Miracle-dz/UniFAR-FTUs huggingface dataset:
PWE-041 Histopathological Uncertainties in the Management of Early Colorectal Cancers Resected through Endoscopic Therapy

Introduction Standards for Colorectal cancer (CRC) resection specimen histology reporting consider factors thought to have apparent significance for prognosis and further therapy. Whilst well validated for surgical resection, the increasing use of advanced endoscopic resection for polyps containing previously unknown early CRC presents challenges in interpretation of these factors. In addition to tumour budding, unfavourable tumour grade, and vascular invasion, Ueno et al[1] proposed parameters for width and depth of submucosal invasion as risk for adverse outcome. This study aims to analyse any association between pathological factors and outcome with endoscopic resection of early CRC. Methods Retrospective review of all CRC removed endoscopically between March 2006 and March 2011. All endoscopic and surgical resection specimens were reviewed by two expert gastrointestinal histopathologists, with measurement of width and depth of submucosal invasion made. All follow up procedures, including radiology, were reviewed. Results 35 cases were identified (24 males, 11 females, median age 69 years). All patients were alive after median follow-up period of 32 months; no residual/recurrent cancers were found in any patient managed with endoscopic therapy alone. Of the 12 patients who had further surgical intervention due to reported incomplete endoscopic resection on histology, none had residual carcinoma in the subsequent resection specimen. Three patients (8.6%) were found to have Dukes C1 cancers (all T1 N1 M0). These cancers were not associated with poor differentiation or lymphovascular invasion (p = 0.546) or tumour budding of low or high intensity (p = 1.000). The relationship between the width and depth of submucosal invasion and Dukes C1 did not reach statistical significance (p = 0.096), although these three cancers did fulfil Ueno criteria. Presence of lymph node metastases was associated with Haggitt level 4 (p = 0.03), but not with the presence of tumour at the excision margin (p = 1.000) in the subsequent surgical resection group. Conclusion Our experience highlights the challenges in applying histopathological criteria to individual cases of early CRC resected via endoscopic therapy. Most patients underwent surgery for an unclear resection margin, however no residual cancer was present in the resection specimens and aside from a Haggit level 4, found no other predictors of risk lymph node metastases. Suggestions for future studies include piloting a more minimally invasive approach, such as regional lymph node dissection in selected cases as well as studying biomarkers for refining risk stratification. Disclosure of Interest None Declared. Reference Ueno H et al. Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology 2004; 127: 385–394
Critical role of mitochondrial oxidative stress in acid aspiration induced ALI in mice

Abstract Acute lung injury (ALI) is a pulmonary inflammatory disorder which causes significant mortality in critically ill patients. Intracellular oxidative stress has been considered to be the major component in the pathogenesis of ALI but exact source of intracellular ROS is not clearly known. The present study has been designed to elucidate the role of NADPH oxidase system and/or mitochondrial oxidative stress and its downstream pathway NLRP3 inflammasomes in mouse model of acid aspiration mediated ALI. Our data showed that acid aspiration induced lung inflammation was associated with enhanced oxidative stress as evident by data on MDA levels, nitrite levels and redox imbalance. Further acid aspiration resulted in elevation of expression of NADPH oxidase subunits (gp91 phox/p22 phox/p67 phox) as well as mitochondrial oxidative stress as reflected by aconitase activity, mitochondrial ROS levels. Interestingly, NADPH oxidase inhibitor, apocynin did not alter lung inflammation upon HCl instillation. Conversely, mitochondrial antioxidant mito-tempo resulted in significant amelioration of lung inflammation as indicated by suppression of pulmonary neutrophils and inflammatory cytokines namely IL-1β, TNF-α, IL-6 in BALF. Analysis of mitochondrial enzymes aconitase/mitochondrial ROS/Mn-SOD confirmed that reduction in lung inflammation by mito-tempo was associated with normalization of oxidative stress in mitochondria. Further, mito-tempo administration blunted phosphorylation of p65- NF-κB at Ser 536. Finally, mito-tempo downregulated HCl-induced NF-κB-dependent pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) drastically at mRNA levels. Overall, our data support that mitochondrial oxidative stress is crucial in modulating the HCl induced lung inflammation and identifies mitochondrial-targeted antioxidant as a potential therapeutic agent.
Uterine epithelial expression of the tumor necrosis factor superfamily: a strategy for immune privilege during pregnancy in a true epitheliochorial placentation species

Abstract The maternal immune system tolerates semi-allogeneic placental tissues during pregnancy. Fas ligand (FASLG) and tumor necrosis factor superfamily 10 (TNFSF10) are known to be components of maternal immune tolerance in humans and mice. However, the role of FASLG and TNFSF10 in the tolerance process has not been studied in pigs, which form a true epitheliochorial type placenta. Thus, the present study examined the expression and function of FASLG and TNFSF10 and their receptors at the maternal-conceptus interface in pigs. The endometrium and conceptus tissues expressed FASLG and TNFSF10 and their receptor mRNAs during pregnancy in a stage-specific manner. During pregnancy, FASLG and TNFSF10 proteins were localized predominantly to endometrial luminal epithelial cells with strong signals on Day 30 to term and on Day 15, respectively, and receptors for TNFSF10 were localized to some stromal cells. Interferon-γ (IFNG) increased the expression of TNFSF10 and FAS in endometrial tissues. Co-culture of porcine endometrial epithelial cells over-expressing TNFSF10 with peripheral blood mononuclear cells yielded increased apoptotic cell death of lymphocytes and myeloid cells. In addition, many apoptotic T cells were found in the endometrium on Day 15 of pregnancy. The present study demonstrated that FASLG and TNFSF10 were expressed at the maternal-conceptus interface and conceptus-derived IFNG increased endometrial epithelial TNFSF10, which, in turn, induced apoptotic cell death of immune cells. These results suggest that endometrial epithelial FASLG and TNFSF10 may be critical for the formation of micro-environmental immune privilege at the maternal-conceptus interface for the establishment and maintenance of pregnancy in pigs. Summary sentence TNFSF expressed in the endometrial epithelia by conceptus-derived interferon-γ contributes immune privilege during early pregnancy in pigs.
Phase I/II parallel double-blind randomized controlled clinical trial of perispinal etanercept for chronic stroke: improved mobility and pain alleviation

ABSTRACT Background Previous open-label studies showed that chronic post-stroke pain could be abated by treatment with perispinal etanercept, although these benefits were questioned. A randomized double-blind placebo controlled clinical trial was conducted to test perispinal etanercept for chronic post-stroke pain. Research design and methods Participants received two treatments, either perispinal etanercept (active) or saline (control). Primary outcomes were the differences in daily pain levels between groups analyzed by SPSS. Results On the 0–100 points visual analog scale, perispinal etanercept reduced mean levels for worst and average daily pain from baseline after two treatments by 19.5 – 24 points (p < 0.05), and pain alleviation was maintained in the etanercept group, with no significant change in the control group. Thirty percent of etanercept participants had near complete pain abatement after first treatment. Goniometry of the paretic arm showed improved mean shoulder rotation by 55 degrees in active forward flexion for the etanercept group (p = 0.003) only. Conclusions Perispinal etanercept can provide significant and ongoing benefits for the chronic post-stroke management of pain and greater shoulder flexion by the paretic arm. Effects are rapid and highly significant, supporting direct action on brain function. Trial registration ACTRN12615001377527 and Universal Trial Number U1111-1174-3242.
The benefit of interleaved presentation in category learning is independent of working memory

ABSTRACT We tested whether working memory (WM) resources were necessary for the interleaved presentation benefit over blocked presentation in category learning. We examined category learning in the Kornell and Bjork [2008. Learning concepts and categories: Is spacing the “enemy of induction”? Psychological Science, 19(6), 585] artistic style task while participants performed the numerical Stroop task as a dual task in order to interfere with WM maintenance and WM dependent executive functions. In addition, we evaluated whether individual differences in WM capacity (WMC), assessed via complex span tasks, would affect learning. The results revealed a superiority for interleaved presentation in both single-task and dual-task conditions, as well as superior performance for participants with relatively high WMC. Importantly, there was no interaction between the presence of the dual task and interleaving, or WMC and interleaving, indicating that the benefits of interleaving are independent of WM. We also probed participants’ metacognitive judgments about whether blocking or interleaving was superior for learning, and found that most participants reported blocking was more effective, contrary to the reality that interleaving led to the best performance. These results support theories of the interleaving effect that are independent of working memory resources and pose a challenge to theories that rely on working memory mediated comparisons of items across trials.
Intensified visual clutter induces increased sympathetic signalling, poorer postural control, and faster torsional eye movements during visual rotation

Many dizzy patients express a hypersensitivity to visual motion and clutter. This study aims to investigate how exposure to rotating visual clutter affects ocular torsion, vertical skewing, body-sway, the autonomic pupillary response, and the subjective feeling of discomfort to the stimulation. Sixteen healthy subjects were exposed to 20 seconds rotational visual stimulation (72 deg/s; 50 deg visual field). Visual stimuli were comprised of black lines on a white background, presented at low and high intensity levels of visual clutter, holding 19 lines and 38 lines respectively. Ocular torsion and vertical skewing were recorded using the Chronos Eye Tracker, which also measured pupil size as a reflection of the autonomic response. Postural control was evaluated by measuring body-sway area on the Wii Balance Board. Values were compared to data retrieved 20 seconds before and after the optokinetic stimulation, as subjects viewed the stationary visual scene. The high intensity stimulus resulted in significantly higher torsional velocities. Subjects who were exposed to low intensity first exhibited higher velocities for both intensities. Both pupil size and body sway increased for the higher intensity to both the moving and stationary visual scene, and were positively correlated to torsional velocity. In conclusion, exposure to visual clutter was reflected in the eye movement response, changes in postural control, and the autonomic response. This response may hold clinical utility when assessing patients suffering from visual motion hypersensitivity, while also providing some context as to why some healthy people feel discomfort in visually cluttered surroundings.
Clinical significance of topoisomerase‐II expression in patients with advanced non‐small cell lung cancer treated with amrubicin

Amrubicin chemotherapy is a treatment option for patients with non‐small cell lung cancer (NSCLC) after third‐line treatment in Japan. Although topoisomerase‐II (Topo‐II), a target of amrubicin, has been reported to be a prognostic or predictive marker for chemosensitivity and clinical outcomes in various types of malignancies, its effects in the Japanese population remain unknown.
Factor VIII: the protein, cloning its gene, synthetic factor and now – 35 years later – gene therapy; what happened in between?

The foundation of haemophilia A therapy in the last 35 years has been critically dependent on isolation of the Factor VIII (FVIII) protein and discovery of the cDNA sequence of the FVIII gene, published in 1984. Identification of the FVIII sequence resulted in a new era of recombinant concentrates and led to significant improvements in safety, set against the tragedy of widespread HIV and hepatitis infections in haemophilia patients from contaminated plasma‐based products. We chronicle the scientific methods and race leading up to the publication of the FVIII DNA sequence and the legacy that follows through to revolutionary gene therapy treatment in clinical trials today.
Open-label phase 3 continuation study of cholic acid in patients with inborn errors of bile acid synthesis.

BACKGROUND In patients with bile acid synthesis disorders (BASD), impairment in the primary bile acid synthetic pathway leads to reduced primary bile acids, upregulated synthesis of cholesterol, and production and accumulation of hepatotoxic atypical bile acids. Primary bile acid therapy downregulates bile acid synthesis, reduces the production of hepatotoxic intermediates, and produces a functional bile acid pool fostering normal liver function. METHODS This phase 3, open-label, single-arm study included patients with BASD who had received cholic acid (10-15 mg/kg/day) as part of a previous study, or were newly diagnosed. Efficacy assessments included urinary atypical bile acids; serum liver chemistries; body weight and height. Efficacy analyses compared baseline with worst post-baseline response (primary) or best post-baseline response (sensitivity). Treatment-emergent adverse events (TEAEs) were summarized. RESULTS Of 53 total patients (single enzyme defects, n = 41; Zellweger spectrum disorders, n = 12), 22 (42%) were treatment-naïve and 31 (58%) were on cholic acid from a previous study. Mean age at diagnosis was 55 months, and at current study baseline was 9 years. Using baseline-to-best post-baseline analyses, statistically significant improvements in urinary bile acids (P = 0.003), height (P < 0.001), and body weight (P < 0.001) were observed. Serum alanine aminotransferase and aspartate aminotransferase levels tended to decrease from baseline in treatment-naïve patients following cholic acid treatment and remained stable in previously treated patients. Treatment-naïve patients improved in all baseline-to-best post-baseline analyses. The most common TEAE was upper respiratory tract infection (17%). SUMMARY/CONCLUSIONS Oral cholic acid provides a safe and efficacious short- and long-term therapy for patients with BASD.
Daily energy expenditure in white storks is lower after fledging than in the nest

ABSTRACT Many juvenile birds turn into long-distance migrants within weeks of fledging. This transition involves upheavals in their energy management as major changes in growth and activity occur. Understanding such ontogenetic transitions in energy allocation has been difficult because collecting continuous data on energy costs in wild developing birds was previously largely impossible. Here, we continuously measured heart rate and fine-scale movements of 20 free-living juvenile white storks (Ciconia ciconia) using on-board bio-loggers to explore individual and environmental factors relating to daily mean heart rate. In addition, we explored which specific energy management strategy storks use during these crucial early life stages. We found that daily mean heart rate increased with overall movement activity, and increasing body temperature, but that it decreased with age. Further, we found that during the nestling period, when growth costs are high, activity costs are low, and post-fledging that activity costs are increased while maintenance costs are low, indicating a constraint on overall energy use in both phases. Our observations are consistent with the hypothesis that individuals invested more energy per unit time while still in the nest than after fledging despite the high costs of flight. Summary: Continuous measurement of heart rate and fine-scale movements of free-living juvenile white storks (Ciconia ciconia) using on-board bio-loggers reveals individual and environmental factors relating to daily mean heart rate.
Extended cognition in plants: is it possible?

ABSTRACT Plants do not possess brains or neurons. However, they present astonishingly complex behaviors such as information acquisition, memory, learning, decision making, etc., which helps these sessile organisms deal with their ever-changing environments. As a consequence, they have been proposed to be cognitive and intelligent, an idea which is becoming increasingly accepted. However, how plant cognition could operate without a nervous central system remains poorly understood and new insights on this topic are urgently needed. According to the Extended Cognition hypothesis, cognition may also occur beyond the limits of the body, encompassing objects from the environment. This was shown possible in humans and spiders, who actively manipulate their external environment to extend their cognitive capacity. Here, we propose that extended cognition may also be found in plants and could partly explain the complexity of plant behavior. We suggest that plants can extend their cognitive abilities to the environment they manipulate through the root influence zone and the mycorrhizal fungi that associate with them. The possibility of a cognitive process involving organisms from different kingdoms is exciting and worthwhile exploring as it may provide key insights into the origin and evolution of cognition.
Loneliness and cortisol are associated with social network regulation

ABSTRACT This study examines how loneliness and the body’s stress response system interact to regulate social connections. We suggest that the drive to reconnect signaled by loneliness can be accompanied physiologically by the production of cortisol, which can offer supportive coping resources. Thus, we investigated how loneliness, cortisol levels, and their interaction predicted changes in network connections in a social organization. Participants (n = 193; 53% female) provided friendship network data at two times. At time 1, participants reported on loneliness and donated saliva (later assayed for cortisol). Results revealed that concurrently, lonely individuals reported fewer friendships, whereas over time, they named more friends. These results support the hypothesis that loneliness is a signal to develop connections. We also explored whom lonely individuals befriended over time. Results showed that cortisol significantly moderated the preference for friends with a similar level of loneliness. Specifically, lonely individuals with higher cortisol befriended those who were less lonely over those who were lonelier. Thus, cortisol levels may serve an adaptive function in mobilizing resources to develop connections that fulfill social belongingness needs. Results supported the theorized signaling function of loneliness and revealed that loneliness and the stress response system interact to shape social connections.
The mediating role of psychological capital on the relation between distress and empathy of medical residents: a cross-sectional survey

ABSTRACT Background: Medical residents usually suffer from work overload and experience both personal and professional distress, which affects their level of the empathy to patients. Psychological capital (PsyCap) is a psychological resource that is negatively associated with indicators of distress. Objective: This study explored the potential mediating effect of PsyCap on the relationship between distress and empathy, which may help healthcare professionals in their defense of empathy erosion due to distress. Design: A total of 620 first-year residents were recruited for this cross-sectional survey. Empathy and PsyCap of residents were assessed by the Chinese version of the Jefferson Scale of Physician Empathy and the Psychological Capital Questionnaire, respectively. In this study, both personal and professional aspects contributing to resident distress were investigated by the Satisfaction with Life Scale and an occupational distress scale. T-tests and one-way ANOVA were used to test differences in empathy of residents. Pearson’s correlation was used to examine correlations between distress, PsyCap, and empathy. Structured equation modeling was used to conduct the pathway analysis to test the mediating effect of PsyCap on the association between distress and empathy. Results: 537 residents (86.6%) completed the survey. Distress, empathy, and PsyCap were significantly correlated (P < .01) and in the expected directions. The first step analysis showed that as distress increased, the empathy of residents significantly decreased (P < .01), with the direct effect coefficient being 0.265. When PsyCap was included, the direct effect coefficient decreased to 0.033. This indirect effect was significant (P < .01). The variance accounted for was 81.14%, which indicated a partial mediating effect of PsyCap. Conclusions: PsyCap may serve a significant protective role against the impact of distress on the level of empathy of medical residents. In addition to reducing distress, PsyCap development could be considered in empathy decline prevention and empathy cultivating strategies. Abbreviations: PsyCap: Psychological capital; JSPE: Jefferson Scale of Physician Empathy; PCQ: Psychological Capital Questionnaire; SWLS: Satisfaction with Life Scale; VAF: Variance accounted for; SD: Standard deviation.
A linguistically-driven response categorisation protocol for Arabic nouns and verbs: clinical and research applications

ABSTRACT Research into language breakdown in Arabic has been growing in the last two decades. The field, however, remains challenged by the lack of assessment materials, normative databases, and standards for categorising responses from participants with language impairment. The aim of this paper is to introduce a linguistically driven protocol for categorising responses from Arabic-speaking patients and healthy participants in language production tasks. The protocol is informed by Arabic morpho-syntactic/morpho-phonological features such as inflection for gender, person, and number; and on a larger scale agreement in noun phrases and verb phrases. The emerging error categories are applicable to different Arabic varieties and sub-varieties. The data supporting the resulting error categorisation protocol stem from responses from patients with aphasia performing various production tasks.