Miracle-dz/UniFAR-FTUs huggingface dataset:
A Combined Computational and Experimental Analysis of PLA and PCL Hybrid Nanocomposites 3D Printed Scaffolds for Bone Regeneration

A combined computational and experimental study of 3D-printed scaffolds made from hybrid nanocomposite materials for potential applications in bone tissue engineering is presented. Polycaprolactone (PCL) and polylactic acid (PLA), enhanced with chitosan (CS) and multiwalled carbon nanotubes (MWCNTs), were investigated in respect of their mechanical characteristics and responses in fluidic environments. A novel scaffold geometry was designed, considering the requirements of cellular proliferation and mechanical properties. Specimens with the same dimensions and porosity of 45% were studied to fully describe and understand the yielding behavior. Mechanical testing indicated higher apparent moduli in the PLA-based scaffolds, while compressive strength decreased with CS/MWCNTs reinforcement due to nanoscale challenges in 3D printing. Mechanical modeling revealed lower stresses in the PLA scaffolds, attributed to the molecular mass of the filler. Despite modeling challenges, adjustments improved simulation accuracy, aligning well with experimental values. Material and reinforcement choices significantly influenced responses to mechanical loads, emphasizing optimal structural robustness. Computational fluid dynamics emphasized the significance of scaffold permeability and wall shear stress in influencing bone tissue growth. For an inlet velocity of 0.1 mm/s, the permeability value was estimated at 4.41 × 10−9 m2, which is in the acceptable range close to human natural bone permeability. The average wall shear stress (WSS) value that indicates the mechanical stimuli produced by cells was calculated to be 2.48 mPa, which is within the range of the reported literature values for promoting a higher proliferation rate and improving osteogenic differentiation. Overall, a holistic approach was utilized to achieve a delicate balance between structural robustness and optimal fluidic conditions, in order to enhance the overall performance of scaffolds in tissue engineering applications.
Study of serum interleukin 35 level in patients with acute myeloid leukemia

Background: Acute myeloid leukaemia (AML) is a dangerous cancer of the blood-forming stem cells, which leads to a rise in the number of myeloid cells in the bone marrow. This may cause severe infections, bleeding, or the invasion of organs, ultimately leading in death. This research aimed to evaluate the significance of serum interleukin IL-35 levels in individuals with AML. Methods: serum IL-35 was measured using enzyme-linked immunosorbent assays and evaluated as biomarkers for the diagnosis and prognosis. Results: There was positive significant correlation between serum IL-35 level and Age, WBC, peripheral blood blasts, BM blasts, lactate dehydrogenase (LDH), cluster of differentiation (CD) 45, myeloperoxidase (MPO), human leukocyte antigen - DR isotype (HLA-DR) and CD34 ( P < 0.001). There was significant negative correlation between serum IL35 level and platelets, CD13 and CD 117 ( p < 0.001, p=0.001, p=0.001 respectively). While there was no significant correlation between serum IL35 level and haemoglobin (Hb), erythrocyte sedimentation rate (ESR) 1st hr, CD14, CD33 and CD64. ROC curve analysis showed that serum IL-35 had diagnostic value for AML with 92% sensitivity, 90% specificity. Conclusions: Serum IL 35 level may have a role in the diagnosis of AML. Serum IL 35 correlates positively with prognostic markers as age, complete blood count (CBC) parameters, peripheral blood blasts, BM blasts, serum LDH, HLA-DR and CD 34, so it may be a useful prognostic marker.
The effect of front and back squat techniques on peak loads experienced by the Achilles tendon

Article statistics Word count: 1,600; Tables: 1; Figures: 1; References: 19 Received: November 2014; Accepted: July 2015; Published: September 2015 Full-text PDF: http://www.balticsportscience. com Copyright © Gdansk University of Physical Education and Sport, Poland Indexation: AGRO, Celdes, CNKI Scholar (China National Knowledge Infrastructure), CNPIEC, De Gruyter IBR (International Bibliography of Reviews of Scholarly Literature in the Humanities and Social Sciences), De Gruyter IBZ (International Bibliography of Periodical Literature in the Humanities and Social Sciences), DOAJ, EBSCO Central & Eastern European Academic Source, EBSCO SPORTDiscus, EBSCO Discovery Service, Google Scholar, Index Copernicus, J-Gate, Naviga (Softweco, Primo Central (ExLibris), ProQuest Family Health, ProQuest Health & Medical Complete, ProQuest Illustrata: Health Sciences, ProQuest Nursing & Allied Health Source, Summon (Serials Solutions/ProQuest, TDOne (TDNet), Ulrich’s Periodicals Directory/ulrichsweb, WorldCat (OCLC) Funding: University’s Code of Conduct for Research can be found at the following web address: http://www.uclan.ac.uk/information/research/research_degrees/ethics_research_governance. php. Conflict of interest: Authors have declared that no competing interest exists. Corresponding author: Dr. Jonathan Sinclair, Division of Sport, Exercise and Nutritional Sciences, School of Sport Tourism and Outdoors, University of Central Lancashire, Preston, Lancashire, PR1 2HE. e-mail: Jksinclair@uclan.ac.uk Open Access License: This is an open access article distributed under the terms of the Creative Commons Attribution-Non-commercial 4.0 International (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non-commercial and is otherwise in compliance with the license. abstract
Quantifying the impact of pre-vaccination titre and vaccination history on influenza vaccine immunogenicity

Epidemiological studies suggest that heterogeneity in influenza vaccine antibody response is associated with host factors, including pre-vaccination immune status, age, gender, and vaccination history. However, the pattern of reported associations varies between studies. To better understand the underlying influences on antibody responses, we combined host factors and vaccine-induced in-host antibody kinetics from a cohort study conducted across multiple seasons with a unified analysis framework. We developed a flexible Bayesian model to estimate associations and interactions between host factors, including pre-vaccine HAI titre, age, sex, vaccine history and study setting, and vaccine-induced HAI titre antibody boosting and waning. We applied the model to derive population-level and individual effects of post-vaccine antibody kinetics for vaccinating and circulating strains for A(H1N1) and A(H3N2) influenza subtypes. We found that post-vaccine HAI titre dynamics were significantly influenced by pre-vaccination HAI titre and vaccination history. In addition, we find the common heuristic of a four-fold rise in titre is valid for detecting seroconversion in an infrequently vaccinated cohort (<2 vaccines in last 5 years) within six months of vaccination if their pre-vaccination HAI titres are equal to or below 1:20. The same heuristic only works for a frequently vaccinated population (2 or more vaccines in last 5 years) for up to 3 months post-vaccination providing their pre-vaccination HAI titres are equal to or below 1:20. In future, seroepidemiological studies should ensure the impact of pre-vaccine HAI and prior vaccination status on vaccine-induced fold-rises is properly quantified, as these significantly influence an individual's post-vaccination antibody kinetics.
A Study of Community-Acquired Pyodermas with Special Reference to Panton–Valentine Leukocidin (PVL)-Positive Methicillin-Resistant Staphylococcus Aureus

Background: Community-acquired (CA) pyodermas are one of the most common infections encountered in the dermatology outpatient clinics. A significant number of these conditions are caused by Staphylococcus aureus. CA-methicillin-sensitive Staphylococcus aureus (MSSA) and CA-methicillin-resistant Staphylococcus aureus (MRSA) have specific virulence genes which are associated with these diseases, particularly the Panton–Valentine leukocidin (PVL) genes. The presence of the PVL gene as a virulence factor may be associated with recurrent and severe skin infections. Materials and Methods: A prospective study was conducted with 205 cases of CA pyodermas, of which five were discarded due to mixed isolates. Clinical details were taken and wound exudate was sent for bacteriological examination. Further, the molecular study was performed on all MRSA (7) isolates and 13 randomly selected MSSA isolates using polymerase chain reaction for mecA and PVL genes. Results: Staphylococcus aureus was the most common organism (90%) isolated from primary or secondary CA pyodermas. The prevalence of CA-MRSA among all pyodermas was 3.5% in our community. The PVL gene was not detected in all tested CA-MRSA and CA-MSSA isolates. Conclusion: While pyodermas are common, the prevalence of MRSA is low in the CA pyodermas in our region. PVL does not appear to be a virulence factor among the isolated MRSA. Larger, multicentric, and periodic studies are, however, required to further justify these claims.
Current trends and challenges: The landscape of perioperative mortality in intracranial surgeries in low‐ and middle‐income settings: A narrative review

Abstract Background and Aims Intracranial surgeries are pivotal in treating cerebral pathologies, particularly in resource‐limited contexts, utilizing techniques such as craniotomy, transsphenoidal approaches, and endoscopy. However, challenges in low and middle income countries (LMICs), including resource scarcity, diagnostic delays, and a lack of skilled neurosurgeons, lead to elevated perioperative mortality (POM). This review seeks to identify major contributors to these challenges and recommend solutions for improved patient outcomes in neurosurgical care within LMICs. Methods This review examines POM in LMICs using a detailed literature search, focusing on studies from these regions. Databases like PubMed, EMBASE, and Google Scholar were utilized using specific terms related to “intracranial surgery,” “perioperative mortality,” “traumatic brain injuries,” and “LMICs. ” Inclusion criteria covered various study designs and both pediatric and adult populations while excluding stand‐alone abstracts and case reports. Results POM rates for intracranial surgeries differ widely across many low and middle‐income regions: Africa sees rates from 2.5% to 39.1%, Asia between 3.6% and 34.8%, and Latin America and the Caribbean have figures ranging from 1.3% to 12%. The POM rates in LMICs were relatively higher compared to most first‐world countries. The high POM rates in LMICs can be attributed to considerable delays and compromises in neurosurgical care delivery, exacerbated by late diagnoses and presentations of neurosurgical pathologies. This, coupled with limited resources, underdeveloped infrastructure, and training gaps, complicates intracranial disease management, leading to elevated POM. Conclusion Intracranial POM is a pronounced disparity within the neurosurgical field in LMICs. To mitigate intracranial POM, it is imperative to bolster healthcare infrastructure, amplify personnel training, foster global partnerships, and harness technologies like telemedicine. Tackling socioeconomic obstacles and prioritizing early detection through sustained funding and policy shifts can substantially enhance patient outcomes.
Characterization of a novel variant in the HR1 domain of MFN2 in a patient with ataxia, optic atrophy and sensorineural hearing loss [version 1; peer review: 2 approved with reservations]

Background: Pathogenic variants in MFN2 cause Charcot-Marie-Tooth disease (CMT) type 2A (CMT2A) and are the leading cause of the axonal subtypes of CMT. CMT2A is characterized by predominantly distal motor weakness and muscle atrophy, with highly variable severity and onset age. Notably, some MFN2 variants can also lead to other phenotypes such as optic atrophy, hearing loss and lipodystrophy. Despite the clear link between MFN2 and CMT2A, our mechanistic understanding of how dysfunction of the MFN2 protein causes human disease pathologies
Identifying critically ill children in Malawi: A modified qSOFA score for low-resource settings

In low-resource settings, a reliable bedside score for timely identification of children at risk of dying, could help focus resources and improve survival. The rapid bedside Liverpool quick Sequential Organ Failure Assessment (LqSOFA) uses clinical parameters only and performed well in United Kingdom cohorts. A similarly quick clinical assessment-only score has however not yet been developed for paediatric populations in sub-Saharan Africa. In a development cohort of critically ill children in Malawi, we calculated the LqSOFA scores using age-adjusted heart rate and respiratory rate, capillary refill time and Blantyre Coma Scale, and evaluated its prognostic performance for mortality. An improved score, the Blantyre qSOFA (BqSOFA), was developed (omitting heart rate, adjusting respiratory rate cut-off values and adding pallor), subsequently validated in a second cohort of Malawian children, and compared with an existing score (FEAST-PET). Prognostic performance for mortality was evaluated using area under the receiver operating characteristic curve (AUC). Mortality was 15.4% in the development (N = 493) and 22.0% in the validation cohort (N = 377). In the development cohort, discriminative ability (AUC) of the LqSOFA to predict mortality was 0.68 (95%-CI: 0.60–0.76). The BqSOFA and FEAST-PET yielded AUCs of 0.84 (95%-CI:0.79–0.89) and 0.83 (95%-CI:0.77–0.89) in the development cohort, and 0.74 (95%-CI:0.68–0.79) and 0.76 (95%-CI:0.70–0.82) in the validation cohort, respectively. We developed a simple prognostic score for Malawian children based on four clinical parameters which performed as well as a more complex score. The BqSOFA might be used to promptly identify critically ill children at risk of dying and prioritize hospital care in low-resource settings.
The emerging role for neutrophil mitochondrial metabolism in lung inflammation

Recent advances shed light on the importance of mitochondrial metabolism in supporting essential neutrophil functions such as trafficking, NETosis, bacterial killing, and modulating inflammatory responses. Mitochondrial metabolism is now recognized to contribute to a number of lung diseases marked by neutrophilic inflammation, including bacterial pneumonia, acute lung injury, and chronic obstructive pulmonary disease. In this mini review, we provide an overview of neutrophil metabolism focusing on the role of mitochondrial programs, discuss select neutrophil effector functions that are directly influenced by mitochondrial metabolism, and present what is known about the role for mitochondrial metabolism in lung diseases marked by neutrophilic inflammation.
Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is an exceptionally immunosuppressive malignancy characterized by limited treatment options and a dismal prognosis. Macrophages constitute the primary and heterogeneous immune cell population within the HCC microenvironment. Our objective is to identify distinct subsets of macrophages implicated in the progression of HCC and their resistance to immunotherapy. Methods Intratumoral macrophage-specific marker genes were identified via single-cell RNA sequencing analyses. The clinical relevance of phospholipase A2 Group VII (PLA2G7), a pivotal enzyme in phospholipid metabolism, was assessed in patients with HCC through immunohistochemistry and immunofluorescence. Flow cytometry and an in vitro co-culture system were used to elucidate the specific role of PLA2G7 in macrophages. Orthotopic and subcutaneous HCC mouse models were employed to evaluate the potential of the PLA2G7 inhibitor in complementing immune checkpoint blockade (ICB) therapy. Results Single-cell RNA sequencing analyses disclosed predominant PLA2G7 expression in intratumoral macrophages within the HCC microenvironment. The macrophage-specific PLA2G7 was significantly correlated with poorer prognosis and immunotherapy resistance in patients with HCC. PLA2G7high macrophages represent a highly immunosuppressive subset and impede CD8 T-cell activation. Pharmacological inhibition of PLA2G7 by darapladib improved the therapeutic efficacy of anti-programmed cell death protein 1 antibodies in the HCC mouse models. Conclusions Macrophage-specific PLA2G7 serves as a novel biomarker capable of prognosticating immunotherapy responsiveness and inhibiting PLA2G7 has the potential to enhance the efficacy of ICB therapy for HCC.
Latin American Consensus for the Evaluation and Treatment of Patients With Metastatic/Locally Advanced Urothelial Carcinoma

PURPOSE Urothelial cancer accounts for approximately 3% of new cancer cases worldwide, with a high burden of disease in countries with medium and low human development indexes where its incidence and mortality are increasing. The purpose of this consensus is to develop statements on the evaluation and treatment of locally advanced and metastatic urothelial carcinoma that would further guide the clinical practice in Latin America. METHODS A systematic review of the literature was conducted by an independent team of methodologists. Then, a modified Delphi method was developed with clinical specialists from different Latin American countries. RESULTS Forty-two consensus statements, based on evidence, were developed to address the staging, the evaluation (suitability for chemotherapy, risk assessment, and biomarkers), and systemic treatment (first-line and subsequent therapies) of locally advanced or metastatic urothelial carcinoma. The statements made in this consensus are suggested practice recommendations in the Latin American context; however, the importance of a complete and individualized patient evaluation as a guide for therapeutic selection is highlighted. The availability and affordability of support tools for the evaluation of the disease, as well as specific therapies, may limit the application of the best practices suggested. Recommendations Therapeutic decisions need to be tailored to the context-specific clinical setting and availability of resources. Local research is promoted to improve outcomes for patients with this challenging cancer in Latin America.
Framing the Debate

The purpose of this chapter is not to force a particular set of definitions or questions. Instead, we hope to lay out a set of definitions as a starting point. Other writers can either agree with these definitions or offer their own. Our goal is to be as precise as possible about what we mean when we use the following terms: symbol, embodiment, grounding. Following the proposed definitions are examples of the theories that are consistent with the definitions, and then a reiteration of the debate questions. Symbols, grounding, and embodiment C. S. Peirce's theory of signs is a good starting point both for how the theory helps and how it doesn't (see Clark, 1996 for a discussion of Peirce). According to Peirce, a sign is member of a triad consisting of an object, a sign, and an interpretant. An interpretant is in the mind of an observer; it is the idea of the object brought about by the sign. On this view, signs are a mechanism for grounding ideas, that is, the sign connects the idea to the object. Peirce proposed three types of signs. Icons connect the interpretant to the object by virtue of perceptual similarity. Photographs are prototypical icons. An index connects object and interpretant by virtue of a causal, spatial, or temporal relation. Thus, a weathervane is an index for the direction of the wind (a causal, spatial, and temporal connection), a pointing gesture is a spatial index for the pointed-to object, and the utterance of " I " is an index for the person speaking (a spatial
A novel strategy for an anti-idiotype vaccine: nanobody mimicking neutralization epitope of porcine circovirus type 2

ABSTRACT Vaccination is the most effective method to protect humans and animals from diseases. Anti-idiotype vaccines are safer due to their absence of pathogens. However, the commercial production of traditional anti-idiotype vaccines using monoclonal and polyclonal antibodies (mAb and pAb) is complex and has a high failure rate. The present study designed a novel, simple, low-cost strategy for developing anti-idiotype vaccines with nanobody technology. We used porcine circovirus type 2 (PCV2) as a viral model, which can result in serious economic loss in the pig industry. The neutralizing mAb-1E7 (Ab1) against PCV2 capsid protein (PCV2-Cap) was immunized in the camel. And 12 nanobodies against mAb-1E7 were screened. Among them, Nb61 (Ab2) targeted the idiotype epitope of mAb-1E7 and blocked mAb-1E7’s binding to PCV2-Cap. Additionally, a high-dose Nb61 vaccination can also protect mice and pigs from PCV2 infection. Epitope mapping showed that mAb-1E7 recognized the 75NINDFL80 of PCV2-Cap and 101NYNDFLG107 of Nb61. Subsequently, the mAb-3G4 (Ab3) against Nb61 was produced and can neutralize PCV2 infection in the PK-15 cells. Structure analysis showed that the amino acids of mAb-1E7 and mAb-3G4 respective binding to PCV2-Cap and Nb61 were also similar on the amino acids sequences and spatial conformation. Collectively, our study first provided a strategy for producing nanobody-based anti-idiotype vaccines and identified that anti-idiotype nanobodies could mimic the antigen on amino acids and structures. Importantly, as more and more neutralization mAbs against different pathogens are prepared, anti-idiotype nanobody vaccines can be easily produced against the disease with our strategy, especially for dangerous pathogens. IMPORTANCE Anti-idiotype vaccines utilize idiotype-anti-idiotype network theory, eliminating the need for external antigens as vaccine candidates. Especially for dangerous pathogens, they were safer because they did not contact the live pathogenic microorganisms. However, developing anti-idiotype vaccines with traditional monoclonal and polyclonal antibodies is complex and has a high failure rate. We present a novel, universal, simple, low-cost strategy for producing anti-idiotype vaccines with nanobody technology. Using a neutralization antibody against PCV2-Cap, a nanobody (Ab2) was successfully produced and could mimic the neutralizing epitope of PCV2-Cap. The nanobody can induce protective immune responses against PCV2 infection in mice and pigs. It highlighted that the anti-idiotype vaccine using nanobody has a very good application in the future, especially for dangerous pathogens.