Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic balance during walking in people with multiple sclerosis: A cross-sectional study

Dynamic balance disorders are common impairments in People with Multiple Sclerosis (PwMS) leading to gait disorders and a higher risk of falling. However, the assessment of dynamic balance is still challenging and instrumented indexes provide objective and quantitative data of CoM movement and Base of Support, which are considered that are two key factors describing dynamic balance. This study aims at validating recent instrumented indexes based on the inverted pendulum model and characterizing dynamic balance disorders in PwMS. We clinically assessed 20 PwMS and we collected instrumented gait data through an optoelectronic system. Data from 20 Healthy Subjects (HS) were also considered as normative reference. Margin of Stability by HoF (MoS_Hof) and by Terry (MoS_Terry) at midstance, and Foot Placement Estimator (DFPE) at heel strike were calculated in mediolateral (ML) and anteroposterior (AP) directions, for both less affected and most affected sides for PwMS and for dominant and non-dominant side for HS. MoS_HOF well discriminated between PwMS and HS, followed by MoS_TERRY in ML direction (Mos_HOF: PwMS = 130.0 ± 27.2 mm, HS = 106.5 ± 18.6 mm, p < 0.001, MoS_TERRY: PwMS = 75.1 ± 24.3 mm, HS = 56.5 ± 23.4 mm, p < 0.02). MoS_HOF and MoS_TERRY discriminated between sides in both directions in PwMS. DFPE did not discriminate between groups and sides. Moderate correlations were found between all three indexes and clinical balance scales (from r = 0.02 to r = 0.66), energy recovery (from r = −0.77 to r = −0.11), single stance time (from r = −0.11 to r = 0.80) and step length (from r = −0.83 to r = −0.20). MoS_HOF resulted in the best index to describe dynamic balance disorders in PwMS: they keep CoM position far from the lateral and as close as possible to the anterior boundary of the Base of Support as preventive strategies to control balance perturbations. Furthermore, PwMS seem to use different preventive strategies in accordance with the specific lower limb impairments. This alters the physiological gait mechanisms increasing the energy expenditure and decreasing gait quality and dynamic balance.
Evaluation of Depression and Anxiety in a Diverse Population With Thyroid Eye Disease Using the Nationwide NIH All of Us Database

Purpose: To evaluate the prevalence of depression and anxiety among individuals with thyroid eye disease (TED) and identify sociodemographic risk factors using the NIH All of Us database. Methods: Three hundred ninety eight cases with TED were compared with 1,592 controls with demographics matching the 2020 US Census. Primary outcomes were diagnosed depression or anxiety; Patient Health Questionnaire-9 (PHQ-9) scores and General Anxiety Disorder-7 (GAD-7) scores were included as secondary outcomes. We performed multivariable logistic regression to generate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between TED and depression and anxiety. Results: Patients with TED were more likely to have depression (OR 2.72, 95% CI 2.08–3.56, p < 0.001) and anxiety (OR 2.82, 95% CI 2.16–3.70, p < 0.001) than controls. In patients with TED, female gender was an independent risk factor for both depression (OR 1.72; 95% CI 1.00–5.07, p = 0.05) and anxiety (OR 2.17, 95% CI 1.25–3.85, p = 0.006). Unemployment (OR 1.72, 95% CI 1.03–2.94, p = 0.04) and lower income (OR 0.88 for income as a continuous variable, 95% CI 0.79–0.99, p = 0.03) were risk factors for anxiety. Risk factors for more severe depression as assessed by PHQ-9 included lower income (OR 0.70, 95% CI 0.57–0.85, p < 0.001), and protective factors included Black race (OR 0.12, 95% CI 0.02–0.45, p = 0.002). Lower income was associated with more severe anxiety as assessed by GAD-7 (OR 0.77, 95% CI 0.64–0.94, p = 0.009). Conclusions: Patients with TED were more likely to develop depression and anxiety compared with controls. This study highlights the psychosocial impact of TED and associated socioeconomic risk factors. The authors evaluate the prevalence and social determinants of depression and anxiety among individuals with thyroid eye disease.
Imaging with blazed-binary diffractive elements

Recent experimental results clearly evidence that blazed-binary diffractive elements, a family of diffractive components composed of subwavelength binary features, offers unusual and attractive properties in the resonance domain. In this paper, we provide further insight into the field-angle behavior of these diffractive elements. We show that blazed-binary gratings operate efficiently under symmetrical mount and over a wide field-angle interval. This interesting feature makes blazed-binary diffractive elements attractive candidates for imaging systems.
Withdrawal of Long-Term Nucleotide Analog Therapy in Chronic Hepatitis B: Outcomes From the Withdrawal Phase of the HBRN Immune Active Treatment Trial

INTRODUCTION: Withdrawal of nucleos(t)ide analog therapy is increasingly being evaluated in chronic hepatitis B infection as a strategy to induce hepatitis B surface antigen (HBsAg) loss. The Hepatitis B Research Network Immune-Active Trial evaluated treatment with tenofovir (TDF) for 4 years ± an initial 6 months of peginterferon-α (PegIFN) (NCT01369212) after which treatment was withdrawn. METHODS: Eligible participants (hepatitis B e antigen [HBeAg]−/anti-HBe+, hepatitis B virus [HBV] DNA <103 IU/mL, no cirrhosis) who discontinued TDF were followed for at least 1 year with optional follow-up thereafter. Retreatment was based on predefined criteria. RESULTS: Among 201 participants who received 4 years of treatment, 97 participants (45 TDF and 52 TDF + PegIFN arm, 79 Asian) discontinued TDF. HBsAg loss occurred in 5 participants, 2 within 25 weeks and 3 within 89–119 weeks postwithdrawal (cumulative rate 4.3% by 2 years). Alanine aminotransferase (ALT) flares (>5× upper limit of normal) after TDF withdrawal occurred in 36 (37.1%) participants and occurred more frequently and earlier in those HBeAg− compared with HBeAg+ at treatment initiation. ALT flares were associated with older age and higher HBV DNA pretreatment and at the visit before the flare. ALT flares were not significantly associated with HBsAg decline or loss but were associated with immune active disease at 1 year (70.6% vs 11.9%, P < 0.0001) and 2 years (66.7% vs 25.9%, P = 0.03) postwithdrawal. Treatment reinitiation was required in 13 (13.4%) participants, and 13 others remained in a sustained inactive carrier state by the end of the study follow-up. No criteria reliably predicted safe treatment withdrawal. DISCUSSION: Results from this trial do not support TDF withdrawal as a therapeutic strategy. HBsAg loss was infrequent within 2 years of stopping long-term TDF. If withdrawal is considered, HBV DNA should be carefully monitored with reinitiation of therapy if levels rise above 4 log10IU/mL to reduce the risk of ALT flares, as they were not associated with subsequent HBsAg decline or loss.
The impact of nucleosome structure on CRISPR/Cas9 fidelity

Abstract The clustered regularly interspaced short palindromic repeats (CRISPR) Cas system is a powerful tool that has the potential to become a therapeutic gene editor in the near future. Cas9 is the best studied CRISPR system and has been shown to have problems that restrict its use in therapeutic applications. Chromatin structure is a known impactor of Cas9 targeting and there is a gap in knowledge on Cas9’s efficacy when targeting such locations. To quantify at a single base pair resolution how chromatin inhibits on-target gene editing relative to off-target editing of exposed mismatching targets, we developed the gene editor mismatch nucleosome inhibition assay (GEMiNI-seq). GEMiNI-seq utilizes a library of nucleosome sequences to examine all target locations throughout nucleosomes in a single assay. The results from GEMiNI-seq revealed that the location of the protospacer-adjacent motif (PAM) sequence on the nucleosome edge drives the ability for Cas9 to access its target sequence. In addition, Cas9 had a higher affinity for exposed mismatched targets than on-target sequences within a nucleosome. Overall, our results show how chromatin structure impacts the fidelity of Cas9 to potential targets and highlight how targeting sequences with exposed PAMs could limit off-target gene editing, with such considerations improving Cas9 efficacy and resolving current limitations.
A Monte Carlo Investigation of the Robustness of Hotelling's One- and Two-Sample T 2 Tests

Abstract The robustness of Hotelling's one- and two-sample tests is investigated by Monte Carlo methods. Samples are presented from uniform, exponential, and lognormal distributions. The results show that the two-sample test is far more robust to departures from normality than the one-sample test, and that the latter may be badly affected by departures due to extreme skewness.
Using the LASSI-L to Detect Robust Interference Effects in Premanifest Huntington Disease

Background: Diagnosis of manifest Huntington disease (HD) is based primarily on motor symptoms, but premanifest HD (preHD) is often associated with subtle cognitive decline. The Loewenstein–Acevedo Scales for Semantic Interference and Learning (LASSI–L) is a validated verbal learning test that can be used to detect early cognitive decline. Objective: To determine the utility of the LASSI–L for detecting early cognitive decline in individuals with preHD and to compare the results of the LASSI–L with those of commonly used neuropsychological tests in HD. Method: We administered the LASSI–L to 13 individuals with preHD and 13 healthy controls matched for age, sex, and education as part of a longitudinal study of disease progression. For comparison purposes, we administered the Mini-Mental State Examination; Stroop Color and Word Test; Symbol Digit Modalities Test; Trail-Making Test, Parts A and B; and category fluency (animals) task. Results: Five of the seven sections on the LASSI–L captured group differences: Proactive Semantic Interference (PSI; P < 0.001), Failure to Recover From PSI (P = 0.038), Retroactive Semantic Interference (RSI; P = 0.013), Delayed Recall (P < 0.001), and B1 Cued Recall Intrusions (P = 0.036). Using a false discovery rate of <0.05, PSI, RSI, and Delayed Recall remained significant. Conclusion: The LASSI–L is a sensitive instrument for detecting early interference effects in individuals with preHD that outperforms commonly used neuropsychological tests. The LASSI–L could be a useful addition to clinical and research protocols involving individuals with preHD.
Novel immune directed therapies in myelodysplastic syndromes and acute myeloid leukemia

Purpose of review Therapies that target the immune system are increasingly used across oncology, including in hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). While allogeneic transplant has been a key therapy in these cancers, new approaches that target the immune system are being explored including immune checkpoint therapies, antibody−drug conjugates, and cellular therapies. Recent findings This review outlines updates in the preclinical rationale for immune directed therapies in MDS and AML, as well as recent clinical trials exploring these therapies. This manuscript summarizes the development of therapies targeting T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) and CD47, which are being evaluated in late phase studies in MDS and AML. It also reviews the landscape of other immune based therapies including antibody-drug conjugates, chimeric antigen receptor-T cells, bispecific antibodies, and tumor vaccines. Summary The treatment landscape in MDS and AML is rapidly changing; with a goal of improving the quality and duration of responses, a number of immune based therapies are under investigation. This review outlines recent advances with these therapies as well as some of the challenges that remain to incorporate them into leukemia care.
PERFUSE: Non-Interventional Cohort Study of Patients Receiving Infliximab Biosimilar SB2: Results in Pediatric Patients

Objectives: PERFUSE is a non-interventional study of 1233 patients [inflammatory rheumatic disease, n = 496; inflammatory bowel disease (IBD), n = 737] receiving infliximab (IFX) biosimilar SB2 therapy. This analysis describes response to treatment and persistence on SB2 for up to 12 months in pediatric IBD patients (n = 126). Methods: Pediatric IBD patients with Crohn disease (CD) or ulcerative colitis (UC), either naïve or switched from originator IFX, who started SB2 in routine practice after September 2017 were eligible. Data were captured for 12 months following SB2 initiation. Disease activity was measured using C-reactive protein (CRP) levels and the Harvey-Bradshaw Index or Pediatric Ulcerative Colitis Activity Index for CD and UC patients, respectively. Body mass index and height z scores were used to assess patient growth between initiation (M0) and month 12 (M12). Results: One hundred twenty-six pediatric IBD patients were included (102 CD patients, 51 naïve and 51 switched; 24 UC patients, 9 naïve and 15 switched). Naive patients’ disease scores decreased between M0 and M12. CRP measurements also decreased in naïve CD patients. Switched patients’ disease scores and CRP levels remained stable between M0 and M12. Height z scores improved significantly over the course of the treatment for all groups except for naïve UC patients. Conclusions: SB2 provides effective disease control for naïve and switched pediatric patients. Clinical remission rates improved in naïve patients and no loss of control was observed in switched patients after 1 year. Growth failure is not observed in IBD patients under SB2 treatment.
Prevalence of modifiable risk factors in primary elective arthroplasty and their association with infections

Background and purpose The aim of this study was to identify the prevalence of modifiable risk factors of surgical site infections (SSI) in patients undergoing primary elective total joint arthroplasty (TJA) receiving conventional preoperative preparation, and to explore their association with infectious outcomes. Patients and methods Information regarding modifiable risk factors (anemia, diabetes, obesity, nutritional status, smoking, physical activity) was prospectively gathered in patients undergoing primary TJA of hip or knee in 2018–2020 at a single institution with 6 weeks’ follow-up time. Results 738 patients (median age 68 years [IQR 61–73], women 57%) underwent TJA (knee 64%, hip 36%). Anemia was detected in 8%, diabetes was present in 9%, an additional 2% had undiagnosed diabetes (HbA1c > 47 mmol/mol), and 8% dysglycemia (HbA1c 42–47 mmol/mol). Obesity (BMI ≥ 30) was observed in 52%. Serum albumin, total lymphocyte count, and vitamin D below normal limits was identified in 0.1%, 18%, and 16%, respectively. Current smokers were 7%. Surgical site complications occurred in 116 (16%), superficial SSI in 57 (8%), progressing to periprosthetic joint infection in 7 cases. Univariate analysis identified higher odds of superficial SSI for BMI ≥ 30 (OR 2.1, 95%CI 1.2–3.8) and HbA1c ≥ 42 mmol/mol (OR 2.2, CI 1.1–4.2), but no association was found with other factors. Conclusion In a general population undergoing primary TJA an association was found between obesity (52%) and dysglycemia/diabetes (19%) and superficial SSI (8%), which progressed to PJI in 12% of cases, generating a 1% total rate of PJI. Modification of these risk factors might mitigate infectious adverse outcomes.
Exploring the potential of eco-friendly silver nanoparticles to inhibit azole-resistant clinical isolates of Candida spp.

Abstract The antimicrobial activity and biological efficiency of silver nanoparticles (AgNps) have been widely described and can be modeled through stabilizing and reducing agents, especially if they exhibit biocidal properties, which can enhance bioactivity against pathogens. The selective action of AgNps remains a major concern. In this regard, the use of plant extracts for the green synthesis of nanoparticles offers advantages because it improves the toxicity of Nps for microorganisms and is harmless to normal cells. However, biological evaluations of the activity of AgNps synthesized using different reducing agents are determined independently, and comparisons are frequently overlooked. Thus, we investigated and compared the antifungal and cytotoxic effects of two ecological AgNps synthesized from Moringa oleifera aqueous leaf extract (AgNp-M) and glucose (AgNp-G) against azole-resistant clinical isolates of Candida spp. and nontumor mammalian cells. Synthesized AgNps exhibited an antifungal effect on planktonic cells of drug-resistant C. albicans and C. tropicalis (MIC 0.21–52.6 µg/mL). The toxicity was influenced by size. However, the use of M. oleifera extracts allows us to obtain AgNps that are highly selective and nongenotoxic to Vero cells due to modifications of the shape and surface. Therefore, these results suggest that AgNp-M has antimicrobial potential and deserves further investigation for biomedical applications.
Conservative Treatment of Parapneumonic Effusion in Children: Experience From a 10-Year Consecutive Case Series

Background: In children with parapneumonic effusion (PPE), it remains unclear when conservative treatment with antibiotics suffixes or when pleural drainage is needed. In this study we evaluate clinical features and outcomes of children with PPE. Methods: A retrospective, multicentre cohort study at 4 Dutch pediatric departments was performed, including patients 1–18 years treated for PPE between January 2010 and June 2020. Results: One hundred thirty-six patients were included (mean age 8.3 years, SD 4.8). 117 patients (86%) were treated conservatively and 19 (14%) underwent pleural drainage. Patients undergoing pleural drainage had mediastinal shift more frequently compared with conservatively treated patients (58 vs. 3%, difference 55%; 95% CI: 32%–77%). The same accounted for pleural septations/pockets (58 vs. 11%, difference 47%; 95% CI: 24%–70%), pleural thickening (47 vs. 4%, difference 43%; 95% CI: 20%–66%) and effusion size (median 5.9 vs. 2.7 cm; P = 0.032). Conservative management was successful in 27% of patients (4 of 15) with mediastinal shift, 54% of patients (13 of 24) with septations/pockets, 36% of patients (5 of 14) with pleural thickening, and 9% of patients (3 of 32) with effusions >3 cm, all radiological signs generally warranting pleural drainage. In patients treated conservatively, median duration of hospitalization was 5 days (IQR 4–112) compared with 19 days (IQR 15–24) in the drainage group (P < 0.001), without significant difference in readmission rate (11 vs. 4%, difference 6%; 95% CI: –8%–21%). Conclusion: This study suggests that the greater amount of children with PPE could be treated conservatively with antibiotics only, especially in absence of mediastinal shift, pleural septations/pockets, pleural thickening or extensive effusions.
P-TEFb promotes cell survival upon p53 activation by suppressing intrinsic apoptosis pathway

Abstract Positive transcription elongation factor b (P-TEFb) is the crucial player in RNA polymerase II (Pol II) pause release that has emerged as a promising target in cancer. Because single-agent therapy may fail to deliver durable clinical response, targeting of P-TEFb shall benefit when deployed as a combination therapy. We screened a comprehensive oncology library and identified clinically relevant antimetabolites and Mouse double minute 2 homolog (MDM2) inhibitors as top compounds eliciting p53-dependent death of colorectal cancer cells in synergy with selective inhibitors of P-TEFb. While the targeting of P-TEFb augments apoptosis by anti-metabolite 5-fluorouracil, it switches the fate of cancer cells by the non-genotoxic MDM2 inhibitor Nutlin-3a from cell-cycle arrest to apoptosis. Mechanistically, the fate switching is enabled by the induction of p53-dependent pro-apoptotic genes and repression of P-TEFb-dependent pro-survival genes of the PI3K-AKT signaling cascade, which stimulates caspase 9 and intrinsic apoptosis pathway in BAX/BAK-dependent manner. Finally, combination treatments trigger apoptosis of cancer cell spheroids. Together, co-targeting of P-TEFb and suppressors of intrinsic apoptosis could become a viable strategy to eliminate cancer cells.
Biologics and severe asthma in children

Purpose of review Severe asthma can carry significant morbidity and mortality for patients, and it places a burden on families and the healthcare system. Biologic agents have revolutionized the care of patients with severe asthma in recent years. Evidence surrounding some of these therapies is limited in the pediatric population, but recent studies show that they significantly improve asthma care when used appropriately. In this review, we discuss the biologic therapies currently approved to treat severe asthma in school-age children and adolescents. Recent findings Randomized controlled trials have been published in support of biologics in children and/or adolescents. These therapies have been shown to reduce the annual rate of severe asthma exacerbations by at least 40–50%, and some up to about 70%. Improvements in asthma control, lung function, oral corticosteroid use, and quality of life have also been demonstrated, although these vary by agent. Furthermore, these therapies have reassuring safety profiles in pediatric patients. Summary With three biologic agents approved for children ages 6–11 years and five approved for adolescents ages >12 years, it can be challenging to select one. The therapy should be chosen after careful consideration of the patient's asthma phenotype and biomarkers. Additional pediatric-specific clinical trials would be helpful in developing evidence-based guidelines on biologic therapies in this population.