Miracle-dz/UniFAR-FTUs huggingface dataset:
Computer-based three-dimensional measurement of carpal alignment: measurement techniques and normal ranges

The three-dimensional carpal alignment was measured in the neutral wrist position in 121 asymptomatic volunteers using computer-based cone-beam CT analysis. Normal values and the reliability of the automated analysis are reported. An analysis software based on segmentation of CT images and mathematical modelling was used to determine several axis variants based on different landmarks and to calculate the intercarpal angles automatically. Twenty wrists were imaged twice to determine intra-observer reliability. Mean values using the preferred axis variants were: scapholunate angle 57° (SD 9°), radiolunate angle 2° (SD 10°), lunocapitate angle –14° (SD 9°). Using alternate axis variants notably changed the angles produced. The intra-observer reliability of the analysis was excellent (mean intraclass correlation coefficient 0.97, SD 0.03). Computer-based CT analysis enables highly reproducible and automated assessment of carpal alignment. This study provides a reference database for measurement techniques and normal carpal angle values in three-dimensional imaging.
Inferring the dynamic of mutated hematopoietic stem and progenitor cells induced by IFNα in myeloproliferative neoplasms.

Classical BCR-ABL-negative myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic stem cells (HSC) caused mainly by recurrent mutations in genes encoding JAK2 (JAK2), calreticulin (CALR), or the thrombopoietin receptor (MPL). Interferon alpha (IFNα) has demonstrated some efficacy in inducing molecular remission in MPN. In order to determine factors that influence molecular response rate, we evaluated the long-term molecular efficacy of IFNα in MPN patients by monitoring the fate of cells carrying driver mutations in a prospective observational and longitudinal study of 48 patients over more than 5 years. We measured several times per year the clonal architecture of early and late hematopoietic progenitors (84,845 measurements) and the global variant allele frequency in mature cells (409 measurements). Using mathematical modeling and hierarchical Bayesian inference, we further inferred the dynamics of IFNα-targeted mutated HSC. Our data support the hypothesis that IFNα targets JAK2V617F HSC by inducing their exit from quiescence and differentiation into progenitors. Our observations indicate that treatment efficacy is higher in homozygous than heterozygous JAK2V617F HSC and increases with high IFNα dosage in heterozygous JAK2V617F HSC. Besides, we found that the molecular responses of CALRm HSC to IFNα were heterogeneous, varying between type 1 and type 2 CALRm, and high dosage of IFNα correlates with worse outcomes. Together, our work indicates that the long-term molecular efficacy of IFNα implies an HSC exhaustion mechanism and depends on both the driver mutation type and IFNα dosage.
Are rib fractures stable? An analysis of progressive rib fracture offset in the acute trauma setting

BACKGROUND Rib fractures serve as both a marker of injury severity and a guide for clinical decision making for trauma patients. Although recent studies have suggested that rib fractures are dynamic, the degree of progressive offset remains unknown. The purpose of this study was to further characterize the change that takes place in the acute trauma setting. METHODS A 4-year (2016–2019) retrospective assessment of adult trauma patients with rib fracture(s) admitted to a level I trauma center was performed. Initial and follow-up computed tomography scans were analyzed to determine the magnitude of offset. Relevant clinical course variables were examined, and location of chest wall instability was examined using the difference of interquartile range of median change. Statistical Product and Services Solutions (Version 25, IBM Corp. Armonk, NY) was then used to generate a neural network—multilayer perceptron that highlighted independent variable importance. RESULTS Fifty-three patients met the inclusion criteria for severe injury. Clinical course variables that either trended or significantly predicted the occurrence of progressive offset were Abbreviated Injury Scale Thoracic Scores (3.1 ± 0.4 no progression vs. 3.4 ± 0.6 yes progression; p = 0.121), flail segment (14% no progression vs. 43% yes progression; p = 0.053), and number of ribs fractured (4 [2–8] no progression vs. 7 [5–9] yes progression; p = 0.023). The location of progressive offset largely corresponded to the posterolateral region as demonstrated by the differences of interquartile range of median change. The neural network demonstrated that ribs 4 to 6 (normalized importance [NI], 100%), the posterolateral region (NI, 87.9%), and multiple fractures per rib (NI, 66.6%) were valuable in predicting whether progressive offset occurred (receiver operating characteristic curve − area under the curve = 0.869). CONCLUSION Rib fractures are not stable, particularly for those patients with multiple fractures in the mid-to-upper ribs localized to the posterolateral region. These findings may identify both trauma patients with worse outcomes and help develop better management strategies for rib fractures. LEVEL OF EVIDENCE Prognostic and epidemiological, level III.
The impact of prehospital time intervals on mortality in moderately and severely injured patients

Supplemental digital content is available in the text. BACKGROUND Modern trauma systems and emergency medical services aim to reduce prehospital time intervals to achieve optimal outcomes. However, current literature remains inconclusive on the relationship between time to definitive treatment and mortality. The aim of this study was to investigate the association between prehospital time and mortality. METHODS All moderately and severely injured trauma patients (i.e., patients with an Injury Severity Score of 9 or greater) who were transported from the scene of injury to a trauma center by ground ambulances of the participating emergency medical services between 2015 and 2017 were included. Exposures of interest were total prehospital time, on-scene time, and transport time. Outcomes were 24-hour and 30-day mortality. Generalized linear models including inverse probability weights for several potential confounders were constructed. A generalized additive model was constructed to enable visual inspection of the association. RESULTS We included 22,525 moderately and severely injured patients. Twenty-four-hour and 30-day mortality were 1.3% and 7.3%, respectively. On-scene time per minute was significantly associated with 24-hour (relative risk [RR], 1.029; 95% confidence interval, 1.018–1.040) and 30-day mortality (RR, 1.013; 1.008–1.017). We found that this association was also present in patients with severe injuries, traumatic brain injury, severe abdominal injury, and stab or gunshot wound. An on-scene time of 20 minutes or longer demonstrated a strong association with 24-hour (RR, 1.797; 1.406–2.296) and 30-day mortality (RR, 1.298; 1.180–1.428). Total prehospital (24-hour: RR, 0.998; 0.990–1.007; 30-day: RR, 1.000, 0.997–1.004) and transport (24-hour: RR, 0.996; 0.982–1.010; 30-day: RR, 0.995; 0.989–1.001) time were not associated with mortality. CONCLUSION A prolonged on-scene time is associated with mortality in moderately and severely injured patients, which suggests that a reduced on-scene time may be favorable for these patients. In addition, transport time was found not to be associated with mortality. LEVEL OF EVIDENCE Prognostic and Epidemiologic; level III.
Vestibular Function in Children with Type 1 Diabetes: Videonystagmography Testing

Background: Vestibular system is critical for maintaining balance and learning complex tasks. This study aimed to determine the frequencies, types, and predictors of vestibular dysfunctions (VDs) in children with type 1 diabetes (T1D) using videonystagmography (VNG). Patients and Methods: This study included 65 patients (children with T1D = 40; controls = 25). The patients underwent VNG. Results: Patients (boys = 15; girls = 25) had a mean age of 14.05 ± 1.82 years and duration of illness of 6.30 ± 2.84 years. The majority had frequent attacks of diabetic ketoacidosis (DKA) (65%) and hypoglycemia (40%). Dizziness was reported in 20%. VNG abnormalities were reported in 70% (n = 28), of them 71.43 and 28.57% had central and peripheral VDs, respectively. Dizziness was associated with peripheral VD. Compared to patients without VDs, those with VDs were older and had earlier age at onset and longer duration of diabetes (>5 years), higher levels of HbA1c (>7%), higher frequencies of DKA and hypoglycemic attacks, comorbid medical conditions, and diabetic complications. Multiple logistic regression analysis showed that presence of VNG abnormalities (VDs) was independently correlated with diabetes duration >5 years (odds ratio [OR] = 4.52 [95% confidence interval [CI] = 3.55–7.04], p = 0.001), HbA1c% levels >7% (OR = 3.42 [95% CI = 2.84–5.75], p = 0.001), and presence of hypoglycemic attacks (OR = 4.65 [95% CI = 2.85–7.55]). Conclusions: -VDs are prevalent in children with T1D and correlated with the duration and severity of diabetes and the occurrence of hypoglycemic attacks. Therefore, optimizing glycemic control and prevention and treatment of diabetic complications and comorbidities are important. Multidisciplinary follow-ups are required for early detection and management of diabetic VDs.
Continuous Glucose Monitoring in the Management of Neonates With Persistent Hypoglycemia and Congenital Hyperinsulinism

Abstract Background Persistent hypoglycemia is common in the newborn and is associated with poor neurodevelopmental outcome. Adequate monitoring is critical in prevention, but is dependent on frequent, often hourly blood sampling. Continuous glucose monitoring (CGM) is increasingly being used in children with type 1 diabetes mellitus, but use in neonatology remains limited. We aimed to introduce real-time CGM to provide insights into patterns of dysglycemia and to support the management of persistent neonatal hypoglycemia. Methods This is a single-center retrospective study of real-time CGM use over a 4-year period in babies with persistent hypoglycemia. Results CGMs were inserted in 14 babies: 8 term and 6 preterm infants, 9 with evidence of congenital hyperinsulinism (CHI). A total of 224 days of data was collected demonstrating marked fluctuations in glucose levels in babies with CHI, with a higher sensor glucose SD (1.52 ± 0.79 mmol/L vs 0.77 ± 0.22 mmol/L) in infants with CHI compared with preterm infants. A total of 1254 paired glucose values (CGM and blood) were compared and gave a mean absolute relative difference of 11%. Conclusion CGM highlighted the challenges of preventing hypoglycemia in these babies when using intermittent blood glucose levels alone, and the potential application of CGM as an adjunct to clinical care.
Review of CFTR modulators 2020

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are small molecules that directly impact the CFTR protein, improving the function of the CFTR chloride and bicarbonate channel. Beginning in 2012 with the Food and Drug Administration approval of the first CFTR modulator, ivacaftor, this class of medications has had largely positive effects on many outcomes in people with cystic fibrosis (PwCF), including lung function, growth, and other clinical parameters. There have been continued exciting developments in the current research on CFTR modulators, expanding beyond original studies. This first part of a three‐part cystic fibrosis (CF) year in review 2020 will focus on research on CFTR modulators. In addition to reviewing new clinical insights, we describe work done on novel outcomes, adverse effects, issues related to cost, and next steps for clinical trials. The review focuses on articles from Pediatric Pulmonology published in 2020, but it includes articles from other journals that are of particular interest to clinicians. New developments in CF research continue to be brought forth to the CF community, deepening the understanding of this disease and improving clinical care.
Pregnancy in women with multiple sclerosis in France from 2010 to 2015: Incidence, outcomes, and exposure to disease-modifying therapies

Background: Multiple sclerosis (MS) is usually diagnosed between 20-40 years old, when women often plan to have children. Objective: Our objectives were to estimate pregnancy incidence rates in women with multiple sclerosis (MS), and to describe the use of disease-modifying therapies (DMTs) before conception and during pregnancy, and pregnancy outcomes. Methods: This retrospective cohort study included all 15- to 49-year-old women with MS in the French national health insurance database over 2010–2015. A pregnancy was exposed if a DMT reimbursement claim occurred during pregnancy or in the 14 preceding days. We used zero-inflated negative binomial (ZINB) regression models to estimate incidence rates and ordinal and multinomial regression models to estimate DMT exposure and pregnancy outcomes. Results: The pregnancy incidence rate was 4.5 per 100 person-years. The probability of having a DMT-exposed pregnancy increased from 0.22 in 2010 to 0.30 in 2015. The probability of live birth was 0.72 (95% CI = 0.70–0.74) for exposed pregnancies (varied considerably among DMTs), 0.77 (95% CI = 0.76–0.79) without treatment, and 0.81 (95% CI = 0.79–0.83) if treatment was stopped within the previous year. Conclusion: In this population-based study, we showed an increase of exposed pregnancies over time, beta-interferon and glatiramer acetate being the most used DMTs and associated with the highest probabilities of live birth. Interrupted exposed pregnancies may reflect undesired pregnancies or fear of an adverse outcome, while recent DMT stop probably reflects pregnancy planning.
Reducing vitamin test ordering in primary care; the effectiveness of professional and patient oriented strategies in a Cluster randomized Intervention Study

Background: Vitamin tests are increasingly ordered by GPs, but a clinical and evidence based indication is often lacking. Harnessing technology, i.e. decision support tools and redesigning request forms, have been shown to reduce vitamin D requests. Aim: Could the number of vitamin tests also be reduced by providing a multi-level intervention program based on training, monitoring and feedback? Design & Setting: In a Cluster Randomized Intervention Study performed in 26 primary care health-centres (200.000 patients) the relative reduction in ordered vitamin D and B12 tests was determined after introduction of two de-implementation strategies (may 2017-may 2018). Method: Health-centers randomized to de-implementation strategy 1 received education and 3-monthly benchmarking of their own vitamin test ordering behavior. Health-centers in deimplementation strategy 2 received the same education and benchmarking but supplemented with educational material for patients. Results: The number of vitamin D tests decreased 23% compared to the one-year preintervention period. For vitamin B12 tests an overall reduction of 20% was found. Provision of patient educational information showed additional value over training and benchmarking of GPs alone, but only for vitamin D test ordering (10% extra reduction, OR 0.88, 95%CI 0.830.92, compared to 4% extra reduction for vitamin B12, OR 0.96, 95%CI 0.91-1.02). Nationwide, this would result in over € 3.200.000 saving on healthcare expenditure per year. Conclusion: A structured intervention program, including training and benchmarking of GPs regarding their diagnostic test ordering resulted in a significant reduction in ordered vitamin tests. Additional information provision to patients resulted in a small but still relevant additional reduction. If implemented on a national level, a substantial cost saving can be achieved.
A hidden Markov model reliably characterizes ketamine-induced spectral dynamics in macaque local field potentials and human electroencephalograms

Ketamine is an NMDA receptor antagonist commonly used to maintain general anesthesia. At anesthetic doses, ketamine causes high power gamma (25-50 Hz) oscillations alternating with slow-delta (0.1-4 Hz) oscillations. These dynamics are readily observed in local field potentials (LFPs) of non-human primates (NHPs) and electroencephalogram (EEG) recordings from human subjects. However, a detailed statistical analysis of these dynamics has not been reported. We characterize ketamine’s neural dynamics using a hidden Markov model (HMM). The HMM observations are sequences of spectral power in seven canonical frequency bands between 0 to 50 Hz, where power is averaged within each band and scaled between 0 and 1. We model the observations as realizations of multivariate beta probability distributions that depend on a discrete-valued latent state process whose state transitions obey Markov dynamics. Using an expectation-maximization algorithm, we fit this beta-HMM to LFP recordings from 2 NHPs, and separately, to EEG recordings from 9 human subjects who received anesthetic doses of ketamine. Our beta-HMM framework provides a useful tool for experimental data analysis. Together, the estimated beta-HMM parameters and optimal state trajectory revealed an alternating pattern of states characterized primarily by gamma and slow-delta activities. The mean duration of the gamma activity was 2.2s([1.7,2.8]s) and 1.2s([0.9,1.5]s) for the two NHPs, and 2.5s([1.7,3.6]s) for the human subjects. The mean duration of the slow-delta activity was 1.6s([1.2,2.0]s) and 1.0s([0.8,1.2]s) for the two NHPs, and 1.8s([1.3,2.4]s) for the human subjects. Our characterizations of the alternating gamma slow-delta activities revealed five sub-states that show regular sequential transitions. These quantitative insights can inform the development of rhythm-generating neuronal circuit models that give mechanistic insights into this phenomenon and how ketamine produces altered states of arousal.
Intakes of Fish and Long-Chain n-3 Polyunsaturated Fatty Acid Supplements During Pregnancy and Subsequent Risk of Type 2 Diabetes in a Large Prospective Cohort Study of Norwegian Women

OBJECTIVE To investigate associations between intakes of total fish, lean fish, fatty fish, and long-chain n-3 polyunsaturated fatty acid (LCn-3PUFA) supplements and risk of type 2 diabetes in women after pregnancy. Furthermore, we sought to compare the estimated intakes of methylmercury (MeHg) and sum of dioxins and dioxin-like polychlorinated biphenyls (dl-PCBs) with tolerable weekly intakes (TWI). RESEARCH DESIGN AND METHODS Women free of diabetes at baseline (n = 60,831) who participated in the population-based Norwegian Mother, Father and Child Cohort Study (MoBa) were prospectively evaluated for incident type 2 diabetes, identified on the basis of medication usage >90 days after delivery, ascertained through the Norwegian Prescription Database. Dietary intake data were obtained with a validated 255-item food-frequency questionnaire (FFQ), which assessed habitual diet during the first 4–5 months of pregnancy. Intakes of MeHg and sum of dioxins and dl-PCBs were derived with use of a contaminant database and the FFQ. RESULTS Median age was 31 years (interquartile range 27, 34) at time of delivery, and follow-up time was 7.5 years (6.5, 8.5). Type 2 diabetes occurred in 683 (1.1%) participants. Multivariable Cox regression analyses identified lower risk of type 2 diabetes with increasing energy-adjusted lean fish intake (25 g/1,000 kcal: hazard ratio 0.71, 95% CI 0.53–0.95, P = 0.022). However, in stratified analyses, a lower risk was found only in women with prepregnancy BMI ≥25 kg/m2. There were no associations between intake of total fish, fatty fish, or LCn-3PUFA supplements and type 2 diabetes. MeHg intake was low, but the intake of the sum of dioxins and dl-PCBs (picograms of toxic equivalents/kilograms of body weight/week) exceeded the TWI set by the European Food Safety Authority (EFSA) for the majority of participants. CONCLUSIONS Intake of lean fish, but not fatty fish or LCn-3PUFA supplements, was associated with lower risk of pharmacologically treated type 2 diabetes in Norwegian women who were overweight or obese. Fatty fish, which contain dioxins and dl-PCBs, did not increase the risk of type 2 diabetes, but the exceedance of the EFSA TWI for dioxins and dl-PCBs is a health concern.
COVID‐19 and the impact of arterial hypertension—An analysis of the international HOPE COVID‐19 Registry (Italy‐Spain‐Germany)

A systematic analysis of concomitant arterial hypertension in COVID‐19 patients and the impact of angiotensin‐converting‐enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) have not been studied in a large multicentre cohort yet. We conducted a subanalysis from the international HOPE Registry (https://hopeprojectmd.com, NCT04334291) comparing COVID‐19 in presence and absence of arterial hypertension.
White matter degeneration revealed by fiber‐specific analysis relates to recovery of hand function after stroke

Recent developments of higher‐order diffusion‐weighted imaging models have enabled the estimation of specific white matter fiber populations within a voxel, addressing limitations of traditional imaging markers of white matter integrity. We applied fixel based analysis (FBA) to investigate the evolution of fiber‐specific white matter changes in a prospective study of stroke patients and upper limb motor deficit over 1 year after stroke. We studied differences in fiber density and macrostructural changes in fiber cross‐section. Motor function was assessed by grip strength. We conducted a whole‐brain analysis of fixel metrics and predefined corticospinal tract (CST) region of interest in relation to changes in motor functions. In 30 stroke patients (mean age 62.3 years, SD ±16.9; median NIHSS 4, IQR 2–5), whole‐brain FBA revealed progressing loss of fiber density and cross‐section in the ipsilesional corticospinal tract and long‐range fiber tracts such as the superior longitudinal fascicle and trans‐callosal tracts extending towards contralesional white matter tracts. Lower FBA metrics measured at the brainstem section of the CST 1 month after stroke were significantly associated with lower grip strength 3 months (p = .009, adjusted R2 = 0.259) and 1 year (T4: p < .001, adj. R2 = 0.515) after stroke. Compared to FA, FBA metrics showed a comparably strong association with grip strength at later time points. Using FBA, we demonstrate progressive fiber‐specific white matter loss after stroke and association with functional motor outcome. Our results promote the application of fiber‐specific analysis to detect secondary neurodegeneration after stroke in relation to clinical recovery.
Red/far-red light signals regulate the activity of the carbon-concentrating mechanism in cyanobacteria

Red/far-red light signals regulate the cyanobacterial CO2-concentrating mechanism by activating/inactivating bicarbonate uptake. Desiccation-tolerant cyanobacteria can survive frequent hydration/dehydration cycles likely affecting inorganic carbon (Ci) levels. It was recently shown that red/far-red light serves as signal-preparing cells toward dehydration. Here, the effects of desiccation on Ci assimilation by Leptolyngbya ohadii isolated from Israel’s Negev desert were investigated. Metabolomic investigations indicated a decline in ribulose-1,5-bisphosphate carboxylase/oxygenase carboxylation activity, and this was accelerated by far-red light. Far-red light negatively affected the Ci affinity of L. ohadii during desiccation and in liquid cultures. Similar effects were evident in the non–desiccation-tolerant cyanobacterium Synechocystis. The Synechocystis Δcph1 mutant lacking the major phytochrome exhibited reduced photosynthetic Ci affinity when exposed to far-red light, whereas the mutant ΔsbtB lacking a Ci uptake inhibitory protein lost the far-red light inhibition. Collectively, these results suggest that red/far-red light perception likely via phytochromes regulates Ci uptake by cyanobacteria and that this mechanism contributes to desiccation tolerance in strains such as L. ohadii.