Miracle-dz/UniFAR-FTUs huggingface dataset:
Nuclear FGFR1 Regulates Gene Transcription and Promotes Antiestrogen Resistance in ER+ Breast Cancer

Purpose: FGFR1 overexpression has been associated with endocrine resistance in ER+ breast cancer. We found FGFR1 localized in the nucleus of breast cancer cells in primary tumors resistant to estrogen suppression. We investigated a role of nuclear FGFR1 on gene transcription and antiestrogen resistance. Experimental Design: Tumors from patients treated with letrozole were subjected to Ki67 and FGFR1 IHC. MCF7 cells were transduced with FGFR1(SP-)(NLS) to promote nuclear FGFR1 overexpression. FGFR1 genomic activity in ER+/FGFR1-amplified breast cancer cells ± FOXA1 siRNA or ± the FGFR tyrosine kinase inhibitor (TKI) erdafitinib was examined by chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq). The nuclear and chromatin-bound FGFR1 interactome was investigated by mass spectrometry (MS). Results: High nuclear FGFR1 expression in ER+ primary tumors positively correlated with post-letrozole Ki67 values. Nuclear FGFR1 overexpression influenced gene transcription and promoted resistance to estrogen suppression and to fulvestrant in vivo. A gene expression signature induced by nuclear FGFR1 correlated with shorter survival in the METABRIC cohort of patients treated with antiestrogens. ChIP-Seq revealed FGFR1 occupancy at transcription start sites, overlapping with active transcription histone marks. MS analysis of the nuclear FGFR1 interactome identified phosphorylated RNA-Polymerase II and FOXA1, with FOXA1 RNAi impairing FGFR1 recruitment to chromatin. Treatment with erdafitinib did not impair nuclear FGFR1 translocation and genomic activity. Conclusions: These data suggest nuclear FGFR1 contributes to endocrine resistance by modulating gene transcription in ER+ breast cancer. Nuclear FGFR1 activity was unaffected by FGFR TKIs, thus supporting the development of treatment strategies to inhibit nuclear FGFR1 in ER+/FGFR1 overexpressing breast cancer.
Variablity in vastus lateralis fiber type distribution, fiber size and myonuclear content along and the between legs.

Human skeletal muscle characteristics such as fiber type composition, fiber size and myonuclear content are widely studied in clinical and sports related contexts. Being aware of the methodological and biological variability of the characteristics is a critical aspect in study design and outcome interpretation, but comprehensive data on the variability of morphological features in human skeletal muscle is currently limited. Accordingly, in the present study, m. vastus lateralis biopsies (10 per subject) from young and healthy individuals, collected in a systematic manner, were analyzed for various characteristics using immunohistochemistry (n=7) and SDS-PAGE (n=25). None of the analyzed parameters; fiber type % (FT%), type I and II CSA (fCSA), percentage fiber type area (fCSA%), myosin heavy chain composition (MyHC%), type IIX content, myonuclear content or myonuclear domain varied in a systematic manner longitudinally along the muscle or between the two legs. The average within subject coefficient of variation for FT%, fCSA, fCSA%, and MyHC% ranged between 13-18%, but was only 5% for fiber specific myonuclear content, which reduced the variability for myonuclear domain size to 11-12%. Pure type IIX fibers and type IIX MyHC were randomly distributed and present in <24% of the analyzed samples, with the average content being 0.1 and 1.1%, respectively. In conclusion, leg or longitudinal orientation does not seem to be an important aspect to consider when investigating human vastus lateralis characteristics. However, single muscle biopsies should preferably not be used when studying fiber type and fiber size related aspects given the notable sample to sample variability.
Reward-enhancing effects of d-amphetamine and its interactions with nicotine were greater in female rats and persisted across schedules of reinforcement

Nicotine enhances the value of environmental stimuli and rewards, and reward enhancement can maintain nicotine consumption. Stimulants such as d-amphetamine are misused more by women and are commonly co-used with nicotine. d-Amphetamine potentiates nicotine’s effects in human and animal research. To date, there are no published studies examining this interaction in a reward-enhancement task. The current study sought to investigate the reward-enhancing effects of nicotine alongside and coadministered with d-amphetamine. Further, we evaluated the persistence of reward enhancement across ratio and temporal schedules of reinforcement. We used 10 male and 10 female Sprague–Dawley rats. Enhancement was assessed within subjects by examining active lever pressing for a visual stimulus reinforcer on variable ratio 3, variable interval 30 s and variable time 30 s – variable ratio 3 schedules. Before 1-h sessions, rats received one injection of saline, 0.1 or 0.3 mg/kg d-amphetamine and one of saline or 0.4 mg/kg nicotine, making six possible drug combinations (saline + saline, saline + nicotine, 0.1 d-amphetamine + aline, 0.1 d-amphetamine + nicotine, 0.3 d-amphetamine + saline and 0.3 d-amphetamine + nicotine) experienced in a randomized order by each rat. When d-amphetamine was coadministered with nicotine, we found an interaction effect on reward enhancement that persisted across schedules of reinforcement. Males and females exhibited reward enhancement by 0.3 d-amphetamine, while only females showed reward enhancement by 0.1 d-amphetamine. Further, females responded more for the visual stimulus than males in all d-amphetamine conditions. Future studies should assess how reward enhancement is involved in high nicotine-amphetamine comorbidity rates and enhanced amphetamine misuse in women.
Victims and Perpetrators of Bullying in Physical Education Lessons: The Role of Peer Support, Weight Status, Gender, and Age in Polish Adolescents

Physical education is a space in which adolescents may become the victims or perpetrators of bullying. The aim of this study was to evaluate the relationship between being a victim or perpetrator of physical, verbal, or social bullying in physical education, and peer support, gender, weight status, and age. The sample consisted of 2, 848 adolescents (1, 512 girls and 1, 336 boys) aged 14–16 from Poland. The participants’ body mass index was determined based on their measured height and weight. The Health Behaviour in School-Aged Children questionnaire was used to assess whether the participants were victims or perpetrators of bullying. Peer support during physical education was assessed using the modified Teacher and Classmate Support Scale. The analysis of logistic regressions revealed that low peer support increased the probability of being the victim of physical, verbal, and social bullying (odds ratio [OR], 1.58–2.91) and becoming a perpetrator of bullying (OR, 1.14–1.37) in physical education. Additionally, being overweight increased the likelihood of being a verbal victim (OR, 1.39) and being obese raised the probability of becoming social victim (OR, 1.60). Boys more often experienced (OR, 1.12–2.06) and caused bullying (OR, 1.25–1.89) than girls. Moreover, victims were mainly younger (14-year-old) students (OR, 1.16–1.21), while perpetrators were more often older (15- and 16-year-old) adolescents (OR, 1.12–1.20). This research indicated that peer support can play a key role in preventing bullying in physical education. Physical education teachers should pay special attention to unpopular and rejected students because they most often become the victims and perpetrators of bullying. Creating a climate that fosters the development of high peer support might protect adolescents from becoming a victim—and a perpetrator—of bullying in physical education.
Canine induced pluripotent stem cell maintenance under feeder‐free and chemically‐defined conditions

Canine induced pluripotent stem cells (ciPSCs) provide a platform for regenerative veterinary medicine, disease modeling, and drug discovery. However, in the conventional method, ciPSCs are maintained using chemically‐undefined media containing unknown animal components under on‐murine embryonic fibroblast feeder conditions, which were reported to modify cell surface of iPSCs and increases the risk of immune rejection when the cells are transplanted into patients. Moreover, in the conventional method, ciPSCs are mechanically passaged, which requires much time and effort. Therefore, the large‐scale expansion of ciPSCs is difficult, which should be resolved for using ciPSCs in clinical application and research. Here, it was shown that StemFit® AK02N and iMatrix‐511 could maintain the pluripotency of ciPSCs using conventional culture method. Furthermore, it was demonstrated that the feeder‐free and chemically‐defined ciPSC culture systems using StemFit® AK02N and iMatrix‐511 could stably maintain and allow the easy expansion of ciPSCs generated using N2B27 and StemFit® AK02N, without causing karyotype abnormalities. ciPSCs expressed several pluripotency markers and formed teratomas, including cells derived from three germ layers.
Genomic landscape of ground glass opacities (GGOs) in East Asians

Background Understanding the genomic landscape of early-stage lung adenocarcinoma (LUAD) may provide new insights into the molecular evolution in the early stages of LUAD. Methods Through sequencing of 79 spatially distinct regions from 37 patients with ground glass opacities (GGOs), we provided a comprehensive mutational landscape of GGOs, highlighting the importance of ancestry differences. Results Our study had several interesting features. First, epidermal growth factor receptor (EGFR), BRAF (v-RAF murine sarcoma viral oncogene homologue B1), and ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2, also known as HER2) were more frequently mutated in our study, which supports the notion that EGFR is considered to be a major driver and tends to drive the occurrence of LUAD. Second, Signature 1, Signature 3, and Signature 6 were identified in patients with GGOs. Our results further suggested that Signature 1 was more prominent among early mutations. Third, compared with LUADs, GGOs exhibited significantly lower levers of arm-level copy number variation (CNV)—which alter the diploid status of DNA, and lower focal CNVs. Conclusions In our study, 79 samples of patients were included to analyze the GGO gene profile, revealing the genetic heterogeneity of GGO in East Asian population, and providing guidance for prognosis analysis of GGO patients by comparison with LUAD. Our study revealed that GGOs had fewer genomic alterations and simpler genomic profiles than LUADs. The most commonly altered processes were related to the receptor tyrosine kinase (RTK)/Ras/phosphatidylinositol-3-kinase (PI3K) signaling pathways in GGOs, and EGFR alterations were the dominant genetic changes across all targetable somatic changes.
Acceptability and feasibility of S-1 plus cisplatin adjuvant chemotherapy for completely resected non-small cell lung cancer: an open-label, single arm, multicenter, phase 2 trial

Background Although platinum-based chemotherapy is accepted as adjuvant chemotherapy for resectable advanced non-small cell lung cancer (NSCLC), its completion rate is low due to severe adverse events. S-1 plus cisplatin is associated with relatively low toxicity and an unimpaired quality of life, and has been used for unresectable advanced lung cancer. We investigated the acceptability and feasibility of combination therapy with S-1 plus cisplatin as postoperative adjuvant chemotherapy following complete resection of pathological stage II-IIIA NSCLC. Methods Enrolled patients received oral S-1 at a dose depending on their body weight twice daily for 21 days with intravenous cisplatin 60 mg/m2 on day 8, with 1 cycle comprising 5 weeks and 4 cycles. Patients received standard precautions against adverse events and received standard treatment when adverse events occurred. The primary endpoint was completion rate; secondary endpoints included safety, status of drug administration, disease-free survival (DFS), and overall survival (OS). Results A total of 19 patients [14 men, 5 women; mean age, 59.1 years; mean body surface area, 1.688 m2; 17 with an Eastern Cooperative Oncology Group performance status (PS) of 0 and 2 with a PS of 1; 7 (36.8%) with stage II disease and 12 (63.2%) with stage IIIA disease] were enrolled. The rate of completion of 4 cycles was 68.4%. Grade 3 adverse events that occurred in ≥10% of patients included neutropenia (21.1%), nausea (21.1%), and anorexia (15.8%). No grade 4 adverse events, febrile neutropenia, or treatment-related deaths occurred. The mean relative dose intensity (RDI) was 79% for S-1 and 80% for cisplatin. The 2-year DFS rate was 42.1%, and 2-year OS rate was 83.3%. Conclusions This study demonstrated the acceptability and feasibility of using S-1 plus cisplatin as adjuvant chemotherapy. Trial registration This study was registered on the UMIN clinical study registration site (protocol ID: UMIN000016191) on December 1, 2015.
Comparison of multiple statistical models for the development of clinical prediction scores to detect advanced colorectal neoplasms in asymptomatic Thai patients

Abstract A good clinical prediction score can help in the risk stratification of patients with colorectal cancer (CRC) undergoing colonoscopy screening. The aim of our study was to compare model performance of binary logistic regression (BLR), polytomous logistic regression (PLR), and classification and regression tree (CART) between the clinical prediction scores of advanced colorectal neoplasia (ACN) in asymptomatic Thai patients. We conducted a cross-sectional study of 1311 asymptomatic Thai patients to develop a clinical prediction model. The possible predictive variables included sex, age, body mass index, family history of CRC in first-degree relatives, smoking, diabetes mellitus, and the fecal immunochemical test in the univariate analysis. Variables with a P value of . 1 were included in the multivariable analysis, using the BLR, CART, and PLR models. Model performance, including the area under the receiver operator characteristic curve (AUROC), was compared between the model types. ACN was diagnosed in 53 patients (4.04%). The AUROCs were not significantly different between the BLR and CART models for ACN prediction with an AUROC of 0.774 (95% confidence interval [95% CI]: 0.706–0.842) and 0.765 (95% CI: 0.698–0.832), respectively (P = .712). A significant difference was observed between the PLR and CART models in predicting average to moderate ACN risk with an AUROC of 0.767 (95% CI: 0.695–0.839 vs AUROC 0.675 [95% CI: 0.599–0.751], respectively; P = .009). The BLR and CART models yielded similar accuracies for the prediction of ACN in Thai patients. The PLR model provided higher accuracy for ACN prediction than the CART model.
Emotional learning retroactively enhances item memory but distorts source attribution

An adaptive memory system should prioritize information surrounding a powerful learning event that may prove useful for predicting future meaningful events. The behavioral tagging hypothesis provides a mechanistic framework to interpret how weak experiences persist as durable memories through temporal association with a strong experience. Memories are composed of multiple elements, and different mnemonic aspects of the same experience may be uniquely affected by mechanisms that retroactively modulate a weakly encoded memory. Here, we investigated how emotional learning affects item and source memory for related events encoded close in time. Participants encoded trial-unique category exemplars before, during, and after Pavlovian fear conditioning. Selective retroactive enhancements in 24-h item memory were accompanied by a bias to misattribute items to the temporal context of fear conditioning. The strength of this source memory bias correlated with participants’ retroactive item memory enhancement, and source misattribution to the emotional context predicted whether items were remembered overall. In the framework of behavioral tagging: Memory attribution was biased to the temporal context of the stronger event that provided the putative source of memory stabilization for the weaker event. We additionally found that fear conditioning selectively and retroactively enhanced stimulus typicality ratings for related items, and that stimulus typicality also predicted overall item memory. Collectively, these results provide new evidence that items related to emotional learning are misattributed to the temporal context of the emotional event and judged to be more representative of their semantic category. Both processes may facilitate memory retrieval for related events encoded close in time.
Correlation between Serum Lipid Parameters and Interleukin-10 Concentration in Obese Individuals

Background The role of interleukin-10 (IL-10) in humans is controversial because IL-10 has been proposed to exhibit both pro- and anti-inflammatory effects. We aimed to determine the relationships between the changes in these parameters in obese individuals participating in a weight-reduction program. Methods We measured cardiometabolic parameters including lipid profile and serum IL-10 concentration before and after completion of a 12-week weight-reduction program in 63 non-diabetic obese subjects with a body mass index ≥27 kg/m2 who had comorbid hypertension or dyslipidemia. All the participants were provided with individual intervention sessions designed to implement lifestyle modifications and administered 120 mg orlistat three times daily for 12 weeks. The relationships between changes in serum IL-10 concentration and changes in cardiometabolic risk factors were analyzed. Results Changes in serum IL-10 concentration were significantly negatively correlated with changes in total cholesterol (r=−0.377), high-density lipoprotein cholesterol (HDL-C; r=−0.377), and low-density lipoprotein cholesterol (LDL-C; r=−0.278) concentrations. However, there were no correlations between changes in serum IL-10 concentration and changes in other cardiometabolic parameters. Conclusion Serum IL-10 concentration can increase as serum total cholesterol decreases. Additional studies are needed to explore the mechanisms linking changes in serum IL-10 with serum LDL-C and HDL-C concentrations.
Enzyme-mediated in situ self-assembly promotes in vivo bioorthogonal reaction for pretargeted multimodality imaging.

Pretargeted imaging has emerged as a promising approach to advance nuclear imaging of malignant tumors, however, the application of pretargeted strategy for multimodality imaging of enzyme activity in vivo is challenging. Herein, we combine the enzyme-mediated fluorogenic reaction and in situ self-assembly with the inverse electron demand Diels-Alder (IEDDA) reaction to develop an activatable pretargeted strategy for multimodality imaging. The trans -cyclooctene (TCO) bearing small-molecule probe, P-FFGd-TCO , can be activated by alkaline phosphatase and in situ self-assembles into nanoaggregates ( FMNPs-TCO ) retained on the membranes, permitting to (1) amplify near-infrared (NIR) fluorescence (FL) and magnetic resonance imaging (MRI) signals, and (2) enrich TCOs to promote IEDDA ligation. The Gallium-68 ( 68 Ga) labeled tetrazine can readily conjugate the tumor-retained FMNPs-TCO to enhance radioactivity uptake in tumors. Hence, strong NIR FL, MRI and positron emission tomography (PET) signals are concomitantly achieved, allowing for pretargeted multimodality imaging of ALP activity in HeLa tumor-bearing mice.
Short-distance versus long-distance deep-seaport container truck drivers’ prevalence and perceived discomfort of musculoskeletal symptoms in the Thailand Eastern Economic Corridor

Objectives. This research aimed to study the prevalence and perceived discomfort of musculoskeletal (MSK) symptoms among short-distance and long-distance deep-seaport truck drivers. Methods. Cross-sectional analysis using a standardized modified version of the Nordic musculoskeletal questionnaire (NMQ) was carried out using direct interviews with 25 male participants: 15 short-distance and 10 long-distance truck drivers. Results. As much as 88% was reported for the existence of MSK symptoms in the past 12 months. Considering all truck groups, regardless of short or long distance, the lower back was found with the highest prevalence (72%) followed by the neck (32%). The χ2 test showed long-distance truck drivers had statistically significantly more prevalence in the neck (p = 0.028) than short-distance drivers. Perceived discomfort by the Borg CR10 scale confirmed the lower back had the highest score (2.4) followed by the neck (1.44). The Kruskal–Wallis test revealed that long-distance truck drivers had significantly higher scores on the lower back and neck (p = 0.039 and p = 0.009, respectively). Conclusion. Longer exposure to prolonged non-natural working postures, vibration, traffic conditions and working stress could be the judicial causes. To minimize this problem, integrated interventions need to be implemented with particular measures among short-distance and long-distance truck drivers.
Flexibility of emerging face categorization at different levels of abstraction

Categorization of visual stimuli at different levels of abstraction relies on the encoding of relevant diagnostic features present at different spatial scales. We used the Eidolon Factory, an image-manipulation algorithm that introduces random disarray fields across spatial scales, to study how such a process flexibly combines perceptual information to perform successful categorization depending on task demands. Images of animal faces, human faces, and everyday objects were disarrayed coherently (random fields correlated) or incoherently (random fields randomized) to create a family of 50 eidolons per stimulus image with increasing disarray. Participants (N = 243) viewed each family of eidolons in a smooth sequence from maximum disarray to no disarray and performed a category verification task either at the superordinate (any face type) or basic (human face only) levels at two levels of uncertainty: participants in one group used their gut feeling to respond, whereas another group had to be sure of their decision. When participants used their gut feeling to respond, we observed a superordinate-level advantage. When they were sure of their response, we observed a basic-level advantage. Coherently disarrayed sequences impaired target detection compared to incoherently disarrayed sequences for both levels of response certainty. Furthermore, participants’ sensitivity in the Any Face condition increased when they observed coherently disarrayed sequences and had to be sure of their response. These results suggest that the visual system does not strictly adhere to feedforward processing but flexibly adjusts to the relevant perceptual information depending on task context.