Miracle-dz/UniFAR-FTUs huggingface dataset:
Experience of Parents of Children with Genetically Determined Leukoencephalopathies Regarding the Adapted Health Care Services During the COVID-19 Pandemic

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. Because of the COVID-19 pandemic, many health care services were suspended, delayed or delivered remotely with telemedicine. We sought to explore the experience of parents of children with genetically determined leukoencephalopathies during the pandemic given the adapted health care services. We conducted semistructured interviews with 13 parents of 13 affected children. Three main themes were identified using thematic analysis: perceived impact of COVID-19 on health care services, benefits and challenges of telemedicine, and expectations of health care after the pandemic. Parents perceived a loss/delay in health care services while having a positive response to telemedicine. Parents wished telemedicine would remain in their care after the pandemic. This is the first study assessing the impact of COVID-19 on health care services in this population. Our results suggest that parents experience a higher level of stress owing to the shortage of services and the children's vulnerability.
Ophthalmic artery angioplasty for age-related macular degeneration

Background There is considerable overlap of contributors to cardiovascular disease and the development of age-related macular degeneration (AMD). Compromised ocular microcirculation due to aging and vascular disease contribute to retinal dysfunction and vision loss. Decreased choroidal perfusion is evident in eyes with dry AMD and is thought to play a role in retinal pigment epithelial dysfunction, the rate of development of geographic atrophy, and the development of neovascularization. The aim of the study was to demonstrate that AMD is correlated with a compromised blood flow in the ocular pathway and show OA angioplasty as a potential treatment of late-stage AMD. Methods Based on the potential for the ophthalmic artery (OA) to be an anatomical target for the treatment of AMD as outlined above, five patients were found to be eligible for compassionate use treatment, presenting clinically significant late-stage AMD with profound vision loss in one or both eyes, and are included in this retrospective study. Results OA narrowing, or significant calcium burden at the ophthalmic segment of the internal carotid artery compromising the origin of the OA was confirmed in all cases. Subsequent OA cannulation was achieved in all patients with some difficulty. Subjective patient reports indicated that all patients perceived a benefit following the procedure; however, improved postoperative visual acuity did not confirm that perceived benefit for one of the patients. Conclusions Feasibility and safety of the OA angioplasty were demonstrated, and a benefit perceived in five patients with profound vision loss and a desire to achieve improved quality of life. A clinical trial with controlled schedule, imaging, and methodologies is needed to confirm these results.
PIEZO1 mediates a mechanothrombotic pathway in diabetes

Description Hematopoietic cell selection based on PIEZO1 expression drives thrombosis risk in type 2 diabetes. An ion channel complicates clots in diabetes Patients with diabetes are at increased risk of thrombosis. Zhu et al. show that the mechanosensitive ion channel PIEZO1 is dysregulated in hematopoietic lineage cells during hyperglycemia. The increased PIEZO1 triggered flow-dependent prothrombotic responses in platelets, RBCs, and neutrophils in peripheral blood samples from patients with diabetes. Pharmacological inhibition of the channel conversely protected against clot formation in the patient blood samples and in a hyperglycemic zebrafish model. This work demonstrates that PIEZO1 drives a mechanothrombotic pathway in diabetes and identifies possible therapeutic strategies for follow-up study. Thrombosis is the leading complication of common human disorders including diabetes, coronary heart disease, and infection and remains a global health burden. Current anticoagulant therapies that target the general clotting cascade are associated with unpredictable adverse bleeding effects, because understanding of hemostasis remains incomplete. Here, using perturbational screening of patient peripheral blood samples for latent phenotypes, we identified dysregulation of the major mechanosensory ion channel Piezo1 in multiple blood lineages in patients with type 2 diabetes mellitus (T2DM). Hyperglycemia activated PIEZO1 transcription in mature blood cells and selected high Piezo1–expressing hematopoietic stem cell clones. Elevated Piezo1 activity in platelets, red blood cells, and neutrophils in T2DM triggered discrete prothrombotic cellular responses. Inhibition of Piezo1 protected against thrombosis both in human blood and in zebrafish genetic models, particularly in hyperglycemia. Our findings identify a candidate target to precisely modulate mechanically induced thrombosis in T2DM and a potential screening method to predict patient-specific risk. Ongoing remodeling of cell lineages in hematopoiesis is an integral component of thrombotic risk in T2DM, and related mechanisms may have a broader role in chronic disease.
Network Theory Based EHG Signal Analysis and its Application in Preterm Prediction

Objective: Preterm birth is the leading cause of neonatal morbidity and mortality. Early identification of high-risk patients followed by medical interventions is essential to the prevention of preterm birth. Based on the relationship between uterine contraction and the fundamental electrical activities of muscles, we extracted effective features from EHG signals recorded from pregnant women, and use them to train classifiers with the purpose of providing high precision in classifying term and preterm pregnancies. Methods: To characterize changes from irregularity to coherence of the uterine activity during the whole pregnancy, network representations of the original electrohysterogram (EHG) signals are established by applying the Horizontal Visibility Graph (HVG) algorithm, from which we extract network degree density and distribution, clustering coefficient and assortativity coefficient. Concerns on the interferences of different noise sources embedded in the EHG signal, we apply Short-Time Fourier Transform (STFT) to expand the original signal in the time-frequency domain. This allows a network representation and the extraction of related features on each frequency component. Feature selection algorithms are then used to filter out unrelated frequency components. We further apply the proposed feature extraction method to EHG signals available in the Term-Preterm EHG database (TPEHG), and use them to train classifiers. We adopt the Partition-Synthesis scheme which splits the original imbalanced dataset into two sets, and synthesizes artificial samples separately within each subset to solve the problem of dataset imbalance. Results: The optimally selected network-based features, not only contribute to the identification of the essential frequency components of uterine activities related to preterm birth, but also to improved performance in classifying term/preterm pregnancies, i.e., the SVM (Support Vector Machine) classifier trained with the available samples in the TPEHG gives sensitivity, specificity, overall accuracy, and $auc$ values as high as 0.89, 0.93, 0.91, and 0.97, respectively.
Effect of High-Power Laser Therapy Versus Shock Wave Therapy on Pain and Function in Knee Osteoarthritis Patients: A Randomized Controlled Trial.

Objective: The aim of this study was to evaluate and compare the effects of extracorporeal shock wave therapy (ESWT) and high-intensity laser therapy (HILT), as outpatient physical therapy modalities, on knee osteoarthritis (KOA) patients. Materials and methods: The treatment program was completed by 40 individuals with stage II KOA (according to Kellgren and Lawrence) who were randomly allocated to one of two groups. They have had more than grade 3 pain on the visual analog scale (VAS) during activities for the last 3 months, with body-mass index less than 30 and no history of knee operation, fracture, cancer, or other neuromuscular or musculoskeletal diseases that may affect study results. The ESWT group (n = 20, mean age = 40.12 ± 9.45 years) received ESWT, 0.05 mJ/mm2, one session/week for 4 weeks, and the HILT group (n = 20, mean age = 46.62 ± 8.68 years) received HILT, 1500 mJ/cm2 in each session, three sessions/week for 4 weeks. Both groups received conservative physical therapy programs. Before and after 4 weeks of intervention, pain, physical function, and disability were assessed using a VAS, 6-min walking test, and the Western Ontario and McMaster Universities Osteoarthritis Index. Results: When the pre- and post-treatment mean values of dependent variables of both groups were compared, there were statistically significant improvements in both groups. Significant differences in the measured variables were also discovered in favor of the HILT group compared with the ESWT group. Conclusions: HILT showed a superior effect compared with ESWT on pain, physical function, and disability in chronic KOA patients. Pan African Clinical Trials Registry number: PACTR202007638955907.
A musculoskeletal model driven by muscle synergy-derived excitations for hand and wrist movements

Objective. Musculoskeletal model (MM) driven by electromyography (EMG) signals has been identified as a promising approach to predicting human motions in the control of prostheses and robots. However, muscle excitations in MMs are generally derived from the EMG signals of the targeted sensor covering the muscle, inconsistent with the fact that signals of a sensor are from multiple muscles considering signal crosstalk in actual situation. To identify more accurate muscle excitations for MM in the presence of crosstalk, we proposed a novel excitation-extracting method inspired by muscle synergy for simultaneously estimating hand and wrist movements. Approach. Muscle excitations were firstly extracted using a two-step muscle synergy-derived method. Specifically, we calculated subject-specific muscle weighting matrix and corresponding profiles according to contributions of different muscles for movements derived from synergistic motion relation. Then, the improved excitations were used to simultaneously estimate hand and wrist movements through musculoskeletal modeling. Moreover, the offline comparison among the proposed method, traditional MM and regression methods, and an online test of the proposed method were conducted. Main results. The offline experiments demonstrated that the proposed approach outperformed the EMG envelope-driven MM and three regression models with higher R and lower NRMSE. Furthermore, the comparison of excitations of two MMs validated the effectiveness of the proposed approach in extracting muscle excitations in the presence of crosstalk. The online test further indicated the superior performance of the proposed method than the MM driven by EMG envelopes. Significance. The proposed excitation-extracting method identified more accurate neural commands for MMs, providing a promising approach in rehabilitation and robot control to model the transformation from surface EMG to joint kinematics.
Association of Radiation Therapy With Risk of Adverse Events in Patients Receiving Immunotherapy: A Pooled Analysis of Trials in the US Food and Drug Administration Database.

Importance Immune checkpoint inhibitors (ICIs) and radiation therapy (RT) are widely used to treat various cancers, but little data are available to guide clinicians on ICI use sequentially with RT. Objective To assess whether there is an increased risk of serious adverse events (AEs) associated with RT given within 90 days prior to an ICI. Design, Setting, and Participants Individual patient data were pooled from 68 prospective trials of ICIs submitted in initial or supplemental licensing applications in the US Food and Drug Administration (FDA) databases through December 2019. Two cohorts were generated: (1) patients who received RT within the 90 days prior to beginning ICI therapy and (2) those who did not receive RT within the 90 days prior to beginning ICI therapy, and AE frequencies were determined. A 1:1 propensity score-matched analysis was performed. Interventions All patients received an ICI (atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, or pembrolizumab); 1733 received RT within the 90 days prior to starting ICI therapy, and 13 956 did not. Main Outcomes and Measures The primary outcome was frequency and severity of AEs. Incidence of AEs was compared descriptively between participants who did vs did not receive RT in the propensity score-matched set. Because all analyses are exploratory (ie, not preplanned and no alpha allocated), assessment for statistical significance of the differences between groups was not considered appropriate. Results A total of 25 469 patients were identified; 8634 were excluded because they lacked comparators who had received RT (n = 976), did not receive an ICI (n = 4949), received RT outside of the target window (n = 2338), or had missing data in 1 or more variables used in the propensity analysis (n = 371), leaving 16 835 patients included in the analysis. The majority were younger than 65 years (9447 [56.1%]), male (10 459 [62.1%]), and White (13 422 [79.7%]). Patients receiving RT had generally similar rates of AEs overall to those patients who did not receive RT. The average absolute difference in rates across the AEs was 1.2%, and the difference ranged from 0% for neurologic AEs to 8% for fatigue. No difference in grade 3 to 4 AEs was observed between the 2 groups (absolute difference ranged from 0.01% to 2%). These findings persisted after propensity score matching. Conclusions and Relevance In this pooled analysis, administration of an ICI within 90 days following RT did not appear to be associated with an increased risk of serious AEs. Thus, it would appear to be safe to administer an ICI within 90 days of receiving RT. These findings should be confirmed in future prospective trials.
Ni (II) detection by 2-amino-5-substituted-1,3,4-oxadiazole as a chemosensor using photo-physical method: Antifungal, antioxidant, DNA binding, and molecular docking studies.

An oxadiazole derivative 2 was prepared by condensation reaction through cyclization of semicarbazone in the presence of bromine and the structural confirmation was supported by 1 H and 13 C NMR, FT-IR spectroscopy, and LC-MS spectrometry. Its sensing ability was examined towards Ni2+ ion with binding constant 1.04 x 105 over the other suitable metal cations (Ca2+ , Co2+ , Cr3+ , Ag+ , Pb2+ , Fe3+ , Mg2+ , and K+ ) by UV-visible and fluorescence spectroscopic studies and the minimum concentration of Ni2+ ion with LOD was found to be 9. 4μM. Job's plot method gives the binding stoichiometry ratio of Ni2+ ion vs oxadiazole derivative 2 to be 2:1. Furthermore, the intercalative binding mode of oxadiazole derivative 2 with Calf Thymus DNA was supported by UV-Vis, fluorescence, viscosity, cyclic voltammetry, time-resolved fluorescence, and circular dichroism measurements. The molecular docking result gives the binding score for oxadiazole derivative 2 to be -6.5 kcal/mol, which further confirms the intercalative interaction. In addition, the anti-fungal activity of oxadiazole derivative 2 was also screened against fungal strains (C. albicans, C. glabrata, and C. tropicalis) by broth dilution and disc diffusion method. In the antioxidant studies, the oxadiazole derivative 2 showed potential scavenging activity against DPPH and H2 O2 free radicals.
Use of Inhaled Nicotine and Cannabis Products among Adults Who Vape Both Substances

Abstract Background Co-occurring use (co-use) of nicotine and cannabis is common, and represents a broad range of use behaviors, including concurrent use, sequential use, and co-administration. Co-use has primarily been examined through the lens of smoked tobacco and cannabis. Little is known about those who co-use vaped nicotine and cannabis, and the degree to which specific co-use behaviors are associated, based on mode of use and/or substance. Methods We conducted an online pilot survey on use behaviors related to inhaled modes of nicotine and cannabis. The survey was administered to 112 concurrent vapers of these substances. Descriptive analyses examined sample characteristics and co-administered vaping and smoking behaviors. Logistic regressions examined associations in use behaviors by mode and substance. Results Participants who vaped nicotine and cannabis monthly also reported monthly smoking of cannabis (100%), and cigarettes (58%). Most exhibited moderate-to-high degrees of mental health and substance use problems requiring clinical intervention. Monthly concurrent use exhibited more differences by mode, and more similarities by substance. Specific sequential use practices showed mode-specific associations; with greater frequency of cigarette smoking and nicotine vaping. Co-administration was associated with more frequent tobacco and cannabis smoking. Conclusions Those who regularly vape nicotine and cannabis tend to engage in some form of smoking. Different subsets of nicotine and cannabis co-use behaviors showed different associations with patterns of use and modes of drug delivery. Findings underscore the diversity of nicotine and cannabis use behaviors among co-users, and the importance of considering associations by both substance and mode of use.
Neuropilin-1, a myeloid cell-specific protein, is an inhibitor of HIV-1 infectivity

Significance Macrophages and dendritic cells represent an important target for HIV-1 replication in vivo as they serve both as a vehicle for virus dissemination throughout the body and a viral reservoir. However, myeloid cells can support persistent replication of HIV-1 and, in contrast to infected T cells, demonstrate lower productivity. Using proteomics, we discovered that NRP-1 is a host restriction factor that inhibits HIV-1 from infecting macrophages and dendritic cells. NRP-1 is incorporated into the HIV-1 virion particle to inhibit its ability to attach to target cells in a viral envelope glycoprotein-independent manner. Overall, these results provide insights into the ability of myeloid lineage cells to utilize NRP-1 to interfere with HIV-1 infection. Myeloid lineage cells such as macrophages and dendritic cells (DCs), targeted by HIV-1, are important vehicles for virus dissemination through the body as well as viral reservoirs. Compared to activated lymphocytes, myeloid cells are collectively more resistant to HIV-1 infection. Here we report that NRP-1, encoding transmembrane protein neuropilin-1, is highly expressed in macrophages and DCs but not CD4+ T cells, serving as an anti-HIV factor to inhibit the infectivity of HIV-1 progeny virions. Silencing NRP-1 enhanced the transmission of HIV-1 in macrophages and DCs significantly and increased the infectivity of the virions produced by these cells. We further demonstrated that NRP-1 was packaged into the progeny virions to inhibit their ability to attach to target cells, thus reducing the infectivity of the virions. These data indicate that NRP-1 is a newly identified antiviral protein highly produced in both macrophages and DCs that inhibit HIV-1 infectivity; thus, NRP-1 may be a novel therapeutic strategy for the treatment of HIV-1 infection.
Adjustment of young women with breast cancer after chemotherapy: A mediation model of emotional competence via emotional distress

Emotional competence (EC) is considered a substantial resource in the adjustment of cancer patients, especially via its effect on anxiety and depression symptoms. This research aimed at assessing the impact of intrapersonal EC in young women (≤45 years) with breast cancer (YWBC) on their specific quality of life (i.e. subjective experience related to daily difficulties and perceived repercussions of the disease and treatments) related to chemotherapy, via anxiety and depression symptoms.
Mouse Models of Osteoarthritis: A Summary of Models and Outcomes Assessment.

Osteoarthritis (OA) is a multidimensional health problem and a common chronic disease. It has a substantial impact onpatient quality of life and is a common cause of pain and mobility issues in older adults. The functional limitations, lack of curative treatments, and cost to society all demonstrate the need for translational and clinical research. The use of OA models in mice is important for achieving a better understanding of the disease. Models with clinical relevance are needed to achieve 2 main goals: to assess the impact of the OA disease (pain and function) and to study the efficacy of potential treatments. However, few OA models include practical strategies for functional assessment of the mice. OA signs in mice incorporate complex interrelations between pain and dysfunction. The current review provides a comprehensive compilation of mousemodels of OA and animal evaluations that include static and dynamic clinical assessment of the mice, merging evaluationof pain and function by using automatic and noninvasive techniques. These new techniques allow simultaneous recordingof spontaneous activity from thousands of home cages and also monitor environment conditions. Technologies such as videographyand computational approaches can also be used to improve pain assessment in rodents but these new tools must first be validated experimentally. An example of a new tool is the digital ventilated cage, which is an automated home-cage monitor that records spontaneous activity in the cages.