bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Invasive Mechanical Ventilation reduces the Motor Decline in Amyotrophic Lateral Sclerosis
Authors: Grassano Maurizio , Koumantakis Emanuele , Manera Umberto , Canosa Antonio , Vasta Rosario , Francesca Palumbo , Fuda Giuseppe , Salamone Paolina , Marchese Giulia , Casale Federico , Charrier Lorena , Mora Gabriele , Moglia Cristina , Calvo Andrea , Chiò Adriano
Published: June 2023

Background

Non-invasive mechanical ventilation (NIMV) improves Amyotrophic Lateral Sclerosis (ALS) quality of life and survival. However, data about its effect on disease progression are still lacking.

Objective

To test whether NIMV use changed the rate of functional decline among ALS patients.

Methods

In this retrospective observational study, we included 465 ALS patients followed up at the ALS Center in Turin, Italy, who underwent NIMV during the disease course. The primary outcome was the change in functional decline after NIMV initiation when adjusting for covariates. Functional decline was based on the non-respiratory items of the ALS Functional Rating Score – Revised (ALSFRS-R).

Results

A slower progression of functional decline followed NIMV initiation (mean improvement 0.13, 95%CI 0.11 to 0.16, p<0.001) regardless of sex, age at diagnosis, and disease duration prior to NIMV initiation. Indeed, the disease stage at NIMV initiation (early or advanced) did not influence the results. Respiratory support exerts its slowing effect mainly on the progression of spinal motor function.

Conclusions

We proved that NIMV influences the rate of motor progression in ALS. This result was not a consequence of the ALSFRS-R floor effect. The functional decline slowed after starting NIMV independently of the site of disease onset. Our results reinforce the importance of not delaying NIMV initiation in all ALS patients. NIMV-induced slowing of disease progression should also be accounted for when evaluating clinical trial outcomes.
Discovery of prognostic and treatment predictive biomarkers in recently diagnosed type 1 diabetes patients treated with anti TNFα
Authors: Kostense S , Klap Jaco M , Ashoor H , Yang R , Weverling GJ , Sweet K , Rigby MR , Hedrick JA
Published: June 2023

Objective

The T1GER study showed that treatment with the TNFα inhibitor golimumab in recently diagnosed type 1 diabetes patients showed better preservation of endogenous insulin production than placebo. However, considerable variation was observed among subjects. Therefore, a range of biomarkers were investigated for their potential to predict treatment response to golimumab.

Research Design and Methods

Baseline blood samples from 79 subjects were tested for autoantibodies, microRNA, metabolites, lipids, inflammatory proteins, and clinical chemistry. Univariate analysis was used to identify biomarkers that correlated with C-peptide change. Multivariate analysis was performed to establish a biomarker algorithm predicting the C-peptide response during the study.

Results

Multivariate analysis showed that baseline metabolites and miRNAs best predicted C- peptide responses both for placebo and treatment arms. Lipids, and inflammatory proteins were moderately predictive, whereas autoantibodies and clinical chemistry showed little predictive value.

An optimal model combining selected clinical variables and metabolites showed a correlation between predicted and observed C-peptide responses for the overall study up to 52 weeks, with an R2of 0.85. An LOOCV model was developed as a surrogate validation test, resulting in an R2of 0.69 overall, and an R2of 0.76 specifically predicting C-peptide responses at week 38.

Conclusions

The exploratory analysis of the T1GER study resulted in a set of baseline biomarkers with promising performance in predicting future C-peptide responses during the study. If validated in independent cohorts, these prognostic and predictive biomarkers and algorithm carry significant translational impacts that can assist clinicians in making treatment decisions.
Multivariable model of postoperative delirium in cardiac surgery patients: proteomic and demographic contributions
Authors: Gonçalves MCB , Khera T , Otu HH , Narayanan S , Dillon ST , Shanker A , Gu X , Jung Y , Ngo LH , Marcantonio ER , Libermann TA , Subramaniam B
Published: June 2023

Background

Delirium following cardiac surgery is common, morbid, and costly, but may be prevented with risk stratification and targeted intervention. Preoperative protein signatures may identify patients at increased risk for worse postoperative outcomes, including delirium. In this study, we aimed to identify plasma protein biomarkers and develop a predictive model for postoperative delirium in older patients undergoing cardiac surgery, while also uncovering possible pathophysiological mechanisms.

Methods

SOMAscan analysis of 1,305 proteins in the plasma from 57 older adults undergoing cardiac surgery requiring cardiopulmonary bypass was conducted to define delirium-specific protein signatures at baseline (PREOP) and postoperative day 2 (POD2). Selected proteins were validated in 115 patients using the ELLA multiplex immunoassay platform. Proteins were combined with clinical and demographic variables to build multivariable models that estimate the risk of postoperative delirium and bring light to the underlying pathophysiology.

Results

A total of 115 and 85 proteins from SOMAscan analyses were found altered in delirious patients at PREOP and POD2, respectively (p<0.05). Using four criteria including associations with surgery, delirium, and biological plausibility, 12 biomarker candidates (Tukey’s fold change (|tFC|)>1.4, Benjamini-Hochberg (BH)-p<0.01) were selected for ELLA multiplex validation. Eight proteins were significantly altered at PREOP, and seven proteins at POD2 (p<0.05), in patients who developed postoperative delirium compared to non-delirious patients. Statistical analyses of model fit resulted in the selection of a combination of age, sex, and three proteins (angiopoietin-2 (ANGPT2); C-C motif chemokine 5 (CCL5); and metalloproteinase inhibitor 1 (TIMP1); AUC=0.829) as the best performing predictive model for delirium at PREOP. The delirium-associated proteins identified as biomarker candidates are involved with inflammation, glial dysfunction, vascularization, and hemostasis, highlighting the multifactorial pathophysiology of delirium.

Conclusion

Our study proposes a model of postoperative delirium that includes a combination of older age, female sex, and altered levels of three proteins. Our results support the identification of patients at higher risk of developing postoperative delirium after cardiac surgery and provide insights on the underlying pathophysiology.ClinicalTrials.gov(NCT02546765).
EuroQol-5D-3L in Long Covid patients After Supplementation with EchA Marine®, a Sea Urchin Eggs Extract: a double-blinded, multicentrical study
Authors: Brichetti V , Rubilar T. , Tejada J. , Montecino P. , Crespi-Abril A. , Barbieri E , de la Rosa N , Iriarte-Vazquez J. , Jajati N. , Volonteri C. , Sivori M. , de Larrañaga G. , Saldarini F.
Published: June 2023

Patients with Long COVID experience a significant decrease in their quality of life and the lack of effective treatment represents an unmet need in medical care and patient health. One proposed strategy for treating Long COVID is to increase the body’s ability to restore immune balance by controlling inflammation with anti-inflammatory substances. For this reason, the aim of this double-blind study was to evaluate the supplementation of patients with EchA Marine®, a dietary supplement based on sea urchin eggs rich in Echinochrome A. This compound has demonstrated anti-inflammatory and antioxidant properties by activating the metabolism of glutathione and improving mitochondrial mass and performance. The EuroQol 5-Dimension (EQ-5D) is a standardized questionnaire assessing five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used as an instrument to measure health-related quality of life in clinical and economic studies. In this multicenter, double-blind, intervention study, we have demonstrated that the dietary supplement EchA Marine®can significantly enhance the quality of life of these patients, particularly in pain and discomfort; notably improving their quality of life and daily activity’s ability. EchA Marine®is an effective treatment option for Long COVID patients and with further research its efficacy could be further strengthened.
Genetic and functional diversity help explain pathogenic, weakly pathogenic, and commensal lifestyles in the genusXanthomonas
Authors: Pena Michelle M. , Bhandari Rishi , Bowers Robert M. , Weis Kylie , Newberry Eric , Wagner Naama , Pupko Tal , Jones Jeffrey B. , Woyke Tanja , Vinatzer Boris A. , Jacques Marie-Agnès , Potnis Neha
Published: June 2023

The genusXanthomonashas been primarily studied for pathogenic interactions with plants. However, besides host and tissue specific pathogenic strains, this genus also comprises nonpathogenic strains isolated from a broad range of hosts, sometimes in association with pathogenic strains, and other environments, including rainwater. Based on their incapacity or limited capacity to cause symptoms on the host of isolation, nonpathogenic xanthomonads can be further characterized as commensal and weakly pathogenic. This study aimed to understand the diversity and evolution of nonpathogenic xanthomonads compared to their pathogenic counterparts based on their co-occurrence and phylogenetic relationship and to identify genomic traits that form the basis of a life-history framework that groups xanthomonads by ecological strategies. We sequenced genomes of 83 strains spanning the genus phylogeny and identified eight novel species, indicating unexplored diversity. While some nonpathogenic species have experienced a recent loss of a type III secretion system, specifically, thehrp2cluster, we observed an apparent lack of association of thehrp2cluster with lifestyles of diverse species. We gathered evidence for gene flow among co-occurring pathogenic and nonpathogenic strains, suggesting the potential of nonpathogenic strains to act as a reservoir of adaptive traits for pathogenic strains and vice versa. We further identified traits enriched in nonpathogens that suggest a strategy of stress tolerance, rather than avoidance, during their association with a broad range of host plants.
Identifying modifiable comorbidities of schizophrenia by integrating electronic health records and polygenic risk
Authors: Vessels Tess , Strayer Nicholas , Choi Karmel W. , Lee Hyunjoon , Zhang Siwei , Han Lide , Morley Theodore J. , Smoller Jordan W. , Xu Yaomin , Ruderfer Douglas M.
Published: June 2023

Patients with schizophrenia have substantial comorbidity contributing to reduced life expectancy of 10-20 years. Identifying which comorbidities might be modifiable could improve rates of premature mortality in this population. We hypothesize that conditions that frequently co-occur but lack shared genetic risk with schizophrenia are more likely to be products of treatment, behavior, or environmental factors and therefore potentially modifiable. To test this hypothesis, we calculated phenome-wide comorbidity from electronic health records (EHR) in 250,000 patients in each of two independent health care institutions (Vanderbilt University Medical Center and Mass General Brigham) and association with schizophrenia polygenic risk scores (PRS) across the same phenotypes (phecodes) in linked biobanks. Comorbidity with schizophrenia was significantly correlated across institutions (r = 0.85) and consistent with prior literature. After multiple test correction, there were 77 significant phecodes comorbid with schizophrenia. Overall, comorbidity and PRS association were highly correlated (r = 0.55, p = 1.29×10−118), however, 36 of the EHR identified comorbidities had significantly equivalent schizophrenia PRS distributions between cases and controls. Fifteen of these lacked any PRS association and were enriched for phenotypes known to be side effects of antipsychotic medications (e.g., “movement disorders”, “convulsions”, “tachycardia”) or other schizophrenia related factors such as from smoking (“bronchitis”) or reduced hygiene (e.g., “diseases of the nail”) highlighting the validity of this approach. Other phenotypes implicated by this approach where the contribution from shared common genetic risk with schizophrenia was minimal included tobacco use disorder, diabetes, and dementia. This work demonstrates the consistency and robustness of EHR-based schizophrenia comorbidities across independent institutions and with the existing literature. It identifies comorbidities with an absence of shared genetic risk indicating other causes that might be more modifiable and where further study of causal pathways could improve outcomes for patients.
Endodermal cells use contact inhibition of locomotion to achieve uniform cell dispersal during zebrafish gastrulation
Authors: LaBelle Jesselynn , Wyatt Tom , Woo Stephanie
Published: June 2023

The endoderm is one of the three primary germ layers that ultimately gives rise to the gastrointestinal and respiratory epithelia and other tissues. In zebrafish and other vertebrates, endodermal cells are initially highly migratory with only transient interactions among one other, but later converge together to form an epithelial sheet. Here, we show that during their early, migratory phase, endodermal cells actively avoid each other through contact inhibition of locomotion (CIL), a characteristic response consisting of 1) actin depolymerization and membrane retraction at the site of contact, 2) preferential actin polymerization along a cell-free edge, and 3) reorientation of migration away from the other cell. We found that this response is dependent on the Rho GTPase RhoA. Expression of dominant-negative (DN) RhoA attenuated migration reorientation after cell-cell contact and increased the amount of time cells spent in contact with each other — behaviors consistent with a loss of CIL. Computational modeling predicted that CIL is required to achieve the efficient and uniform dispersal characteristic of endodermal cells. Consistent with our model, we found that loss of CIL via DN RhoA expression resulted in irregular clustering of cells within the endoderm. Finally, using a combination of pharmacological and genetic perturbations, we identify EphA2 as the cell surface receptor mediating endodermal CIL. Together, our results suggest that endodermal cells use EphA2-and RhoA-dependent CIL as a cell dispersal and spacing mechanism, demonstrating how tissue-scale patterns can emerge from local cell-cell interactions.
Differentiation latency and dormancy signatures define fetal liver HSCs at single cell resolution
Authors: Ishida Takashi , Heck Adam M. , Varnum-Finney Barbara , Dozono Stacey , Nourigat-McKay Cynthia , Kraskouskas Katie , Wellington Rachel , Waltner Olivia , Root  , Jackson Dana L , Delaney Colleen , Rafii Shahin , Bernstein Irwin D. , Trapnell  , Hadland Brandon
Published: June 2023

Decoding the gene regulatory mechanisms mediating self-renewal of hematopoietic stem cells (HSCs) during their amplification in the fetal liver (FL) is relevant for advancing therapeutic applications aiming to expand transplantable HSCs, a long-standing challenge. Here, to explore intrinsic and extrinsic regulation of self-renewal in FL-HSCs at the single cell level, we engineered a culture platform designed to recapitulate the FL endothelial niche, which supports the amplification of serially engraftable HSCs ex vivo. Leveraging this platform in combination with single cell index flow cytometry, serial transplantation assays, and single cell RNA-sequencing, we elucidated previously unrecognized heterogeneity in immunophenotypically defined FL-HSCs and demonstrated that differentiation latency and transcriptional signatures of biosynthetic dormancy are distinguishing properties of self-renewing FL-HSCs with capacity for serial, long-term multilineage hematopoietic reconstitution. Altogether, our findings provide key insights into HSC expansion and generate a novel resource for future exploration of the intrinsic and niche-derived signaling pathways that support FL-HSC self-renewal.
The impact of respiratory infections and probiotic use on the nasal microbiota of frail residents in long-term care homes
Authors: Bowdish DME , Rossi L , Loeb MB , Johnstone J , Schenck LP , Fontes M , Surette MG , Whelan FJ
Published: June 2023

Background

Residents in long-term care (LTC) homes, who tend to be of advanced age and frail, are at increased risk of respiratory infections. The respiratory microbiota is known to change with age, but whether these changes contribute to the risk of infection is not known. Our goal was to determine how the nasal microbiota of frail older adults changes during symptoms of influenza-like illness (ILI) and how this may be impacted by enrollment in a placebo-controlled trial testing the feasibility of administering aLactobacillus rhamnosusGG probiotic to prevent respiratory infection (2014 - 2017). The microbiome of the nasal (mid-turbinate) of 150 residents of LTC homes was interrogated using 16S rRNA gene sequencing.

Results

We identified a diverse and individualized microbiota which could be separated into 9 distinct clusters based on Bray Curtis distances. Samples collected during symptoms of influenza-like illness (ILI) differed statistically from those collected pre- and post-cold and influenza season, and we observed decreased temporal stability – as measured by movement between clusters – in individuals who experienced ILI compared to those who did not.

Conclusions

The use of probiotics decreased ILI-induced changes to the microbiota; however, it is not clear whether this decrease is sufficient to prevent respiratory illness.
Translating metagenomics into clinical practice of complex paediatric neurological presentations
Authors: Penner Justin , Hassell Jane , Brown Julianne R , Mankad Kshitij , Storey Nathaniel , Atkinson Laura , Ranganathan Nisha , Lennon Alexander , Lee Jack C D , Champsas Dimitrios , Kopec Angelika , Shah Divya , Venturini Cristina , Dixon Garth , De Surjo , Hatcher James , Harris Kathryn , Aquilina Kristian , Kusters Maaike A. , Moshal Karyn , Shingadia Delane , Worth Austen JJ , Lucchini Giovanna , Merve Ashirwad , Jacques Thomas S , Bamford Alasdair , Kaliakatsos Marios , Breuer Judith , Morfopoulou Sofia
Published: June 2023

Background

Atypical or complex paediatric neurological presentations are common clinical conundrums and often remain undiagnosed despite extensive investigations. This is particularly pronounced in immunocompromised patients. Here we show that clinical metagenomics (CMg) is a valuable adjunct diagnostic tool to be used by neuro-infection multidisciplinary teams (MDTs).

Methods

We included patients referred to the Great Ormond Street Hospital neuro-infection MDT in whom diagnostic uncertainty remained, despite a standardised comprehensive set of investigations, and who were referred for untargeted CMg on brain tissue and/or cerebrospinal fluid (CSF). In a retrospective review, two clinicians independently assessed whether CMg in conjunction with the MDT resulted in a change of management.

Findings

60 undiagnosed patients met the inclusion criteria. We detected the causative pathogen by CMg in 14/60 (23%), with 12/36 patients known to be immunocompromised. CMg results, even when negative, informed patient care, resulting in changes in clinical management in 42/57 (74%). Six patients had unexpected findings of pathogens not identified on prior samples. In four patients, the pathogen was found solely in the brain biopsy and was absent from all other specimens, including CSF.

Interpretation

CMg is particularly useful when conventional diagnostic techniques for meningoencephalitis are exhausted and proved to be an important diagnostic tool for immunocompromised patients. CMg provided increased reassurance against an infective aetiology prior to recommending immunosuppressive or immunomodulatory treatment. Specialised MDTs should advocate for early brain biopsies and routine CMg in an experienced laboratory for undiagnosed complex neurological cases affecting immunocompromised patients.
Trans-ancestral genetic study of diabetes mellitus risk in survivors of childhood cancer: a report from the St. Jude Lifetime Cohort and the Childhood Cancer Survivor Study
Authors: Im Cindy , Neupane Achal , Baedke Jessica L. , Delaney Angela , Dixon Stephanie B. , Chow Eric J. , Mostoufi-Moab Sogol , Richard Melissa A. , Gramatges M. Monica , Lupo Philip J. , Sharafeldin Noha , Bhatia Smita , Armstrong Gregory T. , Hudson Melissa M. , Ness Kirsten K. , Robison Leslie L. , Yasui Yutaka , Wilson Carmen L. , Sapkota Yadav
Published: June 2023

Type 2 diabetes mellitus (T2D) is an established late effect of treatment for childhood cancer. Leveraging detailed cancer treatment and whole-genome sequencing data among survivors of childhood cancer of European (EUR) and African (AFR) genetic ancestry in the St. Jude Lifetime Cohort (N=3,676; 304 cases), five novel diabetes mellitus (DM) risk loci were identified with independent trans-/within-ancestry replication, including in 5,965 survivors of the Childhood Cancer Survivor Study. Among these, common risk variants at 5p15.2 (LINC02112), 2p25.3 (MYT1L), and 19p12 (ZNF492) modified alkylating agent-related risks across ancestry groups, but AFR survivors with risk alleles experienced disproportionately greater risk of DM (AFR, variant ORs: 3.95-17.81; EUR, variant ORs: 2.37-3.32). Novel risk locusXNDC1Nwas identified in the first genome-wide DM rare variant burden association analysis in survivors (OR=8.65, 95% CI: 3.02-24.74, P=8.1×10-6). Lastly, a general-population 338-variant multi-ancestry T2D polygenic risk score was informative for DM risk in AFR survivors, and showed elevated DM odds after alkylating agent exposures (quintiles: combined OREUR=8.43, P=1.1×10-8; ORAFR=13.85, P=0.033). This study supports future precision diabetes surveillance/survivorship care for all childhood cancer survivors, including those with AFR ancestry.
Clinical consequence of vessel perforations during endovascular treatment of acute ischemic stroke
Authors: van der Sluijs P. Matthijs , Su R. , Cornelissen S.A.P. , van Es A.C.G.M. , Lycklama a Nijeholt G. , Roozenbeek B. , van Doormaal P.J. , Hofmeijer J. , van der Lugt A. , van Walsum T. ,   MR CLEAN Registry investigators
Published: June 2023

Background

Endovascular treatment (EVT) of acute ischemic stroke can be complicated by vessel perforation. We studied the incidence and determinants of vessel perforations. In addition, we studied the association of vessel perforations with functional outcome, and the association between location of perforation on DSA and functional outcome, using a large EVT registry.

Methods

We included all patients in the MR CLEAN Registry who underwent EVT. We used digital subtraction angiography (DSA) to determine whether EVT was complicated by a vessel perforation. We analyzed the association with baseline clinical and interventional parameters using logistic regression models. Functional outcome was measured using the modified Rankin Scale (mRS) at 90 days. The association between vessel perforation and angiographic imaging features and functional outcome was studied using ordinal logistic regression models adjusted for prognostic parameters. These associations were expressed as adjusted common odds ratios (acOR).

Results

Vessel perforation occurred in 74 (2.6%) of 2794 patients who underwent EVT. Female sex (aOR 1.9 [95%CI 1.2-3.1]) and distal occlusion locations (aOR 2.2 [95%CI 1.4-3.7]) were associated with increased risk of vessel perforation. Functional outcome was worse in patients with vessel perforation (acOR 0.41, 95%CI 0.25-0.68) compared to patients without a vessel perforation. No significant association was found between location of perforation or successful reperfusion and functional outcome.

Conclusion

The incidence of vessel perforation during EVT is low, but it has severe clinical consequences. Females and patients with a distal occlusion locations are at higher risk. The location of vessel perforation or successful reperfusion did not affect functional outcome.
Effect of Endovascular therapy in large anterior circulation ischemic strokes -a systematic review and meta-analysis
Authors: Panigrahi Baikuntha , Thakur Hameer Subhangi , Bhatia Rohit , Haldar Partha , Sharma Agrata , Srivastava M.V.Padma
Published: June 2023

Background and purpose

The benefit of endovascular treatment in large anterior circulation ischemic strokes with low ASPECTS score(<6) is uncertain. Recent studies have demonstrated the benefit of endovascular treatment (EVT) in large ischemic strokes. The present meta-analysis aims to assess the combined effect of these studies on efficacy and safety of endovascular treatment in this group of patients.

Materials and Methods

We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Databases MEDLINE, PubMed, EMBASE, SCOPUS, Google Scholar, Tripdatabase were searched for randomised controlled trials with at least 50 participants. The primary efficacy outcome analysed was the relative risk of functional independence defined as mRS-0-2 at 90 days. Secondary efficacy outcomes included early neurological improvement, death due to any cause at 90 days and proportion of patients requiring decompressive hemicraniectomy. The primary safety outcome was the risk of developing symptomatic intracerebral haemorrhage.

Results

A total of 3 studies(RESCUE Japan-LIMIT,SELECT 2 and ANGEL ASPECTS) involving 1011 patients ; 510 in the EVT arm and 501 in the medical management (MM) arm met the defined criteria (ASPECTS-3-5). The combined RR for the primary outcome of mRS 0-2 was 2.53 [1.84-3.47] (p=<0.0001) favouring EVT over MM. The primary safety outcome of symptomatic intracerebral haemorrhage was not significant in the EVT arm with a combined RR of 1.84 [0.94-3.60] (p=0.5157). Mortality rates were similar in both arms (26.67% in EVT arm vs 27.94% in MM arm) with a combined RR of 0.95 [0.78; 1.16] (p=1.000).

Conclusion

In patients with LVO and low ASPECTS (3-5), EVT was associated with higher likelihood of achieving functional independence and early neurologic improvement but did not provide any mortality benefit. The rates of symptomatic ICH were similar in both the groups whereas the risk of any ICH was significantly higher in the EVT arm.

Funding-Nil

The protocol for the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database(CRD42023400675)
The Alk receptor tyrosine kinase regulates Sparkly, a novel activity regulating neuropeptide precursor in theDrosophilaCNS
Authors: Sukumar Sanjay Kumar , Antonydhason Vimala , Molander Linnea , Sandakly Jawdat , Kleit Malak , Umapathy Ganesh , Mendoza-Garcia Patricia , Masudi Tafheem , Schlossser Andreas , Nässel Dick R. , Wegener Christian , Shirinian Margret , Palmer Ruth H.
Published: June 2023

Numerous roles for the Alk receptor tyrosine kinase have been described inDrosophila, including functions in the central nervous system (CNS), however the molecular details are poorly understood. To gain mechanistic insight, we employed Targeted DamID (TaDa) transcriptional profiling to identify targets of Alk signaling in the larval CNS. TaDa was employed in larval CNS tissues, while genetically manipulating Alk signaling output. The resulting TaDa data were analysed together with larval CNS scRNA-seq datasets performed under similar conditions, identifying a role for Alk in the transcriptional regulation of neuroendocrine gene expression. Further integration with bulk/scRNA-seq and protein datasets from larval brains in which Alk signaling was manipulated, identified a previously uncharacterizedDrosophilaneuropeptide precursor encoded byCG4577as an Alk signaling transcriptional target.CG4577, which we namedSparkly (Spar),is expressed in a subset of Alk-positive neuroendocrine cells in the developing larval CNS, including circadian clock neurons. In agreement with our TaDa analysis, overexpression of theDrosophilaAlk ligand Jeb resulted in increased levels of Spar protein in the larval CNS. We show that Spar protein is expressed in circadian (Clock) neurons, and flies lacking Spar exhibit defects in sleep and circadian activity control. In summary, we report a novel activity regulating neuropeptide precursor gene that is regulated by Alk signaling in theDrosophilaCNS.
Wearable sensor and machine learning accurately estimate tendon load and walking speed during immobilizing boot ambulation
Authors: Kwon Michelle P. , Hullfish Todd J. , Humbyrd Casey J. , Boakye Lorraine A.T. , Baxter Josh R.
Published: June 2023

Achilles tendon injuries are treated with progressive weight bearing to promote tendon healing and restore function. Patient rehabilitation progression are typically studied in controlled, lab settings and do not represent the long-term loading experienced during daily living. The purpose of this study is to develop a wearable paradigm to accurately monitor Achilles tendon loading and walking speed using low-cost sensors that reduce subject burden. Ten healthy adults walked in an immobilizing boot under various heel wedge conditions (30°, 5°, 0°) and walking speeds. Three-dimensional motion capture, ground reaction force, and 6-axis inertial measurement unit (IMU) signals were collected per trial. We used Least Absolute Shrinkage and Selection Operator (LASSO) regression to predict peak Achilles tendon load and walking speed. The effects of using only accelerometer data, different sampling frequency, and multiple sensors to train the model were also explored. Walking speed models outperformed (mean absolute percentage error (MAPE): 8.41 ± 4.08%) tendon load models (MAPE: 33.93 ± 23.9%). Models trained with subject-specific data performed significantly better than generalized models. For example, our personalized model that was trained with only subject-specific data predicted tendon load with a 11.5 ± 4.41% MAPE and walking speed with a 4.50 ± 0.91% MAPE. Removing gyroscope channels, decreasing sampling frequency, and using combinations of sensors had inconsequential effects on models performance (changes in MAPE < 6.09%). We developed a simple monitoring paradigm that uses LASSO regression and wearable sensors to accurately predict Achilles tendon loading and walking speed while ambulating in an immobilizing boot. This paradigm provides a clinically implementable strategy to longitudinally monitor patient loading and activity while recovering from Achilles tendon injuries.
Long-term follow-up of subthalamic nucleus deep brain stimulation in patients with Parkinson’s disease: an analysis of survival and disability milestones
Authors: Barbosa Raquel , Guedes Leonor Correia , Begoña Cattoni Maria , Pita Lobo Patricia , Castro Caldas Ana , Fabbri Margherita , Bastos Paulo , Valadas Anabela , Carvalho Herculano , Albuquerque Luisa , Reimão Sofia , Gonçalves Ferreira A , Ferreira Joaquim J , Rosa Mário Miguel , Coelho Miguel
Published: June 2023

Background

Data on the long-term survival and incidence of disability milestones after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD) is limited.

Objectives

To estimate mortality among PD patients 8 years after STN-DBS and to quantify the frequency /time-to-development of disability milestones (falls, freezing, hallucinations, dementia, and institutionalization).

Methods

A longitudinal retrospective study of patients submitted to STN-DBS between 2006-2012 was carried-out. For mortality, Cox proportional hazards regression analysis was performed. For disease milestones, competing risk analyses were performed and cumulative incidence functions calculated. Multivariable regression analysis in the presence of competing risks was performed based on the Gray’s test of sub-distribution hazards of cumulative incidence functions.

Results

An overall mortality rate of 16% (mean 62.1 ± 21.3 months after surgery) was observed. Falls (73%) and freezing (47%) were both the earliest (40.4 ± 25.4 and 39.6 ± 28.4 months, respectively) and most frequently observed milestones. Dementia (34%) and hallucinations (32%) soon follow (56.2 ± 21.2 and mean 60.0 ± 20.7 months after surgery, respectively). Institutionalization occurred in 6% after 62.3 ± 22.0 months. Higher ADL scores in the OFF state and higher age at surgery were associated with falls, freezing, dementia and institutionalization.

Conclusions

Long-term mortality rate is low after STN-DBS, with STN-DBS patients developing the same disability milestones as non-DBS patients. Motor milestones occur first and at a higher frequency than cognitive ones. Milestones cluster together before death.
Identification of hepatocyte immune response in Autoimmune Hepatitis from human plasma cfChIP-seq
Authors: Fialkoff Gavriel , Ya’akov Ami Ben , Sharkia Israa , Sadeh Ronen , Gutin Jenia , Goldstein Chen , Khalaileh Abed , Imam Ashraf , Safadi Rifaat , Milgrom Yael , Galun Eithan , Shteyer Eyal , Friedman Nir
Published: June 2023

Autoimmune hepatitis (AIH) is a self-perpetuating inflammatory liver disease with significant morbidity and mortality risks. Patients undergo liver biopsy to confirm diagnosis and affirm subsequent remission. Advances in liquid biopsies show promise to replace tissue biopsy in cancer, however little research has been done in liver disease. Here, we use plasma chromatin immunoprecipitation and sequencing (cfChIP-seq) to analyze cell-free nucleosomes carrying an active histone modification which reports on gene transcription in the dying cells. Comparing plasma samples from pediatric AIH patients to a control group we identify immune-related transcriptional processes activated in hepatocytes of AIH patients. We devise a classifier that based on cfChIP-seq profiles distinguishes AIH from other conditions involving increased liver damage. Our work demonstrates the potential of plasma cfChIP-seq as a non-invasive diagnostic tool for AIH, which could replace the need for liver biopsy, aid accurate diagnoses, and enable further scientific exploration of AIH pathogenesis.
Evaluation of the performance of GPT-3.5 and GPT-4 on the Medical Final Examination
Authors: Rosoł Maciej , Gąsior Jakub S. , Łaba Jonasz , Korzeniewski Kacper , Młyńczak Marcel
Published: June 2023

Introduction

The rapid progress in artificial intelligence, machine learning, and natural language processing has led to the emergence of increasingly sophisticated large language models (LLMs) enabling their use in various applications, including medicine and healthcare.

Objectives

The study aimed to evaluate the performance of two LLMs: ChatGPT (based on GPT-3.5) and GPT-4, on the Medical Final Examination (MFE).

Methods

The models were tested on three editions of the MFE from: Spring 2022, Autumn 2022, and Spring 2023 in two language versions – English and Polish. The accuracies of both models were compared and the relationships between the correctness of answers with the index of difficulty and discrimination power index were investigated.

Results

The study demonstrated that GPT-4 outperformed GPT-3.5 in all three examinations regardless of the language used. GPT-4 achieved mean accuracies of 80.7% for Polish and 79.6% for English, passing all MFE versions. GPT-3.5 had mean accuracies of 56.6% for Polish and 58.3% for English, passing 2 of 3 Polish versions and all 3 English versions of the test. GPT-4 score was lower than the average score of a medical student. There was a significant positive and negative correlation between the correctness of the answers and the index of difficulty and discrimination power index, respectively, for both models in all three exams.

Conclusions

These findings contribute to the growing body of literature on the utility of LLMs in medicine. They also suggest an increasing potential for the usage of LLMs in terms of medical education and decision-making support.

What’s new?

Recent advancements in artificial intelligence and natural language processing have resulted in the development of sophisticated large language models (LLMs). This study focused on the evaluation of the performance of two LLMs, ChatGPT (based on GPT-3.5) and GPT-4, on the Medical Final Examination across English and Polish versions from three editions. This study, to the best of our knowledge, presents the first validation of those models on the European-based medical final examinations. The GPT-4 outperformed GPT-3.5 in all exams, achieving mean accuracy of 80.7% (Polish) and 79.6% (English), while GPT-3.5 attained 56.6% (Polish) and 58.3% (English) respectively. However, GPT-4’s scores fell short of typical medical student performance. These findings contribute to understanding LLM’s utility in medicine and hint at their potential in medical education and decision-making support.
The microstructure and corrosion behavior of Cr-containing ferrite-pearlite steels in an acidic environment
Authors: Hao Xuehui , Wang Changzheng , Guo Shuai , Ma Jie , Chen Hui , Zhao Xingchuan
Published: June 2023

Purpose

The poor corrosion resistance of the ferrite-pearlite steel limits its application in marine engineering because of the enhanced galvanic effect caused by continuously accumulated cementite. Cr as one principal alloying element is commonly used to improve the corrosion resistance of steels. This paper aims to study the effect of Cr on corrosion behaviors of ferrite-pearlite steels in an acidic environment.

Design/methodology/approach

The tested steels were immersed in a simulated solution of 10 Wt.% NaCl with pH 0.85 for 72 h to evaluate the corrosion rate. After the immersion test, the corrosion morphologies and products were tested by scanning electron microscopy, energy dispersive X-ray analysis and X-ray diffraction. Meanwhile, an electrochemical workstation was used to study the electrochemical behaviors of samples.

Findings

At the initial corrosion stage, the corrosion rate increased in the sequence of Cr0, Cr0.5 and Cr1 steels, which was because of the competitive effect between the area ratio and the driving force caused by alloyed Cr. However, Cr1 steel exhibited the best corrosion resistance after a 72-h immersion test. This was because the alloyed Cr promoted the formation of protective Fe2O3 and FeCr2O4, which suppressed the preferential dissolution of ferrite and, thus, reduced the accumulation rate of carbides, resulting in the weakened galvanic corrosion.

Originality/value

This paper reports the role that Cr plays in the galvanic corrosion of ferrite-pearlite steels, which is important for the engineering application of ferrite-pearlite steels in marine environment.
Influence of the geometric parameters of a vertical rotational single-sheet tester on sample field homogeneity
Authors: Tolentino Guilherme , Parent Guillaume , Ninet Olivier , Rossi Mathieu , Leite Jean Vianei , Blaszkowski Jonathan
Published: June 2023

Purpose

The horizontal rotational single-sheet tester (RSST) suffers from weaknesses such as the reduced size of test samples, measurement disturbances due to magnetic flux leakage and nonhomogeneity of field in the measurement area. Although the vertical RSST allows to overcome the first two aforementioned drawbacks, the heterogeneity of the field in the test sample remains an issue. In addition, there is still a lack of device standardization to ensure test repeatability, as already is well established with the Epstein frame. This paper aims to investigate the influence of several parameters on the field homogeneity in the test sample.

Design/methodology/approach

A fully 3D finite element model of a vertical RSST is developed and used to perform a sensibility study on several geometrical parameters.

Findings

The influence of several parameters on the field homogeneity in the test sample, such as the geometrical dimensions of the yokes, the presence or not of holes drilled inside the test sample for B-coil placement as well as the size of the H-coils and B-coils, is addressed.

Originality/value

It is expected that this study will contribute to the optimization and standardization vertical RSSTs.
25 Years internationalization research in SMEs, a scientometric analysis
Authors: Daei Ali , Zanjirchi Seyed Mahmood , Mirghafoori Seyed Habibolah , Naser Sadrabadi Alireza
Published: June 2023

Purpose

The varying nature of the competitive environment of small- and medium-sized enterprises (SMEs), contributing significantly to gross domestic product in most countries, has made their moving toward internationalization and global competition unavoidable in such a way that the life cycle of research in this area is experiencing a period of rapid growth. This study aims to evaluate the status of research on SME internationalization based on bibliographic records retrieved from the Web of Science Core Collection and Scopus.

Design/methodology/approach

Using a scientometric analysis, reviewing the important points and the boundaries of research on SME internationalization as well as practicing co-occurrence and burst detection analysis.

Findings

Through a rigorous examination of the crucial points and boundaries within the realm of SMEs internationalization research, coupled with an analysis of co-occurrence and burst detection techniques to detect contemporary hotbed topics, this study has uncovered that the predominant focus of current discourse centers around the areas of networks and networking, as well as internationalization models and entry into the global arena. Moreover, it gives insight that future investigations will shift toward enhancing SME internationalization performance, while simultaneously prioritizing the expeditiousness of their entrance into international markets. The insights garnered from this inquiry are expected to facilitate salient contributions to future literature in this area, thereby advancing our understanding of these complex phenomena.

Practical implications

The trend of the research in this field can be useful for enthusiasts. In this context, the life cycle of research on SME internationalization has been drawn that shows the period of research growth of publications is almost between 2005 and 2023, and the saturation will be approximately from 2023 to 2035. The top researching SME internationalization in the world have been occurred in the USA, England, Canada, Sweden countries and in Department of Management, Department of Marketing, School of Management, Faculty of Management Studies institutions. Also, most of the research has been published in Journal of International Business Studies, International Business Review and Strategic Management Journal.

Originality/value

This study accordingly provided a valuable perspective for future research in this line.
The use of human-computer interaction in libraries: a systematic literature review
Authors: Khan Amjid , Hussain Abid , Zareef Muhammad
Published: June 2023

Purpose

This study aims to analyze the status and application/use of human–computer interaction (HCI) in libraries by conducting a systematic literature review (SLR).

Design/methodology/approach

A Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach was used to search Scopus, Web of Science and Google Scholar databases. The search criteria included research studies published in English language between 2010 and 2021, which were 4,167 citations. Out of 4,167 citations, a total of 50 studies were selected for the final analysis.

Findings

The results showed a positive attitude of librarians toward HCI applications in libraries worldwide. The results depict that one-third (30%) of the studies were conducted in the USA, followed by four (8%) studies in China. Out of 50 studies, a portion of 15 (30%) studies were based on digital libraries, followed by seven (14%) studies on academic libraries and five (10%) studies on libraries and their websites. HCI was used for searching and retrieving information, users’ interaction, authentication, online help/support, feedback, library web access, web OPAC, virtual access to resources, indigenous repository and virtual services. The most productive year was 2015, and journal of The Electronic Library had more articles on HCI than other journals.

Practical implications

The findings of this study could assist policymakers and library authorities in reconciling the HCI application in libraries for providing effective and efficient access and services to end-users.

Originality/value

This study is unique as no comprehensive study has been conducted on the use of HCI in librarianship using the SLR method.
Diversified urban housing markets and decentralized market regulation in China
Authors: Li Wenjing , Liu Zhi
Published: June 2023

Purpose

In 2016, the Chinese central government decentralized the responsibilities of housing market regulation to the municipal level. This paper aims to assess whether the decentralized market regulation is effective.

Design/methodology/approach

This study first investigates the fundamental drivers of urban housing prices in China. Taking into consideration the factors driving housing prices, the authors further investigate the effectiveness of decentralized housing market regulation by a pre- and post-policy comparison test using a panel data set of 35 major cities for the years from 2014 to 2019.

Findings

The results reveal heterogenous policy effects on housing price growth among cities with a one-year lag in effectiveness. With the decentralized housing market regulation, cities with fast price growth are incentivized to implement tightening measures, while cities with relatively low housing prices and slow price growth are more likely to do nothing or deregulate the markets. The findings indicate that the shift from a centralized housing market regulation to a decentralized one is more appropriate and effective for the individual cities.

Originality/value

Few policy evaluation studies have been done to examine the effects of decentralized housing market regulation on the performance of urban housing markets in China. The authors devise a methodology to conduct a policy evaluation that is important to inform public policy and decisions. This study helps enhance the understanding of the fundamental factors in China’s urban housing markets and the effectiveness of municipal government interventions.
Cryptocurrency puzzles: a comprehensive review and re-introduction
Authors: Cai Cynthia Weiyi , Xue Rui , Zhou Bi
Published: June 2023

Purpose

This study reviews existing cryptocurrency research to provide answers to three puzzles in the literature. First, is cryptocurrency more like gold (i.e., a commodity) or should it be classified as a new financial asset? Second, can we apply our knowledge of the traditional capital market to the emerging cryptocurrency market? Third, what might be the future of cryptocurrency?

Design/methodology/approach

Bibliometric analysis is used to assess 2,098 finance-related cryptocurrency publications from the Web of Science (WoS) Core Collection database from January 2009 to April 2022. Three key research streams are identified, namely, (1) cryptocurrency features, (2) behaviour of the cryptocurrency market and (3) blockchain implications.

Findings

First, cryptocurrency should be viewed and regulated as a new asset class rather than a currency or a new commodity. While it can provide diversification benefits to the portfolio, cryptocurrency cannot work as a safe haven asset. Second, crypto markets are typically inefficient. Asset bubbles exist and are exacerbated by behavioural finance factors. Third, cryptocurrency demonstrates increasing potential as a medium of exchange and store of value.

Originality/value

Extant review papers primarily study one or two particular research topics, overlooking the interaction between topics. The few existing systematic literature reviews in this area typically have a narrow focus on trend identification. This study is the first study to provide a comprehensive review of all financial-related studies on cryptocurrency, synthesising the research findings from 2,098 publications to answer three cryptocurrency puzzles.