Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic and predictive role of DNA mismatch repair status in stage II‐III colorectal cancer: A systematic review and meta‐analysis

DNA mismatch repair (MMR) status was considered to be a potential prognostic factor for colorectal cancer (CRC) but with conflicting reports, and varied in terms of TNM stages. Its relationship with prognosis in stage II‐III CRC had not yet been systematically established. Therefore, we retrieved eligible studies published through May 2019, and screened out 51 studies that reported survival data (overall survival [OS] and/or disease‐free survival [DFS]) in 28 331 CRC patients at stage II‐III, totally 16.4% of whom were characterized as deficient MMR (dMMR). Significant associations of dMMR status were observed with longer OS (Hazard Ratio [HR] = 0.74, 95% CI: 0.68‐0.82; P < .001), as well as DFS (HR = 0.67, 95% CI: 0.59‐0.75, P < .001). However, dMMR patients received no statistically significant benefit from fluoropyrimidine‐based treatment for either OS (HR = 0.84, 95%CI: 0.60‐1.17; P = .31) or DFS (HR = 0.83, 95%CI: 0.60‐1.15; P = .27), compared with that in proficient MMR (pMMR) patients for both OS (HR = 0.55, 95% CI: 0.43‐0.71; P < .001) and DFS (HR = 0.60, 95% CI: 0.50‐0.73; P < .001). Our analysis indicate that dMMR CRC patients at stage II‐III had higher OS and DFS than pMMR ones, and fluoropyrimidine‐based chemotherapy could improve survival in pMMR patients rather than dMMR ones.
Perceptions of team-based learning using the Team-Based Learning Student Assessment Instrument: an exploratory analysis amongst pharmacy and biomedical students in the United Kingdom

Purpose This study aimed to evaluate students’ perception of team-based learning (TBL) amongst a cohort exposed to this methodology for the first time at a university in the United Kingdom. Methods Between November and December 2018, 26 first-year Master of Pharmacy and 90 second-year Biomedical Science students of the School of Life Sciences, University of Sussex, United Kingdom were invited to participate and requested to complete a questionnaire that contained quantitative and qualitative questions. The quantitative component was based on the Team-Based Learning Student Assessment Instrument (TBL-SAI). It additionally contained questions about key student characteristics. Results The response rate was 60% (70 of 116); of the participants, 74% (n=52) were females and 26% (n=18) males. The percentage of agreement in the TBL-SAI suggested a favourable response to TBL. The overall mean score for the TBL-SAI was 115.6 (standard deviation, 5.6; maximum score, 140), which was above the threshold of 102, thus suggesting a preference for TBL. Statistically significant differences were not found according to demographic characteristics. Students who predicted a final grade of ≥70% strongly agreed that TBL helped improve their grades. Some students highlighted issues with working in teams, and only 56% of students agreed that they could learn better in a team setting. Conclusion This study shows that students exposed to TBL for the first time favoured several aspects of TBL. However, more focused strategies including team-building activities and expert facilitation skills could potentially tackle resistance to working in teams.
Targeted therapy for colorectal cancer metastases: A review of current methods of molecularly targeted therapy and the use of tumor biomarkers in the treatment of metastatic colorectal cancer

Despite recent advances in the management of colorectal cancer, metastatic disease remains challenging, and patients are rarely cured. However, a better understanding of the pathways implicated in the evolution and proliferation of cancer cells has led to the development of targeted therapies, that is, agents with action directed at these pathways/features. This approach is more specific to cells within which these pathways, such as epidermal growth factor receptor (EGFR), are overactive; this is in contrast to the relatively indiscriminate mechanism by which cytotoxic chemotherapy tends to affect rapidly dividing cells, regardless of their role. Although factors unique to a given patient, such as the location of the primary tumor (sidedness) or the presence of mutations that confer resistance, may limit the utility of these agents, targeted therapies are now a part of the treatment paradigm for metastatic colorectal cancer, and survival outcomes have significantly improved. This review provides an overview of the role of targeted therapy in the management of patients with colorectal cancer metastases as well as a discussion of issues in patient selection, with a focus on inhibitors of angiogenesis, EGFR‐targeted therapy, BRAF mutation–targeted therapies, and other novel strategies, including immunotherapy.
Tetracycline Analogs Inhibit Osteoclast Differentiation by Suppressing MMP-9-Mediated Histone H3 Cleavage

Osteoporosis is a common disorder of bone remodeling, caused by the imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Recently, we reported that matrix metalloproteinase-9 (MMP-9)-dependent histone H3 proteolysis is a key event for proficient osteoclast formation. Although it has been reported that several MMP-9 inhibitors, such as tetracycline and its derivatives, show an inhibitory effect on osteoclastogenesis, the molecular mechanisms for this are not fully understood. Here we show that tetracycline analogs, especially tigecycline and minocycline, inhibit osteoclast formation by blocking MMP-9-mediated histone H3 tail cleavage. Our molecular docking approach found that tigecycline and minocycline are the most potent inhibitors of MMP-9. We also observed that both inhibitors significantly inhibited H3 tail cleavage by MMP-9 in vitro. These compounds inhibited receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast formation by blocking the NFATc1 signaling pathway. Furthermore, MMP-9-mediated H3 tail cleavage during osteoclast differentiation was selectively blocked by these compounds. Treatment with both tigecycline and minocycline rescued the osteoporotic phenotype induced by prednisolone in a zebrafish osteoporosis model. Our findings demonstrate that the tetracycline analogs suppress osteoclastogenesis via MMP-9-mediated H3 tail cleavage, and suggest that MMP-9 inhibition could offer a new strategy for the treatment of glucocorticoid-induced osteoporosis.
The influence of the trainer on the motivation and resilience of sportspeople: A study from the perspective of self-determination theory

The aim of this study was to evaluate the influence of a trainer’s interpersonal relations from the perspective of autonomy support and controlling style on sportspeople’s basic need satisfaction and frustration, motivation, and resilience. The study used a cross-sectional design based on self-determination theory (SDT). Sportspeople (N = 324) completed questionnaires to measure their perceptions of trainers’ autonomy-supportive and controlling coaching styles, basic need satisfaction and frustration in the sports context, motivation for sport, and resilience. Structural equation modeling of the proposed relations among variables supported SDT by showing a positive relation between perceived autonomy support and the satisfaction of basic psychological needs (β = .39, p < .001) and a negative relation with the frustration of psychological needs (β = −.17, p < .05). The coach’s perceived interpersonal controlling style showed a positive relation with the frustration of psychological needs (β = .55, p < .001) and a negative relation with the satisfaction of basic psychological needs (β = −.27, p < .05). Furthermore, autonomous motivation showed a negative relation (β = −.46, p < .001) with the frustration of psychological needs and a positive relation (β = .35, p < .05) with the satisfaction of basic psychological needs and resilience (β = .60, p < .001). In addition, the resilience of sportspeople was indirectly affected to the same extent by the trainer’s influence through control (β = −.38, p < .05) and perception of autonomy support (β = .16, p < .05) through the mediators of satisfaction of basic psychological needs and motivation. These results show the influence of the coach on the motivation and resilience of sportspeople.
Neurourology and Urodynamics

Correspondence Hann‐Chorng Kuo, Department of Urology, Hualien Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, 707 Chung‐Yang Rd, Section 3, Hualien 970, Taiwan. Email: hck@tzuchi.com. tw Abstract Aims: To investigate the mechanism of bladder nerve hyperplasia and fibrosis in the patients with ketamine‐associated cystitis (KC). Methods: Sixteen patients with severe KC, six patients with mild KC, and five patients with localized invasive bladder cancer served as control patients. Bladder mucosa specimens were taken during the operations, and the specimens were stained for nerve growth factor (NGF) and S‐100 to evaluated nerve hyperplasia. The quantitative Western blot analysis was performed for NGF, brain‐derived neurotrophic factor (BDNF), growth‐associated protein 43 (GAP‐43), tropomyosin receptor kinase A and B (TrkA and TrkB), transforming growth factor‐β (TGF‐β), phosphorylated extracellular signal‐regulated kinases (p‐ERK), protein kinase B (p‐Akt), and glycogen synthase kinase 3β (p‐GSK‐3β). Results: The results demonstrated diffuse NGF expression in KC bladder epithelium, lamina propria, and muscle. The GAP‐43, NGF, BDNF, TrkA, TGF‐ β, p‐ERK, P‐AKT, and p‐GSK‐3β expression in the bladder mucosa specimens of patients with severe KC was significantly higher than in patients with mild KC and control patients. Expression of neurotrophins was significantly correlated with bladder capacity and pain. NGF and BDNF expression were significantly higher in the KC bladder specimens with strongly positive S‐100 staining. TGF‐ β expression in the bladder specimens was significantly correlated with neurotrophins, p‐ERK, P‐AKT, and p‐GSK‐3β levels. Conclusion: Our findings indicate upregulation of neurotrophins, TGF‐β, and activation of the cell proliferation kinases plays an important role in nerve hyperplasia and fibrosis mechanisms in severe KC bladders. The neurotrophins and TGF‐β interact as cause and effect, leading to bladder hypersensitivity and fibrosis in severe KC.
A scalable and flexible single-level framework for O-D matrix inference using IoT data

This study proposes a scalable and flexible single-level framework for Origin-Destination matrix (ODM) inference using data from IoT (Internet of Things) and other sources. The framework allows the analyst to integrate information from multiple data sources, while controlling for differences in data quality across sources. We assess the effectiveness of the framework through a real-world experiment in Greater Adelaide (GA), Australia. We infer car OD flows within the region using three separate data sources: site-level traffic counts from loop detectors, vehicle trajectories recorded by roadside Bluetooth sensors, and journey-to-work data collected by the Australian Census. We compare our OD inferences with those from the current version of the Metropolitan Adelaide Strategic Transport Model (MASTEM), calibrated using data from traditional household travel surveys. We find remarkable consistency between our inferences and those from MASTEM, despite differences in input data and methodologies. For example, for the morning peak period, we predict the total number of trips made within GA to be around 556 thousands, while the corresponding prediction from MASTEM is about 484 thousands. The two predictions are within 15 per cent of each other. When we compare the spatial distribution of trips, in terms of origins and destinations, we find that our inferred OD matrix has an 86 per cent cosine similarity to the corresponding MASTEM matrix. In summary, our results show that the proposed framework can produce highly comparable ODM, trip production and trip attraction patterns to those inferred from traditional household travel survey-based transportation demand modelling methods.
‘If I knew what was going to happen, it wouldn’t worry me so much’: Children’s, parents’ and health professionals’ perspectives on information for children undergoing a procedure

Children undergoing procedures such as blood tests and X-rays experience less anxiety and upset if they are well prepared and informed. Currently the provision of information about procedures can be ad hoc and there are barriers to children understanding this information. This study explored the perspectives of 32 children undergoing procedures (aged between 8 and 12 years), 27 parents and 19 health professionals on the provision of preparatory information to children. Qualitative interviews, prompted by visual images, were thematically analysed. The three themes, ‘accessing information’, ‘understanding information’ and ‘using information’, resonated with the central tenets of health literacy. Children reported mainly accessing information second-hand through their parents and demonstrated misconceptions about their procedure. Children identified that procedural information would help them to know what was going to happen and enable them to feel less worried and scared about their procedure. This study highlights that children can have low levels of health literacy in relation to a planned procedure. Their health literacy in this context is heavily influenced by the adults (parents and health professionals) around them. There needs to be further work conducted, informed directly by children, to improve the health literacy of children attending hospital for planned procedures.
Skeletal Muscle-Released Extracellular Vesicles: State of the Art

All cells export part of their intracellular content into the extracellular space through the release of various types of extracellular vesicles (EVs). They are synthetized either from the budding of the plasma membrane [i.e., microparticles (MPs, 150–300 nm size)] or from the late endosomes in which intraluminal vesicles progressively (ILVs) accumulate during their maturation into multivesicular bodies (MVBs). ILVs are then released into the extracellular space through MVB fusion with the plasma membrane [i.e., exosomes (50–100 nm size)]. In the context of metabolic diseases, recent data have highlighted the role of EVs in inflammation associated with pancreas dysfunction, adipose tissue homeostasis, liver steatosis, inflammation, and skeletal muscle (SkM) insulin resistance (IR). Among these insulin-sensitive tissues, SkM is the largest organ in human and is responsible for whole-body glucose disposal and locomotion. Therefore, understanding the contribution of SkM-EVs in the development of diabetes/obesity/dystrophy/,-related diseases is a hot topic. In this review, we have summarized the role of SkM-EVs in muscle physiology and in the development of metabolic diseases and identify important gaps that have to be filled in order to have more precise information on SkM-EVs biological actions and to understand the functions of the different subpopulations of SkM-EVs on the whole-body homeostasis.
Computational investigation of dust mite allergens in a realistic human nasal cavity

Abstract Aim: Inhaled allergens from house dust mite (HDM) are a major source of allergic disease such as allergic rhinitis and asthma. It has been a challenge to properly evaluate health risks caused by HDM related allergens including mite bodies, eggs and fecal pellets. This paper presents a numerical study on particle deposition of dust mite allergens in a human nasal cavity. Materials and methods: A realistic nasal cavity model was reconstructed from CT scans and a Computational Fluid Dynamics analysis of steady airflow was simulated. The discrete phase model was used to trace particle trajectories of three dust mite related particles. Results: The flow and particle model were validated by comparing with nasal resistance measurement and previous literature respectively. Aerodynamic characteristics and deposition of dust mite allergens in the nasal cavity were analyzed under different breathing conditions including rest and exercising conditions. Conclusions: The numerical results revealed the roles of different nasal cavity regions in filtering various types of dust mite allergens with consideration of breathing conditions.
Maternal Age and Preeclampsia Outcomes during Delivery Hospitalizations

Abstract Objective To characterize risk and temporal trends for preeclampsia and related outcomes by maternal age. Study Design Deliveries to women aged 15 to 54 years in the 1998 to 2014 National Inpatient Sample who had a diagnosis of preeclampsia, eclampsia, or both were included in the analysis. Age was categorized as 15 to 17, 18 to 24, 25 to 29, 30 to 34, 35 to 39, 40 to 44, and 45 to 54 years. The primary outcome was temporal trends in preeclampsia based on maternal age. Secondary outcomes analyzed included risk for severe maternal morbidity. Results The proportion of women with preeclampsia aged 15 to 24 years decreased from 42.3% in 1998 to 30.1% in 2014, while preeclampsia among those 30 to 54 years increased from 32.9 to 43.7%. Preeclampsia risk increased for all groups over the study period. Risk for severe morbidity by age group with and without transfusion was “U-shaped,” with risk highest for women 18 to 24 and 40 to 54 years. The risk for abruption, acute renal failure, acute heart failure or pulmonary edema, and stroke was lowest for women aged 15 to 24 years and increased in a “dose-dependent” manner with increasing maternal age. In contrast, eclampsia risk was highest for women aged 15 to 17 years. Conclusion With a changing demographic profile of preeclampsia, older women accounted for an increasing proportion of preeclampsia and related adverse outcomes.
Whisker-Mediated Touch System in Rodents: From Neuron to Behavior

A key question in systems neuroscience is to identify how sensory stimuli are represented in neuronal activity, and how the activity of sensory neurons in turn is “read out” by downstream neurons and give rise to behavior. The choice of a proper model system to address these questions, is therefore a crucial step. Over the past decade, the increasingly powerful array of experimental approaches that has become available in non-primate models (e.g., optogenetics and two-photon imaging) has spurred a renewed interest for the use of rodent models in systems neuroscience research. Here, I introduce the rodent whisker-mediated touch system as a structurally well-established and well-organized model system which, despite its simplicity, gives rise to complex behaviors. This system serves as a behaviorally efficient model system; known as nocturnal animals, along with their olfaction, rodents rely on their whisker-mediated touch system to collect information about their surrounding environment. Moreover, this system represents a well-studied circuitry with a somatotopic organization. At every stage of processing, one can identify anatomical and functional topographic maps of whiskers; “barrelettes” in the brainstem nuclei, “barreloids” in the sensory thalamus, and “barrels” in the cortex. This article provides a brief review on the basic anatomy and function of the whisker system in rodents.
Incidence and Related Factors for Hospital-Acquired Pneumonia Among Older Bedridden Patients in China: A Hospital-Based Multicenter Registry Data Based Study

Objective: To identify the incidence and related factors for hospital-acquired pneumonia (HAP) among older bedridden patients in China. Study design and setting: This multicenter registry data-based study conducted between November 2015 and March 2016 surveyed 7,324 older bedridden patients from 25 hospitals in China (six tertiary, 12 non-tertiary, and seven community hospitals). The occurrence of HAP among all participants was monitored by trained investigators. Demographics, hospitalization information and comorbidity differences were compared between patients with and without HAP. A multilevel regression analysis was used to explore the factors associated with HAP. Results: Among 7,324 older bedridden patients, 566 patients were diagnosed with HAP. The incidence of HAP in this study was 13.9 per 1,000 person-days. There were statistical differences in gender, age, length of bedridden days, BMI, smoking, department, undergoing general anesthesia surgery, ventilator application, Charlson comorbity index (CCI) score, disturbance of consciousness, tranquilizer use, glucocorticosteroid use, and antibiotic use between patients with HAP and patients without HAP (all p < 0.05). Multilevel regression analysis found no significant variance for HAP at the hospital level (0.332, t = 1.875, p > 0.05). There were significant differences for the occurrence of HAP among different departments (0.553, t = 4.320, p < 0.01). The incidence density of HAP was highest in the ICU (30.1‰) among the selected departments, followed by the departments of neurosurgery (18.7‰) and neurology medicine (16.6‰). Individual patient-level factors, including older age, disturbance of consciousness, total CCI score, ICU admission, and glucocorticoid and antibiotic use, were found to be associated with the occurrence of HAP (all p < 0.05). Conclusion: A relatively high incidence density of HAP among older bedridden patients was identified, as well as several factors associated with HAP among the population. This suggests that attention should be paid to the effective management of these related factors of older bedridden patients to reduce the occurrence of HAP.
Encoding Pleasant and Unpleasant Expression of the Architectural Window Shapes: An ERP Study

The evaluation of building facades is one of the most important elements in built environments for helping architects and professionals to develop future designs. The form or shape of windows in building facades has direct impacts on perceivers’ affective state and emotions. To understand the impacts of geometric windows on the subject’s feedback and cortical activity, psychophysics experiments and electroencephalogram (EEG) recordings were measured from the participants. Our behavioral results show a distinguished categorization of the window shapes as pleasant and unpleasant stimuli. The rectangular, square, circular and semi-circular arch were determined as the pleasant window shapes, while the triangular and triangular arch window shapes were distinguished as unpleasant. Furthermore, event-related potential (ERP) components (N1, P2 and P3) were investigated to determine the influence of window shapes on the local brain activity. To measure reliable cortical responses, a Butterworth notch filter (50 Hz), band pass filter (0.1–60 Hz) and ADJUST filter were employed to remove the artifacts. The electrophysiological results show increased activity for the unpleasant in comparison to the pleasant windows (p < 0.05, Rank-Sum test) in both frontal (for P2 component) and posterio-occipital (ERP amplitudes; the N1 through to the P3 peak) channels. The ERP amplitudes of the right hemisphere were significantly larger than in the left hemisphere, not only in response to the unpleasant (p < 0.001) but also to the pleasant window stimuli (p < 0.001, Signed-Rank test). However, the unpleasant stimuli evoked significantly larger ERP amplitude than the pleasant stimuli. Moreover, the significant ERPP2 amplitude was more distinguished for unpleasant (p = 0.01, Signed-Rank test) than pleasant windows (p = 0.01, Rank-Sum test) between frontal and central cortical lobes. Overall, our behavioral and electrophysiological studies demonstrate a distinguished categorization of pleasant and unpleasant window shapes and more significant ERP modulations in the right than left hemisphere for unpleasant windows compared to pleasant ones.