EEG complexity measures for detecting mind wandering during video-based learning.

This study explores the efficacy of various EEG complexity measures in detecting mind wandering during video-based learning. Employing a modified probe-caught method, we recorded EEG data from participants engaged in viewing educational videos and subsequently focused on the discrimination between mind wandering (MW) and non-MW states. We systematically investigated various EEG complexity metrics, including metrics that reflect a system's regularity like multiscale permutation entropy (MPE), and metrics that reflect a system's dimensionality like detrended fluctuation analysis (DFA). We also compare these features to traditional band power (BP) features. Data augmentation methods and feature selection were applied to optimize detection accuracy. Results show BP features excelled (mean area under the receiver operating characteristic curve (AUC) 0.646) in datasets without eye-movement artifacts, while MPE showed similar performance (mean AUC 0.639) without requiring removal of eye-movement artifacts. Combining all kinds of features improved decoding performance to 0.66 mean AUC. Our findings demonstrate the potential of these complexity metrics in EEG analysis for mind wandering detection, highlighting their practical implications in educational contexts.

Rhesus monkeys learn to control a directional-key inspired brain machine interface via bio-feedback.

Brain machine interfaces (BMI) connect brains directly to the outside world, bypassing natural neural systems and actuators. Neuronal-activity-to-motion transformation algorithms allow applications such as control of prosthetics or computer cursors. These algorithms lie within a spectrum between bio-mimetic control and bio-feedback control. The bio-mimetic approach relies on increasingly complex algorithms to decode neural activity by mimicking the natural neural system and actuator relationship while focusing on machine learning: the supervised fitting of decoder parameters. On the other hand, the bio-feedback approach uses simple algorithms and relies primarily on user learning, which may take some time, but can facilitate control of novel, non-biological appendages. An increasing amount of work has focused on the arguably more successful bio-mimetic approach. However, as chronic recordings have become more accessible and utilization of novel appendages such as computer cursors have become more universal, users can more easily spend time learning in a bio-feedback control paradigm. We believe a simple approach which leverages user learning and few assumptions will provide users with good control ability. To test the feasibility of this idea, we implemented a simple firing-rate-to-motion correspondence rule, assigned groups of neurons to virtual "directional keys" for control of a 2D cursor. Though not strictly required, to facilitate initial control, we selected neurons with similar preferred directions for each group. The groups of neurons were kept the same across multiple recording sessions to allow learning. Two Rhesus monkeys used this BMI to perform a center-out cursor movement task. After about a week of training, monkeys performed the task better and neuronal signal patterns changed on a group basis, indicating learning. While our experiments did not compare this bio-feedback BMI to bio-mimetic BMIs, the results demonstrate the feasibility of our control paradigm and paves the way for further research in multi-dimensional bio-feedback BMIs.

Temporal segmentation of EEG based on functional connectivity network structure.

In the study of brain functional connectivity networks, it is assumed that a network is built from a data window in which activity is stationary. However, brain activity is non-stationary over sufficiently large time periods. Addressing the analysis electroencephalograph (EEG) data, we propose a data segmentation method based on functional connectivity network structure. The goal of segmentation is to ensure that within a window of analysis, there is similar network structure. We designed an intuitive and flexible graph distance measure to quantify the difference in network structure between two analysis windows. This measure is modular: a variety of node importance indices can be plugged into it. We use a reference window versus sliding window comparison approach to detect changes, as indicated by outliers in the distribution of graph distance values. Performance of our segmentation method was tested in simulated EEG data and real EEG data from a drone piloting experiment (using correlation or phase-locking value as the functional connectivity strength metric). We compared our method under various node importance measures and against matrix-based dissimilarity metrics that use singular value decomposition on the connectivity matrix. The results show the graph distance approach worked better than matrix-based approaches; graph distance based on partial node centrality was most sensitive to network structural changes, especially when connectivity matrix values change little. The proposed method provides EEG data segmentation tailored for detecting changes in terms of functional connectivity networks. Our study provides a new perspective on EEG segmentation, one that is based on functional connectivity network structure differences.

Glycerol-3-Phosphate Acyltransferase GPAT9 Enhanced Seed Oil Accumulation and Eukaryotic Galactolipid Synthesis in Brassica napus.

Glycerol-3-phosphate acyltransferase GPAT9 catalyzes the first acylation of glycerol-3-phosphate (G3P), a committed step of glycerolipid synthesis in Arabidopsis. The role of GPAT9 in Brassica napus remains to be elucidated. Here, we identified four orthologs of GPAT9 and found that BnaGPAT9 encoded by BnaC01T0014600WE is a predominant isoform and promotes seed oil accumulation and eukaryotic galactolipid synthesis in Brassica napus. BnaGPAT9 is highly expressed in developing seeds and is localized in the endoplasmic reticulum (ER). Ectopic expression of BnaGPAT9 in E. coli and siliques of Brassica napus enhanced phosphatidic acid (PA) production. Overexpression of BnaGPAT9 enhanced seed oil accumulation resulting from increased 18:2-fatty acid. Lipid profiling in developing seeds showed that overexpression of BnaGPAT9 led to decreased phosphatidylcholine (PC) and a corresponding increase in phosphatidylethanolamine (PE), implying that BnaGPAT9 promotes PC flux to storage triacylglycerol (TAG). Furthermore, overexpression of BnaGPAT9 also enhanced eukaryotic galactolipids including monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), with increased 36:6-MGDG and 36:6-DGDG, and decreased 34:6-MGDG in developing seeds. Collectively, these results suggest that ER-localized BnaGPAT9 promotes PA production, thereby enhancing seed oil accumulation and eukaryotic galactolipid biosynthesis in Brassica napus.

PLPPR4 haploinsufficiency causes neurodevelopmental disorders by disrupting synaptic plasticity via mTOR signalling.

Phospholipid phosphatase related 4 (PLPPR4), a neuron-specific membrane protein located at the postsynaptic density of glutamatergic synapses, is a putative regulator of neuronal plasticity. However, PLPPR4 dysfunction has not been linked to genetic disorders. In this study, we report three unrelated patients with intellectual disability (ID) or autism spectrum disorder (ASD) who harbour a de novo heterozygous copy number loss of PLPPR4 in 1p21.2p21.3, a heterozygous nonsense mutation in PLPPR4 (NM_014839, c.4C > T, p.Gln2*) and a homozygous splice mutation in PLPPR4 (NM_014839: c.408 + 2 T > C), respectively. Bionano single-molecule optical mapping confirmed PLPPR4 deletion contains no additional pathogenic genes. Our results suggested that the loss of function of PLPPR4 is associated with neurodevelopmental disorders. To test the pathogenesis of PLPPR4, peripheral blood mononuclear cells obtained from the patient with heterozygous deletion of PLPPR4 were induced to specific iPSCs (CHWi001-A) and then differentiated into neurons. The neurons carrying the deletion of PLPPR4 displayed the reduced density of dendritic protrusions, shorter neurites and reduced axon length, suggesting the causal role of PLPPR4 in neurodevelopmental disorders. As the mTOR signalling pathway was essential for regulating the axon maturation and function, we found that mTOR signalling was inhibited with a higher level of p-AKT, p-mTOR and p-ERK1/2, decreased p-PI3K in PLPPR4-iPSCs neurons. Additionally, we found silencing PLPPR4 disturbed the mTOR signalling pathway. Our results suggested PLPPR4 modulates neurodevelopment by affecting the plasticity of neurons via the mTOR signalling pathway.

Characteristics and mechanisms of mosaicism in prenatal diagnosis cases by application of SNP array.

BACKGROUND: With the application of chromosome microarray, next-generation sequencing and other highly sensitive genetic techniques in disease diagnosis, the detection of mosaicism has become increasingly prevalent. This study involved a retrospective analysis of SNP array testing on 4512 prenatal diagnosis samples, wherein the characterization of mosaicism was explored and insights were gained into the underlying mechanisms thereof. RESULTS: Using SNP array, a total of 44 cases of mosaicism were identified among 4512 prenatal diagnostic cases; resulting in a detection rate of approximately 1.0%. The prevalence of mosaicism was 4.1% for chorionic villus sample, 0.4% for amniotic fluid, and 1.3% for umbilical cord blood. Of these cases, 29 were mosaic aneuploidy and 15 were mosaic segmental duplication/deletion. Three cases of mosaic trisomy 16 and three cases of mosaic trisomy 22 were diagnosed in the CVS samples, while four cases of mosaic trisomy 21 were detected in amniotic fluid and umbilical cord blood samples. The distribution pattern of mosaicism suggested trisomy rescue as the underlying mechanism. Structurally rearranged chromosomes were observed, including three cases with supernumerary marker chromosomes, three cases with dicentric chromosomes, and one case with a ring chromosome. All mosaic segmental duplication/deletion cases were the result of mitotic non-disjunction, with the exception of one case involving mosaic11q segmental duplication. CONCLUSION: Improved utilization of SNP arrays enables the characterization of mosaicism and facilitates the estimation of disease mechanisms and recurrence.

Mind wandering state detection during video-based learning via EEG.

The aim of this study is to explore the potential of technology for detecting mind wandering, particularly during video-based distance learning, with the ultimate benefit of improving learning outcomes. To overcome the challenges of previous mind wandering research in ecological validity, sample balance, and dataset size, this study utilized practical electroencephalography (EEG) recording hardware and designed a paradigm consisting of viewing short-duration video lectures under a focused learning condition and a future planning condition. Participants estimated statistics of their attentional state at the end of each video, and we combined this rating scale feedback with self-caught key press responses during video watching to obtain binary labels for classifier training. EEG was recorded using an 8-channel system, and spatial covariance features processed by Riemannian geometry were employed. The results demonstrate that a radial basis function kernel support vector machine classifier, using Riemannian-processed covariance features from delta, theta, alpha, and beta bands, can detect mind wandering with a mean area under the receiver operating characteristic curve (AUC) of 0.876 for within-participant classification and AUC of 0.703 for cross-lecture classification. Furthermore, our results suggest that a short duration of training data is sufficient to train a classifier for online decoding, as cross-lecture classification remained at an average AUC of 0.689 when using 70% of the training set (about 9 min). The findings highlight the potential for practical EEG hardware in detecting mind wandering with high accuracy, which has potential application to improving learning outcomes during video-based distance learning.

Safety and efficacy of topical diquafosol for the treatment of dry eye disease: An updated meta-analysis of randomized controlled trials.

Dry eye disease (DED) is a common multi-factorial disease that is characterized by tear film instability. Diquafosol tetrasodium (DQS), an ophthalmic solution, has been shown to be beneficial in the treatment of DED. The goal of this study was to provide an update on the safety and efficacy of topical 3% DQS in treating DED patients. A thorough search for all the published randomized controlled trials (RCTs) up to March 31, 2022 in CENTRAL, PubMed, Scopus, and Google Scholar databases was performed. Data were reported as standardized mean difference (SMD) with 95% confidence interval (CI). Modified Jadad scale was used for sensitivity analysis. Funnel plot and Egger's regression test assessed the publication bias. Fourteen RCTs evaluating the safety and efficacy of topical 3% DQS treatment in DED patients were included. Eight included RCTs reported data on the DED after cataract surgery. Overall findings suggest that 3% DQS treatment in DED patients was associated with significantly better improvement at 4 weeks in tear breakup time, Schirmer test, fluorescein staining scores, and Rose Bengal staining score as compared to patients treated with others eye drops including artificial tears or 01% sodium hyaluronate. However, no significant difference in ocular surface disease index was observed. Our findings suggest that 3% DQS treatment is safer and had a superior efficacy compared to artificial tears or sodium hyaluronate for treating DED in general and DED after cataract surgery.

Lysine Demethylase 1B Promotes Tear Secretion Disorder in Sjogren's Syndrome by Regulating the PAX6/CLU Axis.

The impacts of lysine demethylase 1B (KDM1B) have been probed in multiple diseases, but the effects of KDM1B on SS remained obscure. The study aimed to unravel the efficiency of KDM1B on SS progression via the paired box 6 (PAX6)/clusterin (CLU) axis. NODB10. H2b mice were selected to establish the SS model. KDM1B, Pax6, and CLU expression in SS mice was assessed. Adeno-associated viruses carrying KDM1B, Pax6, and CLU were injected into the SS mice to detect tear secretion, epithelium corneal fluorescein staining scores, and levels of specific markers of lacrimal gland epithelial cells, neurotransmitter receptors that induce secretion from the lacrimal gland, and genes encoding normal tear components. The relation among KDM1B, Pax6, and CLU was examined. The rescue experiments were conducted for verifying the interaction among KDM1B, Pax6, and CLU. KDM1B expression was elevated, while Pax6 and CLU levels were decreased in the lacrimal gland tissues of SS mouse models. KDM1B decrement and Pax6 augmentation improved tear secretion, reduced corneal fluorescein staining score, decreased levels of specific markers of lacrimal gland epithelial cells, and increased levels of neurotransmitter receptors that induce secretion from the lacrimal gland and genes encoding normal tear components. KDM1D suppressed Pax6 expression by mediating H3K4me2 demethylation. Pax6 promoted the expression of CLU at the transcriptional level by binding to the CLU promoter. Silencing of Pax6 or CLU could reverse the effects of KDM1B reduction on improving the tear secretion disorder of SS mice. Silencing KDM1B mitigates the tear secretion disorder of SS mice via modulating the Pax6/CLU axis.

The Effect of Orthokeratology Lens on the Axial Length of Globe in Children with Myopia in Asia.

The aim of this meta-analysis was to determine the effect of orthokeratology (OK) lens on the axial length of the eye globe of Asian children with myopia of low and moderate degree compared with children treated with glasses. PubMed, Embase, Web of Science, and Cochrane Library were searched to collect relative researches on the treatment of OK lens in myopia children from January 2000 to July 2021. The authors adopted the standardised mean difference (SMD) as effect size, to estimate the pooled changes of axial length in Asian myopic children. Seven articles were identified. In Asian children with myopia of low to a moderate degree, compared with glasses treatment, axial length decreased significantly in the OK Lens group (SMD = -0.84, 95%CI: -1.10 ~ -0.58), with a p-value less than 0.05. According to the follow-up time, the subgroup analysis demonstrated that, SMD = -0.68 (95%CI: -1.43 ~ 0.08, p>0.05) for six months; SMD = -1.00 (95 %CI: -1.38~-0.62, p<0.05) for 12 months; SMD=-0.71 (95%CI: -1.20~-0.21, p<0.05) for two years. In conclusion, in the early treatment, compared with glasses, children with low and moderate myopia wearing OK lenses were more effective in reducing axial elongation in Asia. Key Words: Axial length, Orthokeratology, Myopia, Meta-analysis.

The Relationship between Physical Exercise and Negative Emotions in College Students in the Post-Epidemic Era: The Mediating Role of Emotion Regulation Self-Efficacy.

OBJECTIVE: To investigate the relationship between physical activity and negative emotions among college students in the post-epidemic era and determine if emotional regulation plays a mediating role between physical activity and negative emotions. METHODS: 479 college students (293 males, 186 females, M = 19.94, SD = 1.25) who were under closed campus management during the epidemic period were surveyed using the physical activity rating scale (PARS-3), the self-assessment scale for anxiety (SAS), the self-esteem scale for depression (SDS), and the emotion regulation self-efficacy scale (RES). RESULTS: (1) Physical activity, negative emotions, and emotion regulation self-efficacy among college students were significantly different by gender (p < 0.01). (2) Physical exercise was negatively correlated with anxiety and depression (r = -0.236, p < 0.01; r = -0.198, p < 0.01) and positively correlated with emotion regulation self-efficacy (r = 0.256, p < 0.01) in college students. (3) Emotion regulation self-efficacy was negatively correlated with anxiety and depression (r = -0.440, p < 0.01; r = -0.163, p < 0.01). (4) Emotion regulation self-efficacy also partially mediated the relationship between physical activity and negative emotions. CONCLUSION: (1) Physical activity in the post-epidemic era negatively predicted anxiety and depression in school-isolated college students. (2) Emotion regulation self-efficacy in the post-epidemic era partially mediates the relationship between physical activity and anxiety and depression.

Novel compound heterozygous synonymous and missense variants in the MYO7A gene identified by next-generation sequencing in a Chinese family with nonsyndromic hearing loss.

BACKGROUND: Variants in the MYO7A gene are increasingly identified among patients suffering from Usher syndrome type 1B (USH1B). However, such mutations are less commonly detected among patients suffering from nonsyndromic hearing loss (NSHL), including autosomal recessive deafness (DFNB2) and autosomal dominant deafness (DFNA11). This research attempts to clarify the genetic base of DFNB2 in a Chinese family and determine the pathogenicity of the identified mutations. METHOD: Targeted next-generation sequencing (TGS) of 127 known deafness genes was performed for the 14-year-old proband. Then, Sanger sequencing was performed on the available family members. A minigene splicing assay was performed to verify the impact of the novel MYO7A synonymous variant. After performing targeted next-generation sequencing (TGS) of 127 existing hearing loss-related genes in a 14-year-old proband, Sanger sequencing was carried out on the available family members. Then, to confirm the influence of the novel MYO7A synonymous variants, a minigene splicing assay was performed. RESULTS: Two heteroallelic mutants of MYO7A (NM_000260.3) were identified: a maternally inherited synonymous variant c.2904G > A (p.Glu968=) in exon 23 and a paternally inherited missense variant c.5994G > T (p.Trp1998Cys) in exon 44. The in vitro minigene expression indicated that c.2904G > A may result in skipping of exon 23 resulting in a truncated protein. CONCLUSIONS: We reported a novel missense (c.5994G > T) and identified, for the first time, a novel pathogenic synonymous (c.2904G > A) variant within MYO7A in a patient with DFNB2. These findings enrich our understanding of the MYO7A variant spectrum of DFNB2 and can contribute to accurate genetic counseling and diagnosis of NSHL patients.

Simultaneous quantification of SMN1 and SMN2 copy numbers by MALDI-TOF mass spectrometry for spinal muscular atrophy genetic testing.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder caused by defects in the survival motor neuron 1 (SMN1) gene. Homozygous deletion of the SMN1 gene accounts for 95% of all affected SMA patients. A highly homologous gene survival motor neuron 2 (SMN2) compensates weakly with the loss of SMN1 and its copy number correlates with disease severity. METHODS: We report here the MS-CNV method combining competitive PCR and MALDI-TOF mass spectrometry for simultaneous quantification of SMN1, SMN2 and NAIP dosages. For both SMN1 and SMN2, the exon 7 and exon 8 were analyzed. MS-CNV was validated with parallel analysis by a commercial MLPA assay in two independent cohorts. RESULTS: In the first cohort of 79 blood samples containing 3 SMA patients and 5 carriers, MS-CNV results were highly concordant with MLPA analysis for the copy numbers of SMN1, SMN2 and NAIP. In the second independent and blinded cohort of 62 blood samples containing 21 SMA patients and 14 carriers, MS-CNV results were also highly concordant with MLPA. Both MS-CNV and MLPA quantified SMN1 dosages without ambiguity. CONCLUSIONS: MS-CNV can be used for carrier screening and genetic diagnosis of SMA, providing dosages information for both SMN1 and SMN2 given its accuracy and high sample processing throughput by mass spectrometric analysis.

[Analysis of ARID1B gene variants in two Chinese pedigrees with Coffin-Siris syndrome].

OBJECTIVE: To explore the genetic basis for two Chinese pedigrees affected with Coffin-Siris syndrome (CSS). METHODS: Whole exome sequencing (WES) was carried out for the probands. Candidate variants were verified by Sanger sequencing of the probands and their family members. RESULTS: The two probands were respectively found to harbor a heterozygous c.5467delG (p.Gly1823fs) variant and a heterozygous c.5584delA (p.Lys1862fs) variant of the ARID1B gene, which were both of de novo in origin and unreported previously. Based on the guidelines of American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION: The c.5467delG (p.Gly1823fs) and c.5545delA (p.Lys1849fs) variants of the ARID1B genes probably underlay the CSS in the two probands. Above results have enabled genetic counselling and prenatal diagnosis for the pedigrees.

The distal arthrogryposis-linked p.R63C variant promotes the stability and nuclear accumulation of TNNT3.

BACKGROUND: Distal arthrogryposis (DA) is comprised of a group of rare developmental disorders in muscle, characterized by multiple congenital contractures of the distal limbs. Fast skeletal muscle troponin-T (TNNT3) protein is abundantly expressed in skeletal muscle and plays an important role in DA. Missense variants in TNNT3 are associated with DA, but few studies have fully clarified its pathogenic role. METHODS: Sanger sequencing was performed in three generation of a Chinese family with DA. To determine how the p.R63C variant contributed to DA, we identified a variant in TNNT3 (NM_006757.4): c.187C>T (p.R63C). And then we investigated the effects of the arginine to cysteine substitution on the distribution pattern and the half-life of TNNT3 protein. RESULTS: The protein levels of TNNT3 in affected family members were 0.8-fold higher than that without the disorder. TNNT3 protein could be degraded by the ubiquitin-proteasome complex, and the p.R63C variant did not change TNNT3 nuclear localization, but significantly prolonged its half-life from 2.5 to 7 h, to promote its accumulation in the nucleus. CONCLUSION: The p.R63C variant increased the stability of TNNT3 and promoted nuclear accumulation, which suggested its role in DA.

Mental workload classification based on ignored auditory probes and spatial covariance.

Objective.Estimation of mental workload (MWL) levels by electroencephalography (EEG)-based mental state monitoring systems has been widely explored. Using event-related potentials (ERPs), elicited by ignored auditory probes, minimizes intrusiveness and has shown high performance for estimating MWL level when tested in laboratory situations. However, when facing real-world applications, the characteristics of ERP waveforms, like latency and amplitude, are often affected by noise, which leads to a decrease in classification performance. One approach to mitigating this is using spatial covariance, which is less sensitive to latency and amplitude distortion. In this study, we used ignored auditory probes in a single-stimulus paradigm and tested Riemannian processed covariance-based features for MWL level estimation in a realistic flight-control task.Approach.We recorded EEG data with an eight-channel system from participants while they performed a simulated drone-control task and manipulated MWL levels (high and low) by task difficulty. We compared support vector machine classification performance based on frequency band power features versus features generated via the Riemannian log map operator from spatial covariance matrices. We also compared accuracy of using data segmented as auditory ERPs versus non-ERPs, for which data windows did not overlap with the ERPs.Main results.Classification accuracy of both types of features showed no significant difference between ERPs and non-ERPs. When we ignore auditory stimuli to perform continuous decoding, covariance-based features in the gamma band had area under the receiver-operating-characteristic curve (AUC) of 0.883, which was significantly higher than band power features (AUC = 0.749).Significance.This study demonstrates that Riemannian-processed covariance features are viable for MWL classification under a realistic experimental scenario.

Localization of nerve entry points and the center of intramuscular nerve-dense regions in the adult pectoralis major and pectoralis minor and its significance in blocking muscle spasticity.

The aims of this study were to localize the body surface position and depth of nerve entry points, and the center of the intramuscular nerve-dense regions of the pectoralis major and pectoralis minor in order to provide guidance for blocking muscle spasticity. Formalin-fixed adult cadavers (66.3 ± 5.2 years) were used. The curved line on the skin from the acromion to the most inferior point of the jugular notch was defined as the horizontal reference line (H). The line from the most inferior point of the jugular notch to the xiphisternal joint was defined as the longitudinal reference line (L). The nerve entry points was anatomically exposed. Sihler's staining, barium sulfate labeling, and computed tomography were employed to determine the projection points (P) on the body surface. The intersection of the longitudinal line through the P point and the H line and the horizontal line through the P point and the L line were recorded as PH and PL , respectively. The projection of the nerve entry points or the center of the intramuscular nerve-dense regions were in the opposite direction across the transverse plane and were recorded as P'. The percentage positions of PH and PL on the H and L lines, as well as the nerve entry points and the center of the intramuscular nerve-dense regions depths, were determined using the Syngo system. The pectoralis major had two nerve entry points, while the pectoralis minor had only one. In addition, two intramuscular nerve-dense regions were found in the pectoralis major, while only one region was found in the pectoralis minor. The PH of the nerve entry points were located at 47.83%, 32.31%, and 34.31%, while the PH of the center of the intramuscular nerve-dense regions were at 41.95%, 55.88%, and 32.58% of line H, respectively. The PL of the nerve entry points were at -9.84%, 36.16%, and 2.44%, while the PL for each of three center of the intramuscular nerve-dense regions was at -3.87%, 25.29%, and -7.13% of line L, respectively. The depth for each of the nerve entry points was at 17.76%, 17.53%, and 25.51% of line P-P'', respectively, and the depth of the center of the intramuscular nerve-dense regions was at 5.23%, 6.75%, and 13.73% of line P-P', respectively. These percentage values are all means. The definition of the surface position and depth of these nerve entry points and center of the intramuscular nerve-dense regions can improve the localization efficiency and efficacy of target blocking for pectoralis major and minor spasticity.

Resurgence of Positive qRT-PCR Test Results in Patients Recovered from COVID-19: Case Reports.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a newly emerging coronavirus. This virus poses a great threat to human society and has been marked as the third introduction of a highly pathogenic coronavirus into the human population. This is following severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) in the 21st-century. While China has achieved initial success in controlling the spread of COVID-19 and treating those infected with SARS-CoV-2, up to 14% of COVID-19 convalescents can still be detected with virus nucleic acid. Thus, there is an urgent need for more information to understand this new virus. Here we report the detailed clinical characteristics of three cases of COVID-19 convalescents that had repeated positive quantitative reverse transcription-polymerase chain reaction (qRT-PCR) test results for over three months. This may arouse concerns regarding the present quarantine protocol after convalescence and provide a reference for governments to consider when to reopen the community.

[Analysis of genetic variation for a child affected with congenital insensitivity to pain with anhidrosis and albinism by whole genome sequencing].

OBJECTIVE: To explore the genetic variation of a Chinese family affected with congenital insensitivity to pain with anhidrosis and albinism. METHODS: Whole exome sequencing (WES) was carried out to screen potential variants within genomic DNA extracted from the proband and his parents. Whole genome sequencing (WGS) was applied when variants were not found completely. Suspected variants were validated by Sanger sequencing. RESULTS: WES has identified a heterozygous c.1729G>C (p.G577R) variant of NTRK1 gene and two heterozygous variants of OCA2 gene, namely c.1363A>G (p.R455G) and c.1182+1G>A. WGS has identified two additional heterozygous variants c.(851-798C>T; 851-794C>G) in deep intronic regions of the NTRK1 gene. CONCLUSION: The compound heterozygous variants of the NTRK1 gene probably underlay the congenital insensitivity to pain with anhidrosis. And the compound heterozygous variants of the OCA2 gene probably underlay the albinism in the proband. In the case where no variant is detected by WES in the coding region, WGS should be considered to screen potential variants in the whole genome.

The variations in human orphan G protein-coupled receptor QRFPR affect PI3K-AKT-mTOR signaling.

BACKGROUND: QRFPR is a recently identified member of the G protein-coupled receptor and is an orphan receptor for 26Rfa, which plays important role in the regulation of many physiological functions. METHODS: Here, we employed whole exome sequencing (WES) to examine the patients with intellectual disability (ID) and difficulty in feeding. We performed SIFT and PolyPhen2 predictions for the variants. The structure model was built from scratch by I-TASSER. Here, results derived from a number of cell-based functional assays, including shRNA experiment, intracellular Ca2+ measurement, the expression of PI3 K-AKT-mTOR, and phosphorylation. The functional effect of QRFPR variants on PI3K-AKT-mTOR signaling was evaluated in vitro transfection experiments. RESULT: Here, we identified two QRFPR variants at c.202 T>C (p.Y68H) and c.1111C>T (p.R371W) in 2 unrelated individuals. Structural analysis revealed that p.Y68H and p.R371W variants may affect the side chain structure of adjacent amino acids causing reduced binding of QRFPR to 26Rfa. The results show that QRFPR stimulated by 26Rfa leading to the transient rise of intracellular Ca2+ . The QRFPR variations p.Y68H and p.R371 W can reduce the mobilization of intracellular Ca2+ . The phosphorylation levels of the PI3K, Akt, and mTOR were significantly up- or downregulated by QRFPR overexpression or silencing, respectively. The QRFPR variations inhibited PI3K-AKT-mTOR signaling, resulting in downregulation of p-mTOR. CONCLUSIONS: Our findings suggest that QRFPR acts as important role in neurodevelopment, and the effects of QRFPR are likely to be mediated by the Ca2+ -dependent PI3K-AKT-mTOR pathways. Importantly, these findings provide a foundation for future elucidation of GPCR-mediated signaling and the physiological implications.