Miracle-dz/UniFAR-FTUs huggingface dataset:
Quality of Life in Chinese Patients With Large Congenital Melanocytic Nevi

Background Large congenital melanocytic nevus (LCMN) is a rare skin disease that deeply affects an individual's appearance, may influence patients' self-evaluation and social relationships, and further affects their quality of life (QoL). The Skindex-29 and 36-Item Short Form Survey (SF-36) are valid instruments used to evaluate QoL specifically. It is necessary to assess the QoL of patients with LCMN and summarize potentially impactful factors to help people understand LCMN patients and assist doctors in offering professional advice. Methods Twenty-five patients were recruited from Shanghai Ninth People's Hospital from July 1st, 2019, to March 31st, 2021. Both males and females were included, and the age groups were divided into infants (0–6 y), children (7–12 y), teenagers (13–17 y) and youths (18–45 y). The Skindex-29 and SF-36 were applied as questionnaires for the assessment of QoL. Clinical information was acquired by physical examination. Results QoL in patients with LCMN was diminished, especially in the emotional aspect. However, different genders, ages and distribution patterns of LCMN did not significantly influence QoL, but the patterns of “Bonce” and “Body” affected QoL the most and the severest. The results of Skindex-29 and SF-36 were consistent in that LCMN mainly reduced QoL from an emotional perspective. Conclusions This research shows that LCMN has the strongest impact on patients' emotional wellbeing but weakly influences the whole fettle of QoL. The gender, age and distribution patterns of lesions all have no direct effect on QoL, although a larger proportion of LCMNs probably insinuates worse QoL. Even though patients with LCMN show better QoL than those with other visible skin conditions, their general mental health still requires ample attention from surroundings and professional doctors.
Prognostic Value of Sarcopenia in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP: A Systematic Review and Meta-Analysis

Objective Several studies have reported conflicting results regarding the association between sarcopenia and outcomes in patients with diffuse large B-cell lymphoma (DLBCL). This meta-analysis aimed to evaluate the prognostic value of sarcopenia in patients with DLBCL. Methods PubMed, Embase, and Cochrane Library databases were searched to identify trials exploring the association between sarcopenia and prognosis in patients with DLBCL treated with chemotherapy. A meta-analysis of overall survival (OS), progression-free survival (PFS), treatment completion, and rate of complete response (CR) was performed. Results Twelve studies that involved 2,324 patients with DLBCL were included. Sarcopenia was associated with poor OS and PFS in patients with DLBCL, even after adjusting for confounders. Patients with sarcopenia had lower rates of CR and treatment completion than patients without sarcopenia. Conclusions Sarcopenia is a negative predictor of prognosis in patients with DLBCL. Additional and prospective studies investigating the diagnostic criteria for sarcopenia are warranted.
Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators

Both metabotropic (CBRs) and ionotropic cannabinoid receptors (ICRs) have implications in a range of neurological disorders. The metabotropic canonical CBRs CB1 and CB2 are highly implicated in these pathological events. However, selective targeting at CB2 versus CB1 offers optimized pharmacology due to the absence of psychoactive outcomes. The ICR transient receptor potential vanilloid type 1 (TRPV1) has also been reported to play a role in CNS disorders. Thus, activation of both targets, CB2 and TRPV1, offers a promising polypharmacological strategy for the treatment of neurological events including analgesia and neuroprotection. This brief research report aims to identify chemotypes with a potential dual CB2/TRPV1 profile. For this purpose, we have rationalized key structural features for activation and performed virtual screening at both targets using curated chemical libraries.
Assessment of Extramammary Paget Disease by Two-Photon Microscopy

Two-photon microscopy techniques are non-linear optical imaging methods which are gaining momentum in the investigation of fixed tissue sections, fresh tissue or even for in vivo experiments. Two-photon excited fluorescence and second harmonic generation are two non-linear optical contrast mechanisms which can be simultaneously used for offering complementary information on the tissue architecture. While the former can originate from endogenous autofluorescence sources (e.g., NADH, FAD, elastin, keratin, lipofuscins, or melanin), or exogenous eosin, the latter is generated in fibrillar structures within living organisms (e.g., collagen and myosin). Here we test the ability of both these contrast mechanisms to highlight features of the extramammary Paget disease on fixed tissue sections prepared for standard histological examination using immunohistochemical markers and hematoxylin and eosin staining. We also demonstrate the label-free abilities of both imaging techniques to highlight histological features on unstained fixed tissue sections. The study demonstrated that two-photon microscopy can detect specific cellular features of the extramammary Paget disease in good correlation with histopathological results.
A Pan-Cancer In Silico Analysis of the COVID-19 Internalization Protease: Transmembrane Proteaseserine-2

The new coronavirus (2019-nCoV) is an emerging pathogen that can cause severe respiratory infections in humans. It is worth noting that many of the affected COVID-19 patients have malignant tumors. In addition, cancer has been identified as a personal risk factor for COVID-19. Transmembrane proteaseserine-2 (TMPRSS2) is a crucial host protease that mediates S protein activation and initially promotes virus entry into host cells. Moreover, it is abnormally expressed in a variety of tumors. However, the systematic analysis of TMPRSS2 aberrations in human cancer remains to be elucidated. Here, we analyzed the genetic changes, RNA expression, and DNA methylation of TMPRSS2 in more than 30 tumors. It has been reported that TMPRSS2 is overexpressed in tumors such as prostate adenocarcinoma (PRAD), and in contrast, the expression of TMPRSS2 is decreased in tumors such as head and neck cancer (HNSC). In addition, TMPRSS2 low DNA methylation was also found in most of these TMPRSS2 high-expressing tumors in this study. Clinical studies have found that there is a significant correlation between the expression of TMPRSS2 and the prognosis of some tumor patients. The expression of TMPRSS2 is also related to the infiltration of cancer-related fibroblasts, and the potential pathways and functional mechanisms were analyzed through KEGG/GO enrichment. In the end, our study planned the genetic and epigenetic variation of TMPRSS2 in human malignant tumors for the first time and provided a relatively comprehensive understanding of the carcinogenic effects of TMPRSS2.
Development of Protocols for Regeneration and Transformation of Apomitic and Sexual Forms of Dallisgrass (Paspalum dilatatum Poir.)

Paspalum dilatatum (common name dallisgrass), a productive C4 grass native to South America, is an important pasture grass found throughout the temperate warm regions of the world. It is characterized by its tolerance to frost and water stress and a higher forage quality than other C4 forage grasses. P. dilatatum includes tetraploid (2n = 40), sexual, and pentaploid (2n = 50) apomictic forms, but is predominantly cultivated in an apomictic monoculture, which implies a high risk that biotic and abiotic stresses could seriously affect the grass productivity. The obtention of reproducible and efficient protocols of regeneration and transformation are valuable tools to obtain genetic modified grasses with improved agronomics traits. In this review, we present the current regeneration and transformation methods of both apomictic and sexual cultivars of P. dilatatum, discuss their strengths and limitations, and focus on the perspectives of genetic modification for producing new generation of forages. The advances in this area of research lead us to consider Paspalum dilatatum as a model species for the molecular improvement of C4 perennial forage species.
Congenital Adrenal Hyperplasia and Ehlers-Danlos Syndrome

Congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency is an autosomal recessive disorder. The 21-hydroxylase enzyme P450c21 is encoded by the CYP21A2 gene located on chromosome 6p21.33 within the HLA major histocompatibility complex. This locus also contains the CYP21A1P, a non-functional pseudogene, that is highly homologous to the CYP21A2 gene. Other duplicated genes are C4A and C4B, that encode two isoforms of complement factor C4, the RP1 gene that encodes a serine/threonine protein kinase, and the TNXB gene that, encodes the extracellular matrix glycoprotein tenascin-X (TNX). TNX plays a role in collagen deposition by dermal fibroblasts and is expressed in the dermis of the skin and the connective tissue of the heart and skeletal muscle. During meiosis, misalignment may occur producing large gene deletions or gene conversion events resulting in chimeric genes. Chimeric recombination may occur between TNXB and TNXA. Three TNXA/TNXB chimeras have been described that differ in the junction site (CH1 to CH3) and result in a contiguous CYP21A2 and TNXB gene deletion, causing CAH-X syndrome. TNXB deficiency is associated with Ehlers Danlos syndrome (EDS). EDS comprises a clinically and genetically heterogeneous group of connective tissue disorders. As molecular analysis of the TNXB gene is challenging, the TNX-deficient type EDS is probably underdiagnosed. In this minireview, we will address the different strategies of molecular analysis of the TNXB-gene, as well as copy number variations and genetic status of TNXB in different cohorts. Furthermore, clinical features of EDS and clinical recommendations for long-term follow-up are discussed.
Green Logistics and Health in OBRI Economies: Does Social Marketing Matter?

In this study, our primary focus is to capture the impact of green logistics and social marketing on health outcomes in One Belt Road Initiative (OBRI) countries over the time period 2007–2019. Two estimation techniques, i.e., 2SLS and GMM, are employed to get the estimates of our variables. Findings of the 2SLS model confirmed the negative impact of green logistics on infant mortality in OBRI, European, MENA, and Asian countries. On the other side, the relationship between green logistics and life expectancy is positive in all the regions in 2SLS models. The other estimation technique also supports these findings, GMM, which confirmed the negative impact of green logistics on infant mortality and the positive impact of green logistics on life expectancy OBRI, European, MENA, and Asian economies. From these findings, we can conclude that green logistics helps to improve the health status of OBRI economies. Similarly, social marketing also improves the health status in OBRI and other regions in both models. Therefore, the governments and policymakers in respective economies should focus on the development of green infrastructure and logistics that, on one side, promote economic growth. However, on the other side, it helps improve environmental quality, which ultimately improves the OBRI economies' health status.
Sesquiterpene Lactones Attenuate Paclitaxel Resistance Via Inhibiting MALAT1/STAT3/ FUT4 Axis and P-Glycoprotein Transporters in Lung Cancer Cells

Paclitaxel resistance is a challenging factor in chemotherapy resulting in poor prognosis and cancer recurrence. Signal transducer and activator of transcription factor 3 (STAT3), a key transcription factor, performs a critical role in cancer development, cell survival and chemoresistance, while its inactivation overwhelms drug resistance in numerous cancer types including lung cancer. Additionally, the fucosyltransferase 4 (FUT4) is a crucial enzyme in post-translational modification of cell-surface proteins involved in various pathological conditions such as tumor multidrug resistance (MDR). The P-glycoprotein (P-GP) is the well-known ABC transporter member that imparts drug resistance in different cancer types, most notably paclitaxel resistance in lung cancer cells. LncRNA-MALAT1 exerts a functional role in the cancer development as well as the drug resistance and is linked with STAT3 activation and activity of FUT4. Moreover, STAT3-mediated induction of P-GP is well-documented. Natural compounds of Sesquiterpene Lactone (SL) family are well-known for their anticancer properties with particular emphasis over STAT3 inhibitory capabilities. In this study, we explored the positive correlation of MALAT1 with STAT3 and FUT4 activity in paclitaxel resistant A549 (A549/T) lung cancer cells. Additionally, we investigated the anticancer activity of two well-known members of SLs, alantolactone (ALT) and Brevilin A (Brv-A), in A549/T lung cancer cells. ALT and Brv-A induced apoptosis in A549/T cells. Furthermore, these two natural SLs suppressed MALAT1 expression, STAT3 activation, and FUT4 and P-GP expression which are the hallmarks for paclitaxel resistance in A549 lung cancer cells. The inhibition of MALAT1 enhanced the competence of these SLs members significantly, which accounted for the growth inhibition as well as anti-migratory and anti-invasive effects of ALT and Brv-A. These findings suggest SLs to be the promising agents for overcoming paclitaxel resistance in A549 lung cancer cells.
Rich-Club Organization Disturbances of the Individual Morphological Network in Subjective Cognitive Decline

Background Subjective cognitive decline (SCD) was considered to be the preclinical stage of Alzheimer’s disease (AD). However, less is known about the altered rich-club organizations of the morphological networks in individuals with SCD. Methods This study included 53 individuals with SCD and 54 well-matched healthy controls (HC) from the Alzheimer’s disease Neuroimaging Initiative (ADNI) database. Individual-level brain morphological networks were constructed by estimating the Jensen-Shannon distance-based similarity in the distribution of regional gray matter volume. Rich-club properties were then detected, followed by statistical comparison. Results The characteristic rich-club organization of morphological networks (normalized rich-club coefficients > 1) was observed for both the SCD and HC groups under a range of thresholds. The SCD group showed a reduced normalized rich-club coefficient compared with the HC group. The SCD group exhibited the decreased strength and degree of rich-club connections than the HC group (strength: HC = 79.93, SCD = 74.37, p = 0.028; degree: HC = 85.28, SCD = 79.34, p = 0.027). Interestingly, the SCD group showed an increased strength of local connections than the HC group (strength: HC = 1982.16, SCD = 2003.38, p = 0.036). Conclusion Rich-club organization disturbances of morphological networks in individuals with SCD reveal a distinct pattern between the rich-club and peripheral regions. This altered rich-club organization pattern provides novel insights into the underlying mechanism of SCD and could be used to investigate prevention strategies at the preclinical stage of AD.
Multi-Approach Analysis Reveals Pathways of Cold Tolerance Divergence in Camellia japonica

Understanding the molecular mechanism of the cold response is critical to improve horticultural plant cold tolerance. Here, we documented the physiological, transcriptome, proteome, and hormonal dynamics to cold stress in temperate genotype (Tg) and subtropical genotype (Sg) populations of Camellia japonica. Tg C. japonica suffered minimal osmotic and oxidative damage compared to Sg C. japonica under the same cold treatment. Transcriptional and translational differences increased under the cold treatment, indicating that Tg C. japonica was affected by the environment and displayed both conserved and divergent mechanisms. About 60% of the genes responding to cold had similar dynamics in the two populations, but 1,896 transcripts and 455 proteins differentially accumulated in response to the cold between Tg and Sg C. japonica. Co-expression analysis showed that the ribosomal protein and genes related to photosynthesis were upregulated in Tg C. japonica, and tryptophan, phenylpropanoid, and flavonoid metabolism were regulated differently between the two populations under cold stress. The divergence of these genes reflected a difference in cold responsiveness. In addition, the decrease in the abscisic acid (ABA)/gibberellic acid (GA) ratio regulated by biosynthetic signal transduction pathway enhanced cold resistance in Tg C. japonica, suggesting that hormones may regulate the difference in cold responsiveness. These results provide a new understanding of the molecular mechanism of cold stress and will improve cold tolerance in horticultural plants.
Structure-Activity Relationship (SAR) Model for Predicting Teratogenic Risk of Antiseizure Medications in Pregnancy by Using Support Vector Machine

Teratogenicity is one of the main concerns in clinical medications of pregnant women. Prescription of antiseizure medications (ASMs) in women with epilepsy during pregnancy may cause teratogenic effects on the fetus. Although large scale epilepsy pregnancy registries played an important role in evaluating the teratogenic risk of ASMs, for most ASMs, especially the newly approved ones, the potential teratogenic risk cannot be effectively assessed due to the lack of evidence. In this study, the analyses are performed on any medication, with a focus on ASMs. We curated a list containing the drugs with potential teratogenicity based on the US Food and Drug Administration (FDA)-approved drug labeling, and established a support vector machine (SVM) model for detecting drugs with high teratogenic risk. The model was validated by using the post-marketing surveillance data from US FDA Spontaneous Adverse Events Reporting System (FAERS) and applied to the prediction of potential teratogenic risk of ASMs. Our results showed that our proposed model outperformed the state-of-art approaches, including logistic regression (LR), random forest (RF) and extreme gradient boosting (XGBoost), when detecting the high teratogenic risk of drugs (MCC and recall rate were 0.312 and 0.851, respectively). Among 196 drugs with teratogenic potential reported by FAERS, 136 (69.4%) drugs were correctly predicted. For the eight commonly used ASMs, 4 of them were predicted as high teratogenic risk drugs, including topiramate, phenobarbital, valproate and phenytoin (predicted probabilities of teratogenic risk were 0.69, 0.60 0.59, and 0.56, respectively), which were consistent with the statement in FDA-approved drug labeling and the high reported prevalence of teratogenicity in epilepsy pregnancy registries. In addition, the structural alerts in ASMs that related to the genotoxic carcinogenicity and mutagenicity, idiosyncratic adverse reaction, potential electrophilic agents and endocrine disruption were identified and discussed. Our findings can be a good complementary for the teratogenic risk assessment in drug development and facilitate the determination of pharmacological therapies during pregnancy.
Disentangling the Relationship Between Chronic Kidney Disease and Cognitive Disorders

Chronic kidney disease (CKD) is a rapidly rising global health burden that affects nearly 40% of older adults. Epidemiologic data suggest that individuals at all stages of chronic kidney disease (CKD) have a higher risk of developing cognitive disorders and dementia, and thus represent a vulnerable population. It is currently unknown to what extent this risk may be attributable to a clustering of traditional risk factors such as hypertension and diabetes mellitus leading to a high prevalence of both symptomatic and subclinical ischaemic cerebrovascular lesions, or whether other potential mechanisms, including direct neuronal injury by uraemic toxins or dialysis-specific factors could also be involved. These knowledge gaps may lead to suboptimal prevention and treatment strategies being implemented in this group. In this review, we explore the mechanisms of susceptibility and risk in the relationship between CKD and cognitive disorders.
Unravelling the Biology of EhActo as the First Cofilin From Entamoeba histolytica

Actin-depolymerising factors (ADF) are a known family of proteins that regulate actin dynamics. Actin regulation is critical for primitive eukaryotes since it drives their key cellular processes. Entamoeba histolytica, a protist human pathogen harbours eleven proteins within this family, however, with no actin depolymerising protein reported to date. We present here the NMR model of EhActo, the first Cofilin from E. histolytica that severs actin filaments and also participates in cellular events like phagocytosis and pseudopod formation. The model typically represents the ADF-homology domain compared to other cofilins. Uniquely, EhActo lacks the critical Serine3 residue present in all known actophorins mediating its phospho-regulation. The second mode of regulation that cofilin’s are subjected to is via their interaction with 14-3-3 proteins through the phosphorylated Serine residue and a consensus binding motif. We found a unique interaction between EhActo and 14-3-3 without the presence of the consensus motif or the phosphorylated Serine. These interesting results present unexplored newer mechanisms functional in this pathogen to regulate actophorin. Through our structural and biochemical studies we have deciphered the mechanism of action of EhActo, implicating its role in amoebic biology.
A Neural Controller Model Considering the Vestibulospinal Tract in Human Postural Control

Humans are able to control their posture in their daily lives. It is important to understand how this is achieved in order to understand the mechanisms that lead to impaired postural control in various diseases. The descending tracts play an important role in controlling posture, particularly the reticulospinal and the vestibulospinal tracts (VST), and there is evidence that the latter is impaired in various diseases. However, the contribution of the VST to human postural control remains unclear, despite extensive research using neuroscientific methods. One reason for this is that the neuroscientific approach limits our understanding of the relationship between an array of sensory information and the muscle outputs. This limitation can be addressed by carrying out studies using computational models, where it is possible to make and validate hypotheses about postural control. However, previous computational models have not considered the VST. In this study, we present a neural controller model that mimics the VST, which was constructed on the basis of physiological data. The computational model is composed of a musculoskeletal model and a neural controller model. The musculoskeletal model had 18 degrees of freedom and 94 muscles, including those of the neck related to the function of the VST. We used an optimization method to adjust the control parameters for different conditions of muscle tone and with/without the VST. We examined the postural sway for each condition. The validity of the neural controller model was evaluated by comparing the modeled postural control with (1) experimental results in human subjects, and (2) the results of a previous study that used a computational model. It was found that the pattern of results was similar for both. This therefore validated the neural controller model, and we could present the neural controller model that mimics the VST.