Miracle-dz/UniFAR-FTUs huggingface dataset:
The effectiveness of Kinesio Taping in improving pain and edema during early rehabilitation after Anterior Cruciate Ligament Reconstruction: A Prospective, Randomized, Control Study

Background and aim: The Kinesio Taping (KT) is being increasingly applied in physical therapy and rehabilitation. The aim of this study was to evaluate the effect of KT on an early rehabilitation program, in combination with the standard protocol after ACL reconstruction (ACLR). Methods: This study enrolled 52 male patients, aged 18 to 45 years, who underwent ACLR with doubled gracilis and semitendinosus tendon (DGST) autograft. The patients were randomized into 2 groups: Group A (the control group) which received a standard rehabilitation protocol, and Group B (the experimental group), which had the same rehabilitation protocol plus the KT application. Pain intensity, range of motion, edema, thigh circumference, Tegner-Lysholm Scale and KOOS scale were measured at the second and fourth week follow-ups. Results: Patients in the experimental group showed significant results during the second week for both pain and edema reduction compared to the control group (p< 0.05). After 4 weeks of rehabilitation, pain intensity in the two groups was similar (n.s.), while edema reduction in the experimental group showed a significant result compared to the control group (p< 0.05). Nevertheless, the other outcomes did not show significant differences. Conclusions: The application of KT after ACLR contributed to relieve pain and reduce edema in the early postoperative rehabilitation period. Other potential benefits of KT on muscle activation and strength should be investigated through a longer follow-up and a targeted test. (www.actabiomedica.it)
Assessment of intravitreal anti-VEGF drugs and dexamethasone for retinal diseases in real world setting: A multi-centre prospective study from Southern Italy

Describe drug utilisation and clinical outcomes of intravitreal anti-VEGF drug and dexamethasone use in the real-world setting in Southern Italy using data from multi-centre study of retinal disease. Clinical data of retinal disease patients treated with anti-VEGF drugs and dexamethasone implant in 6 out-patient ophthalmology centres from Southern Italy were collected by means of an electronic case report form. Patients receiving at least one intravitreal injection/implant of the study drugs were followed for up to two years and described in terms of demographics and clinical characteristics. Drug utilisation patterns were described. A sign-rank test was used to compare clinical data on visual acuity and other ophthalmic parameters from baseline at different follow-up times for each indication. Data from 1327 patients was collected. Most patients were diagnosed with age-related macular degeneration (AMD) (660, 49.7%), followed by diabetic macular oedema (423, 31.9%), retinal vein occlusion (164, 12.3%), and myopic choroidal neovascularization (80, 6.0%). Patients were followed for a median of 10.3 months (interquartile range: 3.6 – 24.7 months). Mean patient age was 69.7 (±10.9) years and 54.2% were males. Ranibizumab (55.4%) and aflibercept (27.5%) were the most commonly used drugs. Baseline visual acuity significantly improved by about 0.05 to 0.1 logMAR at all follow-up times for AMD and RVO but less consistently for the other diseases. Intravitreal ranibizumab use accounted for half of all treatment for retinal diseases in a Southern Italian out-patient setting. Patients treated with anti-VEGF drugs for AMD and RVO in Southern Italy experienced significant improvement in VA.
A clinical perspective on the expanding role of artificial intelligence in age-related macular degeneration

ABSTRACT In recent years, there has been intense development of artificial intelligence (AI) techniques, which have the potential to improve the clinical management of age-related macular degeneration (AMD) and facilitate the prevention of irreversible vision loss from this condition. Such AI techniques could be used as clinical decision support tools to: (i) improve the detection of AMD by community eye health practitioners, (ii) enhance risk stratification to enable personalised monitoring strategies for those with the early stages of AMD, and (iii) enable early detection of signs indicative of possible choroidal neovascularisation allowing triaging of patients requiring urgent review. This review discusses the latest developments in AI techniques that show promise for these tasks, as well as how they may help in the management of patients being treated for choroidal neovascularisation and in accelerating the discovery of new treatments in AMD.
Hcp2b of T6SS affects colonization of avian pathogenic Escherichia coli and host keratin filament expression

ABSTRACT T6SS (type VI secretion system) is a type of nano-syringe that exists in APEC (avian pathogenic Escherichia coli). Hcp (haemolysin-coregulated protein) of T6SS participates in the regulation of virulence during APEC infection. However, whether hcp plays a role in bacterial colonization by expression in host cells remains unclear. In this study, we analysed the biological characteristics of the mutant hcp2b strain. Our results showed that the hcp2b gene was involved in the regulation of bacterial motility, biofilm formation, anti-serum and anti-oxidative stress. Moreover, our data indicate that the colonization of the hcp2b mutation strain (Δhcp2b) in the lung, liver and kidney of chickens decreased significantly. Hence, overexpression of Hcp2b protein in DF-1 cells was used to analyse the effect of Hcp2b on colonization of APEC. Proteomics analysis showed that overexpression of Hcp2b induced differentially expressed proteins in DF-1 cells (230 were significantly upregulated and 96 were significantly downregulated) and differentially expressed proteins were enriched in keratin filament. In conclusion, our data indicated that hcp2b promoted the colonization of APEC by affecting the expression of keratin filament.
Inducing somatic cells into pluripotent stem cells is an important platform to study the mechanism of early embryonic development

The early embryonic development starts with the totipotent zygote upon fertilization of differentiated sperm and egg, which undergoes a range of reprogramming and transformation to acquire pluripotency. Induced pluripotent stem cells (iPSCs), a nonclonal technique to produce stem cells, are originated from differentiated somatic cells via accomplishment of cell reprogramming, which shares common reprogramming process with early embryonic development. iPSCs are attractive in recent years due to the potentially significant applications in disease modeling, potential value in genetic improvement of husbandry animal, regenerative medicine, and drug screening. This review focuses on introducing the research advance of both somatic cell reprogramming and early embryonic development, indicating that the mechanisms of iPSCs also shares common features with that of early embryonic development in several aspects, such as germ cell factors, DNA methylation, histone modification, and/or X chromosome inactivation. As iPSCs can successfully avoid ethical concerns that are naturally present in the embryos and/or embryonic stem cells, the practicality of somatic cell reprogramming (iPSCs) could provide an insightful platform to elucidate the mechanisms underlying the early embryonic development.
Enhanced effect of recombinant adenoviruses co‐expression of ING4 and OSM on anti‐tumour activity of laryngeal cancer

The inhibitor of growth family member 4 (ING4) is one of the ING family genes, serves as a repressor of angiogenesis or tumour growth and suppresses loss of contact inhibition. Oncostatin M (OSM) is a multifunctional cytokine that belongs to the interleukin (IL)‐6 subfamily with several biological activities. However, the role of recombinant adenoviruses co‐expressing ING4 and OSM (Ad‐ING4‐OSM) in anti‐tumour activity of laryngeal cancer has not yet been identified. Recombinant Ad‐ING4‐OSM was used to evaluate their combined effect on enhanced anti‐tumour activity in Hep‐2 cells of laryngeal cancer in vivo. Moreover, in vitro function assays of co‐expression of Ad‐ING4‐OSM were performed to explore impact of co‐expression of Ad‐ING4‐OSM on biological phenotype of laryngeal cancer cell line, that is Hep‐2 cells. In vitro, Ad‐ING4‐OSM significantly inhibited the growth, enhanced apoptosis, altered cell cycle with G1 and G2/M phase arrest, and upregulated the expression of P21, P27, P53 and downregulated survivin in laryngeal cancer Hep‐2 cells. Furthermore, in vivo functional experiments of co‐expressing of Ad‐ING4‐OSM demonstrated that solid tumours in the nude mouse model were significantly suppressed, and the co‐expressing Ad‐ING4‐OSM showed a significant upregulation expression of P21, P53, Bax and Caspase‐3 and a downregulation of Cox‐2, Bcl‐2 and CD34. This study for the first time demonstrated the clinical value and the role of co‐expressing Ad‐ING4‐OSM in biological function of laryngeal cancer. This work suggested that co‐expressing Ad‐ING4‐OSM might serve as a potential therapeutic target for laryngeal cancer patients.
Fourth generation of synthetic cannabinoid receptor agonists: a summary on the latest insights

BACKGROUND AND AIM From few years, an emerging number of new psychoactive substances (NPS) entered the illicit market. NPS are designed to be similar to the effects of classical drugs of abuse, with increased effects and duration. Synthetic cannabinoids are cannabinoid receptor agonists (SCRAs), some of the most abused NPS. METHODS We have herein briefly highlighted current relevant available information on the newest SCRAs generation, with relevant structural remarks as to the distinctive traits of such substances. RESULTS Compared to the previous SCRAs generations, the structures of the last generation result in increased affinity for and efficacy at cannabinoid CB1 receptors, which are thought to be mainly responsible for the psychoactive effects of THC and its analogues. Accordingly, these more potent cannabimimetic effects may increase the number of adverse reactions such as neurological disorders, psychiatric episodes and deaths. In the last decade, more than a hundred SCRAs from different chemical classes emerged on the illicit web market. SCRAs have been thoroughly studied and the last generations include increasingly potent and toxic compounds, posing a potentially daunting health threat to consumers. CONCLUSIONS From November 2017 to February 2021, at least 20 new "fourth-generation" SCRAs were formally reported to international drug agencies. Our understanding about the neurotoxicity of these compounds is still limited, due to the lack of global data, but their potency and their toxicity are likely higher than those of the previous generations.
Comparison of Four‐Dimensional Magnetic Resonance Imaging Analysis of Left Ventricular Fluid Dynamics and Energetics in Ischemic and Restrictive Cardiomyopathies

Time‐resolved three‐directional velocity‐encoded (4D flow) magnetic resonance imaging (MRI) enables the quantification of left ventricular (LV) intracavitary fluid dynamics and energetics, providing mechanistic insight into LV dysfunctions. Before becoming a support to diagnosis and patient stratification, this analysis should prove capable of discriminating between clearly different LV derangements.
Development of a Pipeline for Adverse Drug Reaction Identification in Clinical Notes: Word Embedding Models and String Matching

Background Knowledge about adverse drug reactions (ADRs) in the population is limited because of underreporting, which hampers surveillance and assessment of drug safety. Therefore, gathering accurate information that can be retrieved from clinical notes about the incidence of ADRs is of great relevance. However, manual labeling of these notes is time-consuming, and automatization can improve the use of free-text clinical notes for the identification of ADRs. Furthermore, tools for language processing in languages other than English are not widely available. Objective The aim of this study is to design and evaluate a method for automatic extraction of medication and Adverse Drug Reaction Identification in Clinical Notes (ADRIN). Methods Dutch free-text clinical notes (N=277,398) and medication registrations (N=499,435) from the Cardiology Centers of the Netherlands database were used. All clinical notes were used to develop word embedding models. Vector representations of word embedding models and string matching with a medical dictionary (Medical Dictionary for Regulatory Activities [MedDRA]) were used for identification of ADRs and medication in a test set of clinical notes that were manually labeled. Several settings, including search area and punctuation, could be adjusted in the prototype to evaluate the optimal version of the prototype. Results The ADRIN method was evaluated using a test set of 988 clinical notes written on the stop date of a drug. Multiple versions of the prototype were evaluated for a variety of tasks. Binary classification of ADR presence achieved the highest accuracy of 0.84. Reduced search area and inclusion of punctuation improved performance, whereas incorporation of the MedDRA did not improve the performance of the pipeline. Conclusions The ADRIN method and prototype are effective in recognizing ADRs in Dutch clinical notes from cardiac diagnostic screening centers. Surprisingly, incorporation of the MedDRA did not result in improved identification on top of word embedding models. The implementation of the ADRIN tool may help increase the identification of ADRs, resulting in better care and saving substantial health care costs.
In vitro antiproliferative activity of alkaloids isolated from Tabernaemontana catharinensis A.DC (Apocynaceae)

Abstract In this work, four alkaloids from the stem bark of T. catharinensis were isolated, namely: voacangine (1); ethyl apovincaminate (2); affinisine (3) and voachalotine (4). The alkaloids were tested in vitro for antiproliferative capacity in eight tumor cell lines: U251 (glioma), MCF-7 (breast), NCI-ADR/RES (drug resistant ovary), 786-0 (kidney), NCI-H460 (lung), HT-29 (colon), K562 (leukemia) and PC-3 (prostate) and a non-tumor keratinocyte cell line (HaCat). Antiproliferative activity was observed after 48 hours and results expressed as the concentration needed to induce 50% growth inhibition (GI50) in µM. The chemotherapy drug Doxorubicin was used as a standard. The alkaloid affinisine (3) was the most promising, showing moderate inhibition rates in addition to the cytotoxic and cytocidal effect against all strains tested. It also proved to be a very promising compound, showing high selectivity rates when compared to the non-tumor keratinocyte cell line (HaCat). Graphical Abstract
Emerging therapeutic targets for cardiac hypertrophy

ABSTRACT Introduction Cardiac hypertrophy is associated with adverse outcomes across cardiovascular disease states. Despite strides over the last three decades in identifying molecular and cellular mechanisms driving hypertrophy, the link between pathophysiological stress stimuli and specific myocyte/heart growth profiles remains unclear. Moreover, the optimal strategy for preventing pathology in the setting of hypertrophy remains controversial. Areas Covered This review discusses molecular mechanisms underlying cardiac hypertrophy with a focus on factors driving the orientation of myocyte growth and the impact on heart function. We highlight recent work showing a novel role for the spectrin-based cytoskeleton, emphasizing regulation of myocyte dimensions but not hypertrophy per se. Finally, we consider opportunities for directing the orientation of myocyte growth in response to hypertrophic stimuli as an alternative therapeutic approach. Relevant publications on the topic were identified through Pubmed with open-ended search dates. Expert Opinion To define new therapeutic avenues, more precision is required when describing changes in myocyte and heart structure/function in response to hypertrophic stimuli. Recent developments in computational modeling of hypertrophic networks, in concert with more refined experimental approaches will catalyze translational discovery to advance the field and further our understanding of cardiac hypertrophy and its relationship with heart disease.
Phosphorylated TDP-43 aggregates in peripheral motor nerves of patients with amyotrophic lateral sclerosis

Abstract Phosphorylated TDP-43 (pTDP-43) aggregates in the cytoplasm of motor neurons and neuroglia in the brain are one of the pathological hallmarks of amyotrophic lateral sclerosis. Although the axons exceed the total volume of motor neuron soma by several orders of magnitude, systematic studies investigating the presence and distribution of pTDP-43 aggregates within motor nerves are still lacking. The aim of this study is to define the TDP-43/pTDP-43 pathology in diagnostic motor nerve biopsies performed on a large cohort of patients presenting with a lower motor neuron syndrome and to assess whether this might be a discriminating tissue biomarker for amyotrophic lateral sclerosis and non-amyotrophic lateral sclerosis cases. We retrospectively evaluated 102 lower motor neuron syndrome patients referred to our centre for a diagnostic motor nerve biopsy. Histopathological criteria of motor neuron disease and motor neuropathy were applied by two independent evaluators, who were blind to clinical data. TDP-43 and pTDP-43 were evaluated by immunohistochemistry, and results compared to final clinical diagnosis. We detected significant differences between amyotrophic lateral sclerosis and non-amyotrophic lateral sclerosis cases in pTDP-43 expression in myelinated fibres: axonal accumulation was detected in 98.2% of patients with amyotrophic lateral sclerosis versus 30.4% of non-amyotrophic lateral sclerosis samples (P < 0.0001), while concomitant positive staining in Schwan cell cytoplasm was found in 70.2% of patients with amyotrophic lateral sclerosis versus 17.4% of patients who did not have amyotrophic lateral sclerosis (P < 0.001). Importantly, we were also able to detect pTDP-43 aggregates in amyotrophic lateral sclerosis cases displaying normal features at standard histopathological analysis. Our findings demonstrated that a specific pTDP-43 signature is present in the peripheral nervous system of patients with amyotrophic lateral sclerosis, and could be exploited as a specific, accessible tissue biomarker. The detection of pTDP-43 aggregates within motor nerves of living patients with amyotrophic lateral sclerosis, occurring before axonal degeneration, suggests that this is an early event that may contribute to amyotrophic lateral sclerosis pathogenesis.
Group IIA secreted phospholipase A2 controls skin carcinogenesis and psoriasis by shaping the gut microbiota

Besides promoting inflammation by mobilizing lipid mediators, group IIA secreted phospholipase A2 (sPLA2-IIA) prevents bacterial infection by degrading bacterial membranes. Here, we show that, despite the restricted intestinal expression of sPLA2-IIA in BALB/c mice, its genetic deletion leads to amelioration of cancer and exacerbation of psoriasis in distal skin. Intestinal expression of sPLA2-IIA is reduced after treatment with antibiotics or under germ-free conditions, suggesting its upregulation by gut microbiota. Metagenome, transcriptome, and metabolome analyses have revealed that sPLA2-IIA deficiency alters the gut microbiota, accompanied by notable changes in the intestinal expression of genes related to immunity and metabolism, as well as in the levels of various blood metabolites and fecal bacterial lipids, suggesting that sPLA2-IIA contributes to shaping of the gut microbiota. The skin phenotypes in Pla2g2a–/– mice are lost (a) when they are cohoused with littermate WT mice, resulting in the mixing of the microbiota between the genotypes, or (b) when they are housed in a more stringent pathogen-free facility, where Pla2g2a expression in WT mice is low and the gut microbial compositions in both genotypes are nearly identical. Thus, our results highlight a potentially new aspect of sPLA2-IIA as a modulator of gut microbiota, perturbation of which affects distal skin responses.
Impairing RAGE signaling promotes survival and limits disease pathogenesis following SARS-CoV-2 infection in mice

Cellular and molecular mechanisms driving morbidity following SARS-CoV-2 infection have not been well defined. The receptor for advanced glycation end products (RAGE) is a central mediator of tissue injury and contributes to SARS-CoV-2 disease pathogenesis. In this study, we temporally delineated key cell and molecular events leading to lung injury in mice following SARS-CoV-2 infection and assessed efficacy of therapeutically targeting RAGE to improve survival. Early following infection, SARS-CoV-2 replicated to high titers within the lungs and evaded triggering inflammation and cell death. However, a significant necrotic cell death event in CD45– populations, corresponding with peak viral loads, was observed on day 2 after infection. Metabolic reprogramming and inflammation were initiated following this cell death event and corresponded with increased lung interstitial pneumonia, perivascular inflammation, and endothelial hyperplasia together with decreased oxygen saturation. Therapeutic treatment with the RAGE antagonist FPS-ZM1 improved survival in infected mice and limited inflammation and associated perivascular pathology. Together, these results provide critical characterization of disease pathogenesis in the mouse model and implicate a role for RAGE signaling as a therapeutic target to improve outcomes following SARS-CoV-2 infection.
Survival rate, blood feeding habits and sibling species composition of Aedes simpsoni complex: Implications for arbovirus transmission risk in East Africa

Aedes simpsoni complex has a wide distribution in Africa and comprises at least three described sub-species including the yellow fever virus (YFV) vector Ae. bromeliae. To date, the distribution and relative contributions of the sub-species and/or subpopulations including bionomic characteristics in relation to YF transmission dynamics remain poorly studied. In this study conducted in two areas with divergent ecosystems: peri-urban (coastal Rabai) and rural (Rift Valley Kerio Valley) in Kenya, survival rate was estimated by parity in Ae. simpsoni s.l. mosquitoes sampled using CO2-baited BG Sentinel traps. We then applied PCR targeting the nuclear internal transcribed spacer 2 (ITS2), region followed by sequencing and phylogenetic analytics to identify the sibling species in the Ae. simpsoni complex among parous and blood fed cohorts. Our results show that Ae. bromeliae was the most dominant sub-species in both areas, exhibiting high survival rates, human blood-feeding, and potentially, high vectorial capacity for pathogen transmission. We document for the first time the presence of Ae. lilii in Kenya and potentially yet-to-be described species in the complex displaying human feeding tendencies. We also infer a wide host feeding range on rodents, reptile, and domestic livestock besides humans especially for Ae. bromeliae. This feeding trend could likely expose humans to various zoonotic pathogens. Taken together, we highlight the utility of genotype-based analyses to generate precision surveillance data of vector populations for enhanced disease risk prediction and to guide cost-effective interventions (e.g. YF vaccinations).