Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic significance of lymph node ratio after neoadjuvant chemoradiation therapy for esophageal squamous cell carcinoma

Purpose We retrospectively evaluated the prognostic significance of lymph node ratio (LNR) in patients with esophageal squamous cell carcinoma who underwent neoadjuvant concurrent chemoradiation therapy (NCRT) followed by surgery. Materials and Methods In total, 270 patients who underwent NCRT followed by surgery between August 2005 and December 2015 were included. They were divided into three groups: LNR 0 (n = 196), LNR low (0 < LNR ≤ 0.1; n = 63), and LNR high (>0.1; n = 11). The primary endpoint was overall survival (OS), and the secondary endpoints were freedom from local recurrence (FFLR), distant metastasis-free survival (DMFS), and disease-free survival (DFS). Results The median number of retrieved lymph nodes per patient was 33. Pathologically, 74 patients had positive lymph nodes. The median follow-up duration was 36.1 months, and the median survival period was 68.4 months. There was a significant correlation between LNR and the number of positive lymph nodes (correlation coefficient = 0.763, p < 0.001). There was a substantial difference in the OS among the LNR groups, with 2-year survival rates of 79.0%, 54.0%, and 9.1% in the LNR 0, LNR low, and LNR high groups, respectively (p < 0.001). A marked decrease in FFLP, DMFS, and DFS was observed with the increasing LNR. In subgroup analysis, the survival results of patients with clinically positive lymph node were similar from those of entire cohort. Conclusion LNR is a significant prognostic factor in patients with esophageal squamous cell carcinoma who underwent NCRT followed by surgery. Additional treatment and closer follow-up would be necessary for patients with a high LNR.
Structures of Two Paralytic Shellfish Toxins, Gonyautoxins V and VI, Isolated from a Tropical Dinoflagellate, Pyrodinium bahamense var. compressa

Two paralytic shellfish toxins, gonyautoxin V and gonyautoxin VI, isolated from a tropical dinoflagellate, Pyrodinium bahamense var. compressa, were identified respectively to be derivatives of saxitoxin and neosaxitoxin with a sulfonatocarbamoyl moiety.
Stearic-oleic acid nanocarriers for cream formulation / Woo Juin Onn

Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a series of stearic-oleic acid nanoparticles (SON) with different oleic acid compositions were successfully prepared by melt-emulsification combined with ultrasonication method. The SONs prepared have average particle size range from 200 nm to 250 nm depends on the oleic acid concentration in the mixture. TEM micrographs showed that high oleic acid compositions in SON induced the formation of elongated spherical particles. Encapsulation efficiency of SONs increased from 50% to 70% for both salicylic acid and lidocaine as increasing the oleic acid composition in the mixture. Differential scanning calorimetry analysis showed that the SONs prepared have lower crystallinity as compared to pure stearic acid. Different oleic acid composition in the mixture gave different degree of perturbation to the crystalline matrix of SONs hence result in lower degrees of crystallinity, thereby improve their encapsulation efficiencies. The optimized formulation, SON with 30 wt% was further incorporated into cream and evaluated the in vitro release for payload ingredients. The in vitro release showed a gradual release for 24 hours that strongly indicates the incorporation of payloads in solid matrix of SON and thus prolonged the release for both salicylic acid and lidocaine. Cream formulations with SONs containing salicylic acid and lidocaine showed about 3 times slower release rate as compared to their solution form, suggesting the potential use of SONs as carriers to improve therapeutic efficacy in cosmetic and pharmaceutical products.
Long intergenic non‐coding RNA Linc00485 promotes lung cancer progression by modulating miR‐298/c‐Myc axis

Long non‐coding RNAs (lncRNAs), which are non‐protein‐coding transcripts, are emerging as novel biomarkers for cancer diagnosis. Their dysregulation is increasingly recognized to contribute to the development and progression of human cancers, including lung cancer. Linc00485 is a newly discovered cancer‐related lncRNA; however, little is known about its role in lung cancer progression. In this study, we found that the expression of Linc00485 was significantly increased in human lung cancer tissue and associated with malignant phenotypes, including tumour‐node‐metastasis (TNM) stage, metastasis and relapse. Furthermore, the proliferative, migratory and invasive abilities of lung cancer cells in vitro were significantly enhanced by overexpression of Linc00485 but inhibited by its silencing. Mechanistically, Linc00485 regulated the expression of c‐Myc by directly binding to miR‐298; the effects of Linc00485 overexpression could be significantly reversed by a c‐Myc inhibitor or small interfering RNA. Xenotransplantation experiments showed that Linc00485 silencing significantly weakened the proliferation potential of A549 cells in vivo. Overall, these findings indicate that Linc00485 overexpression down‐regulates miR‐298, resulting in the up‐regulation of c‐Myc and thereby promoting the development of lung cancer.
Effects of SGLT2 Inhibitors as an Add-on Therapy to Metformin on Electrocardiographic Indices of Ventricular Repolarization.

Background According to EMPA-REG OUTCOME, trial use of empagliflozin in patients with a history of cardiovascular disease improves hospitalization for heart failure and decreases cardiovascular morbidity and mortality. Recent studies have shown that a prolonged T-peak to T-end interval on the resting electrocardiography is associated with an increased risk of cardiovascular mortality. Tp-e/corrected QT interval (QTc) ratio is a reliable index of prolonged ventricular repolarization. Objectives In this study, we examined the effects of sodium glucose co-transporters 2 (SGLT2) inhibitors as an add-on therapy to metformin on electrocardiographic indices of ventricular repolarization. Methods Electrocardiographic recordings before combination therapy along with three months and six months follow-up of 141 consecutive patients who were switched from monotherapy to combination therapy with two oral agents due to inadequate glycemic control were derived. QT interval (QT), QTc, Tp-e intervals and Tp-e/QT, Tp-e/QTc ratios were calculated and analyzed. Results After the six month follow-up, there was a significant decrease in the QT interval in patients who were using SGLT2 inhibitors as an add-on therapy to metformin compared to other glucose-lowering agents (373.4 ± 9.9 ms vs. 385.4 ± 12.5 ms, 382.9 ± 11.2 ms; p < 0.001 respectively). Furthermore, Tp-e/QT and Tp-e/QTc ratios were significantly lower in this patient population compared to control groups (0.186 ± 0.023 vs. 0.196 ± 0.021, 0.191 ± 0.017; p < 0.001 and 0.174 ± 0.021 vs. 0.199 ± 0.022, 0.195 ± 0.016; p < 0.001 respectively). Conclusions Our data showed that using SGLT2 inhibitors as an add-on therapy to metformin favorably alters ventricular repolarization indices in patients with type 2 diabetes mellitus.
Vitamin D in Toddlers, Preschool Children, and Adolescents

Background: Vitamin D supplementation is known to both prevent and treat rickets, a disease of hypomineralized bone. Childhood is a period of great bone development and, therefore, attention to the vitamin D needed to optimize bone health in childhood is imperative. Summary: Observational studies have pointed to a vitamin D status, as indicated by a 25-hydroxyvitamin D concentration, of 50 nmol/L to ensure avoidance of rickets and of 75 nmol/L to optimize health. However, the benefits of achieving these levels of vitamin D status are less evident when pediatric randomized, controlled trials are performed. In fact, no specific pediatric vitamin D supplementation has been established by the existing evidence. Yet, study of vitamin D physiology continues to uncover further potential benefits to vitamin D sufficiency. This disconnection between vitamin D function and trials of supplementation has led to new paths of investigation, including establishment of the best method to measure vitamin D status, examination of genetic variation in vitamin D metabolism, and consideration that vitamin D status is a marker of another variable, such as physical activity, and its association with bone health. Nevertheless, vitamin D supplementation in the range of 10–50 μg/day appears to be safe for children and remains a promising intervention that may yet be supported by clinical trials as a method to optimize pediatric health. Key Message: Pediatric vitamin D status is associated with avoidance of rickets. Randomized, controlled trials of vitamin D supplementation for pediatric bone health are limited and equivocal in their results. Beyond bone, decreased risk for autoimmune, infectious, and allergic diseases has been associated with higher vitamin D status. The specific vitamin D supplementation to optimize toddler, child, and adolescent outcomes is unknown, but doses 10–50 μg/day are safe and may be beneficial.
Intracranial aneurysms managed by parent artery reconstruction using Tubridge: Study protocol for a prospective, multicenter, post-market clinical trial

Background As a new endovascular reconstruction technique, flow diverter (FD) shows excellent efficacy and safety for treatment of intracranial aneurysms. In a previous multicenter, randomized, controlled, pre-market study, Tubridge FD showed remarkably higher complete occlusion rate compared with traditional stent-assisted coiling. However, a nonsignificant higher complication rate in the Tubridge group was noted. Considering the learning curve, the safety, and long-term outcomes of Tubridge FD should be verified in new prospective, real world, multicenter, post-market trials. Methods This study is a prospective, multicenter, single-arm, post-market clinical trial that evaluates the safety and efficacy of Tubridge in the treatment of patients with intracranial aneurysms by reconstructing parent artery. We expect 200 participants who meet the inclusion and exclusion criteria to be included. Clinical information and angiographic results (Raymond–Roy grading scale, RRGS) will be recorded objectively. The primary endpoint will be the complete occlusion rate of the target aneurysm (RRGS 1) at 12-month follow-up. Secondary endpoints will include the adequate occlusion rate (RRGS 1 & 2) and the rate of major in-stent stenosis (>50%) at 12-month follow-up, technique success rate, changes of modified Rankin Scale before and after the procedure, the rate of aneurysm related disability, neurological mortality, and all-cause mortality within follow-up period. Discussion This post-market, prospective trial may offer more information on the safety and long-term outcomes of Tubridge FD. When the study is complete, the results may provide us a new strategy for the treatment of intracranial aneurysms. Trial registration: WHO-Chinese Clinical Trial Registry: ChiCTR2000032282.
Analysis of Human Mutations in the Supernumerary Subunits of Complex I

Complex I is the largest member of the electron transport chain in human mitochondria. It comprises 45 subunits and requires at least 15 assembly factors. The subunits can be divided into 14 “core” subunits that carry out oxidation–reduction reactions and proton translocation, as well as 31 additional supernumerary (or accessory) subunits whose functions are less well known. Diminished levels of complex I activity are seen in many mitochondrial disease states. This review seeks to tabulate mutations in the supernumerary subunits of humans that appear to cause disease. Mutations in 20 of the supernumerary subunits have been identified. The mutations were analyzed in light of the tertiary and quaternary structure of human complex I (PDB id = 5xtd). Mutations were found that might disrupt the folding of that subunit or that would weaken binding to another subunit. In some cases, it appeared that no protein was made or, at least, could not be detected. A very common outcome is the lack of assembly of complex I when supernumerary subunits are mutated or missing. We suggest that poor assembly is the result of disrupting the large network of subunit interactions that the supernumerary subunits typically engage in.
Reticulated Platelets in Medicine: Current Evidence and Further Perspectives

Reticulated platelets (RPs) are young thrombocytes, newly released from the bone marrow. The identification and quantification of these cells remained difficult for decades due to a lack of standardized preanalytical and analytical methods. With the introduction of automated hematology analyzers in clinical routine, the determination of RPs, either as a total count or as a fraction, became more reliable, faster and more affordable. Currently, RPs are the focus of research in multiple clinical settings. In cardiovascular medicine, recent studies have focused on the relationship between RPs, coronary artery disease (CAD) and clinical outcomes, as well as the impact of RPs on the effects of antiplatelet therapy. Cohort studies showed increased levels of RPs in patients with acute coronary syndrome (ACS) or cardioembolic stroke. In patients with ACS, increased levels of RPs were also associated with an increased incidence of major ischemic cardiovascular events during follow-up. Further studies showed an association of levels of RPs with the antiplatelet response to less-potent P2Y12 inhibitors. In patients with paroxysmal atrial fibrillation undergoing pulmonary vein isolation, levels of RPs differed significantly depending on the achieved rhythm (sinus rhythm vs. recurrent atrial fibrillation). Levels of RPs appear to also be predictive for bleeding events in patients with various hematological diagnoses. Although no causal relationship has so far been proven, RP values have been associated with a large number of pathologies and clinical scenarios. This review summarizes the current evidence with regard to RPs and their potential diagnostic and prognostic value for noncardiovascular patients and for cardiovascular patients in particular. It describes further perspectives on how the testing of these cells might improve the treatment of cardiovascular patients.
Crosstalk between the activated Slit2–Robo1 pathway and TGF‐β1 signalling promotes cardiac fibrosis

Previous reports indicated that the Slit2–Robo signalling pathway is involved in embryonic heart development and fibrosis in other solid organs, but its function in adult cardiac fibrosis has not been investigated. Here, we investigate the role of the Slit2–Robo1 signalling pathway in cardiac fibrosis.
Effects of climate change on parasites and disease in estuarine and nearshore environments

Information on parasites and disease in marine ecosystems lags behind terrestrial systems, increasing the challenge of predicting responses of marine host–parasite systems to climate change. However, here I examine several generalizable aspects and research priorities. First, I advocate that quantification and comparison of host and parasite thermal performance curves is a smart approach to improve predictions of temperature effects on disease. Marine invertebrate species are ectothermic and should be highly conducive to this approach given their generally short generation times. Second, in marine systems, shallow subtidal and intertidal areas will experience the biggest temperature swings and thus likely see the most changes to host–parasite dynamics. Third, for some responses like parasite intensity, as long as the lethal limit of the parasite is not crossed, on average, there may be a biological basis to expect temperature-dependent intensification of impacts on hosts. Fourth, because secondary mortality effects and indirect effects of parasites can be very important, we need to study temperature effects on host–parasite dynamics in a community context to truly know their bottom line effects. This includes examining climate-influenced effects of parasites on ecosystem engineers given their pivotal role in communities. Finally, other global change factors, especially hypoxia, salinity, and ocean acidity, covary with temperature change and need to be considered and evaluated when possible for their contributing effects on host–parasite systems. Climate change–disease interactions in nearshore marine environments are complex; however, generalities are possible and continued research, especially in the areas outlined here, will improve our understanding.
The Effect of Disinfectants on Quinolone Resistant E. coli (QREC) in Biofilm

The aim of disinfection is to reduce the number of microorganisms on surfaces which is a challenge due to biofilms. In the present study, six quinolone resistant Escherichia coli (QREC) strains with three different biofilm matrix compositions were included to assess the log10 colony forming units (CFU) reduction effect of three disinfectants at various exposure times on biofilm of different ages and morphotypes. Biofilm was formed on stainless steel coupons for two and five days before transferred to tubes with Virocid 0, 25%, VirkonS 1%, and TP990 1% and left for various exposure times. The biofilms were scraped off and serial dilutions were spread on blood agar plates where colony forming units (CFU) were counted. A mean log10 CFU reduction ≥4 was seen on two-day-old biofilm with VirkonS and Virocid (30 min) but not on five-day old biofilm. TP990 did not display sufficient effect under the conditions tested. The bactericidal effect was inferior to that reported on planktonic bacteria. The findings of this study should be considered when establishing both disinfectant routines and standard susceptibility tests, which further should accommodate E. coli biofilms and not only Pseudomonas as is the case today.
Polycarbonate mPOF-Based Mach–Zehnder Interferometer for Temperature and Strain Measurement

In this paper, an endlessly single mode microstructured polymer optical fiber (mPOF) in a Mach–Zehnder (M–Z) interferometer configuration is demonstrated for temperature and strain measurement. Because there is no commercial splicer applied for POF-silica optical fiber (SOF) connectorization, prior to the M–Z interferometric sensing, we introduce an imaging projecting method to align a polycarbonate mPOF to a SOF and then the splice is cured permanently using ultraviolet (UV) glue. A He-Ne laser beam at 632.8 nm coupled in a SOF is divided by a 1 × 2 fiber coupler to propagate in two fiber arms. A piece of mPOF is inserted in one arm for sensing implementation and the interference fringes are monitored by a camera. For non-annealed fiber, the temperature sensitivity is found to be 25.5 fringes/°C for increasing temperature and 20.6 fringes/°C for decreasing temperature. The converted sensitivity per unit length is 135.6 fringes/°C/m for increasing temperature, which is twice as much as the silica fiber, or 852.2 rad/°C/m (optical phase change versus fiber temperature), which is more than four times as much as that for the PMMA fiber. To solve the sensitivity disagreement, the fiber was annealed at 125 °C for 36 h. Just after the thermal treatment, the temperature measurement was conducted with sensitivities of 16.8 fringes/°C and 21.3 fringes/°C for increasing and decreasing process, respectively. One month after annealing, the linear response was improved showing a temperature sensitivity of ~20.7 fringes/°C in forward and reverse temperature measurement. For the strain measurement based on non-annealed fiber, the sensitivity was found to be ~1463 fringes/%ε showing repeatable linear response for forward and reverse strain. The fiber axial force sensitivity was calculated to be ~2886 fringes/N, showing a force measurement resolution of ~3.47 × 10−4 N. The sensing methodology adopted in this work shows several advantages, such as very low cost, high sensitivity, a straightforward sensing mechanism, and ease of fabrication.
An Outbreak of Clostridium (Clostridioides) difficile Infections within an Acute and Long-Term Care Wards Due to Moxifloxacin-Resistant PCR Ribotype 176 Genotyped as PCR Ribotype 027 by a Commercial Assay

We aimed to characterize Clostridioides difficile isolates cultured during a six-month single-center study from stool samples of patients with C. difficile infection (CDI) genotyped by the Xpert® C. difficile/Epi assay by polymerase chain reaction (PCR) ribotyping, toxin genes’ detection and multi-locus variable number tandem repeats analysis (MLVA). The susceptibility to metronidazole, vancomycin and moxifloxacin was determined by agar dilution. In addition, the presence of Thr82Ile in the GyrA and a single nucleotide deletion at position (Δ117) in the tcdC gene were investigated. Between January 1 and June 30, 2016, of 114 CDIs, 75 cases were genotyped as presumptive PCR ribotype (RT) 027 infections using a commercial assay. C. difficile isolates cultured from presumptive RT027 stool samples belonged to RT176. These isolates carried genes for toxin A (tcdA), B (tcdB), binary (cdtA/B) and had Δ117 in the tcdC gene. Using MLVA, the 71/75 isolates clustered into two clonal complexes (CCs). Of these, 39 isolates (54.9%) were from patients hospitalized in acute care and 32 isolates (45.1%) were isolated from patients hospitalized in the long-term care department. All isolates were susceptible to metronidazole and vancomycin, and 105 isolates were resistant to moxifloxacin (92%) carrying Thr83Ile in the GyrA. An outbreak of RT176 CDIs, suspected as RT027, was recognized in a Slovakian hospital. In order to monitor the emergence and spread of RT027-variants, the identification of a presumptive RT027 CDI should be confirmed at a strain level by PCR ribotyping.
Antibacterial Activity of Linezolid against Gram-Negative Bacteria: Utilization of ε-Poly-l-Lysine Capped Silica Xerogel as an Activating Carrier

In recent times, many approaches have been developed against drug resistant Gram-negative bacteria. However, low-cost high effective materials which could broaden the spectrum of antibiotics are still needed. In this study, enhancement of linezolid spectrum, normally active against Gram-positive bacteria, was aimed for Gram-negative bacteria growth inhibition. For this purpose, a silica xerogel prepared from a low-cost precursor is used as a drug carrier owing to the advantages of its mesoporous structure, suitable pore and particle size and ultralow density. The silica xerogel is loaded with linezolid and capped with ε-poly-l-lysine. The developed nano-formulation shows a marked antibacterial activity against to Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. In comparison to free linezolid and ε-poly-l-lysine, the material demonstrates a synergistic effect on killing for the three tested bacteria. The results show that silica xerogels can be used as a potential drug carrier and activity enhancer. This strategy could provide the improvement of antibacterial activity spectrum of antibacterial agents like linezolid and could represent a powerful alternative to overcome antibiotic resistance in a near future.