Miracle-dz/UniFAR-FTUs huggingface dataset:
Applications of Finite Element Modeling in Biomechanical Analysis of Foot Arch Deformation: a Scoping Review.

Excessive foot arch deformation is associated with plantar tissue overload and ligamentous injury pathologies. Finite element (FE) analysis, as an effective tool for modeling and simulation, has been utilized clinically for providing insights into arch biomechanics. This systematic scoping review aimed to present an updated overview of computational foot modeling for pathology-related arch biomechanics and shed light on their applicability in clinical conditions. English-language searches of the electronic databases were conducted in the Web of Science, PubMed, and Scopus until July 2022. Articles that investigated arch deformation mechanisms by FE modeling were included. Any studies involving extrinsic manipulations (e.g., footwear, insoles, and arch orthoses) and intrinsic manipulations (e.g., implants and surgical intervention) were excluded from this review. The MQSSFE instrument was used to assess methodological quality. Seventeen articles were identified in this systematic scoping review and were categorized into two groups, FE modeling of the healthy foot and the pathological foot, for further analysis. Most of the existing FE analyses of the foot arch have focused on constructing models for specific pathological conditions, such as adult-acquired flatfoot, valgus foot, and posterior tibial tendinopathy. However, given the complexity of the arch problem, geometric simplifications and linear assumptions of material properties might bring challenges in the formulation of exact models applied to clinical settings. Overall, advances in computational modeling techniques have contributed to reliable foot deformation simulation and analysis in modern personalized medicine.
Papillary thyroid carcinoma with aggressive fused follicular and solid growth pattern: A unique histological subtype with high‐grade malignancy?

Papillary thyroid carcinoma (PTC) is usually indolent; however, some rare subtypes of PTCs, such as columnar cell and hobnail subtypes, carry poor prognosis as an intermediate malignancy between differentiated carcinoma and anaplastic carcinoma. We present the case of a 56‐year‐old Japanese woman having PTC with aggressive behavior showing characteristic histological features of a predominantly fused follicular and focally solid (FFS) pattern. The fused follicular pattern is cribriform‐like without intermingled vessels. This PTC with FFS pattern included frequent mitotic figures, necrosis, lymphovascular invasion, and metastases with high clinical stage. The tumor cells were broadly positive for antibodies to TTF‐1, PAX8, and bcl‐2, and negative for cyclin D1. Ki‐67 labeling index was approximately 10%, and there was occasional positivity of p53. Targeted next generation sequencing analysis only detected a NRAS mutation (Q61K); there was no mutation and no translocation of other genes including BRAF and RET/PTC. To our knowledge, this is first report that PTC shows aggressive FFS growth pattern. The tumor is possibly included in the new category of differentiated high‐grade thyroid carcinoma in the World Health Organization 2022 classification, or in a novel subtype of PTC owing to its characteristic histological feature and intermediate malignancy between differentiated carcinoma and anaplastic carcinoma.
Animal models of Huntington’s disease and their applicability to novel drug discovery and development

ABSTRACT Introduction Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the CAG trinucleotide repeat in huntingtin (Htt) gene. The discovery of the HD-causing gene prompted the creation of new HD animal models, proving that mutations in the HD gene are linked to either loss of function of the wild-type (un-mutated) gene or toxic gain in the function of a mutated gene. Areas Covered Animal models of HD have led to an increased understanding of its pathogenesis and resulted in the discovery of new therapeutic targets/drugs. The focus of this review is on the selection and validation of animal models for HD drug discovery. Furthermore, several drugs tested using various models in the preclinical phase have been compiled to demonstrate the applicability of these HD animal models. Expert opinion The applicability of animal models for HD drug discovery has been well demonstrated. Nevertheless, despite the enormous progression made to date, the development of drug therapy to completely alleviate disease progression has not been achieved. Most of the pre-clinically tested drugs have shown promising results in alleviating HD-associated neurodegeneration and motor and non-motor symptoms, but only a few of them thrived to produce satisfactory results in the clinical phase. This failure has raised concerns about the selection of HD animal models and species, and new strategies for selection are mandated.
Low-intensity focused ultrasound ameliorates depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway.

It is of great social significance and clinical value to explore new effective treatments for depression. Low-intensity focused ultrasound stimulation (LIFUS) has been indicated to have notable neuroprotective effects on depression. However, little is known about how different strategies of LIFUS affect the therapeutic effect. Therefore, the purpose of this study is to investigate whether the effects of LIFUS on depression-like behaviors are associated with the intensity and the underlying mechanisms. We established the depression rats model using the chronic unpredictable stress (CUS) and applied the LIFUS with high/low intensity (Ispta = 500 and 230 mW/cm2, respectively) to the left medial prefrontal cortex (mPFC) after CUS. We found that two intensities of LIFUS both could significantly improve depression-like behaviors to a comparable degree. We further found that theta oscillation synchronization and synaptic functional plasticity in the hippocampal vCA1-mPFC pathway were significantly improved by chronic LIFUS which mainly due to the alternation of synaptic structural plasticity and the expression of post-synaptic proteins in the mPFC. These results suggest that LIFUS ameliorates the depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway. Our study provides preclinical evidence and a theoretical basis for applying LIFUS for depression treatment.
An efficient perturbed parameter scheme in the Lorenz system for quantifying model uncertainty

In the present proof‐of‐concept investigation, a new reliable and efficient perturbed parameter scheme is shown to be comparable to an additive stochastic parametrization scheme in resolving systematic model error. The experiments are conducted using two Lorenz 63 (L63) models coupled to mimic the ocean–atmosphere system, and the atmospheric L63 is further coupled to a spatially resolved convective‐scale Lorenz 96 (L96). The entire system is treated as the ‘truth’, and is simulated using a ‘forecast model’ where L96 is treated as a subgrid‐scale process and parametrized using one of three schemes: (i) deterministic, (ii) additive stochastic parametrization, and (iii) perturbed parameter. Perfect initial conditions are applied to investigate uncertainties caused by model errors. The systematic biases are significantly reduced in the perturbed parameter scheme when ‘informative’ perturbations are applied. An informative perturbation is the difference between the true tendency and the deterministically parametrized tendency. Moreover, the proposed scheme uses a stochastic spectral method, Polynomial Chaos Expansion (PCE), to build a low‐cost surrogate model of the perturbed forecast model. The PCE surrogate is an analytic function of the perturbation which effectively produces unbiased forecast statistics at large ensemble size, without the need to integrate the actual perturbed forecast model.
Designed and validated novel allele-specific primer to differentiate Kernel Row Number (KRN) in tropical field corn

Background Kernel row number (KRN) is an important yield component trait with a direct impact on the productivity of maize. The variability in KRN is influenced by the inflorescence meristem size, which is determined by the CLAVATA-WUSCHEL pathway. A CLAVATA receptor-like protein, encoded by the FASCIATED EAR2 (fea2gene), enhances the growth of inflorescence meristem and is thus involved in the determination of KRN. The amplicon sequencing-based method was employed to dissect the allelic variation of the fea2 gene in tropical field corn. Methodology/Principal finding Amplicon-based sequencing of AI 535 (Low KRN) and AI 536 (High KRN) was undertaken for the gene fea 2 gene that codes for KRN in maize. Upon multiple sequence alignment of both sequences, A to T transversion at the 1311 position was noticed between Low KRN and High KRN genotypes resulting in different allelic forms of a fea2 gene in tropical maize. An allele-specific primer 1311 fea2.1 was designed and validated that can differentiate High and Low KRN genotypes. Conclusion/Significance Maize has high variability for KRN and is exemplified by the wide values ranging from 8–26 KRN in the maize germpalsm. The sequence-based approach of SNP detection through the use of a specific primer facilitated the detection of variation present in the target trait. This makes it possible to capture these variations in the early generation. In the study, the PCR-based differentiation method described for the identification of desirable high KRN genotypes would augment the breeding programs for improving the productivity of field corn.
Gaussian Join Tree classifiers with applications to mass spectra classification

Classifiers based on probabilistic graphical models are very eective. In continuous domains, parameters for those classifiers are usually adjusted by maximum likelihood. When data is scarce, this can easily lead to overfitting. Nowadays, models are sought in domains where the number of data items is small and the number of variables is large. This is particularly true in the realm of bioinformatics. In this work we introduce Gaussian Join Trees (GJT) classifiers to try to partially overcome this issue by performing exact bayesian model averaging over the parameters. We use two die rent mass spectra classification datasets for cancer prediction to compare GJT classifiers with those learnt by maximum likelihood.
Novel Explanted Human Liver Model to Assess Hepatic Extraction, Biliary Excretion and Transporter Function

Realistic models predicting hepatobiliary processes in health and disease are lacking. We therefore aimed to develop a physiologically relevant human liver model consisting of normothermic machine perfusion (NMP) of explanted diseased human livers that can assess hepatic extraction, clearance, biliary excretion, and drug–drug interaction (DDI). Eleven livers were included in the study, seven with a cirrhotic and four with a noncirrhotic disease background. After explantation of the diseased liver, NMP was initiated. After 120 minutes of perfusion, a drug cocktail (rosuvastatin, digoxin, metformin, and furosemide; OATP1B1/1B3, P‐gp, BCRP, and OCT1 model compounds) was administered to the portal vein and 120 minutes later, a second bolus of the drug cocktail was co‐administered with perpetrator drugs to study relevant DDIs. The explanted livers showed good viability and functionality during 360 minutes of NMP. Hepatic extraction ratios close to in vivo reported values were measured. Hepatic clearance of rosuvastatin and digoxin showed to be the most affected by cirrhosis with an increase in maximum plasma concentration (Cmax) of 11.50 and 2.89 times, respectively, compared with noncirrhotic livers. No major differences were observed for metformin and furosemide. Interaction of rosuvastatin or digoxin with perpetrator drugs were more pronounced in noncirrhotic livers compared with cirrhotic livers. Our results demonstrated that NMP of human diseased explanted livers is an excellent model to assess hepatic extraction, clearance, biliary excretion, and DDI. Gaining insight into pharmacokinetic profiles of OATP1B1/1B3, P‐gp, BCRP, and OCT1 model compounds is a first step toward studying transporter functions in diseased livers.
Beyond Standard Model Physics

One era came to an end 4th of July last year when two experiments at the Large Hadron Collider announced the discovery of a resonance consistent with the properties of the Standard Model Higgs boson. The Higgs boson was the last missing piece of the Standard Model and after it mass is unambiguously measured, all the nineteen free parameters of the model are fixed. Although the Standard Model is in agreement with a great number of experimental measurements, it cannot explain all the observations. In this thesis we investigate extensions of the Standard Model where the standard Higgs sector is replaced by a strongly interacting sector. We begin with a brief introduction to the Standard Model and review the reasons why there must be something beyond the Standard Model. After developing tools to study strongly interacting theories, we continue with the Minimal Walking Technicolor model and examine how it possibly manifests itself at the Large Hadron Collider. The last chapter of the thesis in devoted to an extension which only adds more particles on top of the Standard Model. One of the new particle is stable and electrically neutral explaining the existence of a type of matter in the universe which does not shine light i.e. dark matter.
Rethinking assessment in response to generative artificial intelligence

The use of decision-making support tools during assessments, such as electronic differential diagnosis in examinations, 1 is just the tip of the iceberg when it comes to how technology is currently changing assessment practice. We say this, because it appears we have reached a transformative stage in the development of artificial intelligence (AI). So-called generative AI is here. OpenAI's ChatGPT has burst onto the scene, and other tools are coming. ChatGPT-3 is a language model designed to process and generate natural language responses to a wide range of prompts and questions. It was trained on a massive amount data, corresponding to approximately 45 terabytes of text, or hundreds of billions of words. At least this is what ChatGPT told us when we asked. And just as we are all trying to understand the ramifications of all this for education and assessment, the multimodal ChatGPT-4 has been released that can ‘ see ’ and process images, highlighting just how fast this technology is advancing. Generative AI has potentially radical and significant implications for the way we assess our students and trainees. One AI tool has already shown to be capable of passing the US Medical Licensing Exam. 2,3 Another tool has performed reasonably well in a Royal College of Radiologists examination, involving the interpretation of radiographs. 4 Even more significantly, at its launch, ChatGPT-4 was shown to have performed in the top 10% on a range of well-known high-stakes examinations. The ability of these latest generations of AI to respond convincingly to assessment tasks is impressive. Consequently, we can no longer rely on non-invigilated assessments and submitted ‘ artefacts ’ to demonstrate student learning and competence. This is bringing many long-term demands on educators, course coordinators and curriculum designers, forcing us to rethink assessment approaches. It certainly calls into question the role and
Digital mental health interventions for school teachers – A narrative review

School teachers face the paradox of being in a privileged position to act in youth mental health prevention, but in a vulnerable position for not receiving adequate training and personal support. Digital interventions can provide unexpensive tools and narrow this gap in a large scale without major structural changes. We aimed to synthesize the evidence for digital mental health interventions for school teachers.
Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease

Somatic mutations in non-malignant tissues accumulate with age and insult, but whether these mutations are adaptive on the cellular or organismal levels is unclear. To interrogate mutations found in human metabolic disease, we performed lineage tracing in mice harboring somatic mosaicism subjected to non-alcoholic steatohepatitis (NASH). Proof-of-concept studies with mosaic loss of Mboat7, a membrane lipid acyltransferase, showed that increased steatosis accelerated clonal disappearance. Next, we induced pooled mosaicism in 63 known NASH genes, allowing us to trace mutant clones side-by-side. This in vivo tracing platform, which we coined MOSAICS, selected for mutations that ameliorate lipotoxicity, including mutant genes identified in human NASH. To prioritize new genes, additional screening of 472 candidates identified 23 somatic perturbations that promoted clonal expansion. In validation studies, liver-wide deletion of Bcl6, Tbx3, or Smyd2 resulted in protection against NASH. Selection for clonal fitness in mouse and human livers identifies pathways that regulate metabolic disease. Highlights: Mosaic Mboat7 mutations that increase lipotoxicity lead to clonal disappearance in NASH. In vivo screening can identify genes that alter hepatocyte fitness in NASH. Mosaic Gpam mutations are positively selected due to reduced lipogenesis. In vivo screening of transcription factors and epifactors identified new therapeutic targets in NASH.
COMPARISON BETWEEN GROUND REACTION FORCE PATTERNS AND ANGULAR, APPROACH, AND BALL VELOCITIES FOR IN-STEP KICKING

The purpose of this study was to determine if patterns in vertical ground reaction forces resulted in differences in hip, knee and trunk angular velocity and efficiency of the open kinetic chain. 20 subjects performed a maximal in-step kick while ground reaction forces of the plant leg, as well as angular, approach and ball velocities were recorded. Although approach and ball velocity did not change between groups, the decreasing vertical force group had significantly higher initial peak vertical ground reaction forces and angular hip velocities than subjects with a double vertical peak pattern. There was a significant relationship between approach velocity and ball velocity, as well as a negative relationship between posterior lean on contact and leg angular velocity. It seems that the pattern of vertical force with the plant leg is not a key factor in ball velocity.
Relationships between physical traits and subjective impressions of faces ‐ age and gender information

This article presents two studies investigating the relationships between physical measurements and psychological judgments of human faces. The first study is concerned with gender and age classification, the second with femininity-masculinity and childlike-adultlike judgments of Japanese faces. The results indicate that (1) faces can be accurately classified into age categories based on physical measurements, (2) whereas age classification depends on the global information of a face, gender classification depends on its local information and (3) the femininity-masculinity judgment of male faces tends to be made on the basis of age information. The authors relate these results to the processing of KANSEI-information of, or subjective feelings about, a biological stimulus.
Tree density-dependence effects on seed dispersal of a large-seeded tropical tree

Abstract One of the biggest issues in plant ecology is determining the interaction outcome between seeds and scatter-hoarding rodents because the latter has a dual role as dispersers and predators of seeds. Density-dependence contexts involving resource abundance largely influence the outcome of this interaction. Here, we investigated how the variation in the density of a large-seeded tropical tree (Joannesia princeps Vell) affects its probability of seed removal, consumption, dispersal, and burial by a neotropical rodent (Dasyprocta azarae Lichtenstein). We tested whether the elevated resource availability in high tree density areas would cause scatter hoarder’s satiation by decreasing seed removal and consumption (predator satiation hypothesis) or increasing seed dispersal and burial (predator dispersal hypothesis). We tracked the fate of 461 seeds in 14 plots with distinct J. princeps abundances inside a large Atlantic Forest fragment. We used spool-and-line tracking and camera trappings to determine seed fate and identify interacting animals. Agouti was the only species removing J. princeps seeds. Tree density benefitted J. princeps by increasing seed dispersal through buried seed but not affecting seed removal and consumption. This result shows how density-dependent contexts, such as tree density, may alter seed fate in seed–rodent interactions supporting future studies aiming to reestablishing seed dispersal functions in Atlantic Forest fragments.
A Computer Simulation of the Effects of Mass and Momentum of Inertia Alternation in Individual Muscle Forces During Swing Phase of Transtibial Amputee Gait

An inverse dynamics computer simulation was carried out to investigate the forces of lower extremity muscles in the swing phase of a transtibial amputee gait. With each muscle as an ideal force generator, the lower extremity was simulated as a twodegrees of freedom linkage with the hip and knee as its joints. Kinematic data of hip and knee joints were recorded by a motion analysis system. Through a static optimization approach, the forces exerted by muscles were determined so that recorded hip and knee joint angles were produced. Simulation results showed that when the mass of prosthetic foot is increased, muscle forces increase, too. Also, if the moment of inertia of prosthetic foot is increased, muscle forces will increase, too. However, since prosthetic foot moment of inertia is smaller than that of thigh and shank, its alternation does not have noticeable effect on muscle forces. These results are in accord to experimental and theoretical studies that reported an increase in leg mass and moment of inertia lead to higher electromyography activity of leg muscles, and energetic of walking.
Results on Tsallis entropy of order statistics and record values

The Tsallis entropy is a generalization of Type of the Shannon entropy (Tsallis, 1988). Shannon entropy may be negative for some distributions, but Tsallis entropy can always be made non-negative by choosing appropriate value of . In this paper, we study the Tsallis entropy based on order statistics and record values. We show that the parent distributions can be determined uniquely by the equality of Tsallis entropy of order statistics or record values. Also, we characterize symmetric distributions based on Tsallis entropy of order statistics and record values. Finally, we prove that the Tsallis information between order statistics and parent random variable and Tsallis information between record values and parent random variable are distribution free. The results are useful in modeling problems and testing statistical hypotheses.