Miracle-dz/UniFAR-FTUs huggingface dataset:
Splicing factor arginine/serine‐rich 8 promotes multiple myeloma malignancy and bone lesion through alternative splicing of CACYBP and exosome‐based cellular communication

Abstract Background Multiple myeloma (MM) is a distinctive malignancy of plasma cell within the bone marrow (BM), of which alternative splicing factors play vital roles in the progression. Splicing factor arginine/serine‐rich 8 (SFRS8) is the exclusive factor associated with MM prognosis, however its role in MM remains undefined. Methods The analyses of 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐ phenytetrazoliumromide (MTT) assay, immunohistochemistry, flow cytometry and xenograft model were performed to examine cell proliferation, cell cycle and apoptosis in SFRS8 overexpression or knockdown MM cells in vitro and in vivo. The SFRS8‐regulated alternative splicing events were identified by RNA immunoprecipitation sequencing (RIP‐seq) and validated by RIP‐qPCR and Co‐IP methods. Exosomes were extracted from the supernatant of myeloma cells by ultracentrifugation. Bone lesion was evaluated by TRAP staining in vitro and SCID/NOD‐TIBIA mouse model. A neon electroporation system was utilised to deliver siRNA through exosomes. The effect of siRNA‐loaded exosomes in vivo was evaluated by using a patient‐derived tumor xenograft (PDX) model and SCID/NOD‐TIBIA mouse model. Results SFRS8 was significantly upregulated in MM samples and positively associated with poor overall survival (OS) in MM patients. SFRS8 promoted MM cell proliferation in vitro and in vivo. Furthermore, calcyclin binding protein (CACYBP) was identified as the downstream target of SFRS8. Particularly, SFRS8 could reduce CACYBP isoform1 (NM_014412.3) and increase CACYBP isoform2 (NM_001007214.1) by mediating the alternative splicing of CACYBP, thereby altering the ubiquitination degradation of β‐catenin to promote MM progression. In addition, SFRS8 promoted osteoclast differentiation through exosomes in vitro and in vivo. More importantly, exosomal siRNA targeting CACYBP isoform2 inhibited tumour growth in PDX and SCID/NOD‐TIBIA mouse models. Conclusion Our findings demonstrate that targeting the SFRS8/CACYBP/β‐catenin axis may be a promising strategy for MM diagnosis and treatment.
Revision Surgery for a Rod Fracture with Multirod Constructs Using a Posterior-Only Approach Following Surgery for Adult Spinal Deformity

Study Design Single-center retrospective case series. Purpose We aimed to evaluate the clinical results of revision surgery for a rod fracture using a posterior-only approach and determine the best procedure to prevent refracture in patients with adult spinal deformity (ASD). Overview of Literature ASD affects the thoracolumbar spine and often requires surgical correction. However, surgery for extensive spinal fusion causes rod fracture, a major mechanical complication. Few studies have described the treatment methods for rod fractures. Furthermore, the clinical outcomes of revision surgery for rod fractures in patients with ASD are currently unclear. Methods We retrospectively reviewed the medical records of 404 patients who underwent corrective fusion surgery for ASD with a minimum 2-year follow-up. We studied cases of reoperation for postoperative rod fractures and investigated surgical procedure, intraoperative findings, clinical course, and rod refracture following revision surgery. Results Rod fracture was observed in 88 patients (21.8%). Fifty-three patients (average age, 68.3 years; average blood loss, 502.2 mL [% estimated blood volume=16.4%]; and operation time, 203.3 minutes) who suffered from a rod fracture at an average of 28.3 months after the primary operation underwent reoperation. Surgical invasiveness had no significant differences in total or partial rod replacement; however, the procedures with and without an anterior bone graft significantly differed. The replaced rod refractured at an average of 35.3 months after the revision surgery of five patients. The rod also refractured at a level outside multiple rods in two patients and with traumatic episodes in three patients. Three patients had bone grafts in the anterior column. Conclusions Revision surgery involving a multirod with a posterior-only approach for a rod fracture that occurred after ASD was performed successfully. Bone grafting in the anterior column is unnecessary for patients without massive bone defects.
Heavy Drinking among High School Student Athletes and Non-Athletes: Do Differences Emerge as Early as the Ninth Grade?

Abstract Background: High school athletes have been identified as a high-risk group for heavy drinking. Little is known, however, about the timing of when student athlete heavy drinking begins to diverge from that of non-athletes. Objectives: The aim of the current study is to examine differences in changes in heavy drinking among ninth grade student athletes and non-athletes across the academic year. We hypothesized that student athletes would report greater increases in heavy drinking compared to non-athletes from fall to spring semester. Methods: Ninth grade students (N = 217) aged 13 to 15 completed questionnaires on heavy drinking indices, quantity of peak drinking, frequency of binge drinking, and estimated blood alcohol concentration (eBAC) during the fall and spring semesters. Results: Consistent with our hypothesis, student athletes reported significantly greater increases in heavy drinking compared to non-athletes from fall to spring semester. Additionally, there was a significant increase in all three indices of heavy drinking for student athletes, whereas there were no significant changes for non-athletes. Conclusions: Results demonstrate divergence in the quantity and frequency of heavy drinking between student athletes and non-athletes during the ninth grade. These findings indicate the optimal timing of preventive intervention programs may be different for student athletes and non-athletes. Results also suggest that preventive intervention program targeting heavy drinking should be implemented for high school student athletes as early as the fall semester of the ninth grade when students are transitioning to high school.
Living with endometriosis: Comorbid pain disorders, characteristics of pain and relevance for daily life

Pain plays a central role in endometriosis. The complex relationship among pain characteristics, comorbid pain disorders and daily life represents a challenge for medical support. This multicentre cross‐sectional case–control study analysed the association between endometriosis‐related chronic pain and functions of daily life in 510 women with endometriosis, 265 (52%) who experienced chronic pain, either from endometriosis alone (N = 134, 26.3%) or in association with additional pain disorders (N = 131, 25.7%).
Genome-wide characterization of i-motifs and their potential roles in the stability and evolution of transposable elements in rice

Abstract I-motifs (iMs) are non-canonical DNA secondary structures that fold from cytosine (C)-rich genomic DNA regions termed putative i-motif forming sequences (PiMFSs). The structure of iMs is stabilized by hemiprotonated C-C base pairs, and their functions are now suspected in key cellular processes in human cells such as genome stability and regulation of gene transcription. In plants, their biological relevance is still largely unknown. Here, we characterized PiMFSs with high potential for i-motif formation in the rice genome by developing and applying a protocol hinging on an iMab antibody-based immunoprecipitation (IP) coupled with high-throughput sequencing (seq), consequently termed iM-IP-seq. We found that PiMFSs had intrinsic subgenomic distributions, cis-regulatory functions and an intricate relationship with DNA methylation. We indeed found that the coordination of PiMFSs with DNA methylation may affect dynamics of transposable elements (TEs) among different cultivated Oryza subpopulations or during evolution of wild rice species. Collectively, our study provides first and unique insights into the biology of iMs in plants, with potential applications in plant biotechnology for improving important agronomic rice traits.
Virtual screening of small natural compounds against NS1 protein of DENV, YFV and ZIKV

Abstract Diseases caused by viruses of the genus Flavivirus are among the main diseases that affect the world and they are a serious public health problem. Three of them stand out: Dengue, Yellow fever and Zika viruses. The non-structural protein 1 (NS1), encoded by this viral genus, in its dimeric form, plays important roles in the pathogenesis and RNA replication of these viruses. Therefore, the identification of chemicals with the potential to inhibit the formation of the NS1 protein dimer of DENV, YFV and ZIKV would enable them to act as a multi-target drug. For this, we selected conformations of the NS1 protein monomer with similar β-roll domain structure among the three virus species from conformations obtained from molecular dynamics simulations performed in GROMACS in 5 replicates of 150 ns for each species. After selecting the protein structures, a virtual screening of compounds from the natural products catalog of the ZINC database was performed using AutoDock Vina. The 100 best compounds were classified according efficiency criteria. Two compounds were observed in common to the species, with energy scores ranging from −9.2 kcal/mol to −10.1 kcal/mol. The results obtained here demonstrate the high similarity of NS1 proteins in the Flavivirus genus and high affinity for the same compounds; thus justifying the potential of these small molecules act in multitarget therapy. Communicated by Ramaswamy H. Sarma
Genomic variation reveals demographic history and biological adaptation of the ancient relictual, lotus (Nelumbo Adans.)

Abstract Lotus (Nelumbo Adans.), a relict plant, is testimony to long-term sustained ecological success, but the underlying genetic changes related to its survival strategy remain unclear. Here, we assembled the high-quality lotus genome, investigated genome variation of lotus mutation accumulation (MA) lines and reconstructed the demographic history of wild Asian lotus. We identified and validated 43 base substitutions fixed in MA lines, implying a spontaneous mutation rate of 1.4 × 10−9 bases/generation in lotus shoot stem cells. The past history of the lotus revealed that the ancestors of the lotus in eastern and southern Asia could be traced back to ~20 million years ago and twice experienced significant bottlenecks and population splits. We further identified selected genes among three lotus groups in different habitats, suggesting that 453 differed genes between the tropical and temperate group and 410 differed genes between two subgroups from Northeastern China and the Yangtze River–Yellow River Basin might play important roles in natural selection in the lotus’s adaptation and resilience. Our findings not only improve understanding of the evolutionary history of the lotus and the genetic basis of its survival advantages, but also provide valuable data for addressing various questions in evolution and protection for relict plants.
Biomechanical response of human rib cage to cardiopulmonary resuscitation maneuvers: Effects of the compression location

The biomechanical response of a human rib cage to cardiopulmonary resuscitation maneuvers was investigated by means of finite element simulations. We analyzed the effect of the location where the force was applied on the achieved compression depths and stress levels experienced by the breastbone and ribs. For compression locations on the breastbone, a caudal shift of the application area toward the breastbone tip resulted in a 17% reduction of the force required to achieve a target 5 cm compression depth. We found that the use of compression regions located on the costal cartilages would involve higher risk of rib fractures.
I/O Consolidation in the Data Center

Using Fibre Channel over Ethernet (FCoE) and related technologies, data centers can consolidate data traffic onto a single network switch, simplifying their environments, promoting virtualization, and substantially reducing power and cooling costs. This emerging technology is drawing immense excitement, but few enterprise IT decision-makers and implementers truly understand it. I/O Consolidation in the Data Center is the only complete, up-to-date guide to FCoE. FCoE innovators Silvano Gai and Claudio DeSanti (chair of the T11 FCoE standards working group) systematically explain the technology: its benefits, tradeoffs, and what it will take to implement it successfully in production environments. Unlike most other discussions of FCoE, this book fully reflects the final, recently-approved industry standard. The authors also present five detailed case studies illustrating typical FCoE adoption scenarios, as well as an extensive Q and A section addressing the issues enterprise IT professionals raise most often. This is a fully updated version of Silvano Gai's privately-published book on FCoE, written for leading FCoE pioneer Nuova Systems before the company was acquired by Cisco. Nearly 12,000 copies of that book have already been distributed, demonstrating the immense interest in FCoE technology, and the scarcity of reliable information that has existed about it.
ONLINE COLLABORATIVE LEARNING ELEMENTS TO PROPOSE AN ONLINE PROJECT BASED COLLABORATIVE LEARNING MODEL

Interest in collaboration is a natural outgrowth of the trend in education toward active learning. Many researchers have found that the advantages of collaborative learning; improves academic performance, promotes soft skills development (i.e., communications, collaboration, problem-solving and critical thinking skills), and increases satisfaction in the learning experience. Nevertheless, several studies have reported the complete opposite. In that respect, based on previous findings, three elements that are involved in the effectiveness of Online Collaborative Learning Environments are; Learning Environment, Learning Task, and Learning Interaction. This report proposes to determine the elements that can clarify all of the previously identified factors. Using the same approach as prior work, this study was conducted qualitatively; in the form of a document review. The outcome of this work suggests that (i) the learning interaction factor consists of learner-learner interaction and learner-teacher interaction elements, (ii) the elements of the learning design factor are content, process, evaluation, and time constraint, and (iii) usability, accessibility and stability are the ingredients of the learning environment factor. This study also proposes an Online Project-Based Collaborative Learning model. This model is currently only in a conceptual phase and requires significant development before it can be used to gather data. Therefore, in the next stage of this study, a prototype will be designed and developed; based on the proposed model.
Event-related correlates of evolving trust evaluations

ABSTRACT Accurate decisions about whether to trust someone are critical for adaptive social behavior. Previous research into trustworthiness decisions about face stimuli have focused on individuals. Here, decisions about groups of people are made cumulatively on the basis of sequences of faces. Participants chose to either increase or withdraw an initial investment in mock companies based on how trustworthy the company representatives (face stimuli) appeared. Companies were formed using participant trust ratings from the previous week, to create strong trustworthy, weak trustworthy, weak untrustworthy, and strong untrustworthy companies. Participants made faster, more accurate decisions for companies carrying stronger evidence (e.g., faces rated more extremely). Companies with more extreme ratings yielded faster decisions for untrustworthy than trustworthy companies, consistent with a negativity bias. Electrophysiological data revealed that amplitude of the P1 and P3 ERP components, linked to attentional processes, were largest for strong trustworthy faces. This suggests that evidence counter to bias draws special attention. In addition, the first face representing each company provoked larger amplitude P1, P3, and LPP than subsequent faces. This result suggests that when making social decisions about groups of people, the first person one meets receives the most attention.
Deformation of and Interfacial Stress Transfer in Ti3C2 MXene–Polymer Composites

Transitional metal carbides and nitrides (MXenes) have promise for incorporation into multifunctional composites due to their high electrical conductivity and excellent mechanical and tribological properties. It is unclear, however, to what extent MXenes are also able to improve the mechanical properties of the composites and, if so, what would be the optimal flake size and morphology. Herein, Ti3C2Tx MXene is demonstrated to be indeed a good candidate for mechanical reinforcement in polymer matrices. In the present work, the strain-induced Raman band shifts of mono-/few-/multilayer MXenes flakes have been used to study the mechanical properties of MXene and the interlayer/interfacial stress transfer on a polymer substrate. The mechanical performance of MXene was found to be less dependent upon flake thickness compared to that of graphene. This enables Ti3C2Tx MXene to offer an efficient mechanical reinforcement to a polymer matrix with a flake length of >10 μm and a thickness of 10s of nanometers. Therefore, the degree of exfoliation of MXenes is not as demanding as other two-dimensional (2D) materials for the purpose of mechanical enhancement in polymers. In addition, the active surface chemistry of MXene facilitates possible functionalization to enable a stronger interface with polymers for applications, such as strain engineering and mechanical enhancement, and in materials including membranes, coatings, and textiles.
COVID‐19 and community‐based care services: Experiences of people living with dementia and their informal carers in Italy

Abstract The COVID‐19 pandemic has significantly limited access to health and social care support systems for people with dementia and their carers, compounding the severe social restrictions. The aim of this study was to investigate the experiences of COVID‐19 among community‐dwelling people with dementia and their informal carers in Italy. Specifically, we focused on access to community‐based services and adopted solutions to provide support and care during exceptional times. Informal carers, caring for someone with dementia and attending community‐based services in Italy, participated in remote semi‐structured interviews between October and November 2020. Participants were asked about the effects of social isolation and closure of in‐person services on their daily lives as well as the challenges of dementia care. Transcripts were analysed using inductive thematic analysis. 22 informal carers were interviewed. Three themes emerged: (1) Disruptions to people with dementia's lives and health; (2) COVID‐19 as an additional stressor for carers; and (3) New ways of caring for people with dementia during COVID‐19. Face‐to‐face social care and social support services were suddenly interrupted and restrictions on social distancing were introduced, thus leading to people with dementia's impaired health and increased behavioural and psychological symptoms. Not only the amount but also the intensity of care increased, with no chance of respite for informal carers. Overall remote activities provided participants with emotional and social benefits, while allowing the continuity of relationships with services staff and users and of care. However, according to carers, a combination of virtual and face‐to‐face activities could better counterbalance the multiple adverse outcomes of COVID‐19. Public health measures should be designed carefully to consider the safety needs and the physical, psychological and social needs of people with dementia. Within a holistic care approach, social care services need to be enabled better to guarantee high‐quality care even during pandemic times.
The motor profile of obsessive-compulsive rituals: psychopathological and evolutionary implications

Abstract Background Studies investigating obsessive-compulsive disorder from an ethological approach have highlighted a specific motor pattern of compulsive rituals with respect to corresponding ordinary behaviors. Particularly, compulsive motor profile is built through the repetition of acts, with prevalence of nonfunctional ones and redirection of attention to its basic structural units. These formal features would characterize ritual behavior throughout evolution, from nonhuman animals to human cultures. However, no study to date has investigated a possible relationship between such motor profile and underlying psychopathology. Therefore, the first objective of the study was to confirm previous findings on a larger sample size of obsessive patients; the second objective was to elucidate whether motor profile might be associated with obsessive-compulsive psychopathology and/or prepsychotic symptoms of schizophrenia. Methods Twenty-one obsessive-compulsive outpatients provided a videotape of their rituals. An equal number of healthy controls, matched for sex and age, were registered for corresponding ordinary acts. Obsessive patients were administered the Yale-Brown Obsessive-Compulsive Scale, the Brown Assessment of Beliefs Scale, the Hamilton Rating Scale for Depression, and the Frankfurt Complaint Questionnaire. Results The results of the present study confirm that ritual compulsions present a specific motor structure characterized by repetition of both functional and nonfunctional acts and their longer duration. Such a motor pattern is independent from obsessive-compulsive psychopathology, whereas it results specifically associated with prepsychotic symptoms of schizophrenia. Conclusions We argue that this association may reflect the adaptive significance of ritual behavior across evolution, that is, its homeostatic function in conditions of unpredictability.
Embodied Space-pitch Associations are Shaped by Language

Height-pitch associations are claimed to be universal and independent of language, but this claim remains controversial. The present study sheds new light on this debate with a multimodal analysis of individual sound and melody descriptions obtained in an interactive communication paradigm with speakers of Dutch and Farsi. The findings reveal that, in contrast to Dutch speakers, Farsi speakers do not use a height-pitch metaphor consistently in speech. Both Dutch and Farsi speakers' co-speech gestures did reveal a mapping of higher pitches to higher space and lower pitches to lower space, and this gesture space-pitch mapping tended to co-occur with corresponding spatial words (high-low). However, this mapping was much weaker in Farsi speakers than Dutch speakers. This suggests that cross-linguistic differences shape the conceptualization of pitch and further calls into question the universality of height-pitch associations.