Miracle-dz/UniFAR-FTUs huggingface dataset:
Full-Endoscopic Lumbar Discectomy vs Standard Discectomy: A Noninferiority Study on Clinically Relevant Changes

Background Surgery for lumbar disc herniation (LDH) has had a remarkable technological development during the past 20 years. Microscopic discectomy has traditionally been the gold standard method to treat symptomatic LDH before the introduction of full-endoscopic lumbar discectomy (FELD). The FELD procedure allows unsurpassed magnification and visualization and is currently the most minimally invasive surgical technique. In this study, FELD was compared with standard surgery for LDH, with a focus on medically relevant changes in patient-reported outcome measures (PROMs). Purpose The purpose of this study was to investigate whether FELD is noninferior to other surgical methods for LDH surgery in the most common PROMs, including postoperative leg pain and disability, while still reaching the necessary thresholds for relevant clinical and medical improvements. Methods Patients undergoing a FELD procedure at the Sahlgrenska University Hospital, Gothenburg, Sweden, between 2013 to 2018 were included. A total of 80 (41 men and 39 women) patients were enrolled. The FELD patients were matched 1:5 to controls from the Swedish spine register (Swespine) who had a standard microscopic or mini-open discectomy surgery. PROMs, including the Oswestry Disability Index (ODI) and the Numerical Rating Scale (NRS), as well as the patient acceptable symptom states (PASS) and the minimal important change (MIC), were used to compare the efficacy of the 2 surgical approaches. Results The FELD group achieved medically relevant and significant improvements noninferior to standard surgery within the predefined thresholds of MIC and PASS. No differences could be found in disability measured by ODI FELD −28.4 (SD 19.2) vs standard surgery −28.7 (SD 18.9) or leg pain NRSLeg FELD −4.35 (SD 2.93) vs standard surgery −4.99 (SD 3.12). All intragroup score changes were significant. Conclusions The FELD results are not inferior to standard surgery 1 year postoperatively after LDH surgery. There were no medically significant differences regarding MIC achieved or final PASS in any of the measured PROMs, including leg pain, back pain, or disability (ODI) between the surgical methods. Clinical Relevance The present study highlights that FELD is noninferior to standard surgery in clinically relevant PROMs. Level of Evidence 2.
When do discretized data have a good behavior in functional nonparametric regression

In the context of nonparametric regression, we study condi- tions under which the consistency (and rates of convergence) of estimators built from discretely sampled curves can be derived from the consistency of estimators based on the unobserved whole trajectories. As a consequence, we derive asymptotic results for most of the regularization techniques used in functional data analysis, including smoothing and basis representation.
Trends in Endoscopic and Microscopic Approaches to Transsphenoidal Pituitary Surgery in the US

Among the transsphenoidal (TSS) approaches to pituitary tumors, the microscopic approach (MA) has historically been the predominant technique with the increasing adoption of the endoscopic approach (EA). This study investigates national trends in TSS approaches and postoperative outcomes for MA and EA through 2021.
Autonomous IL-36R signaling in neutrophils activates potent antitumor effector functions

While the rapid advancement of immunotherapies has revolutionized cancer treatment, only a small fraction of patients derive clinical benefit. Eradication of large, established tumors appears to depend on engaging and activating both innate and adaptive immune system components to mount a rigorous and comprehensive immune response. Identifying such agents is a high unmet medical need, because they are sparse in the therapeutic landscape of cancer treatment. Here, we report that IL-36 cytokine can engage both innate and adaptive immunity to remodel an immune-suppressive tumor microenvironment (TME) and mediate potent antitumor immune responses via signaling in host hematopoietic cells. Mechanistically, IL-36 signaling modulates neutrophils in a cell-intrinsic manner to greatly enhance not only their ability to directly kill tumor cells but also promote T and NK cell responses. Thus, while poor prognostic outcomes are typically associated with neutrophil enrichment in the TME, our results highlight the pleiotropic effects of IL-36 and its therapeutic potential to modify tumor-infiltrating neutrophils into potent effector cells and engage both the innate and adaptive immune system to achieve durable antitumor responses in solid tumors.
Sex differences in the psychometric properties of the Center for Epidemiological Studies–Depression (CES-D) Scale in older Filipinos

The literature has yet to fully account for sex differences in the symptomatology and measurement of depressive symptoms, especially in developing settings like the Philippines. Thus, we established the factor structure and assessed the reliability of the 11-item version of the Center for Epidemiological Studies–Depression (CES-D) Scale for assessing depressive symptoms in older Filipino men and women. Using cross-sectional data from 5,209 community-dwelling Filipinos aged 60 and above from a nationally representative survey, Confirmatory Factor Analysis (CFA) and methods in Item Response Theory (IRT) were applied to provide complementary insights into the properties of the scale and its individual items. CFA supported the multidimensionality of the scale. The scale is also sex-invariant, but the relationship between the subfactors and the higher-order factor may differ between men and women. In addition, findings from IRT analysis confirmed the overall utility of the CES-D scale, but positively stated items were found to be internally inconsistent with the rest of the scale. The scale is desirably informative for assessing more severe symptoms, although sex differences were found in the precision of individual items. In general, the 11-item CES-D Scale is an adequate multidimensional tool for assessing moderate to severe depressive symptoms in the older population, especially in older men.
Moisture and Precipitation Evolution during Tropical Cyclone Formation as Revealed by the SSM/I–SSMIS Retrievals

AbstractThe simultaneous precipitation and column water vapor retrievals from the SSM/I and SSMIS passive microwave instruments were used to examine the convective and moisture evolution during tropical cyclone formation. Using a wave-pouch-track dataset, composites of precipitation and column water vapor were constructed with more than 2000 satellite overpasses for a 3-day time period prior to genesis. It was found that high column water vapor occurs near the pouch center and starts to increase about 42 h prior to genesis while a substantial increase in precipitation occurs within 24 h prior to genesis. These features are consistent with a recently proposed two-stage conceptual model for tropical cyclone formation, in which gradual moisture preconditioning precedes an abrupt transition to sustained deep convection leading up to genesis.The relationship between precipitation and saturation fraction (SF) is examined for the developing waves and compared with the general tropical North Atlantic. Precipitati.
Invasive meningococcal disease epidemiology and vaccination strategies in four Southern European countries: a review of the available data

ABSTRACT Introduction Invasive meningococcal disease (IMD) is a major health concern which can be prevented through vaccination. Conjugate vaccines against serogroups A, C, W, and Y and two protein-based vaccines against serogroup B are currently available in the European Union. Areas covered We present epidemiologic data for Italy, Portugal, Greece, and Spain using publicly available reports from national reference laboratories and national or regional immunization programs (1999–2019), aiming to confirm risk groups, and describe time trends in overall incidence and serogroup distribution, as well as impact of immunization. Analysis of circulating MenB isolates in terms of the surface factor H binding protein (fHbp) using PubMLST is discussed as fHbp represents an important MenB vaccine antigen. Predictions of potential reactivity of the two available MenB vaccines (MenB-fHbp and 4CMenB) with circulating MenB isolates are also provided as assessed using the recently developed MenDeVAR tool. Expert opinion Understanding dynamics of IMD and continued genomic surveillance are essential for evaluating vaccine effectiveness, but also prompting proactive immunization programs to prevent future outbreaks. Importantly, the successful design of further effective meningococcal vaccines to fight IMD relies on considering the unpredictable epidemiology of the disease and combining lessons learnt from capsule polysaccharide vaccines and protein-based vaccines.
Real Hypersurfaces in Complex Two-plane Grassmannians with Reeb Parallel Ricci Tensor in the GTW Connection

Abstract There are several kinds of classification problems for real hypersurfaces in complex two-plane Grassmannians ${{G}_{2}}\left( {{\mathbb{C}}^{m+2}} \right)$ . Among them, Suh classified Hopf hypersurfaces in ${{G}_{2}}\left( {{\mathbb{C}}^{m+2}} \right)$ with Reeb parallel Ricci tensor in Levi–Civita connection. In this paper, we introduce the notion of generalized Tanaka–Webster $\left( \text{GTW} \right)$ Reeb parallel Ricci tensor for Hopf hypersurfaces in ${{G}_{2}}\left( {{\mathbb{C}}^{m+2}} \right)$ . Next, we give a complete classification of Hopf hypersurfaces in ${{G}_{2}}\left( {{\mathbb{C}}^{m+2}} \right)$ with $\text{GTW}$ Reeb parallel Ricci tensor.
Fulminant echovirus 11 hepatitis in male non-identical twins in northern Italy, April 2023

Echovirus 11 (E11) has recently been associated with a series of nine neonatal cases of severe hepatitis in France. Here, we present severe hepatitis caused by E11 in a pair of twins. In one of the neonates, the clinical picture evolved to fulminant hepatitis. The E11 genome showed 99% nucleotide identity with E11 strains reported in the cases in France. Rapid genome characterisation using next generation sequencing is essential to identify new and more pathogenetic variants.
Comprehensive functional characterization of SGCB coding variants predicts pathogenicity in limb-girdle muscular dystrophy type R4/2E

Genetic testing is essential for patients with a suspected hereditary myopathy. More than 50% of patients clinically diagnosed with a myopathy carry a variant of unknown significance in a myopathy gene, often leaving them without a genetic diagnosis. Limb-girdle muscular dystrophy (LGMD) type R4/2E is caused by mutations in β-sarcoglycan (SGCB). Together, β-, α-, γ-, and δ-sarcoglycan form a 4-protein transmembrane complex (SGC) that localizes to the sarcolemma. Biallelic loss-of-function mutations in any subunit can lead to LGMD. To provide functional evidence for the pathogenicity of missense variants, we performed deep mutational scanning of SGCB and assessed SGC cell surface localization for all 6,340 possible amino acid changes. Variant functional scores were bimodally distributed and perfectly predicted pathogenicity of known variants. Variants with less severe functional scores more often appeared in patients with slower disease progression, implying a relationship between variant function and disease severity. Amino acid positions intolerant to variation mapped to points of predicted SGC interactions, validated in silico structural models, and enabled accurate prediction of pathogenic variants in other SGC genes. These results will be useful for clinical interpretation of SGCB variants and improving diagnosis of LGMD; we hope they enable wider use of potentially life-saving gene therapy.
Sodium bicarbonate treatment for QRS widening in bupropion overdoses

Abstract Introduction Bupropion cardiotoxicity widens QRS complexes by inhibiting cardiac gap junctions. Sodium bicarbonate is the standard treatment for QRS widening from sodium channel blockade, but its effect on QRS widening in bupropion cardiotoxicity is not well-studied. Methods This is a retrospective cohort study of bupropion overdoses from 10 hospitals between January 2010 and June 2022. Patients with documented administration of sodium bicarbonate and QRS duration > 100 milliseconds on pre-bicarbonate electrocardiogram were included. Patients with no electrocardiogram within four hours of treatment or with baseline pre-overdose wide QRS and < 10 milliseconds widening from baseline were excluded. The primary outcome was a change in QRS duration between the pre-bicarbonate electrocardiogram and the first electrocardiogram after initial bicarbonate administration. Secondary outcomes included prevalence of post-bicarbonate QRS < 100 milliseconds, change in electrocardiogram intervals after total bicarbonate administration, and change in metabolic parameters and hemodynamics. Wilcoxon signed-rank testing was performed on the primary outcome. Linear regression modeling was performed to test for an association between change in QRS and bicarbonate dosing. Results Thirteen patients were included for final analysis. The median age was 32 years, and 54% were male. Six patients developed seizures; one developed ventricular tachycardia, and four received vasopressors. The median QRS and QTc pre-bicarbonate were 116 and 495 milliseconds, respectively. The median change in QRS duration was −2.0 milliseconds, which was not statistically significant (P = 0.42). The median bicarbonate dose administered before the first post-bicarbonate electrocardiogram was 100 milliequivalents. We did not identify an association between QRS change and bicarbonate dosing (P = 0.9, R-squared = 0.001). No patient had a QRS duration < 100 milliseconds after the initial bicarbonate dose. There was minimal change in QTc, electrolytes, heart rate, or blood pressure; alkalemia post-bicarbonate was achieved in eight patients. Conclusion Sodium bicarbonate did not significantly decrease QRS duration in this small retrospective cohort of bupropion overdoses.
Functional Degeneracy in Paracoccus denitrificans Pd1222 Is Coordinated via RamB, Which Links Expression of the Glyoxylate Cycle to Activity of the Ethylmalonyl-CoA Pathway

Carbon metabolism provides organisms with energy and building blocks for cellular functions and growth. The tight regulation between degradation and assimilation of carbon substrates is central for optimal growth. ABSTRACT Metabolic degeneracy describes the phenomenon that cells can use one substrate through different metabolic routes, while metabolic plasticity, refers to the ability of an organism to dynamically rewire its metabolism in response to changing physiological needs. A prime example for both phenomena is the dynamic switch between two alternative and seemingly degenerate acetyl-CoA assimilation routes in the alphaproteobacterium Paracoccus denitrificans Pd1222: the ethylmalonyl-CoA pathway (EMCP) and the glyoxylate cycle (GC). The EMCP and the GC each tightly control the balance between catabolism and anabolism by shifting flux away from the oxidation of acetyl-CoA in the tricarboxylic acid (TCA) cycle toward biomass formation. However, the simultaneous presence of both the EMCP and GC in P. denitrificans Pd1222 raises the question of how this apparent functional degeneracy is globally coordinated during growth. Here, we show that RamB, a transcription factor of the ScfR family, controls expression of the GC in P. denitrificans Pd1222. Combining genetic, molecular biological and biochemical approaches, we identify the binding motif of RamB and demonstrate that CoA-thioester intermediates of the EMCP directly bind to the protein. Overall, our study shows that the EMCP and the GC are metabolically and genetically linked with each other, demonstrating a thus far undescribed bacterial strategy to achieve metabolic plasticity, in which one seemingly degenerate metabolic pathway directly drives expression of the other. IMPORTANCE Carbon metabolism provides organisms with energy and building blocks for cellular functions and growth. The tight regulation between degradation and assimilation of carbon substrates is central for optimal growth. Understanding the underlying mechanisms of metabolic control in bacteria is of importance for applications in health (e.g., targeting of metabolic pathways with new antibiotics, development of resistances) and biotechnology (e.g., metabolic engineering, introduction of new-to-nature pathways). In this study, we use the alphaproteobacterium P. denitrificans as model organism to study functional degeneracy, a well-known phenomenon of bacteria to use the same carbon source through two different (competing) metabolic routes. We demonstrate that two seemingly degenerate central carbon metabolic pathways are metabolically and genetically linked with each other, which allows the organism to control the switch between them in a coordinated manner during growth. Our study elucidates the molecular basis of metabolic plasticity in central carbon metabolism, which improves our understanding of how bacterial metabolism is able to partition fluxes between anabolism and catabolism.
Prediction of local recurrence in tenosynovial giant cell tumor of the knee: Based on preoperative MRI evaluation into disease subtypes and severity

Objective Tenosynovial giant cell tumors (TSGCTs) of the knee differ in their clinical outcome according to disease subtypes and severity. The aim of this study was to determine the predictive MRI features related to local recurrence in TSGCT of the knee regarding disease subtypes and severity. Methods This retrospective study included 20 patients with pathology-proven TSGCT of the knee who underwent preoperative MRI and surgery from Jan. 2007 to Jan. 2022. The anatomical point of the lesion was determined with a knee mapping. And then MRI features related to disease subtype including nodularity (single vs. multinodular); margin (circumscribed vs. infiltrative); peripheral hypointenseity (present vs. absent); internal hypointensity reflecting hemosiderin deposition (speckled vs. granular) were assessed. Third, MRI features related to disease severity including involvement of bone, cartilage, and tendon were evaluated. MRI features for predicting local recurrence of TSGCT were tested using chi-square test and logistic regression analysis. Results Ten patients with diffuse-type TSGCT (D-TSGCT) and 10 patients with localized-type TSGCT (L-TSGCT) were included. There were six cases of local recurrence and all of them were D-TSGCT and none for L-TSGCT with statistical difference (P = 0.015). D-TSGCT that was direct risk factor for local recurrence showed more multinodular (80.0% vs. 10.0%; P = 0.007), infiltrative margin (90.0% vs. 10.0%; P = 0.002), and absent peripheral hypointensity (100.0% vs. 20.0%; P = 0.001) than L-TSGCT. Multivariate analysis showed infiltrative margin (odds ratio [OR], 81.0; P = 0.003) was independent MRI factor for D-TSGCT. Disease severity for risk of local recurrence included cartilage (66.7% vs. 7.1%; P = 0.024) and tendon (100.0% vs. 28.6%; P = 0.015) involvement compared to no local recurrence. Multivariate analysis showed tendon involvement (OR, 12.5; P = 0.042) was predictive MRI parameter for local recurrence. By combining tumor margin and tendon involvement, local recurrence was predicted sensitively on preoperative MRI (sensitivity, 100%; specificity, 50%; accuracy, 65%). Conclusion D-TSGCTs was associated with local recurrence and showed multinodularity infiltrative margin, and absent peripheral hypointensity. Disease severity including cartilage and tendon involvement was associated with local recurrence. Preoperative MRI evaluation by combining disease subtypes and severity can predict local recurrence sensitively.
Intolerance-of-uncertainty therapy versus metacognitive therapy for generalized anxiety disorder in primary health care: A randomized controlled pilot trial

Objective This randomized controlled pilot study investigated the feasibility of a future full-scale RCT to compare the effects of intolerance-of-uncertainty therapy (IUT) and metacognitive therapy (MCT) in primary health care patients with generalized anxiety disorder (GAD). Preliminary treatment effects were also evaluated. Materials and methods 64 patients with GAD at a large primary health care center in Stockholm, Sweden, were randomized to IUT or MCT. Feasibility outcomes included participant recruitment and retention, willingness to receive psychological treatment, and therapists’ competence in and adherence to treatment protocols. Self-reported scales were used to assess treatment outcomes, including worry, depression, functional impairment, and quality of life. Results Recruitment was satisfactory, and dropout was low. On a scale from 0 to 6, participants were satisfied with participating in the study (M = 5.17, SD = 1.09). Following brief training, therapists’ competence was rated as moderate, and adherence was rated as weak to moderate. From pre- to post-treatment, reductions on the primary treatment outcome measure of worry were of a large effect size and statistically significant in both the IUT and MCT conditions (Cohen’s d for IUT = -2.69, 95% confidence interval [-3.63, -1.76] and d for MCT = -3.78 [-4.68, -2.90]). The between-group effect size from pre- to post-treatment was large and statistically significant (d = -2.03 [-3.31, -0.75]), in favor of the MCT condition. Conclusion It is feasible to carry out a full-scale RCT to compare the effects of IUT to MCT for patients with GAD in primary health care. Both protocols seem effective, and MCT seems superior to IUT, but a full-scale RCT is needed to confirm these conclusions. Trial registration ClinicalTrials.gov (no. NCT03621371).
Transvenous lead extraction, factors affecting procedural difficulty

Abstract Background A complex transvenous lead extraction (TLE) procedure could be associated with lower success and higher complication rates in inexperienced hands. In this study, we aim to assess the factors that determine procedural difficulty in TLE. Methods We retrospectively studied 200 consecutive patients undergoing TLE in a single referral centre from June 2020 to December 2021. Lead extraction difficulty was assessed by the success of simple manual traction with or without a locking stylet, the need for advanced extraction tools and the number of tools required to extract the lead. Logistic and linear regression analyses were used to determine the factors independently affecting these 3 parameters. Results 363 leads were extracted from 200 patients (79% males, mean age 66.85 years). The indication for TLE was device-related infection in 51.5%. Multivariate analysis revealed the lead indwelling time to be the only factor affecting the 3 parameters of difficulty. Passive fixation leads and dual coil leads increased procedural difficulty by affecting 2 parameters each. Factors that affected one parameter included infected leads, coronary sinus leads, older age of the patient and a history of valvular heart disease, all associated with a simpler procedure. Right ventricular leads were associated with a more complex one. Conclusion The most important factor that increased TLE procedural difficulty was a longer lead indwelling time, followed by passive fixation and dual-coil leads. Other contributing factors were the presence of infection, coronary sinus leads, older patients, a history of valvular heart disease and right ventricular leads.