Miracle-dz/UniFAR-FTUs huggingface dataset:
Block-Constraint Laplacian-Regularized Low-Rank Representation and Its Application for Cancer Sample Clustering Based on Integrated TCGA Data

Low-Rank Representation (LRR) is a powerful subspace clustering method because of its successful learning of low-dimensional subspace of data. With the breakthrough of “OMics” technology, many LRR-based methods have been proposed and used to cancer clustering based on gene expression data. Moreover, studies have shown that besides gene expression data, some other genomic data in TCGA also contain important information for cancer research. Therefore, these genomic data can be integrated as a comprehensive feature source for cancer clustering. How to establish an effective clustering model for comprehensive analysis of integrated TCGA data has become a key issue. In this paper, we develop the traditional LRR method and propose a novel method named Block-constraint Laplacian-Regularized Low-Rank Representation (BLLRR) to model multigenome data for cancer sample clustering. The proposed method is dedicated to extracting more abundant subspace structure information from multiple genomic data to improve the accuracy of cancer sample clustering. Considering the heterogeneity of different genome data, we introduce the block-constraint idea into our method. In BLLRR decomposition, we treat each genome data as a data block and impose different constraints on different data blocks. In addition, graph Laplacian is also introduced into our method to better learn the topological structure of data by preserving the local geometric information. The experiments demonstrate that the BLLRR method can effectively analyze integrated TCGA data and extract more subspace structure information from multigenome data. It is a reliable and efficient clustering algorithm for cancer sample clustering.
Doing things differently: Exploring attachment patterns and parental intentions in families where a child has a diagnosis of autism

The article examines the experience of parenting a child with a diagnosis of autism with a focus on scripts and intentions in relation to the parents’ own childhood experiences of being parented. Five parents participated in a multiple case study design involving in-depth interviews, Adult Attachment Interviews and a parenting intentions scaling task. The findings revealed that all of the parents had experienced significant adverse events in their own childhoods, including trauma and losses. They also expressed intentions to offer parenting that was ‘corrective’ in terms of providing a better emotional environment for their children. Their corrective attempts and also intentions to repeat positive aspects of being parented were moderated by unconscious aspects of their early childhood experiences and also by the autistic features of their children. The interplay between early embodied experiences, theories of autism, parenting experiences and intentions is discussed along with clinical implications.
Surgical harm of cytoreductive nephrectomy in the era of targeted therapy

In the September issue of Urology , Wallis et al . (1) examine the effect of disseminated cancer on perioperative outcomes in renal cell carcinoma (RCC) patients following radical nephrectomy. They utilized the National Surgical Quality Improvement Program (NSQIP), which is an American College of Surgeons initiative that supports the collection of risk-adjusted perioperative data to facilitate the assessment of surgical outcomes and complications in (within) 30 days of surgery. In contrast to previous studies that reported outcomes after cytoreductive nephrectomy, the strength of this study lies in the presence of a comparator group to merely assess the effect of “disseminated disease”. Wallis and colleagues therefore stratified the total of 7,800 NCC patients according to “disseminated” (8.4%) or “non-disseminated cancer” (91.6%) status. By relying on robust methodology the authors demonstrate a greater risk of major complications including mortality and reoperation [adjusted odds ratio (aOR) 2.04, 95% confidence interval (CI): 1.46–2.86), prolonged length of hospital stay (aOR 1.27, 95% CI: 1.06–1.53) and pulmonary (aOR 1.68, 95% CI: 1.09–2.59), venous thromboembolic (aOR 1.72, 95% CI: 1.01–2.96), as well as bleeding complications (aOR 2.12, 95% CI: 1.73–2.60) in the presence of disseminated cancer compared to non-disseminated status.
An overview of cannabis based treatment in Crohn’s disease

ABSTRACT Introduction: Cannabis use among inflammatory bowel disease (IBD) patients is common. There are many studies of various laboratory models demonstrating the anti–inflammatory effect of cannabis, but their translation to human disease is still lacking. Areas covered: The cannabis plant contains many cannabinoids, that activate the endocannabinoid system. The two most abundant phytocannabinoids are the psychoactive Tetrahydrocannabinol (THC), and the (mostly) anti–inflammatory cannabidiol (CBD). Approximately 15% of IBD patients use cannabis to ameliorate disease symptoms. Unfortunately, so far there are only three small placebo controlled study regarding the use of cannabis in active Crohns disease, combining altogether 93 subjects. Two of the studies showed significant clinical improvement but no improvement in markers of inflammation. Expert opinion: Cannabis seems to have a therapeutic potential in IBD. This potential must not be neglected; however, cannabis research is still at a very early stage. The complexity of the plant and the diversity of different cannabis chemovars create an inherent difficulty in cannabis research. We need more studies investigating the effect of the various cannabis compounds. These effects can then be investigated in randomized placebo controlled clinical trials to fully explore the potential of cannabis treatment in IBD.
Transcriptome-wide piRNA profiling in human brains for aging genetic factors.

Objective Piwi-interacting RNAs (piRNAs) represent a molecular feature shared by all nonaging biological systems, including the germline and somatic cancer stem cells, which display an indefinite renewal capacity and lifespan-stable genomic integrity and are potentially immortal. Here, we tested the hypothesis that piRNA is a critical genetic determinant of aging in humans. Methods Expression of transcriptome-wide piRNAs (n=24k) was profiled in the human prefrontal cortex of 12 subjects (84.9±9.5, range 68-100, years of age) using microarray technology. We examined the correlation between these piRNAs' expression levels and age, adjusting for covariates including disease status. Results A total of 9,453 piRNAs were detected in brain. Including seven intergenic and three intronic piRNAs, ten piRNAs were significantly associated with age after correction for multiple testing (|r|=0.9; 1.9×10-5≤p≤9.9×10-5). Conclusion We conclude that piRNAs might play a potential role in determining the years of survival of humans. The underlying mechanisms might involve the suppression of transposable elements (TEs) and expression regulation of aging-associated genes.
The Role of Hypoxia-Inducible Factor 1α in the Regulation of Human Meibomian Gland Epithelial Cells

Purpose We recently discovered that a hypoxic environment is beneficial for meibomian gland (MG) function. The mechanisms underlying this effect are unknown, but we hypothesize that it is due to an increase in the levels of hypoxia-inducible factor 1α (HIF1α). In other tissues, HIF1α is the primary regulator of cellular responses to hypoxia, and HIF1α expression can be induced by multiple stimuli, including hypoxia and hypoxia-mimetic agents. The objective of this study was to test our hypothesis. Methods Human eyelid tissues were stained for HIF1α. Immortalized human MG epithelial cells (IHMGECs) were cultured for varying time periods under normoxic (21% O2) or hypoxic (1% O2) conditions, in the presence or absence of the hypoxia-mimetic agent roxadustat (Roxa). IHMGECs were then processed for the analysis of cell number, HIF1α expression, lipid-containing vesicles, neutral and polar lipid content, DNase II activity, and intracellular pH. Results Our results show that HIF1α protein is present in human MG acinar epithelial cells in vivo. Our findings also demonstrate that exposure to 1% O2 or to Roxa increases the expression of HIF1α, the number of lipid-containing vesicles, the content of neutral lipids, and the activity of DNase II and decreases the pH in IHMGECs in vitro. Conclusions Our data support our hypothesis that the beneficial effect of hypoxia on the MG is mediated through an increased expression of HIF1α.
Activity Recognition From Newborn Resuscitation Videos

<italic>Objective:</italic> Birth asphyxia is one of the leading causes of neonatal deaths. A key for survival is performing immediate and continuous quality newborn resuscitation. A dataset of recorded signals during newborn resuscitation, including videos, has been collected in Haydom, Tanzania, and the aim is to analyze the treatment and its effect on the newborn outcome. An important step is to generate timelines of relevant resuscitation activities, including <italic>ventilation</italic>, <italic>stimulation</italic>, <italic>suction</italic>, etc., during the resuscitation episodes. <italic>Methods:</italic> We propose a two-step deep neural network system, ORAA-net, utilizing low-quality video recordings of resuscitation episodes to do activity recognition during newborn resuscitation. The first step is to detect and track relevant objects using Convolutional Neural Networks (CNN) and post-processing, and the second step is to analyze the proposed activity regions from step 1 to do activity recognition using 3D CNNs. <italic>Results:</italic> The system recognized the activities <italic>newborn uncovered</italic>, <italic>stimulation</italic>, <italic>ventilation</italic> and <italic>suction</italic> with a mean precision of 77.67%, a mean recall of 77,64%, and a mean accuracy of 92.40%. Moreover, the accuracy of the estimated number of Health Care Providers (HCPs) present during the resuscitation episodes was 68.32%. <italic>Conclusion:</italic> The results indicate that the proposed CNN-based two-step ORAA-net could be used for object detection and activity recognition in noisy low-quality newborn resuscitation videos. <italic>Significance:</italic> A thorough analysis of the effect the different resuscitation activities have on the newborn outcome could potentially allow us to optimize treatment guidelines, training, debriefing, and local quality improvement in newborn resuscitation.
Human Temporal Bone Study of Vestibular Histopathology in Cochlear Implant Patients With Cochlear Hydrops.

HYPOTHESIS Endolymphatic hydrops (EH) associated with cochlear implantation are associated with vestibular dysfunction. BACKGROUND Vestibular dysfunction is a known risk after cochlear implantation (CI). CI has been shown to cause cochlear hydrops due to fibrosis surrounding the ductus reuniens. However, the association of cochlear hydrops with vestibular hydrops and the relationship to vestibular symptoms remain unknown. METHODS Histopathological analysis and clinical evaluation of the vestibular end organs of 17 human temporal bones (HTB)s exhibiting cochlear hydrops from 15 CI recipients. RESULTS Eight of 15 patients with cochlear hydrops due to CI had complaints of dizziness, vertigo, or imbalance following CI. In all 17 HTBs with cochlear hydrops, there was fibrosis, atrophy, or obstruction of the ductus reuniens, and all had straight electrode CI via cochleostomy. In one of the eight reporting postoperative dizziness, labyrinthitis ossificans was deemed causative. Six of the seven remaining patients had EH of both the saccule and utricle. Fifteen of 17 HTBs (88.2%) had saccular EH. In contrast, 8 of 17 HTBs (47.0%) in 7 patients had utricular EH, of which 6 patients had postoperative vertigo spells. It seems that hydrops of the utricle closely corresponds to postoperative vertigo spells and vestibular complaints. CONCLUSION Implantation of the CI, when complicated by ductus reuniens fibrosis, may cause both cochlear hydrops and vestibular endolymphatic hydrops. Hydrops of the vestibular periphery when involving the utricle seems to be more likely associated with disabling vertigo symptoms. This study supports the round window technique of insertion rather than cochleostomy.
Intrinsic antiviral immunity drives neurodegeneration in Alzheimer disease.

β-amyloid aggregates found in brain plaques are viewed as triggers of cytotoxicity and neuroinflammation in Alzheimer disease (AD). However, the main β-amyloid (Aβ) species and what imbues the aggregates with such toxic potential are still not yet understood. In this issue of the JCI, Roy et al. show that Aβ complexed with nucleic acids triggers an antiviral type I interferon response in neuroglia, resulting in complement-mediated synapse elimination in AD models. These findings identify a putative endogenous immune signaling axis that drives neurodegeneration in AD and has strong implications for the development of precise therapeutic strategies.
A Dual-Sensing Thermo-Chemical ISFET Array for DNA-Based Diagnostics

This paper presents a 32 × 32 ISFET array with in-pixel dual-sensing and programmability targeted for on-chip DNA amplification detection. The pixel architecture provides thermal and chemical sensing by encoding temperature and ion activity in a single output PWM, modulating its frequency and its duty cycle respectively. Each pixel is composed of an ISFET-based differential linear OTA and a 2-stage sawtooth oscillator. The operating point and characteristic response of the pixel can be programmed, enabling trapped charge compensation and enhancing the versatility and adaptability of the architecture. Fabricated in 0.18 $\mu \rm{m}$ standard CMOS process, the system demonstrates a quadratic thermal response and a highly linear pH sensitivity, with a trapped charge compensation scheme able to calibrate 99.5% of the pixels in the target range, achieving a homogeneous response across the array. Furthermore, the sensing scheme is robust against process variations and can operate under various supply conditions. Finally, the architecture suitability for on-chip DNA amplification detection is proven by performing Loop-mediated Isothermal Amplification (LAMP) of phage lambda DNA, obtaining a time-to-positive of 7.71 minutes with results comparable to commercial qPCR instruments. This architecture represents the first in-pixel dual thermo-chemical sensing in ISFET arrays for Lab-on-a-Chip diagnostics.
How often are outcomes other than change in substance use measured? A systematic review of outcome measures in contemporary randomised controlled trials.

ISSUES Recovery is a theoretical construct and empirical object of inquiry. The aim was to review whether outcome measures used in randomised controlled trials of drug treatment reflect a comprehensive conceptualisation of recovery. APPROACH Systematic review using the following databases: Cochrane Database of Systematic Reviews, Cochrane Controlled Register of Trials, Database of Abstracts of Reviews of Effect, Web of Science, MEDLINE, Embase and PsycINFO. Search returned 6556 original articles and 504 met the following inclusion criteria: randomised controlled trial in English-language peer-reviewed journal; sample meets criteria for drug dependence or drug use disorder; reports non-substance use treatment outcomes. Review protocol registration: PROSPERO (CRD42018090064). KEY FINDINGS 3.8% of the included studies had a follow up of 2 years or more. Withdrawal/craving was present in 31.1% of short-term versus 0% of long-term studies. Social functioning in 8% of short-term versus 36.8% of long-term studies. Role functioning (0.9 vs. 26.3%), risk behaviour (15.6 vs. 36.8%) and criminality (3.8 vs. 21.1%) followed a similar pattern. Housing was not examined short-term and unregularly long-term (2.0%). 'Use of health-care facilities', clinical psychological, behavioural factors were frequently reported. Physiological or somatic health (15.2 vs. 10.5%), motivation (14.2 vs. 15.8%) and quality of life (7.1 vs. 0%) were less frequently reported. CONCLUSION The short time interval of the follow up and lack of information on relevant factors in recovery prevents the development of evidence-based approaches to improve these factors. Particularly, measures of social and role functioning should be added to reflect an adequate conceptualisation of recovery.
Antimicrobial resistance and antibiotic usage: what can surgeons do?

1. Watters D, Civil I. Foreword. In: Surgical Competence and Performance. Royal Australasian College of Surgeons and The College of Surgeons of Australia and New Zealand, 2011. Available from URL: https:// umbraco.surgeons. org/media/1663/2011-06-23_pos_fes-pst-024_surgical_ competence_and_performance_guide_2nd_edition. pdf. 2. Shine R, Bui A, Burgess A. Quality indicators in colonoscopy: an evolving paradigm. ANZ J. Surg. 2020; 90: 215–21.
Panel Design and Optimization for High‐Dimensional Immunophenotyping Assays Using Spectral Flow Cytometry

Technological advances in fluorescence flow cytometry and an ever‐expanding understanding of the complexity of the immune system have led to the development of large (20+ parameters) flow cytometry panels. However, as panel complexity and size increase, so does the difficulty involved in designing a high‐quality panel, accessing the instrumentation capable of accommodating large numbers of parameters, and analyzing such high‐dimensional data. A recent advancement is spectral flow cytometry, which in contrast to conventional flow cytometry distinguishes the full emission spectrum of each fluorophore across all lasers, rather than identifying only the peak of emission. Fluorophores with a similar emission maximum but distinct off‐peak signatures can therefore be accommodated within the same flow cytometry panel, allowing greater flexibility in terms of panel design and fluorophore detection. Here, we highlight the specific characteristics of spectral flow cytometry and aim to guide users through the process of building, designing, and optimizing high‐dimensional spectral flow cytometry panels using a comprehensive step‐by‐step protocol. Special considerations are also given for using highly overlapping dyes, and a logical selection process for optimal marker‐fluorophore assignment is provided. © 2020 by John Wiley & Sons, Inc.
The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial

Objective Since sperm abnormalities are known to be a major reason for recurrent pregnancy loss (RPL), any defects in DNA structure and chromatin condensation can place embryos at risk in the early stage of development and implantation. As antioxidants such as vitamin C may play a protective role against the destruction of protamine genes in sperm chromatin, this study was conducted to evaluate the effects of vitamin C on chromatin and the expression of protamine genes in the male partners of couples with RPL. Methods Twenty male partners of couples with RPL were selected as the intervention group and received vitamin C supplementation (250 mg daily for 3 months). Healthy fertile men (n=20) were included as controls. Sperm chromatin, DNA integrity, and the expression levels of protamine genes were evaluated before and after treatment. Results Significant differences were found in sperm morphology, protamine deficiency, and apoptosis between the two groups and before and after vitamin C administration. A significant change was found in mRNA levels of PRM1, PRM2, and the PRM1/PRM2 ratio after treatment. Conclusion Daily oral administration of vitamin C may improve human sperm parameters and DNA integrity by increasing protamine gene expression levels in the male partners of couples with RPL. The beneficial effects of vitamin C supplementation as an antioxidant for the male partners of couples with RPL could lead to improved pregnancy outcomes in these cases.
The fragmentation patterns of maternal plasma cell‐free DNA and its applications in non‐invasive prenatal testing

The discovery of cell‐free DNA (cfDNA) in maternal plasma has opened up new promises for the development of non‐invasive prenatal testing (NIPT). Application of cfDNA in NIPT of fetus diseases and abnormalities is restricted by the low amount of fetal DNA molecules in maternal plasma. Fetus‐derived cfDNA in maternal plasma are shorter than maternal DNA, thus leveraging the maternal and fetus‐derived cfDNA molecules size difference has become a novel and more accurate method for NIPT. However, multiple biological properties such as size distribution of plasma DNA, proportion of fetal‐derived DNA and methylation levels in maternal plasma across different gestational ages still remain largely unknown. Further insights into the size distribution and fragmentation pattern of circulating plasma cfDNA will shed light on the origin and fragmentation mechanisms of cfDNA during physiological and pathological processes in prenatal diseases and enhance our ability to take the advantage of plasma cfDNA as a molecular diagnostic tool. In the review, we start by summarizing the research techniques for the determination of the fragmentation profiles of cfDNA in maternal plasma. We then summarize the main progress and findings in size profiles of maternal plasma cfDNA and cffDNA. Finally, we discuss the potential diagnostic applications of plasma cfDNA size profiling.
Breaking the fast for procedural sedation: changing risk or risking change?

1 Specialty Registrar, Department of Anaesthesia, Royal Victoria Hospital, Belfast, UK 2Consultant, Department of Anaesthesia, Royal Lancaster Infirmary, Lancaster, UK . Correspondence to: G. C.McCracken Email: gc.mccracken@doctors.org. uk Accepted: 28 January 2020
Correlation of sociodemographic profiles with psychological problems among hospitalized patients receiving unplanned hemodialysis

Abstract Purpose In this prospective study, we aimed to examine the sociodemographic factors and clinical factors associated with psychological disorders in chronic kidney disease (CKD) patients receiving unplanned hemodialysis (HD). Methods We prospectively enrolled 187 CKD stage 5 patients receiving unplanned HD at a tertiary hospital from January 2015 to December 2016. We used structured questionnaires to gather data about participants’ anxiety, depression, and sleep disturbance. Generalized linear regression analysis was used to examine the relationships between sociodemographic and laboratory parameters, and severity of psychological distress. Results The mean age of the participants was 60 years, and the number of men and women was 97 and 90, respectively. We did not find a significant association between anxiety, depression, and sleep disturbance scores and gender, age, marital status, religion status, education levels, and employment status and number of comorbidities. Generalized linear regression analysis showed that a multidisciplinary CKD care program in outpatient clinic disclosed a significant negative association with psychological disorders in participants. Conclusions CKD patients exhibited psychological distress when receiving unplanned HD, not closely associated with sociodemographic profiles.