Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathologic Evaluation of Endoscopically Resected Non-Ampullary Duodenal Lesions: A Single Center Experience

Objective: Endoscopic resections are increasingly being used for superficial gastrointestinal lesions. However, application of these techniques in the duodenum remains challenging, due to the technical difficulties and high complication rates. This study projects a western tertiary center’s experience in the endoscopic treatment and diagnostic workup of 19 cases of non-ampullary duodenal lesions. Material and Method: Specimens (12 endoscopic mucosal resections, 6 endoscopic submucosal dissections, and one endoscopic full-thickness resection) were processed following a strict protocol (photographed, mapped digitally and submitted totally) for histopathologic examination. Clinicopathologic characteristics, margin status and follow-up information were analyzed. Results: The mean age of the 16 patients was 52 years (range: 22-81). Mean lesion size was 1.4 cm (range: 0.3-3.6 cm) for all cases, 2 cm for endoscopic submucosal dissections and 1.1 cm for endoscopic mucosal resections. Mean number of blocks submitted was 4/case. Seven neuroendocrine tumors, 3 tubulovillous adenomas were diagnosed along with nine benign lesions. For endoscopic submucosal dissections, en-bloc and R0 resection rates were 100% (n=6/6) and 83% (n=5/6); for endoscopic mucosal resections, they were 92% (n=11/12) and 83% (n=10/12), respectively. Only one patient had procedure-related late perforation that was managed endoscopically. No mortality was encountered. Conclusion: Duodenal endoscopic resections proved successful, safe and feasible methods in a tertiary center. The pathologist’s role is to designate the accurate diagnosis, related histopathologic parameters and margin status. The gross protocol was found to be essential in evaluating specimen margins and orientation, as well as in size measurement. We recommend following a standardized approach including gross photography and digital mapping when handling these specimens, for both diagnostic and data collection purposes.
Artificial Intelligence and Surgical Decision-Making.

Importance Surgeons make complex, high-stakes decisions under time constraints and uncertainty, with significant effect on patient outcomes. This review describes the weaknesses of traditional clinical decision-support systems and proposes that artificial intelligence should be used to augment surgical decision-making. Observations Surgical decision-making is dominated by hypothetical-deductive reasoning, individual judgment, and heuristics. These factors can lead to bias, error, and preventable harm. Traditional predictive analytics and clinical decision-support systems are intended to augment surgical decision-making, but their clinical utility is compromised by time-consuming manual data management and suboptimal accuracy. These challenges can be overcome by automated artificial intelligence models fed by livestreaming electronic health record data with mobile device outputs. This approach would require data standardization, advances in model interpretability, careful implementation and monitoring, attention to ethical challenges involving algorithm bias and accountability for errors, and preservation of bedside assessment and human intuition in the decision-making process. Conclusions and Relevance Integration of artificial intelligence with surgical decision-making has the potential to transform care by augmenting the decision to operate, informed consent process, identification and mitigation of modifiable risk factors, decisions regarding postoperative management, and shared decisions regarding resource use.
Bridging the Gap in the Technology Commercialization Process: Using a Three-Stage Technology–Product–Market Model

This study proposes a new “three-stage technology–product–market” model to analyze the technology commercialization process. This model revises the technology acceptance model to more accurately consider the market potential of new technologies from a consumer perspective. This approach can be used to supplement developers’ own evaluations of technology. To test the model empirically, an online survey of 350 end users was conducted regarding their intention to purchase the “Wireless USB,” which uses “Zing” technology and was developed by the Electronics and Telecommunications Research Institute. The data was used to test the model using a structural equations approach. We indirectly confirmed the existence of gaps in the technology commercialization process by verifying the mediating effects of the productization stage. Results suggest that end users may not purchase a product, even if they perceive the technology to be innovative; the product purchase intention is significantly influenced by its perceived value. Therefore, developers must understand the concept of technology value for productization in order to refine a technology according to market demand.
IKZF1 deletions in pediatric acute lymphoblastic leukemia: still a poor prognostic marker?

Improved personalized adjustment of primary therapy to the perceived risk of relapse by employing new prognostic markers for treatment stratification may be beneficial to patients with acute lymphoblastic leukemia (ALL). Here, we review the advances that have shed light on the role of IKZF1 aberration as prognostic factor in pediatric ALL and summarize emerging concepts in this field. Continued research on the interplay of disease biology with exposure and response to treatment will be key to further improve treatment strategies.
Extracellular ATP and purinergic P2Y2 receptor signaling promote liver tumorigenesis in mice by exacerbating DNA damage.

Release of adenosine triphosphate (ATP) to the extracellular compartment and subsequent activation of purinergic receptors is a conserved mechanism mediating inflammatory responses and cell fate decisions in various organs including the liver. Previous findings suggest that extracellular ATP may promote liver tumorigenesis; however, the underlying mechanisms are poorly understood. Therefore, our aim was to dissect the functions of extracellular ATP and P2Y2 receptors (P2Y2R) during hepatocarcinogenesis. Liver tumors were induced in wild-type and P2y2r-/- knock-out mice by intraperitoneal diethylnitrosamine (DEN) injection. Tumorigenesis was analyzed after 8-10 months and molecular analyses were performed at different stages of tumorigenesis in vivo, as well as in primary mouse hepatocytes in vitro. Liver tumor incidence and tumor numbers were strongly reduced in P2y2r-/- mice, whereas tumor size and morphology were comparable to wild-type controls, suggesting that P2Y2R contributes to tumor initiation. Mechanistically, hepatocyte proliferation in DEN-treated P2y2r-/- mice was reduced, which correlated with reduced c-JUN and CCND1 but increased p21 expression. Moreover, DNA damage as determined by hepatocellular expression of γH2A. X and of genes related to genotoxic stress, as well as STAT3 phosphorylation, was reduced in the absence of P2y2r. Administration of genotoxic agents to primary hepatocytes in vitro confirmed that DNA damage was indeed exacerbated by extracellular ATP, subsequent P2Y2R activation and downstream intracellular calcium-dependent signal transduction. In conclusion, our data reveal that extracellular ATP and subsequent P2Y2R function stimulate DNA damage responses and hepatocyte proliferation, thereby promoting hepatocarcinogenesis. Targeting this pathway may be an attractive approach for chemoprevention of hepatocellular carcinoma.
Modulatory effects of stonebreaker (Phyllanthus amarus) and bitter gourd (Momordica charantia) on enzymes linked with cardiac function in heart tissue of doxorubicin-stressed rats

Abstract Doxorubicin (DOX) has been linked with impairment in cardiovascular function and redox balance. In the present study, the effect of Phyllanthus amarus (PA) and Momordica charantia (MC) leaves on some biomolecules [Angiotensin-I converting enzyme (ACE), arginase, acetylcholinesterase (AChE), adenosine deaminase (ADA), lactate dehydrogenase (LDH)] and antioxidant [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA)] linked with cardiac function in DOX-stressed rats was evaluated. Animals were grouped and pretreated with PA and MC leaf extracts at different doses (200 and 400 mg/kg/bwt orally), while DOX (15 mg/kg/bwt) was administered intraperitoneally on the last day of the experiment. Result revealed an increase of ACE, arginase, AChE, ADA, LDH activities and MDA level as well as a significant reduction in CAT and SOD activities, and GSH level in the rats treated with DOX compared to the control. However, these were significantly mitigated in the rats pretreated with PA and MC dose dependently. Chemical characterization of the leaf extracts via high performance liquid chromatography revealed the presence of some phenolic compounds which included kaempferol, catechin, epicatechin, ellagic acid, gallic acid quercetin, isoquercitrin and rutin. These findings revealed a significant improvement in redox imbalance and other biomolecules associated with cardiac function, which was altered by DOX. This improvement could be linked to the presence of cardioprotective agents present in PA and MC, thereby making these plants therapeutic agents for the treatment of cardiovascular complications associated with drugs such as DOX.
Older Teens’ Understanding and Perceptions of Risks in Studies With Genetic Testing: A Pilot Study

Abstract Background: The consent process used in clinical research today falls markedly short of the ideal process envisioned nearly 30 years ago. Critics have suggested that the informed consent process has become challenging, formalistic, and incompletely understood by researchers and participants alike. Hence, the purpose of this pilot study was to identify and characterize important aspects of the informed consent process that teens believe impact their understanding of risks of participation in studies with genetic testing. Methods: The personal research experiences of 15 teens regarding consent/assent and research participation in studies with genetic testing were solicited through focus-group interviews. All participants had enrolled in at least one research study involving genetic testing in the prior 2 years. All groups were facilitated by the same experienced focus-group moderator. Themes and subthemes were identified, summarized, and interpreted using conventional qualitative content analysis. Results: Three overarching themes emerged from the interviews: fear of what could happen, need for additional information regarding risks, and need for autonomy and decision-making control throughout the consent process. Conclusion: Results of this pilot study provide preliminary evidence that teens can identify and characterize key issues in the informed consent/assent process when it comes to the risks of research participation. These findings are consistent with other research regarding teens’ perceptions and recommendations for genetic testing research.
Obesity-Induced Sympathoexcitation is Associated with Nrf2 Dysfunction in the Rostral VentroLateral Medulla.

Increases in sympathetic nerve activity (SNA) have been implicated in obesity-induced risk for cardiovascular diseases, especially hypertension. Previous studies indicate that oxidative stress in the rostral ventrolateral medulla (RVLM), a key brainstem region that regulates sympathetic outflow to peripheral tissues, plays a pathogenic role in obesity-mediated sympathoexcitation. However, the molecular mechanisms underlying this phenomenon are not clear. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the expression of anti-oxidant and anti-inflammatory genes and confers cytoprotection against oxidative stress. The present study was designed to investigate whether Nrf2 dysfunction was associated with obesity-induced oxidative stress in the RVLM and sympathoexcitation. C57BL/6J mice were fed with chow or high fat diet (HFD) for 16 weeks. Blood pressure parameters were assessed by radiotelemeters in conscious freely moving mice. SNA was measured by heart rate variability analysis and also through assessment of depressor response to ganglionic blockade. RVLM was micro-dissected for gene expression and protein analysis (western blotting and activity assay) related to Nrf2 signaling. Our results showed that HFD-induced obesity resulted in significant increases in SNA, although we only observed a mild increase in mean arterial pressure. Obesity-induced oxidative stress in the RVLM was associated with impaired Nrf2 signaling marked by decreased Nrf2 activity, downregulation of Nrf2 target genes (NQO1 and SOD2) and inflammation. Our findings suggest that obesity results in Nrf2 dysfunction which likely causes maladaptation to oxidative stress and inflammation in the RVLM. These mechanisms could potentially contribute to obesity-induced sympathoexcitation.
Vaping: The new wave of nicotine addiction

Vaping devices, introduced to the US market in 2007 as aids for smoking cessation, have become popular among youth and young adults because of their enticing flavors and perceived lack of negative health effects. However, evidence is emerging that vaping may introduce high levels of dangerous chemicals into the body and cause severe lung injury and death. This article reviews the history and prevalence of vaping and available research on its health effects and efficacy in smoking cessation, and proposes recommendations for clinicians and legislators to reduce harms associated with vaping. Despite perceptions that vaping is harmless and claims that it can aid in smoking cessation, risks are emerging.
CD8+ T cells target cerebrovasculature in children with cerebral malaria.

BACKGROUND Cerebral malaria (CM) accounts for nearly 400,000 deaths annually in African children. Current dogma suggests that CM results from infected RBC (iRBC) sequestration in the brain microvasculature and resulting sequelae. Therapies targeting these events have been unsuccessful; findings in experimental models suggest that CD8+ T cells drive disease pathogenesis. However, these data have largely been ignored because corroborating evidence in humans is lacking. This work fills a critical gap in our understanding of CM pathogenesis that is impeding development of therapeutics. METHODS Using multiplex immunohistochemistry, we characterized cerebrovascular immune cells in brain sections from 34 children who died from CM or other causes. Children were grouped by clinical diagnosis (CM+ or -), iRBC sequestration (Seqhi, lo, or 0) and HIV status (HIV+ or -). RESULTS We identified effector CD3+CD8+ T cells engaged on the cerebrovasculature in 69% of CM+ HIV- children. The number of intravascular CD3+CD8+ T cells was influenced by CM status (CM+ vs -, P = 0.004) and sequestration level (Seqhi > lo, P = 0.010). HIV co-infection significantly increased T cell numbers and shifted cells from an intravascular (P = 0.004) to perivascular (P < 0.0001) distribution. CONCLUSION Within the studied cohort, CM is associated with cerebrovascular engagement of CD3+CD8+ T cells, which is exacerbated by HIV coinfection. Thus, CD3+CD8+ T cells are highly promising targets for CM adjunctive therapy, opening new avenues for the treatment of this deadly disease. FUNDING This research was supported by the Intramural Research Program of the National Institutes of Health.
A direct heterotypic interaction between the DIX domains of Dishevelled and Axin mediates signaling to β-catenin

Interactions between the DIX domains of Dishevelled and Axin drive repression of the β-catenin destruction complex. DIX domains drive Wnt–β-catenin signaling Dishevelled (Dvl) stimulates Wnt–β-catenin signaling by recruiting Axin, a component of the β-catenin destruction complex, to the Wnt signalosome, thus stabilizing β-catenin. Both Dvl-mediated activation and Axin-mediated repression of signaling require homopolymerization through the DIX domains of each protein. Through structural analysis and biochemical assays with the DIX domain of human Dvl and the DIX domain of human Axin (DAX), Yamanishi et al. found that the heterotypic interface between DIX and DAX resembled the interfaces observed in the individual homopolymers and that DIX-DAX heteropolymerization was favored over DAX-DAX homopolymerization. These findings support a model in which Dvl-Axin heterodimerization, mediated by DIX domains, drives the recruitment of Axin to the Wnt signalosome and disruption of the β-catenin destruction complex. The Wnt–β-catenin signaling pathway regulates embryonic development and tissue homeostasis throughout the animal kingdom. Signaling through this pathway crucially depends on the opposing activities of two cytoplasmic multiprotein complexes: the Axin destruction complex, which destabilizes the downstream effector β-catenin, and the Dishevelled signalosome, which inactivates the Axin complex and thus enables β-catenin to accumulate and operate a transcriptional switch in the nucleus. These complexes are assembled by dynamic head-to-tail polymerization of the DIX domains of Axin or Dishevelled, respectively, which increases their avidity for signaling effectors. Axin also binds to Dishevelled through its DIX domain. Here, we report the crystal structure of the heterodimeric complex between the two DIX domains of Axin and Dishevelled. This heterotypic interface resembles the interfaces observed in the individual homopolymers, albeit exhibiting a slight rearrangement of electrostatic interactions and hydrogen bonds, consistent with the heterotypic interaction being favored over the homotypic Axin DIX interaction. Last, cell-based signaling assays showed that heterologous polymerizing domains functionally substituted for the DIX domain of Dishevelled provided that these Dishevelled chimeras retained a DIX head or tail surface capable of binding to Axin. These findings indicate that the interaction between Dishevelled and Axin through their DIX domains is crucial for signaling to β-catenin.
Risk Factors for Inspiratory Muscle Weakness in Chronic Heart Failure

BACKGROUND: Chronic heart failure is commonly associated with inspiratory muscle weakness. However, few studies have investigated the risk factors for inspiratory muscle weakness in individuals with chronic heart failure and systolic dysfunction (left-ventricular ejection fraction [LVEF] <40%). METHODS: Seventy subjects were recruited in a cardiac center. We assessed clinical parameters, smoking history, peripheral muscle strength, pulmonary function, echocardiographic variables, and brain natriuretic peptide. The subjects were classified with inspiratory muscle weakness when the maximum inspiratory pressure was <70% of predicted values. RESULTS: Thirty-six subjects (51%) had inspiratory muscle weakness. The subjects with inspiratory muscle weakness and the subjects with no inspiratory muscle weakness were similar in age, sex, body mass index, medication use, and physical activity. However, the subjects with inspiratory muscle weakness had lower LVEF (P = .003), systolic blood pressure (P = .01), diastolic blood pressure (P = .042), quadriceps muscle strength (P = .02), lung function (P = .035), increased brain natriuretic peptide (P = .02), smoking history (P = .01), and pulmonary hypertension incidence (P = .03). Multivariate logistic regression analysis found a lower LVEF, increased smoking history, and lower systolic blood pressure as significant independent predictors for inspiratory muscle weakness. CONCLUSIONS: The combination of lower LVEF, lower systolic blood pressure, and smoking history predicted inspiratory muscle weakness. Patients with suspected inspiratory muscle weakness should be examined and, if inspiratory muscle weakness exists, then inspiratory muscle training should be provided. Reducing inspiratory muscle weakness has the potential to improve many of the deleterious effects of chronic heart failure.
Vitamin D Intake from Supplemental Sources but Not from Food Sources Has Increased in the Canadian Population Over Time.

BACKGROUND Evidence is lacking to determine whether there have been any changes in dietary or total usual intakes of vitamin D among Canadians, in the light of recent evidence of beneficial health effects beyond bone. OBJECTIVE We aimed to examine trends in dietary and total usual intake of vitamin D among Canadians aged ≥1 y. METHODS This study used nationally representative nutrition data from the Canadian Community Health Survey Cycle 2.2 (CCHS 2004) and CCHS Nutrition in 2015. Dietary intake data were collected with use of two 24-h dietary recalls and dietary supplement use was determined by questionnaire. The National Cancer Institute method was used to estimate the usual intake of vitamin D as well as the prevalence of vitamin D inadequacy among Canadians aged ≥1 y. RESULTS From 2004 to 2015, the usual intake of vitamin D from food significantly decreased (P < 0.05) by 1 μg/d only in vitamin D supplement nonusers. The contribution of Milk and Alternatives food group (i.e., fluid milk, fortified soy beverages, powdered milk, and other milk alternatives) to dietary vitamin D intake significantly decreased (P < 0.05) in both supplement users (by 7.1%) and nonusers (by 5.8%). Prevalence of vitamin D supplement use and percentage contribution of vitamin D from supplemental sources significantly increased (P < 0.05) by 5.0% and 14.9%, respectively, from 2004 to 2015. Total usual intake of vitamin D (food + supplement) significantly increased (P < 0.05) from 15.1 ± 0.3 μg/d in 2004 to 31.5 ± 1.8 μg/d in 2015 in vitamin D supplement users. In contrast to vitamin D supplement nonusers, the prevalence of vitamin D inadequacy significantly decreased (P < 0.05) from 20.6% to 14.1% among users of vitamin D supplements. CONCLUSIONS The prevalence of vitamin D supplement use and the percentage contribution of vitamin D from supplemental sources has increased in the Canadian population over an 11-y period.
A mathematical model of cerebral blood flow control in anaemia and hypoxia

The control of cerebral blood flow in hypoxia, anaemia and hypocapnia is reviewed with an emphasis on the links between cerebral blood flow and possible stimuli. A mathematical model is developed to examine the changes in the partial pressure of oxygen in brain tissue associated with changes in cerebral blood flow regulation produced by carbon dioxide, anaemia and hypoxia. The model demonstrates that hypoxia, anaemia and hypocapnia, alone or in combination, produce varying degrees of cerebral hypoxia, an effect exacerbated when blood flow regulation is impaired. The suitability of brain hypoxia as a common regulator of cerebral blood flow in hypoxia and anaemia was explored, although we failed to find support for this hypothesis. Rather, cerebral blood flow appears to be related to arterial oxygen concentration in both anaemia and hypoxia.