Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene expression profiling identified significantly different neuregulin-2 gene (NRG2) expression between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23 ± 2.80) was significantly lower than that in the controls (9.27 ± 4.78, p < 0.001). Next, we conducted resequencing of all the exons of NRG2 in a sample of 349 individuals with ASD, aiming to identify variants of the NRG2 associated with ASD. We identified three variants, including two single nucleotide variants (SNVs), IVS3 + 13A > G (rs889022) and IVS10 + 32T > A (rs182642591), and one small deletion at exon 11 of NRG2 (delGCCCGG, rs933769137). Using data from the Taiwan Biobank as the controls, we found no significant differences in allele frequencies of rs889022 and rs182642591 between two groups. However, there is a significant difference in the genotype and allele frequency distribution of rs933769137 between ASDs and controls (p < 0.0001). The small deletion is located in the EGF-like domain at the C-terminal of the NRG2 precursor protein. Our findings suggest that NRG2 might be a susceptibility gene for ASD.

Investigation of Mechanochromic Luminescence of Pyrene-based Aggregation-Induced Emission Luminogens: Correlation between Molecular Packing and Luminescence Behavior.

To better understand the correlation between molecular structure and optical properties such as aggregation-induced emission (AIE) and mechanochromic luminescence (MCL) emission, two new pyrene-based derivatives with substitutions at the 4- and 5-positions (1HH) and at the 4-, 5-, 9-, and 10-positions (2HH) were designed and synthesized. Cyano groups were introduced at the periphery of the synthesized compounds (1HCN, 1OCN, 1BCN, 2HCN, 2OCN, and 2BCN) to investigate the influence of these groups on the emission properties of the pyrene derivatives both in solution and in the solid state. The fluorescence emission performance of these compounds in water/acetone mixtures was simultaneously studied, revealing outstanding aggregation-induced emission properties. The typical shift in emission maxima to higher values was attributed to J-aggregate formation in the aggregate state. Careful investigation of the crystal structures demonstrated abundant and intense intermolecular interactions, such as C-H…π and C-H…N hydrogen bonds, contributing to the remarkable mechanochromic luminescence performance of these compounds. The MCL properties of all the compounds were investigated using powder X-ray diffraction, and the remarkable mechanochromic properties were attributed to J-aggregate phenomena in the solid state. These results provide valuable insights into the structure-property relationship of organic MCL materials, guiding the design of efficient organic MCL materials.

The Effect of Bicycle Saddle Widths on Saddle Pressure in Female Cyclists.

Choosing an unsuitable bicycle saddle increases the saddle pressure and discomfort during cycling. Women contract sports injuries more easily than men during cycling owing to their anatomy. To investigate the effect of saddle widths on the saddle pressure in female cyclists. Ten healthy women with an average age of 20.7 ± 1.3 years, height of 162 ± and 5.9 cm, weight of 56.1 ± 7.5 kg, and a sciatic bone width of 15.5 ± 1.4 cm were recruited for this study. The distributions of saddle pressure for four different saddle widths (i.e., narrow, moderate, wide, and self-chosen) were recorded using a saddle pressure mat. Participants were instructed to pedal steadily with a frequency of 90 RPM and a load of 150 watts. Thirty seconds of riding data was randomly retrieved for analysis. The trials were conducted with a counter-balanced design to minimize random errors. One-way repeated measures ANOVA was used to compare the saddle pressure of different saddle widths, and the significance level was set at α = 0.05. When wide saddles were used, the maximum and average pressure on the right surface of the posterior ischium were lower than those with narrow (p = 0.001, p = 0.012) and moderate (p = 0.016, p = 0.019) saddles. The area of pressure on the pubic bone was smaller when using a wide saddle than when using narrow (p = 0.005) and moderate (p = 0.018) saddles, and the area of pressure on the right posterior sciatic bone was larger under the wide saddle than under the narrow (p = 0.017) and moderate (p = 0.036) saddles. The average force was greater with the moderate saddle than with the wide (p = 0.008) and self-chosen (p = 0.025) saddles. Using a saddle with a width that is longer than the width of the cyclist's ischium by 1 cm can effectively improve the distribution of saddle pressure during riding, while providing better comfort.

Whole Genome Sequencing Revealed Inherited Rare Oligogenic Variants Contributing to Schizophrenia and Major Depressive Disorder in Two Families.

Schizophrenia and affective disorder are two major complex mental disorders with high heritability. Evidence shows that rare variants with significant clinical impacts contribute to the genetic liability of these two disorders. Also, rare variants associated with schizophrenia and affective disorders are highly personalized; each patient may carry different variants. We used whole genome sequencing analysis to study the genetic basis of two families with schizophrenia and major depressive disorder. We did not detect de novo, autosomal dominant, or recessive pathogenic or likely pathogenic variants associated with psychiatric disorders in these two families. Nevertheless, we identified multiple rare inherited variants with unknown significance in the probands. In family 1, with singleton schizophrenia, we detected four rare variants in genes implicated in schizophrenia, including p.Arg1627Trp of LAMA2, p.Pro1338Ser of CSMD1, p.Arg691Gly of TLR4, and Arg182X of AGTR2. The p.Arg691Gly of TLR4 was inherited from the father, while the other three were inherited from the mother. In family 2, with two affected sisters diagnosed with major depressive disorder, we detected three rare variants shared by the two sisters in three genes implicated in affective disorders, including p.Ala4551Gly of FAT1, p.Val231Leu of HOMER3, and p.Ile185Met of GPM6B. These three rare variants were assumed to be inherited from their parents. Prompted by these findings, we suggest that these rare inherited variants may interact with each other and lead to psychiatric conditions in these two families. Our observations support the conclusion that inherited rare variants may contribute to the heritability of psychiatric disorders.

Actin-related protein 6 facilitates proneural protein-induced gene activation for rapid neural differentiation.

Neurogenesis is initiated by basic helix-loop-helix proneural proteins. Here, we show that Actin-related protein 6 (Arp6), a core component of the H2A.Z exchange complex SWR1, interacts with proneural proteins and is crucial for efficient onset of proneural protein target gene expression. Arp6 mutants exhibit reduced transcription in sensory organ precursors (SOPs) downstream of the proneural protein patterning event. This leads to retarded differentiation and division of SOPs and smaller sensory organs. These phenotypes are also observed in proneural gene hypomorphic mutants. Proneural protein expression is not reduced in Arp6 mutants. Enhanced proneural gene expression fails to rescue retarded differentiation in Arp6 mutants, suggesting that Arp6 acts downstream of or in parallel with proneural proteins. H2A.Z mutants display Arp6-like retardation in SOPs. Transcriptomic analyses demonstrate that loss of Arp6 and H2A.Z preferentially decreases expression of proneural protein-activated genes. H2A.Z enrichment in nucleosomes around the transcription start site before neurogenesis correlates highly with greater activation of proneural protein target genes by H2A.Z. We propose that upon proneural protein binding to E-box sites, H2A.Z incorporation around the transcription start site allows rapid and efficient activation of target genes, promoting rapid neural differentiation.

Atrophy, hypometabolism and implication regarding pathology in late-life major depression with suspected non-alzheimer pathophysiology (SNAP).

BACKGROUND: A substantial proportion of individuals with late-life major depression could be classified as having a suspected non-Alzheimer disease pathophysiology (SNAP), as indicated by a negative test for the biomarker ß-amyloid (Aß-) but a positive test for neurodegeneration (ND+). This study investigated the clinical features, characteristic patterns of brain atrophy and hypometabolism, and implications regarding pathology in this population. METHODS: Forty-six amyloid-negative patients with late-life major depressive disorder (MDD) patients, including 23 SNAP (Aß-/ND+) and 23 Aß-/ND- MDD subjects, and 22 Aß-/ND-healthy control subjects were included in this study. Voxel-wise group comparisons between the SNAP MDD, Aß-/ND- MDD and control subjects were performed, adjusting for age, gender and level of education. For exploratory comparisons, 8 Aß+/ND- and 4 Aß+/ND + MDD patients were included in the Supplementary Material. RESULTS: The SNAP MDD patients had atrophy extending to regions outside the hippocampus, predominately in the medial temporal, dorsomedial and ventromedial prefrontal cortex; hypometabolism involving a large portion of the lateral and medial prefrontal cortex in addition to the bilateral temporal, parietal and precuneus cortex within typical Alzheimer disease regions were observed. Metabolism ratios of the inferior to the medial temporal lobe were significantly elevated in the SNAP MDD patients. We further discussed the implications with regards to underlying pathologies. CONCLUSION: The present study demonstrated characteristic patterns of atrophy and hypometabolism in patients with late-life major depression with SNAP. Identifying individuals with SNAP MDD may provide insights into currently unspecified neurodegenerative processes. Future refinement of neurodegeneration biomarkers is essential in order to identify potential pathological correlates while in vivo reliable pathological biomarkers are not forthcoming.

Effect of Load Carriage Lifestyle on Kinematics and Kinetics of Gait.

Backpacks are commonly worn by many people for multiple purposes. This study investigated the effects of habitual wearing of backpacks on lower limb kinematics and kinetics. Fourteen participants were recruited for analysis. All participants performed four randomly assigned scenarios, including running and walking at speeds of 3.5 and 1.5 m/s, respectively, with and without load carriage. The motion analysis system and force plate were used to investigate the lower limb kinematics and kinetics. A paired sample t-test was performed for statistical measurement with a significance level of α = .05. The results indicated that active force, breaking force, impact peak, loading rate, active peak, maximum braking, hip flexion, and hip range of motion were substantially higher under load carriage conditions than under walking condition, however, time to peak was lower. Conversely, during load carriage running, active force, braking impulse, time to peak, ankle plantarflexion, and ankle range of motion were all higher than those during running. Carrying a backpack weighing 10% of the body weight induced different foot strike patterns at both speeds; during load carriage walking, the hip tended to flex more; whereas, during load carriage running, the ankle tended to flex more. In conclusion, human body seems to adopt different gait strategies during load carriage walking and running. That is, the hip strategy is used during walking, while the ankle strategy is used during running.

Altered synaptic protein expression, aberrant spine morphology, and impaired spatial memory in Dlgap2 mutant mice, a genetic model of autism spectrum disorder.

A microdeletion of approximately 2.4 Mb at the 8p23 terminal region has been identified in a Taiwanese autistic boy. Among the products transcribed/translated from genes mapped in this region, the reduction of DLGAP2, a postsynaptic scaffold protein, might be involved in the pathogenesis of autism spectrum disorder (ASD). DLGAP2 protein was detected in the hippocampus yet abolished in homozygous Dlgap2 knockout (Dlgap2 KO) mice. In this study, we characterized the hippocampal phenotypes in Dlgap2 mutant mice. Dlgap2 KO mice exhibited impaired spatial memory, indicating poor hippocampal function in the absence of DLGAP2. Aberrant expressions of postsynaptic proteins, including PSD95, SHANK3, HOMER1, GluN2A, GluR2, mGluR1, mGluR5, ßCAMKII, ERK1/2, ARC, BDNF, were noticed in Dlgap2 mutant mice. Further, the spine density was increased in Dlgap2 KO mice, while the ratio of mushroom-type spines was decreased. We also observed a thinner postsynaptic density thickness in Dlgap2 KO mice at the ultrastructural level. These structural changes found in the hippocampus of Dlgap2 KO mice might be linked to impaired hippocampus-related cognitive functions such as spatial memory. Mice with Dlgap2 deficiency, showing signs of intellectual disability, a common co-occurring condition in patients with ASD, could be a promising animal model which may advance our understanding of ASD.

Spatiotemporal Characteristics of Fish Larvae and Juveniles in the Waters around Taiwan from 2007 to 2019.

Taiwan is located at the intersection of tropical and subtropical islands in the western Pacific Ocean. This area is an important spawning and breeding ground for many economic and noneconomic species; however, little is known about the long-term dynamics of fish larvae and juveniles in these waters. In this study, we conducted an in-depth exploration of their spatial characteristics using 2007-2019 field survey samples. Our results demonstrated the seasonality and spatiality of the larvae and juveniles of different fish species. We also found that the continental shelf and offshore distance were key factors affecting fish larvae and juveniles. Changes in community structure were temporally correlated with the extreme rainfall of Typhoon Morakot (the worst typhoon ever recorded in Taiwan). These data can be used as a management reference for fisheries' policymaking and provide key insights into nearby marine ecosystems and the early life history of fish.

Two Genetic Mechanisms in Two Siblings with Intellectual Disability, Autism Spectrum Disorder, and Psychosis.

Intellectual disability (ID) and autism spectrum disorder (ASD) are complex neurodevelopmental disorders with high heritability. To search for the genetic deficits in two siblings affected with ID and ASD in a family, we first performed a genome-wide copy number variation (CNV) analysis using chromosomal microarray analysis (CMA). We found a 3.7 Mb microdeletion at 22q13.3 in the younger sister. This de novo microdeletion resulted in the haploinsufficiency of SHANK3 and several nearby genes involved in neurodevelopment disorders. Hence, she was diagnosed with Phelan-McDermid syndrome (PMS, OMIM#606232). We further performed whole-genome sequencing (WGS) analysis in this family. We did not detect pathogenic mutations with significant impacts on the phenotypes of the elder brother. Instead, we identified several rare, likely pathogenic variants in seven genes implicated in neurodevelopmental disorders: KLHL17, TDO2, TRRAP, EIF3F, ATP10A, DICER1, and CDH15. These variants were transmitted from his unaffected parents, indicating these variants have only moderate clinical effects. We propose that these variants worked together and led to the clinical phenotypes in the elder brother. We also suggest that the combination of multiple genes with moderate effects is part of the genetic mechanism of neurodevelopmental disorders.

Decreased Cerebral Amyloid-ß Depositions in Patients With a Lifetime History of Major Depression With Suspected Non-Alzheimer Pathophysiology.

Cerebral amyloid-ß (Aß) depositions in depression in old age are controversial. A substantial proportion of individuals with late-life major depressive disorder (MDD) could be classified as having suspected non-Alzheimer's disease pathophysiology (SNAP) by a negative test for the biomarker amyloid-ß (Aß-) but positive neurodegeneration (ND+). This study aimed to evaluate subthreshold Aß loads in amyloid-negative MDD, particularly in SNAP MDD patients. This study included 46 amyloid-negative MDD patients: 23 SNAP (Aß-/ND+) MDD and 23 Aß-/ND- MDD, and 22 Aß-/ND- control subjects. All subjects underwent 18F-florbetapir PET, FDG-PET, and MRI. Regions of interest (ROIs) and voxel-wise group comparisons were performed with adjustment for age, gender, and level of education. The SNAP MDD patients exhibited significantly deceased 18F-florbetapir uptakes in most cortical regions but not the parietal and precuneus cortex, as compared with the Aß-/ND- MDD and control subjects (FDR correction, p < 0.05). No correlations of neuropsychological tests or depression characteristics with global cortical uptakes, but significant positive correlations between cognitive functions and adjusted hippocampal volumes among different groups were observed. The reduced Aß depositions in the amyloid-negative MDD patients might be attributed mainly to the SNAP MDD patients. Our results indicated that meaningfully low amounts of subclinical Aß might contain critical information on the non-amyloid-mediated pathogenesis.

Identification of rare mutations of the vasoactive intestinal peptide receptor 2 gene in schizophrenia.

OBJECTIVE: Studies showed that rare copy number variations (CNVs) encompassing the vasoactive intestinal peptide receptor 2 gene (VIPR2) were associated with schizophrenia, indicating VIPR2 is a risk gene for schizophrenia. We hypothesized that besides CNV, rare pathogenic single-nucleotide variant (SNV) or small insertion/deletion (Indel) of VIPR2 might be present in some patients and contribute to the pathogenesis of schizophrenia. METHODS: We performed genome-wide CNV analysis to screen CNV at the VIPR2 locus and targeted sequencing of all the exons of VIPR2 to search for SNV and indel in a sample of patients with chronic schizophrenia from Taiwan. RESULTS: We detected a 230-kb microduplication encompassing the VIPR2 in 1 out of 200 patients. Furthermore, we identified six ultrarare SNVs, including one splicing SNV and five missense SNVs, in 516 patients. In-silico analyses showed these SNVs had a damaging effect on the function of VIPR2. CONCLUSION: Our findings support the idea that besides CNV, rare pathogenic SNVs of VIPR2 might contribute to the pathogenesis of schizophrenia in some patients.

Middle-Aged Worker Bees Express Higher Innate Immunity than Young Worker Bees in the Abdomen without the Digestive Tract of Worker Bees Reared in an Incubator.

Honey bees (Apis mellifera) can be reared in an incubator to study the mechanisms of aging and longevity; however, whether breeding in an incubator and using the abdomen without the digestive tract influences the expression of immune genes is unclear. In this study, we assayed the immune genes including abaecin, hymenoptaecin, defensin-2, glucose dehydrogenase, phenoloxidase, and lysozyme from the whole body of young and middle-aged worker bees reared in field hives, the whole body of young and middle-aged worker bees reared in a 34 °C incubator, and the abdomen without the digestive tract of young and middle-aged worker bees reared in a 34 °C incubator. The results showed that three groups of middle-aged worker bees have higher immunity than young worker bees. Furthermore, the similarity of immune genes expression in three groups indicated that the abdomen without the digestive tract of honey bees reared in an incubator can be used to study the relationship between immunity and aging and longevity to avoid the interference of pathogens and parasites from field hives.

Synthesis of Distorted Nitrogen-Doped Nanographenes by Partially Oxidative Cyclodehydrogenation Reaction.

A series of partially fused N-doped nanographenes (2-4) are synthesized via the oxidative cyclodehydrogenation of oligoaryl-substituted dibenzo[e,l]pyrene (1), and five, six, and seven new C-C bonds are formed, respectively, implying stepwise C-C bond fusion and extended π-conjugation. Single-crystal X-ray diffraction analysis of compound 4 a revealed that the presence of sterically demanding groups hindered the formation of planar and fully fused nanographene in the oxidative cyclodehydrogenation reaction step. Optical study of compounds 2 to 4 showed that extended π-conjugation leads to a regular stepwise bathochromic shift in the absorption and emission spectra. Furthermore, the HOMO-LUMO gaps of these compounds exhibit a decrease as C-C bond formation proceeds. Thus, the optoelectronic properties of nanographenes are highly dependent on the formation of new C-C bonds in the molecular skeleton.

Involvement of Rare Mutations of SCN9A, DPP4, ABCA13, and SYT14 in Schizophrenia and Bipolar Disorder.

Rare mutations associated with schizophrenia (SZ) and bipolar disorder (BD) usually have high clinical penetrance; however, they are highly heterogeneous and personalized. Identifying rare mutations is instrumental in making the molecular diagnosis, understanding the pathogenesis, and providing genetic counseling for the affected individuals and families. We conducted whole-genome sequencing analysis in two multiplex families with the dominant inheritance of SZ and BD. We detected a G327E mutation of SCN9A and an A654V mutation of DPP4 cosegregating with SZ and BD in one three-generation multiplex family. We also identified three mutations cosegregating with SZ and BD in another two-generation multiplex family, including L711S of SCN9A, M4554I of ABCA13, and P159L of SYT14. These five missense mutations were rare and deleterious. Mutations of SCN9A have initially been reported to cause congenital insensitivity to pain and neuropathic pain syndromes. Further studies showed that rare mutations of SCN9A were associated with seizure and autism spectrum disorders. Our findings suggest that SZ and BD might also be part of the clinical phenotype spectra of SCN9A mutations. Our study also indicates the oligogenic involvement in SZ and BD and supports the multiple-hit model of SZ and BD.

Identification of a Rare Novel KMT2C Mutation That Presents with Schizophrenia in a Multiplex Family.

Schizophrenia is a complex genetic disorder involving many common variants with modest effects and rare mutations with high penetrance. Rare mutations associated with schizophrenia are highly heterogeneous and private for affected individuals and families. Identifying such mutations can help establish the molecular diagnosis, elucidate the pathogenesis, and provide helpful genetic counseling for affected patients and families. We performed a whole-exome sequencing analysis to search for rare pathogenic mutations co-segregating with schizophrenia transmitted in a dominant inheritance in a two-generation multiplex family. We identified a rare missense mutation H1574R (Histidine1574Arginine, rs199796552) of KMT2C (lysine methyltransferase 2C) co-segregating with affected members in this family. The mutation is a novel deleterious mutation of KMT2C, not reported before in the literature. The KMT2C encodes a histone 3 lysine 4 (H3K4)-specific methyltransferase and involves epigenetic regulation of brain gene expression. Mutations of KMT2C have been found in neurodevelopmental disorders, such as Kleefstra syndrome, intellectual disability, and autism spectrum disorders. Our finding suggests that schizophrenia might be one of the clinical phenotype spectra of KMT2C mutations, and KMT2C might be a novel risk gene for schizophrenia. Nevertheless, the co-segregation of this mutation with schizophrenia in this family might also be due to chance; functional assays of this mutation are needed to address this issue.

Synthetic Poly(lactic-co-glycolic Acid) Microvesicles as a Feasible Carbon Monoxide-Releasing Platform for Cancer Treatment.

Biogenic microvesicles (MVs) play a pivotal role in intercellular signal communication, thus initiating critical biological responses such as the proliferation of cancer cells, gene and protein transport, and chemo-drug resistance. In addition, they have been recognized as having great potential in drug delivery applications. However, the productivity of biologically produced MVs is not sufficient for clinical applications. In this study, synthetic poly(lactic-co-glycolic acid) (PLGA) MVs were prepared via a double emulsion method. The PLGA MVs had a biogenic MV-mimic vesicular structure with a hydrophilic core/surface and hydrophobic interior of the shell, showing great potential for drug delivery. We successfully embedded hydrophobic iron carbonyl (IC), a carbon monoxide (CO) donor, in the PLGA shell region, enabling the delivery of IC in an aqueous solution. Because of the intrinsic properties of PLGA, it was susceptible to temperature, and the MVs could easily collapse in a warm environment, leading to the decomposition of IC into CO. The in vitro result indicated that the cell viability of A549 lung carcinoma cells significantly decreased to 14% after treatment with IC-loaded PLGA MVs for 24 h, suggesting that these synthetic PLGA MVs constitute an excellent drug delivery platform.

Identification of Rare Mutations of Two Presynaptic Cytomatrix Genes BSN and PCLO in Schizophrenia and Bipolar Disorder.

Schizophrenia and bipolar disorder are severe mental disorders with a major component of genetic factors in their etiology. Rare mutations play a significant role in these two disorders, and they are highly heterogeneous and personalized. Identification of personalized mutations is essential for the establishment of molecular diagnosis, providing insight into pathogenesis and guiding the personalized treatment for each affected patient. We conducted whole-genome sequencing analysis of families with schizophrenia and bipolar disorder to search for their genetic underpinnings. This report identified a rare missense mutation Arg1087Gln of BSN (bassoon presynaptic cytomatrix protein) co-segregating with schizophrenia in a family with multiple affected members. Furthermore, we identified the rare missense mutation Ser1535Leu of PCLO (piccolo presynaptic cytomatrix protein) in two sisters with bipolar disorder and another rare missense mutation, His5142Arg in PCLO, in a patient with schizophrenia. These three missense mutations were very rare and were predicted to be pathogenic. The BSN and PCLO genes encode two structurally related proteins of the presynaptic cytomatrix at the active zone that regulates neurotransmission at the presynaptic neuronal terminal. Our findings suggest the involvement of the presynaptic matrix in the pathogenesis of schizophrenia and bipolar disorder, and BSN and PCLO are the risk genes for schizophrenia and bipolar disorder.

Chromosomal Microarray Analysis as First-Tier Genetic Test for Schizophrenia.

Schizophrenia is a chronic, devastating mental disorder with complex genetic components. Given the advancements in the molecular genetic research of schizophrenia in recent years, there is still a lack of genetic tests that can be used in clinical settings. Chromosomal microarray analysis (CMA) has been used as first-tier genetic testing for congenital abnormalities, developmental delay, and autism spectrum disorders. This study attempted to gain some experience in applying chromosomal microarray analysis as a first-tier genetic test for patients with schizophrenia. We consecutively enrolled patients with schizophrenia spectrum disorder from a clinical setting and conducted genome-wide copy number variation (CNV) analysis using a chromosomal microarray platform. We followed the 2020 "Technical Standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)" to interpret the clinical significance of CNVs detected from patients. We recruited a total of 60 patients (36 females and 24 males) into this study. We detected three pathogenic CNVs and one likely pathogenic CNV in four patients, respectively. The detection rate was 6.7% (4/60, 95% CI: 0.004-0.13), comparable with previous studies in the literature. Also, we detected thirteen CNVs classified as uncertain clinical significance in nine patients. Detecting these CNVs can help establish the molecular genetic diagnosis of schizophrenia patients and provide helpful information for genetic counseling and clinical management. Also, it can increase our understanding of the pathogenesis of schizophrenia. Hence, we suggest CMA is a valuable genetic tool and considered first-tier genetic testing for schizophrenia spectrum disorders in clinical settings.

The Validity and Reliability of a Tire Pressure-Based Power Meter for Indoor Cycling.

The purpose of this study was to evaluate the validity and reliability of a tire pressure sensor (TPS) cycling power meter against a gold standard (SRM) during indoor cycling. Twelve recreationally active participants completed eight trials of 90 s of cycling at different pedaling and gearing combinations on an indoor hybrid roller. Power output (PO) was simultaneously calculated via TPS and SRM. The analysis compared the paired 1 s PO and 1 min average PO per trial between devices. Agreement was assessed by correlation, linear regression, inferential statistics, effect size, and Bland-Altman LoA. Reliability was assessed by ICC and CV comparison. TPS showed near-perfect correlation with SRM in 1 s (rs = 0.97, p < 0.001) and 1-min data (rs = 0.99, p < 0.001). Differences in paired 1 s data were statistically significant (p = 0.04), but of a trivial magnitude (d = 0.05). There was no significant main effect for device (F(1,9) = 0.05, p = 0.83, ηp2 = 0.97) in 1 min data and no statistical differences between devices by trial in post hoc analysis (p < 0.01-0.98; d < 0.01-0.93). Bias and LoA were -0.21 ± 16.77 W for the 1 min data. Mean TPS bias ranged from 3.37% to 7.81% of the measured SRM mean PO per trial. Linear regression SEE was 7.55 W for 1 min TPS prediction of SRM. ICC3,1 across trials was 0.96. No statistical difference (p = 0.09-0.11) in TPS CV (3.6-5.0%) and SRM CV (4.3-4.7%). The TPS is a valid and reliable power meter for estimating average indoor PO for time periods equal to or greater than 1 min and may have acceptable sensitivity to detect changes under less stringent criteria (±5%).