin, the specific inhibiter of calpains, was used to conduct the intervention experiment. Our results showed, APAP exposure produced severe liver injury. Moreover, TDP-43 was obviously accumulated within mitochondria whereas mitochondrial protease LonP1 was significantly decreased. However, these changes exhibited significant recovery at 48 h. By contrast, the mitochondrial protease ClpP and chaperone mtHSP70 and HSP60 were consistently increased, which supported the UPRmt was activated to promote protein homeostasis. Further investigation revealed that calpain-mediated cleavage of TDP-43 could promote the accumulation of TDP-43 in mitochondria compartment, thereby facilitating the activation of UPRmt. Additionally, Calpeptin pretreatment not only protected against APAP-induced liver injury, but also suppressed the formation of TDP-43 aggregates and the activation of UPRmt. Taken together, our findings indicated that in APAP-induced acute liver injury, calpain-mediated cleavage of TDP43 caused its aberrant aggregation on the mitochondria. As a stress-protective response, the induction of UPRmt contributed to the recovery of mitochondrial function.
Serum Neurofilament Light and Postoperative Delirium in Cardiac Surgery: A Preplanned Secondary Analysis of a Prospective Observational Study
Authors: Khalifa Céline , Robert Annie , Cappe Maximilien , Lemaire Guillaume , Tircoveanu Robert , Dehon Valérie , Ivanoiu Adrian , Piérard Sophie , de Kerchove Laurent , Jacobs Sariyar Aurélie , Teunissen Charlotte Elisabeth , Momeni Mona
Published: January 2024

Background

Impaired cognition is a major predisposing factor for postoperative delirium, but it is not systematically assessed. Anesthesia and surgery may cause postoperative delirium by affecting brain integrity. Neurofilament light in serum reflects axonal injury. Studies evaluating the perioperative course of neurofilament light in cardiac surgery have shown conflicting results. The authors hypothesized that postoperative serum neurofilament light values would be higher in delirious patients, and that baseline concentrations would be correlated with patients’ cognitive status and would identify patients at risk of postoperative delirium.

Methods

This preplanned secondary analysis included 220 patients undergoing elective cardiac surgery with cardiopulmonary bypass. A preoperative cognitive z score was calculated after a neuropsychological evaluation. Quantification of serum neurofilament light was performed by the Simoa (Quanterix, USA) technique before anesthesia, 2 h after surgery, on postoperative days 1, 2, and 5. Postoperative delirium was assessed using the Confusion Assessment Method for Intensive Care Unit, the Confusion Assessment Method, and a chart review.

Results

A total of 65 of 220 (29.5%) patients developed postoperative delirium. Delirious patients were older (median [25th percentile, 75th percentile], 74 [64, 79] vs. 67 [59, 74] yr; P < 0.001) and had lower cognitive z scores (–0.52 ± 1.14 vs. 0.21 ± 0.84; P < 0.001). Postoperative neurofilament light concentrations increased in all patients up to day 5, but did not predict delirium when preoperative concentrations were considered. Baseline neurofilament light values were significantly higher in patients who experienced delirium. They were influenced by age, cognitive z score, renal function, and history of diabetes mellitus. Baselines values were significantly correlated with cognitive z scores (r, 0.49; P < 0.001) and were independently associated with delirium whenever the patient’s cognitive status was not considered (hazard ratio, 3.34 [95% CI, 1.07 to 10.4]).

Conclusions

Cardiac surgery is associated with axonal injury, because neurofilament light concentrations increased postoperatively in all patients. However, only baseline neurofilament light values predicted postoperative delirium. Baseline concentrations were correlated with poorer cognitive scores, and they independently predicted postoperative delirium whenever patient’s cognitive status was undetermined.

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Cortical Auditory Evoked Potential Indices of Impaired Sensory Gating in People With Chronic Tinnitus
Authors: Morse Kenneth , Vander Werff Kathy R.
Published: January 2024

Objectives:

The primary aim of this study was to evaluate whether there is cortical auditory evoked potential (CAEP) evidence of impaired sensory gating in individuals with tinnitus. On the basis of the proposed mechanism of tinnitus generation, including a thalamocortical inhibitory deficit, it was hypothesized that individuals with tinnitus would lack the normal inhibitory effect on the second CAEP response in a paired-click sensory gating paradigm, resulting in larger sensory gating ratios in individuals with tinnitus relative to age-, sex-, and hearing-matched controls. Further, this study assessed the relative predictive influence of tinnitus presence versus other related individual characteristics (hearing loss, age, noise exposure history, and speech perception in noise) on sensory gating.

Design:

A paired-click CAEP paradigm was used to measure sensory gating outcomes in an independent group’s experimental design. Adults who perceived chronic unilateral or bilateral tinnitus were matched with control group counterparts without tinnitus by age, hearing, and sex (n = 18; 10 females, eight males in each group). Amplitude, area, and latency sensory gating ratios were determined for measured P1, N1, and P2 responses evoked by the first and second click in the paradigm and compared between groups by independent t tests. The relative influence of tinnitus (presence/absence), age (in years), noise exposure history (subjective self-report), hearing loss (pure-tone audiometric thresholds), and speech perception in noise (signal to noise ratio-50) on sensory gating was determined based on the proportional reduction in error associated with each variable using multiple regression.

Results:

A significantly larger

was identified in the tinnitus group relative to the control group, consistent with the hypothesis of poorer sensory gating and poorer thalamocortical inhibition in individuals with chronic tinnitus. On the basis of the proportional reduction in error, the influence of tinnitus presence better predicted

compared with other related individual characteristics (age, noise exposure history, hearing loss, and speech perception in noise).

Conclusions:

Results consistent with poorer sensory gating, including a larger

, were found for the tinnitus group compared with the controls. This finding supported a thalamocortical inhibitory deficit in the tinnitus group and suggests that individuals with tinnitus may have poorer sensory gating. However, the tinnitus group did differ from controls in meaningful ways including having worse pure-tone thresholds in the extended high-frequency region, lower high-frequency distortion product otoacoustic emissions, and poorer speech perception in noise. Although tinnitus best predicted sensory gating outcomes, the specific effects of tinnitus presence versus absence and other individual characteristics on sensory gating cannot be completely separated.
Electrophysiological Measures of Listening-in-Noise With and Without Remote Microphone System Use in Autistic and Non-Autistic Youth
Authors: Key Alexandra P. , Thompson Emily C. , Benítez-Barrera Carlos , Feldman Jacob I. , Woynaroski Tiffany , Picou Erin , Tharpe Anne Marie
Published: January 2024

Objectives:

This study examined the neural mechanisms by which remote microphone (RM) systems might lead to improved behavioral performance on listening-in-noise tasks in autistic and non-autistic youth.

Design:

Cortical auditory evoked potentials (CAEPs) were recorded in autistic (n = 25) and non-autistic (n = 22) youth who were matched at the group level on chronological age (M= 14.21 ± 3.39 years) and biological sex. Potentials were recorded during an active syllable identification task completed in quiet and in multi-talker babble noise with and without the use of an RM system. The effects of noise and RM system use on speech-sound-evoked P1-N1-P2 responses and the associations between the cortical responses and behavioral performance on syllable identification were examined.

Results:

No group differences were observed for behavioral or CAEP measures of speech processing in quiet or in noise. In the combined sample, syllable identification in noise was less accurate and slower than in the quiet condition. The addition of the RM system to the noise condition restored accuracy, but not the response speed, to the levels observed in quiet. The CAEP analyses noted amplitude reductions and latency delays in the noise compared with the quiet condition. The RM system use increased the N1 amplitude as well as reduced and delayed the P2 response relative to the quiet and noise conditions. Exploratory brain-behavior correlations revealed that larger N1 amplitudes in the RM condition were associated with greater behavioral accuracy of syllable identification. Reduced N1 amplitude and accelerated P2 response were associated with shorter syllable identification response times when listening with the RM system.

Conclusions:

Findings suggest that although listening-in-noise with an RM system might remain effortful, the improved signal to noise ratio facilitates attention to the sensory features of the stimuli and increases speech sound identification accuracy.
Health-related Quality of Life in Idiopathic Toe Walkers: A Multicenter Prospective Cross-sectional Study
Authors: Morrow Eileen , Harris Jennifer , Gelfer Yael , Cashman John , Kothari Alpesh ,   on behalf of the FOOTT-UK Collaborators
Published: January 2024

Objective:

Despite idiopathic toe walking (ITW) being a significant source of stress and anxiety for children and parents alike, little is known about the effect on health-related quality of life (HRQoL). The primary research question for this study was “Is ITW associated with impaired HRQoL, and is the degree of equinus contracture related to the degree of impairment?”

Methods:

Twelve pediatric orthopaedic centers across the United Kingdom participated in this prospective, cross-sectional observational study of children younger than 18 years with ITW. Data were collected between May 2022 and July 2022. Using a standardized, piloted proforma, data collected included: demographics, toe-walking duration, passive ankle range of motion (Silfverskiold test), associated autism spectrum disorder or attention deficit hyperactivity disorder, previous and planned treatments, and Oxford Ankle Foot Questionnaire for Children scores. Domain scores were compared with a healthy control group and correlation was made to plantarflexion contracture using standard nonparametric statistical methods.

Results:

Data were collected from 157 children. Significant reductions in physical, school and play, and emotional domain scores were noted compared with healthy controls. A significant moderate correlation was noted between passive ankle dorsiflexion and physical domain scores. There were no significant differences in Oxford Ankle Foot Questionnaire for Children scores among patient groups by treatment.

Conclusions:

ITW in children is associated with an impairment in HRQoL, not only across the physical domain but also the school and play and emotional domains. The more severe the equinus contracture, the worse the physical domain scores.

Level of Evidence:

Level II—prospective cross-sectional observational study.
Allogenic Simple Limbal Epithelial Transplantation: An Approach to Bilateral Recurrent Pterygia and Limbal Stem Cell Deficiency
Authors: Mazumdar Shefali , Singh Samya , Asija Nandini , Madhur Lavi
Published: January 2024

A 44-year-old man presented with bilateral total limbal stem cell deficiency after multiple failed surgeries for recurrent pterygia in both eyes over the last 11 years. His best corrected visual acuity (BCVA) in both eyes at the time of presentation was hand movement, projection of rays accurate. Owing to bilateral involvement, allogenic simple limbal epithelial transplantation (Allo SLET) was performed in the right eye. The limbal biopsy was taken from the wife of the patient. Complete ocular surface epithelialization was achieved in 26 days. The patient has completed 15 months of postoperative follow-up with stable ocular surface and BCVA 6/12 in the RE. He is on systemic and topical immunosuppressants with no side effects to date.
Cell therapy for retinal disease
Authors: Yalla Goutham R. , Kuriyan Ajay E.
Published: January 2024

Purpose of review

This review presents an update on completed stem cell therapy trials aimed at retinal diseases.

Recent findings

In recent years, several clinical trials have been conducted examining the safety and role of cell therapy in diseases, including age-related macular degeneration, Stargardt's macular dystrophy, and retinitis pigmentosa. Studies have utilized a variety of cell lines, modes of delivery, and immunosuppressive regimens. The prevalence of fraudulent cell therapy clinics poses threats to patients.

Clinical trials have begun to characterize the safety of cell therapy in retinal disease. While studies have described the potential benefits of cell therapy, larger studies powered to evaluate this efficacy are required to continue progressing toward preventing retinal disease. Nonapproved cell therapy clinics require regulation and patient education to avoid patient complications.