Miracle-dz/UniFAR-FTUs huggingface dataset:
Gonadal Soma‐Derived Factor Expression is a Potential Biomarker for Predicting the Effects of Endocrine‐Disrupting Chemicals on Gonadal Differentiation in Japanese Medaka (Oryzias Latipes)

Chemicals with androgenic or estrogenic activity induce the sex reversal and/or intersex condition in various teleost fish species. Previously, we reported that exposure to 17α‐methyltestosterone, bisphenol A, or 4‐nonylphenol induces changes in expression of the gonadal soma‐derived factor (gsdf) gene accompanied by disruption of gonadal differentiation in Japanese medaka (Oryzias latipes). These findings suggest that gsdf expression might be a useful biomarker for predicting the potential effect of chemicals on gonadal differentiation. We examined the gsdf expression in Japanese medaka exposed to chemicals with estrogenic or androgenic activity. Exposure to the androgenic steroid 17β‐trenbolone at 0.5–22.1 μg/L induced the development of ovotestis (presence of ovarian tissue with testicular tissue) and female‐to‐male sex reversal in XX embryos, and exposure at 6.32 and 22.1 μg/L significantly increased gsdf expression in XX embryos compared with controls at developmental stage 38 (1 day before hatching). In the present study, no statistically significant difference in gsdf mRNA expression was observed after exposure to 17β‐estradiol, 17α‐ethinylestradiol, and 4‐t‐octylphenol, which have estrogenic activity. In addition, antiandrogenic chemicals or chemicals without endocrine‐disrupting activity did not induce changes in gsdf expression in XX or XY embryos. Thus, an increase in gsdf expression after androgen exposure was observed in XX embryos. Together, these findings indicate that gsdf expression might be useful for predicting the adverse effect of chemicals on gonadal differentiation. Environ Toxicol Chem 2022;41:1875–1884. © 2022 SETAC
AutoPhy: Automated phylogenetic identification of novel protein subfamilies

Phylogenetic analysis of protein sequences provides a powerful means of identifying novel protein functions and subfamilies, and for identifying and resolving annotation errors. However, automation of functional clustering based on phylogenetic trees has been challenging, and most of it is done manually. Clustering phylogenetic trees usually requires the delineation of tree-based thresholds (e.g., distances), leading to an ad hoc problem. We propose a new phylogenetic clustering approach that identifies clusters without using ad hoc distances or other pre-defined values. Our workflow combines uniform manifold approximation and projection (UMAP) with Gaussian mixture models as a k-means like procedure to automatically group sequences into clusters. We then apply a “second pass” clade identification algorithm to resolve non-monophyletic groups. We tested our approach with several well-curated protein families (outer membrane porins, acyltransferase, and dehydrogenases) and showed our automated methods recapitulated known subfamilies. We also applied our methods to a broad range of different protein families from multiple databases, including Pfam, PANTHER, and UNIPROT. Our results showed that AutoPhy rapidly generated monophyletic clusters (subfamilies) within phylogenetic trees evolving at very different rates both within and among phylogenies. The phylogenetic clusters generated by AutoPhy resolved misannotations, determined new protein functional groups, and detected novel viral strains.
The Application of One-Cycle Control Technology in Electric Spring System

This paper first introduced the function, application and the control algorithm of the electric spring (ES), then the working principle of ES are explained. Aiming at the problems that the existing control algorithms have complex structures and are not conducive to accurate tracking of AC voltage signals on sensitive loads, this paper proposes the ES control strategy based on one-cycle control (OCC) technology. In Matlab/SimulinK, the ES system based on the OCC strategy is modeled and simulated. Through the waveform analysis, it is known that when the power of the photovoltaic system injected into the power grid fluctuates, the ES based on the OCC strategy system can operate in a capacitive, inductive or resistive mode automatically, which can achieve a direct and accurate tracking of a given AC voltage signal under the condition that a small amount of reactive power is injected into the grid, thus the voltage of the sensitive load is stabilized, and at the same time the voltage fluctuations on the grid side voltage can be transferred to non-sensitive loads in series with the ES.
Human Brain Development: a cross-sectional and longitudinal study integrating multiple neuromorphological features

Brain maturation studies typically examine relationships linking a single morphometric feature with aspects of cognition, behavior, age, or other demographic characteristics. However, the coordinated spatiotemporal arrangement of morphological features across development and their associations with behavior are unclear. Here, we examine covariation across multiple cortical features (cortical thickness [CT], surface area [SA], local gyrification index [GI], and mean curvature [MC]) using magnetic resonance images from the long-running National Institute of Mental Health developmental cohort (ages 5-25). Neuroanatomical covariance was examined using non-negative matrix factorization (NMF), which decomposes covariance resulting in a parts-based representation. Cross-sectionally, we identified six components of covariation which demonstrate differential contributions of CT, GI, and SA in hetero- vs. unimodal areas. We sought to use this technique longitudinally to examine covariance in rates of change, which highlighted a preserved SA in unimodal areas and changes in CT and GI in heteromodal areas. Using behavioral partial least squares (PLS), we identified a single latent variable (LV; 96 % covariance explained) that recapitulated patterns of reduced CT, GI, and SA that are generally related to older age, with limited contributions of IQ and SES. Longitudinally, PLS revealed three LVs that demonstrated a nuanced developmental pattern that highlighted a higher rate of maturational change in SA and CT in higher IQ and SES females. This novel characterization of brain maturation provides an important understanding of the interdependencies between morphological measures, their coordinated development, and their relationship to biological sex, cognitive ability, and the resources of the local environment. Significance The complex anatomy of the cortical sheet is best characterized using multiple morphometric characteristics. We expanded on recent developments in matrix factorization to identify spatial patterns of covariance across the cortical sheet. Using a large, well-characterized dataset, we examined the differential contributions of neuroanatomical features to cortical covariation in a single analytical framework using both cross-sectional and longitudinal data. We identified dominant modes of covariance between cortical morphometric features and their coordinated pattern of change, demonstrating sexually differentiated patterns and a strong association with variability in age, socioeconomic status, and cognitive ability. This novel characterization of cortical morphometry provides an important understanding of the interdependencies between neuroanatomical measures in the brain and behavioral development context.
Computational design of peptides to target NaV1.7 channel with high potency and selectivity for the treatment of pain

The voltage-gated sodium NaV1.7 channel plays a key role as a mediator of action potential propagation in C-fiber nociceptors and is an established molecular target for pain therapy. ProTx-II is a potent and moderately selective peptide toxin from tarantula venom that inhibits human NaV1.7 activation. Here we used available structural and experimental data to guide Rosetta design of potent and selective ProTx-II-based peptide inhibitors of human NaV1.7 channels. Functional testing of designed peptides using electrophysiology identified the PTx2-3127 and PTx2-3258 peptides with IC50s of 7 nM and 4 nM for hNaV1.7 and more than 1,000-fold selectivity over human NaV1.1, NaV1.3, NaV1.4, NaV1.5, NaV1.8, and NaV1.9 channels. PTx2-3127 inhibits NaV1.7 currents in mouse and human sensory neurons and shows efficacy in rat models of chronic and thermal pain when administered intrathecally. Rationally-designed peptide inhibitors of human NaV1.7 channels have transformative potential to define a new class of biologics to treat pain.
Centroidal Trajectory Generation and Stabilization Based on Preview Control for Humanoid Multi-Contact Motion

Multi-contact motion is important for humanoid robots to work in various environments. We propose a centroidal online trajectory generation and stabilization control for humanoid dynamic multi-contact motion. The proposed method features the drastic reduction of the computational cost by using preview control instead of the conventional model predictive control that considers the constraints of all sample times. By combining preview control with centroidal state feedback for robustness to disturbances and wrench distribution for satisfying contact constraints, we show that the robot can stably perform a variety of multi-contact motions through simulation experiments.
Logistics contracting effectiveness: the perspective of Thai electronics

Drawing from the literature and on the insights from customers, the current study empirically developed a six-factor model that explains logistics contracting effectiveness. These six factors include: (1) long-term orientation, (2) information sharing, (3) risk aversion, (4) conflict handling, (5) trust, and (6) proactive improvement. Based upon the study results, the researcher suggests that to enhance logistics contracting effectiveness, both customers and LSPs should emphasize developing long-term relationships, sharing appropriate information, and managing conflict effectively. Apart from these, LSPs should also emphasize building competence trust and trust in integrity. For policymakers, this study suggests that they should emphasize raising the awareness of Thai manufactures, particularly the small- and medium-sized firms, about the benefits of internally-integrated logistics. They should be encouraged to contract out their logistics activities to competent LSPs from whom they will gain almost instant access to sophisticated logistics expertise and technologies without incurring a substantial upfront investment.
FCNNLib: A Flexible Convolution Algorithm Library for Deep Learning on FPGAs

Convolution features huge complexity and demands high computation capability. Among hardware platforms, field programmable gate array (FPGA) emerges as a promising solution for its substantial available parallelism and energy efficiency. Besides, convolution can be implemented with different algorithms, including conventional, general matrix–matrix multiplication (GEMM), Winograd, and fast Fourier transformation (FFT) algorithms, which are diverse in arithmetic complexity, resource requirement, etc. Different convolutional neural network (CNN) models have different topologies and structures, favoring different convolution algorithms. In response, software libraries such as cuDNN provide a variety of computational primitives to support these algorithms. However, supporting such libraries on FPGAs is challenging. First, multiple algorithms can share the FPGA resources spatially as well as temporally, introducing either reconfiguration overhead or resource underutilization. Second, FPGA implementation remains a significant challenge for library developers. It typically requires significant specialized hardware knowledge. In this article, we propose <monospace>FCNNLib</monospace>, an efficient and scalable convolution algorithm library on FPGAs. To coordinate multiple convolution algorithms on FPGAs, we develop three schedulings: 1) spatial; 2) temporal; and 3) hybrid, which exhibit different tradeoffs in latency and throughput. We explore these schedulings by balancing the reconfiguration overhead, resource utilization, and optimization objectives of the CNNs. Then, we provide efficient and tunable algorithm templates that allow performance tuning through performance and resource models. To arm the users, <monospace>FCNNLib</monospace> exposes a set of interfaces to support high-level application designs. We demonstrate the usability of <monospace>FCNNLib</monospace> with state-of-the-art CNNs. <monospace>FCNNLib</monospace> achieves up to <inline-formula> <tex-math notation="LaTeX">$44.6\times $ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$1.76\times $ </tex-math></inline-formula> energy efficiency in various scenarios compared with software libraries for CPUs and GPUs, respectively.
The neurobiology of misophonia and implications for novel, neuroscience-driven interventions

Decreased tolerance in response to specific every-day sounds (misophonia) is a serious, debilitating disorder that is gaining rapid recognition within the mental health community. Emerging research findings suggest that misophonia may have a unique neural signature. Specifically, when examining responses to misophonic trigger sounds, differences emerge at a physiological and neural level from potentially overlapping psychopathologies. While these findings are preliminary and in need of replication, they support the hypothesis that misophonia is a unique disorder. In this theoretical paper, we begin by reviewing the candidate networks that may be at play in this complex disorder (e.g., regulatory, sensory, and auditory). We then summarize current neuroimaging findings in misophonia and present areas of overlap and divergence from other mental health disorders that are hypothesized to co-occur with misophonia (e.g., obsessive compulsive disorder). Future studies needed to further our understanding of the neuroscience of misophonia will also be discussed. Next, we introduce the potential of neurostimulation as a tool to treat neural dysfunction in misophonia. We describe how neurostimulation research has led to novel interventions in psychiatric disorders, targeting regions that may also be relevant to misophonia. The paper is concluded by presenting several options for how neurostimulation interventions for misophonia could be crafted.
Holocene evolution of the shelf mud deposits in the north-western South China Sea

Marine mud deposits contain rich information on past interactions between riverine sediment fluxes and marine processes. Massive mud deposits attached to a major river from South China, the Pearl River, are distributed on the north-western shelf of the South China Sea. This study examines the evolution history using cores penetrating through Holocene strata and deciphers its response to the river system, sea-level change, monsoon variations, human activities, etc. Geochemical and sedimentological data constrained by robust radiocarbon data show the difference in the evolution of mud deposits in shallow waters and on the middle shelf. Muddy wedges in shallow waters along the coast have formed since 7 ka BP, when modern current systems were established during the middle Holocene sea-level highstand. However, wide-spread muddy deposits in the middle shelf initiated after 3 ka BP which are associated with enhanced sediment fluxes and strengthened winter monsoon. Human activities on recent millennia have play a significant role in influencing the mud deposition on the north-west shelf of the South China Sea, as evidenced by the enrichment of heavy metals in marine sediments.
Impaired fasting glucose, oxidative distress, and cognitive impairment. Is this the starting point on DBT cognitive decline?

Different studies performed in human patients, animal models, and in vitro cell cultures, show a correlation between type 2 diabetes (DBT2) and certain neurodegenerative pathologies. Also, it was proposed that increased inflammation and- or oxidative distress are a possible cause of DBT2-accelerated cognitive decline. The onset of DBT2 is characterized by an increase in blood glucose levels due to (an inability of the body’s cells to use insulin properly) called impaired fasting glucose (IFG). Genetic and/or molecular causes of IFG have not yet been established, but metabolic syndrome, obesity, unbalanced diets, and sedentary lifestyle would be responsible, at least in part, for the multiplication in the number of this disease. It has been proposed that hyperglycemia itself causes an imbalance in the redox state and could compromise blood-brain barrier (BBB) causing neurodegeneration. For this reason, we propose, in this review, to evaluate the available data about redox state and neurocognitive studies during the IFG period.
Evaluation of myocardial work in patients with hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy based on non-invasive pressure-strain loops

Background The capacity to distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on morphological features obtained by conventional echocardiography is limited. We investigated the global myocardial work of the left ventricle in two types of hypertrophies using the non-invasive myocardial work index (NMWI). Methods Conventional echocardiography was performed on 107 subjects with preserved left ventricular ejection fraction (LVEF ≥ 50%), who comprised patients with HCM (n = 40), H-LVH (n = 35), and healthy people with normal blood pressure and left ventricular structure (n = 32). Except for the conventional echocardiographic parameters, the left ventricular myocardial work parameters based on pressure-strain loops, including global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were evaluated in three groups. Multivariate discriminant analysis and receiver operating characteristic (ROC) curve were used to evaluate the incremental value of NMWI for distinguishing HCM from H-LVH. Results Compared to the control group, GWI and GCW were significantly lower in HCM patients (P < 0.05), whereas GWI was significantly higher in H-LVH patients. GWW was higher and GWE was significantly decreased in both HCM and H-LVH patients than in the control group (P < 0.05). Multivariate discriminant analysis and ROC curve revealed that the inter-ventricular septum thickness (IVST)/left ventricular posterior wall thickness (LVPWT) and GCW were each able to distinguish HCM from H-LVH. The combination of IVST/LVPWT and GCW discriminated HCM and H-LVH with a higher predictive accuracy of 94.7%. Conclusion NMWI may provide additional information in evaluating the myocardial function in patients with HCM and H-LVH. Myocardial work combined with conventional echocardiography could improve the clinical diagnostic accuracy of distinguishing HCM and H-LVH.
Case Report: Durable partial response to icotinib plus crizotinib in a lung adenocarcinoma patient with double uncommon EGFR G719D/L861Q mutations and an acquired novel CUX1-MET fusion

Non-small cell lung cancer (NSCLC) patients harboring MET exon 14 skipping or high MET amplification display a high rate of response to MET inhibitors. However, MET fusions in NSCLC have rarely been revealed. In this report, a 63-year-old woman with lung adenocarcinoma (LADC), harboring EGFR exon 18 G719D and exon 21 L861Q mutations, received first-generation, EGFR-tyrosine kinase inhibitor (TKI) icotinib therapy. Next generation sequencing (NGS) results only displayed an EGFR T790M point mutation following icotinib resistance. Thus, the patient was treated with osimertinib and achieved a stable disease (SD). However, disease progressed after 15 months and a novel MET fusion (CUX1 exon14-MET exon15) in addition to EGFR G719D/L861Q mutations were simultaneously detected in a tissue biopsy sample. After more than nine months, the patient subsequently achieved a PR with the combination of icotinib and crizotinib. To our knowledge, this is the first case of LADC patient displaying the presence of EGFR double uncommon mutations and an acquired novel CUX1-MET fusion that has benefited from icotinib plus crizotinib treatment. Following nine months of PR with icotinib plus crizotinib, the patient, until the time of publication, is exhibiting stable disease. The results suggest that the CUX1-MET fusion may be sensitive to crizotinib, although previous reports indicated that some MET fusion cases did not respond to crizotinib. Given this disparity, distinguishing MET fusion partners when crizotinib is used in LADC treatment is also very important.
Case report: Zanubrutinib-induced dermatological toxicities: A single-center experience and review

Zanubrutinib, a next-generation non-covalent Bruton’s tyrosine kinase (BTK) inhibitor, shows great efficacy in the treatment of B cell malignancies. Some patients may experience a series of side effects after the treatment of zanubrutinib. Grade 4 dermatological toxicities are rare, which present as severe rash and skin infection. Herein, we retrospectively reported the grade 4 dermatological toxicities of zanubrutinib in three consecutive patients. They were treated with zanubrutinib 160 mg twice daily orally. One patient was diagnosed with Primary Breast Diffuse Large B-cell Lymphoma(PB-DLBCL) and two patients were diagnosed with Chronic Lymphocytic Leukemia(CLL). Within one month after zanubrutinib treatment, all three patients developed grade 4 dermatological toxicities, including bruising, maculopapular rash, petechiae, ecchymosis, hemorrhagic blister, acne-Like rash, papulopustular rash, and skin infections. Zanubrutinib was discontinued in two patients due to unacceptable dermatological toxicities. Safety data from pre-licensing clinical trials showed that zanubrutinib-related side effects were frequent but well tolerated. To date, no severe dermatological toxicities were reported. The majority of patients can be relieved with symptomatic treatment, but a very small percentage of patients may face discontinuation of the drug.
School’s outdoor area as an educational and health-promoting resource for young teenagers

Regular physical activity (PA) is positive for the health of young people, but previous research has indicated that the proportion of the population attaining recommended levels of activity decreases with age. Several studies indicate that the PA pupils get during school hours represents an important part of their total PA. The purpose of this study was to examine the relation between the size of the school’s total outdoor area and pupils’ PA behavior during schooltime. ActiGraph GT1M accelerometers were used to measure objectively 12–13-year-old schoolchildren’s minutes of moderate-to-vigorous PA (MVPA) during schooltime. The pupils (n = 300, 155 girls and 145 boys) came from 18 primary schools in two medium-sized municipalities in mid-Norway. Linear regression analysis was used to examine the relationship between the schools’ total outdoor area and outdoor area per pupil in relation to pupils’ weekly minutes of MVPA during schooltime. The results show no association with either the schools’ total outdoor area or the outdoor area per pupil, and the pupils’ weekly minutes of MVPA during schooltime. This finding indicates that there are probably factors in the school environment affecting young people’s level of activity during schooltime, other than the size of the schools’ outdoor area.