Miracle-dz/UniFAR-FTUs huggingface dataset:
Significance of Ligand-Anchored Polymers for Drug Targeting in the Treatment of Colonic Disorders

Treatment of a variety of bowel diseases like Crohn’s disease, ulcerative colitis, colonic cancers, colonic pathologies, and systemic delivery of drugs at the target sites can be done with the help of targeted drug delivery technique. Conventional colon specific drug delivery systems lack specificity and release significant amount of drug prior reaching the target site. Hence, efficient drug delivery system that ensures effective release of the drug at the colon is still a sought after research arena. Ligand anchored therapy is a strong and effective approach to execute drug delivery in selective target cells, for both, diagnostic, as well as therapeutic reasons. Compared to the regular drugs, such ligand anchored therapy provides added benefit of minimum toxicity and few side effects. Discovery of overexpressed receptors on diseased cells, as compared to healthy cells led to the emergence of active drug targeting. Further, drug resistance constitutes one of the major reasons of the failure of chemotherapy and presents a major obstacle for the effective treatment. The reason behind drug resistance is exposure of pathological cells/pathogens to sub-therapeutic levels of drugs due lack of specificity of therapeutics. Active targeting, specifically taken up by the target cells, can warrant exposure of pathological cells/pathogens to high drug load at the target and sparing non-target cells hence minimal damage to normal cells and least chance of drug resistance. Many ligands like antibodies, aptamers, peptides, folate, and transferrin have been discovered in the past few years. The design of nanocarriers can be incorporated with many different functions which enables functions like imaging and triggered intracellular drug release. The present review article focuses on advances in ligand anchored therapy and its significance on the progress of targeted nanocarriers. It will also establish novel concepts like multi-targeting and multi-functional nanocarriers for the treatment of colonic disorders.
Cirrhosis Hampers Early and Rapid Normalization of Natural Killer Cell Phenotype and Function in Hepatitis C Patients Undergoing Interferon-Free Therapy

Background: Chronic hepatitis C virus (HCV) infection impairs natural killer (NK) cell phenotype and function. Whether restoration of NK cells occurs after successful interferon (IFN)-free therapies remains a controversial issue. Aim: To analyze how HCV-related liver cirrhosis impacts changes in NK cells prior and post-IFN-free therapies. Methods: NK cell analysis by multicolor flow cytometry was performed in HCV-infected patients with (n = 17) and without (n = 14) cirrhosis at baseline, week 4 during therapy, and weeks 12 and 48 after the end of therapy (FU12 and FU48, respectively). Non-HCV cirrhotic patients (n = 12) and healthy individuals (n = 12) served as controls. Results: At baseline, HCV cirrhotic patients presented an altered distribution of NK subsets (CD56dim and CD56bright) with higher expression of NKp46, HLA-DR, NKp30, KIR2DL2/L3, NKG2A, and CD85j receptors compared to healthy controls. All frequencies normalized by FU48, except for CD85j+ cells. Likewise, substantial alterations were detected in NK cell function assessed by (i) signal transducer and activator of transcription 1 (STAT1) and phosphorylated levels of STAT1 and STAT4, (ii) degranulation (CD107a), (iii) cytotoxicity [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)], and (iv) cytokine production [IFN-γ and tumor necrosis factor-α (TNF-α)]. Of note, NK cell function at FU48 remained partially impaired. In contrast, non-cirrhotics showed normal baseline frequencies of HLA-DR-, NKG2A-, and CD85j-expressing NK cells. Importantly, altered baseline frequencies of NK cell subsets and NKp46+ CD56dim cells, as well as NK cell function, were rapidly and completely restored. Conclusions: NK cell phenotype alterations persist after HCV eradication in cirrhotic patients, while their function is only partially restored, compromising immune restoration and immunosurveillance.
miRNAs in NK Cell-Based Immune Responses and Cancer Immunotherapy

The incidence of certain forms of tumors has increased progressively in recent years and is expected to continue growing as life expectancy continues to increase. Tumor-infiltrating NK cells may contribute to develop an anti-tumor response. Optimized combinations of different cancer therapies, including NK cell-based approaches for targeting tumor cells, have the potential to open new avenues in cancer immunotherapy. Functional inhibitory receptors on NK cells are needed to prevent their attack on healthy cells. Nevertheless, disruption of inhibitory receptors function on NK cells increases the cytotoxic capacity of NK cells against cancer cells. MicroRNAs (miRNAs) are small non-coding RNA molecules that target mRNA and thus regulate the expression of genes involved in the development, maturation, and effector functions of NK cells. Therapeutic strategies that target the regulatory effects of miRNAs have the potential to improve the efficiency of cancer immunotherapy. Interestingly, emerging evidence points out that some miRNAs can, directly and indirectly, control the surface expression of immune checkpoints on NK cells or that of their ligands on tumor cells. This suggests a possible use of miRNAs in the context of anti-tumor therapy. This review provides the current overview of the connections between miRNAs and regulation of NK cell functions and discusses the potential of these miRNAs as innovative biomarkers/targets for cancer immunotherapy.
Place of Serology in the Diagnosis of Zoonotic Leishmaniases With a Focus on Visceral Leishmaniasis Due to Leishmania infantum

Leishmaniases are a group of parasitic diseases transmitted through the bite of female phlebotomine sandflies. Depending on the Leishmania species, the reservoirs can be humans (anthroponosis) or different animals (zoonosis). Zoonotic leishmaniasis present several clinical forms in function of the species involved: visceral leishmaniasis (VL), cutaneous leishmaniasis (CL), and muco-cutaneous leishmaniasis (MCL). The biological diagnosis is of utmost importance because the clinical features are not specific. In addition to parasitological and molecular biology (polymerase chain reaction, PCR) assays, serology is routinely used for the diagnosis of leishmaniasis. Indeed, although PCR is more sensitive than serological assays, its implementation is limited to referral laboratories and research centers. Therefore, serology is still a key element for their diagnosis. Here, we discuss the different serological assays available for the diagnosis of zoonotic leishmaniasis. We will review the enzyme-linked immunosorbent assay, immunofluorescence antibody test, immunochromatography test (ICT), direct agglutination test, and western blot as well as the different diagnostic strategies in function of the clinical form (VL, CL, and MCL). We will also discuss the place of serology for detecting asymptomatic carriers and for the follow-up of VL. Depending on the laboratory, different assays can be used, from ICT, which is appropriate for field testing, to a combination of serological tests to improve the sensitivity.
Study on Large Deformation Behavior of Polyacrylamide Hydrogel Using Dissipative Particle Dynamics

Meso-scale models for hydrogels are crucial to bridge the conformation change of polymer chains in micro-scale to the bulk deformation of hydrogel in macro-scale. In this study, we construct coarse-grain bead-spring models for polyacrylamide (PAAm) hydrogel and investigate the large deformation and fracture behavior by using Dissipative Particle Dynamics (DPD) to simulate the crosslinking process. The crosslinking simulations show that sufficiently large diffusion length of polymer beads is necessary for the formation of effective polymer. The constructed models show the reproducible realistic structure of PAAm hydrogel network, predict the reasonable crosslinking limit of water content and prove to be sufficiently large for statistical averaging. Incompressible uniaxial tension tests are performed in three different loading rates. From the nominal stress-stretch curves, it demonstrated that both the hyperelasticity and the viscoelasticity in our PAAm hydrogel models are reflected. The scattered large deformation behaviors of three PAAm hydrogel models with the same water content indicate that the mesoscale conformation of polymer network dominates the mechanical behavior in large stretch. This is because the effective chains with different initial length ratio stretch to straight at different time. We further propose a stretch criterion to measure the fracture stretch of PAAm hydrogel using the fracture stretch of C-C bonds. Using the stretch criterion, specific upper and lower limits of the fracture stretch are given for each PAAm hydrogel model. These ranges of fracture stretch agree quite well with experimental results. The study shows that our coarse-grain PAAm hydrogel models can be applied to numerous single network hydrogel systems.
Effect of Tumor Location on Clinicopathological and Molecular Markers in Colorectal Cancer in Eastern China Patients: An Analysis of 2,356 Cases

Colorectal cancer (CRC) has become a major health concern in China due to its increasing incidence and mortality. This study aimed to clarify the relationship between tumor locations and the clinicopathological molecular marker features in eastern China CRC patients. We continuously collected data on 2,356 CRC patients who underwent surgical resection from January 2017 to April 2019. Right-sided colorectal cancer (RCC), was located from the cecum to the transverse colon and left-side colorectal cancer (LCRC) was located from the splenic flexure to the rectum. The clinicopathological indices (including age, sex, pTNM stage, mucinous production, and distant metastasis) and frequency of molecular markers such as KRAS, NRAS, BRAF, and microsatellite instability (MSI) were statistically analyzed between the RCC and LCRC groups. The associations between clinicopathological characters and molecular markers were also investigated. LCRC and RCC proportions in eastern China CRC patients were 81.75% and 18.25%, respectively. RCC (vs. LCRC) was more frequently observed with higher frequencies of MSI-high (MSI-H) and BRAF mutations in female and younger patients, and was closely associated with metastasis, poor differentiation, and mucinous tumors. Tumor location also showed significant differences in bowel wall infiltration degree and pTNM stage. Mutation rates of KRAS, NRAS, MSI, and BRAF were 40.15%, 3.85%, 6.31%, and 2.30%, respectively. Patients with a KRAS mutation tended to be female, had mucinous, perineural invasive, and polypoid tumor. Those with NRAS mutation tended to develop well-differentiated ulcerative tumors. The BRAF mutation was more relevant with lymph node involvement, deeper infiltration of the bowel wall, mucinous, poorly-differentiated tumor with thrombus, and perineural invasion. Furthermore, MSI-H was more commonly found in younger patients with deeper bowel wall infiltration and a poorly-differentiated polypoid tumor, whereas MSS patients tended to develop lymph node involvement, and a mucinous and perineural invasive tumor. In our study, we found that LCRC and RCC showed different features on the clinicopathological and molecular markers in eastern China CRC patients. Since our data differ from those of Western countries and other regions in China, further studies are required to clarify the regional differences of the clinicopathological and molecular markers in CRC patients.
Mobile Phone Use in Education and Learning by Faculty Members of Technical-Engineering Groups: Concurrent Mixed Methods Design

The purpose of this study was to evaluate Mobile Learning Acceptance among faculty members. The research methodology was a concurrent mixed methods design. The research method in the quantitative part was descriptive-survey, and in the qualitative part a phenomenological approach was applied. In the quantitative part, the study population consisted of all female and male faculty members of technical-engineering groups at Shiraz University (N = 147), where 87 participants were selected using stratified random sampling method. In the qualitative part, the participants included a small fraction of the same faculty members who had also participated in the quantitative part, and were selected by purposive sampling approach with criteria technique. Research instruments consisted of a researcher-made scale of mobile learning acceptance. Upon verifying the validity and reliability of the scale, it was distributed among the subjects, and the collected data were analyzed using SPSS 21 software. Qualitative data were collected from semi-structured interviews with faculty members who had an experience of mobile learning. The quantitative results indicated that in all areas, except for Usefulness, the faculty members' acceptance of mobile learning was higher than average, and Usefulness was at a moderate level. In the qualitative part, after integrating and summarizing the data, a total of 17 basic themes and three organizing themes were extracted, including the benefits of mobile learning, the barriers and limitations of mobile learning, and the required infrastructure for effective implementation of mobile learning.
Study of brainstem evoked response audiometry in medical students having long time mobile usage

Background: Mobile phones are undoubtedly one of the most revolutionizing inventions of the 21st century and are indispensable communication tools. Concomitantly, there has also been a potential increase in the health risks associated with prolonged mobile phone usage. Electromagnetic radiations emitted from telecommunication systems absorbed by the recipient's body may bring about changes in the brain electrical activity. Brainstem evoked response audiometry allows quantifying the activity of auditory pathway, and hence, the present study was undertaken to evaluate the auditory evoked potentials in the MBBS students who have been long-term mobile users. Materials and Methods: The study was conducted using Evoked Potential Recorder (RMS EMGEP MARK-II) in the Neurophysiology unit, Department of Physiology, Mahatma Gandhi Institute of Medical Sciences. This was an observational noninterventional study design incorporating a total of 50 MBBS students, from institutional campus using mobile phones for >1 year. 25 students who used mobile phones for <30 min/day formed the controls whereas, 25 students who used mobile phones for >30 min/day formed the test group. Results: The mean age among the test group was 17.5 ± 1.4 years and among controls was 16.2 ± 2.0 years. The average latency (both the right and left ear) of waves I–V and interpeak latencies (IPLs) I–III, III–V, and I–V waves were found to be prolonged (P > 0.001) in the test group when compared to controls. The mean latencies of the left ear were significantly (P < 0.05) prolonged as compared to the right ear in the test group. Conclusion: This study revealed that there is a significant prolongation in the absolute latencies and IPLs in mobile phone users associated with the duration of usage.
Selected Cognitive Factors Associated with Individual Variability in Clinical Measures of Speech Recognition in Noise Amplified by Fast-Acting Compression Among Hearing Aid Users

Objective: Previous work examining speech recognition in more challenging listening environments has revealed a large variability in both persons with normal and hearing impairments. Although this is clinically very important, up to now, no consensus has been reached about which factors may provide better explanation for the existing individual variability in speech recognition ability among hearing aid users, when speech signal is degraded. This study aimed to examine hearing-sensitivity skills and cognitive ability differences between listeners with good and poor speech recognition abilities. Materials and Methods: A total of 195 experienced hearing aid users (33–80 years) were grouped by higher or lower speech recognition ability based on their performance on the Hagerman sentences task in multi-talker babble using fast-acting compression algorithm. They completed a battery of cognitive abilities tests, hearing-in-noise and the auditory thresholds test. Results: The results showed that the two groups did differ significantly overall on cognitive abilities tests like working memory, cognitive processing speed and attentional shifting, but not on the attentional inhibitory test and non-verbal intelligence test. Conclusions: Listeners with poor compared to those with better speech recognition abilities exhibit poorer cognitive abilities, which place them in a disadvantaged position, and /or more susceptible to signal modifications (as a result of fast-acting compression signal processing), resulting in limited benefits from hearing aids strategies. The findings may have implications for hearing aid signal processing strategies selection in rehabilitations.
Combination of Oligofructose and Metformin Alters the Gut Microbiota and Improves Metabolic Profiles, Contributing to the Potentiated Therapeutic Effects on Diet-Induced Obese Animals

Accumulating studies implicate that the metformin (MET)- and oligofructose (OFS)-altered gut microbiota may play roles in the improvement of type 2 diabetes mellitus (T2DM) and obesity. However, whether the combined administration of OFS and MET could effectively affect the gut microbiota and improve metabolic profiles remains unknown. Here, we randomized diet-induced obesity (DIO) rats to OFS, MET, or MET+OFS for 8 weeks and demonstrated that the combined administration of OFS+MET possessed potentiated effects on the glycemia, body weight, and gut microbiome. In addition, fecal samples from the MET and MET+OFS group were exchanged and transferred to germ-free rats induced by antibiotics. Not surprisingly, the glucose tolerance and serum levels of endotoxin, free fatty acids (FFA), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and interleukin-6 (IL-6) were all sustainably improved among OFS+MET fecal microbiota-treated DIO rats while the MET fecal microbiota-treated ones presented a relatively reverse trend. Furthermore, transfer of fecal samples from the rats after 8 weeks of treatment to antibiotics-treated germ-free mice significantly improved metabolic profiles, including glucose tolerance and weight reduction in mice that received MET+OFS-altered microbiota. In conclusion, the present study illustrated that the effects of OFS and MET combined treatment on gut microbiota, especially for the MET-induced side effect-related ones, and host metabolism were of greater magnitude than individual OFS or MET treatment in obese rats and mice. Therefore, it is likely that combined administration of OFS and MET may offer a novel and promising strategy for reducing side effects induced by MET and improving metabolic outcomes, particularly glycemia control and weight reduction.
Effect of Transcranial Direct Current Stimulation Combined With Patient-Controlled Intravenous Morphine Analgesia on Analgesic Use and Post-Thoracotomy Pain. A Prospective, Randomized, Double-Blind, Sham-Controlled, Proof-of-Concept Clinical Trial

Background Transcranial direct current stimulation (tDCS) is used for various chronic pain conditions, but experience with tDCS for acute postoperative pain is limited. This study investigated the effect of tDCS vs. sham stimulation on postoperative morphine consumption and pain intensity after thoracotomy. Methods This is a single-center, prospective, randomized, double-blind, sham-controlled trial in lung cancer patients undergoing thoracotomy under general anesthesia. All patients received patient-controlled (PCA) intravenous morphine and intercostal nerve blocks at the end of surgery. The intervention group (a-tDCS, n = 31) received anodal tDCS over the left primary motor cortex (C3-Fp2) for 20 min at 1.2 mA, on five consecutive days; the control group (n = 31) received sham stimulation. Morphine consumption, number of analgesia demands, and pain intensity at rest, with movement and with cough were recorded at the following intervals: immediately before (T1), immediately after intervention (T2), then every hour for 4 h (Т3–Т6), then every 6 h (Т7–Т31) for 5 days. We recorded outcomes on postoperative days 1 and 5 and conducted a phone interview inquiring about chronic pain 1 year later (NCT03005548). Results A total of 62 patients enrolled, but tDCS was prematurely stopped in six patients. Fifty-five patients (27 a-tDCS, 28 sham) had three or more tDCS applications and were included in the analysis. Cumulative morphine dose in the first 120 h after surgery was significantly lower in the tDCS [77.00 (54.00–123.00) mg] compared to sham group [112.00 (79.97–173.35) mg, p = 0.043, Cohen’s d = 0.42]. On postoperative day 5, maximum visual analog scale (VAS) pain score with cough was significantly lower in the tDCS group [29.00 (20.00–39.00) vs. 44.50 (30.00–61.75) mm, p = 0.018], and pain interference with cough was 80% lower [10.00 (0.00–30.00) vs. 50.00 (0.00–70.00), p = 0.013]. One year after surgery, there was no significant difference between groups with regard to chronic pain and analgesic use. Conclusion In lung cancer patients undergoing thoracotomy, three to five tDCS sessions significantly reduced cumulative postoperative morphine use, maximum VAS pain scores with cough, and pain interference with cough on postoperative day 5, but there was no obvious long-term benefit from tDCS.
Attenuation of the Hepatoprotective Effects of Ileal Apical Sodium Dependent Bile Acid Transporter (ASBT) Inhibition in Choline-Deficient L-Amino Acid-Defined (CDAA) Diet-Fed Mice

Non-alcoholic fatty liver disease (NAFLD) is a major growing worldwide health problem. We previously reported that interruption of the enterohepatic circulation of bile acids using a non-absorbable apical sodium-dependent bile acid transporter inhibitor (ASBTi; SC-435) reduced the development of NAFLD in high fat diet fed mice. However, the ability of ASBTi treatment to impact the progression of NAFLD to non-alcoholic steatohepatitis (NASH) and fibrosis in a diet-induced mouse model remains untested. In the current study, we assessed whether ASBTi treatment is hepatoprotective in the choline-deficient, L-amino acid-defined (CDAA) diet model of NASH-induced fibrosis. Methods: Male C57Bl/6 mice were fed with: (A) choline-sufficient L-amino acid-defined diet (CSAA) (31 kcal% fat), (B) CSAA diet plus ASBTi (SC-435; 60 ppm), (C) CDAA diet, or (D) CDAA diet plus ASBTi. Body weight and food intake were monitored. After 22 weeks on diet, liver histology, cholesterol and triglyceride levels, and gene expression were measured. Fecal bile acid and fat excretion were measured, and intestinal fat absorption was determined using the sucrose polybehenate method. Results: ASBTi treatment reduced bodyweight gain in mice fed either the CSAA or CDAA diet, and prevented the increase in liver to body weight ratio observed in CDAA-fed mice. ASBTi significantly reduced hepatic total cholesterol levels in both CSAA and CDAA-fed mice. ASBTi-associated significant reductions in hepatic triglyceride levels and histological scoring for NAFLD activity were observed in CSAA but not CDAA-fed mice. These changes correlated with measurements of intestinal fat absorption, which was significantly reduced in ASBTi-treated mice fed the CSAA (85 vs. 94%, P < 0.001) but not CDAA diet (93 vs. 93%). As scored by Ishak staging of Sirius red stained liver sections, no hepatic fibrosis was evident in the CSAA diet mice. The CDAA diet-fed mice developed hepatic fibrosis, which was increased by the ASBTi. Conclusions: ASBT inhibition reduced intestinal fat absorption, bodyweight gain and hepatic steatosis in CSAA diet-fed mice. The effects of the ASBTi on steatosis and fat absorption were attenuated in the context of dietary choline-deficiency. Inhibition of intestinal absorption of fatty acids may be involved in the therapeutic effects of ASBTi treatment.