Miracle-dz/UniFAR-FTUs huggingface dataset:
Young people’s experiences of orthodontic retainers: A qualitative study

Objective: To investigate young people’s experiences of retainers, the associated impact of retainers on their lives and their perceptions of what influences their own co-operation. Design: Qualitative, cross-sectional study. Setting: An orthodontic department in a UK dental hospital. Participants: Purposive sampling was used to recruit young people, aged 11–17 years, wearing a range of different types of retainers. Methods: Semi-structured interviews were conducted and transcribed. The resultant data were analysed using codebook thematic analysis. Results: Ten patients were recruited before thematic saturation was achieved. Four themes were identified: impact and experiences of wearing retainers; facilitators and barriers to retainer adherence; finding out about retainers; and, finally, involvement in decisions about retainers. Although some initial negative impacts were described, participants generally adapted quickly to retainers. Several factors were perceived to influence co-operation with removable retainers, including concerns about relapse and the associated waste of personal effort and wider resources. There were perceived deficiencies in the information provided by clinicians, which led participants to seek advice from other sources, including social media. Some young people wanted to be more involved in decisions about their retainers. Conclusion: While patients perceived retainers to be easier to wear than active appliances, some transient negative impacts occurred, largely related to initial periods of full-time wear. There were a range of factors which patients perceived to influence their adherence with removable retainers.
Extrachromosomal DNA in Cancer.

In cancer, complex genome rearrangements and other structural alterations, including the amplification of oncogenes on circular extrachromosomal DNA (ecDNA) elements, drive the formation and progression of tumors. ecDNA is a particularly challenging structural alteration. By untethering oncogenes from chromosomal constraints, it elevates oncogene copy number, drives intratumoral genetic heterogeneity, promotes rapid tumor evolution, and results in treatment resistance. The profound changes in DNA shape and nuclear architecture generated by ecDNA alter the transcriptional landscape of tumors by catalyzing new types of regulatory interactions that do not occur on chromosomes. The current suite of tools for interrogating cancer genomes is well suited for deciphering sequence but has limited ability to resolve the complex changes in DNA structure and dynamics that ecDNA generates. Here, we review the challenges of resolving ecDNA form and function and discuss the emerging tool kit for deciphering ecDNA architecture and spatial organization, including what has been learned to date about how this dramatic change in shape alters tumor development, progression, and drug resistance. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 23 is October 2022. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Stress‐induced vesicular assemblies of dual leucine zipper kinase are signaling hubs involved in kinase activation and neurodegeneration

Mitogen‐activated protein kinases (MAPKs) drive key signaling cascades during neuronal survival and degeneration. The localization of kinases to specific subcellular compartments is a critical mechanism to locally control signaling activity and specificity upon stimulation. However, how MAPK signaling components tightly control their localization remains largely unknown. Here, we systematically analyzed the phosphorylation and membrane localization of all MAPKs expressed in dorsal root ganglia (DRG) neurons, under control and stress conditions. We found that MAP3K12/dual leucine zipper kinase (DLK) becomes phosphorylated and palmitoylated, and it is recruited to sphingomyelin‐rich vesicles upon stress. Stress‐induced DLK vesicle recruitment is essential for kinase activation; blocking DLK‐membrane interaction inhibits downstream signaling, while DLK recruitment to ectopic subcellular structures is sufficient to induce kinase activation. We show that the localization of DLK to newly formed vesicles is essential for local signaling. Inhibition of membrane internalization blocks DLK activation and protects against neurodegeneration in DRG neurons. These data establish vesicular assemblies as dynamically regulated platforms for DLK signaling during neuronal stress responses.
Small Molecule Inhibitors of Interferon‐Induced JAK‐STAT Signalling

Abstract Interferons (IFN) are cytokines which, upon binding to cell surface receptors, trigger a series of downstream biochemical events including Janus Kinase (JAK) activation, phosphorylation of Signal Transducer and Activator of Transcription protein (STAT), translocation of pSTAT to the nucleus and transcriptional activation. Dysregulated IFN signalling has been linked to cancer progression and auto‐immune diseases. Here, we report the serendipitous discovery of a small molecule that blocks IFNγ activation of JAK‐STAT signalling. Further lead optimisation gave rise to a potent and more selective analogue that exerts its activity by a mechanism consistent with direct IFNγ targeting in vitro, which reduces bleeding in model of haemorrhagic colitis in vivo. This first‐in‐class small molecule also inhibits type I and III IFN‐induced STAT phosphorylation in vitro. Our work provides the basis for the development of pan‐IFN inhibitory drugs.
The Use of Mechanical Insufflation-Exsufflation in Invasively Ventilated Critically Ill Adults

Mechanical insufflation-exsufflation (MI-E) is traditionally used in the neuromuscular population. There is growing interest of MI-E use in invasively ventilated critically ill adults. We aimed to map current evidence on MI-E use in invasively ventilated critically ill adults. Two authors independently searched electronic databases MEDLINE, Embase, and CINAHL via the Ovid platform; PROSPERO; Cochrane Library; ISI Web of Science; and International Clinical Trials Registry Platform between January 1990–April 2021. Inclusion criteria were (1) adult critically ill invasively ventilated subjects, (2) use of MI-E, (3) study design with original data, and (4) published from 1990 onward. Data were extracted by 2 authors independently using a bespoke extraction form. We used Mixed Methods Appraisal Tool to appraise risk of bias. Theoretical Domains Framework was used to interpret qualitative data. Of 3,090 citations identified, 28 citations were taken forward for data extraction. Main indications for MI-E use during invasive ventilation were presence of secretions and mucus plugging (13/28, 46%). Perceived contraindications related to use of high levels of positive pressure (18/28, 68%). Protocolized MI-E settings with a pressure of ±40 cm H2O were most commonly used, with detail on timing, flow, and frequency of prescription infrequently reported. Various outcomes were re-intubation rate, wet sputum weight, and pulmonary mechanics. Only 3 studies reported the occurrence of adverse events. From qualitative data, the main barrier to MI-E use in this subject group was lack of knowledge and skills. We concluded that there is little consistency in how MI-E is used and reported, and therefore, recommendations about best practices are not possible.
Effectiveness of instrument-assisted soft tissue mobilization for the management of upper body, lower body, and spinal conditions. An updated systematic review with meta-analyses

Abstract Purpose To critically appraise randomized controlled trials (RCTs) on Instrument-Assisted Soft Tissue Mobilisation (IASTM) and quantify the effects of IASTM compared with other treatment in individuals with or without pathologies on function, pain, and range of motion. Materials and methods We search four electronic databases from January 1999 to January 2022 and included RCTs of healthy participants/athletes and people with upper, lower, or spinal conditions, who received IASTM versus other active treatment for clinical outcomes (function, pain, and range of motion). Results Forty-six RCTs were considered eligible for data analysis. Effects of IASTM plus other treatment versus other treatment on function and pain intensity were not statistically significant or clinically meaningful (very low quality, SMD −0.28, 95% CI −0.66 to 0.09) and (very low quality, SMD −0.05, 95% CI −0.53 to 0.43) at up to one-year follow-up respectively. No clinically meaningful improvements were found on range of motion outcomes. Out of the 46 included RCTs, only 10 assessed and reported IASTM-related adverse events. Conclusion Evidence of very low-quality certainty does not support the efficacy of IASTM in individuals with or without various pathologies on function, pain, and range of motion in the management of upper body, lower body, or spinal conditions. IMPLICATIONS FOR REHABILITATION The included RCTs had a high risk of bias and were assessed as very-low quality evidence for all the included outcomes. IASTM does not lead to clinically meaningful improvements in function, pain, or range of motion in individuals with upper body, lower body, and spinal conditions. The publication of IASTM trials in suspected predatory journals is increasing. The available evidence on IASTM does not support its use to improve function, pain, or range of motion in individuals with upper body, lower body, and spinal conditions. Health care practitioners should consider other evidence-based management strategies (physical activity and exercise) to improve function, pain, or range of motion in individuals with musculoskeletal injuries and disorders. Given the rise of publications on IASTM in suspected predatory journals, health care practitioners should be judicious to examine the legitimacy of a journal when searching for evidence on IASTM treatment technique.
Ovarian tumor frozen section, a multidisciplinary affair

Abstract Background Ovarian Cancer (OC) constitute the eighth most common cancers among women worldwide. Surgery remains the cornerstone in the management of OC. Intraoperative frozen section (FS) diagnosis is widely used to decide the surgery course. We aimed to assess the reliability of intraoperative FS diagnosis for treatment planning of patients with suspected OC from a multidisciplinary perspective. The clinical consequences of reclassification and the multidisciplinary management of the therapy plan, is the secondary aim of this study. To our knowledge, this information is sparely investigated. Methods A single-center, retrospective population-based study of patients who underwent surgery for suspected OC between 2018 and 2020. Histopathological outcomes were classified as benign, borderline, or malignant. The FS diagnosis was the diagnostic test, and the final histopathology report was the gold standard. Diagnostic capability for treatment planning was assessed, and modifications made possible by overall clinical knowledge were discussed. Results A total of 358 patients were identified, of whom 187 were included in the FS group. Overall accuracy was 89.8%, and 19 patients were reclassified; the malignancy grade of 15 tumors was underestimated. Prevalence, sensitivity, specificity, positive predictive value, and negative predictive value for invasive malignancies on FS were 54.0% (CI 46.6–61.3%), 88.1% (CI 80.2–93.7%), 98.8% (CI 93.7–99.9%), 98.9% (CI 92.7–99.8%), and 87.6% (CI 80.6–92.4%), respectively. Tumors incorrectly graded by FS tended to be of borderline-related. Conclusions The reliability of the FS methodology was an accurate test to help perform appropriate surgery and plan swift oncological treatment. FS is a reliable method to diagnose invasive malignancies and benign pathology. The communication between the pathologist, surgeon, and medical oncologist is highly important for both intraoperative decision-making and postoperative patient care.
Mothers at risk of postpartum depression in Sri Lanka: A population-based study using a validated screening tool

Background Postpartum depression is an important public health concern. The prevalence of postpartum depression is estimated to be 18% worldwide. The purpose of this study was to estimate the prevalence of mothers at risk of postpartum depression in Sri Lanka and to investigate its associated risk factors. Methods This was a cross-sectional study conducted among 975 mothers in Galle district, Sri Lanka. The prevalence of mothers at risk of postpartum depression was assessed using the Edinburgh Postpartum Depression scale (EPDS) which has been validated for screening for mothers at risk of postpartum depression in Sri Lanka with a cut-off score 9 or more. Prevalence was estimated using a cut-off 9 or more, 10 or more, 11 or more and 12 or more to assess the difference in prevalence using unvalidated cut-offs for screening. Data from routine records on pregnancy, delivery and postnatal care was collected to investigate possible predictors of EPDS score 9 or more (risk of postpartum depression). Univariate and multivariable logistic regressions were performed to identify risk factors for EPDS score 9 or more (risk of postpartum depression). Results The prevalence of mothers with EPDS score 9 or more was found to be 9.4% (95%CI: 7.8–11.4); EPDS score 10 or more was 5.6% (95%CI: 4.4–7.3). EPDS score 9 or more (risk of postpartum depression) was associated with the following risk factors: Former history of mental illness (aOR 32.9, 95%CI: 7.9–136.2), high maternal age 30–39 (aOR 2.2, 95%CI: 1.3–3.8), BMI 25.0–29.9 (aOR 2.6, 95%CI: 1.5–4.5), hypertension (aOR 3.6, 95%CI: 1.2–10.9) and newborn death (aOR 28.9, 95%CI: 4.5–185.1). One in five women reported thoughts of self-harm. Conclusion Around one in ten mothers in Sri Lanka experience symptoms of postpartum depression, highest risk among mothers who reported former history of mental illness and newborn death. The prevalence estimates were lower with a higher cut-off for screening and this highlights the importance of using the validated cut-off for screening in future studies on postpartum depression in Sri Lanka. Mothers at increased risk should be identified in antenatal care and are important targets of referral.
Oxymatrine induces anti-tumor response in cervical cancer by modulating circ_0008460/miR-197-3p/ribonucleotide reductase subunit M2 (RRM2)

ABSTRACT Oxymatrine (OMT) has exhibited an anti-cancer role in human cancers, including cervical cancer (CC). The dysregulated circular RNAs (circRNAs) are key regulators in cancer biology, and circ_0008460 was upregulated in CC. This study was performed to investigate the circRNA-based molecular mechanism for OMT in CC. RNA detection for circ_0008460, microRNA-197-3p (miR-197-3p), or ribonucleotide reductase subunit M2 (RRM2) was completed using reverse transcription-quantitative polymerase chain reaction assay. Cell behaviors were assessed by Cell Counting Kit-8 assay for cell viability, colony formation assay or Edu assay for cell proliferation, flow cytometry for cell apoptosis, and wound healing assay/transwell assay for migration/invasion. Protein expression examination was conducted using western blot. Dual-luciferase reporter assay and RNA pull-down assay were applied to confirm target binding. Tumor xenograft assay was performed for OMT research in vivo. OMT induced circ_0008460 downregulation in CC cells. OMT-induced inhibitory effects on cell growth, migration, and invasion but promoting effect on cell apoptosis were attenuated by circ_0008460. Circ_0008460 directly interacted with miR-197-3p, and OMT inhibited malignant behaviors of CC cells via mediating circ_0008460/miR-197-3p axis. RRM2 acted as a target for miR-197-3p and circ_0008460 affected the RRM2 level through absorbing miR-197-3p. OMT upregulated miR-197-3p to inhibit RRM2 expression to impede CC cell development. CC tumorigenesis was suppressed by OMT via targeting circ_0008460/miR-197-3p/RRM2 axis in vivo. These results suggested that OMT restrained CC cell progression in vitro and tumor growth in vivo by downregulating circ_0008460 to mediate miR-197-3p/RRM2 axis. GRAPHICAL ABSTRACT
Effectiveness of Yoga versus Exercise for Reducing Falling Risk in Older Adults: Physical and Psychological Indices

Our purpose in this study was to examine the effectiveness of yoga to address multiple risk factors of falling in active and low active older adults. Community–dwelling older adults (N = 35) over the age of 65 actively participated in either a yoga program, an exercise program, or a no–program control. Participants completed measures associated with falling risks. Physical measures included lower body strength, static balance, and lower body flexibility. Psychological measures included perceived self-efficacy with respect to falls and health–related quality of life. We determined between–group differences using planned comparisons, effect size, confidence intervals, and probability of superiority. Results of planned comparisons and practical significance testing indicated that yoga participants scored higher than the exercise and control participants on both right and left lower body flexibility tests. Yoga participants also scored higher than the control participants on right leg static balance, and the right and left lower body flexibility tests. The exercise participants scored higher than yoga participants on the RAND-36 Quality of Life subscales of Energy/Fatigue, Pain, and General Health. The probability of superiority results indicated that the no–program older adult participants would benefit by enrolling in the yoga rather than the exercise program to reduce physical risks of falling. These findings were discussed in relation to promoting physical activity programs to reduce risks of falling, and the roles of the protocol, practical significance, and measures employed when determining program effectiveness.
PaintOmics 4: new tools for the integrative analysis of multi-omics datasets supported by multiple pathway databases

Abstract PaintOmics is a web server for the integrative analysis and visualisation of multi-omics datasets using biological pathway maps. PaintOmics 4 has several notable updates that improve and extend analyses. Three pathway databases are now supported: KEGG, Reactome and MapMan, providing more comprehensive pathway knowledge for animals and plants. New metabolite analysis methods fill gaps in traditional pathway-based enrichment methods. The metabolite hub analysis selects compounds with a high number of significant genes in their neighbouring network, suggesting regulation by gene expression changes. The metabolite class activity analysis tests the hypothesis that a metabolic class has a higher-than-expected proportion of significant elements, indicating that these compounds are regulated in the experiment. Finally, PaintOmics 4 includes a regulatory omics module to analyse the contribution of trans-regulatory layers (microRNA and transcription factors, RNA-binding proteins) to regulate pathways. We show the performance of PaintOmics 4 on both mouse and plant data to highlight how these new analysis features provide novel insights into regulatory biology. PaintOmics 4 is available at https://paintomics.org/.
Virtual Reality Case Study throughout the Curriculum to Address Competency Gaps

While most instruction aims to provide students with content knowledge accompanied by practical application, the classroom experience typically has difficulty providing students with non-trivial examples. Graduating students also express a lack of confidence in integrating knowledge gained in disparate courses regarding identifying problems and synthesizing solutions. Many programs include industry-based projects as a solution to these issues. This approach has various drawbacks, including the difficulty of implementing such a project in a sizable number of the courses, the need for a significant commitment of class time, establishing contacts and ensuring that students have sufficient access to them to develop a model. The Industrial and Manufacturing Engineering Department at Wichita State University is developing an integrated set of realistic virtual reality models of a manufacturing line at Boeing Wichita. This line and the virtual models will serve as a mega-case that will be used throughout the curriculum to vertically integrate the concepts across the curriculum and provide a situated learning experience for students. This large-scale virtual reality factory module, `Innovation in Aircraft Manufacturing through System-Wide Virtual Reality Models and Curriculum Integration', is funded by the National Science Foundation through the Partnerships for Innovation program. The virtual reality models being developed include a Quest discrete-event simulation model of the 767 strut torque box manufacturing line and work cell level models in IGRIP and Jack software applications. Virtual Reality Markup Language (VRML) 2.0 files are generated from these models for use in case studies in various classes in the curriculum. Further details are available on the website (http://www.slvr.org). This paper recounts the gaps identified by the Society of Manufacturing Engineers and from surveys of our graduating seniors. A matrix that maps our plan to bridge some of these gaps in courses in the curriculum is presented. The use of virtual reality in general, and specifically in the classroom, is then discussed. The primary pedagogical approach used, situated learning, which places the learner at the center of the instructional process, is presented. Examples of course modules are then discussed to show practical applications of using the mega-case to bridge the gaps in manufacturing engineering education. A rubric developed for assessment of the critical elements required for an effective situated learning experience and the realization of these characteristics in the VR modules is presented. Lastly, the benefits and problems of this approach are discussed.