Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating the Anticarcinogenic Activity of Surface Modified/Functionalized Nanochitosan: The Emerging Trends and Endeavors

Chitosan begins its humble journey from marine food shell wastes and ends up as a versatile nutraceutical. This review focuses on briefly discussing the antioxidant activity of chitosan and retrospecting the accomplishments of chitosan nanoparticles as an anticarcinogen. The various modified/functionalized/encapsulated chitosan nanoparticles and nanoforms have been listed and their biomedical deliverables presented. The anticancer accomplishments of chitosan and its modified composites have been reviewed and presented. The future of surface modified chitosan and the lacunae in the current research focus have been discussed as future perspective. This review puts forth the urge to expand the scientific curiosity towards attempting a variety of functionalization and surface modifications to chitosan. There are few well known modifications and functionalization that benefit biomedical applications that have been proven for other systems. Being a biodegradable, biocompatible polymer, chitosan-based nanomaterials are an attractive option for medical applications. Therefore, maximizing expansion of its bioactive properties are explored. The need for applying the ideal functionalization that will significantly promote the anticancer contributions of chitosan nanomaterials has also been stressed.
Relationship between longitudinal changes in type‐2 inflammation, immunoglobulin E sensitization, and clinical outcomes in young asthmatics

Abstract Background Asthma is a heterogeneous condition where biomarkers may be of considerable advantage in diagnosis and therapy monitoring. However, the changes in asthma biomarkers and immunoglobulin E (IgE) over the course of life has not been extensively investigated. Objective To study longitudinal changes in type‐2 inflammatory biomarkers, IgE, and clinical outcomes, and the association between these changes, in young asthmatics. Methods Asthmatics (age 10–35 years, n = 253) were examined at baseline and at a follow‐up visit, 43 [23–65] (median [range]) months later. Subjects were analyzed using the multi‐allergen tests Phadiatop and fx5 (ImmunoCAP) and grouped based on the baseline allergen‐specific IgE antibody (sIgE) concentration: <0.10, 0.10–0.34, and ≥0.35 kUA/L. The relationship between changes (Δ values) in type‐2 biomarkers (individualized fraction of exhaled nitric oxide [FeNO%], blood eosinophil [B‐Eos] count, total IgE [tIgE] and sIgE, lung function [% predicted forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC)], and Asthma Control Test [ACT]) score were determined. Results At follow up, FEV1 and FEV1/FVC had decreased (93.6% vs. 95.8%, and 93.4% vs. 94.7% of predicted, respectively [p < 0.001 both]), whereas ACT score had increased (21.6 vs. 20.6, p = 0.001). A significant decline in lung function was seen in subjects with sIgE ≥ 0.10 kUA/L, but not in those with undetectable sIgE (<0.10 kUA/L). Furthermore, tIgE and sIgE declined over time (p < 0.001 all) whereas FeNO% and B‐Eos count were not significantly changed. In univariate analysis, significant negative correlations between ∆B‐Eos count and ∆FeNO%, on one hand, and changes in lung function, on the other hand, were seen, and multivariate analysis showed an independent relationship between ΔFeNO%, and ΔFEV1 (p < 0.05) and ΔFEV1/FVC% (p < 0.01). Sex‐specific analysis showed that the independent association between ΔFeNO%, and ΔFEV1 remained only in females (p = 0.005), and there was a significant interaction with sex (p = 0.02). Conclusion In young asthmatics, IgE levels declined over 43 months, whereas FeNO and B‐Eos remained unchanged. In spite of improved asthma control, an accelerated lung function decline was seen in patients with detectable sIgE at baseline, and the decline correlated with changes in type‐2 biomarkers. Particularly, the increase in individualized FeNO associated independently with decline in FEV1 in females.
Efficacy and safety of PCSK9 inhibition in cardiovascular disease: A meta-analysis of 45 randomized controlled trials

Background Safety concerns about proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors make physicians reluctant to prescribe agents for patients. The present aim was to assess the efficacy and safety of alirocumab, evolocumab and bococizumab in patients with atherosclerotic cardiovascular disease (ASCVD). Methods Medline, the Cochrane Library and Clinicaltrials.gov were searched for 45 randomized controlled trials, involving 97,297 patients. Results Compared with the control group, PCSK9 inhibitors could significantly reduce low-density lipoprotein cholesterol, total cholesterol, triglycerides and increase high-density lipoprotein cholesterol. Alirocumab was associated with lower incidence of unstable angina (p < 0.05) and myocardial infarction (p < 0.05), compared with the control group. Alirocumab (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.60–0.97, p < 0.05), evolocumab (OR 0.79, 95% CI 0.66–0.95, p < 0.05) and bococizumab (OR 0.60, 95% CI 0.42–0.84, p < 0.05) were associated with lower incidence of stroke, compared with control group. The incidence of injection-site reactions was significantly higher in alirocumab (OR 1.68, 95% CI 1.45–1.93, p < 0.05), evolocumab (OR 1.64, 95% CI 1.41–1.91, p < 0.05) and bococizumab (OR 8.03, 95% CI 6.85–9.41, p < 0.05) group than in the control group. Conclusions Alirocumab and evolocumab could ameliorate lipid profile and reduce the risk of cardiac disorders and stroke with satisfactory safety and tolerability. However, injection-site reactions should be paid attention to.
Regulatory variants at 2q33.1 confer schizophrenia risk by modulating distal gene TYW5 expression

Abstract Genome-wide association studies have shown that genetic variants at 2q33.1 are strongly associated with schizophrenia. However, potential causal variants in this locus and their roles in schizophrenia remain unknown. Here, we identified two functional variants (rs796364 and rs281759) that disrupt CTCF, RAD21 and FOXP2 binding at 2q33.1. We systematically investigated the regulatory mechanisms of these two variants with serial experiments, including reporter gene assays and electrophoretic mobility shift assay. Intriguingly, these two single nucleotide polymorphisms physically interacted with TYW5 and showed the most significant associations with TYW5 expression in human brain. Consistently, CRISPR-Cas9-mediated genome editing confirmed the regulatory effect of the two single nucleotide polymorphisms on TYW5 expression. Additionally, expression analysis indicated that TYW5 was significantly upregulated in brains of schizophrenia cases compared with controls, suggesting that rs796364 and rs281759 might confer schizophrenia risk by modulating TYW5 expression. We over-expressed TYW5 in mouse neural stem cells and rat primary neurons to mimic its upregulation in schizophrenia and found significant alterations in the proliferation and differentiation of neural stem cells, as well as dendritic spine density following TYW5 overexpression, indicating its important roles in neurodevelopment and spine morphogenesis. Furthermore, we independently confirmed the association between rs796364 and schizophrenia in a Chinese cohort of 8202 subjects. Finally, transcriptome analysis revealed that TYW5 affected schizophrenia-associated pathways. These lines of evidence consistently revealed that rs796364 and rs281759 might contribute to schizophrenia risk by regulating the expression of TYW5, a gene whose expression dysregulation affects two important schizophrenia pathophysiological processes (i.e. neurodevelopment and dendritic spine formation).
Two-step complete splenic artery embolization for the management of symptomatic sinistral portal hypertension

Abstract Background Sinistral portal hypertension (SPH) is a rare clinical syndrome. The purpose of this study was to assess the clinical outcomes and safety of splenic artery embolization (SAE) in the treatment of SPH. Methods This retrospective study included 39 SPH patients who underwent SAE treatment between August 2009 and May 2021. The cases had esophageal, gastric, or ectopic varices detected by endoscopy or enhanced CT, with symptoms or signs of upper gastrointestinal (GI) bleeding and/or postprandial fullness. Clinical symptom improvement rate, complications, and symptomatic recurrence rate were observed and analyzed after treatment. Results All the procedures were performed successfully. Of all patients, 17 received the 2-step complete SAE procedure, 19 received only the first step of the 2-step protocol (i.e., partial splenic embolization [PSE] procedure), and the remaining three received the 1-step complete SAE procedure. After the procedures, the symptoms completely disappeared in all patients, and the main complications were post-embolization syndromes, with 27 patients (69.2%) developing a low-grade fever, 24 (61.5%) developing abdominal pain and 4 (10.3%) developing nausea or mild vomiting. During the prolonged follow-up, varicose veins were gradually reduced as detected by enhanced CT; liver function parameters and platelet count remained in the normal range. Only one patient who underwent PSE treatment developed upper GI rebleeding 7 months after the procedure. Conclusion Two-step complete SAE is a safe and feasible procedure for the treatment of symptomatic SPH.
Sequential Organ Failure Assessment score in predicting the prognosis of necrotising fasciitis: a prospective study

INTRODUCTION Necrotising soft tissue infections represent a spectrum of severe skin and soft tissue infections that are characterised by extensive rapidly progressing soft tissue necrosis and systemic signs of sepsis. The estimated incidence of the disease is 0.3–15 cases per 100,000 population. [1,2] Necrotising fasciitis (NF) is a surgical challenge because of the difficulty in establishing a diagnosis and managing the associated morbidity and mortality. While the local infectious component requires incision, drainage and debridement of the tissue with resulting debilitation and tissue defects, the systemic component is more directly responsible for organ dysfunction and death. Despite advances in surgical and medical care, mortality still remains high at about 20%–30%. [3‐6]
Comparison of myocardial reperfusion between intracoronary versus intravenous cangrelor administration in patients undergoing primary percutaneous coronary intervention

Background Myocardial reperfusion is the main target of treatment in patients with ST-segment elevation myocardial infarction (STEMI). The intracoronary administration of cangrelor bolus could favor a higher local drug concentration, favoring an earlier thrombotic resolution and a reduced distal micro-embolization. Methods Seventy-one patients undergoing primary percutaneous coronary intervention (PCI) for STEMI: 37 treated with intracoronary and 34 with intravenous bolus administration of cangrelor. The primary endpoint was ST-segment elevation resolution (STR) ≥ 50% after 30 min from the end of the PCI. Other explorative reperfusion indices investigated were: STR ≥ 50% at 24 hours, STR ≥ 70% at 30 min, Thrombolysis In Myocardial Infarction frame count and the QT dispersion. Moreover, acute and subacute stent thrombosis, bleeding events and 30-day mortality have been evaluated. Results More frequent STR ≥ 50% was observed in the intravenous cangrelor bolus group as compared to the intracoronary administration at 30 min (71.9% vs. 45.5%; p = 0.033), the difference was maintained 24 hours after PCI (87.1% vs. 63.6%; p = 0.030). STR ≥ 70% at 30 min was statistically more frequent in the intravenous bolus administration cohort (66.7% vs. 28.6% p = 0.02). At multivariable analysis, intravenous cangrelor administration was significantly related to STR ≥ 50% (odds ratio: 3.586; 95% confidence interval: 1.134–11.335; p = 0.030). The incidence of Bleeding Academic Research Consortium 3–5 bleedings was 15.5% and mortality was 4.2% without any significant difference between the two groups. Conclusions In conclusion the results of the study do not show any advantages in the administration of intracoronary bolus of cangrelor in patients affected by STEMI and treated with primary PCI.
Coping response and family communication of cancer risk in men harboring a BRCA mutation: A mixed methods study

Providing genetic counseling and genetic testing to at‐risk blood relatives (cascade screening) is important for improving BRCA cancer outcomes. Intra‐familial communication of risk is critical for cascade screening efforts yet relatively little is known about men's role in communicating BRCA risk. We sought to examine men's coping response to their BRCA status and intra‐familial communication of risk to inform the development of tailored interventions that could promote cascade screening.
Identifying individuals with Alzheimer's disease‐like brains based on structural imaging in the Human Connectome Project Aging cohort

Given the difficulty in factoring out typical age effects from subtle Alzheimer's disease (AD) effects on brain structure, identification of very early, as well as younger preclinical “at‐risk” individuals has unique challenges. We examined whether age‐correction procedures could be used to better identify individuals at very early potential risk from adults who did not have any existing cognitive diagnosis. First, we obtained cross‐sectional age effects for each structural feature using data from a selected portion of the Human Connectome Project Aging (HCP‐A) cohort. After age detrending, we weighted AD structural deterioration with patterns quantified from data of the Alzheimer's Disease Neuroimaging Initiative. Support vector machine was then used to classify individuals with brains that most resembled atrophy in AD across the entire HCP‐A sample. Additionally, we iteratively adjusted the pipeline by removing individuals classified as AD‐like from the HCP‐A cohort to minimize atypical brain structural contributions to the age detrending. The classifier had a mean cross‐validation accuracy of 94.0% for AD recognition. It also could identify mild cognitive impairment with more severe AD‐specific biomarkers and worse cognition. In an independent HCP‐A cohort, 8.8% were identified as AD‐like, and they trended toward worse cognition. An “AD risk” score derived from the machine learning models also significantly correlated with cognition. This work provides a proof of concept for the potential to use structural brain imaging to identify asymptomatic individuals at young ages who show structural brain patterns similar to AD and are potentially at risk for a future clinical disorder.
Changes of antibiotic resistance over time among Escherichia coli peritonitis in Southern China

Escherichia coli (E. coli) is the main cause of Gram-negative bacterial peritonitis among peritoneal dialysis patients. According to the 2016 update of the International Society for Peritoneal Dialysis Peritonitis Recommendations, drug susceptibilities of specific organisms should be regularly monitored. The aim of this study was to examine the evolution of antimicrobial resistance of E. coli peritonitis from 2006 to 2018. Two hundred and fifty-three episodes of E. coli peritonitis were enrolled in our study, corresponding to a rate of 0.024 episodes per patient-year. According to drug sensitivity test results, isolates were most sensitive to carbapenems, followed by cefmetazole, piperacillin/tazobactam, cefotetan and amikacin, with an overall rate of more than 90% in both cohorts. Cefazolin and ciprofloxacin resistance increased significantly from 2006–2011 to 2012–2018. Conversely, cefepime and ceftazidime resistance decreased significantly. The extended-spectrum β-lactamase (ESBL) rate fluctuated from 34.7% in 2006–2011 to 46.8% in 2012–2018. Compared with the ESBL-negative strains, ESBL-producing E. coli were more likely be resistant to ampicillin, ampicillin/sulbactam, cephalosporins, quinolones, aminoglycosides, furadantin and sulfamethoxazole and accounted for over 50% of the drug resistance. In the correlation analysis, E. coli displayed significantly increased resistance to cefazolin and ciprofloxacin, a finding correlated with ESBL production (r = 0.883 and 0.276 respectively, p < 0.001 and p = 0.003). In conclusion, the rate of E. coli peritonitis declined stably in recent years, but the resistance to antimicrobial was high.
Topologically Protected Photonic Edge States in the Visible in Plasmo‐Gyroelectric Metamaterials

Gyroelectric materials can be used to realize nontrivial photonic topological states. The usual strategy to maximize this effect is to increase the strength of the typically very small, off‐diagonal dielectric permittivity tensor components. This is a very difficult task, in particular at high frequencies. Here, an alternative method is proposed: reducing the strength of the diagonal permittivity tensor components. It is shown that this can be achieved by employing a layered plasmo‐gyroelectric metamaterial as the background medium of a 2D photonic crystal. It is demonstrated that by applying magnetic field, which breaks time reversal invariance, a topologically nontrivial photonic gap opens in the band structure of square and hexagonal photonic crystals. This is confirmed by detecting the presence of a topologically protected edge state at the boundary of this structure. This state is a photonic analog of the edge state in the conventional integer quantum Hall effect, also characterized by suppressed backscattering.
Playing surface traction influences movement strategies during a sidestep cutting task in futsal: implications for ankle performance and sprain injury risk

ABSTRACT This descriptive laboratory crossover trial study examined the intervention of high friction synthetic vs lower friction natural sport surfaces on the ankle joint biomechanics in a sidestep cutting task. Twenty-nine male futsal players performed 5 trials of sidestep cutting task in a laboratory, recorded by an 18-camera motion capture system to obtain the ankle joint orientation, velocity and moment. Utilised friction was obtained by the peak ratio of the horizontal to vertical ground reaction force during the stance. Repeated measures (MANOVA) suggested a significant effect of the playing surface and post hoc paired t-tests revealed significantly higher utilised coefficient of friction, higher peak plantarflexion angle, lower peak eversion angle, higher peak inversion velocity, lower peak inversion moment and higher peak internal rotation moment. In performing a sidestep cutting task, futsal players demonstrated higher utilised ground friction when available friction from the playing surface was higher, resulting in higher peak inversion velocity and higher peak internal rotation moment, which may make the ankle joint more prone to sprain injury. Floorings for futsal should have an adequate coefficient of friction for agility and avoidance of the risk of slipping. Increasing the coefficient of friction may not only enhance performance but also endanger the ankle joint.
Supercritical carbon dioxide decellularized porcine cartilage graft with PRP attenuated OA progression and regenerated articular cartilage in ACLT‐induced OA rats

Knee osteoarthritis (OA) is a common degenerative articular disorder and considered one of the primary causes of pain and functional disability. Knee OA is prevalent in 10% of men and 13% of women aged 60 years above. The study aims to use cartilage tissue engineering that combines the triads of decellularized porcine cartilage graft as “scaffold,” plasma rich platelet (PRP) as “signal” and chondrocytes from rat as “cell” to attenuate ACLT‐induced OA progression and regenerate the knee cartilage in rats. Decellularization of the porcine cartilage was characterized by hematoxylin and eosin, 4,6‐Diamidino‐2‐phenylindole staining, scanning electron microscopy and residual DNA quantification. The protective effect of decellularized porcine cartilage graft (dPCG) was evaluated by intra‐articular administration in surgically induced anterior cruciate ligament transection (ACLT) rat osteoarthritis (OA) model. Supercritical carbon dioxide technology completely decellularized the porcine cartilage. Intra‐articular administration of dPCG with or without PRP significantly reduced the ACLT‐induced OA symptoms and attenuated the OA progression. Pain‐relief by dPCG with or without PRP was assessed by capacitance meter and improved articular cartilage damage in the rat knee was characterized by X‐ray and micro‐CT. Besides, the histological analysis depicted cartilage protection by dPCG with or without PRP. The repairation and attenuation effect by dPCG with or without PRP in the articular knee cartilage damage were also explored by safranin‐O, type II collagen, aggrecan and SOX‐9 immuno‐staining. To conclude, intra‐articular administration of dPCG with or without PRP is efficient in repairing the damaged cartilage in the experimental OA model.
A Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis: Interim Clinical Trial Results

Purpose To report the initial safety and efficacy results of a second-generation (44-channel) suprachoroidal retinal prosthesis at 56 weeks after device activation. Methods Four subjects, with advanced retinitis pigmentosa and bare-light perception only, enrolled in a phase II trial (NCT03406416). A 44-channel electrode array was implanted in a suprachoroidal pocket. Device stability, efficacy, and adverse events were investigated at 12-week intervals. Results All four subjects were implanted successfully and there were no device-related serious adverse events. Color fundus photography indicated a mild postoperative subretinal hemorrhage in two recipients, which cleared spontaneously within 2 weeks. Optical coherence tomography confirmed device stability and position under the macula. Screen-based localization accuracy was significantly better for all subjects with device on versus device off. Two subjects were significantly better with the device on in a motion discrimination task at 7, 15, and 30°/s and in a spatial discrimination task at 0.033 cycles per degree. All subjects were more accurate with the device on than device off at walking toward a target on a modified door task, localizing and touching tabletop objects, and detecting obstacles in an obstacle avoidance task. A positive effect of the implant on subjects’ daily lives was confirmed by an orientation and mobility assessor and subject self-report. Conclusions These interim study data demonstrate that the suprachoroidal prosthesis is safe and provides significant improvements in functional vision, activities of daily living, and observer-rated quality of life. Translational Relevance A suprachoroidal prosthesis can provide clinically useful artificial vision while maintaining a safe surgical profile.