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To date, approximately 50 short tandem repeat (STR) disorders have been identified; yet, clinical laboratories rarely conduct STR analysis on exomes. To assess its diagnostic value, we analyzed STRs in 6099 exomes from 2510 families with mostly suspected neurogenetic disorders. We employed ExpansionHunter and REViewer to detect pathogenic repeat expansions, confirming them using orthogonal methods. Genotype-phenotype correlations led to the diagnosis of thirteen individuals in seven previously undiagnosed families, identifying three autosomal dominant disorders: dentatorubral-pallidoluysian atrophy (n= 3), spinocerebellar ataxia type 7 (n= 2), and myotonic dystrophy type 1 (n= 2), resulting in a diagnostic gain of 0.28% (7/2510). Additionally, we found expanded ATXN1alleles (≥39 repeats) with varying patterns of CAT interruptions in twelve individuals, accounting for approximately 0.19% in the Korean population. Our study underscores the importance of integrating STR analysis into exome sequencing pipeline, broadening the application of exome sequencing for STR assessments.

Background parenchymal enhancement assessed at postoperative surveillance breast MRI was independently associated with the future second breast cancer risk in women with a personal history of breast cancer.

The Korean Genetic Diagnosis Program for Rare Disease (KGDP) enrolled 1890 patients with rare diseases between March 2017 and October 2022. Children and adolescents accounted for the majority of the patients, and systemic disease was the most common presenting symptom. The exome-based virtual disease-specific multigene panel was the most frequently used analytical method, with an overall diagnostic yield of 33.3%. A total of 629 positive cases were diagnosed, involving 297 genes. All 297 genes identified in these cases were confirmed to be known genes listed in the OMIM database. The nationwide KGDP network and its cooperation with the Korean Undiagnosed Diseases Program (KUDP) provide a more comprehensive genetic analysis of undiagnosed cases. The partnership between the KGDP and KUDP has the potential to improve the diagnosis and treatment options for patients. In conclusion, KGDP serves as the primary access point or gateway to KUDP.

In a stand-alone inverter, a high-quality sinusoidal output of a constant voltage and constant frequency must be supplied to the load regardless of the load condition. Therefore, the THD of the output voltage in steady-state should be low and the ability to recover from the transient period needs to be fast for the load variations. However, when the inverter employs an LC filter at the output stage, a damping technique is required to suppress voltage oscillations due to resonance when the load changes. This paper proposes a damping control method to stabilize the output voltage using cooperative control of two single-phase inverters connected in parallel. The Master inverter controls the output voltage, and the Damping inverter controls the output current to support output voltage damping and power capacity. Each inverter output stage consists of a lossless filter with no damping resistor to prevent efficiency degradation and robust against system parameter changes. The output voltage distortion is less than the conventional method, regardless of loads and load variations. We carried out PSIM simulations and experiments to verify the superiority of the proposed approach.

In women with a personal history of breast cancer, screening with abbreviated breast MRI showed comparable sensitivity and superior specificity to the full-protocol MRI.

COVID-19 vaccine–associated lymphadenopathy should be interpreted considering the vaccine type and interval from vaccination; follow-up US examination at least 12 weeks after vaccination may be reasonable, particularly for recipients of the messenger RNA vaccine.

Microcalcifications on mammograms obtained before neoadjuvant chemotherapy (NAC), peritumoral edema on MRI scans obtained after NAC, and clinical-pathologic variables were associated with survival of luminal breast cancer treated with NAC.

AbstractThe international investment agreement regime (IIA Regime) is composed of thousands of IIAs and a system of investor–state dispute settlement. Historically, high-income developing countries (HIDCs) were part of the global South and thus ‘hosts’ of foreign direct investment (FDI). Increasingly, however, these countries have become ‘home’ to investors who are hosted and exposed to political risk abroad. Representing both home and host country interests simultaneously, how do HIDCs balance these crosscutting pressures? We argue that as the position of an HIDC shifts from mostly a recipient towards a sender of significant amounts of FDI, it will be more willing to provide protection to foreign investors at the expense of state regulatory space in its IIAs, thereby increasing its exposure to the IIA Regime. Employing an original data set that measures this exposure for sixty-four HIDCs over six decades, we first show that the degree of HIDC exposure to the IIA Regime varies a great deal. Using a general method of moments (GMM) analysis and controlling for a host of confounding factors, we demonstrate that, indeed, higher levels of FDI outflows as a share of the national economy result in greater exposure to the IIA Regime.

Supplemental breast US screening in women with a personal history of early-stage breast cancer had lower sensitivity and higher interval cancer rate but higher specificity compared with women without a personal history of breast cancer.

BackgroundWhole-exome sequencing-based diagnosis of rare diseases typically yields 40%–50% of success rate. Precise diagnosis of the patients with neuromuscular disorders (NMDs) has been hampered by locus heterogeneity or phenotypic heterogeneity. We evaluated the utility of transcriptome sequencing as an independent approach in diagnosing NMDs.MethodsThe RNA sequencing (RNA-Seq) of muscle tissues from 117 Korean patients with suspected Mendelian NMD was performed to evaluate the ability to detect pathogenic variants. Aberrant splicing and CNVs were inspected to identify additional causal genetic factors for NMD. Aberrant splicing events in Dystrophin (DMD)were investigated by using antisense oligonucleotides (ASOs). A non-negative matrix factorisation analysis of the transcriptome data followed by cell type deconvolution was performed to cluster samples by expression-based signatures and identify cluster-specific gene ontologies.ResultsOur pipeline called 38.1% of pathogenic variants exclusively from the muscle transcriptomes, demonstrating a higher diagnostic rate than that achieved via exome analysis (34.9%). The discovery of variants causing aberrant splicing allowed the application of ASOs to the patient-derived cells, providing a therapeutic approach tailored to individual patients. RNA-Seq data further enabled sample clustering by distinct gene expression profiles that corresponded to clinical parameters, conferring additional advantages over exome sequencing.ConclusionThe RNA-Seq-based diagnosis of NMDs achieves an increased diagnostic rate and provided pathogenic status information, which is not easily accessible through exome analysis.

Introduction: In recent years, the erector spinae plane block (ESPB) has seen widespread use to treat acute and chronic pain in the regions of the thoracic spine. While limited data suggest its increasing utilization for pain management distal to the thoracic, abdomen and trunk, the anesthetic spread and analgesic mechanism of ESPB at the level of the lumbar spine has not been fully described or understood. Methods: This is an observational anatomic cadaveric study to assess the distribution of solution following an ESPB block performed at the fourth lumbar vertebrae (L4) using ultrasound guidance to evaluate the spread of a 20 ml solution consisting of local anesthetic and methylene blue. The study was performed in an anatomy lab in a large academic medical center. Following injection of local anesthetic with contrast dye, cadaveric dissection was performed to better understand the extent of contrast dye and to determine the degree of staining to further predict analgesic potential. We reviewed the findings of other ESPB cadaveric studies currently available for comparison. Results: Following cadaveric dissection in an anatomy lab, the contrast dye was observed in the ESP space, and staining was found most cranially at L2 and extending caudally underneath the sacrum. Evaluating the depth of its spread, we found it to be confined to the posterior compartment of the spine sparing the nerve roots bilaterally, which is consistent with the only other cadaveric study of ESPB performed at L4. Conclusion: Our results demonstrate the clinical utility of lumbar ESPB where posterior confinement of local anesthesia is preferred. However, further investigation is needed to determine the efficacy of ESPB in lower extremity analgesia which is predicated on ventral nerve root involvement.

•The purpose of this study is to investigate the effect of low cortical thickness or volume of medial temporal sub-regions on risk of incident psychosis in patients with AD•We found a low cortical thickness or volume of medial temporal area was associated with a higher risk of incident psychosis in patients with AD; low cortical thickness of left entorhinal cortex (HR [95% CI]: 4.291 [1.196–15.384]), and low cortical volume of right hippocampus (HR [95% CI]: 2.680 [1.003–1.196]).•Our study demonstrates that low cortical thickness or volume of medial temporal sub-regions is a risk factor for incident psychosis in patients with AD. A careful assessment of medial temporal sub-regional thickness or volume in AD may improve early detection and intervention of psychosis in AD.

As of July 31, 2021, SARS-CoV-2 had infected almost 200 million people worldwide. The growing burden of survivorship is substantial in terms of the complexity of long-term health effects and the number of people affected. Persistent symptoms have been reported in patients with both mild and severe acute COVID-19, including those admitted to the intensive care unit (ICU). Early reports on the post-acute sequelae of SARS-CoV-2 infection (PASC) indicate that fatigue, dyspnoea, cough, headache, loss of taste or smell, and cognitive or mental health impairments are among the most common symptoms. These complex, multifactorial impairments across the domains of physical, cognitive, and mental health require a coordinated, multidisciplinary approach to management. Decades of research on the multifaceted needs of and models of care for patients with post-intensive care syndrome provide a framework for the development of PASC clinics to address the immediate needs of both hospitalised and non-hospitalised survivors of COVID-19. Such clinics could also provide a platform for rigorous research into the natural history of PASC and the potential benefits of therapeutic interventions.

ABSTRACTThe orphan nuclear receptor ESRRA (estrogen related receptor alpha) is critical in mitochondrial biogenesis and macroautophagy/autophagy function; however, the roles of ESRRA in intestinal function remain uncharacterized. Herein we identified that ESRRA acts as a key regulator of intestinal homeostasis by amelioration of colonic inflammation through activation of autophagic flux and control of host gut microbiota. Esrra-deficient mice presented with increased susceptibility to dextran sodium sulfate (DSS)-induced colitis with upregulation of intestinal inflammation. In addition, esrra-null mice had depressed AMP-activated protein kinase phosphorylation (AMPK), lower levels of TFEB (transcription factor EB), and accumulation of SQSTM1/p62 (sequestosome 1) with defective mitochondria in intestinal tissues. Esrra-deficient mice showed distinct gut microbiota composition and significantly higher microbial diversity than wild-type (WT) mice. Cohousing or fecal microbiota transplantation from WT mice to Esrra-deficient mice ameliorated DSS-induced colitis severity. Importantly, patients with ulcerative colitis (UC) had significantly decreased ESRRAexpression in intestinal mucosal tissues that correlated with disease activity, suggesting clinical relevance of ESRRA in UC. Taken together, our results show that ESRRA contributes to intestinal homeostasis through autophagy activation and gut microbiota control to protect the host from detrimental inflammation and dysfunctional mitochondria.Abbreviations:ABX, antibotics; AMPK, AMP-activated protein kinase; ATP5A1, ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1; BECN1, beclin1, autophagy related, CCL, C-C motif chemokine ligand; CD, Crohn disease; CLDN, claudin; COX4I1, cytochrome c oxidase subunit 4I1; cKO, conditional knockout; cWT, conditional wild-type; CXCL, C-X-C motif chemokine ligand; DAI, disease activity index; DSS, dextran sodium sulfate; EGFP, enhanced green fluorescent protein; ESRR, estrogen related receptor; ESRRA, estrogen related receptor alpha; Esrra+/+, Esrra wild type; esrra–/-, esrra homozygous knockout; FMT, fecal microbiota transplantation; GABARAP, gamma-aminobutyric acid receptor associated protein; GSEA, gene set enrichment analysis; IBD, inflammatory bowel disease; IL, interleukin; KO, knockout; LAMP1, lysosomal-associated membrane protein 1; LCN2, lipocalin 2; LEfSe, linear discriminant analysis (LDA) effect size; LPS, lipopolysachharide; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; NDUFAB1, NADH: ubiquinone oxidoreductase subunit AB1; OCLN, occludin; OUT, operational taxonomic unit; OXPHOS, oxidative phosphorylation; PCoA, principal coordinate analysis; PPARGC1A, PPARG coactiva- tor 1 alpha; PRKAA, 5’-AMP-activated protein kinase catalytic subunit alpha; PTGS2/COX2, prostaglandin-endoperoxide synthase 2; RAB7, member RAS oncogene family; SDHB, succinate dehydrogenase complex, subunit B, iron sulfur (Ip); SQSTM1/p62, sequestosome 1; S100A9, S100 calcium binding protein A9 (calgranulin B); TCA, tricarboxylic acid; TFEB, transcription factor EB; TNF, tumor necrosis factor; UC, ulcerative colitis; UCP2, uncoupling protein 2 (mitochondrial, proton carrier); UQCRC1, ubiquinol-cytochrome c reductase core protein 1; UVRAG, UV radiation resistance associated gene; Vil1, villin; VPS11, VPS11, CORVET/HOPS core sub-unit; WT, wild type.

The glandular tissue component of the fibroglandular tissue as assessed by using screening breast US is an independent predictor of future breast cancer risk in women with dense breasts.

Methiozolin is a novel herbicide used to control annual bluegrass. It has low vapor pressure and high hydrophobicity, which could result in persistence in water and bioaccumulation. We measured the bioconcentration factors (BCFs) of methiozolin in ricefish (Oryzias latipes). Two radiolabels were used to quantify the parent compound and identify its metabolites. Ricefish were exposed to 2.0 and 20.0 ng/L methiozolin for 28 days in the uptake phase with a 96-h LC50of 2.2 mg/L(95% confidence limit: 2.1–2.5 mg/L) and water solubility of 4.2 mg/L after 48 h was observed. On the basis of total radioactivity residues (TRRs), BCFssand BCFkvalues of 797.0–851.9 and 992.9–1077.4 were observed, respectively, while BCFssvalues for methiozolin were 251.9–257.5. Several minor metabolites with TRR < 3.4% were detected. Among them, 4-(2,6-difluorobenzyloxy-methyl)-3-hydroxy-3-methyl-1-(3-methylthiophen-2-yl)butan-1-one, 2,6-difluorobenzyl alcohol, and 4,5-dihydro-5-methyl-3-(3-methylthiophen-2-yl)isoxazol-5-yl)methanol were identified. Methiozolin is metabolized into numerous minor metabolites with potentially low bioaccumulation capacity in ricefish. These findings can facilitate risk assessments regarding methiozolin use, particularly its movements and final stages in aquatic environments.

Survivors of COVID-19 are a vulnerable population, with complex needs because of lingering symptoms and complications across multiple organ systems. Those who required hospitalization or intensive care are also at risk for post-hospital syndrome and post-ICU syndromes, with attendant cognitive, psychological, and physical impairments, and high levels of health care utilization. Effective ambulatory care for COVID-19 survivors requires coordination across multiple subspecialties, which can be burdensome if not well coordinated. With growing recognition of these needs, post-COVID-19 clinics are being created across the country. We describe the design and implementation of multidisciplinary post-COVID-19 clinics at two academic health systems, Johns Hopkins and the University of California-San Francisco. We highlight components of the model which should be replicated across sites, while acknowledging opportunities to tailor offerings to the local institutional context. Our goal is to provide a replicable framework for others to create these much-needed care delivery models for survivors of COVID-19.

Interval cancers were associated with a family history of breast cancer, estrogen receptor and progesterone receptor negativity, and moderate or marked background parenchymal enhancement at screening breast MRI for women with a personal history of breast cancer.

A nomogram incorporating hormone receptor status, Ki-67 index, and post–neoadjuvant chemotherapy (NAC) MRI variables can predict pathologic compete response following NAC in breast cancer.

In women who underwent neoadjuvant chemotherapy for breast cancer, residual tumor size at histopathologic examination showed greater agreement with findings at either conventional or late delayed-phase MRI compared with early-phase MRI (intraclass correlation coefficient, 0.74–0.76 for delayed phase vs 0.56 for early phase; P˂.001).

When thickness-dependent carrier mobility is coupled with Thomas–Fermi screening and interlayer resistance effects in two-dimensional (2D) multilayer materials, a conducting channel migrates from the bottom surface to the top surface under electrostatic bias conditions. However, various factors including (i) insufficient carrier density, (ii) atomically thin material thickness, and (iii) numerous oxide traps/defects considerably limit our deep understanding of the carrier transport mechanism in 2D multilayer materials. Herein, we report the restricted conducting channel migration in 2D multilayer ReS2after a constant voltage stress of gate dielectrics is applied. At a given gate bias condition, a gradual increase in the drain bias enables a sensitive change in the interlayer resistance of ReS2, leading to a modification of the shape of the transconductance curves, and consequently, demonstrates the conducting channel migration along the thickness of ReS2before the stress. Meanwhile, this distinct conduction feature disappears after stress, indicating the formation of additional oxide trap sites inside the gate dielectrics that degrade the carrier mobility and eventually restrict the channel migration. Our theoretical and experimental study based on the resistor network model and Thomas–Fermi charge screening theory provides further insights into the origins of channel migration and restriction in 2D multilayer devices.

The current study was conducted to investigate mental health levels in Korean adults during the coronavirus 2019 (COVID-19) pandemic and determine their predictors. The study was conducted online, and 334 adults from 14 locations in Korea participated. Data collection was conducted from May 19 to May 24, 2020, using a questionnaire consisting of general and COVID-19–related characteristics, perceived physical health, individual and community resilience, and mental health. For data analysis, descriptive statistics, The current study was conducted to investigate mental health levels in Korean adults during the coronavirus 2019 (COVID-19) pandemic and determine their predictors. The study was conducted online, and 334 adults from 14 locations in Korea participated. Data collection was conducted from May 19 to May 24, 2020, using a questionnaire consisting of general and COVID-19–related characteristics, perceived physical health, individual and community resilience, and mental health. For data analysis, descriptive statistics, ttest, one-way analysis of variance, and hierarchical regression were used. In cases where women were more vulnerable to mental health problems and gender was controlled, regression analysis showed that individual resilience (β = −0.212, p< 0.001), perceived physical health (β = −0.160, p= 0.004), and community resilience (β = −0.119, p= 0.031) had an effect on mental health. Following the COVID-19 pandemic, communities should screen groups vulnerable to mental health problems and develop an integrated mental health program that incorporates predictors of mental health difficulties. [Journal of Psychosocial Nursing and Mental Health, 59(3), 18–27.]

BackgroundUbiquitination has a central role in numerous biological processes, including cell development, stress responses and ageing. Perturbed ubiquitination has been implicated in human diseases ranging from cancer to neurodegenerative diseases. SIAH1encodes a RING-type E3 ubiquitin ligase involved in protein ubiquitination. Among numerous other roles, SIAH1 regulates metabotropic glutamate receptor signalling and affects neural cell fate. Moreover, SIAH1 positively regulates Wnt signalling through ubiquitin-mediated degradation of Axin and accumulation of β-catenin.MethodsTrio exome sequencing followed by Sanger validation was undertaken in five individuals with syndromic developmental delay. Three-dimensional structural modelling was used to predict pathogenicity of affected residues. Wnt stimulatory activity was measured by luciferase reporter assays and Axin degradation assays in HEK293 cells transfected with wild-type and mutant SIAH1 expression plasmids.ResultsWe report five unrelated individuals with shared features of developmental delay, infantile hypotonia, dysmorphic features and laryngomalacia, in whom exome sequencing identified de novo monoallelic variants in SIAH1. In silico protein modelling suggested alteration of conserved functional sites. In vitro experiments demonstrated loss of Wnt stimulatory activity with the SIAH1 mutants, suggesting variant pathogenicity.ConclusionOur results lend support to SIAH1as a candidate Mendelian disease gene for a recognisable syndrome, further strengthening the connection between SIAH1and neurodevelopmental disorders. Furthermore, the results suggest that dysregulation of the Wnt/β-catenin pathway may be involved in the pathogenesis.

Background:This study developed a structural model of the professional socialization of nursing students with clinical practice experience and tested its validity based on Meleis's transition theory.Method:Participants were third- and fourth-year nursing students with at least one semester of clinical experience. Cross-sectional data from 412 participants were analyzed.Results:The goodness of fit of the model was satisfactory. Regarding the differences in educational year, the effects of the clinical learning environment on adaptation to a clinical practicum were not significant for third-year students but were significant for fourth-year students. The effects of clinical practice competency on professional socialization were significant only for fourth-year students. Transition shock and adaptation to clinical practicum paths were significant factors in both groups.Conclusion:Clinical adaptation is important for developing professional socialization in nursing students. Clinical adaptation can be achieved by improving the clinical learning environment and facilitating the development of clinical practice competency. Clinical adaptation is important for developing professional socialization in nursing students. Clinical adaptation can be achieved by improving the clinical learning environment and facilitating the development of clinical practice competency. [[J Nurs Educ. 2020;59(3):133–141.]

We observed that younger age (ie, ≤ 40 years) or the presence of nonmass enhancement on preoperative MR images was independently associated with worse local-regional recurrence-free survival in patients who had undergone breast-conserving surgery after neoadjuvant chemotherapy.

In women with clinically node-positive breast cancer who undergo neoadjuvant chemotherapy, a predictive model that incorporates clinical-pathologic features, changes in size of the primary tumor, and axillary lymphadenopathy at examinations after treatment was able to identify those patients who will achieve axillary pathologic complete response and be suitable candidates for sentinel lymph node biopsy.

The use of chlorofluorocarbons and hydrochlorofluorocarbons has been banned since the Montreal Protocol. Hydrofluorocarbon (HFC) series refrigerants were developed as an alternative, but HFC-134a has been found to have a high global warming potential. Thus, an eco-friendly, economical, and stable technology for removing waste HFCs is required. Existing methods involving pyrolysis for destruction of waste HFC include incineration, catalytic oxidation, and plasma pyrolysis. In this study, an economical and eco-friendly combustor that consumes little auxiliary fuel and easily neutralising hydrofluoric acid gas was developed to destroy waste HFC-134a. The conceptual design of a double-swirl combustor was developed based on numerical simulations and used to manufacture a prototype, which was used in a combustion experiment. When the auxiliary fuel LPG was used at a flow rate of 1.0 kg/h with an air ratio of 1.1, the average temperature at the vertical section in the combustion chamber was 1,300 K, which is sufficient to destroy waste HFCs. In the waste refrigerant destruction test, the destruction ratio of waste HFCs was 100% when waste HFCs were injected at a flow rate of 2.8 kg/h or less and 99.37% at a flow rate of 2.9 kg/h.