Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical outcome of decompressing colostomy for acute left-sided colorectal obstruction: a consecutive series of 100 patients

Abstract Purpose Aim of our study was to evaluate the outcomes of a consecutive series of patients who were treated with a decompressing colostomy (DC) for acute left-sided colorectal obstruction. Method A consecutive series of 100 patients with acute left-sided colorectal obstruction who underwent DC from January 2015 to August 2020 was retrospectively analyzed. Demographic characteristics, etiology of the obstruction, postoperative morbidity- and mortality rates, DC-related complication and stoma reversal rates were evaluated. Results Of the 100 included patients, 64 had malignant- and 36 had benign obstruction. The mean age was 69 years, 42% was male, and the ASA score was 2. Morbidity and mortality rates after DC construction were 20 and 2%, respectively. In 39% of the patients, DC ended up as a permanent stoma and in 61% as bridge to surgery (BtS). DC related complication rate was 32%, with a re-intervention rate of 9%. Elective colorectal resection was performed in 59 cases (59%) with subsequent postoperative morbidity rate of 20%. Stoma reversal rate was 77% for the patients who underwent DC as BtS. Stoma reversal was performed in 66% of the patients with benign obstruction and in 36% for oncological obstruction. Conclusion DC as bridge to possible elective resection for acute left-sided colorectal obstruction is an effective strategy with low morbidity and mortality rates and a high stoma reversal rate, especially for benign obstruction. However, DC is less appropriate for patients in whom DC turns out to be a permanent stoma due to a relatively high stoma related complications.
Melanoma with genetic alterations beyond the BRAFV600 mutation: management and new insights

Purpose of review Molecular-targeted therapy with BRAF-/MEK-inhibitors has shown impressive activity in patients with advanced BRAFV600 mutant melanoma. In this review, we aim to summarize recent data and possible future therapeutic strategies involving small-molecule molecular-targeted therapies for advanced BRAFV600 wild-type melanoma. Recent findings In patients with NRASQ61 mutant melanoma, downstream MEK-inhibition has shown some albeit low activity. MEK-inhibitors combined with novel RAF dimer inhibitors, such as belvarafenib, or with CDK4/6-inhibitors have promising activity in NRAS mutant melanoma in early-phase trials. In patients with non-V600 BRAF mutant melanoma, MEK-inhibition with or without BRAF-inhibition appears to be effective, although large-scale prospective trials are lacking. As non-V600 BRAF mutants signal as dimers, novel RAF dimer inhibitors are also under investigation in this setting. MEK-inhibition is under investigation in NF1 mutant melanoma. Finally, in patients with BRAF/NRAS/NF1 wild-type melanoma, imatinib or nilotinib can be effective in cKIT mutant melanoma. Despite preclinical data suggesting synergistic activity, the combination of the MEK-inhibitor cobimetinib with the immune checkpoint inhibitor atezolizumab was not superior to the immune checkpoint inhibitor pembrolizumab. Summary As of today, no molecular-targeted therapies have shown to improve survival in patients with advanced BRAFV600 wild-type melanoma. Combinatorial strategies, involving MEK-inhibitors, RAF dimer inhibitors and CDK4/6-inhibitors, are currently under investigation and have promising activity in advanced BRAFV600 wild-type melanoma.
SCOT: Single-Cell Multi-Omics Alignment with Optimal Transport

Recent advances in sequencing technologies have allowed us to capture various aspects of the genome at single-cell resolution. However, with the exception of a few of co-assaying technologies, it is not possible to simultaneously apply different sequencing assays on the same single cell. In this scenario, computational integration of multi-omic measurements is crucial to enable joint analyses. This integration task is particularly challenging due to the lack of sample-wise or feature-wise correspondences. We present single-cell alignment with optimal transport (SCOT), an unsupervised algorithm that uses the Gromov-Wasserstein optimal transport to align single-cell multi-omics data sets. SCOT performs on par with the current state-of-the-art unsupervised alignment methods, is faster, and requires tuning of fewer hyperparameters. More importantly, SCOT uses a self-tuning heuristic to guide hyperparameter selection based on the Gromov-Wasserstein distance. Thus, in the fully unsupervised setting, SCOT aligns single-cell data sets better than the existing methods without requiring any orthogonal correspondence information.
Circulating Metabolome and White Matter Hyperintensities in Women and Men

Background: White matter hyperintensities (WMH), identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness, are a major risk factor of stroke, dementia, and death. There are no large-scale studies testing associations between WMH and circulating metabolites. Methods: We studied up to 9290 individuals (50.7% female, average age 61 years) from 15 populations of 8 community-based cohorts. WMH volume was quantified from T2-weighted or fluid-attenuated inversion recovery images or as hypointensities on T1-weighted images. Circulating metabolomic measures were assessed with mass spectrometry and nuclear magnetic resonance spectroscopy. Associations between WMH and metabolomic measures were tested by fitting linear regression models in the pooled sample and in sex-stratified and statin treatment–stratified subsamples. Our basic models were adjusted for age, sex, age×sex, and technical covariates, and our fully adjusted models were also adjusted for statin treatment, hypertension, type 2 diabetes, smoking, body mass index, and estimated glomerular filtration rate. Population-specific results were meta-analyzed using the fixed-effect inverse variance–weighted method. Associations with false discovery rate (FDR)–adjusted P values (PFDR)<0.05 were considered significant. Results: In the meta-analysis of results from the basic models, we identified 30 metabolomic measures associated with WMH (PFDR<0.05), 7 of which remained significant in the fully adjusted models. The most significant association was with higher level of hydroxyphenylpyruvate in men (PFDR.full.adj=1.40×10−7) and in both the pooled sample (PFDR.full.adj=1.66×10−4) and statin-untreated (PFDR.full.adj=1.65×10−6) subsample. In men, hydroxyphenylpyruvate explained 3% to 14% of variance in WMH. In men and the pooled sample, WMH were also associated with lower levels of lysophosphatidylcholines and hydroxysphingomyelins and a larger diameter of low-density lipoprotein particles, likely arising from higher triglyceride to total lipids and lower cholesteryl ester to total lipids ratios within these particles. In women, the only significant association was with higher level of glucuronate (PFDR=0.047). Conclusions: Circulating metabolomic measures, including multiple lipid measures (eg, lysophosphatidylcholines, hydroxysphingomyelins, low-density lipoprotein size and composition) and nonlipid metabolites (eg, hydroxyphenylpyruvate, glucuronate), associate with WMH in a general population of middle-aged and older adults. Some metabolomic measures show marked sex specificities and explain a sizable proportion of WMH variance.
Flexible Strain-Sensitive Silicone-CNT Sensor for Human Motion Detection

This article describes the manufacturing technology of biocompatible flexible strain-sensitive sensor based on Ecoflex silicone and multi-walled carbon nanotubes (MWCNT). The sensor demonstrates resistive behavior. Structural, electrical, and mechanical characteristics are compared. It is shown that laser radiation significantly reduces the resistance of the material. Through laser radiation, electrically conductive networks of MWCNT are formed in a silicone matrix. The developed sensor demonstrates highly sensitive characteristics: gauge factor at 100% elongation −4.9, gauge factor at 90° bending −0.9%/deg, stretchability up to 725%, tensile strength 0.7 MPa, modulus of elasticity at 100% 46 kPa, and the temperature coefficient of resistance in the range of 30–40 °C is −2 × 10−3. There is a linear sensor response (with 1 ms response time) with a low hysteresis of ≤3%. An electronic unit for reading and processing sensor signals based on the ATXMEGA8E5-AU microcontroller has been developed. The unit was set to operate the sensor in the range of electrical resistance 5–150 kOhm. The Bluetooth module made it possible to transfer the received data to a personal computer. Currently, in the field of wearable technologies and health monitoring, a vital need is the development of flexible sensors attached to the human body to track various indicators. By integrating the sensor with the joints of the human hand, effective movement sensing has been demonstrated.
Discovering the Potential of Natural Antioxidants in Age-Related Macular Degeneration: A Review

Age-related macular degeneration (AMD) is a multifactorial disease associated with anatomical changes in the inner retina. Despite tremendous advances in clinical care, there is currently no cure for AMD. This review aims to evaluate the published literature on the therapeutic roles of natural antioxidants in AMD. A literature search of PubMed, Web of Science and Google Scholar for peer-reviewed articles published between 1 January 2011 and 31 October 2021 was undertaken. A total of 82 preclinical and 18 clinical studies were eligible for inclusion in this review. We identified active compounds, carotenoids, extracts and polysaccharides, flavonoids, formulations, vitamins and whole foods with potential therapeutic roles in AMD. We evaluated the integral cellular signaling pathways including the activation of antioxidant pathways and angiogenesis pathways orchestrating their mode of action. In conclusion, we examined the therapeutic roles of natural antioxidants in AMD which warrant further study for application in clinical practice. Our current understanding is that natural antioxidants have the potential to improve or halt the progression of AMD, and tailoring therapeutics to the specific disease stages may be the key to preventing irreversible vision loss.
High Redox Status as the Basis for Heavy Metal Tolerance of Sesuvium portulacastrum L. Inhabiting Contaminated Soil in Jeddah, Saudi Arabia

Because sewage sludge is contaminated with heavy metals, its disposal in the soil may pose risks to the ecosystem. Thus, heavy metal remediation is necessary to reduce the associated risks. The goal of this research is to introduce a heavy metal resistant species and to assess its phytoremediation, oxidative damage markers and stress tolerance mechanisms. To this end, field research was done to compare the vegetation of polluted sites to that of a healthy site. We found 42 plant species identified in the study, Sesuvium portulacastrum L. was chosen because of its high relative density (10.3) and maximum frequency (100 percent) in the most contaminated areas. In particular, S. portulacastrum plants were characterized by strong Cu, Ni, and As uptake. At the organ level, to control growth reduction and oxidase damage, particularly in roots, increased detoxification (e.g., metallothionein, phytochelatins) and antioxidants mechanisms (e.g., tocopherols, glutathione, peroxidases). On the other hand, flavonoids content and the activity of glutathione-S transferase, glutathione reductase and dehydroascorbate reductase were increased manly in the shoots. These biochemical markers can be applied to select tolerance plant species grown under complex heavy metal contamination. Our findings also introduced S. portulacastrum to reduce soil contamination0associated risks, making the land resource available for agricultural production.
Molecular and cellular evidence for hsa‐miR‐1254 suppressor effect against HER2 signaling in breast cancer

HER2 signaling upregulation is a hallmark of breast cancer which is the second cause of cancer‐related death in women. Here, we were looking for the candidate microRNAs which is capable of regulating the HER2 receptor and the genes of its downstream. To this aim, preliminary bioinformatics analysis introduced hsa‐miR‐1254 (miR‐1254) as a potential common regulator of HER2, HER3, PIK3R2, and AKT1 genes. Then, reverse‐transcription quantitative polymerase chain reaction (RT‐qPCR) analysis indicated a lower expression level of miR‐1254 in breast cancer specimens, compared to their normal pairs. Furthermore, overexpression of miR‐1254 resulted in HER2, HER3, PIK3R2, and AKT1 genes downregulation, detected by RT‐qPCR and confirmed by western blot analysis and enzyme‐linked immunosorbent assay test against AKT1, BAX, FADD, and HER2 protein levels in SKBR3 cells. Dual‐luciferase assay also supported direct interaction of miR‐1254 with MREs within 3' untranslated region sequences of HER2, HER3, PIK3R2, and AKT1 target genes. Overexpression of miR‐1254 in SKBR3 cells was followed by increased BAX/BCL2 expression ratio, detected by RT‐qPCR, and increased proportion of G1 cell population, detected by flow cytometry. Corroborated by cell cycle analysis, MTT, Annexin V‐FITC, and Live‐Dead cell staining assays, overexpression of miR‐1254 in MDA‐MB‐231 cells showed opposing results following the overexpression of miR‐1254. Taken together, results indicated that miR‐1254 acts as cell‐type‐specific tumor suppressor that targets HER2, HER3, PIK3R2, and AKT1 transcripts. These results suggest miR‐1254 as a potential therapeutic candidate for breast cancer subtypes.
Premature Termination Codon in 5′ Region of Desmoplakin and Plakoglobin Genes May Escape Nonsense-Mediated Decay through the Reinitiation of Translation

Arrhythmogenic cardiomyopathy is a heritable heart disease associated with desmosomal mutations, especially premature termination codon (PTC) variants. It is known that PTC triggers the nonsense-mediated decay (NMD) mechanism. It is also accepted that PTC in the last exon escapes NMD; however, the mechanisms involving NMD escaping in 5′-PTC, such as reinitiation of translation, are less known. The main objective of the present study is to evaluate the likelihood that desmosomal genes carrying 5′-PTC will trigger reinitiation. HL1 cell lines were edited by CRISPR/Cas9 to generate isogenic clones carrying 5′-PTC for each of the five desmosomal genes. The genomic context of the ATG in-frame in the 5′ region of desmosomal genes was evaluated by in silico predictions. The expression levels of the edited genes were assessed by Western blot and real-time PCR. Our results indicate that the 5′-PTC in PKP2, DSG2 and DSC2 acts as a null allele with no expression, whereas in the DSP and JUP gene, N-truncated protein is expressed. In concordance with this, the genomic context of the 5′-region of DSP and JUP presents an ATG in-frame with an optimal context for the reinitiation of translation. Thus, 5′-PTC triggers NMD in the PKP2, DSG2* and DSC2 genes, whereas it may escape NMD through the reinitiation of the translation in DSP and JUP genes, with no major effects on ACM-related gene expression.
Review on Natural, Incidental, Bioinspired, and Engineered Nanomaterials: History, Definitions, Classifications, Synthesis, Properties, Market, Toxicities, Risks, and Regulations

Nanomaterials are becoming important materials in several fields and industries thanks to their very reduced size and shape-related features. Scientists think that nanoparticles and nanostructured materials originated during the Big Bang process from meteorites leading to the formation of the universe and Earth. Since 1990, the term nanotechnology became very popular due to advances in imaging technologies that paved the way to specific industrial applications. Currently, nanoparticles and nanostructured materials are synthesized on a large scale and are indispensable for many industries. This fact fosters and supports research in biochemistry, biophysics, and biochemical engineering applications. Recently, nanotechnology has been combined with other sciences to fabricate new forms of nanomaterials that could be used, for instance, for diagnostic tools, drug delivery systems, energy generation/storage, environmental remediation as well as agriculture and food processing. In contrast with traditional materials, specific features can be integrated into nanoparticles, nanostructures, and nanosystems by simply modifying their scale, shape, and composition. This article first summarizes the history of nanomaterials and nanotechnology. Followed by the progress that led to improved synthesis processes to produce different nanoparticles and nanostructures characterized by specific features. The content finally presents various origins and sources of nanomaterials, synthesis strategies, their toxicity, risks, regulations, and self-aggregation.
Application Statement of Intelligent Vehicle Environment Perception Sensor

Advantages and disadvantages of Intelligent Vehicle(IV) environment perception sensor is introduced,application and development trends of them used in the IV especially in lane recognition and obstacle detection are analyzed.Because of limitation of sensor and complexity of operating environment,it is difficult to supply the completely reliable information by some sensor in any time.So,the application and development direction of multi-sensor information fusion technology in the IV is introduced,in order to choose suitable sensor and detection method.
Effectiveness of Physiotherapy in Patients with Ankylosing Spondylitis: A Systematic Review and Meta-Analysis

This study aimed to evaluate the safety and effectiveness of non-pharmacological interventions supervised by a physiotherapist in patients with Ankylosing Spondylitis, PROSPERO Protocol number CRD42020209453. Five databases (PubMed, PEDro, Scopus, Web of Science Core, and EMBASE) and reference lists with relevant articles were searched. Randomised controlled trials (RCTs) on the effectiveness of non-pharmacological interventions supervised by a physiotherapist were compared with usual care or home-based exercise programmes. Two investigators independently screened eligible studies. A total of 12 RCTs satisfied eligible criteria. The risk of bias ranged between medium and high. The meta-analysis results indicated that between supervised physiotherapy and usual care, the former was significantly associated with improvement in disease activity (standardised mean difference = −0.37, 95% CI, −0.64; −0.11; p < 0.001, I2 = 71.25%, n = 629), and functional capacity (standardised mean difference = −0.36, 95% CI, −0.61; −0.12, p < 0.05; n = 629). No statistically significant differences emerged when interventions were compared with home-based exercise programmes. Supervised physiotherapy is more effective than usual care in improving disease activity, functional capacity, and pain in patients with ankylosing spondylitis. No significant improvements emerged when supervised physiotherapy and home-based exercise programmes were compared. Further investigation and RCTs with larger samples are needed.
Use of Mobile Apps for Self-care in People With Parkinson Disease: Systematic Review

Background Self-care is essential for people with Parkinson disease (PD) to minimize their disability and adapt to alterations in physical abilities due to this progressive neurodegenerative disorder. With rapid developments in mobile technology, many health-related mobile apps for PD have been developed and used. However, research on mobile app–based self-care in PD is insufficient. Objective This study aimed to explore the features and characteristics of mobile apps for self-care in people with PD. Methods This study was performed sequentially according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Web of Science, and PsycINFO were searched in consultation with a librarian on June 8, 2021. We used keywords including ”Parkinson disease” and ”mobile. ” Results A total of 17 studies were selected based on the inclusion criteria, including 3 randomized controlled trials and 14 observational studies or quasi-experimental studies. The use of mobile apps for self-care in people with PD focused on symptom monitoring, especially motor symptoms. Motor symptoms were objectively measured mainly through the sensors of smartphones or wearable devices and task performance. Nonmotor symptoms were monitored through task performance or self-reported questionnaires in mobile apps. Most existing studies have focused on clinical symptom assessment in people with PD, and there is a lack of studies focusing on symptom management. Conclusions Mobile apps for people with PD have been developed and used, but strategies for self-management are insufficient. We recommend the development of mobile apps focused on self-care that can enhance symptom management and health promotion practices. Studies should also evaluate the effects of mobile apps on symptom improvement and quality of life in people with PD. Trial Registration PROSPERO International Prospective Register of Systematic Reviews CRD42021267374; https://www.crd. york.ac. uk/prospero/display_record. php? ID=CRD42021267374.
The Use of Drosophila to Understand Psychostimulant Responses

The addictive properties of psychostimulants such as cocaine, amphetamine, methamphetamine, and methylphenidate are based on their ability to increase dopaminergic neurotransmission in the reward system. While cocaine and methamphetamine are predominately used recreationally, amphetamine and methylphenidate also work as effective therapeutics to treat symptoms of disorders including attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Although both the addictive properties of psychostimulant drugs and their therapeutic efficacy are influenced by genetic variation, very few genes that regulate these processes in humans have been identified. This is largely due to population heterogeneity which entails a requirement for large samples. Drosophila melanogaster exhibits similar psychostimulant responses to humans, a high degree of gene conservation, and allow performance of behavioral assays in a large population. Additionally, amphetamine and methylphenidate reduce impairments in fly models of ADHD-like behavior. Therefore, Drosophila represents an ideal translational model organism to tackle the genetic components underlying the effects of psychostimulants. Here, we break down the many assays that reliably quantify the effects of cocaine, amphetamine, methamphetamine, and methylphenidate in Drosophila. We also discuss how Drosophila is an efficient and cost-effective model organism for identifying novel candidate genes and molecular mechanisms involved in the behavioral responses to psychostimulant drugs.