Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantum field theory without divergence: the method of the interaction operators

The recently proposed interior boundary conditions approach [S. Teufel and R. Tumulka: Avoiding Ultraviolet Divergence by Means of Interior Boundary Conditions, arXiv:1506.00497] is a method for defining Hamiltonians without UV divergence for quantum field theories. In this approach the interactions between sectors of the Fock space with different number of particles (inter-sector interactions) are obtained by extending the domain of the free Hamiltonian to include functions with singularities. In this paper a similar but alternative strategy is proposed, in which the inter-sector interactions are implemented by specific interaction operators. In its simplest form, an interaction operator is obtained by symmetrizing the asymmetric operator $\|\hat{\textbf{x}} \|^{-1} \Delta \|\hat {\textbf{x}}\|^{-1}$. The inter-sector interactions derive from the singularities generated by the factors $\|\hat{\textbf{x}}\|^{-1}$ enclosing the Laplacian, while the domain of the interaction operator does not include singular functions. As a consequence the interaction operators and the free Hamiltonian have a common dense domain, and they can be added together to form the complete Hamiltonian with interaction.
Substance P Inhibitor Promotes Tendon Healing in a Collagenase-Induced Rat Model of Tendinopathy

Background: The substance P–neurokinin 1 receptor pathway has been proposed as a therapeutic target for tendinopathy. However, there is a lack of evidence regarding its practical applications. Purpose: To investigate the therapeutic effects of substance P inhibitor (SPI) on inflamed tenocytes in vitro and in a collagenase-induced rat model of tendinopathy in vivo. Study Design: Controlled laboratory study. Methods: We analyzed the mRNA levels of inflammatory (cyclooxygenase [COX]-2 and interleukin [IL]-6) and tenogenic (Mohawk and scleraxis [SCX]) markers using reverse transcription quantitative polymerase chain reaction to demonstrate the effects of SPI on lipopolysaccharide-treated (inflamed) tenocytes. A collagenase-induced rat model of tendinopathy was created by injecting 20 µL of collagenase into the Achilles tendon. A behavior test using an incapacitance apparatus was performed to detect changes in postural equilibrium. The tendon specimens were obtained, and their gross findings were examined. The tensile strength was measured, and histopathological evaluation was performed (hematoxylin and eosin, alcian blue, and immunohistochemical staining). Results: The mRNA levels of COX-2, IL-6, Mohawk, and SCX differed significantly between inflamed tenocytes and those treated with SPI. SPI improved the weight burden in a rat model of tendinopathy in a behavioral test. The specimens of the SPI group showed a normal tendon-like appearance. In the biomechanical test, the tensile strength of the SPI group was significantly greater than that of the tendinopathy group. In the histopathological evaluation, the degree of collagen matrix breakdown was mild in the SPI group. In alcian blue staining, only small focal depositions of proteoglycans and glycosaminoglycans were observed in the SPI group. The SPI group showed decreased expression of IL-6 and neurokinin 1 receptor. Conclusion: This study suggests that SPI has therapeutic effects on tendon healing and restoration in a collagenase-induced rat model of tendinopathy. Clinical Relevance: SPI is a promising agent for tendinopathy in humans.
Life satisfaction, resilience and coping mechanisms among medical students during COVID-19

Purpose Life satisfaction influences well-being. Medical students often experience more stress as compared to their counterparts in other disciplines as they are required to meet the demands of both academic workload and clinical responsibilities. However, during the current pandemic, in addition to academic changes, inability to complete clinical placements, loss of peer interaction and social connectedness and, deployment to areas in times of crisis could exacerbate their stress. This would impact their ability to cope with stress and eventually influence their life satisfaction. Students approach these challenges in various ways, either positively, religiously, or by avoiding. This study aimed to explore the association between resilience, coping mechanisms and life satisfaction in medical students during the pandemic. Methods A cross-sectional web-based survey was conducted from undergraduate medical students from year 1 to year 5. Three instruments were used to measure life satisfaction, resilience, and coping, namely The Brief Resilience Scale, The Satisfaction with Life Scale and the COPE inventory. Mean and standard deviation were calculated for all continuous variables. Robust linear regression model was used for analysis. Hierarchical (forward) stepwise model building technique was used for final model. Alpha cut off was kept at 0.05. Results A total of 351 students (out of 500 students) completed the questionnaires. A moderately negative, slightly linear correlation between life satisfaction and avoidant coping was reported. Life satisfaction showed moderately positive, slightly linear correlation with resilience score. Three variables stayed significant in the final model: Resilience, avoidant coping, and religion coping. Conclusion Life satisfaction can be improved among medical students by focusing on strategies which enhance resilience. Religion is identified as a significant coping strategy among medical students. Students coping mechanism can vary and more research is needed to assess which types of coping strategies could contribute positively to the quality of their personal and professional lives
Coronal‐plane leg alignment in adolescence and the effects of activity: A full leg length MRI study

The aim of this study was to explore the association between developing coronal‐plane leg alignment and activity levels during adolescence. We performed a cross‐sectional cohort study with individuals from soccer club academies and an age‐matched control population. Outcome measures were the hip knee angle (HKA), medial proximal tibial physeal angle (MPTPhyA), lateral distal femoral physeal angle (LDFPhyA) on full leg length magnetic reasonance imagine scans, and the physical activity questionnaire (PAQ) score. The cohort comprised 57 elite male soccer players, 34 male and 34 female controls aged 11−21 years. Mean HKA became more varus with age, with little change after 16 years or skeletal maturity. Skeletally mature elite male soccer players were significantly more varus than male controls with a HKA 2.28° less than male controls (p < 0.001). Skeletally mature male controls had a HKA 1.34° less than female controls (p < 0.001). A negative correlation existed between HKA and PAQ score (coefficient −0.24, p = 0.029). A positive correlation existed between HKA and MPTPhyA (coefficient 0.32, p = 0.008). In conclusion, high activity levels during adolescence are associated with the development of varus leg alignment. Mean HKA becomes more varus with age until skeletal maturity. The development of varus alignment may represent a physiological adaptation to load at the proximal tibial physis. Clinical Significance: A time period may exist for intervention before the development of varus leg alignment in young athletes, such as training load modification or proximal tibial morphology monitoring.
Assessing Liver-to-Plasma Partition Coefficients and In Silico Calculation Methods: When Does the Hepatic Model Matter in PBPK?

The primary models used in pharmacokinetics to assess hepatic clearance (CLh) are the well-stirred model (WSM), the parallel tube model (PTM), and the dispersion model (DM) that differ in their internal flow patterns and assumed unbound liver concentrations. Physiologically based pharmacokinetic (PBPK) models require a hepatic intrinsic clearance (CLint) and tissue-to-plasma partition coefficient (Kp). Given measured systemic and liver concentration-time profiles, these hepatic models perform similarly but yield model-specific CLint and Kp estimates. This work provides mathematical relationships for the three basic hepatic models and assesses their corresponding PBPK-relevant Kp values with literature-reported single-dose blood and liver concentration-time data of 14 compounds. Model fittings were performed with an open-loop approach where the CLh and extraction ratio (ER) were first estimated from fitting the blood data yielding CLint values for the three hepatic models. The prefitted blood data served as forcing input functions to obtain PBPK-operative Kp estimates that were compared with those obtained by the tissue/plasma area ratio (AR), the Chen and Gross (C&G) method, and published in silico methods. The CLint and Kp values for the hepatic models increased with the ER and both showed a rank order being WSM > DM > PTM. Drugs with low ER showed no differences as expected. With model-specific CLint and Kp values, all hepatic models predict the same steady-state Kp that is comparable to those from the AR and C&G methods and reported by direct measurement. All in silico methods performed poorly for most compounds. Hepatic model selection requires cautious application and interpretation in PBPK modeling. SIGNIFICANCE STATEMENT The three hepatic models generate different single-dose (nonsteady-state) values of hepatic intrinsic clearance (CLint) and tissue-to-plasma partition coefficient in physiologically based pharmacokinetic models especially for drugs with a high extraction ratio; however, all steady-state tissue-to-plasma partition coefficient values expected from constant rate infusion studies were the same. These findings are relevant when using these models for in vitro-to-in vivo extrapolation where a model-dependent CLint is used to correct measured drug concentrations for depletion of the tissue by metabolism. This model dependency may also have an impact when assessing pharmacokinetic/pharmacodynamic relationships when effects relate to assumed hepatic concentrations.
Intravenous therapy device labeling in Intensive Care Units: an integrative review

ABSTRACT Objectives: to synthesize the evidence on intravenous device labeling used to identify medications administered to patients in Intensive Care Units, with a view to preventing medication errors. Methods: an integrative review, in the LILACS, IBECS, Embase, MEDLINE, Scopus, Web of Science and CINAHL databases, from November to December 2021, using descriptors and selection criteria. Data were collected in 11 articles and subsequently classified, summarized and aggregated. Results: pre-designed labels, with pre-defined colors and information, help to prevent medication identification errors. There is still a lack of standardization in the practice of labeling syringes, intravenous lines, infusion pumps and saline solution bags. There are errors related to the lack of labeling devices or to their performance with incomplete information. Conclusions: device labeling is a barrier to defending the medication system safety and should be standardized.
Correlation of Esophageal Mean Nocturnal Baseline Impedance With Markers of Laryngopharyngeal Reflux

Mean nocturnal baseline impedance (MNBI) is a measure of the esophageal epithelial barrier function calculated via high‐resolution impedance manometry and can be used as a diagnostic tool and treatment response predictor for gastroesophageal reflux disease (GERD). However, its utility for laryngopharyngeal reflux (LPR) has been minimally studied. We aimed to investigate the relationship of MNBI between patients with suspected LPR, healthy controls, and their 24‐h multichannel intraluminal impedance‐pH (MII‐pH) study results.
SUMO pathway is required for ribosome biogenesis

Ribosomes, acting as the cellular factories for protein production, are essential for all living organisms. Ribosomes are composed of both proteins and RNAs and are established through the coordination of several steps, including transcription, maturation of ribosomal RNA (rRNA), and assembly of ribosomal proteins. In particular, diverse factors required for ribosome biogenesis, such as transcription factors, small nucleolar RNA (snoRNA)-associated proteins, and assembly factors, are tightly regulated by various post-translational modifications. Among these modifications, small ubiquitin-related modifier (SUMO) targets lots of proteins required for gene expression of ribosomal proteins, rRNA, and snoRNAs, rRNA processing, and ribosome assembly. The tight control of SUMOylation affects functions and locations of substrates. This review summarizes current studies and recent progress of SUMOylation-mediated regulation of ribosome biogenesis.
Compression of an intensive light pulse in photonic-band-gap structures with a dense resonant medium

Intensive light pulse interaction with a dense resonant medium is considered. The possibilities of optical switching and pulse compression at realistic parameters of the medium are analyzed. Pulse-shape transformation in different photonic-band-gap structures containing a dense resonant medium is studied. In particular, the effect of dispersion compensation due to nonlinear interaction with a medium is reported. The possibility of pulse control with another pulse is considered in the schemes of copropagating and counterpropagating pulses. It is shown that a photonic crystal makes controlling more effective, at least in the case of copropagating pulses.
Evaluation of urinary neutrophil gelatinase‐associated lipocalin to detect renal tubular damage in dogs with stable myxomatous mitral valve disease

Abstract Background Dogs with myxomatous mitral valve disease (MMVD) can experience progressive renal tubular damage and dysfunction. The prevalence of renal tubular damage is not known in dogs with stable MMVD. Objective To evaluate renal tubular damage in dogs with stable MMVD by evaluation of urinary neutrophil gelatinase‐associated lipocalin (NGAL). Animals Ninety‐eight MMVD dogs grouped according to the American College of Veterinary Internal Medicine (ACVIM) staging (group B1, n = 23; group B2, n = 27; group C + D, n = 48) and 46 healthy dogs. Methods Multicenter prospective observational study. Serum and urine chemistry including NGAL reported as uNGAL concentration (uNGAL) and normalized with urinary creatinine (uNGALC) were compared between MMVD dogs and healthy controls, and among different MMVD ACVIM stages. Results The MMVD dogs had significantly higher uNGAL and uNGALC (1204 pg/mL; range, 30‐39 732 and 1816 pg/mg; range, 22‐127 693, respectively) compared to healthy dogs (584 pg/mL; range, 56‐4072 and 231 pg/mg; range, 15‐2407, respectively; P = .002 and P < .0001, respectively). Both uNGAL and uNGALC increased with the increasing ACVIM stage (P = .001 and P < .001, respectively). Conclusions and Clinical Importance Renal tubular damage is present in dogs with stable MMVD, as measured by increased uNGAL. This tubular damage is subclinical, occurs in all stages of MMVD even in the absence of azotemia, and increases with the severity of MMVD. Reno‐protective approaches to manage MMVD dogs should be explored to slow the progression of renal tubular damage in these patients.
Antiproliferative effects of dried Moringa oleifera leaf extract on human Wharton’s Jelly mesenchymal stem cells

Mesenchymal stem cells (MSCs) have seen an elevated use in clinical works like regenerative medicine. Its potential therapeutic properties increases when used in tandem with complementary agents like bio-based materials. Therefore, the present study is the first to investigate the cytotoxicity of a highly valued medicinal plant, Moringa oleifera, on human Wharton’s Jelly mesenchymal stem cells (hWJMSCs) and its effects on the cells’ gene expression when used as a pre-treatment agent in vitro. M. oleifera leaves (MOL) were dried and subjected to UHPLC-QTOF/MS analysis, revealing several major compounds like apigenin, kaempferol, and quercetin in the MOL, with various biological activities like antioxidant and anti-cancer properties. We then treated the hWJMSCs with MOL and noticed a dose-dependant inhibition on the cells’ proliferation. RNA-sequencing was performed to explain the possible mechanism of action and revealed genes like PPP1R1C, SULT2B1, CDKN1A, mir-154 and CCNB1, whose expression patterns were closely associated with the negative cell cycle regulation and cell cycle arrest process. This is also evident from gene set enrichment analysis where the GO and KEGG terms for down-regulated pathways were closely related to the cell cycle regulation. The Ingenuity pathway analysis (IPA) software further predicted the significant activation of (p < 0.05, z-score > 2) of the G2/M DNA damage checkpoint regulation pathway. The present study suggests that MOL exhibits an antiproliferative effect on hWJMSCs via cell cycle arrest and apoptotic pathways. We believe that this study provides an important baseline reference for future works involving MOL’s potential to accompany MSCs for clinical works. Future works can take advantage of the cell’s strong anti-cancer gene expression found in this study, and evaluate our MOL treatment on various cancer cell lines.
How the public evaluates media representations of uncertain science: An integrated explanatory framework

Understanding how to portray uncertain science to the public is a pressing goal for science communication. This study compared US public audience reactions to a news article depicting a novel discovery in neurogenomics as certain or uncertain, with statements of (un)certainty attributed to either affiliated or unaffiliated scientists. The uncertainty disclosure had no main effect on perceived news article credibility, scientist trustworthiness, objectivity of the scientists’ depiction, or willingness to participate in genomic research. However, news credibility and scientist objectivity ratings were higher for uncertainty disclosure attributed to the affiliated scientists. Participants with greater preference for information about uncertainty found the scientists more trustworthy, their depictions more balanced, and the news article more credible when the research was described as uncertain, and these effects were stronger for affiliated scientist attribution. Findings underscore the important roles of disclosure source and audience characteristics in public reactions to media representations of scientific uncertainty.
An update on genetically engineered mouse models of pancreatic neuroendocrine neoplasms.

Pancreatic neuroendocrine neoplasms (PanNENs) are rare and clinically challenging entities. At the molecular level, PanNENs' genetic profile is well-characterized but there is limited knowledge regarding the contribution of the newly identified genes to tumor initiation and progression. Genetically engineered mouse models (GEMMs) are the most versatile tool for studying the plethora of genetic variations influencing PanNENs etiopathogenesis and behavior over time. In this review, we present the state-of-the-art of the most relevant PanNEN GEMMs available and correlate their findings with the human neoplasms' counterparts. We discuss the historic GEMMs as the most used and with higher translational utility models. GEMMs with Men1 and glucagon receptor gene germline alterations stand out as the most faithful models in recapitulating human disease; RIP-Tag models are unique models of early onset, highly vascularized, invasive carcinomas. We also include a section of the most recent GEMMs that evaluate pathways related to cell cycle and apoptosis, Pi3k/Akt/mTOR and Atrx/Daxx. For the latter, their tumorigenic effect is heterogeneous. In particular, for Atrx/Daxx, we will require more in-depth studies to evaluate their contribution; even though they are prevalent genetic events in PanNENs, they have low/inexistent tumorigenic capacity per se in GEMMs. Researchers planning to use GEMMs can find a roadmap of the main clinical features in this review, presented as a guide that summarizes the chief milestones achieved. We identify pitfalls to overcome, concerning the novel designs and standardization of results, so that future models can replicate human disease more closely.
Pharmacological basis of the putative therapeutic effect of Topical Vitamin D3 on the experimental model of atopic dermatitis in mice.

OBJECTIVE The aim of the study was to explore the effect of topical vitamin D3 in atopic dermatitis (AD) induced by ovalbumin (OVA) in contrast with topical betamethasone in mice. MATERIALS AND METHODS 35 BALB/c adult male mice, weighing between 25-30 gm were used to induce AD by topically sensitizing the dorsal surface of the skin with the OVA patch. Subsequently, treatments were performed in each group by application of vitamin D3 cream (0.0003%), betamethasone cream (0.1%), or vehicles (QV cream) on the skin. RESULTS Remarkably, vitamin D3 had a marked improvement in the skin of OVA-induced AD mice. Additionally, vitamin D3 revealed a considerable diminution in the levels of IgE, IL-5, filaggrin, and epidermal thickness, whereas a significant augmentation in the levels of IL-4 and IL-13 was observed when compared with the control group, and histopathological studies had further confirmed these findings. CONCLUSIONS This study essentially highlighted the anti-inflammatory effect of vitamin D3 by effective alteration in the immunological components responsible for AD. Moreover, this pioneer experimental work represents a new paradigm and sheds a light on the importance of vitamin D3 in the implications of AD. A comprehensive creative approach is crucial to concretely establish and further corroborate vitamin D3 for this therapeutic role.
Individual differences in brain aging: heterogeneity in cortico-hippocampal but not caudate atrophy rates

Abstract It is well documented that some brain regions, such as association cortices, caudate, and hippocampus, are particularly prone to age-related atrophy, but it has been hypothesized that there are individual differences in atrophy profiles. Here, we document heterogeneity in regional-atrophy patterns using latent-profile analysis of 1,482 longitudinal magnetic resonance imaging observations. The results supported a 2-group solution reflecting differences in atrophy rates in cortical regions and hippocampus along with comparable caudate atrophy. The higher-atrophy group had the most marked atrophy in hippocampus and also lower episodic memory, and their normal caudate atrophy rate was accompanied by larger baseline volumes. Our findings support and refine models of heterogeneity in brain aging and suggest distinct mechanisms of atrophy in striatal versus hippocampal-cortical systems.