Miracle-dz/UniFAR-FTUs huggingface dataset:
Oncologic Benefit of Adjuvant Chemoradiation after D2 Gastrectomy: A Stepwise Hierarchical Pooled Analysis and Systematic Review

Our study aimed to evaluate the benefits of chemoradiotherapy (CRT) after D2 gastrectomy, as compared to adjuvant chemotherapy, alone. PubMed, MEDLINE, Embase, and the Cochrane Library were systematically searched. We applied stepwise analyses that enabled the evaluation of data from randomized controlled trials (RCTs), balanced studies, and all studies separately and in a hierarchical manner. Thirteen controlled studies, including six RCTs involving 2603 patients, were included. Overall pooled analysis revealed a disease-free survival benefit of CRT (odds ratio (OR): 1.264, p = 0.053), which was more evident in the subgroup analysis of RCTs (OR: 1.440, p = 0.006) and balanced studies (OR: 1.417, p < 0.001). Overall survival was insignificantly different in the overall pooled analysis (OR: 1.124, p = 0.347). However, the difference was marginally significant in the subgroup analysis of balanced studies (OR: 1.279, p = 0.055) and significant in the subgroup analysis of studies involving stage ≥III patients only (OR: 1.663, p = 0.005). Locoregional recurrence (LRR) reduction was noted in the overall pooled analysis (OR: 0.559, p = 0.012; pooled rate: 11.3% vs. 18.1%) and was more robust in the subgroup analyses. Grade ≥3 leukopenia was higher in the CRT arm (OR: 1.387, p = 0.004; pooled rate: 26.4% vs. 15.7%). CRT after D2 gastrectomy should be applied for patients with high risk of LRR (e.g., stage ≥ III), along with efforts to reduce leukopenia.
Emerging Role of Extracellular Vesicles in Embryo–Maternal Communication throughout Implantation Processes

In ruminants, the establishment of proper conceptus–endometrial communication is essential for conceptus implantation and subsequent successful placentation. Accumulated evidence supports the idea that extracellular vesicles (EVs) present in uterine lumen are involved in conceptus–endometrial interactions during the preimplantation period. EVs make up a new field of intercellular communicators, which transport a variety of bioactive molecules, including soluble and membrane-bound proteins, lipids, DNA, and RNAs. EVs thus regulate gene expression and elicit biological effects including increased cell proliferation, migration, and adhesion in recipient cells. Uterine EVs are interactive and coordinate with ovarian progesterone (P4), trophectoderm-derived interferon tau (IFNT) and/or prostaglandins (PGs) in the physiological or pathological microenvironment. In this review, we will focus on intrauterine EVs in embryo–maternal interactions during the early stage of pregnancy, especially the implantation period in ruminant ungulates.
Formulation and Characterisation of a Combination Captopril and Hydrochlorothiazide Microparticulate Dosage Form

Cardiovascular diseases such as hypertension and cardiac failure in South African children and adolescents are effectively managed long term, using a combination treatment of captopril and hydrochlorothiazide. The majority of commercially available pharmaceutical products are designed for adult patients and require extemporaneous manipulation, prior to administration to paediatric patients. There is a need to develop an age appropriate microparticulate dosing technology that is easy to swallow, dose and alter doses whilst overcoming the pharmacokinetic challenges of short half-life and biphasic pharmacokinetic disposition exhibited by hydrochlorothiazide and captopril. An emulsion solvent evaporation approach using different combinations of polymers was used to manufacture captopril and hydrochlorothiazide microparticles. Design of experiments was used to develop and analyse experimental data, and identifyoptimum formulation and process conditions for the preparation of the microparticles. Characterisation studies to establish encapsulation efficiency, in vitro release, shape, size and morphology of the microparticles were undertaken. The microparticles produced were in the micrometre size range, with an encapsulation efficiency >75% for both hydrochlorothiazide and captopril. The microparticulate technology is able to offer potential resolution to the half-life mediated dosing frequency of captopril as sustained release of the molecule was observed over a 12-h period. The release of hydrochlorothiazide of >80% suggests an improvement in solubility limited dissolution.
Performance of Sheep Fed on Annatto Byproduct

This study aimed to evaluate intake, digestibility, and performance in sheep fed increasing levels of annatto byproduct (AB). A total of 32 male sheep without defined breed were used. Their initial weight was 23.17±1.45 kg. The animals were housed in individual pens and offered feed twice a day. Nutrient intake was quantified by the difference between the fractions present in the offered feed and the remains. The apparent digestibility was estimated with the aid of the external marker LIPE®. Weight gain was measured by the difference between the initial and final weight of the animals. The intake of dry matter (DM; g/day; g/kg BW; g/kg0.75), organic matter (g/day), crude protein (CP; g/day), and neutral detergent fibre (g/day) was not affected (P>0.05) by addition of AB. The intake of ether extract (EE; g/day) and non-fibre carbohydrates (g/day) was influenced by the inclusion of AB. The apparent digestibility of DM, organic matter, CP, and EE was not affected (P>0.05) by the addition of AB. The AB can be included in the diet at levels up 300 g/kg of total DM without affecting consumption, digestibility, and weight gain in sheep.
Updating the Risk Stratification for Sudden Cardiac Death in Cardiomyopathies: The Evolving Role of Cardiac Magnetic Resonance Imaging. An Approach for the Electrophysiologist

The prevention of sudden cardiac death (SCD) in cardiomyopathies (CM) remains a challenge. The current guidelines still favor the implantation of devices for the primary prevention of SCD only in patients with severely reduced left ventricular ejection fraction (LVEF) and heart failure (HF) symptoms. The implantation of an implantable cardioverter-defibrillator (ICD) is a protective barrier against arrhythmic events in CMs, but the benefit does not outweigh the cost in low risk patients. The identification of high risk patients is the key to an individualized prevention strategy. Cardiac magnetic resonance (CMR) provides reliable and reproducible information about biventricular function and tissue characterization. Furthermore, late gadolinium enhancement (LGE) quantification and pattern of distribution, as well as abnormal T1 mapping and extracellular volume (ECV), representing indices of diffuse fibrosis, can enhance our ability to detect high risk patients. CMR can also complement electro-anatomical mapping (EAM), a technique already applied in the risk evaluation and in the ventricular arrhythmias ablation therapy of CM patients, providing a more accurate assessment of fibrosis and arrhythmic corridors. As a result, CMR provides a new insight into the pathological substrate of CM. CMR may help identify high risk CM patients and, combined with EAM, can provide an integrated evaluation of scar and arrhythmic corridors in the ablative therapy of ventricular arrhythmias.
Optimal Revascularization Strategy in Non–ST‐Segment–Elevation Myocardial Infarction With Multivessel Coronary Artery Disease: Culprit‐Only Versus One‐Stage Versus Multistage Revascularization

Background Few studies have investigated optimal revascularization strategies in non–ST‐segment–elevation myocardial infarction with multivessel disease. We investigated 3‐year clinical outcomes according to revascularization strategy in patients with non–ST‐segment–elevation myocardial infarction and multivessel disease. Methods and Results This retrospective, observational, multicenter study included patients with non–ST‐segment–elevation myocardial infarction and multivessel disease without cardiogenic shock. Data were analyzed at 3 years according to the percutaneous coronary intervention strategy: culprit‐only revascularization (COR), 1‐stage multivessel revascularization (MVR), and multistage MVR. The primary outcome was major adverse cardiac events (MACE: a composite of all‐cause death, nonfatal spontaneous myocardial infarction, or any repeat revascularization). The COR group had a higher risk of MACE than those involving other strategies (COR versus 1‐stage MVR; hazard ratio, 0.65; 95% CI, 0.54–0.77; P<0.001; and COR versus multistage MVR; hazard ratio, 0.74; 95% CI, 0.57–0.97; P=0.027). There was no significant difference in the incidence of MACE between 1‐stage and multistage MVR (hazard ratio, 1.14; 95% CI, 0.86–1.51; P=0.355). The results were consistent after multivariate regression, propensity score matching, inverse probability weighting, and Bayesian proportional hazards modeling. In subgroup analyses stratified by the Global Registry of Acute Coronary Events score, 1‐stage MVR lowered the risk of MACE compared with multistage MVR in low‐to‐intermediate risk patients but not in patients at high risk. Conclusions MVR reduced 3‐year MACE in patients with non–ST‐segment–elevation myocardial infarction and multivessel disease compared with COR. However, 1‐stage MVR was not superior to multistage MVR for reducing MACE except in low‐to‐intermediate risk patients.
GlycA Levels during the Earliest Stages of Rheumatoid Arthritis: Potential Use as a Biomarker of Subclinical Cardiovascular Disease

This study aimed at evaluating the clinical relevance of glycoprotein profiles during the earliest phases of rheumatoid arthritis (RA) as biomarkers of cardiovascular (CV) risk and treatment response. Then, GlycA and GlycB serum levels were measured using 1H-nuclear magnetic resonance in 82 early RA patients, 14 clinically-suspect arthralgia (CSA), and 28 controls. Serum glycosyltransferase activity was assessed by a colorimetric assay. Subclinical CV disease was assessed by Doppler-ultrasound. We found that GlycA and GlycB serum levels were increased in RA (both p < 0.001), but not in CSA, independently of cardiometabolic risk factors. Increased serum glycosyltransferase activity paralleled GlycA (r = 0.405, p < 0.001) and GlycB levels (r = 0.327, p = 0.005) in RA. GlycA, but not GlycB, was associated with atherosclerosis occurrence (p = 0.012) and severity (p = 0.001). Adding GlycA to the mSCORE improved the identification of patients with atherosclerosis over mSCORE alone, increasing sensitivity (29.7 vs. 68.0%) and accuracy (55.8 vs. 76.6%) and allowing reclassification into more appropriate risk categories. GlycA-reclassification identified patients with impaired lipoprotein metabolism. Finally, baseline GlycA levels predicted poor clinical response upon anti-rheumatic treatment at 6 and 12 months in univariate and multivariate analysis. In sum, increased GlycA levels during the earliest stage of RA can be considered a powerful biomarker for CV risk stratification and treatment response.
Augmenting Neuromuscular Disease Detection Using Optimally Parameterized Weighted Visibility Graph

In this contribution, we propose a novel neuromuscular disease detection framework employing weighted visibility graph (WVG) aided analysis of electromyography signals. WVG converts a time series into an undirected graph, while preserving the signal properties. However, conventional WVG is sensitive to noise and has high computational complexity which is problematic for lengthy and noisy time series analysis. To address this issue in this article, we investigate the performance of WVG by varying two important parameters, namely penetrable distance and scale factor, both of which have shown promising results by eliminating the problem of signal adulteration and decreasing the computational complexity, respectively. We also aim to unfold the combined effect of these two aforesaid parameters on the WVG performance to discriminate between myopathy, amyotrophic lateral sclerosis (ALS) and healthy EMG signals. Using graph theory based features we demonstrated that the discriminating capability between the three classes increased significantly with the increase in both penetrable distance and scale factor values. Three binary (healthy vs. myopathy, myopathy vs. ALS and healthy vs. ALS) and one multiclass problems (healthy vs. myopathy vs. ALS) have been addressed in this study and for each problem, we obtained optimum parameter values determined on the basis of F-value computed using one way analysis of variance (ANOVA) test. Using optimal parameter values, we obtained mean accuracy of 98.57%, 98.09% and 99.45%, respectively for three binary and 99.05% for the multi-class classification problem. Additionally, the computational time was reduced by 96% with optimally selected WVG parameters compared to traditional WVG.
The Relationship between the IFNG (rs2430561) Polymorphism and Metabolic Syndrome in Perimenopausal Women

Background and Objectives: Metabolic syndrome (MetS) is a multiple risk factor for atherosclerosis, cardiovascular disease, type 2 diabetes and strokes. One-third of middle-age women are at risk of MetS, which predisposes them to type 2 diabetes and cardiovascular disease. Changes in the regulation of anti-inflammatory cytokines―which play an important role in pathologic processes―may contribute to inflammatory disorders. Cytokine polymorphisms are known to have an impact on gene expression. The purpose of this study was to search for the relationship between the IFNG polymorphisms and the levels of proinflammatory cytokines. Materials and Methods: This study, conducted in West Pomeranian Voivodeship, Poland, involved 416 women. Of these women, 33.6% of them had primary education, 44.8% lived in cities with a population of over 100,000, and 82.7% were married. Of the participants, 28.4% met the criteria for MetS. The study involved: interview performed to collect sociodemographic and medical data, anthropometric measurements, as well as venous blood collection for biochemical analysis, genetic testing and the measurement of inflammatory markers. Results: The link between the IFNG (rs2430561) polymorphism and serum PIC (proinflammatory cytokines) levels was tested with regard to MetS. In the MetS+ subgroup, the T/T and A/T genotypes of the IFNG gene were accompanied by higher IL-6 levels than in the MetS− subgroup. Conclusion: Our study has not confirmed a direct link between the IFNG polymorphisms and the levels of inflammatory biomarkers. Nevertheless, the T/T and A/T genotypes of the IFNG gene may predispose to elevated IL-6 levels.
Network Classification Based on Reducibility With Respect to the Stability of Canalizing Power of Genes in a Gene Regulatory Network – A Boolean Network Modeling Perspective

A key objective of studying biological systems is to design therapeutic intervention strategies for beneficially altering cell dynamics. Derivation of control policies is hindered by the high-dimensional state spaces associated with gene regulatory networks. Hence, it is critical to reduce the network complexity and the paper aims to address this issue by focusing on the distribution of the canalizing power (CP) of the genes in the model. Canalizing genes enforce broad corrective actions on cellular processes and play a crucial role in producing optimal reactions to external stimuli. Therefore, it is critical to reduce the network while preserving the canalizing power of genes. We reduce Boolean networks with perturbation by removing genes with the smallest canalizing power consecutively, and evaluate the stability of canalizing power. A systematic empirical study demonstrates that there are two classes of networks, reducible and irreducible with respect to the preservation of canalizing power of the genes. Based on these observations, we introduce the definition of reducible networks and proceed with the problem of selecting the relevant network features that allow for discriminating networks from the two different classes. We demonstrate the efficacy of the selected features on synthetic and real gene regulatory networks.
Antiradical potential and antifungal activities of essential oils of the leaves of Citrus latifolia against Phaeoramularia angolensis

Investigations were conducted to determine the chemical composition, antiradical and antifungal activities of the essential oil extracted from the fresh leaves of Citrus latifolia var. Tahiti from Cameroon against Phaeoramularia angolensis. The essential oil obtained by hydrodistillation was analysed by GC and GC/MS. The disc diffusion method was used to evaluate the zone of fungal growth inhibition at various concentrations of the oil while the antiradical activity of the oil was studied by the DPPH (diphenyl picryl hydrazyl) method. The chemical analysis revealed 26 components among which limonene (45.76%), geranial (13.12%) and neral (10.35%) were the main components. The antiradical activity of C. latifolia essential oil (SC50 = 9.93 g/l) was less than that of butylated hydroxyl toluene (BHT) which was used as the reference compound (SC50 = 7.02 x 10-3 g/l). After 40 days of incubation on oil – supplemented medium, the growth of P. angolensis was totally inhibited by 1600 mg/l of C. latifolia oil. Results obtained in the present study indicate the possibility of exploiting C. latifolia var Tahiti essential oil to combat P. angolensis which is responsible for heavy losses of Citrus fruits harvests.
Knockdown of microRNA-103a-3p inhibits the malignancy of thyroid cancer cells through Hippo signaling pathway by upregulating LATS1.

MicroRNA (miR)-103a-3p has been shown to be involved in the development and progression of several types of cancer. However, the role of miR-103a-3p in thyroid cancer remains unclear. This study investigated the effects of miR-103a-3p on the biological characteristics of thyroid cancer cells and related mechanisms. In the present study, we found that the expression of miR-103a-3p was increased in thyroid cancer tissues compared to that in non-cancerous tissues. Additionally, the expression of miR-103a-3p in thyroid cancer cell lines (TPC-1, SW579, BHT101, K1) was markedly higher than that in the human thyroid cell line (Nthy-ori3-1). Silencing of miR-103a-3p obviously inhibited proliferation, migration, and invasion and promoted apoptosis of BHT101 cells. miR-103a-3p upregulation promoted the proliferation, migration, and invasion and inhibited apoptosis of K1 cells. Mechanistically, LATS1was identified as a functional target of miR-103a-3p and miR-103a-3p negatively regulated LATS1 expression. miR-103a-3p knockdown (or upregulation) partially reversed the effects of LATS1 knockdown (or overexpression) on proliferation, apoptosis, migration, and invasion of thyroid cancer cells. LATS1 knockdown inhibited the phosphorylation of YAP in BHT101 cells and promoted the nuclear translocation of YAP. Whereas, miR-103a-3p downregulation reversed the inhibitory effect of LATS1 knockdown on Hippo signaling pathway. Moreover, overexpression of LATS1 induced YAP phosphorylation in K1 cells and inhibits nuclear translocation of YAP, and the upregulation of miR-103a-3p reversed this effect. Knockdown of miR-103a-3p inhibited tumor growth and progression in vivo. Taken together, knockdown of miR-103a-3p inhibits proliferation, migration, and invasion and promotes apoptosis of thyroid cancer cells through the Hippo signaling pathway by upregulating LATS1.
Proposal for an integrated silicon-photonics terahertz gas detector using photoacoustics.

A design and multiphysical model is presented for an on-chip gas sensor that transduces terahertz gas absorption through sound generation into a mechanical motion that can be read out externally. The signal is triply enhanced by designing a structure that functions simultaneously as an optical, an acoustical and a mechanical resonator. The structure is made in high-resistivity silicon and can be fabricated using CMOS and MEMS fabrication technologies. The sensor is a purely passive element, so an external THz source and read-out are required. The chip has a footprint of 3 mm2. A detection limit of 234 ppb of methanol for a source power of 1 mW and an integration time of 1 ms is predicted.
Preliminary application of 3D-printed individualised guiding templates for total hip arthroplasty in Crowe type IV developmental dysplasia of the hip

Objective: To evaluate the feasibility and accuracy of three-dimensional (3D)-printed individualised guiding templates in total hip arthroplasty (THA) for the treatment of developmental dysplasia of the hip (DDH). Methods: 12 hips in 12 patients with Crowe type IV DDH were treated with THA. A 3D digital model of the pelvis and lower limbs was reconstructed using the computed tomography data of the patients. Preoperative surgical simulations were performed to determine the most suitable surgical planning, including femoral osteotomy and prosthesis placement. Based on the ideal surgical planning, individualised guiding templates were designed by software, manufactured using a 3D printer, and used in acetabulum reconstruction and femoral osteotomy during surgery. Results: 12 patients were followed up for an average of 72.42 months (range 38–135 months). During surgery, the guiding template for each case was matched to the bony markers of the acetabulum and proximal femur. Preoperative and follow-up Harris Hip Scores were 34.2 ± 3.7 and 85.2 ± 4.2; leg-length discrepancy, 51.5 ± 6.5 mm and 10.2 ± 1.5 mm; and visual analogue scale scores, 6.2 ± 0.8 and 1.3 ± 0.3, respectively, with statistical difference. Shortened deformity and claudication of the affected limb were obviously improved after surgery. However, 1 patient had artificial hip dislocation 2 weeks after surgery, and another patient had sciatic nerve traction injury, both of whom recovered after physical treatment. Conclusions: Preoperative surgical simulation and 3D-printed individualised guiding templates can fulfil surgeon-specific requirements for the treatment of Crowe type IV DDH. Accurate THA can be achieved using 3D-printed individualised templates, which provide a new personalised surgical plan for the precise positioning and orientation of acetabular reconstruction and femoral osteotomy.
In Vitro Evaluation of Lignin-Containing Nanocellulose

The increasing importance of environmental sustainability has led to the development of new materials that are environmentally friendly, functional, and cost-effective. Lignin-containing cellulose nanomaterials are a common example of these. The advantages of lignocelluloses include their renewability, sustainability, and functionality combined with molecular rigidity and enhanced hydrophobicity. In order to valorize these beneficial traits from lignin-containing nanocellulose, various approaches have been examined in industrial applications. However, the safety of these materials has not been tested or validated in humans. In this study, we tested 21 wt% lignin-containing nanocellulose (L-MFC) in vitro using the human lung and kidney cell lines, H460 and HEK293 cells, respectively. The cytotoxicity of cellulose, L-MFC, and lignin was compared using the water-soluble tetrazolium salt assays. In addition, the gene expressions of HSP70 and HSP90 as cellular stress markers treated with cellulose, L-MFC, and lignin were quantified using real-time polymerase chain reaction (PCR) and Western blotting. Our data indicated little cytotoxicity for cellulose and significant cytotoxicity for lignin and a relatively low level of cytotoxicity for L-MFC, providing the lethal median concentration (LC50) values of L-MFC and lignin. The gene expression of HSP70 and HSP90 was little affected by moderate concentrations of L-MFC. Interestingly, the lignin contained in L-MFC influenced the cell viability and the gene expression of HSP70 and HSP90 less than the same amount of lignin alone. These results indicate that L-MFC displays cell-type-dependent sensitivity and suggest that L-MFC could serve as a new eco-friendly material that is relatively safe for humans.