Comparative analysis of Student's live online learning readiness during the coronavirus (COVID-19) pandemic in the higher education sector.

Amid the coronavirus outbreak, many countries are facing a dramatic situation in terms of the global economy and human social activities, including education. The shutdown of schools is affecting many students around the world, with face-to-face classes suspended. Many countries facing the disastrous situation imposed class suspension at an early stage of the coronavirus outbreak, and Asia was one of the earliest regions to implement live online learning. Despite previous research on online teaching and learning, students' readiness to participate in the real-time online learning implemented during the coronavirus outbreak is not yet well understood. This study explored several key factors in the research framework related to learning motivation, learning readiness and student's self-efficacy in participating in live online learning during the coronavirus outbreak, taking into account gender differences and differences among sub-degree (SD), undergraduate (UG) and postgraduate (PG) students. Technology readiness was used instead of conventional online/internet self-efficacy to determine students' live online learning readiness. The hypothetical model was validated using confirmatory factor analysis (CFA). The results revealed no statistically significant differences between males and females. On the other hand, the mean scores for PG students were higher than for UG and SD students based on the post hoc test. We argue that during the coronavirus outbreak, gender differences were reduced because students are forced to learn more initiatively. We also suggest that students studying at a higher education degree level may have higher expectations of their academic achievement and were significantly different in their online learning readiness. This study has important implications for educators in implementing live online learning, particularly for the design of teaching contexts for students from different educational levels. More virtual activities should be considered to enhance the motivation for students undertaking lower-level degrees, and encouragement of student-to-student interactions can be considered.

Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease.

BACKGROUND: Success in personalized medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay [PEA] to identify diagnostic and prognostic biomarkers in inflammatory bowel disease [IBD]. METHODS: We conducted a prospective case-control study in an inception cohort of 552 patients [328 IBD, 224 non-IBD], profiling proteins recruited across six centres. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross-validation was used to examine the performance of diagnostic and prognostic proteins. RESULTS: A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls, including matrix metallopeptidase-12 [MMP-12; Holm-adjusted p = 4.1 × 10-23] and oncostatin-M [OSM; p = 3.7 × 10-16]. Nine of these proteins are associated with cis-germline variation [59 independent single nucleotide polymorphisms]. Fifteen proteins, all members of tumour necrosis factor-independent pathways including interleukin-1 (IL-1) and OSM, predicted escalation, over a median follow-up of 518 [interquartile range 224-756] days. Nested cross-validation of the entire data set allowed characterization of five-protein models [96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7 and IL8], which define a high-risk subgroup in IBD [hazard ratio 3.90, confidence interval: 2.43-6.26], or allowed distinct two- and three-protein models for ulcerative colitis and Crohn's disease respectively. CONCLUSION: We have characterized a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings.

Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease.

BACKGROUND: MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. METHODS: In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn's disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. RESULTS: In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [p = 0.01], miR-3615 [p = 0.02] and miR-4792 [p = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20-3.27; logrank p = 1.80 × 10-3), in particular CD [HR 2.81; IQR: 1.11-3.53, p = 6.50 × 10-4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. INTERPRETATION: We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.

Fecal calprotectin predicts the clinical course of acute severe ulcerative colitis.

OBJECTIVES: Calprotectin is a granulocyte neutrophil-predominant cytosolic protein. Fecal concentrations are elevated in intestinal inflammation and may predict relapse in quiescent inflammatory bowel disease. We aim to investigate fecal calprotectin (FC) as a biomarker in predicting the clinical course of acute severe ulcerative colitis (ASUC). METHODS: In 90 patients with ASUC requiring intensive in-patient medical therapy (January 2005-September 2007), we investigated the discriminant ability of FC to predict colectomy and corticosteroid and infliximab nonresponse. All patients received parenteral corticosteroids as first-line treatment; 21 (23.3%) were also treated with infliximab (5 mg/kg), after failure of corticosteroid therapy. RESULTS: Of 90 patients, 31 (34.4%) required colectomy, including 11 (52.4%) of those treated with infliximab. Overall FC was high (1,020.0 microg/g interquartile range: 601.5-1,617.5). FC was significantly higher in patients requiring colectomy (1,200.0 vs. 887.0; P=0.04), with a trend toward significance when comparing corticosteroid nonresponders and responders (1,100.0 vs. 863.5; P=0.08), as well as between infliximab nonresponders and responders (1,795.0 vs. 920.5; P=0.06). Receiver-operator characteristic curve analysis yielded an area under the curve of 0.65 to predict colectomy (P=0.04), with a maximum likelihood ratio of 9.23, specificity 97.4%, and sensitivity 24.0% at a cutoff point of 1,922.5 microg/g. Kaplan-Meier analyses showed that using 1,922.5 microg/g over a median follow-up of 1.10 years, 87% of patients will need subsequent colectomy. CONCLUSIONS: This is the first data set to demonstrate that FC levels are dramatically elevated in severe UC. These data raise the possibility that this biomarker can predict response to first or second-line medical therapy in this setting.

Regional variation in gene expression in the healthy colon is dysregulated in ulcerative colitis.

OBJECTIVE: To investigate differential intestinal gene expression in patients with ulcerative colitis and in controls. DESIGN: Genome-wide expression study (41,058 expression sequence tags, 215 biopsies). SETTING: Western General Hospital, Edinburgh, UK, and Genentech, San Francisco, USA. PATIENTS: 67 patients with ulcerative colitis and 31 control subjects (23 normal subjects and 8 patients with inflamed non-inflammatory bowel disease biopsies). INTERVENTIONS: Paired endoscopic biopsies were taken from 5 specific anatomical locations for RNA extraction and histology. The Agilent microarray platform was used and confirmation of results was undertaken by real time polymerase chain reaction and immunohistochemistry. RESULTS: In healthy control biopsies, cluster analysis showed differences in gene expression between the right and left colon. (chi(2) = 25.1, p<0.0001). Developmental genes, homeobox protein A13 (HOXA13), (p = 2.3x10(-16)), HOXB13 (p<1x10(-45)), glioma-associated oncogene 1 (GLI1) (p = 4.0x10(-24)), and GLI3 (p = 2.1x10(-28)) primarily drove this separation. When all ulcerative colitis biopsies and control biopsies were compared, 143 sequences had a fold change of >1.5 in the ulcerative colitis biopsies (0.01>p>10(-45)) and 54 sequences had a fold change of <-1.5 (0.01>p>10(-20)). Differentially upregulated genes in ulcerative colitis included serum amyloid A1 (SAA1) (p<10(-45)) the alpha defensins 5 and 6 (DEFA5 and 6) (p = 0.00003 and p = 6.95x10(-7), respectively), matrix metalloproteinase 3 (MMP3) (p = 5.6x10(-10)) and MMP7 (p = 2.3x10(-7)). Increased DEFA5 and 6 expression was further characterised to Paneth cell metaplasia by immunohistochemistry and in situ hybridisation. Sub-analysis of the inflammatory bowel disease 2 (IBD2) and IBD5 loci, and the ATP-binding cassette (ABC) transporter genes revealed a number of differentially regulated genes in the ulcerative colitis biopsies. CONCLUSIONS: Key findings are the expression gradient in the healthy adult colon and the involvement of novel gene families, as well as established candidate genes in the pathogenesis of ulcerative colitis.

Outcomes of the rectal remnant following colectomy for ulcerative colitis.

OBJECTIVE: Controversy surrounds the optimal surgical management of the distal rectal remnant during colectomy for ulcerative colitis (UC) and the potential benefit from the placement of a rectal catheter for remnant drainage. This study reviews the clinical outcomes of patients who have undergone colectomy for UC with intra-peritoneal closure of the rectal remnant. METHOD: Analysis of prospective data lodged on Lothian Surgical Audit databases from patients treated in a tertiary coloproctology unit over 11 years. RESULTS: One hundred and fifty-nine patients were identified, the mean age was 41.9 years, 63% were men. Failure of maximal medical therapy necessitated surgery for 78.1% patients, while 12.6% had acute perforation and 11.9% had toxic megacolon. Complications included five (3.1%) stump dehiscences, eight (5.0%) intra-abdominal/pelvic collections, four (2.5%) significant wound infections, three (1.9%) small bowel obstructions and three (1.9%) deaths. Within the follow-up period, 62.3% patients had an ileo-pouch anal anastomosis (IPAA), 7.5% patients had a completion proctectomy, 10.1% patients within the series had a retained rectal remnant after 1 year follow up, the remaining patients had less than 1 year follow up. CONCLUSION: The intra-peritoneal rectal stump following colectomy for UC is associated with low rates of pelvic sepsis and a high proportion of patients successfully proceeding to IPAA.

MDR1 deficiency impairs mitochondrial homeostasis and promotes intestinal inflammation.

The multidrug resistance-1 (MDR1) gene encodes an ATP-dependent efflux transporter that is highly expressed in the colon. In mice, loss of MDR1 function results in colitis with similarities to human inflammatory bowel diseases (IBD). Here, we show that MDR1 has an unexpected protective role for the mitochondria where MDR1 deficiency results in mitochondrial dysfunction with increased mitochondrial reactive oxygen species (mROS) driving the development of colitis. Exogenous induction of mROS accelerates, while inhibition attenuates colitis in vivo; these effects are amplified in MDR1 deficiency. In human IBD, MDR1 is negatively correlated to SOD2 gene expression required for mROS detoxification. To provide direct evidential support, we deleted intestinal SOD2 gene in mice and showed an increased susceptibility to colitis. We exploited the genome-wide association data sets and found many (∼5%) of IBD susceptibility genes with direct roles in regulating mitochondria homeostasis. As MDR1 primarily protects against xenotoxins via its efflux function, our findings implicate a distinct mitochondrial toxin+genetic susceptibility interaction leading to mitochondrial dysfunction, a novel pathogenic mechanism that could offer many new therapeutic opportunities for IBD.

A retrospective analysis of the efficacy and safety of infliximab as rescue therapy in acute severe ulcerative colitis.

BACKGROUND: Forty per cent of patients with acute severe ulcerative colitis will not respond to intravenous corticosteroids and require second-line medical therapy or colectomy. A recent controlled trial has suggested that infliximab may be effective as rescue therapy. AIM: To assess the value of infliximab as rescue therapy for acute severe colitis in a retrospective cohort of ulcerative colitis patients in Scotland. METHODS: All patients satisfied Truelove and Witts criteria on admission, failed to respond to intravenous corticosteroids and received infliximab (5 mg/kg) as rescue therapy. Response was defined as need for colectomy at hospital discharge and by 90 days. RESULTS: A total of 39 patients (median age 31.7 years) were treated. 26/39 (66%) responded, avoiding colectomy during the acute admission, and were followed up for a median of 203 days (Interquartile range = 135.5-328.5). Hypoalbuminaemia was a consistent predictor of non-response on univariate and multivariate analysis. At day 3 of intravenous steroids, 9/18 (50.0%) with serum albumin <34 g/L had urgent colectomy vs. 1/13 (7.7%) >or=34 g/L (P = 0.02, OR = 12.0, C.I. 1.28-112.7). Two serious adverse events occurred - one death due to Pseudomonas pneumonia, and one post-operative fungal septicaemia. CONCLUSIONS: Infliximab represents a moderately effective rescue therapy for patients with acute severe ulcerative colitis. Serious adverse events, including death, do occur and should be discussed with patients prior to therapy.

The efficacy of corticosteroid therapy in inflammatory bowel disease: analysis of a 5-year UK inception cohort.

BACKGROUND: Corticosteroids remain the mainstay of first-line therapy in active inflammatory bowel disease. AIMS: To determine the clinical outcome after the first corticosteroid-therapy and to identify factors which predict response/failure. METHODS: 216 (136 ulcerative colitis and 80 Crohn's disease) patients were identified in this 5-year inception cohort. The outcomes of early (30 days) and late (1 year) responses were used. Multivariate analyses were performed to identify factors associated with outcome. RESULTS: 86 (63%) and 60 (75%) ulcerative colitis and Crohn's disease required corticosteroid therapy, respectively. In ulcerative colitis, at 30 days, 69 (51%), 42 (31%) and 25 (18%) patients demonstrated complete response, partial response and no response, respectively. For Crohn's disease, these outcomes were observed in 32 (40%), 28 (35%) and 20 (25%). After 1 year, 75 (55%), 23 (17%) and 29 (21%) patients with ulcerative colitis demonstrated prolonged response, corticosteroid-dependence or required surgery, respectively. For Crohn's disease, these outcomes were observed in 30 (38%), 19 (24%) and 27 (35%) patients. Extensive ulcerative colitis was a predictor of surgery (P = 0.001, OR: 15.2). In Crohn's disease, inflammatory disease behaviour was negatively associated with surgery (P = 0.02, OR: 0.13). CONCLUSION: Although corticosteroids are effective, dependence/resistance remains common. Patients with extensive ulcerative colitis and fistulizing/stricturing Crohn's are most at risk of failing corticosteroid therapy.

Gut mucosal DAMPs in IBD: from mechanisms to therapeutic implications.

Endogenous damage-associated molecular patterns (DAMPs) are released during tissue damage and have increasingly recognized roles in the etiology of many human diseases. The inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are immune-mediated conditions where high levels of DAMPs are observed. DAMPs such as calprotectin (S100A8/9) have an established clinical role as a biomarker in IBD. In this review, we use IBD as an archetypal common chronic inflammatory disease to focus on the conceptual and evidential importance of DAMPs in pathogenesis and why DAMPs represent an entirely new class of targets for clinical translation.

Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery.

BACKGROUND: The failure rate of medical therapy in severe ulcerative colitis is high. A risk index, to aid the identification of patients of not responding at an early stage to intravenous corticosteroid therapy, would be useful to facilitate second-line treatment or surgery. METHODS: We recruited 167 consecutive patients with severe ulcerative colitis between January 1995 and March 2002; and employed multiple logistic regression to analyse parameters within the first 3 days of medical therapy. We applied statistical modelling to formulate a risk score according to the likelihood of medical failure. RESULTS: Sixty-seven (40%) patients failed to respond to medical therapy. Multiple logistic regression analysis identified mean stool frequency and colonic dilatation within the first 3 days and hypoalbuminaemia as independent predictors of outcome (P < 0.001, 0.001 and 0.002 respectively). A numerical risk score was formulated based on these variables. Patients with scores of 0-1, 2-3 and > or =4 had a medical therapy failure rate of 11%, 43% and 85% respectively. Receiver-operator characteristic analysis of this score yielded area under curve of 0.88, with a sensitivity of 85% and specificity of 75% using score > or =4 in predicting non-response. CONCLUSION: This risk score allows the early identification of patients with severe ulcerative colitis who would be suitable for second-line medical therapy or surgery.

The utility of patient age in evaluating prostate cancer.

The utility of age in examining patients for prostate cancer was assessed. Of the 462 patients in the study, 138 had prostate cancer. The age distribution of the patients with cancer was similar to that found in patients with prostate cancer in the US population, and a correlation between age and the serum prostate-specific antigen (PSA) value was noted (r = .4, P < .002). Selection of reference intervals had a significant effect on test performance. Using an interval of 0 to 4.0 ng/mL, sensitivity of the PSA assay was 90% overall and varied from 78% (patients aged 50-59 years) to 94% (patients aged 70-79 years). In contrast, age-adjusted reference ranges yielded corresponding sensitivities of 84%, 78%, and 88%. With a single, fixed reference range, specificity decreased with advancing patient age (P < .001). This trend was eliminated by adjusting the cutoff in different age groups. In addition, age-adjusted reference ranges improved specificity by 10%, and by using the results of examination of a biopsy specimen as the "gold standard," the total number of patients classified correctly by PSA increased from 226 to 250 (49%-54%). For staging before treatment, patient age, clinical stage, and Gleason score were combined to yield a single probability estimate for organ-confined disease (P < .001). The use of age-adjusted reference ranges is supported by this study, which demonstrates that assay efficiency and specificity improve and sensitivity, although decreased overall, becomes more uniform across age groups. In this patient population, age was useful in determining the probability of organ-confined prostate cancer. Use of this model in clinical decision making should await evaluation in a prospective trial.

The effect of testicular nongerm cell tumors on local spermatogenesis.

OBJECTIVE: To assess ipsilateral spermatogenesis in men with malignant and benign nongerm cell tumors of the testis. DESIGN, PATIENTS: Histologic review of radical orchiectomy specimens performed for 20 men with malignant nongerm cell tumors and 15 with benign testicular lesions, including five Leydig cell tumors with benign clinical features. MAIN OUTCOME MEASURES: Degree of spermatogenesis was determined on a 1 to 10 scale, with 10 representing mature sperm within a seminiferous tubule. For each patient "near" and "far" scores were determined by obtaining the mean score of 50 tubules adjacent (< 3 mm) to the tumor and 50 tubules distant (> 3 mm) from the tumor, respectively. RESULTS: Total, near, and far scores were all lower for malignant tumors than for benign lesions. Scores for Leydig cell tumors were similar to benign lesions. Malignant tumors demonstrated a gradient effect, with greatest impairment of spermatogenesis occurring adjacent to tumor. In contrast, a distinction between near and far scores was not observed for benign lesions or Leydig cell tumors. CONCLUSIONS: Malignant nongerm cell tumors of the testis were associated with significant impairment of ipsilateral spermatogenesis, particularly in areas adjacent to tumor. These findings are similar to those observed for testicular germ cell tumors, suggesting a generalized negative influence on ipsilateral spermatogenesis by malignant tumors.

Efficacy of endoscopic hydrocele ablation.

We describe a new endoscopic technique that was used for the treatment of symptomatic scrotal hydroceles in 10 men. Through a small skin incision, the parietal surface of the tunica vaginalis was ablated endoscopically using either electrocautery or the KTP:YAG laser. This approach permitted visual inspection of the scrotal contents with minimal manipulation and was performed using monitored local anesthesia with bilateral spermatic cord blocks. With a mean follow-up interval of 6.1 months, no hydrocele recurrences, wound infections, or hematomas have been detected. The mean operative time was comparable (53 minutes) to that in a historical control group consisting of 15 men who had undergone open hydrocelectomy at our institution (46 minutes). Postoperative scrotal discomfort was minimal, with 6 of the 10 patients requiring no analgesics. Patients were able to resume their preoperative lifestyles an average of 2 days after surgery. In contrast, 11 of the 15 men in the control group was still complaining of scrotal pain, requiring oral analgesics, at their 2-week follow-up visit. Thus, endoscopic hydrocele ablation appears to be an effective and well-tolerated alternative to treat hydroceles with minimal postoperative discomfort.

A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease.

BACKGROUND: Adalimumab is efficacious therapy for adults with Crohn's disease (CD). AIM: To summarise the United Kingdom and Republic of Ireland paediatric adalimumab experience. METHODS: British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) members with Inflammatory Bowel Disease (IBD) patients <18 years old commencing adalimumab with at least 4 weeks follow-up. Patient demographics and details of treatment were then collected. Response and remission was assessed using the Paediatric Crohn's Disease Activity Index (PCDAI)/Physicians Global Assessment (PGA). RESULTS: Seventy-two patients [70 CD, 1 ulcerative colitis (UC), 1 IBD unclassified (IBDU)] from 19 paediatric-centres received adalimumab at a median age of 14.8 (IQR 3.1, range 6.1-17.8) years; 66/70 CD (94%) had previously received infliximab. A dose of 80 mg then 40 mg was used for induction in 41(59%) and 40 mg fortnightly for maintenance in 61 (90%). Remission rates were 24%, 58% and 41% at 1, 6 and 12 months, respectively. Overall 43 (61%) went into remission at some point, with 24 (35%) requiring escalation of therapy. Remission rates were higher in those on concomitant immunosuppression cf. those not on immunosuppression [34/46 (74%) vs. 9/24 (37%), respectively, (χ(2) 8.8, P=0.003)]. There were 15 adverse events (21%) including four (6%) serious adverse events with two sepsis related deaths in patients who were also on immunosuppression and home parenteral nutrition (3% mortality rate). CONCLUSIONS: Adalimumab is useful in treatment of refractory paediatric patients with a remission rate of 61%. This treatment benefit should be balanced against side effects, including in this study a 3% mortality rate.

The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up.

BACKGROUND: Anti-TNF agents are now widely used in Crohn's disease (CD), and in ulcerative colitis (UC). AIM: To review the safety profile of anti-TNF agents in all patients treated with infliximab in Edinburgh from 1999 to 2007. METHODS: Complete data were available on 202/207 patients comprising 157 CD, 42 UC and three coeliac disease. Median follow-up was 2.4 years (1.0-4.9) with a total of 620 patient-years follow-up. About 19.1% of CD patients were subsequently treated with adalimumab. RESULTS: Seven deaths (3.3%) occurred in follow-up; only one death was <1 year post-infliximab (at day 72, from lung cancer). A total of six malignancies (three haematological, three bronchogenic) and six cases of suspected demyelination (three with confirmed neurological disease) were reported. In the 90 days following infliximab, 95 adverse events (36 serious) occurred in 58/202 (28.7%) patients. In all, 42/202 (20.8%) had an infectious event (22 serious) and 27/202 (13.4%) of patients had an infusion reaction: 19 acute (four serious) and eight delayed (three serious). CONCLUSIONS: Serious infections, malignancies and neurological disease complicate anti-TNF use in clinical practice. Although evidence for causality is unclear, potential mechanisms and predisposing factors need to be explored. In individual patients, the risk/benefit analysis needs to be carefully assessed and discussed prior to commencement of therapy.