Miracle-dz/UniFAR-FTUs huggingface dataset:
Delivery of nutritional management services to people with amyotrophic lateral sclerosis (ALS)

Abstract Objectives The aim of this study was to investigate how nutritional management services for people with Amyotrophic Lateral Sclerosis (pwALS) are structured in the UK, in order to gain insight into current practice and identify key barriers and enablers to delivering and providing services. Methods: A three-part, sequential mixed-methods study was conducted that comprised (i) a thematic analysis of data from five focus groups (with 47 ALS health professionals from 41 UK organizations and four service user representatives), (ii) a nationwide cross-sectional survey (281 ALS healthcare professionals) and (iii) a freedom of information request (251 organizations). Results: UK nutritional management services for pwALS are coordinated from specialist (n = 22) and non-specialist care centers (n = 89), with national variability in the organization and delivery of services. Multidisciplinary working was highlighted to facilitate the coordination of nutritional care. However, the need to provide evidence-based continuing education for HCPs was evident. Overall, the lack of clear guidelines on the nutritional management of people with ALS was identified as a key barrier to the delivery of effective nutritional care, as was the lack of transparency and consistency in the commissioning of nutritional services. Further concerns over the timeliness of the dietetic intervention and equity of access and provision were raised. Conclusions: Our findings suggest that development of guidelines for nutritional management, particularly at diagnosis and pre-gastrostomy, could drive standardization of high quality nutritional care for pwALS. Such guidance has the potential to reduce inequalities in geographical provision by providing clarity for those commissioning specialist nutrition services.
Non‐invasive assessment of soluble skin surface biomarkers in atopic dermatitis patients—Effect of treatment

Skin biomarkers are important tools for characterizing specific disease processes in atopic dermatitis (AD) patients and can be used for monitoring and potentially predicting treatment response. Recent developments of minimally invasive skin sampling methods have made sampling easier and less inconvenient for patients. The objective of this study was to evaluate the non‐invasive patch technique developed by FibroTx for skin biomarker analysis.
Orally Administered Drug Solubility-Enhancing Formulations: Lesson Learnt from Optimum Solubility-Permeability Balance

Although oral drug delivery is considered as most acceptable route for administering the active pharmaceutical ingredients to patients of all age-groups with the exceptions of bed-ridden patients and infants, the extent and rate of drug reaching the systemic circulation (in other word, drug bioavailability) always depends on many factors such as drug solubility in gastrointestinal fluids and drug permeation into intraluminal epithelial membrane structure, absence (fasting state) and presence (fed state) of food materials in the gastrointestinal tract, and individual variations in gastric emptying time. Taking the most influential factors like drug solubility and its permeability into consideration, these two factors play a pivotal role and even act as the litmus test for the formulation scientists who involve in oral dosage form development. It is very clear that there should be an optimum solubility and permeability balance to be reachable for getting the desired drug bioavailability to exert the intended therapeutic activity. The objectives of current review are (1) to provide an overview of two-different categories of poorly water soluble API molecules, (2) to describe briefly three-different case studies taken from drug solubility-enhancing formulations dealing with interplay between solubility and permeability, and (3) to showcase selected examples of solubility-permeability interplay phenomena arising out from the various orally administrable dosage forms. The lessons learnt from the past and current literatures are certainly encouraging to go ahead for oral dosage form development but with the prior knowledge about the possible existence of solubility-permeability interplay/tradeoff phenomenon.
Comparative genetic analyses of Korean bat coronaviruses with SARS-CoV and the newly emerged SARS-CoV-2

Background Bats have been considered natural reservoirs for several pathogenic human coronaviruses (CoVs) in the last two decades. Recently, a bat CoV was detected in the Republic of Korea; its entire genome was sequenced and reported to be genetically similar to that of the severe acute respiratory syndrome CoV (SARS-CoV). Objectives The objective of this study was to compare the genetic sequences of SARS-CoV, SARS-CoV-2, and the two Korean bat CoV strains 16BO133 and B15-21, to estimate the likelihood of an interaction between the Korean bat CoVs and the human angiotensin-converting enzyme 2 (ACE2) receptor. Methods The phylogenetic analysis was conducted with the maximum-likelihood (ML) method using MEGA 7 software. The Korean bat CoVs receptor binding domain (RBD) of the spike protein was analyzed by comparative homology modeling using the SWISS-MODEL server. The binding energies of the complexes were calculated using PRODIGY and MM/GBGA. Results Phylogenetic analyses of the entire RNA-dependent RNA polymerase, spike regions, and the complete genome revealed that the Korean CoVs, along with SARS-CoV and SARS-CoV-2, belong to the subgenus Sarbecovirus, within BetaCoVs. However, the two Korean CoVs were distinct from SARS-CoV-2. Specifically, the spike gene of the Korean CoVs, which is involved in host infection, differed from that of SARS-CoV-2, showing only 66.8%–67.0% nucleotide homology and presented deletions within the RBD, particularly within regions critical for cross-species transmission and that mediate interaction with ACE2. Binding free energy calculation revealed that the binding affinity of Korean bat CoV RBD to hACE2 was drastically lower than that of SARS-CoV and SARS-CoV-2. Conclusions These results suggest that Korean bat CoVs are unlikely to bind to the human ACE2 receptor.
Diet as a Potential Moderator for Genome Stability and Immune Response in Pediatric Leukemia

Simple Summary Pediatric acute lymphoblastic leukemia (ALL) is the most prevalent cancer affecting children in developed societies. Here, we review the role of diet in control of the incidence and progression of childhood ALL. Prenatally, ALL risk is associated with higher birthweights of newborns, suggesting that ALL begins to evolve in-utero. Indeed, maternal diet influences the fetal genome and immune development. Postnatally, breastfeeding associates with decreased risk of ALL development. Finally, for the ALL-affected child, certain dietary regimens that impact the hormonal environment may impede disease progression. Improved understanding of the dietary regulation of hormones and immunity may inform better approaches to predict, protect, and ultimately save children afflicted with pediatric leukemia. Abstract Pediatric leukemias are the most prevalent cancers affecting children in developed societies, with childhood acute lymphoblastic leukemia (ALL) being the most common subtype. As diet is a likely modulator of many diseases, this review focuses on the potential for diet to influence the incidence and progression of childhood ALL. In particular, the potential effect of diets on genome stability and immunity during the prenatal and postnatal stages of early childhood development are discussed. Maternal diet plays an integral role in shaping the bodily composition of the newborn, and thus may influence fetal genome stability and immune system development. Indeed, higher birth weights of newborns are associated with increased risk of ALL, which suggests in-utero biology may shape the evolution of preleukemic clones. Postnatally, the ingestion of maternal breastmilk both nourishes the infant, and provides essential components that strengthen and educate the developing immune system. Consistently, breast-feeding associates with decreased risk of ALL development. For children already suffering from ALL, certain dietary regimens have been proposed. These regimens, which have been validated in both animals and humans, alter the internal hormonal environment. Thus, hormonal regulation by diet may shape childhood metabolism and immunity in a manner that is detrimental to the evolution or expansion of preleukemic and leukemic ALL clones.
Superpixel-Based Quality Assessment of Multi-Exposure Image Fusion for Both Static and Dynamic Scenes

Multi-exposure image fusion (MEF) algorithms have been used to merge a stack of low dynamic range images with various exposure levels into a well-perceived image. However, little work has been dedicated to predicting the visual quality of fused images. In this work, we propose a novel and efficient objective image quality assessment (IQA) model for MEF images of both static and dynamic scenes based on superpixels and an information theory adaptive pooling strategy. First, with the help of superpixels, we divide fused images into large- and small-changed regions using the structural inconsistency map between each exposure and fused images. Then, we compute the quality maps based on the Laplacian pyramid for large- and small-changed regions separately. Finally, an information theory induced adaptive pooling strategy is proposed to compute the perceptual quality of the fused image. Experimental results on three public databases of MEF images demonstrate the proposed model achieves promising performance and yields a relatively low computational complexity. Additionally, we also demonstrate the potential application for parameter tuning of MEF algorithms.
The impact of telemedicine on patients with uncontrolled type 2 diabetes mellitus during the COVID-19 pandemic in Saudi Arabia: Findings and implications

Introduction Routine diabetes care changed during the COVID-19 pandemic due to precautionary measures such as lockdowns, cancellation of in-person visits, and patients’ fear of being infected when attending clinics. Because of the pandemic, virtual clinics were implemented to provide diabetes care. Therefore, we conducted this study to assess the impact of these virtual clinics on glycaemic control among high-risk patients with type 2 diabetes mellitus (DM). Methods A prospective single-cohort pre-/post telemedicine care intervention study was conducted on 130 patients with type 2 DM attending a virtual integrated care clinic at a chronic Illness center in a family and community medicine department in Riyadh, Saudi Arabia during the COVID-19 pandemic. Results The mean age of the participants was 57 years (standard deviation (SD) = 12) and the mean (SD) duration of diabetes was 14 (7) years. Over a period of 4 months, the HbA1c decreased significantly from 9.98 ± 1.33 pre-intervention to 8.32 ± 1.31 post-intervention (mean difference 1.66 ± 1.29; CI = 1.43–1.88; P <0.001). In addition, most in-person care visits were successfully replaced, as most patients (64%) needed only one or two in-person visits during the 4-month period, compared with typically one visit every 1–2 weeks in the integrated care programme before the pandemic for this group of high-risk patients. Discussion The current study found a significant positive impact of telemedicine care on glycaemic control among high-risk patients with DM during the COVID-19 pandemic. Moreover, it showed that telemedicine could be integrated into diabetic care to successfully replace many of the usual in-person care visits. Consequently, health policy makers need to consider developing comprehensive guidelines in Saudi Arabia for telemedicine care to, ensure the quality of care and address issues such as financial reimbursement and patient information privacy.
The effects of fatty acid amide hydrolase inhibition and monoacylglycerol lipase inhibition on habit formation in mice

Emerging data indicate that endocannabinoid signaling is critical to the formation of habitual behavior. Previous work demonstrated that antagonism of cannabinoid receptor type 1 (CB1R) with AM251 during operant training impairs habit formation, but it is not known if this behavioral effect is specific to disrupted signaling of the endocannabinoid ligands anandamide or 2‐arachidonoyl glycerol (2‐AG). Here, we used selective pharmacological compounds during operant training to determine the impact of fatty acid amide hydrolase (FAAH) inhibition to increase anandamide (and other n‐acylethanolamines) or monoacylglycerol lipase (MAGL) inhibition to increase 2‐AG levels on the formation of habitual behaviors in mice using a food‐reinforced contingency degradation procedure. We found, contrary to our hypothesis, that inhibition of FAAH and of MAGL disrupted the formation of habits. Next, AM251 was administered during training to verify that impaired habit formation could be assessed using contingency degradation. AM251‐exposed mice responded at lower rates during training and at higher rates in the test. To understand the inconsistency with published data, we performed a proof‐of‐principle dose–response experiment to compare AM251 in our vehicle‐solution to the published vehicle‐suspension on response rates. We found consistent reductions in response rate with increasing doses of AM251 in solution and an inconsistent dose–response relationship with AM251 in suspension. Together, our data suggest that further characterization of the role of CB1R signaling in the formation of habitual responding is warranted and that augmenting endocannabinoids may have clinical utility for prophylactically preventing aberrant habit formation such as that hypothesized to occur in substance use disorders.
Reaction of NO2 with Zn and ZnO: Photoemission, XANES, and Density Functional Studies on the Formation of NO3

Synchrotron-based high-resolution photoemission and X-ray absorption near-edge spectroscopy (XANES) have been used to study the interaction of NO2 with polycrystalline surfaces of metallic zinc and zinc oxide. NO2 exhibits a complex chemistry on metallic zinc. After adsorbing nitrogen dioxide, N, O, NO, NO2, and NO3 are present on the surface of the metal. At room temperature the NO2 molecule mainly dissociates into O adatoms and gaseous NO, whereas at low temperatures (<250 K) chemisorbed NO2 and NO3 dominate on the surface. NO2 is a very good oxidizing agent for preparing ZnO from metallic zinc. Zn reacts more vigorously with NO2 than metals, such as Rh, Pd, or Pt which are typical catalysts for the removal of NOx molecules (DeNOx process). At 300 K, the main product of the reaction of NO2 with polycrystalline ZnO is adsorbed NO3 with little NO2 or NO present on the surface of the oxide. No evidence was found for the full decomposition of the NO2 molecule (i.e., no NO2 → N + 2O). The results of density .
ROR1 targeting with the antibody drug-conjugate VLS-101 is effective in Richter syndrome patient-derived xenograft mouse models.

Richter syndrome (RS) represents the transformation of chronic lymphocytic leukemia (CLL), typically to an aggressive lymphoma. Treatment options for RS are limited and the disease is often fatal. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is expressed on CLL cells and other cancers but not on normal adult tissues, making it an attractive, tumor-specific therapeutic target. VLS‑101 is being developed as an antibody-drug conjugate (ADC) for therapy of ROR1-expressing (ROR1+) cancers. VLS-101 comprises UC‑961 (a humanized immunoglobulin IgG1 monoclonal antibody that binds an extracellular epitope of human ROR1), a maleimidocaproyl-valine-citrulline-para-aminobenzoate (mc-vc-PAB) linker, and the anti‑microtubule cytotoxin monomethyl auristatin E (MMAE). VLS‑101 binding to ROR1 results in rapid cellular internalization and delivery of MMAE to induce tumor cell death. We studied 4 RS patient-derived xenografts (RS‑PDXs) with varying levels of ROR1 expression (11%, 32%, 85%, 99% of cells). VLS-101 showed no efficacy in the lowest-expressing RS-PDX but induced complete remissions in those with higher levels of ROR1 expression. Responses were maintained during the post-therapy period, particularly after higher VLS-101 doses. In systemic ROR1+ RS-PDXs, VLS-101 dramatically decreased tumor burden in all RS-colonized tissues and significantly prolonged survival. Animals showed no adverse effects or weight loss. Our results confirm ROR1 as a target in RS and demonstrate the therapeutic potential of using an ADC directed toward ROR1 for the treatment of hematological cancers. A Phase 1 clinical trial of VLS‑101 (NCT03833180) is ongoing in patients with RS and other hematological malignancies.
Study the Antifungal and Ocular Permeation of Ketoconazole from Ophthalmic Formulations Containing Trans-Ethosomes Nanoparticles

Ketoconazole (KET), a synthetic imidazole broad-spectrum antifungal agent, is characterized by its poor aqueous solubility and high molecular weight, which might hamper its corneal permeation. The aim was to develop an ophthalmic formulation loaded with optimized trans-ethosomal vesicles to enhance KET ocular permeation, antifungal activity, rapid drug drainage, and short elimination half-life. Four formulation factors affecting the vesicles’ size, zeta potential, entrapment efficiency, and flexibility of the trans-ethosomes formulations were optimized. The optimum formulation was characterized, and their morphological and antifungal activity were studied. Different ophthalmic formulations loaded with the optimized vesicles were prepared and characterized. The ocular irritation and in vivo corneal permeation were investigated. Results revealed that the drug-to-phospholipid-molar ratio, the percentage of edge activator, the percentage of ethanol, and the percentage of stearyl amine significantly affect the characteristics of the vesicles. The optimized vesicles were spherical and showed an average size of 151.34 ± 8.73 nm, a zeta potential value of +34.82 ± 2.64 mV, an entrapment efficiency of 94.97 ± 5.41%, and flexibility of 95.44 ± 4.33%. The antifungal activity of KET was significantly improved following treatment with the optimized vesicles. The developed in situ gel formulations were found to be nonirritating to the cornea. The trans-ethosomes vesicles were able to penetrate deeper into the posterior eye segment without any toxic effects. Accordingly, the in situ developed gel formulation loaded with KET trans-ethosomes vesicles represents a promising ocular delivery system for the treatment of deep fungal eye infections.
Molecular basis of ciliary defects caused by compound heterozygous IFT144/WDR19 mutations found in cranioectodermal dysplasia.

Primary cilia contain specific proteins to achieve their functions as cellular antennae. Ciliary protein trafficking is mediated by the intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes. Mutations in genes encoding the IFT-A subunits (IFT43, IFT121/WDR35, IFT122, IFT139/TTC21B, IFT140, and IFT144/WDR19) often result in skeletal ciliopathies, including cranioectodermal dysplasia (CED). We here characterized the molecular and cellular defects of CED caused by compound heterozygous mutations in IFT144 [the missense variant IFT144(L710S) and the nonsense variant IFT144(R1103*)]. These two variants were distinct with regard to their interactions with other IFT-A subunits and with the IFT-B complex. When exogenously expressed in IFT144-knockout (KO) cells, IFT144(L710S) as well as IFT144(WT) rescued both moderately compromised ciliogenesis and the abnormal localization of ciliary proteins. As the homozygous IFT144(L710S) mutation was found to cause autosomal recessive retinitis pigmentosa, IFT144(L710S) is likely to be hypomorphic at the cellular level. In striking contrast, the exogenous expression of IFT144(R1103*) in IFT144-KO cells exacerbated the ciliogenesis defects. The expression of IFT144(R1103*) together with IFT144(WT) restored the abnormal phenotypes of IFT144-KO cells. However, the coexpression of IFT144(R1103*) with the hypomorphic IFT144(L710S) variant in IFT144-KO cells, which mimics the genotype of compound heterozygous CED patients, resulted in severe ciliogenesis defects. Taken together, these observations demonstrate that compound heterozygous mutations in IFT144 cause severe ciliary defects via a complicated mechanism, where one allele can cause severe ciliary defects when combined with a hypomorphic allele.
Review of Pharmacologic Considerations in the Use of Azole Antifungals in Lung Transplant Recipients

Mold-active azole antifungals are commonly prescribed for the prevention of invasive fungal infections in lung transplant recipients. Each agent exhibits a unique pharmacologic profile, an understanding of which is crucial for therapy selection and optimization. This article reviews pharmacologic considerations for three frequently-used azole antifungals in lung transplant recipients: voriconazole, posaconazole, and isavuconazole. Focus is drawn to analysis of drug-interactions, adverse drug reactions, pharmacokinetic considerations, and the role of therapeutic drug monitoring with special emphasis on data from the post-lung transplant population.
Time Window for Ischemic Stroke First Mobilization Effectiveness (TIME): Protocol for an Investigator-Initiated Prospective Multicenter Randomized 3-Arm Clinical Trial.

OBJECTIVE The purpose of this study is to investigate the optimal time window for initiating mobilizing after acute ischemic stroke. METHODS The TIME trial is a pragmatic, investigator-initiated, multi-center, randomized, 3-arm parallel group, clinical trial. This trial will be conducted in 57 general hospitals in mainland China affiliated with the China Stroke Databank Center and will enroll 6,033 eligible patients with acute ischemic stroke. Participants will be randomly allocated to either (1) the very early mobilization group in which mobilization is initiated within 24 hours from stroke onset, (2) the early mobilization group in which mobilization begins between 24 and 72 hours poststroke, or (3) the late mobilization group in which mobilization is started after 72 hours poststroke. The mobilization protocol is otherwise standardized and identical for each comparison group. Mobilization is titrated by baseline mobility level and progress of patients throughout the intervention period. The primary outcome is death or disability assessed with the modified Rankin scale at 3 months poststroke. Secondary outcomes include impairment score of the National Institutes of Health Stroke Scale, dependence in activities of daily living as measured using the modified Barthel Index, cognitive ability assessed with the Mini-Mental State Examination, incidence of adverse events, hospital length of stay, and total medical costs. CONCLUSIONS The TIME trial is designed to answer the question "when is the best time to start mobilization after stroke? " The effect of timing is isolated from the effect of type and dose of mobilization by otherwise applying a standard mobilization protocol across groups. The TIME trial may, therefore, contribute to increasing the knowledge base regarding the optimal time window for initiating mobilization after acute ischemic stroke.