Miracle-dz/UniFAR-FTUs huggingface dataset:
Child Witness Expressions of Certainty Are Informative

Children are frequently witnesses of crime. In the witness literature and legal systems, children are often deemed to have unreliable memories. Yet, in the basic developmental literature, young children can monitor their memory. To address these contradictory conclusions, we reanalyzed the confidence–accuracy relationship in basic and applied research. Confidence provided considerable information about memory accuracy, from at least age 8, but possibly younger. We also conducted an experiment where children in young (4–6 years), middle (7–9 years), and late (10–17 years) childhood (N = 2,205) watched a person in a video and then identified that person from a police lineup. Children provided a confidence rating (an explicit judgment) and used an interactive lineup—in which the lineup faces can be rotated—and we analyzed children’s viewing behavior (an implicit measure of metacognition). A strong confidence–accuracy relationship was observed from age 10 and an emerging relationship from age 7. A constant likelihood ratio signal-detection model can be used to understand these findings. Moreover, in all ages, interactive viewing behavior differed in children who made correct versus incorrect suspect identifications. Our research reconciles the apparent divide between applied and basic research findings and suggests that the fundamental architecture of metacognition that has previously been evidenced in basic list-learning paradigms also underlies performance on complex applied tasks. Contrary to what is believed by legal practitioners, but similar to what has been found in the basic literature, identifications made by children can be reliable when appropriate metacognitive measures are used to estimate accuracy.
The Reactive Species Interactome in the brain.

SIGNIFICANCE Redox pioneer Helmut Sies attempted to explain reactive species' challenges faced by organelles, cells, tissues, and organs via three complementary definitions: (1) oxidative stress, i.e. the disturbance in the prooxidant-antioxidant defense balance in favor of the prooxidants, (2) oxidative eustress, the low physiological exposure to prooxidants, and (3) oxidative distress, the supraphysiological exposure to prooxidants. Recent Advances: Identification, concentration and interactions are the most important elements to improve our understanding of reactive species in physiology and pathology. In this context, the reactive species interactome (RSI) is a new multilevel redox regulatory system that identifies reactive species families, reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS), and integrates their interactions with their downstream biological targets. CRITICAL ISSUES We propose a united view to fully combine reactive species identification, oxidative eustress and distress, and the RSI system. In this view, we also propose including the forgotten reactive carbonyl species (RCS), an increasingly rediscovered reactive species family related to the other reactive families, and key enzymes within the RSI. We focus on brain physiology and pathology to demonstrate why this united view should be considered. FUTURE DIRECTIONS More studies are needed for an improved understanding of the contributions of reactive species through their identification, concentration, and interactions, including in the brain. Appreciating the reactive species interactome in its entirety should unveil new molecular players and mechanisms in physiology and pathology in the brain and elsewhere.
Clonal dynamics of tumor-infiltrating T-cell receptor beta-chain repertoires in the peripheral blood in response to concurrent chemoradiotherapy for Epstein–Barr virus-associated nasopharyngeal carcinoma

ABSTRACT The nasopharyngeal epithelium is highly susceptible to pathogenic infection. More than 95% of nasopharyngeal carcinomas (NPCs) are Epstein–Barr virus (EBV)-associated epithelial cancers densely infiltrated with EBV-free lymphocytes. It remains unknown whether the immune modulating effects of concurrent chemoradiotherapy (CCRT) on the tumor-infiltrating T-cell priming against EBV, tumor-associated antigens, and/or neoantigens can elicit systemic anti-tumor immunity and decrease recurrence or distant metastasis. Using matched EBV-associated NPCs, nasopharyngeal mucosal tissues, and longitudinal serial peripheral blood samples, we explored the spatiotemporal and quantitative changes in expansion and contraction of intratumoral T-cell clonotypes (ITCs) in peripheral blood samples from before, during, and after CCRT. The pre-treatment nasopharyngeal ITC repertoire contained unique mucosa-resident and commonly system-shared T-cell receptors (TCRs), portraying an individualized tumor-associated and/or metagenomic landscape. We found that the long-term disease-free patients had significantly more robust unique mucosa-resident ITCs that migrated into and expanded in the peripheral blood after CCRT than in the patients with recurrence or distant metastasis (Mann–Whitney U test, p = .0110). However, the system-shared productive ITC TCRs specific to the common viruses, such as EBV, cytomegalovirus, and influenzaA, in all the patients with and without recurrence demonstrated almost no expansion after CCRT. Thus, these findings underline the importance of determining the impact of unique intratumoral immune responses, reflected in the peripheral blood, on disease prognosis after treatment and challenge of mechanistically understanding the common systemic immune evasion of EBV in NPC patients.
Outcomes of endoscopic resection for superficial duodenal tumors: 10 years’ experience in 18 Japanese high volume centers

Abstract Background Data on endoscopic resection (ER) for superficial duodenal epithelial tumors (SDETs) are insufficient owing to their rarity. There are two main ER techniques for SDETs: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). In addition, modified EMR techniques, such as underwater EMR (UEMR) and cold polypectomy, are becoming popular. We conducted a large-scale retrospective multicenter study to clarify the detailed outcomes of duodenal ER. Methods Patients with SDETs who underwent ER at 18 institutions from January 2008 to December 2018 were included. The rates of en bloc resection and delayed adverse events (AEs; defined as delayed bleeding or perforation) were analyzed. Local recurrence was analyzed using the Kaplan–Meier method. Results In total, 3107 patients (including 1017 undergoing ESD) were included. En bloc resection rates were 79.1 %, 78.6 %, 86.8 %, and 94.8 %, and delayed AE rates were 0.5 %, 2.2 %, 2.8 %, and 6.8 % for cold polypectomy, UEMR, EMR and ESD, respectively. The delayed AE rate was significantly higher in the ESD group than in non-ESD groups for lesions < 19 mm (7.4 % vs. 1.9 %; P < 0.001), but not for lesions > 20 mm (6.1 % vs. 7.1 %; P = 0.64). The local recurrence rate was significantly lower in the ESD group than in the non-ESD groups (P < 0.001). Furthermore, for lesions > 30 mm, the cumulative local recurrence rate at 2 years was 22.6 % in the non-ESD groups compared with only 1.6 % in the ESD group (P < 0.001). Conclusions ER outcomes for SDETs were generally acceptable. ESD by highly experienced endoscopists might be an option for very large SDETs.
Evaluation of the Low Carb Program Digital Intervention for the Self-Management of Type 2 Diabetes and Prediabetes in an NHS England General Practice: Single-Arm Prospective Study

Background Type 2 diabetes mellitus has serious health consequences, including blindness, amputation, and stroke. Researchers and clinicians are increasingly in agreement that type 2 diabetes may be effectively treated with a carbohydrate-reduced diet. Digital apps are increasingly used as an adjunct to traditional health care provisions to support remote self-management of long-term health conditions. Objective Our objective was to evaluate the real-world 12-month outcomes of patients prescribed the Low Carb Program digital health intervention at a primary care National Health Service (NHS) site. The Low Carb Program is a nutritionally focused, 12-session, digitally delivered, educational behavior change intervention for glycemic control and weight loss for adults with prediabetes and type 2 diabetes. The program educates and supports sustainable dietary changes focused on carbohydrate restriction by utilizing behavior change techniques, including goal setting, peer support, and behavioral self-monitoring, as well as personalized downloadable resources, including recipes and meal plans tailored to ethnicity, weekly shopping budget, and dietary preferences. Methods This study evaluated the real-world outcomes of patients recruited to the Low Carb Program at an NHS general practice in Southport, United Kingdom. All of the NHS patients recruited to the program were diagnosed with type 2 diabetes or prediabetes and were given access to the program at no cost. A total of 45 participants, with a mean age of 54.8 years (SD 13.2), were included in the study. Women made up 42% (19/45) of the sample. The mean hemoglobin A1c (HbA1c) of the sample was 56.7 mmol/mol (SD 16.95) and the mean body weight was 89.4 kg (SD 13.8). Results Of the 45 study participants recruited to the program, all of them (100%) activated their accounts and 37 (82%) individuals reported outcomes at 12 months. All 45 (100%) patients completed at least 40% of the lessons and 32 (71%) individuals completed more than nine out of 12 core lessons of the program. Glycemic control and weight loss improved, particularly for participants who completed more than nine core lessons in the program over 12 months. The mean HbA1c went from 58.8 mmol/mol at baseline to 54.0 mmol/mol, representing a mean reduction of 4.78 mmol/mol (SD 4.60; t31=5.87; P<.001). Results showed an average total body weight reduction of 4.17%, with an average weight reduction of 3.85 kg (SD 2.49; t31=9.27; P<.001) at the 12-month follow-up point. Conclusions A digital app prescribed to adults with type 2 diabetes and prediabetes in a primary care setting supporting a transition to a low-carbohydrate diet has been shown to be effective in improving glycemic control and enabling weight loss. Further research to understand more about factors affecting engagement with the app and further positive health implications would be valuable.
A Long‐Term Extension Study of Bevacizumab in Patients With Solid Tumors

Abstract Background Bevacizumab has been studied in numerous clinical trials in multiple types of cancer; however, patients may receive bevacizumab over an extended period of time. This study assessed the long‐term safety and tolerability of bevacizumab among patients with solid tumors. Materials and Methods Patients enrolled in a Roche/Genentech‐sponsored trial who had derived benefit from bevacizumab therapy as monotherapy or in combination with anticancer drugs were eligible for continuation of bevacizumab in this long‐term extension (LTE) study. The primary endpoints were the incidence of adverse events (AEs) of Common Terminology Criteria for AEs (CTCAE) grade ≥3 related to bevacizumab treatment, serious AEs (SAEs), and deaths. Results Ninety‐five patients with the following cancer types were enrolled in the LTE: ovarian cancer or peritoneal carcinoma (n = 41), non‐small cell lung cancer (n = 16), glioblastoma multiforme (n = 14), breast cancer (n = 11), colorectal cancer (n = 7), or renal cell carcinoma (n = 6). The median (range) duration of bevacizumab treatment was 15.6 (0.0–81.0) months during the LTE and 57.5 (16.4–134.9) months overall (parent trial + LTE), with three patients receiving bevacizumab for >10 years. Overall, 17 patients (17.9%) experienced SAEs, and 21 (22.1%) had a bevacizumab‐related AE of CTCAE grade ≥3 (proteinuria and hypertension were the most common). Four patients died: three from disease progression and one from an AE considered unrelated to bevacizumab. Conclusion The safety outcomes observed support the tolerability of long‐term bevacizumab in patients with various solid tumors, with a median extended treatment duration of almost 5 years overall and >10 years in some individual patients. ClinicalTrials.gov identifier: NCT01588184. Implications for Practice In this long‐term extension study of patients with solid tumors, the median duration of bevacizumab treatment (including parent trials) was just under 5 years, with a long‐term exposure in some patients of 7 to >10 years. Grade ≥3 adverse events related to bevacizumab were consistent with the established safety profile, with proteinuria and hypertension being the most common. Patients received bevacizumab over an extended period of time (beyond the length of most clinical trials), and the overall safety outcomes observed support the tolerability of long‐term bevacizumab treatment in patients with solid tumors, with clinical benefit achieved over an extended period.
miR-328a-3p stimulates endothelial cell migration and tubulogenesis

Endothelial cells have important biological roles after peripheral nerve injury by forming blood vessels within the nerve gap and guiding Schwann cell migration. MicroRNAs (miRNAs/miRs) affect cellular behavior and regulate a wide variety of physiological and pathological activities, including peripheral nerve regeneration. Emerging studies have identified the essential roles of miRNAs in the phenotype modulation of Schwann cells, while the effects of miRNAs on endothelial cells have remained to be thoroughly investigated. miR-328a-3p was differentially expressed in peripheral nerve stumps after nerve injury. In the present study, the effects of miR-328a-3p on biological functions of endothelial cells were determined by transfecting cultured human umbilical vein endothelial cells (HUVECs) with miR-328a-3p mimics or inhibitor. Transfection with miR-328a-3p mimics led to slightly decreased HUVEC proliferation and robustly increased HUVEC migration and tubulogenesis, while transfection with miR-328a-3p inhibitor led to opposite results. Using bioinformatics analysis, potential regulators and effectors of miR-328a-3p were further discovered and a miR-328a-3p-centered competing endogenous RNA network was constructed. Collectively, the present study demonstrated that dysregulated miR-328a-3p after peripheral nerve injury may affect the migration and angiogenesis of endothelial cells and contribute to peripheral nerve regeneration.
Hypoparathyroidism Associated with Vascular Centrum Semiovale Calcifications

We present an 86-year-old woman with a progressive cognitive deficit. The patient had a recent history of idiopathic hypoparathyroidism (parathyroid hormone level < 1ng/l, normal range = 15–88), discovered following decreased calcium blood levels (1.45mmol/l, normal range = 2.2–2.55). Computed tomography (Fig, axial [A] and coronal [B] 10mm-thick multiplanar reconstruction images), performed because of persistent cognitive deficit despite correction of hypocalcemia, showed bilateral (peri)vascular centrum semiovale calcifications, and dentate nuclei calcifications (Fig, C, arrowheads) in the absence of basal ganglia involvement (Fig, D) on standard axial views. Centrum semiovale perivascular spaces were not dilated on magnetic resonance imaging. We attributed the (peri)vascular spaces and dentate nuclei calcifications to the associated hypoparathyroidism (often referred to as Fahr syndrome or disease). Delacour described, almost a century before Fahr’s original report, an 81-year-old demented patient with bilateral cerebral calcifications most prominent in the striatum at postmortem, corresponding to what would now probably be called striopallidal or striopallidodentate calcifications (often further categorized as idiopathic vs symptomatic, and sporadic vs familial). This latter condition is often erroneously called Fahr syndrome or disease. Actually, the original report of Theodor Fahr in 1930 described a postmortem analysis of a patient (possibly suffering from hypoparathyroidism) with diffuse idiopathic arterial and venous calcification predominant in the white matter (and nearly absent in the basal ganglia), as in our patient. Basal ganglia calcification, and not white matter calcification, has been reported to be associated with hypoparathyroidism. Fahr’s original report and our patient probably represent rare cases of hypoparathyroidism with
Focal segmental glomerulosclerosis histologic variants and renal outcomes based on nephrotic syndrome, immunosuppression, and proteinuria remission.

BACKGROUND The associations of focal segmental glomerulosclerosis (FSGS) histologic variants with renal outcomes have rarely been investigated comprehensively by clinically relevant subgroups in this modern age. METHODS Data on 304 (173 nephrotic and 131 non-nephrotic) patients with biopsy-confirmed FSGS from 2010 to 2013 were analyzed using the Japanese nationwide renal biopsy registry. The primary outcome was a composite of a 30% decline in estimated glomerular filtration rate or progression to end stage kidney disease 5 years from the biopsy. We compared outcomes of FSGS variants according to the Columbia classification using survival analyses. Subgroup analyses were performed based on nephrotic syndrome (NS), immunosuppression, and proteinuria remission (PR, proteinuria <0.3 g/day) during follow-up. Additionally, associations of NS, immunosuppression, and PR with outcomes were examined for each variant. RESULTS The distribution of variants was 48% (n = 145) FSGS not otherwise specified (NOS), 19% (n = 57) tip, 15% (n = 47) perihilar, 13% (n = 40) cellular, and 5% (n = 15) collapsing. The outcome event occurred in 87 patients (29%). No significant differences in the outcome were found among the variants. Subgroup analyses yielded similar results. However, there was a trend toward improved outcome in patients with PR irrespective of variants (hazard ratio adjusted for histologic variant and potential confounders [adjusted HR]: 0.19 [95% confidence interval (CI), 0.10-0.34]). NS was marginally associated with better outcome compared with non-NS (adjusted HR: 0.50 [95% CI, 0.25-1.01]. CONCLUSIONS FSGS variants alone might not have significant impacts on the renal outcome after 5 years, while PR could be predictive of improved renal prognosis for any variant. Specific strategies and interventions to achieve PR for each variant should be implemented for better renal outcomes.
Evolution and prevention of meltback etching: Case study of semipolar GaN growth on patterned silicon substrates

Meltback etching, a deteriorating chemical reaction occurring between gallium and silicon under typical metal organic chemical vapor deposition growth conditions, is a common problem that often limits the development of GaN on silicon substrates, in particular, patterned substrates, and therefore must be circumvented. To further understand this reaction, energy dispersive X-ray spectroscopy was performed in cross-section, and a proposed 2-dimensional model on how meltback etching evolves throughout the growth process is discussed, which indicated an inter-diffusion reaction occurring primarily between gallium and silicon where gallium from GaN diffuses into the silicon substrate while silicon from the substrate diffuses out and incorporates into the GaN crystal. Moreover, we demonstrate an anisotropic behavior of the gallium penetrating the silicon substrate, which has shown to be delimited by the Si {111} planes. Finally, an approach to prevent meltback etching by changing the fractions of nitrogen and h.
Risk factors associated with intra-stent restenosis after percutaneous coronary intervention

The present study aimed to explore the correlations between clinical, biological, imagistic and procedural factors with the risk of intra-stent restenosis (ISR) in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI). An observational cross-sectional study was conducted in a high-volume PCI center over a period of 2 years. A total of 235 consecutive patients diagnosed with angina or acute coronary syndrome treated by PCI were included in the study. Diagnosis of ISR was documented by coronary angiography in patients with suggestive coronary symptoms and ischemic changes in non-invasive or invasive paraclinical investigations. Thus, they were assigned to two groups: With or without ISR. All patients underwent clinical and laboratory examination, providing clinical and paraclinical variables that could be considered risk factors for ISR. Current smokers [risk ratio (RR)=1.63; 95% confidence interval (95% CI): 1.25-2.13], arterial hypertension (RR=1.86; 95% CI: 1.41-2.45), diabetes (RR=1.83; 95% CI: 1.42-2.36), high C-reactive protein (CRP) levels (RR=1.44; 95% CI: 0.93-2.24), chronic kidney disease (CKD) (RR=1.90; 95% CI: 1.53-2.36) and thrombolysis in myocardial infarction (TIMI) score were found to have a significant role in estimating the risk for ISR. Moreover, the ISR group (119 patients) presented with a lower stent inflation pressure when compared to the control group (116 patients) (14.47 vs. 16.14 mmHg, P=0.004). An increased mean stent diameter used for PCI was not associated with a high ISR incidence (P=0.810) as well as complex coronary treated lesions with longer stents (mean length of 24.98 mm in patients without ISR vs. 25.22 mm in patients with ISR; P=0.311). There was an estimated two times higher risk (RR=2.13; 95% CI: 1.17-3.88) concerning multi-stenting and restenosis degree >70%. To conclude, smoking, hypertension, diabetes mellitus, high CRP levels, CKD, TIMI score, stent type, low pressure for stent implantation and multi-stenting were found to be associated with ISR in patients following PCI. Therefore, a close follow-up should be targeted in such patients.
Prognosis of poorly cohesive gastric cancer after complete cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CYTO-CHIP study).

BACKGROUND The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.