Miracle-dz/UniFAR-FTUs huggingface dataset:
Care and treatment needs of immunosuppressive therapy patients with warts and impact on everyday life: a qualitative study

Abstract Introduction Patients receiving immunosuppressive therapy have an increased risk of developing verrucae vulgaris (warts). They often suffer from dissemination of numerous warts, complicated by low treatment response and long-term treatment. How patients experience these challenges is not well characterized. The aim of this study was to explore how patients on immunosuppressive therapy experience everyday life with warts on the hands and feet, and their needs related to care and treatment. Methods The study took a phenomenological-hermeneutic approach. Semi-structured interviews were conducted with 10 adults. Data were analyzed using the thematic analysis described by Braun and Clark. Results Warts on the hands and feet impact everyday life and cause feelings of stigma and pain. Patients request treatment and hope to be cured although the prospects are poor. Self-treatment is experienced as a burden, because of the need for more specific information about and skills to treat the warts, and because individual patients’ resources are not considered. Patients experience a lack of care continuity. Conclusions Patients request a person-centred care and treatment approach, to establish a relationship with health care professionals. Establishing care continuity might reduce patients’ treatment-related insecurity.
Glycosylation with Sulfoxides and Sulfinates as Donors or Promoters

The efficient, stereocontrolled formation of glycosidic bonds is arguably the most fundamental reaction in glycoscience. This chapter surveys four recent distinct glycosylation methods united by the common theme of employing sulfoxides, or closely related sulfinates, either in the glycosyl donor itself or as an integral part of the promoter. In the first method (the sulfoxide method), a glycosyl sulfoxide, the donor, is coupled to an acceptor alcohol by means of an activating agent to give the glycosidic bond. The activating agent is typically triflic anhydride, but other compounds have been used. In the second method (the thiogylcoside method) the donor is thioglycoside. It is activated by means of a promoter derived from the reaction of trifluoromethanesulfonic anhydride and thiosulfinate, a sulfinaminde, or diphenylsulfoxide before coupling to an acceptor alcohol. The third method is dehydrative coupling. This chapter is concerned only with the recent variations in which dehydration is achieved by means of a combination of diaryl sulfoxides and trifluoromethanesulfonic acid. The last method (the oxidative method), involves the direct oxidative glycosylation of glycals. This method differs significantly from the other methods since it does not employ a traditional anomeric derivative as glycosly donor, but derives one from the formal oxidation of glycal. At some time in the activation process, all four methods typically involve the reaction of a sulfoxide, or sulfinate with trifluoromethanesulfonic anhydride. All four methods possess the distinct advantage of using readily prepared, stable gylcosyl donors. Three of them are metal-free and two of them are capable of coupling to enable the most hindered unreactive alcohols in a matter of minutes at low temperature. These methods are some of the most powerful available for the formation of glycosidic linkages. Keywords: glycoslyation; mechanisms; oxidative method; sulfoxide method; dehydrative method; thioglycoside/sulfinate method; scope; limitations; donors; acceptors; N-Glycosides; nucleosides; C-Glycosides; sulfoxides; promoters; bond formation; synthesis applications; method comparisons; solvents; functional group compatibility; pyranoside; furnanosides; experimental procedures
Oscillatory and structural signatures of language plasticity in brain tumor patients: A longitudinal study

Recent evidence suggests that damage to the language network triggers its functional reorganization. Yet, the spectro‐temporal fingerprints of this plastic rearrangement and its relation to anatomical changes is less well understood. Here, we combined magnetoencephalographic recordings with a proxy measure of white matter to investigate oscillatory activity supporting language plasticity and its relation to structural reshaping. First, cortical dynamics were acquired in a group of healthy controls during object and action naming. Results showed segregated beta (13–28 Hz) power decreases in left ventral and dorsal pathways, in a time‐window associated to lexico‐semantic processing (~250–500 ms). Six patients with left tumors invading either ventral or dorsal regions performed the same naming task before and 3 months after surgery for tumor resection. When longitudinally comparing patients' responses we found beta compensation mimicking the category‐based segregation showed by controls, with ventral and dorsal damage leading to selective compensation for object and action naming, respectively. At the structural level, all patients showed preoperative changes in white matter tracts possibly linked to plasticity triggered by tumor growth. Furthermore, in some patients, structural changes were also evident after surgery and showed associations with longitudinal changes in beta power lateralization toward the contralesional hemisphere. Overall, our findings support the existence of anatomo‐functional dependencies in language reorganization and highlight the potential role of oscillatory markers in tracking longitudinal plasticity in brain tumor patients. By doing so, they provide valuable information for mapping preoperative and postoperative neural reshaping and plan surgical strategies to preserve language function and patient's quality of life.
Abnormal cerebellar function and tremor in a mouse model for non‐manifesting partially penetrant dystonia type 6

Loss‐of‐function mutations in the Thap1 gene cause partially penetrant dystonia type 6 (DYT6). Some non‐manifesting DYT6 mutation carriers have tremor and abnormal cerebello‐thalamo‐cortical signalling. We show that Thap1 heterozygote mice have action tremor, a reduction in cerebellar neuron number, and abnormal electrophysiological signals in the remaining neurons. These results underscore the importance of Thap1 levels for cerebellar function. These results uncover how cerebellar abnormalities contribute to different dystonia‐associated motor symptoms.
Cation-Zwitterionic Lipid Interactions Are Affected by the Lateral Area per Lipid.

Interactions of the divalent cations Ca2+ and Mg2+ with the zwitterionic lipid bilayers prepared of a fully saturated dipalmitoylphosphatidylcholine (DPPC) or a di-monounsaturated dioleoylphosphatidylcholine (DOPC) were studied by using the neutron scattering methods and molecular dynamics simulations. The effect on the bilayer structural properties confirms the direct interactions in all cases studied. The changes are observed in the bilayer thickness and lateral area. The extent of these structural changes, moreover, suggests various mechanisms of the cation-lipid interactions. First, we have observed a small difference when studying DPPC bilayers in the gel and fluid phases, with somewhat larger effects in the former case. Second, the hydration proved to be a factor in the case of DOPC bilayers, with the larger effects in the case of less hydrated systems. Most importantly, however, there was a qualitative difference between the results of the fully hydrated DOPC bilayers and the others examined. These observations then prompt us to suggest an interaction model that is plausibly governed by the lateral area of lipid, though affected indirectly also by the hydration level. Namely, when the interlipid distance is small enough to allow for the multiple lipid-ion interactions, the lipid-ion-lipid bridges are formed. The bridges impose strong attractions that increase the order of lipid hydrocarbon chains, resulting in the bilayer thickening. In the other case, when the interlipid distance extends beyond a limiting length corresponding to the area per lipid of ∼65 Å2, Mg2+ and Ca2+ continue to interact with the lipid groups by forming the separate ion-lipid pairs. As the interactions proposed affect the lipid membrane structure in the lateral direction, they may prove to play their role in other mechanisms lying within the membrane multicomponent systems and regulating for example the lipid-peptide-ion interactions.
Symptom cluster profiles following traumatic orthopedic injuries: A protocol.

Traumatic injuries affect millions of Americans annually, resulting in $671 billion in healthcare costs and lost productivity. Postinjury symptoms, like pain, sleep disturbance, anxiety, depression, and stressor-related disorders are highly prevalent following traumatic orthopedic injuries (TOI) and may contribute to negative long-term outcomes. Symptoms rarely present in isolation, but in clusters of two or more symptoms that co-occur to affect health in aggregate. Identifying symptom cluster profiles following TOI may identify those at highest risk for negative outcomes. Dysregulation of brain-derived neurotrophic factor (BDNF) is a potential biological mechanism responsible for symptom cluster profile membership after TOI and may be targeted in future precision-health applications. The purpose of this paper is to present the protocol of a cross-sectional study designed to identify symptom cluster profiles and measure the extent to which the BDNF val66met mutation and serum concentration of BDNF are associated with membership in symptom cluster profiles. We plan to recruit 150 TOI survivors within the first 72 h of injury. The study aims are to (1) describe TOI survivors' membership in symptom cluster profiles, indicated by pain, sleep disturbance, and symptoms of anxiety, depression, and stressor-related disorders, immediately following a TOI; (2) examine associations between demographic and clinical factors and symptom cluster profile membership among TOI survivors; (3) test the hypothesis that low serum concentrations of BDNF are associated with membership among symptom cluster profiles following TOI; and (4) test the hypothesis that the presence of the val66met mutation on one or both alleles of the BDNF gene is associated with membership among symptom cluster profiles following TOI.
Treatment Deescalation Strategies for Nasopharyngeal Cancer: A Review.

Importance Since the advent of modern radiotherapy techniques and incorporation of systemic chemotherapy for nasopharyngeal cancer, locoregional control has been excellent. However, the rate of treatment-related complications, many of which are irreversible, remains high. New approaches are being explored to determine whether the toxic effects of treatment can be relieved while maintaining disease control. This review presents the current state of deescalation strategies for nasopharyngeal cancer. Observations A review of the literature shows that deescalation approaches can be generally categorized into deescalating systemic therapy vs deescalating radiotherapy. This review discusses studies that have explored sparing chemotherapy in selected patients with stage II cancer as well as altering the chemotherapy scheduling, dosing, and agent from the current standard of care, cisplatin. Deescalating radiotherapy has involved decreasing the dose and the treatment volume. In many cases, these approaches are being guided by measuring Epstein-Barr virus DNA levels, which is a robust biomarker for screening, treatment monitoring, and surveillance. Ongoing work with various imaging modalities, such as fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced or diffusion-weighted magnetic resonance imaging sequences, have shown promise as another biomarker to safely guide practitioners toward deescalation. Conclusions and Relevance Various strategies to deescalate treatment in nasopharyngeal cancer have been explored, and outcomes have remained excellent in most approaches. Patient selection remains key, and long-term outcomes and late complications are still to be determined. Continued investigation with prospective, multi-institutional studies are needed to better elucidate how treatment for nasopharyngeal carcinoma can best be individualized and deescalated.
Development of a Machine Learning Model Using Multiple, Heterogeneous Data Sources to Estimate Weekly US Suicide Fatalities

Key Points Question Can real-time streams of secondary information related to suicide be used to accurately estimate suicide fatalities in the US in real time? Findings In this national cross-sectional study, combining information from 8 data streams encompassing various health services and online data sources enabled accurate, real-time estimation of US suicide fatalities with meaningful correlation to week-to-week epidemiological trends and a less than 1% error compared with actual counts. Meaning These findings advance the first efforts to create a population-level system for enabling real-time epidemiological trend monitoring of suicide fatalities.
Resolving Cargo-motor-track Interactions in Living Cells with Bifocal Parallax Single Particle Tracking

Resolving coordinated biomolecular interactions in living cellular environments is vital for understanding the mechanisms of molecular nanomachines. The conventional approach relies on localizing and tracking target biomolecules and/or subcellular organelles labeled with imaging probes. However, it is challenging to gain information on rotational dynamics, which can be more indicative of the work done by molecular motors and their dynamic binding status. Herein, a bifocal parallax single particle tracking method using half-plane point spread functions has been developed to resolve the full-range azimuth angle (0-360°), polar angle, and 3D displacement in real time under complex living cell conditions. Using this method, quantitative rotational and translational motion of the cargo in a 3D cell cytoskeleton was obtained. Not only well-known active intracellular transport and free diffusion were observed but new interactions, tight attachment and tethered rotation, were discovered for better interpretation of the dynamics of cargo-motor-track interactions at various types of microtubule intersections. Significance Statement Translation and rotational motion of cargo during pauses at the microtubule intersections in living cells were revealed by high-accuracy three-dimensional single particle rotational tracking. The current study demonstrates the potential of studying coordinated interactions in living cellular environments by resolving characteristic rotational motions.
In-silico identification of new inhibitors for Low-density lipoprotein receptor-related protein6 (LRP6)

Abstract Low-density lipoprotein receptor-related protein 6 (LRP6) is an important therapeutic target for diseases such as osteoporosis, Alzheimer, cancer, and neurodegenerative disease. Computational methods such as ligand-based and structure-based virtual screening have been introduced as an extremely efficient and accurate tool for finding new drug targets and candidates. In this study, we aimed to screen the National Cancer Institute (NCI) Diversity Set II and parts of the ZINC database by virtual screening to identify potential and safe compounds that can inhibit the LRP6 protein. By utilizing various screening methods such as rigid and flexible molecular docking and Lipinski’s rule of five, we identified 10 potential compounds. Then, their validity was further tested by molecular dynamics simulation and MMPBSA binding free energy calculations. Eventually, it was concluded that ZINC03954520, ZINC01729523, ZINC03898665, ZINC13152226, ZINC26730911 and ZINC01069082 compounds can be potential drug compounds for inhibiting LRP6 protein. These compounds in complex with β-propeller domains of LRP6 showed that they are capable of altering the backbone of these domains and interfere with their structural dynamics which may lead to the inhibition of the signal transmission. Communicated by Ramaswamy H. Sarma
How do children with autism spectrum disorder form gist memory during sleep? A study of slow oscillation–spindle coupling

Abstract Sleep is assumed to support memory through an active systems consolidation process that does not only strengthen newly encoded representations but also facilitates the formation of more abstract gist memories. Studies in humans and rodents indicate a key role of the precise temporal coupling of sleep slow oscillations (SO) and spindles in this process. The present study aimed at bolstering these findings in typically developing (TD) children, and at dissecting particularities in SO-spindle coupling underlying signs of enhanced gist memory formation during sleep found in a foregoing study in children with autism spectrum disorder (ASD) without intellectual impairment. Sleep data from 19 boys with ASD and 20 TD boys (9–12 years) were analyzed. Children performed a picture-recognition task and the Deese–Roediger–McDermott (DRM) task before nocturnal sleep (encoding) and in the next morning (retrieval). Sleep-dependent benefits for visual-recognition memory were comparable between groups but were greater for gist abstraction (recall of DRM critical lure words) in ASD than TD children. Both groups showed a closely comparable SO-spindle coupling, with fast spindle activity nesting in SO-upstates, suggesting that a key mechanism of memory processing during sleep is fully functioning already at childhood. Picture-recognition at retrieval after sleep was positively correlated to frontocortical SO-fast-spindle coupling in TD children, and less in ASD children. Critical lure recall did not correlate with SO-spindle coupling in TD children but showed a negative correlation (r = −.64, p = .003) with parietal SO-fast-spindle coupling in ASD children, suggesting other mechanisms specifically conveying gist abstraction, that may even compete with SO-spindle coupling.
Pre-Diabetes and What It Means: The Epidemiological Evidence.

Prediabetes is an intermediate stage between normal glycemia and diabetes and is highly prevalent, especially in older age groups and obese individuals. Five different definitions of prediabetes are presently used in current practice, which are based on different cut points of HbA1C, fasting glucose, and 2-h glucose. A major challenge for the field is a lack of guidance on when one definition might be preferred over another. Risks of major complications in persons with prediabetes, including diabetes, cardiovascular disease, kidney disease, and death, also vary depending on the prediabetes definition used. Randomized clinical trials have demonstrated that lifestyle and pharmacologic interventions can be cost-effective, prevent diabetes, and improve cardiovascular risk factors in adults with prediabetes. However, the practical implementation of lifestyle modification or the use of metformin for treating prediabetes is inadequate and complicated by a lack of agreement on how to define the condition. Establishing consensus definitions for prediabetes should be a priority and will help inform expansion of insurance coverage for lifestyle modification and improve current screening and diagnostic practices. Expected final online publication date for the Annual Review of Public Health, Volume 42 is April 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Evaluation of upper labial frenectomy: A randomized, controlled comparative study of conventional scalpel technique and Er:YAG laser technique

Abnormalities in the maxillary frenum may lead to esthetic or functional limitations and need to be corrected with a surgical intervention called frenectomy. The aim of the study was to compare frenectomies performed using Er:YAG laser technology with those using a conventional scalpel technique. Comparisons were of patients' experiences, treatment times, bleeding during treatment and wound healing.
Social isolation, loneliness and functional disability in Chinese older women and men: a longitudinal study.

OBJECTIVE This study investigated whether loneliness or social isolation is associated with the onset of functional disability over 4 years among Chinese older populations. SETTING AND SUBJECTS This study used data from the China Health and Retirement Longitudinal Study (CHARLS). Functional status was assessed by activities of daily living (ADL) and instrumental activities of daily living (IADL). Analyses were conducted with data from two waves (2011 and 2015) and were restricted to those respondents aged 50 and older and free of functional disability at baseline [n = 5,154, mean age (SD) = 60.72 (7.51); male, 52.3%]. METHOD Social isolation, loneliness and covariates were measured at baseline. Follow-up measures of new-onset ADL and IADL disability were obtained 4 years later. We stratified the sample by gender, and then used binary logistic regressions to evaluate the associations between baseline isolation, loneliness and new-onset ADL and IADL disability. RESULTS For women, baseline social isolation was significantly associated with new-onset ADL (OR = 1.18, 95% CI = 1.07-1.30) and IADL (OR = 1.11, 95% CI = 1.01-1.21) disability; no significant association between loneliness and ADL or IADL disability was found. For men, neither social isolation nor loneliness was found to be significantly associated with ADL or IADL disability. CONCLUSION This longitudinal study found that social isolation, rather than loneliness, was significantly associated with functional disability over 4 years among women (but not men) in China. These findings expand our knowledge about the association between social relationships and functional status among non-Western populations.
Applications and implications of manufactured nanoparticles in soils: a review

The environmental application and risk assessment of manufactured nanoparticles (MNPs) in soil greatly depend on our understanding of the interactions between MNPs and soil components. Because of the complexity of the soil system and the very early stage of MNP research in soil, our understanding of MNP behaviour in this system is very limited. This review summarizes the progress of research on MNPs and their implications for soils. Manufactured nanoparticles are applied deliberately for soil remediation and are also released unintentionally through various other pathways to soil. Their colloidal behaviour in the soil system is discussed by analysing the effect of dissolved organic matter, light irradiation, water chemistry conditions and biological processes. The methods currently used for modelling MNP leaching and transport are summarized and several requirements for model improvement are proposed. The current topics regarding the environmental risks of MNPs (such as identifying the toxicity of MNPs and their dissolved ions, evidence that MNPs may be taken up by soil organisms or the risks of other pollutants as affected by the presence of MNPs) are described. Future research directions are discussed and proposed.