Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene expression and prognosis of x-ray repair cross-complementing family members in non-small cell lung cancer

ABSTRACT The X-ray repair cross-complementing gene (XRCC) family participates in DNA damage repair and its dysregulation is associated with the development and progression of a variety of cancers. However, XRCCs have not been systematically studied in non-small cell lung cancer (NSCLC). Using The Cancer Genome Atlas (TCGA) and Oncomine databases, we compared the expression levels of XRCCs between NSCLC and normal tissues and performed survival analysis using the data from TCGA. The correlations of XRCCs with the clinical parameters were then analyzed using UCSC Xena. Genetic alterations in XRCCs in NSCLC and their effects on the prognosis of patients were presented using cBioPortal. SurvivalMeth was used to explore the differentially methylated sites associated with NSCLC and their effect on prognosis. Next, the immunological correlations of XRCCs expression level were analyzed using TIMER 2.0. Finally, GeneMANIA was used to visualize and analyze the functionally relevant genes, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for functional and pathway enrichment analyses of prognostic genes. Our results revealed that XRCCs were overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Univariate and multivariate Cox analyses showed that XRCC4/5/6 were independent risk factors for LUAD. Additionally, genetic alterations, methylation, and immune cell infiltration demonstrated an association between XRCC4/5/6 and poor prognosis in LUAD. Finally, the KEGG-enriched and non-homologous end-joining (NHEJ) pathways were shown to be associated with XRCC4/5/6. In conclusion, our study demonstrated that XRCC4/5/6 could be used as diagnostic and prognostic biomarkers for LUAD.
miR-195-5p regulates cell proliferation, apoptosis, and invasion of thyroid cancer by targeting telomerase reverse transcriptase

ABSTRACT In most human primary cancers, the expression, or telomerase activity, of telomerase reverse transcriptase (TERT) is detectable. However, the mechanism ofTERTactivity within oncogenesis of thyroid cancer remains largely unknown. In this study, we identified miR-195-5p as having involvement in cell proliferation, apoptosis, and invasion in human thyroid cancer. MTT was used to measure cell proliferation, Transwell chamber was used to measure invasion. Western blotting was used to detect the expressions of TERT, PCNA, and Ki67. Target gene prediction software predicted that TERT may be the target gene of miR-195-5p. Luciferase reporting system was used to identify the targeting relationship. A significant increase of in TERT expression was observed by immunohistochemistry compared with normal tissue, however, a decrease in miR-195-5p expression using qRT-PCRand western blot compared with normal cells. Functional analysis demonstrates that miR-195-5p negatively correlated withTERTand inhibitedTERTexpression through its interaction with theTERT3ʹ-untranslatedregion (3ʹ-UTR). Overexpression of miR-195-5p was shown to inhibit proliferation and invasion, and promote apoptosis of CAL-62 thyroid cancer cells. miR-195-5p-mediatedeffects were rescued by the overexpression ofTERT. Altogether, our data demonstrate that miR-195-5p regulates cell proliferation, apoptosis, and invasion in human thyroid cancer viaTERT, providing evidence of a new potential therapeutic target for further investigation.
Non‐negative blind deconvolution for signal processing in a CRISPR‐edited iPSC‐cardiomyocyte model of dilated cardiomyopathy

We developed an integrated platform for analysis of parameterized data from human disease models. We report a non‐negative blind deconvolution (NNBD) approach to quantify calcium (Ca2+) handling, beating force and contractility in human‐induced pluripotent stem cell‐derived cardiomyocytes (iPSC‐CMs) at the single‐cell level. We employed CRISPR/Cas gene editing to introduce a dilated cardiomyopathy (DCM)‐causing mutation in troponin T (TnT), TnT‐R141W, into wild‐type control iPSCs (MUT). The NNDB‐based method enabled data parametrization, fitting and analysis in wild‐type controls versus isogenic MUT iPSC‐CMs. Of note, Cas9‐edited TnT‐R141W iPSC‐CMs revealed significantly reduced beating force and prolonged contractile event duration. The NNBD‐based platform provides an alternative framework for improved quantitation of molecular disease phenotypes and may contribute to the development of novel diagnostic tools.
Alcohol use disorder severity moderates clinical response to varenicline.

BACKGROUND In a multisite clinical trial, varenicline was effective in reducing drinking in both smoking- and nonsmoking patients with alcohol dependence. However, given the heterogeneous nature of alcohol use disorder (AUD), research aimed a characterizing features associated with treatment response could advance personalized pharmacotherapies. The current study examines the utility of a multidimensional assessment of AUD severity to identify key responders to varenicline. METHODS The study utilized data from the Phase 2 randomized, double-blind, placebo-controlled multisite 13-week trial of varenicline in alcohol-dependent patients (n = 200) (J Addict Med, 7, 2013, 277). Four hypothesized measures of AUD severity (i.e., DSM-IV criterion count, withdrawal, craving, and alcohol-related consequences) were combined into a single severity factor. A series of multilevel models that included the severity factor were conducted to examine its effects on treatment outcomes. RESULTS All of the hypothesized indices of AUD severity loaded significantly onto a singular severity factor. Among low-severity groups, varenicline significantly reduced drinking (i.e., percent heavy drinking days, drinks per day, and drinks per drinking day) more that placebo. Varenicline also improved the quality of life (i.e., mental health) more than placebo in low-severity groups. CONCLUSIONS Treatment response to varenicline may be maximized among individuals with less-severe AUD presentation, as determined by both reductions in drinking outcomes and improvements in psychosocial functioning.
The Impact of Oenological Means on Glycerol Content in Montenegrin Wines Vranac and Kratošija

The influence of three different commercial yeasts (BDX, BM4X4 and ICV D21) and two different lactic acid bacteria (LAB), on glycerol content in Montenegrin wines Vranac and Kratosija were studied during 2012 vintage. Basic quality parameters of grape must (sugar content, total acidity, pH, tartaric and malic acid) were determined, as well as glycerol content after alcoholic and malolactic fermentation. It was found that within both wines, the highest content of glycerol was reached when BDX yeast was used. There were no significant differences within glycerol content when different LAB was used. In Kratosija wine glycerol content for BDX treatment varied between 9.02 – 9.09 g L-1, while in Vranac wine varied from 8.88 – 8.95 g L-1. Slightly higher glycerol content in wines with BM4X4 and ICV D21 commercial yeast were achieved also in Kratosija wine.
Two-component organogels of phosphorous-based organic acids and diamine

ABSTRACT Phosphorous-based organic acids (P) and diamine (M) were used to produce a supramolecular PM complex at a 2:1 molar ratio, which then formed a stable gel in dimethyl sulfoxide (DMSO) and N, N-dimethylformamide (DMF). According to SEM, the morphologies of the aggregates depended on the steric substitute of phosphorous-based organic acids and the structure of the complementary diamine. 31P NMR and FTIR spectroscopies revealed that hydrogen bonding within the PM complex was the main driving force for the self-aggregation. XRD studies revealed that the two-component gelators mainly assemble into a stricter lamellar structure when increasing the rigidity of the complementary component. In contrast, the gelators with the aliphatic unit mainly assembled into a random lamellar structure and showed more possibility of deforming. As such, the results in this paper demonstrate how structure effects in two-component gel system of phosphorous-based organic acids and diamine can control self-assembly process.
In silico prediction of natural compounds as potential multi-target inhibitors of structural proteins of SARS-CoV-2

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a colossal loss to human health and lives and has deeply impacted socio-economic growth. Remarkable efforts have been made by the scientific community in containing the virus by successful development of vaccines and diagnostic kits. Initiatives towards drug repurposing and discovery have also been undertaken. In this study, we compiled the known natural anti-viral compounds using text mining of the literature and examined them against four major structural proteins of SARS-CoV-2, namely, spike (S) protein, nucleocapsid (N) protein, membrane (M) protein and envelope (E) protein. Following computational approaches, we identified fangchinoline and versicolactone C as the compounds to exhibit strong binding to the target proteins and causing structural deformation of three structural proteins (N, S and M). We recommend the inhibitory effects of these compounds from our study should be experimentally validated against SARS-CoV-2. Communicated by Ramaswamy H. Sarma
Metabolic Cost and Performance of Athletes With Lower Limb Amputation and Nonamputee Matched Controls During Running

Abstract The elastic function of running-specific prostheses likely contributes to a lower metabolic cost of running. However, it remains unclear whether running-specific prostheses provide advantages concerning the metabolic cost of running in relationship with nonamputee runners. This study aimed to systematically review the scientific literature to examine the peak performance (peak oxygen consumption—VO2peak and peak speed) and the metabolic cost between paired amputees and nonamputees during running and between amputee runners with traditional prostheses and running-specific prostheses. A literature search on three databases (MEDLINE/PubMed, Scopus, and Web of Science) was conducted using the following key words: (amputation OR amputee) AND (run OR running OR runner) AND (prosthesis OR prosthetics), resulting in 2060 records and 4 studies within the inclusion criteria. A methodological quality assessment was carried out using a modified version of the Downs and Black checklist. VO2peak of the amputees athletes (54 ± 2 mL kg−1 min−1) is similar (mean difference = −0.80 mL kg−1 min−1, confidence interval = −4.63 to 3.03) to nonamputees athletes (55 ± 2 mL kg−1 min−1). The average metabolic cost of the paired amputee athletes (4.94 ± 1.19 J kg−1 m−1) also does not differ (mean difference = 0.73 J kg−1 m−1, confidence interval = −0.74 to 2.20) from nonamputee runners (4.21 ± 0.16 J kg−1 m−1). The research on running in amputee and nonamputee athletes is limited. The few existing studies have limited methodological quality. The metabolic cost data from amputee athletes running with running-specific prostheses are within the range of nonamputee data.
Enhanced Terahertz Shielding of MXenes with Nano‐Metamaterials

Terahertz (THz) shielding becomes increasingly important with the growing development of THz electronics and devices. Primarily materials based on carbon nanostructures or polymer–carbon nanocomposites have been explored for this application. Herein, significantly enhanced THz shielding efficiencies for 2D titanium carbide (Ti3C2 MXene) thin films with nanoscale THz metamaterials are presented. Nanoscale slot antenna arrays with strong resonances at certain frequencies enhance THz electromagnetic waves up to three orders of magnitude in transmission, which in turn enormously increases the shielding performance in combination with MXene films. Drop‐casting of a colloidal solution of MXene (a few micrograms of dry material) can produce an ultrathin film (several tens of nanometers in thickness) on a slot antenna array. Consequently, THz waves strongly localized in the near‐field regime by the slot antenna undergo enhanced absorption through the film with a magnified effective refractive index. Finally, the combination of an ultrathin MXene film and a nano‐metamaterial shows excellent shielding performance in the THz range.
Translational Strategies for Repotrectinib in Neuroblastoma

Limited clinical data are available regarding the utility of multikinase inhibition in neuroblastoma. Repotrectinib (TPX-0005) is a multikinase inhibitor that targets ALK, TRK, JAK2/STAT, and Src/FAK, which have all been implicated in the pathogenesis of neuroblastoma. We evaluated the preclinical activity of repotrectinib monotherapy and in combination with chemotherapy as a potential therapeutic approach for relapsed/refractory neuroblastoma. In vitro sensitivity to repotrectinib, ensartinib, and cytotoxic chemotherapy was evaluated in neuroblastoma cell lines. In vivo antitumor effect of repotrectinib monotherapy, and in combination with chemotherapy, was evaluated using a genotypically diverse cohort of patient-derived xenograft (PDX) models of neuroblastoma. Repotrectinib had comparable cytotoxic activity across cell lines irrespective of ALK mutational status. Combination with chemotherapy demonstrated increased antiproliferative activity across several cell lines. Repotrectinib monotherapy had notable antitumor activity and prolonged event-free survival compared with vehicle and ensartinib in PDX models (P < 0.05). Repotrectinib plus chemotherapy was superior to chemotherapy alone in ALK-mutant and ALK wild-type PDX models. These results demonstrate that repotrectinib has antitumor activity in genotypically diverse neuroblastoma models, and that combination of a multikinase inhibitor with chemotherapy may be a promising treatment paradigm for translation to the clinic.
Questioning the renoprotective role of L-type calcium channel blockers in chronic kidney disease using physiological modeling.

Chronic kidney disease (CKD) is characterized by the progressive functional loss of nephrons and hypertension (HTN). Some antihypertensive regimens attenuate the progression of CKD (blockers of the renin-angiotensin system). While studies suggest that calcium channel blocker (CCB) therapy mitigates the decline in renal function in humans with essential HTN, there are few long-term clinical studies that determine the impact of CCBs in patients with hypertensive CKD. Dihydropyridine (DHP) or L-type CCBs preferentially vasodilate the afferent arteriole and have been associated with glomerular HTN and increases in proteinuria in animal models with low renal function. Small clinical studies in vulnerable populations with renal disease such as African Americans, children, and diabetics, also suggest DHP CCBs exacerbate glomerular injury, which questions the renoprotective effect of this class of antihypertensive drug. We used an established integrative mathematical model of human physiology, HumMod, to test the hypothesis that DHP CCB therapy exacerbates pressure-induced glomerular injury in hypertensive CKD. Over a simulation of three years, CCB therapy reduced mean blood pressure by ~14-16 mmHg in HTN both with and without CKD. Both impaired tubuloglomerular feedback (TGF) and low baseline renal function exacerbated glomerular pressure, glomerulosclerosis, and the decline in renal function during L-type CCB treatment. However, simulating CCB therapy that inhibited both L and T-type calcium channels increased efferent arteriolar vasodilation and alleviated glomerular damage. These simulations support the evidence that DHP (L-type) CCBs potentiate glomerular HTN during CKD and suggest T/L-type CCBs are valuable in proteinuric renal disease treatment.
Reconstruction of volume averaging effect‐free continuous photon beam profiles from discrete ionization chamber array measurements using a machine learning technique

Abstract Purpose The use of the ionization chamber array ICProfiler (ICP) is limited by its relatively poor detector spatial resolution and the inherent volume averaging effect (VAE). The purpose of this work is to study the feasibility of reconstructing VAE‐free continuous photon beam profiles from ICP measurements with a machine learning technique. Methods In‐ and cross‐plane photon beam profiles of a 6 MV beam from an Elekta linear accelerator, ranging from 2 × 2 to 10 × 10 cm2 at 1.5 cm, 5 cm, and 10 cm depth, were measured with an ICP. The discrete measurements were interpolated with a Makima method to obtain continuous beam profiles. Artificial neural networks (ANNs) were trained to restore the penumbra of the beam profiles. Plane‐specific (in‐ and cr‐plane) ANNs and a combined ANN were separately trained. The performance of the ANNs was evaluated using the penumbra width difference (PWD, the difference between the penumbra widths of the reconstructed and the reference profile). The plane‐specific and the combined ANNs were compared to study the feasibility of using a single ANN for both in‐ and cross‐plane. Results The profiles reconstructed with all the ANNs had excellent agreement with the reference. For in‐plane, the ANNs reduced the PWD from 1.6 ± 0.7 mm at 1.5 cm depth to 0.1 ± 0.1 mm, from 1.8 ± 0.6 mm at 5.0 cm depth to 0.1 ± 0.1 mm, and from 2.4 ± 0.1 mm at 10.0 cm depth to 0.0 ± 0.0 mm; for cross‐plane, the ANNs reduced the PWD from 1.2 ± 0.4 mm at 1.5 cm depth, 1.2 ± 0.3 mm at 5.0 cm depth, and 1.6 ± 0.1 mm at 10.0 cm depth, to 0.1 ± 0.1 mm. Conclusions This study demonstrated the feasibility of using simple ANNs to reconstruct VAE‐free continuous photon beam profiles from discrete ICP measurements. A combined ANN can restore the penumbra of in‐ and cross‐plane beam profiles of various fields at different depths.
Apparatus and method for using ozone as a disinfectant

A method of sterilizing a closed environment is provided in which an disinfection apparatus is placed into the closed environment; it then generates ozone to a predetermined ozone concentration, following which the humidity of the closed environment is rapidly increased. A catalytic converter then reduces the ozone concentration to safe levels. When the ozone concentration is reduced to a predetermined safe level, the disinfection apparatus signals.
Burnout and anxiety level of healthcare professionals during the COVID-19 pandemic in Turkey.

BACKGROUND COVID-19 has affected many countries in the world and has been known as one of the fast-spreading viruses in recent history. OBJECTIVE Our aim is to reveal the level of anxiety and burnout, attitudes, thoughts, and behaviors of healthcare professionals about COVID-19 in Turkey. METHODS The individuals included in the study answered seven questions containing demographic information, 27 questions determining their views and perspectives on COVID-19. Anxiety level was measured by Beck Anxiety Scale (BAI), and State Anxiety Inventory (SAI); burnout was measured by Maslach Burnout Inventory (MBI). RESULTS We included 66 health staff (50 female, 16 male) whose mean age was 31.71±5.18 years (22-46 ranged). Twenty-two (33.3%) of the participants worked on the COVID-19 frontline while 44 (66.6%) of them worked on usual wards.We found that participants' anxiety was at a moderate level in BAI (mean: 14.00±12.66). The mean of the SAI was 49.93±13.06. MBI subscales were low. We found that there was a significant difference in BAI between COVID-19 frontline healthcare professionals and those who worked on the usual wards (p = 0.01). CONCLUSIONS It is important to consider the level of anxiety and burnout in all healthcare professionals and to help them to protect their mental health.
Systematic Review of Motor Function Scales and Patient-Reported Outcomes in Spinal Muscular Atrophy

Abstract Spinal muscular atrophy is a heterogeneous disease that results in loss of motor function. In an evolving treatment landscape, establishing the suitability and limitations of existing motor function scales and patient-reported outcomes used to monitor patients with this disease is important. A systematic review was conducted to examine utility of motor function scales and patient-reported outcomes in evaluating patients with spinal muscular atrophy. Published literature was reviewed up to June 2021 with no start date restriction. Of the reports screened, 122 were deemed appropriate for inclusion and are discussed in this review (including 24 validation studies for motor function scales or patient-reported outcomes). Fifteen motor function scales and patient-reported outcomes were identified to be commonly used (≥5 studies), of which 11 had available validation assessments. Each instrument has its strengths and limitations. It is imperative that the patient population (e.g., age, mobility), goals of treatment, and outcomes or endpoints of interest be considered when selecting the appropriate motor function scales and patient-reported outcomes for clinical studies.
Practical AI Transparency

How does one do research on algorithms and their outputs when confronted with the inherent algorithmic opacity and black box-ness as well as with the limitations of API-based research and the data access gaps imposed by platforms’ gate-keeping practices? This article outlines the methodological steps we undertook to manoeuvre around the above-mentioned obstacles. It is a “byproduct” of our investigation into datafication and the way how algorithmic identities are being produced for personalisation, ad delivery and recommendation. Following Paßmann and Boersma’s (2017) suggestion for pursuing “practical transparency” and focusing on particular actors, we experiment with different avenues of research. We develop and employ an approach of letting the platforms speak and making the platforms speak. In doing so, we also use non-traditional research tools, such as transparency and regulatory tools, and repurpose them as objects of/for study. Empirically testing the applicability of this integrated approach, we elaborate on the possibilities it offers for the study of algorithmic systems, while being aware and cognizant of its limitations and shortcomings.
Perceived Economic Impact of Religious Tourism: The Case of Zimbabwe

Purpose: The purpose of the study was to assess the perceived economic impact of religious tourism in Zimbabwe. The research objectives were (1) to determine the nature of religious tourism in Zimbabwe, (2) to determine the key success factor for economically viable religious tourism in Zimbabwe, (3) to ascertain the perceived economic contribution of religious tourism, and finally (4) to propose strategies for economically sustainable religious tourism in Zimbabwe. Methods: The research adopted a qualitative approach and was descriptive in nature. The study focused on Harare and the study population was made up of a cross-section of tourism service providers in Harare, religious leaders, and the Zimbabwe Tourism Authority. Purposive sampling was used for service providers and as well as religious leaders. Results: The research findings revealed that there are a lot of religious tourism activities that take place in Zimbabwe, particularly Harare and normally take the form of pilgrimages, religious conferencing, healing and deliverance nights, and worship. The perceived economic value derived includes employment creation for the locals, an increase in foreign currency generation, and an increase in sales revenue. The research findings also show that for religious tourism to be economically sustainable there is a need for government involvement, re-packaging of the product, and investment in local infrastructure. Implications: Zimbabwe Tourism Authority and the private sector need to take the religious tourism market seriously and make deliberate efforts to harness this growing market.