Miracle-dz/UniFAR-FTUs huggingface dataset:
First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies

Purpose: This first-in-human study assessed the safety, tolerability, dose-limiting toxicities (DLT), antitumor activity, and pharmacokinetics of cemiplimab, a monoclonal anti-programmed cell death-1 (PD-1), as monotherapy and in combination with hypofractionated radiotherapy (hfRT) and/or cyclophosphamide (CPA) in patients with advanced solid tumors. Patients and Methods: Patients were enrolled in 1 of 10 dose escalation cohorts and received cemiplimab 1, 3, or 10 mg/kg every 2 weeks intravenously for up to 48 weeks. Depending on the cohort, patients received hfRT and/or low-dose (200 mg/m2) CPA. Safety was evaluated. Antitumor activity was assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Results: Sixty patients were enrolled. The median duration of follow-up was 19.3 weeks (range, 2.3–84.3). There were no DLTs. The most common treatment-emergent adverse events (TEAEs) of any grade were fatigue (45.0%), nausea (36.7%), and vomiting (25.0%). The most common immune-related adverse events (irAEs) of any grade were arthralgia (10.0%), hypothyroidism (8.3%), and maculopapular rash (8.3%). Cemiplimab pharmacokinetic parameters increased in a close to dose-proportional manner and were similar regardless of combination therapy regimen. Two patients (one with cutaneous squamous cell carcinoma and one with cervical cancer) experienced a complete response; 7 had a partial response. Observed duration of response was ≥12 months in 6 patients. Conclusions: The safety profile of cemiplimab was comparable with other anti–PD-1 agents. Addition of hfRT and/or CPA did not appear to increase grade ≥3 irAEs, suggesting that cemiplimab can be safely administered with hfRT and/or CPA. Cemiplimab exhibited encouraging antitumor activity with 2 complete responses and 7 partial responses observed; responses were also durable.
SpaB, an atypically adhesive basal pilin from the lactobacillar SpaCBA pilus: crystallization and X-ray diffraction analysis.

The SpaB pilin is recognized as the basal subunit of the sortase-dependent SpaCBA pilus, which is known to be produced by the Gram-positive Lactobacillus rhamnosus GG, a gut-adapted commensal advocated to have health benefits. Despite seeming to function as an archetypal basal pilin by serving as the terminal subunit in pilus assembly, SpaB also assumes an atypical role as a mucoadhesive protein. To shed light on the structural factors that contribute to this dual functional behaviour, a recombinant form of the L. rhamnosus GG SpaB pilin was produced and purified for crystallization and X-ray diffraction experiments. The crystallization of SpaB remained particularly challenging until the implementation of a three-pronged crystallization approach involving C-terminal tail truncation, surface lysine methylation and magnesium additives. Ultimately, hexagonal crystals of SpaB were produced and were able to diffract to a resolution of 2.4 Å. This crystal form belonged to space group P6522 or P6122, with unit-cell parameters a = b = 51.53, c = 408.22 Å, α = β = 90.0, γ = 120.0°. Obtaining an interpretable electron-density map via single-wavelength anomalous diffraction (SAD) using iodide-derivative data sets did not succeed owing to the weak anomalous signal. As an alternative, attempts to provide phases by molecular replacement using the iodide-SAD data from SpaB and a collection of distant homology models (<28% sequence identity) are in progress.
Relevance of Translation Initiation in Diffuse Glioma Biology and its Therapeutic Potential

Cancer cells are continually exposed to environmental stressors forcing them to adapt their protein production to survive. The translational machinery can be recruited by malignant cells to synthesize proteins required to promote their survival, even in times of high physiological and pathological stress. This phenomenon has been described in several cancers including in gliomas. Abnormal regulation of translation has encouraged the development of new therapeutics targeting the protein synthesis pathway. This approach could be meaningful for glioma given the fact that the median survival following diagnosis of the highest grade of glioma remains short despite current therapy. The identification of new targets for the development of novel therapeutics is therefore needed in order to improve this devastating overall survival rate. This review discusses current literature on translation in gliomas with a focus on the initiation step covering both the cap-dependent and cap-independent modes of initiation. The different translation initiation protagonists will be described in normal conditions and then in gliomas. In addition, their gene expression in gliomas will systematically be examined using two freely available datasets. Finally, we will discuss different pathways regulating translation initiation and current drugs targeting the translational machinery and their potential for the treatment of gliomas.
Development of a Sensor with a Lipid/Polymer Membrane Comprising Na+ Ionophores to Evaluate the Saltiness Enhancement Effect

The saltiness enhancement effect is the effect whereby saltiness is enhanced by adding specific substances to salt (sodium chloride). Since this effect can be used in the development of salt-reduced foods, a method to objectively evaluate the saltiness with this effect is required. A taste sensor with lipid/polymer membranes has been used to quantify the taste of food and beverages in recent years. The sensor electrodes of this taste sensor have the feature of selectively responding to each of the five basic tastes, which is realized by the lipid/polymer membranes. In this study, we developed a new saltiness sensor based on the lipid/polymer membrane with the aim of quantifying the saltiness enhancement effect. In addition to the conventional components of a lipid, plasticizer, and polymer supporting reagent, the membrane we developed comprises ionophores, which selectively capture sodium ions. As a result, the response of the sensor increased logarithmically with the activity of NaCl in measured samples, similarly to the taste response of humans. In addition, all of the sensor responses increased upon adding saltiness-enhancing substances, such as citric acid, tartaric acid and branched-chain amino acids (BCAAs), to NaCl samples. These findings suggest that it is possible to quantify the saltiness enhancement effect using a taste sensor with lipid/polymer membranes.
MOTHERS AND HEALTH PROMOTION: CLOSING THE GAP FOR 100% MEASLES IMMUNIZATION IN NORTH VIETNAM

Objectives: This study aims to develop a better understanding of mothers’ knowledge, understanding, and attitude towards children’s measles immunization and explore the relationship between mothers’ understanding of measles immunization and health promotion programs in North Vietnam. Methods: Semistructured interviews were conducted with 15 mothers of children aged 1 or 6 years old between 2006 and 2010 in two provinces in North Vietnam. Ten interviews were transcribed and analysed to explore themes while other five interviews were cross-referenced for congruency. Among the ten mothers whose interviews were analysed, there were five mothers whose children received the full measles immunization schedule (two doses) and five mothers whose children received one or none of measles vaccination. Results: Mothers had different levels of understanding and a strong positive attitude towards measles immunization. Mothers considered health officers at the commune health centres who played an important role in the promotion of measles immunization, as the main source of information. The relationship between the mother’s understanding about measles immunization and health promotion programs was found to be both positive and negative. Conclusion: Mothers whose children received the full measles immunization schedule paid more attention to measles immunization and health promotion programs compared with mothers whose children received one or none of measles vaccination. Mothers’ misunderstanding about the measles immunization schedule was the main reason for choosing not to receive the measles immunizations. These findings help to improve communication with mothers about measles immunization and close the gap for 100% measles immunization in North Vietnam. Please download Vol. 19 (2013): (December) Malaysian Journal of Paediatrics and Child Health from here
Treatment options for tic disorders

ABSTRACT Introduction: Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder, characterized by the presence of multiple motor and, at least one, phonic tics, for more than one year, beginning before 18 years of age; its treatment is often a challenge for the clinician Areas covered: GTS treatment requires a multidisciplinary management to treat each patient’s symptom. Although individuals with GTS often have comorbid psychiatric disorders, the focus of this review will only be on the management of tics. Expert opinion: The authors summarized the steps that clinicians should follow treating GTS patient; the impact of the tics on a patients’ life should be the first step; different patients could present different levels of tolerance to the symptoms. Second, comorbidities should be considered before starting a treatment for tic. Finally, clinicians must focus the attention of the patient and family, on the length of the treatment and the duration of time after which the effects of the drug will occur. Before the treatment, the potential side effects must be mentioned to the parents, and the choice of treatment must be made in the light of the patient’s tolerance to these.
Transport-Layer Limitations for NFV Orchestration in Resource-Constrained Aerial Networks

In this paper, we identify the main challenges and problems related with the management and orchestration of Virtualized Network Functions (VNFs) over aerial networks built with Small Unmanned Aerial Vehicles (SUAVs). Our analysis starts from a reference scenario, where several SUAVs are deployed over a delimited geographic area, and provide a mobile cloud environment that supports the deployment of functions and services using Network Functions Virtualization (NFV) technologies. After analyzing the main challenges to NFV orchestration in this reference scenario from a theoretical perspective, we undertake the study of one specific but relevant aspect following a practical perspective, i.e., the limitations of existing transport-layer solutions to support the dissemination of NFV management and orchestration information in the considered scenario. While in traditional cloud computing environments this traffic is delivered using TCP, our simulation results suggest that using this protocol over an aerial network of SUAVs presents certain limitations. Finally, based on the lessons learned from our practical analysis, the paper outlines different alternatives that could be followed to address these challenges.
TCGA-TCIA Impact on Radiogenomics Cancer Research: A Systematic Review

In the last decade, the development of radiogenomics research has produced a significant amount of papers describing relations between imaging features and several molecular ‘omic signatures arising from next-generation sequencing technology and their potential role in the integrated diagnostic field. The most vulnerable point of many of these studies lies in the poor number of involved patients. In this scenario, a leading role is played by The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA), which make available, respectively, molecular ‘omic data and linked imaging data. In this review, we systematically collected and analyzed radiogenomic studies based on TCGA-TCIA data. We organized literature per tumor type and molecular ‘omic data in order to discuss salient imaging genomic associations and limitations of each study. Finally, we outlined the potential clinical impact of radiogenomics to improve the accuracy of diagnosis and the prediction of patient outcomes in oncology.
The Performance of Deep Learning Algorithms on Automatic Pulmonary Nodule Detection and Classification Tested on Different Datasets That Are Not Derived from LIDC-IDRI: A Systematic Review

The aim of this study was to systematically review the performance of deep learning technology in detecting and classifying pulmonary nodules on computed tomography (CT) scans that were not from the Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) database. Furthermore, we explored the difference in performance when the deep learning technology was applied to test datasets different from the training datasets. Only peer-reviewed, original research articles utilizing deep learning technology were included in this study, and only results from testing on datasets other than the LIDC-IDRI were included. We searched a total of six databases: EMBASE, PubMed, Cochrane Library, the Institute of Electrical and Electronics Engineers, Inc. (IEEE), Scopus, and Web of Science. This resulted in 1782 studies after duplicates were removed, and a total of 26 studies were included in this systematic review. Three studies explored the performance of pulmonary nodule detection only, 16 studies explored the performance of pulmonary nodule classification only, and 7 studies had reports of both pulmonary nodule detection and classification. Three different deep learning architectures were mentioned amongst the included studies: convolutional neural network (CNN), massive training artificial neural network (MTANN), and deep stacked denoising autoencoder extreme learning machine (SDAE-ELM). The studies reached a classification accuracy between 68–99.6% and a detection accuracy between 80.6–94%. Performance of deep learning technology in studies using different test and training datasets was comparable to studies using same type of test and training datasets. In conclusion, deep learning was able to achieve high levels of accuracy, sensitivity, and/or specificity in detecting and/or classifying nodules when applied to pulmonary CT scans not from the LIDC-IDRI database.
Associations Between Microstructure, Amyloid, and Cognition in Amnestic Mild Cognitive Impairment and Dementia.

BACKGROUND Although amyloid-β (Aβ) and microstructural brain changes are both effective biomarkers of Alzheimer's disease, their independent or synergistic effects on cognitive decline are unclear. OBJECTIVE To examine associations of Aβ and brain microstructure with cognitive decline in amnestic mild cognitive impairment and dementia. METHODS Restriction spectrum imaging, cerebrospinal fluid Aβ, and longitudinal cognitive data were collected on 23 healthy controls and 13 individuals with mild cognitive impairment or mild to moderate Alzheimer's disease. Neurite density (ND) and isotropic free water diffusion (IF) were computed in fiber tracts and cortical regions of interest. We examined associations of Aβ with regional and whole-brain microstructure, and assessed whether microstructure mediates effects of Aβ on cognitive decline. RESULTS Lower ND in limbic and association fibers and higher medial temporal lobe IF predicted baseline impairment and longitudinal decline across multiple cognitive domains. ND and IF predicted cognitive outcomes after adjustment for Aβ or whole-brain microstructure. Correlations between microstructure and cognition were present for both amyloid-positive and amyloid-negative individuals. Aβ correlated with whole-brain, rather than regional, ND and IF. CONCLUSION Aβ correlates with widespread microstructural brain changes, whereas regional microstructure correlates with cognitive decline. Microstructural abnormalities predict cognitive decline regardless of amyloid, and may inform about neural injury leading to cognitive decline beyond that attributable to amyloid.
HIV pre-exposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and changes in kidney function and tubular health.

OBJECTIVE To evaluate the effects of HIV preexposure prophylaxis (PrEP) with tenofovir disoproxial fumurate (TDF)/emtricitabine (FTC) on kidney function and kidney tubular health. DESIGN The Iniciativa Profilaxis Pre-Exposicion open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC. This study included 123 iPrEx-OLE participants who demonstrated PrEP adherence. METHODS We compared estimated glomerular filtration rate calculated using serum creatinine (eGFRcr), serum cystatin C (eGFRcys), and in combination (eGFRcr-cys), and a panel of 14 urine biomarkers reflecting kidney tubular health before and 6 months after PrEP initiation. RESULTS At baseline, mean eGFRcr, eGFRcys, and eGFRcr-cys were 108.3, 107.0, and 111.1 ml/min/1.73 m, respectively. Six months after PrEP initiation, eGFRcr declined by -4% (95% CI: -5.7 to -2.4%), eGFRcys declined by -3.3% (95% CI: -8.3 to 1.9%), and eGFRcr-cys declined by -4.1% (95% CI: -7.5 to -0.7%). From the urine biomarker panel, α1-microglobulin and β2-microglobulin increased by 22.7% (95% CI: 11.8--34.7%) and 14.1% (95% CI: -6.1 to 38.6%), whereas chitinase-3-like 1 protein and monocyte chemoattractant protein-1 decreased by -37.7% (95% CI: -53.0 to -17.3%) and -15.6% (95% CI: -31.6 to 4.2%), respectively. Ten of the 14 urine biomarkers, including albumin, had estimated changes of less than 12% with wide confidence intervals. CONCLUSION Six months of PrEP with TDF/FTC was associated with decreases in eGFRcr and eGFRcys. We also observed for the first time changes in 4 of 14 urine biomarkers reflecting kidney tubular health. These findings demonstrate that PrEP has direct effects on eGFR and the proximal tubule.
Effects of Hyperoxia on the Refraction in Murine Neonatal and Adult Models

Whether hyperoxia affects the refraction in neonatal and adult mice is unknown. The mice exposed to 85% oxygen at postnatal 8 days (P8d) for 3 days and the mice exposed to normal air were assigned to the neonatal hyperoxia and normoxia groups, respectively. The refraction, the corneal curvature radius (CR) and the axial length (AL) were measured at P30d and P47d. Postnatal 6 weeks (P6w) adult mice were divided into the adult hyperoxia and normoxia groups. These parameters were measured before oxygen exposure, after 1 and 6 weeks, and every 7 weeks. The lens elasticity was measured at P7w and P26w by enucleation. The neonatal hyperoxia group showed a significantly larger myopic change than the neonatal normoxia group (P47d −6.56 ± 5.89 D, +4.11 ± 2.02 D, p < 0.001), whereas the changes in AL were not significantly different (P47d, 3.31 ± 0.04 mm, 3.31 ± 0.05 mm, p = 0.852). The adult hyperoxia group also showed a significantly larger myopic change (P12w, −7.20 ± 4.09 D, +7.52 ± 2.54 D, p < 0.001). The AL did not show significant difference (P12w, 3.44 ± 0.03 mm, 3.43 ± 0.01 mm, p = 0.545); however, the CR in the adult hyperoxia group was significantly smaller than the adult normoxia group (P12w, 1.44 ± 0.03 mm, 1.50 ± 0.03 mm, p = 0.003). In conclusion, hyperoxia was demonstrated to induce myopic shift both in neonatal and adult mice, which was attributed to the change in the CR rather than the AL. Elucidation of the mechanisms of hyperoxia and the application of this result to humans should be carried out in future studies.
Remotely supervised transcranial direct current stimulation: A feasibility study for amyotrophic lateral sclerosis.

BACKGROUND Transcranial direct current stimulation (tDCS) has been investigated as a therapeutic neuromodulation tool in several neurological disorders. However, evidence supporting its efficacy in disorders such as amyotrophic lateral sclerosis (ALS) is limited possibly due to limited patient accessibility for research, particularly for individuals with advanced disease progression. Telerehabilitation using home-based protocols allows for remote supervision of tDCS over longer durations, thereby increasing participation, compliance and adherence. In this study, we explored the safety, feasibility and preliminary effects of a remotely supervised tDCS (RS-tDCS) protocol in ALS. MATERIAL AND METHODS In this pre-post case series study, two individuals with ALS completed 24 remotely supervised anodal tDCS sessions (20 minutes, 2 mA). Outcomes included adherence, compliance, disease progression, walking speed, risk of fall, endurance, fatigue and depression. RESULTS Both participants successfully completed the study without any major adverse effects. Minor side effects included mild sensations of itching and throbbing under the electrodes during stimulation. Clinical outcomes showed minimal to no change for any of the measures. CONCLUSIONS Preliminary findings suggest that the RS-tDCS protocol is safe and feasible in individuals with ALS. Our protocol serves as a model for future long-term studies to evaluate the clinical and neurophysiological effects of tDCS using a telerehabilitation protocol in ALS.
Forensic genetic polymorphisms and population structure of the Guizhou Bouyei people based on 19 X-STR loci

Abstract Background: Guizhou province is located in southwest China with abundant genetic, linguistic and cultural diversity. The Bouyei is one of the 18 officially recognised minority groups in Guizhou, accounting for about 97% of the total Bouyei population in China. However, the genetic history and forensic characterisation of the Bouyei people is largely unknown due to a lack of genetic data. Aim: We aim to investigate genetic polymorphisms and forensic characterisation of the Guizhou Bouyei population, as well as the relationships between the Bouyei and other East Asian populations. Subjects and methods: We genotyped 19 X-STRs in 188 males and 165 females of Guizhou Bouyei using the AGCU X19 STR Kit. We estimated allele frequencies, forensic parameters and genetic distances between the Bouyei and other East Asian populations. We presented the genetic distances in a phylogenetic tree, an MDS plot and a PCA plot. Results: In Guizhou Bouyei individuals, we observed 216 alleles with corresponding frequencies ranging from 0.0019 to 0.6757. All of the six combined powers of PDm, PDf, MEC Krüger, MEC Kishida, MEC Desmarais and MEC Desmarais in allele diversity and haplotype diversity are larger than 0.99999995. We found genetic affinities among the Bouyei people and their geographical neighbouring populations in Guizhou, such as the Sui, Miao and Han. Conclusions: The highly polymorphic and informative forensic parameters of the 19 X-STRs in Bouyei people show the powerful potential of those markers in forensic identification and parentage tests. The genetic relationships of the Bouyei with other East Asian populations correspond well with geographic affiliations as well as linguistic classifications.