Miracle-dz/UniFAR-FTUs huggingface dataset:
Unexpected Finding of a Small Intestinal Neuroendocrine Tumor: A Case Report and Literature Review

Patient: Male, 70-year-old Final Diagnosis: Neuroendocrine tumor Symptoms: Abdominal pain Medication: — Clinical Procedure: CT scan • laparoscopy Specialty: Surgery Objective: Unusual clinical course Background: The incidence of neuroendocrine tumors (NETs) has increased in recent years. They can affect every area of the human body that presents cells with a secretory function. In this report, we focus on gastrointestinal NETs. The small bowel (SI) is the most affected area and SI-NETs have recently become more common than adenocarcinomas. Inside the small intestine, the appendix suffers from this pathology more than other organs. Case Report: Our case report deals with a 70 years-old man with extensive abdominal pain due to ingestion of an apricot kernel. A CT abdominal scan showed, around the kernel, a mechanical ileus with inflammation of the distal ileum and thickening of the intestinal wall. During the operation, we replaced laparoscopy with mini-laparotomy, performing an ileocecectomy due to suspicion of a tumor lesion. The histopathological exam revealed a well-differentiated neuroendocrine tumor (NET G1) of the distal ileum. Conclusions: This case report shows that SI-NETs can be found in cases of small bowel occlusion. Depending on the size and distinction, such patients can have good survival rates.
The cost of prevalent and incident cardiovascular disease in people with type 2 diabetes in Scotland: data from the Scottish Care Information–Diabetes Collaboration

To compare costs for three groups of people with type 2 diabetes, those at high risk of future cardiovascular disease, those without cardiovascular disease and those with established cardiovascular disease, and to also compare costs incurred by people with type 2 diabetes with an incident cardiovascular disease event with those who remain incident event‐free over a 3‐year period.
The role of innate immune cells in systemic sclerosis in the context of autologous hematopoietic stem cell transplantation

Systemic sclerosis (SSc) is a complex, heterogeneous autoimmune connective tissue disease. Autologous hematopoietic stem‐cell transplantation (AHSCT) has emerged as a valuable treatment option for rapidly progressive diffuse cutaneous SSc (dcSSc) patients, and thus far is the only treatment that has been shown to have a long‐term clinical benefit. AHSCT is thought to reintroduce immune homeostasis through elimination of pathogenic self‐reactive immune cells and reconstitution of a new, tolerant immune system. However, the mechanism of action underlying this reset to tolerance remains largely unknown. In this study we review the immune mechanisms underlying AHSCT for SSc, with a focus on the role of the innate immune cells, including monocytes and natural killer (NK) cells, in restoring immune balance after AHSCT.
Origin Recognition Complex (ORC) Evolution Is Influenced by Global Gene Duplication/Loss Patterns in Eukaryotic Genomes

Abstract The conservation of orthologs of most subunits of the origin recognition complex (ORC) has served to propose that the whole complex is common to all eukaryotes. However, various uncertainties have arisen concerning ORC subunit composition in a variety of lineages. Also, it is unclear whether the ancestral diversification of ORC in eukaryotes was accompanied by the neofunctionalization of some subunits, for example, role of ORC1 in centriole homeostasis. We have addressed these questions by reconstructing the distribution and evolutionary history of ORC1-5/CDC6 in a taxon-rich eukaryotic data set. First, we identified ORC subunits previously undetected in divergent lineages, which allowed us to propose a series of parsimonious scenarios for the origin of this multiprotein complex. Contrary to previous expectations, we found a global tendency in eukaryotes to increase or decrease the number of subunits as a consequence of genome duplications or streamlining, respectively. Interestingly, parasites show significantly lower number of subunits than free-living eukaryotes, especially those with the lowest genome size and gene content metrics. We also investigated the evolutionary origin of the ORC1 role in centriole homeostasis mediated by the PACT region in human cells. In particular, we tested the consequences of reducing ORC1 levels in the centriole-containing green alga Chlamydomonas reinhardtii. We found that the proportion of centrioles to flagella and nuclei was not dramatically affected. This, together with the PACT region not being significantly more conserved in centriole-bearing eukaryotes, supports the notion that this neofunctionalization of ORC1 would be a recent acquisition rather than an ancestral eukaryotic feature.
Perspectives on electrical neural recording: a revisit to the fundamental concepts

Objective. This paper aims to promote understanding on the fundamental concepts and mechanisms of extracellular electrical neural recording. Approach. First, the electrode-electrolyte interface is reviewed to clarify some of the frequent misunderstandings. Second, analytical solutions to the extracellular field potential and recorded signal are derived based on equivalent electrical circuit models, using a planar substrate microelectrode as a particular example. And third, factors affecting the recording quality are thoroughly assessed. Main results. Passive neural recording electrodes function as a pure capacitor. The extracellular field potential has two phases, with its subthreshold depolarization phase proportional to the first time derivative of the membrane depolarization and its action potential phase proportional to the negative first time derivative of the intracellular action potential. The recorded signal represents a portion of the extracellular field potential with both amplitude attenuation and phase distortion according to a voltage-divider circuit formed between the recording electrode and amplifier. A larger cell, a larger cell-substrate junctional membrane area, and a tighter membrane-substrate seal all help to improve the recording quality, while the effective electrode impedance should be minimized and the effective amplifier’s input impedance maximized. Significance. This paper develops in-depth insights to offer a clear image on the recording mechanism, nature of the signal, and interplays between key interface parameters. This work will make a foundational contribution to the field by providing such an in-depth understanding on this topic to clear the widespread ambiguities and confusions and inform rational neural electrode designs and proper interpretations of neural recordings.
Clinical Features of Severely Constipated Children: Comparison of Infrequent Bowel Movement and Fecal Soiling Groups

Purpose To compare the clinical features, diagnostic findings, and medications of children with infrequent bowel movements or fecal soiling. Methods This study enrolled 333 children (189 male; age range, 1 month to 18 years) diagnosed with functional constipation by Rome III or IV criteria. We classified them into 3 groups (infrequent bowel movement without fecal soiling [G3-a], infrequent bowel movement with fecal soiling [G3-b], and fecal soiling only [G3-c]) and into 2 subgroups of fecal soiling (G2-b) or not (G2-a). Retrospective data on clinical characteristics, colon transit time (CTT) test results, and medications were collected. The Wilcoxon rank-sum test, Kruskal-Wallis test, Chi-square test, and Fisher's exact test were used for the statistical analysis. Results The median age (months) and interquartile range (IQR) was 33 (45) in G3-a, 54 (40) in G3-b, and 73 (48) in G3-c (p<0.0001). G3-c had the latest onset (median, 18; IQR, 18; p=0.0219) and longest symptom duration (24 [24], p=0.0148). PEG 4000 was used in 60.6% (G3-a), 96.8% (G3-b), and 83.2% (G3-c) of patients (p<0.0001). The median age (months) and IQR were 33.0 (45.0) in G2-a and 63.5 (52.5) in G2-b (p<0.0001). G2-b had later onset (median, 12; IQR, 19.5; p=0.0062) and longer symptom duration than G2-a (24 [12], p=0.0070). PEG 4000 was used in 60.6% (G2-a) and 88.3% (G2-b) of children (p<0.0001). No statistically significant intergroup differences were seen in maintenance laxative dose, CTT, or CTT type. Conclusion Infrequent bowel movement and fecal soiling represent the advanced stage of chronic functional constipation.
A Practical Approach to Diagnosis of B-Cell Lymphomas With Diffuse Large Cell Morphology.

CONTEXT. — Large B-cell lymphomas represent the most common non-Hodgkin lymphomas and often present as extranodal masses with advanced stage similar to metastatic tumors. Without proper intraoperative, microscopic, immunophenotypic, and cytogenetic evaluation they may be mistaken for other hematopoietic or even nonhematopoietic tumors. Also, diffuse large B-cell lymphomas often have clinical, morphologic, immunophenotypic, and cytogenetic clinical features that are similar to those of other less common B-cell lymphomas. Furthermore, classification of these neoplasms is continually becoming more refined. OBJECTIVE. — To provide a rational, methodic approach to the evaluation of large B-cell lymphomas for community practice pathologists who provide general pathology services. DATA SOURCES. — This review incorporates guidelines detailed in the 2017 update to the World Health Organization's Classification of Tumours of Haematopoietic and Lymphoid Tissues in addition to other recent peer-reviewed publications. CONCLUSIONS. — Many large B-cell neoplasms respond favorably to current treatments, but these cases also require accurate and timely diagnoses. We propose a process following a brief checklist that focuses on diffuse large B-cell lymphoma, the most common entity, and rules out other similar lymphomas in a stepwise fashion.
AB0198 In Vitro Protective Effects of Soluble Klotho (SKL) Protein on Endothelial Cells in Systemic Sclerosis (SSC)

Background Systemic Sclerosis (SSc) is an autoimmune connective tissue disease characterized by impairs angiogenesis, alterations of microcirculation, senescence and apoptosis of endothelial cells (ECs). A recent study demonstrated that soluble Klotho (sKl) protein interacts with the vascular endothelial growth factor receptor 2 (VEGFR-2) and with transient receptor potential canonical-1 (TRPC-1) by forming a complex on the surface of endothelial cells. This heterotrimeric complex is internalized in response to vascular endothelial growth factor (VEGF) stimulation, thus regulating VEGFR-2/TRPC-1–mediated Ca2+ influx, to maintain endothelial biological homeostasis. Objectives The aim of this study was to evaluate, if soluble Klotho might act as protective humoral factor on SSc Microvascular Endothelial Cells (MVECs) by inhibiting cellular senescence and inducing angiogenesis. Methods Wound healing capacity was performed in healthy and SSc-MVECs under standard conditions and after sKl stimulation. Angiogenesis was evaluated by in vitro capillary morphogenesis on Matrigel in healthy and SSc-MVECs at basal condition, upon challenge with sKl, SSc and healthy sera, and sKl in combination with SSc and healthy sera. Western blot was performed in order to evaluate TRPC-1 and VEGFR-2 expression level in SSc and healthy MVECs at basal condition, after stimulation with sKl, SSc sera (n=5), healthy sera (n=5), and with sKl in combination with SSc and healthy sera before and after wound injury. Results Wound healing capacity significantly increased in healthy and SSc-MVECs after sKl challenge in respect to basal condition. Angiogenesis was significantly higher in SSc-MVECs upon challenge with sKl compared to both basal SSc and healthy MVEC. Moreover, angiogenesis was significantly increased in healthy MVECs challenged with SSc sera in combination with sKl respect to MVECs with SSc sera alone. TRPC-1 and VEGFR-2 expression level significantly increased under injury in both healthy and SSc-MVECs cultured with sKl respect to basal condition. Conclusions Our findings suggest that, under vascular injury conditions, sKl increases the wound healing ability and induces blood vessels formation in SSc-MVECs. Disclosure of Interest None declared
Future Directions in Cardio-Oncology

Ten years ago, few people would have imagined an entire issue of a journal devoted to the field of cardio-oncology or dreamt that there would be entire journals—such as Cardio-Oncology or JACC Cardio-Oncology—dedicated solely to this field. Cancer and cardiac disease race neck and neck as the leading causes of death, which makes the field of cardio-oncology almost an inevitable amalgam. While anthracyclines are the forerunners of this field, novel cancer therapies with potential for cardiotoxicity are being created on a weekly basis. Scientific vigilance and clinical experience have led to discoveries that many of these “targeted” therapies have off-target cardiac side effects. In fact, recent discoveries have been made regarding coexisting genetic and environmental risk factors for both cancer and cardiac disease. For example, age-related clonal hematopoiesis, a common condition associated with an increased risk of malignancy, has also been associated with an increased risk of cardiovascular disease.1
No carbon limitation after lower crown loss in Pinus radiata

Abstract Background and Aims Biotic and abiotic stressors can cause different defoliation patterns within trees. Foliar pathogens of conifers commonly prefer older needles and infection with defoliation that progresses from the bottom crown to the top. The functional role of the lower crown of trees is a key question to address the impact of defoliation caused by foliar pathogens. Methods A 2 year artificial defoliation experiment was performed using two genotypes of grafted Pinus radiata to investigate the effects of lower-crown defoliation on carbon (C) assimilation and allocation. Grafts received one of the following treatments in consecutive years: control–control, control–defoliated, defoliated–control and defoliated–defoliated. Results No upregulation of photosynthesis either biochemically or through stomatal control was observed in response to defoliation. The root:shoot ratio and leaf mass were not affected by any treatment, suggesting prioritization of crown regrowth following defoliation. In genotype B, defoliation appeared to impose C shortage and caused reduced above-ground growth and sugar storage in roots, while in genotype A, neither growth nor storage was altered. Root C storage in genotype B decreased only transiently and recovered over the second growing season. Conclusions In genotype A, the contribution of the lower crown to the whole-tree C uptake appears to be negligible, presumably conferring resilience to foliar pathogens affecting the lower crown. Our results suggest that there is no C limitation after lower-crown defoliation in P. radiata grafts. Further, our findings imply genotype-specific defoliation tolerance in P. radiata.
Visualization of the human enteric nervous system by confocal laser endomicroscopy in Hirschsprung's disease: An alternative to intraoperative histopathological diagnosis?

Hirschsprung's disease is a congenital abnormality of the enteric nervous system (ENS) presenting severe constipation soon after birth due to the lack of ganglion cells in the distal gut. Surgery for Hirschsprung's disease requires an intraoperative histopathological diagnosis to assess the extent of aganglionosis. Confocal laser endomicroscopy (CLE) is a novel endoscopic technique allowing real‐time, in vivo analysis of cellular details during ongoing endoscopy. In this study, we evaluated the possibility of a new application of CLE to provide real‐time observations of the ENS in patients with Hirschsprung's disease. In this preclinical feasibility study, we assessed the visualization of the ENS by CLE using surgically resected intestines.
Patient-oriented research can be meaningful for clinicians and trialists as well as patients

We read with interest the CMAJ Analysis by Aubin and colleagues,[1][1] which identified issues in developing and measuring the impact of patient-oriented research. We are studying cerebral venous thrombosis (CVT), an uncommon cause of stroke, in a national trial (Study of rivaroxaban in CeREbral
Proteomic changes in skeletal muscle of aged rats in response to resistance training

Sarcopenia is a multifactorial process defined by loss of strength and skeletal muscle mass, which leads to a reduction in muscle cross‐sectional area (CSA). Although resistance training (RT) has been indicated as a tool to counteract sarcopenia, the protein profile associated with skeletal muscle adaptations remains to be determined. We investigated the effects of 12 weeks of RT on the skeletal muscle proteome profile and CSA of young and older rats. Twenty‐four animals were divided into four groups: young sedentary or trained and older sedentary or trained (six animals per group). A 12‐week RT protocol was performed, which consisted of climbing a vertical ladder. The proteins from the gastrocnemius were analysed by LC‐ESI‐MS/MS. One‐hundred and thirty‐one proteins were identified, of which 28 were assessed between the groups. Ageing induced an increase in proteins associated with the glycolytic pathway, transport and stress response, which represent crucial mechanisms for muscle adaptation. RT upregulated metabolic enzymes, anti‐oxidant activity and transport proteins, besides increasing hypertrophy, regardless of age, suggesting a beneficial adaptation to mitigate age‐related sarcopenia. RT reduced muscle atrophy through the regulation of stress response and by increasing proteins related to energy production and transport, which in turn might protect tissue damage arising from exercise and ageing.
Protective effects of beet (Beta vulgaris) leaves extract against oxidative stress in endothelial cells in vitro

Beetroot is an herb used worldwide as a food product, raw material for food industry, ethanol production and source of food coloring. Beet leaves are an unconventional food with antioxidant properties, which might neutralize reactive oxygen species (ROS) induced by oxidized Low‐Density Lipoprotein (LDL) present in dyslipidemias. This study aimed to elucidate the effects of beet leaves on the suppression of LDL oxidative processes. Beet leaves extract was produced, characterized, and tested for its antioxidant capacity using endothelial cells in vitro. A model of human umbilical vein endothelial cells was used in various tests, including viability assay, molecular analysis of antioxidant genes, ROS labeling, and macrophage adhesion assay. The extract improved the antioxidative protection of endothelial cells against different agents including oxidized LDL‐cholesterol and H2O2. It acted on ROS directly due to its high content of natural antioxidants, but also due to the activation and improvement of cellular defenses such as Superoxide dismutase 1, Superoxide dismutase 2, and catalase. The inhibition of LDL‐mediated oxidative effects on endothelial cells may turn this unconventional food a functional food with great potential for phytotherapy of atherosclerosis as an adjuvant for medicinal treatments.
Genetic architecture study of rheumatoid arthritis and juvenile idiopathic arthritis

Background Rheumatoid arthritis and juvenile idiopathic arthritis are two types of autoimmune diseases with inflammation at the joints, occurring to adults and children respectively. There are phenotypic overlaps between these two types of diseases, despite the age difference in patient groups. Methods To systematically compare the genetic architecture of them, we conducted analyses at gene and pathway levels and constructed protein-protein-interaction network based on summary statistics of genome-wide association studies of these two diseases. We examined their difference and similarity at each level. Results We observed extensive overlap in significant SNPs and genes at the human leukocyte antigen region. In addition, several SNPs in other regions of the human genome were also significantly associated with both diseases. We found significantly associated genes enriched in 32 pathways shared by both diseases. Excluding genes in the human leukocyte antigen region, significant enrichment is present for pathways like interleukin-27 pathway and NO2-dependent interleukin-12 pathway in natural killer cells. Discussion The identification of commonly associated genes and pathways may help in finding population at risk for both diseases, as well as shed light on repositioning and designing drugs for both diseases.
Chromosome mis-segregation in yeast by Agrobacterium tumefaciens virulence protein VirD5

Agrobacterium tumefaciens delivers a segment of transferred DNA (T-DNA) as well as effector proteins through a type IV secretion system into host cells. Here, we report that one of these effector proteins, VirD5, has growth inhibitory effects. Its expression in both Saccharomyces cerevisiae and Arabidopsis thaliana leads to growth inhibition and cell death. This toxicity is conserved among VirD5 proteins from different Agrobacterium strains. Using budding yeast as a model organism, we found that VirD5 is present at the yeast centromeres/kinetochores. Toxicity is relieved by deletion of the Spt4 protein, which is also present at the centromeres. VirD5 can interact with Spt4 and in its absence VirD5 is no longer located at the centromeres/kinetochores. The centromere is a specific chromosomal locus required for the assembly of the kinetochore which mediates the accurate separation of the duplicated sister chromatids over daughter cells during mitosis. The expression of VirD5 generates DNA damage and chromosome mis-segregation. These results highlight a novel role of a bacterial virulence protein to hijack host cells through disturbing the essential mitosis process. This may enhance the tumorigenic potential of the bacterium on its natural hosts, dicotyledonous plants.
NBER WORKING PAPER SERIES MARKET FRICTIONS, ARBITRAGE, AND THE CAPITALIZATION OF AMENITIES

We would like to thank Joël David, Morris Davis, Mariacristina De Nardi, Anthony Heyes, Matthew E. Kahn, Patrick Kehoe, Adam Lavecchia, Robert Lucas, Fabrizio Perri, Hashem Pesaran for helpful comments, as well as the audience of the Federal Reserve of Minneapolis seminar series, the University of Southern California’s conference on housing and the macroeconomy, the meeting of the Canadian Economics Association, and seminar series at the University of Ottawa and Université Laval. The authors acknowledge financial support from HEC, INET, and USC. The views expressed herein are those of the authors and do not necessarily reflect the views of the National Bureau of Economic Research.
Gender Diversity: Changing Stereotypes in Organizations

Diversity has been established to be a compulsory imperative in Organizations today. Human Resource policies are being tweaked to accommodate a workforce who is diversified in a multitude of aspects including gender, which appears to be a popular variant in diversity. This study investigates the nuances of changing perceptions of people towards stereotypes of gender. The implication of gender based character is considered important in making assumptions about the behaviours of the gender. In this study, 440 respondents of various ages and occupations were contacted as primary data, to mark their perceptions of character associated with gender like aggression, domination and being excitable. The findings appear to be counter intuitive to popular stereotype perception where 34 per cent of women are considered aggressive, 35 per cent of women are considered dominating and 35 per cent of women are established to be excitable and volatile. These findings reflect the changing scenario and environment of female gender today which is being manifested in their non stereotype behaviour.