bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between diagnostic time intervals and health-related quality of life, clinical anxiety and depression in adolescents and young adults with cancer: cross-sectional analysis of the BRIGHTLIGHT cohort
Authors: Forster Alice S. , Herbert Annie , Koo Minjoung Monica , Taylor Rachel M. , Gibson Faith , Whelan Jeremy S. , Lyratzopoulos Georgios , Fern Lorna A. 
Published: February 2022

Abstract
Background
The association of diagnostic intervals and outcomes is poorly understood in adolescents and young adults with cancer (AYA). We investigated associations between diagnostic intervals and health-related quality of life (HRQoL), anxiety and depression in a large AYA cohort.

Methods
Participants aged 12–24 completed interviews post-diagnosis, providing data on diagnostic experiences and the patient-reported outcomes (PROs) HRQoL, anxiety and depression. Demographic and cancer information were obtained from clinical and national records. Six diagnostic intervals were considered. Relationships between intervals and PROs were examined using regression models.

Results
Eight hundred and thirty participants completed interviews. In adjusted models, across 28 of 30 associations, longer intervals were associated with poorer PROs. Patient intervals (symptom onset to first seeing a GP) of ≥1 month were associated with greater depression (adjusted odds ratio (aOR):1.7, 95% Confidence Interval (CI):1.1–2.5) compared to <1 month. ≥3 pre-referral GP consultations were associated with greater anxiety (aOR:1.6, CI:1.1–2.3) compared to 1–2 consultations. Symptom onset to first oncology appointment intervals of ≥2 months was associated with impaired HRQoL (aOR:1.8, CI:1.2–2.5) compared to <2 months.

Conclusions
Prolonged diagnostic intervals in AYA are associated with an increased risk of impaired HRQoL, anxiety and depression. Identifying and delivering interventions for this high-risk group is a priority.
ERK1/2 inhibits Cullin 3/SPOP-mediated PrLZ ubiquitination and degradation to modulate prostate cancer progression
Authors: Fan Yizeng , Hou Tao , Dan Weichao , Zhu Yasheng , Liu Bo , Wei Yi , Wang Zixi , Gao Yang , Zeng Jin , Li Lei 
Published: February 2022

AbstractThe gene encoding the E3 ubiquitin ligase substrate-binding adaptor SPOP is frequently mutated in prostate cancer (PCa), but how SPOP functions as a tumor suppressor and contributes to PCa pathogenesis remains poorly understood. Prostate Leucine Zipper (PrLZ) serves as a prostate-specific and androgen-responsive gene, which plays a pivotal role in the malignant progression of PCa. However, the upstream regulatory mechanism of PrLZ protein stability and its physiological contribution to PCa carcinogenesis remain largely elusive. Here we report that PrLZ can be degraded by SPOP. PrLZ abundance is elevated in SPOP-mutant expressing PCa cell lines and patient specimens. Meanwhile, ERK1/2 might regulate SPOP-mediated PrLZ degradation through phosphorylating PrLZ at Ser40, which blocks the interaction between SPOP and PrLZ. In addition, we identify IL-6 might act as an upstream PrLZ degradation regulator via promoting its phosphorylation by ERK1/2, leading to its impaired recognition by SPOP. Thus, our study reveals a novel SPOP substrate PrLZ which might be controlled by ERK1/2-mediated phosphorylation, thereby facilitating to explore novel drug targets and improve therapeutic strategy for PCa.
High-throughput identification and quantification of single bacterial cells in the microbiota
Authors: Jin Jianshi , Yamamoto Reiko , Takeuchi Tadashi , Cui Guangwei , Miyauchi Eiji , Hojo Nozomi , Ikuta Koichi , Ohno Hiroshi , Shiroguchi Katsuyuki 
Published: February 2022

AbstractThe bacterial microbiota works as a community that consists of many individual organisms, i.e., cells. To fully understand the function of bacterial microbiota, individual cells must be identified; however, it is difficult with current techniques. Here, we develop a method, Barcoding Bacteria for Identification and Quantification (BarBIQ), which classifies single bacterial cells into taxa–named herein cell-based operational taxonomy units (cOTUs)–based on cellularly barcoded 16S rRNA sequences with single-base accuracy, and quantifies the cell number for each cOTU in the microbiota in a high-throughput manner. We apply BarBIQ to murine cecal microbiotas and quantify in total 3.4 × 105 bacterial cells containing 810 cOTUs. Interestingly, we find location-dependent global differences in the cecal microbiota depending on the dietary vitamin A deficiency, and more differentially abundant cOTUs at the proximal location than the distal location. Importantly, these location differences are not clearly shown by conventional 16S rRNA gene-amplicon sequencing methods, which quantify the 16S rRNA genes, not the cells. Thus, BarBIQ enables microbiota characterization with the identification and quantification of individual constituent bacteria, which is a cornerstone for microbiota studies.
Multi-parameter photon-by-photon hidden Markov modeling
Authors: Harris Paul David , Narducci Alessandra , Gebhardt Christian , Cordes Thorben , Weiss Shimon , Lerner Eitan 
Published: February 2022

AbstractSingle molecule Förster resonance energy transfer (smFRET) is a unique biophysical approach for studying conformational dynamics in biomacromolecules. Photon-by-photon hidden Markov modeling (H2MM) is an analysis tool that can quantify FRET dynamics of single biomolecules, even if they occur on the sub-millisecond timescale. However, dye photophysical transitions intertwined with FRET dynamics may cause artifacts. Here, we introduce multi-parameter H2MM (mpH2MM), which assists in identifying FRET dynamics based on simultaneous observation of multiple experimentally-derived parameters. We show the importance of using mpH2MM to decouple FRET dynamics caused by conformational changes from photophysical transitions in confocal-based smFRET measurements of a DNA hairpin, the maltose binding protein, MalE, and the type-III secretion system effector, YopO, from Yersinia species, all exhibiting conformational dynamics ranging from the sub-second to microsecond timescales. Overall, we show that using mpH2MM facilitates the identification and quantification of biomolecular sub-populations and their origin.
Virtual intracranial EEG signals reconstructed from MEG with potential for epilepsy surgery
Authors: Cao Miao , Galvis Daniel , Vogrin Simon J. , Woods William P. , Vogrin Sara , Wang Fan , Woldman Wessel , Terry John R. , Peterson Andre , Plummer Chris , Cook Mark J. 
Published: February 2022

AbstractModelling the interactions that arise from neural dynamics in seizure genesis is challenging but important in the effort to improve the success of epilepsy surgery. Dynamical network models developed from physiological evidence offer insights into rapidly evolving brain networks in the epileptic seizure. A limitation of previous studies in this field is the dependence on invasive cortical recordings with constrained spatial sampling of brain regions that might be involved in seizure dynamics. Here, we propose virtual intracranial electroencephalography (ViEEG), which combines non-invasive ictal magnetoencephalographic imaging (MEG), dynamical network models and a virtual resection technique. In this proof-of-concept study, we show that ViEEG signals reconstructed from MEG alone preserve critical temporospatial characteristics for dynamical approaches to identify brain areas involved in seizure generation. We show the non-invasive ViEEG approach may have some advantage over intracranial electroencephalography (iEEG). Future work may be designed to test the potential of the virtual iEEG approach for use in surgical management of epilepsy.
Randomized controlled trial for time-restricted eating in healthy volunteers without obesity
Authors: Xie Zhibo , Sun Yuning , Ye Yuqian , Hu Dandan , Zhang Hua , He Zhangyuting , Zhao Haitao , Yang Huayu , Mao Yilei 
Published: February 2022

AbstractTime-restricted feeding (TRF) improves metabolic health. Both early TRF (eTRF, food intake restricted to the early part of the day) and mid-day TRF (mTRF, food intake restricted to the middle of the day) have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a five-week randomized trial to compare the effects of the two TRF regimens in healthy individuals without obesity (ChiCTR2000029797). The trial has completed. Ninety participants were randomized to eTRF (n=30), mTRF (n=30), or control groups (n=30) using a computer-based random-number generator. Eighty-two participants completed the entire five-week trial and were analyzed (28 in eTRF, 26 in mTRF, 28 in control groups). The primary outcome was the change in insulin resistance. Researchers who assessed the outcomes were blinded to group assignment, but participants and care givers were not. Here we show that eTRF was more effective than mTRF at improving insulin sensitivity. Furthermore, eTRF, but not mTRF, improved fasting glucose, reduced total body mass and adiposity, ameliorated inflammation, and increased gut microbial diversity. No serious adverse events were reported during the trial. In conclusion, eTRF showed greater benefits for insulin resistance and related metabolic parameters compared with mTRF. Clinical Trial Registration URL: http://www.chictr.org.cn/showproj.aspx?proj=49406.
Effects of preoperative sagittal spinal imbalance on pain after lateral lumbar interbody fusion
Authors: Hiyama Akihiko , Katoh Hiroyuki , Sakai Daisuke , Sato Masato , Watanabe Masahiko 
Published: February 2022

AbstractSagittal misalignment has been associated with negative quality of life (QOL). However, there is no report on whether differences in preoperative sagittal misalignment in patients with lumbar degenerative diseases affect postoperative results after lateral lumbar interbody fusion (LLIF). We investigated whether preoperative sagittal alignment influences the correction of alignment after surgery and whether the preoperative sagittal alignment affects the rating of low back pain, leg pain, and leg numbness. The subjects were 81 patients (48 male, 33 females, average age at surgery 70.2 years) who underwent anterior–posterior combined surgery with LLIF and percutaneous pedicle screws from May 2018 to July 2020. Cluster analysis was performed using the preoperative sagittal vertical axis (SVA) value, and patients were classified into two groups (group 1; n = 30, SVA = 129.0 ± 53.4 mm, group 2; n = 51, SVA = 30.8 ± 23.5 mm). Baseline demographics and treatment data were compared between groups. Sagittal and pelvic parameters and pain scores, such as low back pain, leg pain, and leg numbness, were also compared. Operative time, blood loss, and length of hospital stay did not differ significantly between groups. The changes (Δ) in SVA and lumbar lordosis (LL) for all patients from before to after surgery were not significant (ΔSVA; p = 0.218, ΔLL; p = 0.189, respectively). The SVA, LL, and PI − LL changed significantly after the surgery in group 1, but no marked improvement in sagittal imbalance was obtained after LLIF surgery. The improvement in each pain score from before to after the surgery did not differ significantly between groups. LLIF surgery has a limited chance of recovering sagittal imbalance. However, postoperative low back pain, leg pain, and leg numbness may be improved by LLIF surgery, regardless of the preoperative sagittal alignment.
Pemafibrate suppresses NLRP3 inflammasome activation in the liver and heart in a novel mouse model of steatohepatitis-related cardiomyopathy
Authors: Kanno Kotaro , Koseki Masahiro , Chang Jiuyang , Saga Ayami , Inui Hiroyasu , Okada Takeshi , Tanaka Katsunao , Asaji Masumi , Zhu Yinghong , Ide Seiko , Saito Shigeyoshi , Higo Tomoaki , Okuzaki Daisuke , Ohama Tohru , Nishida Makoto , Kamada Yoshihiro , Ono Masafumi , Saibara Toshiji , Yamashita Shizuya , Sakata Yasushi 
Published: February 2022

AbstractAlthough patients with nonalcoholic fatty liver disease have been reported to have cardiac dysfunction, and appropriate model has not been reported. We established a novel mouse model of diet-induced steatohepatitis-related cardiomyopathy and evaluated the effect of pemafibrate. C57Bl/6 male mice were fed a (1) chow diet (C), (2) high-fat, high-cholesterol, high-sucrose, bile acid diet (NASH diet; N), or (3) N with pemafibrate 0.1 mg/kg (NP) for 8 weeks. In the liver, macrophage infiltration and fibrosis in the liver was observed in the N group compared to the C group, suggesting steatohepatitis. Free cholesterol accumulated, and cholesterol crystals were observed. In the heart, free cholesterol similarly accumulated and concentric hypertrophy was observed. Ultrahigh magnetic field magnetic resonance imaging revealed that the left ventricular (LV) ejection fraction (EF) was attenuated and LV strain was focally impaired. RNA sequencing demonstrated that the NOD-like receptor and PI3 kinase-Akt pathways were enhanced. mRNA and protein expression of inflammasome-related genes, such as Caspase-1, NLRP3, and IL-1β, were upregulated in both the liver and heart. In the NP compared to the N group, steatohepatitis, hepatic steatosis, and cardiac dysfunction were suppressed. Sequential administration of pemafibrate after the development of steatohepatitis-related cardiomyopathy recovered hepatic fibrosis and cardiac dysfunction.
Deep learning for fully automatic detection, segmentation, and Gleason grade estimation of prostate cancer in multiparametric magnetic resonance images
Authors: Pellicer-Valero Oscar J. , Marenco Jiménez José L. , Gonzalez-Perez Victor , Casanova Ramón-Borja Juan Luis , Martín García Isabel , Barrios Benito María , Pelechano Gómez Paula , Rubio-Briones José , Rupérez María José , Martín-Guerrero José D. 
Published: February 2022

AbstractAlthough the emergence of multi-parametric magnetic resonance imaging (mpMRI) has had a profound impact on the diagnosis of prostate cancers (PCa), analyzing these images remains still complex even for experts. This paper proposes a fully automatic system based on Deep Learning that performs localization, segmentation and Gleason grade group (GGG) estimation of PCa lesions from prostate mpMRIs. It uses 490 mpMRIs for training/validation and 75 for testing from two different datasets: ProstateX and Valencian Oncology Institute Foundation. In the test set, it achieves an excellent lesion-level AUC/sensitivity/specificity for the GGG$$\ge$$
≥
2 significance criterion of 0.96/1.00/0.79 for the ProstateX dataset, and 0.95/1.00/0.80 for the IVO dataset. At a patient level, the results are 0.87/1.00/0.375 in ProstateX, and 0.91/1.00/0.762 in IVO. Furthermore, on the online ProstateX grand challenge, the model obtained an AUC of 0.85 (0.87 when trained only on the ProstateX data, tying up with the original winner of the challenge). For expert comparison, IVO radiologist’s PI-RADS 4 sensitivity/specificity were 0.88/0.56 at a lesion level, and 0.85/0.58 at a patient level. The full code for the ProstateX-trained model is openly available at https://github.com/OscarPellicer/prostate_lesion_detection. We hope that this will represent a landmark for future research to use, compare and improve upon.
Determinants of interchain coupling properties of Te atomic chains
Authors: Han Jie , Li Quan Ming , Gao Wang 
Published: February 2022

AbstractThe coupling effect of one-dimensional (1D) materials is of great significance for the practical application of 1D materials in high-density memory devices and ultra-micro nanometer array lasers. However, the determinants of the coupling effect remain debated. Here, using first principles methods, we investigate the effects of chirality, size and stacking mode on the stability and electronic properties of few-chain Te nanowires. We find that the stacking mode and size play a dominant role in the stability of the nanowires, while the chirality and size have a key effect on the electronic structures. These phenomena are mainly due to the quantum size effect and the special helical structure of the Te chain. Our findings provide the means for adjusting the band gap and the candidates for constructing n-type spin devices, which serve as a basis for the research and manufacture of new nano electronic devices.
Fatigue-free visual perception of high-density super-multiview augmented reality images
Authors: Lim Sungjin , Jeon Hosung , Jung Minwoo , Lee Chulwoong , Moon Woonchan , Kim Kwangsoo , Kim Hwi , Hahn Joonku 
Published: February 2022

AbstractIt is well known that wearing virtual reality (VR) and augmented reality (AR) devices for long periods can cause visual fatigue and motion sickness due to vergence-accommodation conflict (VAC). VAC is considered the main obstacle to the development of advanced three-dimensional VR and AR technology. In this paper, we present a novel AR high-density super-multiview (HDSMV) display technique capable of eliminating VAC in wide range. The designed binocular time-sequential AR HDSMV projection, which delivers 11 views to each eye pupil, is experimentally demonstrated, confirming that VAC is eliminated over a wide-range of viewer’s focus distance. It is believed that the proposed time-sequential AR HDSMV method will pave the way for the development of VAC-free AR technology.
Shared mechanisms underlie mental imagery and motor planning
Authors: Bennet Rotem , Reiner Miriam 
Published: February 2022

AbstractMany studies have associated mental imagery with motor control mechanisms by showing mutually active brain areas and functions, as well as similar temporal patterns of imagining and executing the same motor actions. One of the main conjectured mutual mechanisms is the Cerebellar forward-model, commonly believed to generate sensory predictions as part of both motor control and mental imagery processes. Nevertheless, trials to associate one’s overall individual mental and motor capacities have shown only mild and inconsistent correlations, hence challenging the mutual mechanism assumption. We hypothesized that one cause to this inconsistency is the forward-model’s dominance in the motor-planning stage only when adapting to novel sensorimotor environments, while the inverse-model is gradually taking the lead along the adaptation, and therefore biasing most attempts to measure motor-mental overlapping functions and correlate these measurements under regular circumstances. Our current study aimed to tackle and explore this gap using immersive virtual embodiment, by applying an experience of a fundamental sensorimotor conflict, thereby manipulating the sensory prediction mechanism, and presumably forcing an increased involvement of the forward-model in the motor planning stage throughout the experiment. In the study, two groups of subjects (n = 48) performed mental and manual rotation within an immersive, motion-captured, virtual reality environment, while the sensorimotor dynamics of only the test group were altered by physical-virtual speed re-mapping making the virtual hand move twice as fast as the physical hand controlling it. Individual mental imagery capacities were assessed before and after three blocks of manual-rotation, where motor planning durations were measured as the time until motion onset. The results show that virtual sensorimotor alteration extremely increases the correlation of mental imagery and motor planning (r = 0.9, p < .0001) and leads to higher mental imagery performance improvement following the physical blocks. We particularly show that virtual embodiment manipulation affects the motor planning stage to change and functionally overlap with imagery mechanisms, rather than the other way around, which supports our conjecture of an increased sensory-prediction forward-model involvement. Our results shed new light on the embodied nature of mental imagery, support the view of the predictive forward-model as a key mechanism mutually underlying motor control and imagery, and suggest virtual sensorimotor alteration as a novel methodology to increase physical-mental convergence. These findings also suggest the applicability of using existing motion-tracked virtual environments for continuous cognitive evaluation and treatment, through kinematic analysis of ongoing natural motor behaviors.
Protein and miRNA profile of circulating extracellular vesicles in patients with primary sclerosing cholangitis
Authors: Povero Davide , Tameda Masahiko , Eguchi Akiko , Ren Wenhua , Kim Jihoon , Myers Robert , Goodman Zachary D. , Harrison Stephen A. , Sanyal Arun J. , Bosch Jaime , Ohno-Machado Lucila , Feldstein Ariel E. 
Published: February 2022

AbstractPrimary sclerosing cholangitis (PSC) is an idiopathic and heterogenous cholestatic liver disease characterized by chronic inflammation and fibrosis of the biliary tree. Currently, no effective therapies are available for this condition, whose incidence is rising. At present, specificity and sensitivity of current serum markers used to diagnose PSC are limited and often unreliable. In this study, we characterize circulating extracellular vesicles and provide supporting data on their potential use as novel surrogate biomarkers for PSC. EVs are membrane surrounded structures, 100–1000 nm in size, released by cells under various conditions and which carry a variety of bioactive molecules, including small non-coding RNAs, lipids and proteins. In recent years, a large body of evidence has pointed to diagnostic implications of EVs and relative cargo in various human diseases. We isolated EVs from serum of well-characterized patients with PSC or control subjects by differential centrifugation and size-exclusion chromatography. A complete characterization identified elevated levels of circulating EVs in PSC patients compared to healthy control subjects (2000 vs. 500 Calcein-FITC + EVs/μL). Tissue and cell specificity of circulating EVs was assessed by identification of liver-specific markers and cholangiocyte marker CK-19. Further molecular characterization identified 282 proteins that were differentially regulated in PSC-derived compared to healthy control-EVs. Among those, IL-13Ra1 was the most significantly and differentially expressed protein in PSC-derived EVs and correlated with the degree of liver fibrosis. In addition to protein profiling, we performed a miRNA-sequencing analysis which identified 11 among established, liver-specific (e.g., miR-122 and miR-192) and novel miRNAs. One of the newly identified miRNAs, miR-4645-3p, was significantly up-regulated fourfold in PSC-derived EVs compared to circulating EVs isolated from healthy controls. This study provides supporting evidence of the potential role of circulating EVs and associated protein and miRNA cargo as surrogate noninvasive and reliable biomarker for PSC.
Min-entropy estimation for semiconductor superlattice true random number generators
Authors: Liu Jing , Xie Jianguo , Chao Lu , Wu Han , Ding Peng , Chen Xiaoming , Feng Huamin 
Published: February 2022

AbstractSemiconductor superlattice true random number generator (SSL-TRNG) has an outstanding practical property on high-throughput and high-security cryptographic applications. Security in random number generators is closely related to the min-entropy of the raw output because feeding cryptographic applications with insufficient entropy leads to poor security and vulnerability to malicious attacks. However, no research has focused on the min-entropy estimation based on the stochastic model for SSL-TRNG, which is a highly recommended method for evaluating the security of a specific TRNG structure. A min-entropy estimation method is proposed in this paper for the SSL-TRNG by extending the Markov stochastic model derived from the memory effects. By calculating the boundary of the transition matrix, the min-entropy result is the average value of each sample (1 bit) is 0.2487. Moreover, the experimental results show that the estimator is accurate enough to adjust compression rate dynamically in post-processing to reach the required security level, estimating entropy on the fly rather than off-line.