Application of a bioinformatics training delivery method for reaching dispersed and distant trainees.

Many initiatives have addressed the global need to upskill biologists in bioinformatics tools and techniques. Australia is not unique in its requirement for such training, but due to its large size and relatively small and geographically dispersed population, Australia faces specific challenges. A combined training approach was implemented by the authors to overcome these challenges. The "hybrid" method combines guidance from experienced trainers with the benefits of both webinar-style delivery and concurrent face-to-face hands-on practical exercises in classrooms. Since 2017, the hybrid method has been used to conduct 9 hands-on bioinformatics training sessions at international scale in which over 800 researchers have been trained in diverse topics on a range of software platforms. The method has become a key tool to ensure scalable and more equitable delivery of short-course bioinformatics training across Australia and can be easily adapted to other locations, topics, or settings.

The Alzheimer's Association international guidelines for handling of cerebrospinal fluid for routine clinical measurements of amyloid ß and tau.

The core cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers amyloid beta (Aß42 and Aß40), total tau, and phosphorylated tau, have been extensively clinically validated, with very high diagnostic performance for AD, including the early phases of the disease. However, between-center differences in pre-analytical procedures may contribute to variability in measurements across laboratories. To resolve this issue, a workgroup was led by the Alzheimer's Association with experts from both academia and industry. The aim of the group was to develop a simplified and standardized pre-analytical protocol for CSF collection and handling before analysis for routine clinical use, and ultimately to ensure high diagnostic performance and minimize patient misclassification rates. Widespread application of the protocol would help minimize variability in measurements, which would facilitate the implementation of unified cut-off levels across laboratories, and foster the use of CSF biomarkers in AD diagnostics for the benefit of the patients.

The role of HE4 for prediction of recurrence in epithelial ovarian cancer patients-results from the OVCAD study.

Patients with epithelial ovarian cancer (EOC) are at high risk of tumor recurrence. Human epididymis protein 4 (HE4) has been shown to be overexpressed in EOC. The primary aim of our study was to evaluate the role of HE4 in predicting recurrence in EOC patients. Furthermore, we assessed the role of HE4 in predicting recurrence after second-line chemotherapy. We retrospectively analyzed data of 92 out of 275 primary EOC patients of the multicenter project "Ovarian Cancer: Diagnosis of a silent killer" (OVCAD). The concentrations of HE4 and CA125 were determined preoperatively and 6 months after the end of platinum-based first-line chemotherapy (FU) using ELISA and Luminex technique, respectively. The role of HE4 and CA125 for prediction of recurrence was determined using receiver operating characteristics (ROC) curves. Out of 92 patients included, 70 (76 %) were responders and 22 (23 %) non-responders in terms of response to platinum-based first-line chemotherapy. Median HE4 concentrations at follow-up (FU) differed between responders and non-responders (60.5 vs. 237.25 pM, p = 0.0001), respectively. The combined use of HE4 and CA125 at FU with cut-off values of 49.5 pM and 25 U/ml for HE4 and CA125, respectively, for predicting recurrence within 12 months after first-line chemotherapy performed better than HE4 or CA125 alone (area under the curve (AUC) 0.928, 95 % confidence intervals (CI) 0.838-1, p < 0.001). HE4 at FU could predict recurrence within 6 months after second-line chemotherapy (AUC 0.719, 95 % CI 0.553-0.885, p = 0.024). The combination of both elevated biomarkers revealed significantly worse estimated median progression-free survival (PFS; hazard ratio (HR) 8.14, 95 % CI 3.75-17.68, p < 0.001) and slightly worse PFS in those in whom only one biomarker was elevated (HR 1.46, 95 % CI 0.72-2.96, p = 0.292) compared to those patients in whom no biomarker was elevated. For the estimated median overall survival (OS), our analysis revealed similar results. HE4 in combination with CA125 performed better than CA125 and HE4 alone in predicting recurrence within 12 months after first-line chemotherapy.

Blast neurotrauma impairs working memory and disrupts prefrontal myo-inositol levels in rats.

Working memory, which is dependent on higher-order executive function in the prefrontal cortex, is often disrupted in patients exposed to blast overpressure. In this study, we evaluated working memory and medial prefrontal neurochemical status in a rat model of blast neurotrauma. Adult male Sprague-Dawley rats were anesthetized with 3% isoflurane and exposed to calibrated blast overpressure (17 psi, 117 kPa) while sham animals received only anesthesia. Early neurochemical effects in the prefrontal cortex included a significant decrease in betaine (trimethylglycine) and an increase in GABA at 24 h, and significant increases in glycerophosphorylcholine, phosphorylethanolamine, as well as glutamate/creatine and lactate/creatine ratios at 48 h. Seven days after blast, only myo-inositol levels were altered showing a 15% increase. Compared to controls, short-term memory in the novel object recognition task was significantly impaired in animals exposed to blast overpressure. Working memory in control animals was negatively correlated with myo-inositol levels (r=-.759, p<0.05), an association that was absent in blast exposed animals. Increased myo-inositol may represent tardive glial scarring in the prefrontal cortex, a notion supported by GFAP changes in this region after blast overexposure as well as clinical reports of increased myo-inositol in disorders of memory.

HE4 expression in plasma correlates with surgical outcome and overall survival in patients with first ovarian cancer relapse.

BACKGROUND: Epithelial ovarian cancer (EOC) remains the main cause of mortality due to gynecological malignancies. Optimal tumor debulking and platinum response are the most important prognostic factors for overall survival (OS) in primary EOC. In the setting of recurrence, the role of cytoreduction is not clear. A critical point is to predict preoperatively the subgroup of patients with optimal surgical outcome. The aim of the study was to analyze the predictive role of HE4 for surgical outcome and platinum response in EOC patients experiencing a first relapse. Secondary aims were the prognostic role of HE4 for OS and progression-free survival (PFS). METHODS: Plasma was obtained before secondary cytoreduction from 73 EOC patients. A total of 66.7 % underwent a total macroscopic tumor clearance; 86.3 % of the patients had disease that responded to platinum therapy. HE4 was detected by enzyme-linked immunosorbent assay. For statistical analysis, the chi-square test, Fisher's exact test, Kendall's tau b, and Mann-Whitney U test were used. OS, PFS rates, and respective 95 % confidence intervals (CI) were estimated according to the Kaplan-Meier method. RESULTS: At a HE4 cutoff value of 250 pMk, a sensitivity of 52 % and a specificity of 93.8 % (p = 0.001, 95 % CI 0.601-0.861) were reached in predicting total macroscopic tumor clearance. Plasma HE4 concentrations together with platinum response were the only independent prognostic factors for OS (p < 0.001, hazard ratio [HR] 18.77, 95 % CI 4.68-75.25; and p = 0.044, HR 3.33, 95 % CI 1.03-10.7, respectively). Together with ascites, HE4 was the only independent predictive factor for surgical outcome (p = 0.029, odds ratio [OR] 7.2, 95 % CI 1.22-42.19 and p = 0.036, OR 10.18, 95 % CI 1.16-88.69, respectively). CONCLUSIONS: HE4 is an independent predictive marker for surgical outcome and OS in patients with recurrent EOC. Larger population studies are needed to validate these results.

Video brochures in a mailed fecal immunochemical test outreach program provide cancer screening information in a user-friendly format for rural Appalachian community members.

PURPOSE: Colorectal cancer (CRC) screening is recommended for average-risk adults, yet many adults are not up-to-date with screening. One recommended CRC screening approach is the annual completion of a fecal immunochemical test (FIT). However, usually, fewer than half of mailed FIT tests are returned. METHODS: To address barriers to FIT return, a video brochure was developed providing targeted CRC screening information and step-by-step FIT instructions as a component in a mailed FIT program. This pilot study occurred in 2021-2022 and partnered with a federally qualified health center in Appalachian Ohio to send a FIT to patients who were 50-64 years old, of average risk, and not up-to-date on CRC screening. Patients were randomly assigned to 1 of 3 groups that differed on materials sent with the FIT: usual care (manufacturer's instructions), a video brochure (video instructions, disposable gloves, disposable stool collection device), or an audio brochure (audio instructions, disposable gloves, disposable stool collection device). FINDINGS: Overall, 16 of 94 patients (17%) returned the FIT, and return was higher among those sent the video brochure (28%) compared to the other 2 groups (OR: 3.1; 95% CI: 1.02, 9.2; P = .046). Two patients had positive tests and were referred for colonoscopy. Patients sent the video brochure reported the content was important, relevant, and made them think about completing the FIT. CONCLUSIONS: Using a video brochure to provide understandable information in a mailed FIT kit is a promising strategy to improve CRC screening outreach programs in rural regions.

An international consensus on effective, inclusive, and career-spanning short-format training in the life sciences and beyond.

Science, technology, engineering, mathematics, and medicine (STEMM) fields change rapidly and are increasingly interdisciplinary. Commonly, STEMM practitioners use short-format training (SFT) such as workshops and short courses for upskilling and reskilling, but unaddressed challenges limit SFT's effectiveness and inclusiveness. Education researchers, students in SFT courses, and organizations have called for research and strategies that can strengthen SFT in terms of effectiveness, inclusiveness, and accessibility across multiple dimensions. This paper describes the project that resulted in a consensus set of 14 actionable recommendations to systematically strengthen SFT. A diverse international group of 30 experts in education, accessibility, and life sciences came together from 10 countries to develop recommendations that can help strengthen SFT globally. Participants, including representation from some of the largest life science training programs globally, assembled findings in the educational sciences and encompassed the experiences of several of the largest life science SFT programs. The 14 recommendations were derived through a Delphi method, where consensus was achieved in real time as the group completed a series of meetings and tasks designed to elicit specific recommendations. Recommendations cover the breadth of SFT contexts and stakeholder groups and include actions for instructors (e.g., make equity and inclusion an ethical obligation), programs (e.g., centralize infrastructure for assessment and evaluation), as well as organizations and funders (e.g., professionalize training SFT instructors; deploy SFT to counter inequity). Recommendations are aligned with a purpose-built framework-"The Bicycle Principles"-that prioritizes evidenced-based teaching, inclusiveness, and equity, as well as the ability to scale, share, and sustain SFT. We also describe how the Bicycle Principles and recommendations are consistent with educational change theories and can overcome systemic barriers to delivering consistently effective, inclusive, and career-spanning SFT.

Mental Health in Student Athletes: Associations With Sleep Duration, Sleep Quality, Insomnia, Fatigue, and Sleep Apnea Symptoms.

Purpose: To quantify the relationship between sleep difficulties and poor mental health among student athletes using validated measures. Methods: Data were collected from 190 National Collegiate Athletic Association Division I student athletes. Sleep assessments included measures of sleep duration, sleep quality, insomnia, fatigue, and sleep apnea symptoms. Mental well-being was assessed as depression, anxiety, mental health days, stress, and social support from family, friends, significant other, and teammates. Results: Shorter sleep duration, poor sleep quality, insomnia, and fatigue were consistently and independently associated with stress, depression, anxiety, mental health days, and social support. Sleep apnea symptoms were associated with stress, depression, and social support. Conclusions: Short sleep duration, poor sleep quality, and daytime fatigue in student athletes are all associated with depression, anxiety, stress, poor mental health days, and decreased social support. These associations are not accounted for solely by stress.

Brief Therapist-Guided Exposure Treatment of Panic Attacks: A Pilot Study.

A three-session therapist-guided exposure treatment was tested in a consecutive series of eight primary health care patients suffering from panic attacks who specifically used distraction techniques as their primary safety behavior. The Panic Disorder Severity Scale Self-Report (PDSS-SR) was administered at baseline (1-3 weeks before the first session), and 1, 2, and 3 weeks after treatment. Weekly ratings on the Body Sensations Questionnaire (BSQ) and the Agoraphobic Cognitions Questionnaire (ACQ) during treatment were undertaken to explore when reliable change took place on these measures. The results showed a large within-group effect size on PDSS-SR ( d = 1.63); six of the eight patients were classified as responders, and four of them showed remission. Large effect sizes ( ds between 1.17 and 3.00) were seen also on BSQ and ACQ, as well as on agoraphobic avoidance, general level of anxiety, and depression. The results on BSQ and ACQ suggest that the fear of body sensations in most cases was reduced before a change occurred in agoraphobic cognitions. These results indicate that a brief three-session exposure-based treatment may be sufficient for this subgroup of panic patients. The findings need to be replicated under controlled conditions with larger samples and different therapists before more firm conclusions can be drawn. Future research should also focus on the relevance of dividing patients into subgroups based on type of safety behavior.

Phage display for site-specific immunization and characterization of high-risk human papillomavirus specific E7 monoclonal antibodies.

The paper describes a method to use filamentous phage to display specific regions of proteins for immunization in order to direct the immune response towards a pre-defined region of the protein. The method called site-specific immunization (SSI) was evaluated using the E7 protein of oncogenic (high-risk) human papillomavirus (HPV) type 16 as a model system. This protein consists of sequence blocks also present in other viral and cellular proteins and in the corresponding protein of low-risk HPVs. A fragment of the HPV16 E7 oncoprotein specific for a group of high-risk viruses was identified by sequence comparison and displayed on filamentous phages in fusion with the major phage coat protein VIII. The recombinant phages triggered an immune response in mice against the full-length HPV16 E7 protein. Fusion of B-lymphocytes from the immunized animals with myeloma cells resulted in three hybridomas producing monoclonal antibodies (MAbs) with reactivity against the endogenous E7 protein. The specificity of the MAbs for the HPV16 E7 protein in cancer cell lines was confirmed by Western blot analyses and immunocytochemistry. The epitope of each MAb was roughly mapped by determining the reactivity against overlapping E7 fragments displayed on phage particles. The mimotopes of the MAbs were further determined by biopanning against a randomized peptide library displayed on phage and found to be unique for a sub-set of high-risk HPV E7 proteins. The combination of different phage display techniques for immunization and epitope mapping was efficient for generation and characterization of highly specific MAbs.

Enduring deficits in memory and neuronal pathology after blast-induced traumatic brain injury.

Few preclinical studies have assessed the long-term neuropathology and behavioral deficits after sustaining blast-induced neurotrauma (BINT). Previous studies have shown extensive astrogliosis and cell death at acute stages (<7 days) but the temporal response at a chronic stage has yet to be ascertained. Here, we used behavioral assays, immmunohistochemistry and neurochemistry in limbic areas such as the amygdala (Amy), Hippocampus (Hipp), nucleus accumbens (Nac), and prefrontal cortex (PFC), to determine the long-term effects of a single blast exposure. Behavioral results identified elevated avoidance behavior and decreased short-term memory at either one or three months after a single blast event. At three months after BINT, markers for neurodegeneration (FJB) and microglia activation (Iba-1) increased while index of mature neurons (NeuN) significantly decreased in all brain regions examined. Gliosis (GFAP) increased in all regions except the Nac but only PFC was positive for apoptosis (caspase-3). At three months, tau was selectively elevated in the PFC and Hipp whereas α-synuclein transiently increased in the Hipp at one month after blast exposure. The composite neurochemical measure, myo-inositol+glycine/creatine, was consistently increased in each brain region three months following blast. Overall, a single blast event resulted in enduring long-term effects on behavior and neuropathological sequelae.

Examining lethality risk for rodent studies of primary blast lung injury.

While protective measures have been taken to mitigate injury to the thorax during a blast exposure, primary blast lung injury (PBLI) is still evident in mounted/in vehicle cases during military conflicts. Moreover, civilians, who are unprotected from blast exposure, can be severely harmed by terrorist attacks that use improvised explosive devices (IEDs). Since the lungs are the most susceptible organ due to their air-filled nature, PBLI is one of the most serious injuries seen in civilian blast cases. Determining lethality threshold for rodent studies is crucial to guide experimental designs centered on therapies for survival after PBLI or mechanistic understanding of the injury itself. Using an Advanced Blast Simulator, unprotected rats were exposed to a whole body blast to induce PBLI. The one-hour survival rate was assessed to determine operating conditions for a 50% lethality rate. Macroscopic and histological analysis of lung was conducted using hematoxylin and eosin staining. Results demonstrated lethality risk trends based on static blast overpressure (BOP) for rodent models, which may help standardized animal studies and contribute to scaling to the human level. The need for a standardized method of producing PBLI is pressing and establishing standard curves, such as a lethality risk curve for lung blasts, is crucial for this condensing of BOP methods.

HE4 tissue expression in borderline ovarian tumors: a pilot study by the tumorbank ovarian cancer network.

AIM: Our purpose was to analyze the tissue expression of human epididymis protein-4 (HE4) in borderline tumors of the ovary (BOT) and to correlate it with histological subtypes and clinical features. PATIENTS AND METHODS: Tumor tissue samples from 25 patients with BOT were stained on tissue microarrays. The percentage of stained tumor cells was represented by grouped immunoreactivity scores (IRS) 0 to 4. RESULTS: The median patient age was 47 (range=22-73) years. Tumors in most patients (19/25) were staged-FIGO I and presented serous (52%) or mucinous (40%) histology. HE4 immunoreactivity occurred exclusively within the tumor cells. No association between grouped IRS and histological type, age, CA125 and FIGO stage was found. Correlation between HE4 positivity cells and HE4 IRS was significant (p<0.001). CONCLUSION: The role of HE4 in BOT remains unclear. Multicenter surveys are needed to more profoundly help in the understanding of the biological and clinical features of BOT.