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A computational pipeline for data augmentation towards the improvement of disease classification and risk stratification models: A case study in two clinical domains.

Comput Biol Med 2021 Jun 6;134:104520. Epub 2021 Jun 6.

Unit of Medical Technology and Intelligent Information Systems, Department of Materials Science and Engineering, University of Ioannina, Ioannina, GR45110, Greece; Department of Biomedical Research, FORTH-IMBB, Ioannina, GR45110, Greece. Electronic address:

Virtual population generation is an emerging field in data science with numerous applications in healthcare towards the augmentation of clinical research databases with significant lack of population size. However, the impact of data augmentation on the development of AI (artificial intelligence) models to address clinical unmet needs has not yet been investigated. In this work, we assess whether the aggregation of real with virtual patient data can improve the performance of the existing risk stratification and disease classification models in two rare clinical domains, namely the primary Sjögren's Syndrome (pSS) and the hypertrophic cardiomyopathy (HCM), for the first time in the literature. Read More

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Clinical correlates of white matter lesions in Parkinson's disease using automated multi-modal segmentation measures.

J Neurol Sci 2021 Jun 1;427:117518. Epub 2021 Jun 1.

Singapore General Hospital, Singapore; Duke-NUS Medical School, Singapore. Electronic address:

Background: Age-related white matter lesions (WML) are common, impact neuronal connectivity, and affect motor function and cognition. In addition to pathological nigrostriatal losses, WML are also common co-morbidities in Parkinson's disease (PD) that affect postural stability and gait. Automated brain volume measures are increasingly incorporated into the clinical reporting workflow to facilitate precision in medicine. Read More

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Large-scale evaluation of the Positive and Negative Syndrome Scale (PANSS) symptom architecture in schizophrenia.

Asian J Psychiatr 2021 Jun 3;62:102732. Epub 2021 Jun 3.

Research Division, Institute of Mental Health, Singapore; Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, United States; Feinstein Institute of Medical Research, The Zucker Hillside Hospital, New York, United States. Electronic address:

Although the Positive and Negative Syndrome Scale (PANSS) is widely utilized in schizophrenia research, variability in specific item loading exist, hindering reproducibility and generalizability of findings across schizophrenia samples. We aim to establish a common PANSS factor structure from a large multi-ethnic sample and validate it against a meta-analysis of existing PANSS models. Schizophrenia participants (N = 3511) included in the current study were part of the Singapore Translational and Clinical Research Program (STCRP) and the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE). Read More

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A homozygous nonsense mutation early in exon 5 of BRCA2 is associated with very severe Fanconi anemia.

Eur J Med Genet 2021 Jun 9:104260. Epub 2021 Jun 9.

Department of Pediatrics III, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany; Department of Otorhinolaryngology & Head/Neck Surgery, University Hospital Düsseldorf, Heinrich Heine University, 40225 Düsseldorf, Germany. Electronic address:

Fanconi anemia (FA) due to biallelic mutations in the BRCA2 gene is very rare and associated with an extremely high risk of early-onset of aggressive childhood malignancies, predominantly brain tumors, leukemia, and nephroblastoma. Here, we present a consanguineous family with three affected children of the D1 subtype of FA and describe the clinical consequences of the earliest known biallelic nonsense/stop-gain germ-line mutation in BRCA2, exon 5 c.469A>T, that leads to a premature stop of translation, p. Read More

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Short-term and Long-term Psychological Impact and Quality of Life of Patients Undergoing Orthognathic Surgery.

Biomed J 2021 Jun 9. Epub 2021 Jun 9.

Department of Craniofacial Research Center, Chang Gung Memorial Hospital and College of Medicine, Taoyuan, Taiwan.

Background: Orthognathic Surgery (OGS) is a surgery for patients with dento-facial deformity but not all patients are satisfied with its outcome. The purpose of this study is to find out the short-term and long-term psychological impact and quality-of-life of OGS.

Methods: 77 participants receiving OGS and 32 age and gender-matched controls were enrolled. Read More

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Combining tunable proteolytic sequences and a VEGF-mimetic peptide for the spatiotemporal control of angiogenesis within Elastin-Like Recombinamer scaffolds.

Acta Biomater 2021 Jun 9. Epub 2021 Jun 9.

G.I.R. BIOFORGE (Group for Advanced Materials and Nanobiotechnology), CIBER-BBN, Edificio LUCIA, Universidad de Valladolid, Paseo Belén 19, 47011 Valladolid, Spain. Electronic address:

One of the main challenges in regenerative medicine is the spatiotemporal control of angiogenesis, which is key for the successful repair of many tissues, and determines the proper integration of the implant through the generation of a functional vascular network. To this end, we have designed a three-dimensional (3D) model consisting of a coaxial binary elastin-like recombinamer (ELR) tubular construct. It displays fast and slow proteolytic hydrogels on its inner and outer part, respectively, both sensitive to the urokinase plasminogen activator protease. Read More

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Positive Selection as a Key Player for SARS-CoV-2 Pathogenicity: Insights into ORF1ab, S and E genes.

Virus Res 2021 Jun 9:198472. Epub 2021 Jun 9.

Center for Informatics Sciences (CIS), Nile University, Giza, Egypt.

The human β-coronavirus SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China. It causes Covid-19 disease which has become pandemic. Each of the five-known human β-coronaviruses has four major structural proteins (E, M, N and S) and 16 non-structural proteins encoded by ORF1a and ORF1b together (ORF1ab) that are involved in virus pathogenicity and infectivity. Read More

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Expression profiling, immune functions, and molecular characteristics of the tetraspanin molecule CD63 from Amphiprion clarkii.

Dev Comp Immunol 2021 Jun 9:104168. Epub 2021 Jun 9.

Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju 63243, Republic of Korea; Marine Science Institute, Jeju National University, Jeju 63333, Republic of Korea. Electronic address:

CD63, a member of the tetraspanin family, is involved in the activation of immune cells, antiviral immunity, and signal transduction. The economically important anemonefishes Amphiprion sp. often face disease outbreaks, and the present study aimed to characterize CD63 in Amphiprion clarkii (denoted AcCD63) to enable better disease management. Read More

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Talin mechanosensitivity is modulated by a direct interaction with cyclin-dependent kinase-1.

J Biol Chem 2021 Jun 9:100837. Epub 2021 Jun 9.

School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK. Electronic address:

Talin (TLN1) is a mechanosensitive component of adhesion complexes that directly couples integrins to the actin cytoskeleton. In response to force, talin undergoes switch-like behavior of its multiple rod domains that modulate interactions with its binding partners. Cyclin-dependent kinase-1 (CDK1) is a key regulator of the cell cycle, exerting its effects through synchronized phosphorylation of a large number of protein targets. Read More

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Epigenetic clock and methylation studies in elephants.

Aging Cell 2021 Jun 12:e13414. Epub 2021 Jun 12.

Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA.

Age-associated DNA-methylation profiles have been used successfully to develop highly accurate biomarkers of age ("epigenetic clocks") in humans, mice, dogs, and other species. Here we present epigenetic clocks for African and Asian elephants. These clocks were developed using novel DNA methylation profiles of 140 elephant blood samples of known age, at loci that are highly conserved between mammalian species, using a custom Infinium array (HorvathMammalMethylChip40). Read More

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Clinical presentation and outcomes of COVID-19 in older hospitalised patients assessed by the record-based multidimensional prognostic index, a cross-sectional study.

Eur Geriatr Med 2021 Jun 12. Epub 2021 Jun 12.

Department of Geriatrics, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark.

Purpose: Older people are the most frequently hospital admitted patients with COVID-19. We aimed to describe the clinical presentation of COVID-19 among frail and nonfrail older hospitalised patients and to evaluate the potential association between frailty and clinical course, decision of treatment level with outcomes change in functional capacity and survival.

Methods: We performed a multi-center, retrospective cross-sectional cohort study examining data on clinical presentation and frailty-related domains for hospitalised people aged 75 + years with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test. Read More

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Sequence-Specific Control of Mitochondrial Gene Transcription Using Programmable Synthetic Gene Switches Called MITO-PIPs.

Methods Mol Biol 2021 ;2275:217-225

Institute of Integrated Cell Material Sciences (WPI-iCeMS), Kyoto University Institute for Advanced Study, Kyoto, Japan.

Mitochondria possess multiple copies of mitochondrial DNA (mtDNA) that encode 37 genes and their transcription and replication get controlled by unique molecular codes different from that in the nuclear DNA. The mtDNA has been gaining increased attention as one of the critical therapeutic targets as mutations in them impair the function of mitochondria and cause mitochondrial diseases like MELAS. In this chapter, we describe artificial control of mitochondrial transcription based on mtDNA sequence information with a new type of compounds termed MITO-PIPs, which encompasses two domains: pyrrole-imidazole polyamide as DNA recognition domain and mitochondrial penetrating peptide as the mitochondria-targeting domain. Read More

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January 2021

Backbone resonance assignment of the cAMP-binding domains of the protein kinase A regulatory subunit Iα.

Biomol NMR Assign 2021 Jun 12. Epub 2021 Jun 12.

Department of Chemistry and Chemical Biology and Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4M1, Canada.

Protein kinase A (PKA) is the main receptor for the universal cAMP second messenger. PKA is a tetramer with two catalytic (C) and two regulatory (R) subunits, each including two tandem cAMP-binding domains, i.e. Read More

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Peptide Toxins Targeting K Channels.

Handb Exp Pharmacol 2021 Jun 13. Epub 2021 Jun 13.

Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.

A number of peptide toxins isolated from animals target potassium ion (K) channels. Many of them are particularly known to inhibit voltage-gated K (K) channels and are mainly classified into pore-blocking toxins or gating-modifier toxins. Pore-blocking toxins directly bind to the ion permeation pores of K channels, thereby physically occluding them. Read More

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Multiplex CRISPR-Cas9 editing of DNA methyltransferases in rice uncovers a class of non-CG methylation specific for GC-rich regions.

Plant Cell 2021 Jun 12. Epub 2021 Jun 12.

School of Life Sciences & Institute of Plant and Food Science & Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

DNA methylation in the non-CG context is widespread in the plant kingdom and abundant in mammalian tissues such as the brain and pluripotent cells. Non-CG methylation in Arabidopsis thaliana is coordinately regulated by DOMAINS REARRANGED METHYLTRANSFERASE (DRM) and CHROMOMETHYLASE (CMT) proteins but has yet to be systematically studied in major crops due to difficulties in obtaining genetic materials. Here, utilizing the highly efficient multiplex CRISPR-Cas9 genome-editing system, we created single- and multiple-knockout mutants for all nine DNA methyltransferases in rice (Oryza sativa) and profiled their whole-genome methylation status at single-nucleotide resolution. Read More

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MT5-MMP controls APP and β-CTF/C99 metabolism through proteolytic-dependent and -independent mechanisms relevant for Alzheimer's disease.

FASEB J 2021 Jul;35(7):e21727

Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, Marseille, France.

We previously discovered the implication of membrane-type 5-matrix metalloproteinase (MT5-MMP) in Alzheimer's disease (AD) pathogenesis. Here, we shed new light on pathogenic mechanisms by which MT5-MMP controls the processing of amyloid precursor protein (APP) and the fate of amyloid beta peptide (Aβ) as well as its precursor C99, and C83. We found in human embryonic kidney cells (HEK) carrying the APP Swedish familial mutation (HEKswe) that deleting the C-terminal non-catalytic domains of MT5-MMP hampered its ability to process APP and release the soluble 95 kDa form (sAPP95). Read More

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The Impact of Combat Ocular Trauma and Traumatic Brain Injury on Vision- and Health-Related Quality of Life Among U.S. Military Casualties.

Mil Med 2021 Jun 12. Epub 2021 Jun 12.

Department of Surgery, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA.

Purpose: The purpose of this study was to assess visual and health-related quality of life (QOL) among U.S. military service members who sustained combat ocular trauma (COT) with or without associated traumatic brain injury (TBI). Read More

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High resolution crystal structure of the Borreliella burgdorferi PlzA protein in complex with c-di-GMP: new insights into the interaction of c-di-GMP with the novel xPilZ domain.

Pathog Dis 2021 Jun 12. Epub 2021 Jun 12.

Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, 1112 East Clay Street, Room 101 McGuire Hall, Richmond, VA 23298-0678 USA.

In the tick-borne pathogens, Borreliella burgdorferi and Borrelia hermsii, c-di-GMP is produced by a single diguanylate cyclase (Rrp1). In these pathogens, the Plz proteins (PlzA, B and C) are the only c-di-GMP receptors identified to date and PlzA is the sole c-di-GMP receptor found in all Borreliella isolates. Bioinformatic analyses suggest that PlzA has a unique PilZN3-PilZ architecture with the relatively uncommon xPilZ domain. Read More

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Features of hippocampal astrocytic domains and their spatial relation to excitatory and inhibitory neurons.

Glia 2021 Jun 12. Epub 2021 Jun 12.

Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University of Jerusalem, Jerusalem, Israel.

The mounting evidence for the involvement of astrocytes in neuronal circuits function and behavior stands in stark contrast to the lack of detailed anatomical description of these cells and the neurons in their domains. To fill this void, we imaged >30,000 astrocytes in hippocampi made transparent by CLARITY, and determined the elaborate structure, distribution, and neuronal content of astrocytic domains. First, we characterized the spatial distribution of >19,000 astrocytes across CA1 lamina, and analyzed the morphology of thousands of reconstructed domains. Read More

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The largest moss carpet transplant in Antarctica and its bryosphere cryptic biodiversity.

Extremophiles 2021 Jun 11. Epub 2021 Jun 11.

Departamento de Microbiologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

As part of the reconstruction of the Brazilian Antarctic Station on King George Island, three areas of moss carpet were transplanted to minimize the impact of the new facilities on the local biodiversity. A total of 650 m of moss carpet was transplanted to neighboring but previously uncolonized locations and has subsequently survived for the last 3 years. Antarctic moss carpets typically comprise low moss species diversity and are often monospecific. Read More

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mSWI/SNF promotes Polycomb repression both directly and through genome-wide redistribution.

Nat Struct Mol Biol 2021 Jun 11;28(6):501-511. Epub 2021 Jun 11.

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.

The mammalian SWI/SNF complex, or BAF complex, has a conserved and direct role in antagonizing Polycomb-mediated repression. Yet, BAF also promotes repression by Polycomb in stem cells and cancer. How BAF both antagonizes and promotes Polycomb-mediated repression remains unknown. Read More

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Implementation of Patient Safety Structures and Processes in the Patient-Centered Medical Home.

J Healthc Qual 2021 Jun 9. Epub 2021 Jun 9.

Abstract: Although most patient-clinician interactions occur in ambulatory care, little research has addressed measuring ambulatory patient safety or how primary care redesign such as the patient-centered medical home (PCMH) addresses patient safety. Our objectives were to identify PCMH standards relevant to patient safety, construct a measure of patient safety activity implementation, and examine differences in adoptions of these activities by practice and community characteristics. Using a consensus process, we selected elements among a widely adopted, nationally representative PCMH program representing activities that, according to a physician panel, represented patient safety overall and in four domains (diagnosis, treatment delays, medications, and communication and coordination) and generated a score for each. Read More

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Perturbation of ribosomal subunits dynamics by inhibitors of tRNA translocation.

RNA 2021 Jun 11. Epub 2021 Jun 11.

Max Planck Institute for Biophysical Chemistry

Many antibiotics that bind to the ribosome inhibit translation by blocking the movement of tRNAs and mRNA or interfering with ribosome dynamics, which impairs the formation of essential translocation intermediates. Here we show how translocation inhibitors viomycin (Vio), neomycin (Neo), paromomycin (Par), kanamycin (Kan), spectinomycin (Spc), hygromycin B (HygB), and streptomycin (Str, an antibiotic that does not inhibit tRNA movement), affect principal motions of the small ribosomal subunits (SSU) during EF-G-promoted translocation. Using ensemble kinetics, we studied the SSU body domain rotation and SSU head domain swiveling in real time. Read More

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Development of a predictive risk model for all-cause mortality in patients with diabetes in Hong Kong.

BMJ Open Diabetes Res Care 2021 Jun;9(1)

Cardiovascular Analytics Group, Laboratory of Cardiovascular Physiology, Hong Kong

Introduction: Patients with diabetes mellitus are risk of premature death. In this study, we developed a machine learning-driven predictive risk model for all-cause mortality among patients with type 2 diabetes mellitus using multiparametric approach with data from different domains.

Research Design And Methods: This study used territory-wide data of patients with type 2 diabetes attending public hospitals or their associated ambulatory/outpatient facilities in Hong Kong between January 1, 2009 and December 31, 2009. Read More

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The Relationship Between COVID-19 Confinement, Psychological Adjustment, and Sexual Functioning, in a Sample of Portuguese Men and Women.

J Sex Med 2021 Apr 21. Epub 2021 Apr 21.

CPUP: Center for Psychology of Porto University, Faculty of Psychology and Educational Sciences, Porto University, Porto, Portugal.

Background: Past research has revealed the detrimental effects of social isolation and physical distancing measures in health related outcomes. However, only recently COVID-19 confinement measures provided a context to test whether such detrimental effects exist in the human sexuality domain.

Aim: This study was aimed at testing the relationship between COVID-19 confinement levels and sexual functioning domains in men and women, while accounting for the mediating role of psychological adjustment during lockdown. Read More

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The influence of bariatric surgery on hip and knee joint pain: a systematic review.

Surg Obes Relat Dis 2021 Apr 28. Epub 2021 Apr 28.

Department of Orthopaedics, Rijnstate Hospital, Arnhem, The Netherlands. Electronic address:

Obesity increases the risk of osteoarthritis and the chance of needing joint replacement arthroplasty to reduce lower limb joint pain. Although nonsurgical weight loss interventions can reduce hip and knee joint pain, bariatric surgery may be a more feasible treatment option for people with severe obesity. However, it is unclear whether weight loss through bariatric surgery can positively influence hip and knee joint pain. Read More

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Characterizations of the endolysin Lys84 and its domains from phage qdsa002 with high activities against Staphylococcus aureus and its biofilms.

Enzyme Microb Technol 2021 Aug 24;148:109809. Epub 2021 Apr 24.

College of Food Science and Engineering, Ocean University of China, No. 5, Yushan Road, Qingdao, Shandong Province, 266003, PR China.

Staphylococcus aureus (S. aureus), particularly methicillin-resistant S. aureus (MRSA), and its biofilms are great threats in the food industry. Read More

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Patient Reported Traditional Chinese Medicine Spleen Deficiency Syndrome (TCM-SDS) Scale for Colorectal Cancer: Development and Validation in China.

Integr Cancer Ther 2021 Jan-Dec;20:15347354211020105

China Academy of Chinese Medical Sciences, Xiyuan Hospital, Haidian District, Beijing, P.R. China.

Introduction: Spleen Deficiency Syndrome (SDS) is recognized as one of the most common Traditional Chinse Medicine (TCM) syndromes in patients with colorectal cancer (CRC). However so far there is no existing patient-reported outcome (PRO) to evaluate SDS. Our study aimed to develop and validate a PRO TCM-SDS scale for CRC in China. Read More

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Hands-On Workshops Improve Emergency Department Physicians' Self-Reported Understanding of Pediatric Hand Injuries.

Pediatr Emerg Care 2021 May 18. Epub 2021 May 18.

From the University of Ottawa Divisions of Plastic Surgery Emergency Medicine, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.

Objectives: The aims of this study were to assess emergency department (ED) physician perception of hand injuries and improve their understanding and confidence in treating these injuries.

Methods: Combined didactic and hands-on workshops for ED physicians were developed and run by a team of medical students, plastic surgeons, and ED physicians. The workshops consisted of a short review by a hand surgeon followed by hands-on sessions involving radiograph assessment, administration of local anesthetic, closed reduction, and splinting. Read More

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ADP-ribosylation of DNA and RNA.

DNA Repair (Amst) 2021 Jun 3;105:103144. Epub 2021 Jun 3.

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom. Electronic address:

ADP-ribosylation is a chemical modification of macromolecules found across all domains of life and known to regulate a variety of cellular processes. Notably, it has a well-established role in the DNA damage response. While it was historically known as a post-translational modification of proteins, recent studies have shown that nucleic acids can also serve as substrates of reversible ADP-ribosylation. Read More

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