bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha 9 integrin expression enables reconstruction of the spinal cord sensory pathway
Authors: Stepankova Katerina , Smejkalova Barbora , Machova Urdzikova Lucia , Haveliková Katerina , de Winter Fred , Suchankova Stepanka , Verhaagen Joost , Herynek Vit , Turecek Rostislav , Kwok Jessica , Fawcett James , Jendelova Pavla 
Published: March 2023

AbstractFull recovery from spinal cord injury can only occur if the axon pathways connecting the brain and spinal cord regenerate and restore motor and sensory connections. Neither sensory nor motor axons can regenerate spontaneously in the spinal cord in mammals. This failure is partly due to the lack of suitable adhesion molecules on the sensory axons that allows them to interact with the environment of the damaged spinal cord. In this rat study, an integrin adhesion molecule along with its activator was expressed in sensory neurons using an adeno-associated viral (AAV) vector. Expression of these adhesion molecules allowed sensory axons to regenerate through the spinal cord injury and all the way back to the brainstem, restoring the sensory pathway. Treated animals regained touch sensation and sensory behaviours.The integrin ligands in the injured spinal cord are tenascin-C and osteopontin, but adult PNS and CNS neurons lack receptors to them. Sensory neurons were transduced with α9 integrin, which combines with endogenous β1 as α9β1 (which is a tenascin/osteopontin receptor) together with the integrin activator kindlin-1. Regeneration from sensory neurons transduced with α9integrin and kindlin-1 was examined after C4 and after T10 dorsal column lesions with C6,7 and L4.5 sensory ganglia injected with AAV1 vectors. In animals treated with α9 integrin and kindlin-1, sensory axons regenerated through tenascin-C-expressing connective tissue strands and bridges across the lesion and then re-entered the CNS tissue.Many axons regenerated rostrally to the level of the medulla. Regenerated axons were particularly visible at the border between white and grey matter in the dorsal cord. Stimulation of the median/sciatic nerve caused many neurons rostral to the injury to activate and express cFos. VGLUT1/2 staining indicated newly formed functional synapses above the lesion. Behavioural recovery was seen in heat, mechanical sensation and tape removal tests. Many axons regenerated from the thoracic lesions to the brainstem, a distance of 4-5 cm, equivalent to the length of 1 or 2 spinal segments in humans.
Evaluating the performance of machine learning methods for risk estimation of delirium in patients hospitalized from the emergency department
Authors: Mueller Brianna , Street W. Nick , Carnahan Ryan M. , Lee Sangil 
Published: March 2023

AbstractIntroductionDelirium is a cerebral dysfunction seen commonly in the acute care setting. It is associated with increased mortality and morbidity and is frequently missed in the emergency department (ED) and inpatient care by clinical gestalt alone. Identifying those at risk of delirium may help prioritize screening and interventions in the hospital setting.ObjectiveOur objective was to leverage electronic health records to identify a clinically valuable risk estimation model for prevalent delirium in patients being transferred from the ED to inpatient units.MethodsThis was a retrospective cohort study to develop and validate a risk model to detect delirium using patient data available from prior visits and ED encounter. Electronic health records were extracted for patients hospitalized from the ED between January 1, 2014, and December 31, 2020. Eligible patients were aged 65 or older, admitted to an inpatient unit from the emergency department, and had at least one DOSS assessment or CAM‐ICU recorded within 72 h of hospitalization. Six machine learning models were developed to estimate the risk of delirium using clinical variables including demographic features, physiological measurements, medications administered, lab results, and diagnoses.ResultsA total of 28,531 patients met the inclusion criteria with 8057 (28.4%) having a positive delirium screening within the outcome observation period. Machine learning models were compared using the area under the receiver operating curve (AUC). The gradient boosted machine achieved the best performance with an AUC of 0.839 (95% CI, 0.837–0.841). At a 90% sensitivity threshold, this model achieved a specificity of 53.5% (95% CI 53.0%–54.0%) a positive predictive value of 43.5% (95% CI 43.2%–43.9%), and a negative predictive value of 93.1% (95% CI 93.1%–93.2%). A random forest model and L1‐penalized logistic regression also demonstrated notable performance with AUCs of 0.837 (95% CI, 0.835–0.838) and 0.831 (95% CI, 0.830–0.833) respectively.ConclusionThis study demonstrated the use of machine learning algorithms to identify a combination of variables that enables an estimation of risk of positive delirium screens early in hospitalization to develop prevention or management protocols.
The limitations of overtime limits to reduce long working hours: Evidence from the 2018 to 2021 working time reform in Korea
Authors: Carcillo Stéphane , Hijzen Alexander , Thewissen Stefan 
Published: March 2023

AbstractThis article provides a first assessment of the causal impact of the 2018–2021 reform in Korea meant to combat its long working‐hour culture. The reform consists of lowering the statutory limit on total weekly working hours from 68 to 52. We apply a difference‐in‐difference approach in which we take advantage of the stepwise implementation of the reform by firm size using individual‐level data. We present three main findings. First, the introduction of the 52‐h limit reduced but far from eliminated the incidence of working more than 52 h. Second, there is some evidence that the introduction led to a reallocation of working hours, with more employees shifting from working fulltime to working overtime within the new limit (41–52 h). Third, and more tentatively, this reallocation more likely took place within firms to account for fewer overtime hours worked by their employees, rather than within households to compensate for any income effects. Overall, our results show that a lower statutory limit can help to lessen a long working‐hour culture, but is an insufficient measure by itself to fully eradicate it.
Impact of pre‐existing type 2 diabetes with and without cardiovascular disease on patients with COVID‐19
Authors: Nguyen Chi , Crowe Christopher L. , Kuti Effie , Narsipur Nihal , Donato Bonnie , Pepe Rebecca S. , Djaraher Rachel , Seman Leo , Graeter Nancy , Power Thomas P. , Mehra Rinku , Willey Vincent J. 
Published: March 2023

AbstractAimTo compare adverse outcomes among COVID‐19 patients with pre‐existing type 2 diabetes (T2D) only, T2D and cardiovascular disease (CVD), or neither.MethodsThis retrospective cohort study used administrative claims, laboratory and mortality data from the HealthCore Integrated Research Database. Patients with COVID‐19 were identified from 3 January 2020 to 31 May 2021 and stratified by the presence of T2D and CVD. Outcomes included hospitalization, intensive care unit (ICU) admission, mortality and complications following COVID‐19 infection. Propensity score matching and multivariable analyses were performed.ResultsA total of 321 232 COVID‐19 patients were identified (21 651 T2D + CVD, 28 184 T2D only, and 271 397 neither) with a mean (SD) follow‐up of 5.4 (3.0) months. After matching, 6 967 patients were identified for each group, and residual baseline differences remained. Adjusted analyses showed that COVID‐19 patients with T2D + CVD were 59% more probable to be hospitalized, 74% more probable to be admitted to the ICU, and had a 26% higher mortality risk than those with neither. COVID‐19 patients with T2D only were 28% and 32% more probable to be admitted to the hospital and ICU than those with neither, respectively. Among all T2D + CVD patients, acute respiratory distress syndrome (31%) and acute kidney disease (24%) were observed.ConclusionOur study highlights the incrementally poorer outcomes associated with pre‐existing T2D + CVD in COVID‐19 patients compared with those without T2D/CVD and suggests consideration of a more optimal management approach in these patients.
On resistance: As evinced in Iranian political affairs
Authors: Shabani Omid P. 
Published: March 2023

AbstractAlong with fundamental rights such as liberty and property, the Declaration of the Rights of Man and of the Citizen in 1789 also envisions a right to resist oppression. Irrespective of one's place on the political spectrum, resistance has been employed as an alternative both to submission and to revolt. After briefly sketching a historical and theoretical account of resistance I propose two parallel sets of criteria to further characterize good resistance. I submit that the first set is normative (I call it emancipatory) and the second set is critical (meaning it can be empirically assessed). I further break this typology down as follows: (1) Resistance is emancipatory when it is (a) nonviolent, (b) progressive, and (c) civil; and (2) it is critical when it seeks to (a) change policies and practices that are unjust, and (b) empower citizens to enjoy their full rights. I show the usefulness of this scheme by applying it to the political situation in Iran and by evincing these criteria in three instances of resistance there. Thus, in this context, I argue, resistance is a preferable alternative to both revolution and reform.
Identification of ultrastructural and biochemical cuticular markers influencing temperature of ice nucleation in selected genotypes of corn
Authors: Hamilton Kaila , Rahman Tawhidur , Sadowski Jason , Karunakaran Chithra , Tanino Karen 
Published: March 2023

AbstractCorn is an economically important yet frost‐sensitive crop, injured at the moment of ice nucleation. However, the influence of autumn temperatures on subsequent ice nucleation temperature is unknown. A 10‐day chilling treatment under phytotron conditions (“mild”, 18/6°C) or (“extreme”, 10/5°C) generated no‐visible damage but induced changes in the cuticle of the four genotypes in this study. The putatively more cold hardy Genotypes 884 and 959 leaves nucleated at colder temperatures compared to the more sensitive Genotypes 675 and 275. After chilling treatment, all four genotypes displayed warmer ice nucleation temperatures, with Genotype 884 expressing the largest shift to warmer nucleation temperatures. Cuticular hydrophobicity reduced while cuticular thickness remained unchanged under the chilling treatment. By contrast, under five‐week field conditions, cuticle thickness increased in all genotypes, with Genotype 256 expressing a significantly thinner cuticle. FTIR spectroscopy revealed increases in the spectral regions of cuticular lipids in all genotypes after phytotron chilling treatment, while those spectral regions decreased under field conditions. A total of 142 molecular compounds were detected, with 28 compounds significantly induced under either phytotron or field conditions. Of these, seven compounds were induced under both conditions (Alkanes C31–C33, Ester C44, C46, β‐amyrin, and triterpene). While clear differential responses were observed, chilling conditions preceding a frost modified physical and biochemical properties of the leaf cuticle under both phytotron and field conditions indicating this response is dynamic and could be a factor in selecting corn genotypes better adapted to avoiding frost with lower ice nucleation temperature.
Review of industry response to an earthquake in a large natural gas field: Raton Basin, Colorado
Authors: Macartney* Hal 
Published: March 2023

ABSTRACT
This chapter is a narrative review of how an oil and gas company responded to an earthquake within their operating area, and it is offered as an example for others who might be contemplating what to do in a similar situation. The chapter describes a process and practical steps that help to manage the operational, regulatory, and other consequences of seismicity potentially attributable to industry activity, and ultimately the possibility of large and damaging earthquakes in the future. The process involved collecting high-quality (and proprietary) data, ongoing monitoring, and collaboration with regulators and science agencies. The outcome in this case was continuation of producing operations and a better understanding of local seismicity. This chapter does not address the seismicity in detail, or its cause, nor what studies found.
121 Viral & bacterial RNA transcripts of substantia nigra and olfactory bulb in parkinson disease
Authors: Kaye Steve , Abbott James , Gentleman Steve , Oertel Wolfgang , McClure Myra , Hawkes Christopher H 
Published: March 2023

IntroductionIt is known that several viral species can induce parkinsonism in animals and humans, but no specific virus has been discovered in the classical human form of PD.MethodsTo investigate this further, we used next generation sequencing (NGS) to analyse post-mortem transcriptomes of substantia nigra (SN) and olfactory bulb (OB) in four PD cases and four multiple sclerosis patients who acted as positive controls. Bioinformatic analysis of the data set removed the majority of human transcripts and the remaining sequence data were compared to existing viral sequence data sets to search for signature viral sequences.ResultsDespite high read numbers and good quality NGS data, no viral or bacterial transcripts could be identified from either of the tissues examined. The few matches to existing viral databases were to viruses which rarely, if ever, infect humans and no multiple hits (matches to more than one gene of the same virus) were observed. Similarly, no bacterial sequences were found although it should be noted the analysis was carried out at the mRNA level.ConclusionThis small but detailed analysis provided no evidence of RNA viral signatures in the OB or SN in the four samples taken from Parkinson’s disease brains. It is still possible that other brain areas known to display Lewy body pathology may contain viral sequences.
132 Does the use of a patient passport improve patient care in MND? A qualitative study
Authors: Abdelgalil Reem , Gaur Akshay , Hewamadduma Channa 
Published: March 2023

BackgroundCare provision for Motor Neurone Disease (MND) patients require a Multidisciplinary Team (MDT) approach. Healthcare Professionals (HCPs) and MND patients often find it challenging to communicate effectively. Communication is particularly difficult and discontinuous in patients with rapidly changing conditions such as MND. Patient Passports (PP) can be used as a tool to improve communication and patient experience. We studied the place of PP in MND care.AimTo explore the views of MND patients and staff involved in MND care regarding the use of PP.MethodsMND patients (n=35) and staff involved in MND care were consulted using semi-structured interviews and focus group discussions.ResultsOverall, themes emerged overwhelmingly favoured the use of a MND passport. These include improvement in communication, standardising healthcare provision across different regions and allowing for greater coordination of care. The emergency care providers and community HCP felt the PP was paramount to communicate with the parent team. However, concern was raised for the need to tailor it to the patient.ConclusionThe PP was recognised as a distinct need. However, to validate the above findings, wider MND patient/carer and HCP survey is necessary.
142 Influence of baseline OFF-time on opicapone efficacy in Parkinson’s disease patients with motor fluctuations
Authors: Korlipara P , Ferreira J , Gama H , Santos A , Ikedo F , Rocha J , Soares-Da-Silva P 
Published: March 2023

BackgroundOpicapone (OPC), a novel once-daily peripheral COMT inhibitor, has shown to be safe and effective in reducing OFF-time in Parkinson’s disease (PD) patients with motor fluctuations.ObjectiveTo evaluate the efficacy of OPC in levodopa-treated PD patients with motor fluctuations and subdivided by their baseline OFF-time.MethodsBIPARK-I was a multinational, multicentre, double-blind, 14–15-week, placebo and active-controlled study to evaluate the efficacy of OPC in PD patients with end-of-dose motor fluctuations. This post-hoc subgroup analysis investigated efficacy of OPC 50 mg and entacapone (ENT), in levodopa-treated PD patients who were subdivided by baseline OFF-time (>90 mins and every additional 30 mins interval up to an interval with minimum sample size of 40 patients per active arm).ResultsSubjects with higher baseline OFF-times had a greater response under both OPC 50 mg and ENT with an average difference of -26.6 mins OFF-time reduction favouring OPC 50 mg. The estimated difference increased with increasing baseline OFF-time, reaching statistically significance (p<0.05) for subjects with >390 mins baseline OFF-time.ConclusionHigher baseline OFF-time correlated with greater response for both OPC 50 mg and ENT. OPC 50 mg presented a greater OFF-time reduction than ENT for all subgroup intervals, reaching statistically significance for subjects with >390 mins baseline OFF-time.
148 Longitudinal resting state changes in parkinson’s disease
Authors: Naidu Saadnah , Xing Lily Yue , Mohammadi-Nejad Ali-Reza , Sotiropoulos Stamatios , Auer Dorothee 
Published: March 2023

IntroductionThere is currently no objective method of monitoring progression of Parkinson’s disease (PD). We demonstrate resting-state magnetic resonance imaging (rs-MRI) as a potential biomarker of PD progression.Methods15 patients with idiopathic PD (age at baseline: mean±std, 66.43±7.16 years; follow-up: 69.46±7.09; Male, 10; H&Y baseline: 1.9±0.63; follow-up: 2.2±1.08) were recruited. Baseline and follow-up visits occurred 3.03± 0.18 years apart (Disease duration baseline: 3.61±1.33; follow-up: 6.64±1.38). (Disease severity: MDS-UPDRS-III baseline 27.17±15.28; follow-up: 35.53±16.45).Image acquisitionrs-MRI was performed using 3T GE 750 MRI; 32-channel head coil; TR=2000ms; TE=30ms; Eyes open, medicated.AnalysisAn in-house optimised standardised pipeline was used based on FSL (1), MRIQC algorithm (2). Functional connectivity (FC) was derived from the following seeds (5 mm radius): primary motor cortex (M1), anterior and posterior putamen, caudate, supplementary motor area (SMA) and substantia nigra (SN). (Coordinates determined using AAL template and FSL atlas). Z score >2.3 used to report significance in a paired t test.ResultsOverall, we found greater FC at baseline vs follow-up in the motor cortex and SN, while FC with the posterior putamen and SMA showed a dissociated pattern of increased and decreased FC changes with disease progression.ConclusionOur preliminary analysis of a longitudinal dataset of >2 years mean duration show promising change patterns in line with progressive motor cortex and SN disconnection and complex putaminal and SMA disconnection.
163 Development of clinical and patient-reported quality metrics for multiple sclerosis: a UK pilot study report
Authors: Giovannoni Gavin , White Sarah , Mistry Niraj , Calhoun Samantha , Young Carolyn , Coutts Mhairi , Roberts Megan , Anderson Philip , Bernstein Rachel , Hobart Jeremy 
Published: March 2023

BackgroundQuality standards (QS) for people with multiple sclerosis (PwMS) are suboptimal, ambiguous and restricted to certain patient subgroups and care pathways.AimDevelop and pilot MS metrics measuring service provision quality to identify areas for improvement.MethodsA multidisciplinary Working Group developed clinician and patient-reported metrics and standardised data collection forms through an iterative process.ResultsMetrics covered: referral; diagnosis; treatment; annual review; general management; education. Pilot (n=76) showed: 31% of PwMS were referred to MS specialist within 4 weeks of suspected/confirmed demyelination; 28% and 56% had uncomplicated MS confirmed and were offered specialist MS nurse appointment, respectively, within 4 weeks of specialist referral; 75% of eligible PwMS were offered disease-modifying therapy within 8 weeks of confirmed MS diagnosis; 85% had comprehensive multidisciplinary team (MDT) annual review; 90% had a defined point of contact within the MS service; 86% of unscheduled contacts by PwMS, MDT or general practitioners were responded to within 3 days; 53% of MS services maintained a single database of PwMS; and 76% of PwMS were offered ongoing education. Data collection continues and updated findings will be reported.DiscussionMS metrics/data forms are feasible for routine clinical settings, simple to interpret and provide a valuable benchmark for guiding MS service improvements.
198 A population study of temporal changes in MS disease modifying drug management and cost
Authors: McCarron Mark , Mullan Fiona , Hinchcliff Carol , McVerry Ferghal 
Published: March 2023

BackgroundMultiple sclerosis (MS) management is changing. The prevalence of MS is increasing. We sought to investigate changes in disease modifying treatment (DMT) rates and costs in a defined population.MethodsAmong a population of 296,000 (Western Health and Social Care Trust) all MS patients taking DMTs were annually recorded including sequential DMT changes over an 11-year period (2008 to 2018 inclusive). Individual patient frequency of DMT switches were recorded. Drug costs were calculated over 10 years.ResultsFrom 2008 until 2018 there was more than a threefold increase in the number of MS patients taking a DMT (113 versus 394, Cochran-Armitage test for trend P<0.0001), representing by 2018 approximately 50% of all MS patients in this population. 216 patients switched drugs ranging from once (N=216) to 5 times (N=6 patients). Drug prices escalated sixfold from £832,351 in 2008 to £5,074,276 in 2018.ConclusionThe increasing use of DMTs suggest that most NHS neurologists should become skilled in managing MS. As DMT coverage continues to increase in the MS population, drug costs should cover the funding of neurology teams to care for DMT-treated MS patients.
11.51 Stiff person and related syndromes: review of 21 patients and their response to treatment
Authors: Thompson Joseph , Sadalage Girija , Karim Abid , Jacob Saiju 
Published: March 2023

IntroductionIn patients with stiff person syndrome (SPS) and related syndromes the objective of treatment is to provide symptomatic relief from stiffness and spasms. Intravenous immunoglobulin (IVIG) therapy is a commonly prescribed treatment for SPS patients, however there is no widely used method of assessing the effectiveness of IVIG treatment in SPS. This issue has been addressed by the introduction of the Birmingham Response to IVIG Treatment (BRIT) scale.MethodsData from 21 patients was retrospectively analysed to explore a number of outcomes including: time to diagnosis, antibody statuses, clinical phenotype, first symptom, distribution of stiffness and EMG changes and treatments received.9/21 patients had pre- and post-IVIG BRIT data, which was analysed using paired t-tests.ResultsAverage time from first presentation to diagnosis was 37 months (range: 1–180 months). Anti-GAD antibody was positive in 18/21 (85.7%) with two glycine positive and one seronegative patient. EMG changes were found in 5/15 (33.3%) of patients.Both functional ability score (p=0.0422) and quality of life score (p=0.0175) improved with statistical significance after receiving IVIG treatment.ConclusionIVIG treatment is effective in improving quality of life and functional ability in SPS patients. Treatment response can be comprehensively measured using the BRIT scale.