Miracle-dz/UniFAR-FTUs huggingface dataset:
Gross morphological studies on the liver of goat foetii (Capra hircus).

The present study was conducted on the liver of 18 goat foetii. During the initial stage of development, the liver occupied almost all of the space of abdominal cavity. The lobes were marked by oesophageal and umbilical notches. In the foetus with 5.40 cm CRL (47 days of gestation), the visceral surface of the right lobe showed interiorly a rounded deep omasal impression. The gall bladder was embedded in a fossa between right and quadrate lobe. In the foetus bearing 13.80 cm CRL (82 days of gestation), the umbilical fissure was quite prominent. The visceral surface of the left and right lobe showed depressions for visceral organs. In the foetus with 38.50 cm CRL (145 days of gestation), no impressions of ribs on parietal surface of liver were seen. In the foetus with 38.90 cm CRL (148 days of gestation), the size of the liver was smaller than abdominal cavity when compared with earlier stages of foetal life.
The Bezold–Jarisch reflex in a patient with coronary spastic angina

Acute inferior myocardial damage can induce transient bradycardia and hypotension—the Bezold–Jarisch reflex, which is explained by the preferential distribution of vagal nerves in the inferior wall of the left ventricle. We report a 76‐year‐old man who showed a perfusion defect in the inferior wall with redistribution on exercise scintigraphy with thallium‐201. Of note, during exercise at an intensity of 100 watts, the patient's heart rate transiently decreased from 122 to 95 bpm in sinus rhythm, accompanied by ST‐segment depression. A diagnosis of coronary spastic angina was made since no stenotic lesions were observed on conventional coronary angiography.
Tendon regeneration induced by umbilical cord graft in a rabbit tendon defect model

Whether tendon regeneration can be induced using the umbilical cord as a whole‐graft structure is unknown. In this study, we explored the potential for tendon regeneration induction using an umbilical cord graft in a rabbit model of patella tendon defects. In 52 of 54 New Zealand White rabbits, the central third of the patella tendons of both hind legs was removed to create tendon defects. The rabbits were randomly divided into four groups, nonfilling (empty defect), refilling (defect refilled with resected tendon portion), Wharton's jelly (WJ) outside (WJO; defect filled with umbilical cord graft, WJ side facing outward), and WJ inside (WJI; same as WJO with WJ side facing inward) groups. Four rabbits from WJO and WJI groups were sacrificed for human CD 105 evaluation 1 month after surgery. Further histological, biomechanical, and gene expression analyses were performed at 3 and 6 months after surgery. The untreated patella tendons in the remaining two rabbits were harvested as normal biomechanical controls. Histological evaluation showed that the formed tissue structure fibers in the tendon defect area were much denser and more mature in the WJI group than in all other groups. Biomechanical testing showed that the failure load of the final tissue structure was the highest in the WJI group. Real‐time polymerase chain reaction indicated that the expression of most tendon‐related genes was upregulated in the WJI group at 6 months after surgery. We concluded that umbilical cord grafting induces effective tendon regeneration, particularly when the WJ side faces inward.
Novel regulation and function of the actin bundling protein fascin

The parallel actin filament bundling protein Fascin is a critical protein in both disease and development. Overexpression of Fascin is linked to increased aggressiveness in a number of cancer types, including breast and colon carcinomas. Importantly, Fascin is not normally expressed in adult epithelial cells from which many of these cancers arise. Therefore, Fascin is increasingly cited as both a potential biomarker and therapeutic target in many types of cancer. Fascin is most commonly associated with the formation of filopodia and invadapodia (parallel actin filament bundle structures) to drive migration and invasion. However, Fascin activity and regulation remain poorly understood. In order for Fascin to be an effective target for cancer therapeutics, a better understanding of the mechanisms regulating Fascin activities in the cell is necessary. Prostaglandins (PGs) are short-lived lipid signaling molecules that mediate a wide range of biological activities. PGs act through G protein-coupled receptors to initiate signaling cascades that affect downstream targets, including actin cytoskeletal remodeling. Importantly, the key enzymes in the synthesis of PGs, cyclooxygenase (COX) 1 and 2, are the targets of non-steroidal anti-inflammatory drugs like aspirin. Interestingly, like Fascin, PGs have been independently implicated in cancer development and metastasis and aspirin may reduce the risk of aggressive cancer. However, the exact mechanisms by which PGs mediate cancer development are unknown. The work presented in this thesis focused on novel PG-dependent regulation and activity of Fascin. The research presented here utilized Drosophila oogenesis as a model system to analyze PG-dependent Fascin activity. Drosophila oogenesis is an ideal model in which to study the activity and regulation of actin binding proteins like Fascin. Oogenesis consists of 14 morphologically defined stages, which are observable many times over within a single isolated pair of ovaries. A developing follicle consists of 16 germline cells
Metabolic flux analysis of the neural cell glycocalyx reveals differential utilization of monosaccharides

Abstract Saccharides in our diet are major sources of carbon for the formation of biomass such as proteins, lipids, nucleic acids and glycans. Among the dietary monosaccharides, glucose occupies a central role in metabolism, but human blood contains regulated levels of other monosaccharides as well. Their influence on metabolism and how they are utilized have not been explored thoroughly. Applying metabolic flux analysis on glycan synthesis can reveal the pathways that supply glycosylation precursors and provide a snapshot of the metabolic state of the cell. In this study, we traced the incorporation of six 13C uniformly labeled monosaccharides in the N-glycans, O-glycans and glycosphingolipids of both pluripotent and neural NTERA-2 cells. We gathered detailed isotopologue data for hundreds of glycoconjugates using mass spectrometry methods. The contributions of de novo synthesis and direct incorporation pathways for glucose, mannose, fructose, galactose, N-acetylglucosamine and fucose were determined based on their isotope incorporation. Co-feeding studies revealed that fructose incorporation is drastically decreased by the presence of glucose, while mannose and galactose were much less affected. Furthermore, increased sialylation slowed down the turnover of glycans, but fucosylation attenuated this effect. Our results demonstrated that exogenous monosaccharide utilization can vary markedly depending on the cell differentiation state and monosaccharide availability, and that the incorporation of carbons can also differ among different glycan structures. We contend that the analysis of metabolic isotope labeling of glycans can yield new insights about cell metabolism.
PHTF2 regulates lipids metabolism in gastric cancer

Identification of hub genes and key pathways of gastric cancer was recognized to be essential to elucidate the tumorigenesis of GC. This study was aimed to identify the differentially expressed genes (DEGs) in GC via bioinformatics methods and their related pathways involved in the pathological process of GC. Gene expression profile datasets acquired by microarray chips or RNA-seq were downloaded from GEO dataset and TCGA, and 298 differentially expressed genes was identified. The Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) pathways of DEGs were then analyzed by the DAVID database to elucidate the potential molecular functions of DEGs. The protein-protein interaction (PPI) network of DEGs was further analyzed with the STRING database and PHTF2 was identified as a hub gene in the PPI network. Subsequently, PHTF2 was found to be highly expressed in different subtypes of gastric cancer tissues obtained from TCGA database or clinical patients, resulting with a poor prognosis. By GSEA, PHTF2 was found to significantly enrich the fatty acid metabolism pathway in gastric cancer. Moreover, PHTF2-regulated lipids metabolism significantly affected the tumorigenesis of GC cells. In summary, this work identified a new mechanism by which PHTF2 precipitated in the pathological process of GC by regulating cellular lipid metabolism.
Independent risk factors and the potential predictors of bladder cancer-related ischemic stroke

Objective To investigate the independent risk factors and potential predictors of bladder cancer-related ischemic stroke (BCRIS). Methods This was a multi-center retrospective study including patients with active bladder cancer and acute ischemic stroke without traditional stroke risk factors (BCRIS group), and sex- and age-matched patients with active bladder cancer alone (control group). Data were collected between January 2006 and December 2018. Uni- and multivariate analyses were performed to identify independent risk factors for BCRIS. The predictive performance of these risk factors was assessed using receiver operating characteristic (ROC) curves. Results Records were retrospectively reviewed from 60 BCRIS patients and 120 bladder cancer controls. Univariate analysis revealed that serum D-dimer and carcinoembryonic antigen (CEA) levels and the platelet and neutrophil counts were significantly higher in BCRIS patients compared with controls. Multivariate analysis identified the three above-mentioned variables as independent risk factors for BCRIS. The product of all three factors gave the largest area under the ROC curve. Conclusions Elevated serum D-dimer and CEA levels and increased platelet count were independent risk factors for BCRIS, and the cut-off value based on the product of the three independent risk factors (≥2,640,745.29) could serve as a potential predictor of BCRIS.
Weekly Osteopathic Manipulative Treatment to Improve Measures of Sympathetic Tone in Women With Polycystic Ovary Syndrome: A Randomized, Controlled Pilot Study

Abstract Background Polycystic ovary syndrome (PCOS), a common hormone disorder affecting reproductive and metabolic health of reproductive-age women, was shown in a previous study from these authors to be associated with increased sympathetic tone. Increased sympathetic tone contributes to long-term health risks for cardiovascular disease and promotes PCOS pathogenesis. Objective To determine whether weekly osteopathic manipulative treatment (OMT) improves physiologic measures of sympathetic tone in women with PCOS. Methods In the second phase of a larger study from this author group, 25 women with PCOS, aged 22 to 43 years, living in Erie, Pennsylvania, were recruited to participate in a randomized, controlled evaluation of OMT intervention. Participants were randomly assigned to either an OMT intervention or control group. The OMT group received weekly manipulation of Chapman points and rib-raising for viscerosomatic reflexes associated with the ovaries, adrenal glands, and heart for 12 consecutive weeks. Physiologic measures of sympathetic tone were collected, along with metabolic, endocrine, and reproductive measurements, both before the 3-month intervention and within 1 week of completing the intervention. Measurements included heart rate and blood pressure at rest and after 15 minutes of aerobic exercise, heart rate recovery after exercise, resting heart rate variability, serum androgen levels, body mass index, fasting blood glucose and insulin levels, and menstrual cycle length. Results Nineteen women completed the study. Comparing pre- and postintervention parameters, women with PCOS in the OMT intervention group experienced an improvement in postexercise systolic blood pressure (135.8 vs 129.1 mm Hg) and a trend toward heart rate recovery (23.2 vs 29.4 seconds). No significant improvements were found in the control group or in any other physiologic parameters measured. No significant improvements were found in the endocrine, metabolic, or reproductive parameters measured, although free testosterone was slightly lower after 3 months of weekly OMT (5.69 vs 4.64 pg/mL). Conclusion Improvements in sympathetic tone after OMT suggest that weekly manipulation of Chapman points and viscerosomatic reflexes can be a useful adjunctive therapeutic option for women with PCOS. (ClinicalTrials.gov No. NCT03383484)
Precision and Sample Size Requirements for Regression-Based Norming Methods for Change Scores

To interpret a person’s change score, one typically transforms the change score into, for example, a percentile, so that one knows a person’s location in a distribution of change scores. Transformed scores are referred to as norms and the construction of norms is referred to as norming. Two often-used norming methods for change scores are the regression-based change approach and the T Scores for Change method. In this article, we discuss the similarities and differences between these norming methods, and use a simulation study to systematically examine the precision of the two methods and to establish the minimum sample size requirements for satisfactory precision.
An Affinity-Chromatography and Glycoproteomics Workflow to Profile the Chondroitin Sulfate Proteoglycans that interact with malarial VAR2CSA in the Placenta and in Cancer.

Chondroitin sulfate (CS) is the placental receptor for the VAR2CSA malaria protein, expressed at the surface of infected erythrocytes during Plasmodium falciparum infection. Infected cells adhere to syncytiotrophoblasts or get trapped within the intervillous space by binding to a determinant in a 4-O-sulfated CS chains. However, the exact structure of these glycan sequences remains unclear. VAR2CSA-reactive CS is also expressed by tumor cells, making it an attractive target for cancer diagnosis and therapeutics. The identities of the proteoglycans carrying these modifications in placental and cancer tissues remains poorly characterized. This information is clinically relevant since presentation of the glycan chains may be mediated by novel core proteins or by a limited subset of established proteoglycans. To address this question, VAR2CSA-binding proteoglycans were affinity-purified from human placenta, tumor tissue, and cancer cells, and analyzed through a specialized glycoproteomics workflow. We show that VAR2CSA-reactive CS chains associate with a heterogenous group of proteoglycans, including novel core proteins. Additionally, this work demonstrates how affinity purification in combination with glycoproteomics analysis can facilitate the characterization of CSPGs with distinct CS epitopes. A similar workflow can be applied to investigate the interaction of CSPGs with other CS binding lectins as well.
Impact on the use and cost of other services following intervention by an inpatient pathway homelessness team in an acute mental health hospital

Abstract Background Mental illness in people experiencing homelessness is common and a key reason for attendance at emergency departments and admission to hospital. Aims This paper describes how the KHP Pathway homeless team impacted use and cost of health and wider services. The Pathway model had never been adopted by a mental health hospital, and there had never been an economic analysis to evaluate service use before and after intervention. Method Service use was measured using an adapted version of the Client Service Receipt Inventory (CSRI) with a simple before and after design at admission, 3 months and 6 months after discharge from hospital. Results During the first 3-month follow-up, over half the participants saw a GP, with an increase in the proportion seeing a psychiatrist, social worker and a mental health nurse. Attendance at emergency departments was substantially lower than at baseline. The mean total service cost was £818 at base line and £414 at 3 months. Conclusions The adapted version of the CSRI demonstrates that patients seen by the Pathway Homelessness Team were supported to use community and scheduled health and care services. The service overcomes barriers, frequently experienced by people experiencing homelessness, in accessing support and community healthcare in the UK.
A co‐designed framework to support and sustain patient and family engagement in health‐care decision making

Patient and family engagement in health care has emerged as a critical priority. Understanding engagement, from the perspective of the patient and family member, coupled with an awareness of how patient and family members are motivated to be involved, is an important component in increasing the effectiveness of patient engagement initiatives. The purpose of this research was to co‐design a patient and family engagement framework.
Ctenophthalmus baeticus boisseauorum (Beaucournu, 1968) and Ctenophthalmus apertus allani (Smit, 1955) (Siphonaptera: Ctenophthalmidae) as synonymous taxa: morphometric, phylogenetic, and molecular characterization

Abstract The family Ctenophthalmidae (Order Siphonaptera) has been considered as a ‘catchall’ for a wide range of divergent taxa showing a paraphyletic origin. In turn, Ctenophthalmus sp. (Ctenophthalmidae) includes 300 valid described taxa. Within this genus, males are easily distinguishable basing on the size, shape, and chaetotaxy of their genitalia; however, females show slight morphological differences with each other. The main objective of this work was to carry out a comparative morphometric, phylogenetic, and molecular study of two different subspecies: Ctenophthalmus baeticus boisseauorum and Ctenophthalmus apertus allani in order to clarify and discuss its taxonomic status. From a morphological and biometrical point of view, we found clear differences between modified abdominal segments of males of both subspecies and slight differences in the margin of sternum VII of all female specimens which did not correspond with molecular and phylogenetic results based on four different molecular markers (Internal Transcribed Spacer 1 and 2 of ribosomal DNA, and the partial cytochrome c oxidase subunit 1 and cytochrome b of mitochondrial DNA). Thus, we observed a phenotypic plasticity between both subspecies, which did not correspond with a real genotypic variability nor different environmental or ecological conditions. Basing on these results, we could consider that there are no solid arguments to consider these two ‘morphosubspecies’ as two different taxa. We propose that C. b. boisseauorum should be considered as a junior synonym of C. a. allani.
Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Coronary Heart Disease (PROSPECTIVE)

Aims: Although intensive statin therapy reduced cardiovascular risks, cardiovascular events have not been completely prevented. Probucol is a potent antioxidant and reduces tendon xanthomas in familial hypercholesterolemia patients despite reduction of high-density lipoprotein (HDL)-cholesterol (HDL-C). We investigated whether probucol can reduce cardiovascular events on top of conventional lipid-lowering therapy in patients with coronary heart disease (CHD). Methods: PROSPECTIVE is a multicenter, randomized, prospective study that recruited 876 Japanese patients with CHD and dyslipidemia with a low-density lipoprotein (LDL)-cholesterol (LDL-C) level of ≥ 140 mg/dL without medication or those treated with lipid-lowering drugs. Lipid-lowering agents were administered during the study period in the control group (n = 438), and probucol 500 mg/day was added to lipid-lowering therapy in the probucol group (n = 438). Patients were randomly assigned to two treatment groups by adjusting the LDL-C level and presence of diabetes and hypertension and followed up for more than 3 years. The primary end point was a composite of cerebrovascular and cardiovascular events (cardiovascular disease death including sudden death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, hospitalization for heart failure, or coronary revascularization). The secondary end point was carotid intima-media thickness in a subset of patients. Results: The incidence of the primary end point showed a trend to be lower in the probucol group compared with that in the control group despite reduced HDL-C without serious adverse events. Anti-atherogenic effects of probucol may be attributed to its potent antioxidative function and enhancement of reverse cholesterol transport. Conclusion: Since there was no statistical significance between the probucol and control groups despite a marked reduction of HDL-C, further studies on the clinical outcomes of probucol on top of conventional therapy may be necessary in the future (UMIN000003307).
Sex Differences in Motor Unit Discharge Rates at Maximal and Submaximal Levels of Force Output.

This study evaluated potential sex differences in motor unit (MU) behaviour at maximal and submaximal force outputs. Forty-eight, 24 females and 24 males, performed isometric dorsiflexion contractions at 20, 40, 60, 80, and 100% of a maximum voluntary contraction (MVC). Tibialis anterior electromyography was recorded both by surface and intramuscular electrodes. Compared to males, females had a greater MU discharge rate (MUDR) averaged across all submaximal intensities (Δ 0.45 pps, 2.56%). Males exhibited greater increases in MUDR above 40% MVC, surpassing females at 100% MVC (p's<0.01). Averaged across all force outputs, females had a greater incidence of doublet and rapid discharges and a greater percentage of MU trains with doublet and rapid (5-10ms) discharges (Δ 75.55% and 61.48% respectively, p's<0.01). A sub-set of males (n=8) and females (n=8), matched for maximum force output, revealed that females had even greater MUDR (Δ 1.38 pps, 7.47%) and percentage of MU trains with doublet and rapid discharges (Δ 51.62%, 56.68% respectively, p's<0.01) compared to males at each force output, including 100% MVC. Analysis of the sub-set of strength matched males and females suggest that sex differences in MU behaviour may be a result of females needing to generate greater neural drive to achieve fused tetanus. Novelty bullets: • Females had higher MUDRs, and greater percentage of motor unit trains with doublets across submax force outputs (20-80%MVC). • Differences were even greater for a strength matched sub-set. • Differences in motor unit behaviour may arise from musculoskeletal differences requiring greater neural drive in females.
Brain-targeting by optimized 99mTc-olanzapine: in vivo and in silico studies

Abstract Purpose: Olanzapine (OLZ) is an atypical antipsychotic agent that is characterized by low brain porousness. The present work aimed to develop radiolabeled olanzapine (OLZ) without colloidal impurities and evaluate its biodistribution following intravenous (I.V.) and intranasal (I.N.) administration as a potential agent for brain diagnosis. Materials and methods: OLZ was radiolabeled with technetium-99m by using sodium dithionite as the reducing agent. Biodistribution of 99mTc-OLZ complex in mice following I.V. and I.N. administrations was examined. Furthermore, a molecular docking study was performed. Results: Sodium dithionite labeling procedure resulted in highest radiochemical yield (96.30 ± 0.09%) and in vitro stability in serum up to 8 h. Biodistribution study of 99mTc-OLZ complex showed high brain uptake following I.N. (6.2 ± 0.12% ID/g) and I.V. (5.5 ± 0.09% ID/g) at 0.5 and 1 h post administration (P.I.), respectively. Docking into two brain targets predicts higher affinity of 99mTc-OLZ than free OLZ. Additionally, docking to P-glycoproteins shows less affinity for the radiolabelled OLZ and hence it is expected to be associated with better brain exposure than free OLZ. Conclusion: These chemical and preliminary biological merits strongly suggest that the 99mTc-OLZ complex with new reducing agent could be used as a potential diagnostic agent for brain.