Revealing unexpected complex encoding but simple decoding mechanisms in motor cortex via separating behaviorally relevant neural signals.

In motor cortex, behaviorally relevant neural responses are entangled with irrelevant signals, which complicates the study of encoding and decoding mechanisms. It remains unclear whether behaviorally irrelevant signals could conceal some critical truth. One solution is to accurately separate behaviorally relevant and irrelevant signals at both single-neuron and single-trial levels, but this approach remains elusive due to the unknown ground truth of behaviorally relevant signals. Therefore, we propose a framework to define, extract, and validate behaviorally relevant signals. Analyzing separated signals in three monkeys performing different reaching tasks, we found neural responses previously considered to contain little information actually encode rich behavioral information in complex nonlinear ways. These responses are critical for neuronal redundancy and reveal movement behaviors occupy a higher-dimensional neural space than previously expected. Surprisingly, when incorporating often-ignored neural dimensions, behaviorally relevant signals can be decoded linearly with comparable performance to nonlinear decoding, suggesting linear readout may be performed in motor cortex. Our findings prompt that separating behaviorally relevant signals may help uncover more hidden cortical mechanisms.

The Timing and Dose Effect of Acupuncture on Pregnancy Outcomes for Infertile Women Undergoing In Vitro Fertilization and Embryo Transfer: A Systematic Review and Meta-Analysis.

Background: Women undergoing in vitro fertilization and embryo transfer (IVF-ET) often utilize acupuncture to enhance pregnancy outcomes. Yet, the optimal timing for acupuncture sessions and the relationship between dosage and effect remain uncertain. Objectives: To investigate the impact of the timing and dosage of acupuncture on pregnancy outcomes, drawing on existing research. Methods: A comprehensive search of eight databases was conducted from their inception to January 14th, 2023, without restrictions on language. Only randomized controlled trials comparing acupuncture with either sham acupuncture or no adjuvant treatment were selected for inclusion. This meta-analysis assessed the efficacy of acupuncture in IVF-ET, analyzing the influence of varied timing and dosage on pregnancy outcomes. Subgroup analyses were undertaken to address any heterogeneity across the studies. Results: A total of 38 RCTs involving 5,991 participants were analyzed. In infertile women undergoing IVF fresh cycles, acupuncture performed during controlled ovarian hyperstimulation (COH) significantly increased the clinical pregnancy rate (CPR) (relative risk [RR] = 1.33, 95% confidence interval [CI]: 1.07-1.65, p = 0.01), whereas acupuncture administered either before COH or on the day of ET did not demonstrate reproductive benefits. Regarding frozen cycles, acupuncture before freeze-thaw embryo transfer (FET) significantly enhanced the CPR (RR = 1.71, 95% CI: 1.36-2.16, p < 0.00001) and live birth rate (LBR) (RR = 2.40, 95% CI: 1.20-4.79, p = 0.01). Improvements in CPR were observed across all dosage groups, but only the high-dosage group showed a significant increase in LBR (RR = 1.75, 95% CI: 1.05-2.92, p = 0.03). Conclusions: Timing and dosage of acupuncture are crucial factors affecting pregnancy outcomes in IVF-ET. For women undergoing IVF fresh cycles, acupuncture during COH yielded more significant reproductive benefits. In addition, acupuncture before freeze-thaw embryo transfer (FET) was associated with improved pregnancy outcomes in frozen cycles. Furthermore, higher dosages of acupuncture were linked to more favorable outcomes.

[Newborn screening, clinical features and genetic analysis for Citrin deficiency in Henan province].

OBJECTIVE: To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China. METHODS: A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired-t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. RESULTS: Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c.852_855delTATG, c.615+5G>A, c.550C>T and IVS16ins3kb were known pathogenic variants, whilst c.1111_1112delAT and c.837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis. CONCLUSION: The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c.852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Mechanism insights into the pleiotropic effects of nobiletin as a potential therapeutic agent on non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases and is emerging as one of the fastest-growing causes of liver-related deaths worldwide. It is necessary to find strategies to effectively prevent and treat NAFLD, as no definitive drug has been approved. Nobiletin (NOB) is the critical active ingredient of Chinese herbal medicines such as Citrus aurantium and Citri Reticulatae Pericarpium, which have anti-inflammatory, antioxidant, lipid regulating, and insulin resistance regulating effects. Numerous studies have demonstrated that NOB can prevent and treat the onset and progression of NAFLD. In this review, the mechanisms of NOB for treating NAFLD have been summarized, hoping to provide a basis for subsequent studies of NOB and to provide a research ground for the development of therapeutic drugs for NAFLD.

Genetic analysis of isolated methylmalonic acidemia in Henan, China: c.1663G>A variant of MMUT prevalent in the Henan population.

BACKGROUND: Methylmalonic acidemia (MMA) is the most common organic acidemia in China, and isolated MMA accounts for approximately 30 % of all types of MMA. Common variants of the MMUT gene vary greatly around the world. The present study aims to determine the high-frequency and novel genetic variants of the MMUT gene in the Henan population of China and evaluate the prognosis of patients carrying the c.1663G>A (p.Ala555Thr) variant. METHODS: We performed next-generation sequencing for 41 patients with isolated MMA screened by tandem mass spectrometry (MS/MS) and analysed the genetic results. We also evaluated the prognosis of patients with the c.1663G>A variant. We used Jalview software for multispecies sequence alignment and Missense3D and DynaMut to predict the protein function of the detected novel variants. RESULTS: A total of 43 variants from 41 patients with isolated MMA were detected, of which c.1663G>A (14.63 %), c.729_730insTT (10.98 %), and c.1106G>A (8.53 %) are high-frequency variants of the MMUT gene in the Henan population. The patients carrying the c.1663G>A variant tended to be responsive to vitamin B12, have a low mortality rate. We also identified 5 novel variants (c.479C>T, c.811G>C, c.965T>A, c.1142G>A and c.1667C>T). CONCLUSION: The rare variant c.1663G>A is prevalent in the Henan population, and infants with this variant tend to have good prognosis. Our findings, especially novel variants, will help broaden the spectrum of genetic variants and facilitate clinical diagnosis and genetic counselling for affected families.

Construction of Data-Driven Performance Digital Twin for a Real-World Gas Turbine Anomaly Detection Considering Uncertainty.

Anomaly detection and failure prediction of gas turbines is of great importance for ensuring reliable operation. This work presents a novel approach for anomaly detection based on a data-driven performance digital twin of gas turbine engines. The developed digital twin consists of two parts: uncertain performance digital twin (UPDT) and fault detection capability. UPDT is a probabilistic digital representation of the expected performance behavior of real-world gas turbine engines operating under various conditions. Fault detection capability is developed based on detecting UPDT outputs that have low probability under the training distribution. A novel anomaly measure based on the first Wasserstein distance is proposed to characterize the entire flight data, and a threshold can be applied to this measure to detect anomaly flights. The proposed UPDT with uncertainty quantification is trained with the sensor data from an individual physical reality and the outcome of the UPDT is intended to deliver the health assessment and fault detection results to support operation and maintenance decision-making. The proposed method is demonstrated on a real-world dataset from a typical type of commercial turbofan engine and the result shows that the F1 score reaches a maximum of 0.99 with a threshold of 0.45. The case study demonstrated that the proposed novel anomaly detection method can effectively identify the abnormal samples, and it is also possible to isolate anomalous behavior in a single performance signal, which is helpful for further fault diagnosis once an anomaly is detected.

Tensor Recovery Based on a Novel Non-Convex Function Minimax Logarithmic Concave Penalty Function.

Non-convex relaxation methods have been widely used in tensor recovery problems, compared with convex relaxation methods, and can achieve better recovery results. In this paper, a new non-convex function, Minimax Logarithmic Concave Penalty (MLCP) function, is proposed, and some of its intrinsic properties are analyzed, among which it is interesting to find that the Logarithmic function is an upper bound of the MLCP function. The proposed function is generalized to tensor cases, yielding tensor MLCP and weighted tensor Lγ -norm. Consider that its explicit solution cannot be obtained when applying it directly to the tensor recovery problem. Therefore, the corresponding equivalence theorems to solve the such problem are given, namely, tensor equivalent MLCP theorem and equivalent weighted tensor Lγ -norm theorem. In addition, we propose two EMLCP-based models for classic tensor recovery problems, namely low-rank tensor completion (LRTC) and tensor robust principal component analysis (TRPCA), and design proximal alternate linearization minimization (PALM) algorithms to solve them individually. Furthermore, based on the Kurdyka-Åasiwicz property, it is proved that the solution sequence of the proposed algorithm has a finite length and converges to the critical point globally. Finally, extensive experiments show that the proposed algorithm achieves good results, and it is confirmed that the MLCP function is indeed better than the Logarithmic function in the minimization problem, which is consistent with the analysis of theoretical properties.

Newborn screening and genomic analysis of duchenne muscular dystrophy in Henan, China.

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is a rare disorder caused by mutations in the dystrophin gene. Recent availability in treatment for DMD raised the need of early screening in our center, but newborn screening (NBS) for DMD has not been carried out in Henan Province. OBJECTIVES: To determine an optimal cutoff value through the quantitative determination of the creatine kinase isoform MM (CK-MM) concentration dried blood spot (DBS) to identify male DMD, and to evaluate assess the detection rate and mutation spectrum of DMD in Henan, China. METHODS: The CK-MM level in DBS was measured using with a GSP® neonatal creatine kinase -MM kit from 13,110 male newborns to establish the cut-off value for CK-MM. Multiplex ligation-dependent probe amplification (MLPA) were carried out for infants with elevated CK levels to detect DMD gene deletions/ duplications, NGS and sanger sequencing were then applied to exclude MLPA-negative samples to single-nucleotide variants. Phenotype-genotype correlations were analyzed using REVEL For novel missense mutations. RESULTS: Statistical analysis of CK-MM value of the 13,110 neonates suggested that the cut-off value may be set as 472 ng/mL. 3 cases of DMD were screened among 13,110 newborns, all of whom had CK-MM levels >600 ng/mL. We detected 4 rare variants in DMD gene, including 2 exon deletions (deletion of exon 52 and deletion from exon 3 to exon 7) and 2 point variants (c.9568C>T and c.4030C>T). Two cases were all exon deletions, one case was compound heterozygous variants. CONCLUSIONS: The estimated incidence of male neonatal DMD was 1:4,370 in Henan province. NBS is of great value to the early intervention and treatment of the disease, and is fundamental to support public health decision-making. The experience from this study provided a model that will allow further expansion and facilitate establishment a universal public health screening in Henan hospital systems.

Effect of transcutaneous electrical acupoint stimulation on pregnancy outcomes in women with in vitro fertilization-embryo transfer: A systematic review and meta-analysis.

Objective: The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) on pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer (IVF-ET), in order to provide evidence-based medical support. Methods: We searched the Cochrane Library, Embase, PubMed, Web of Science, SinoMed, and CNKI for relevant randomized controlled trials (RCTs) from inception to 31 May 2022, using the search terms "transcutaneous electrical acupoint stimulation," "TEAS," "in vitro fertilization-embryo transfer," "IVF-ET," "randomized controlled trial," and "clinical trials." The experimental group was treated with TEAS or combined with ovulation-inducing medication, and the control group was treated with mock TEAS (mTEAS), ovulation-inducing medication, or no intervention. The main outcome was the clinical pregnancy rate. Secondary outcomes were the embryo implantation rate, live birth rate, biochemical pregnancy rate, and number of oocytes retrieved. Stata15.1 software was used for data summary and analysis. Results: This review involved 15 RCTs and 4,281 participants. TEAS were superior to the control group for improving the clinical pregnancy rate [RR: 1.29, 95% CI: 1.19 to 1.40; p < 0.001; I2 = 23.0%], embryo implantation rate [RR: 1.43, 95% CI: 1.22 to 1.69; p < 0.001; I2 = 35.9%], live birth rate [RR: 1.33, 95% CI: 1.14 to 1.54; p < 0.001; I2 = 47.3%], and biochemical pregnancy rate [RR: 1.15, 95% CI: 1.05 to 1.26; p = 0.003; I2 = 49.1%], without significant heterogeneity. TEAS had no statistically significant effect on the number of oocytes retrieved as compared with the control group, and the heterogeneity was high [SMD: 0.34, 95% CI: -0.04 to 0.72; p = 0.081; I2 = 77.6%]. We performed subgroup analysis based on the sample size, interventions and intervention time-point. The results showed that the sample size had no effect on the results. There was no significant difference between TEAS and ovulation-inducing medication in the clinical pregnancy rate or the embryo implantation rate. In addition, TEAS did not significantly increase the embryo implantation rate or the live birth rate, compared with no intervention. In terms of safety, mild allergic symptoms were found in both the experimental group and the control group. Conclusion: In general, existing evidence supports the potential value of TEAS as an adjunctive treatment for improving pregnancy outcomes. High-quality, large-sample RCTs are needed to further support this conclusion. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=334892, identifier PROSPERO CRD42022334892.

Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital.

Considerable attention has been focused on the clinical features of coronavirus disease 2019 (COVID-19), but it is also important for clinicians to differentiate it from influenza virus infections. In the present study, the rate of coexisting disease was lower in the severe COVID-19 group than in the influenza A group (p = 0.003). Radiologically, severe COVID-19 patients had fewer instances of pleural effusion (p < 0.001). Clinically, severe COVID-19 patients had relatively better disease severity scores, less secondary bacterial infections, shorter times to beginning absorption on computed tomography, but longer durations of viral shedding from the time of admission (p < 0.05). Although the more severe influenza A patients required noninvasive respiratory support, these two groups ultimately yielded comparable mortalities. Based on the multiple logistic regression analysis, severe COVID-19 infection was associated with a lower risk of severe acute respiratory distress syndrome [odds ratio (OR) 1.016, 95% [confidence interval (CI)] 1.001-1.032, p = 0.041] and a better pneumonia severity index (OR 0.945, 95% [CI] 0.905-0.986, p = 0.009); however, these patients exhibited longer durations of viral shedding (OR 1.192, 95% [CI] 1.047-1.357, p = 0.008) than patients with severe influenza A infection. In conclusion, the conditions of severe influenza A patients appeared to be more critical than that of severe COVID-19 patients. However, relatively lower mortalities of these two severe cases are expected in the context of sufficient medical supplies.