Digital phenotyping correlates of mobile cognitive measures in schizophrenia: A multisite global mental health feasibility trial.

Traditional cognitive assessments in schizophrenia are time-consuming and necessitate specialized training, making routine evaluation challenging. To overcome these limitations, this study investigates the feasibility and advantages of utilizing smartphone-based assessments to capture both cognitive functioning and digital phenotyping data and compare these results to gold standard measures. We conducted a secondary analysis of data from 76 individuals with schizophrenia, who were recruited across three sites (one in Boston, two in India) was conducted. The open-source mindLAMP smartphone app captured digital phenotyping data and Trails A/B assessments of attention / memory for up to 12 months. The smartphone-cognitive tasks exhibited potential for normal distribution and these scores showed small but significant correlations with the results from the Brief Assessment of Cognition in Schizophrenia, especially the digital span and symbol coding tasks (r2 = 0.21). A small but significant correlation (r2 = 0.29) between smartphone-derived cognitive scores and health-related behaviors such as sleep duration patterns was observed. Smartphone-based cognitive assessments show promise as cross-cultural tools that can capture relevant data on momentary states among individuals with schizophrenia. Cognitive results related to sleep suggest functional applications to digital phenotyping data, and the potential of this multimodal data approach in research.

Investigational applications of transcranial magnetic stimulation (TMS) in Mood Disorders: Studies from a tertiary care center in India.

The investigational potential of TMS in psychiatry is largely underutilized. In the current article, we present the results of five studies with similar TMS protocols that looked at the investigative applications of TMS via measuring cortical reactivity as potential biomarkers in mood disorders. The first two studies, evaluate potential of TMS parameters and Motor neuron system (MNS) as state or trait markers of BD. Third and fourth studies evaluate these as endophenotypic markers of BD. The fifth study which is an RCT evaluating add-on yoga in UD, evaluates if markers of CI can index the therapeutic response of yoga. In study one MT1 was significantly greater in the SM (symptomatic-mania) group compared to HC (healthy-control) (P=0.032). The cortical inhibition measures SICI was reduced in SM(P=0.021) and BD (remitted Bipolar) (P=0.023) groups compared to HC. LICI was increased in the SM(0.021) and BD(P=0.06) groups compared to HC. In study two, a significant group x time interaction effect was observed indicating higher putative MNS-activity mediation in patients compared to HC on SlCl(P=0.024), LlCl(P=0.033). There were no significant group differences noted in the endophenotype studies. The fifth study showed a significant time X group interaction for CSP, favoring improvement in YG (yoga-group) (p<0.01).No significant change was observed for LICI(p=0.2), SICI(p=0.5). Limitations of these studies notwithstanding, we conclude that cortical reactivity measured using TMS is a potential biomarker across the course of mood disorders, starting from state and trait markers to understanding the therapeutic mechanism of a particular treatment modality in these disorders.

Synthesis, characterization, DFT studies and evaluation of the potential anti-tumour activity of nicotinic hydrazide based Schiff base using in vitro and molecular docking techniques.

Breast cancer, one of the most serious issues worldwide, has been raising day by day. It has now become a necessary to develop a suitable drug to combat this terrible illness. Schiff bases are increasingly being used as powerful medications for a number of illnesses. BNH has now synthesized from Benzil and Nicotinic hydrazide and characterized experimentally by FT-IR, UV, 1H NMR,13CNMR and Mass analysis. DFT calculations were done using Gaussian 16 W with B3LYP/6-311 + G (d,p) and geometry of the compound is optimized. Frontier Molecular orbit (FMO), Mullikan atomic charges and Molecular Electrostatic Potential (MEP) were studied. Invitro antimicrobial studies were done using various bacteria and fungi. The synthesized compound is appropriate against bacterial and fungal actions. Invitro study were done using MCF-7 cell lines to analyze the anticancer property of the ligand. The outcome suggests that BNH may be employed in the future as a novel anticancer medication.

Oculomotor Abnormalities and Aberrant Neuro-Developmental Markers: Composite Endophenotype for Bipolar I Disorder: Anomalies Oculomotrices et Marqueurs Neuro-Développementaux Aberrants : Endophénotype Composite du Trouble Bipolaire I.

BACKGROUND: Neurological soft signs (NSSs), minor physical anomalies (MPAs), and oculomotor abnormalities were plausible biomarkers in bipolar disorder (BD). However, specific impairments in these markers in patients after the first episode mania (FEM), in comparison with first-degree relatives (high risk [HR]) of BD and healthy subjects (health control [HC]) are sparse. AIM OF THE STUDY: This study aimed at examining NSSs, MPAs, and oculomotor abnormalities in remitted adult subjects following FEM and HR subjects in comparison with matched healthy controls. Investigated when taken together, could serve as composite endophenotype for BD. METHODS: NSSs, MPAs, and oculomotor abnormalities were evaluated in FEM (n = 31), HR (n = 31), and HC (n = 30) subjects, matched for age (years) (p = 0.44) and sex (p = 0.70) using neurological evaluation scale, Waldrop's physical anomaly scale and eye tracking (SPEM) and antisaccades (AS) paradigms, respectively. RESULTS: Significant differences were found between groups on NSSs, MPAs, and oculomotor parameters. Abnormalities are higher in FEM subjects compared to HR and HC subjects. Using linear discriminant analysis, all 3 markers combined accurately classified 72% of the original 82 subjects (79·2% BD, 56·70% HR, and 82·1% HC subjects). CONCLUSIONS: AS and SPEM could enhance the utility of NSSs, and MPAs as markers for BD. The presence of these abnormalities in FEM suggests their role in understanding the etiopathogenesis of BD in patients who are in the early course of illness. These have the potential to be composite endophenotypes and have further utility in early identification in BD.

Eye movement abnormalities and Atypical Neurodevelopmental markers as Composite Measurable components in the pathway between disease manifestation and genetics in Bipolar I DisorderPlain Language SummaryWhy was the study done?Neurological soft signs, Minor physical anomalies, and eye-movement abnormalities are known disease makers of Bipolar disorder but their utility in being intermediate markers between the disease manifestation and genetics has not been studied before. Hence we took up this study with the above aim.What did the researchers do?We compared the above-mentioned biomarkers between the patients diagnosed with first-episode mania (considered as early bipolar), the high-risk population (people with a family history of bipolar), and healthy subjects (without any self or family history of any psychiatric illnesses). Each group had 30 participants. We wanted to see if these markers taken together could predict the groups or classify the subjects into the three groups accurately.What did the researchers find?We found that in all the biomarkers there was a significant group difference between the the three groups. The abnormalities showed a pattern wherein they are higher in the first episode mania group compared to at-risk, and higher in at-risk compared to healthy subjects. When all these markers were combined and linear discriminant analysis was run, we noted they accurately classified 72% of the original participants (79·2% first episode bipolar 56·70% High risk, and 82·1% Healthy Subjects).What do the findings mean?The above findings indicate that the eye-movement or oculomotor abnormalities enhance the utility of neurodevelopmental markers as biomarkers of bipolar disorder. The presence of these abnormalities fairly early in the disease also means that they have a role in the etiopathogenesis of bipolar disorder. All the markers taken together can be composite measurable components in the pathway between disease manifestation and genetics in Bipolar I Disorder, and thus help in early identification.

Identification of Potential Inhibitors Targeting GTPase-Kirsten RAt Sarcoma Virus (K-Ras) Driven Cancers via E-Pharmacophore-Based Virtual Screening and Drug Repurposing Approach.

BACKGROUND: Mutations in the K-Ras gene are among the most frequent genetic alterations in various cancers, and inhibiting RAS signaling has shown promising results in treating solid tumors. However, finding effective drugs that can bind to the RAS protein remains challenging. This drove us to explore new compounds that could inhibit tumor growth, particularly in cancers that harbor K-Ras mutations. METHODS: Our study used bioinformatic techniques such as E-pharmacophore virtual screening, molecular simulation, principal component analysis (PCA), extra precision (XP) docking, and ADMET analyses to identify potential inhibitors for K-Ras mutants G12C and G12D. RESULTS: In our study, we discovered that inhibitors such as afatinib, osimertinib, and hydroxychloroquine strongly inhibit the G12C mutant. Similarly, hydroxyzine, zuclopenthixol, fluphenazine, and doxapram were potent inhibitors for the G12D mutant. Notably, all six of these molecules exhibit a high binding affinity for the H95 cryptic groove present in the mutant structure. These molecules exhibited a unique affinity mechanism at the molecular level, which was further enhanced by hydrophobic interactions. Molecular simulations and PCA revealed the formation of stable complexes within switch regions I and II. This was particularly evident in three complexes: G12C-osimertinib, G12D-fluphenazine, and G12D-zuclopenthixol. Despite the dynamic nature of switches I and II in K-Ras, the interaction of inhibitors remained stable. According to QikProp results, the properties and descriptors of the selected molecules fell within an acceptable range compared to sotorasib. CONCLUSIONS: We have successfully identified potential inhibitors of the K-Ras protein, laying the groundwork for the development of targeted therapies for cancers driven by K-Ras mutations.

Neurocognitive Deficits in Recently Diagnosed Young Remitted Bipolar I Disorder and At-Risk Subjects: Potential Endophenotypes?

Background: Neurocognitive deficits have been reported consistently in euthymic bipolar disorder (BD) across studies. Endophenotype potential of such deficits have been reported in a few studies. However, data from the Indian subcontinent is sparse, and no studies had a sample (patients and high-risk group) aged 20-25 years, which is the actual risk period for developing BD. We studied cognitive deficits, as a potential endophenotype for BD, in recently diagnosed BD (FEM-first episode mania) in remission, young unaffected first-degree relatives (HR) of patients with BD, and healthy controls (HC). Methods: Cross-sectional study design using convenient sampling was employed. We recruited FEM (n = 25), HR (n = 25), and age-matched HC (n = 25) between 18 and 30 years. All HR subjects were <25 years of age, which is the period of vulnerability for BD. All the groups were screened using MINI Version 6. Neurocognitive assessments were done using the NIMHANS neuropsychology battery. The cognitive domains assessed were processing speed, attention, working memory, executive functions, and visual and verbal memory. Results: The three groups were comparable in age and sex (all P > 0.06). The mean (SD) age of the FEM subjects was 23.7 (3.47) years, and the mean duration of illness was 5.92 (2.94) months. Compared to the HC group, the FEM group performed poorly on multiple cognitive domains (all P < 0.05). Performance of the HR group was comparable to the FEM group, but they showed significantly poorer performance compared to HC on the verbal fluency test-controlled oral word association (COWA, F = 12.36, P = 0.001), and the visual learning and memory test-complex figure test-immediate recall (CFT-IR, F = 8.10 and p = 0.001). Conclusions: Cognition is impaired very early in the course of BD. Visual memory and executive function (verbal fluency) have endophenotypic potential. These findings are particularly important given that the HR group were still within the vulnerable period to develop BD. These findings imply a tremendous potential for early diagnosis and prevention by early interventions in BD.

Exploration of the performance of iron-based superhydrophilic meshes for oil-water separation.

This study investigates the oil-water separation capability of iron-based superhydrophilic meshes. It also intends to provide an optimistic view of their potential for industrial application. Oil-water separation performance of the 150 mesh, 300 mesh, and 400 mesh is primarily examined by analyzing the efficiency and speediness of separation as well as the limit of oil intrusion using petroleum based oils. The superhydrophilic meshes are further applied for oil-water separation of locomotive wash effluent. The superhydrophilic meshes showed good oil-water separation behavior. The 300 mesh is observed to have superior separation performance. It is also tested to have good reusability and resistance in harsh conditions. The separation effectiveness of 94.7%, reduced turbidity of 21.8 NTU, and chemical oxygen demand of around 70 ppm, along with reasonable flux and intrusion pressure values of 73.28 Lm-2min-1 and 0.848 kPa, respectively, are noticed for the separation study conducted for locomotive wash effluent using the designated superhydrophilic mesh. This study hence as well demonstrates a prospective future of superhydrophilic mesh for practical utility.

Multiple Complement Pathway-related Proteins Might Regulate Immunopathogenesis of Major Depressive Disorder.

Objective: Exacerbated inflammatory pathway has emerged as a predominant etiological construct of major depressive disorder (MDD). Innate immune molecules like complement proteins induce inflammatory responses and also regulate key neurobiological processes. However, there is a dearth of literature on the impact of critical complement proteins in MDD. Herein, plasma profiling of seven complement proteins was carried out to obtain a better insight into the role of the complement pathway in MDD. Methods: Plasma levels of C1q, C3, C3b/iC3b, C4, Factor B, Factor H, and properdin were assayed in 22 patients with MDD and 27 healthy controls by multiplex suspension assay. The patients with MDD were diagnosed as per DSM IV-TR. Hamilton Depression Rating Scale (HAM-D), Montgomery Depression Rating Scale and Clinical Global Improvement were used for clinical assessments of the patients. The plasma levels of these complement proteins were also correlated with various clinical scores and phenotypes of MDD. Results: The patients with MDD and healthy controls did not differ in terms of age and gender (p > 0.1). The patients with MDD had a mean duration of illness of around 3 years, with average number of depressive episodes being 6 and the mean HAM-D score was 19. Of the seven complement components, the plasma levels of C1q, Factor B, and Factor H (p ≤ 0.05) were significantly elevated in MDD patients compared to healthy controls. However, the plasma levels of these complement proteins were not found to correlate with the clinical profile of MDD patients. Conclusion: Both Factor B and Factor H are crucial in the induction and regulation of the alternative pathway of complement activation. The alternative pathway also plays a critical role in inflammation. These findings suggest an important role of the alternative complement pathway in immuno-inflammation in MDD.

Relapse prediction in schizophrenia with smartphone digital phenotyping during COVID-19: a prospective, three-site, two-country, longitudinal study.

Smartphone technology provides us with a more convenient and less intrusive method of detecting changes in behavior and symptoms that typically precede schizophrenia relapse. To take advantage of the aforementioned, this study examines the feasibility of predicting schizophrenia relapse by identifying statistically significant anomalies in patient data gathered through mindLAMP, an open-source smartphone app. Participants, recruited in Boston, MA in the United States, and Bangalore and Bhopal in India, were invited to use mindLAMP for up to a year. The passive data (geolocation, accelerometer, and screen state), active data (surveys), and data quality metrics collected by the app were then retroactively fed into a relapse prediction model that utilizes anomaly detection. Overall, anomalies were 2.12 times more frequent in the month preceding a relapse and 2.78 times more frequent in the month preceding and following a relapse compared to intervals without relapses. The anomaly detection model incorporating passive data proved a better predictor of relapse than a naive model utilizing only survey data. These results demonstrate that relapse prediction models utilizing patient data gathered by a smartphone app can warn the clinician and patient of a potential schizophrenia relapse.

Multiple Complement Pathway-related Proteins Might Regulate Immunopathogenesis of Major Depressive Disorder

Objective@#Exacerbated inflammatory pathway has emerged as a predominant etiological construct of major depressive disorder (MDD). Innate immune molecules like complement proteins induce inflammatory responses and also regulate key neurobiological processes. However, there is a dearth of literature on the impact of critical complement proteins in MDD. Herein, plasma profiling of seven complement proteins was carried out to obtain a better insight into the role of the complement pathway in MDD. @*Methods@#Plasma levels of C1q, C3, C3b/iC3b, C4, Factor B, Factor H, and properdin were assayed in 22 patients with MDD and 27 healthy controls by multiplex suspension assay. The patients with MDD were diagnosed as per DSM IV-TR. Hamilton Depression Rating Scale (HAM-D), Montgomery Depression Rating Scale and Clinical Global Improvement were used for clinical assessments of the patients. The plasma levels of these complement proteins were also correlated with various clinical scores and phenotypes of MDD. @*Results@#The patients with MDD and healthy controls did not differ in terms of age and gender (p ＞ 0.1). The patients with MDD had a mean duration of illness of around 3 years, with average number of depressive episodes being 6 and the mean HAM-D score was 19. Of the seven complement components, the plasma levels of C1q, Factor B, and Factor H (p ≤ 0.05) were significantly elevated in MDD patients compared to healthy controls. However, the plasma levels of these complement proteins were not found to correlate with the clinical profile of MDD patients. @*Conclusion@#Both Factor B and Factor H are crucial in the induction and regulation of the alternative pathway of complement activation. The alternative pathway also plays a critical role in inflammation. These findings suggest an important role of the alternative complement pathway in immuno-inflammation in MDD.

Long-term Add-on Yoga Therapy Modulates Oxidative Stress Pathway and Offers Clinical Benefits in Major Depressive Disorder: A Randomized Controlled Trial.

Background: Yoga therapy (YT) as an adjunct treatment has reportedly been demonstrated to offer clinical benefits in major depressive disorder (MDD). Although a few biological pathways are suggested to mediate the effects of yoga, the precise mechanistic basis remains unknown. Oxidative stress pathway activation has consistently been linked to the pathobiology of MDD. Whether YT has a modulatory effect on the oxidative stress pathway in MDD is not adequately understood. Aim and Objectives: In this study, we examined the impact of a course (3 months) of yoga as an add on therapy on the markers of the oxidative stress pathway in MDD patients. Methods: Thirty-three MDD patients were randomized to the YT (n = 16) and waitlist control (WC) (n = 17) groups. Colorimetric estimation of the plasma malondialdehyde (MDA) and total antioxidant (AO) levels was performed in all the study participants using commercially available kits at the baseline and after 3 months. Results: A significant reduction of plasma MDA levels was observed in MDD patients of YT group (P = 0.05) after 3 months of YT. Notably, the plasma MDA levels also decreased in MDD patients of WC group (P = 0.015) after the trial period. In addition, levels of total AO showed a trend toward significance only in MDD patients after 3 months of YT (P = 0.07). Conclusion: The current study suggests that the benefits of YT might be mediated through its modulatory role on the oxidative stress pathway in MDD.

Smartphone digital phenotyping, surveys, and cognitive assessments for global mental health: Initial data and clinical correlations from an international first episode psychosis study.

Objective: To examine feasibility and acceptability of smartphone mental health app use for symptom, cognitive, and digital phenotyping monitoring among people with schizophrenia in India and the United States. Methods: Participants in Boston, USA and Bhopal and Bangalore, India used a smartphone app to monitor symptoms, play cognitive games, access relaxation and psychoeducation resources and for one month, with an initial clinical and cognitive assessment and a one-month follow-up clinical assessment. Engagement with the app was compared between study sites, by clinical symptom severity and by cognitive functioning. Digital phenotyping data collection was also compared between three sites. Results: By Kruskal-Wallis rank-sum test, we found no difference between app activities completed or digital phenotyping data collected across the three study sites. App use also did not correlate to clinical or cognitive assessment scores. When using the app for symptom monitoring, preliminary findings suggest app-based assessment correlate with standard cognitive and clinical assessments. Conclusions: Smartphone app for symptom monitoring and digital phenotyping for individuals with schizophrenia appears feasible and acceptable in a global context. Clinical utility of this app for real-time assessments is promising, but further research is necessary to determine the long-term efficacy and generalizability for serious mental illness.

Platelet augmentation activity of mature leaf juice of Sri Lankan wild type cultivar of Carica papaya L: Insights into potential cellular mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Carica papaya L., a common fruit crop of the family Caricaceae and its leaf juice/extract is a traditionally commended preparation against dengue and other thrombocytopenic diseases by many Asian countries. AIM OF THE STUDY: The present study posits the potential cellular mechanisms of platelet augmentation activity of mature leaf juice of Sri Lankan wild-type Carica papaya. MATERIALS AND METHODS: C. papaya leaf juice prepared from different cultivar types, maturity of the leaf, agro-climatic region, and preparation methods were orally administered to hydroxyurea-induced thrombocytopenic rats at 0.72 ml/100 g BW dosage to investigate the most potent platelet increasing preparation. The papaya juice doses; low dose (LD-0.18 ml/100 g BW), human equivalent dose (HED-0.36 ml/100 g BW), and high dose (HD-0.72 ml/100 g BW), were administered to thrombocytopenic rats (N = 6/group) daily for three consecutive days and post-treatment plasma levels of interleukin 6 (IL-6), thrombopoietin (TPO), and platelet-activating factor (PAF) were quantified using specific rat ELISA kits. The mature leaf juice of C. papaya induced IL-6 secretion from bone marrow cell (BMC) cultures was quantified using ELISA. The ability of papaya juice to protect the platelet membrane, from the damage caused by the lytic agent was analyzed in vitro using the lactate dehydrogenase (LDH) assay. The effect of the mature leaf juice of C. papaya on secondary hemostasis was investigated using blood coagulation and clot hydrolyzing activity. RESULTS: The comparative analysis revealed that the platelet increasing activity of C. papaya leaf did not significantly differ among different types of cultivar, maturity of the leaf, agro-climatic regions and preparation methods (p > 0.05). Both TPO and PAF levels in thrombocytopenic rats diminished when treated with all three doses of the mature leaf juice of C. papaya (p < 0.05), yet IL-6 plasma level was unaltered (p > 0.05). Nevertheless, ex vivo treatment of the mature leaf juice of C. papaya had significantly enhanced IL-6 levels of rat BMC cultures (p < 0.05). Pre-treatment of platelets with the mature leaf juice of C. papaya at different concentrations significantly inhibited LDH leakage from platelets and may have reduced the membrane damage caused by the lytic agent (p < 0.05). Treatment of mature leaf juice of C. papaya also significantly reduced blood clotting time through the extrinsic pathway of the blood coagulation cascade (p < 0.05). Further, prolonged incubation of the plasma clot with different concentrations of the papaya leaf juice revealed dose-dependent hydrolysis of the blood clot, indicating fibrinolysis activity. CONCLUSIONS: The current study exceeded the traditional medicinal claims, and scientifically affirmed the platelet augmentation activity of mature leaf juice of C. papaya. The mechanistic rationale tested herein explicated that the platelet augmentation activity of the papaya leaf juice can be partially attributed to the stimulation of bone marrow megakaryocytes via modulating thrombopoietic cytokines TPO and IL-6, and by inhibiting the secretion of PAF, while reducing the peripheral platelet destruction by stabilizing the platelet membrane. Further, mature leaf juice of C. papaya imparted both pro-coagulation and fibrinolysis activity of secondary hemostasis endorsing its potential against thrombocytopenia.

Heterostructured γ-Fe2O3/FeTiO3 magnetic nanocomposite: An efficient visible-light-driven photocatalyst for the degradation of organic dye.

The catalyst recovery is the major concern in commercialization of photocatalysts for the industrial effluent treatment process. To overcome this major issue, Fe2O3 based magnetic photocatalytic heterostructure É£-Fe2O3/FeTiO3 nanocomposite was synthesized by hydrothermal method. Fe2O3 is the cheapest visible active magnetic photocatalytic material, but it has the limitation of fast e-/h + recombination. Titanium (Ti) was loaded on γ-Fe2O3 to overcome this issue. The loaded Ti has grown as FeTiO3 on the surface of É£-Fe2O3 nanocrystals and emerged as heterostructure É£- Fe2O3/FeTiO3 nanocomposites, which was confirmed by XRD and TEM results. The loading concentration of Ti on γ-Fe2O3 was optimized to achieve the maximum photocatalytic efficiency without compromising the magnetic property of γ-Fe2O3 to facilitate the magnetic separation. DRS-UV spectra revealed the strong visible light response of γ- Fe2O3/FeTiO3 nanocomposite. The photocatalytic efficiencies of the synthesized materials were evaluated using methylene blue (MB) as a model pollutant under sunlight. The built-in electric field between p-n junction between FeTiO3 and Fe2O3 and type II charge transfer mechanism extended the lifetime of the charge carriers at the heterojunction of γ- Fe2O3/FeTiO3, which was confirmed by PL spectra. The vibrating sample magnetometer (VSM) study revealed the decreasing magnetization, coercivity (Hc), and retentivity (Mr) of γ-Fe2O3 with increasing concentration of Ti. 92% of the used-up 20 wt% Ti loaded γ-Fe2O3/FeTiO3 magnetic nanocomposite was recovered from the treated wastewater using an electromagnet. Both magnetic properties and efficiency of the nanocomposite increased up to 20 wt% of Ti loading, beyond that decreased due to the increasing composition of antiferromagnetic FeTiO3 and the increasing number of defect sites as recombination centers. Hence, 20 wt% loading of Ti was concluded as the optimum to enhance the efficiency and to retain the magnetic properties. This work aims the commercialization of magnetic photocatalytic materials for the industrial effluent treatment.

Integrative ontology and pathway-based approach identifies distinct molecular signatures in transcriptomes of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) remains a serious concern globally due to many factors that including late diagnosis, lack of an ideal biomarker for diagnosis and prognosis, and high rate of mortality. In this study, we aimed to identify the essential dysregulated genes and molecular signatures associated with the progression and development of ESCC. The dataset with 15 ESCCs and the 15 adjacent normal tissue samples from the surrounding histopathologically tumor-free mucosa was selected. We applied bioinformatics pipelines including various topological parameters from MCODE, CytoNCA, and cytoHubba to prioritize the most significantly associated DEGs with ESCC. We performed functional enrichment annotation for the identified DEGs using DAVID and MetaCore™ GeneGo platforms. Furthermore, we validated the essential core genes in TCGA and GTEx datasets between the normal mucosa and ESCC for their expression levels. These DEGs were primarily enriched in positive regulation of transferase activity, negative regulation of organelle organization, cell cycle mitosis/S-phase transition, spindle organization/assembly, development, and regulation of angiogenesis. Subsequently, the DEGs were associated with the pathways such as oocyte meiosis, cell cycle, and DNA replication. Our study identified the eight-core genes (AURKA, AURKB, MCM2, CDC20, TPX2, PLK1, FOXM1, and MCM7) that are highly expressed among the ESCC, and TCGA dataset. The multigene comparison and principal component analysis resulted in elevated signals for the AURKA, MCM2, CDC20, TPX2, PLK1, and FOXM1. Overall, our study reported GO profiles and molecular signatures that might help researchers to grasp the pathological mechanisms underlying ESCC development and eventually provide novel therapeutic and diagnostic strategies.

Emotion Processing Deficit in Euthymic Bipolar Disorder: A Potential Endophenotype.

Background: Emotion processing deficits have been described in patients with bipolar disorder (BD) and are considered one of the core cognitive abnormalities in BD with endophenotype potential. However, the literature on specific impairments in emotion processing cognitive strategies (directive/cortical/higher versus intuitive/limbic/lower) in euthymic adult BD patients and healthy first-degree relatives/high-risk (HR) subjects in comparison with healthy controls (HCs) is sparse. Methods: We examined facial emotion recognition deficits (FERD) in BD (N = 30), HR (N = 21), and HC (N = 30) matched for age (years), years of education, and sex using computer-administered face emotions-Matching And Labeling Task (eMALT). Results: The three groups were significantly different based on labeling accuracy scores for fear and anger (FA) (P < 0.001) and sad and disgust (SD) (P < 0.001). On post-hoc analysis, HR subjects exhibited a significant deficit in the labeling accuracy of FA facial emotions (P < 0.001) compared to HC. The BD group was found to have significant differences in all FA (P = 0.004) and SD (P = 0.003) emotion matching as well as FA (P = 0.001) and SD (P < 0.001) emotion labeling accuracy scores. Conclusions: BD in remission exhibits FERD in general, whereas specific labeling deficits of fear and anger emotions, indicating impaired directive higher order aspect of emotion processing, were demonstrated in HR subjects. This appears to be a potential endophenotype. These deficits could underlie the pathogenesis in BD, with possible frontolimbic circuitry impairment. They may have potential implications in functional recovery and prognosis of BD.

Mutations in G6PC2 gene with increased risk for development of type 2 diabetes: Understanding via computational approach.

An increase in the fast blood glucose (FBG) levels has been linked to an increased risk of developing a chronic condition, type 2 diabetes (T2D). The mutation in the G6PC2 gene was identified to have a lead role in the modulation of FBG levels. The abnormal regulation of this enzyme influences glucose-stimulated insulin secretion (GSIS), which controls the insulin levels corresponding to the system's glucose level. This study focuses on the mutations at the G6PC2 gene, which cause the variation from normal expression levels and increase the risk of T2D. We examined the non-synonymous single nucleotide polymorphisms (nsSNPs) present in the G6PC2 and subjected them to pathogenicity, stability, residue conservation, and membrane simulation. The individual representation of surrounding amino acids in the mutant (I63T) model showed the loss of hydrophobic interactions compared to the native G6PC2. In addition, the trajectory results from the membrane simulation exhibited reduced stability, and the least compactness was identified for the I63T mutant model. Our study shed light on the structural and conformational changes at the transmembrane region due to the I63T mutation in G6PC2. Additionally, the Gibbs free energy landscape analysis against the two principal components showed structural differences and decreased the conformational stability of the I63T mutant model compared to the native. Like those presented in this study, dynamical simulations may indeed be crucial to comprehending the structural insights of G6PC2 mutations in cardiovascular-associated mortality and T2D.

Plant based radioprotectors as an adjunct to radiotherapy: advantages and limitations.

Radioprotectors are agents that have the potential to act against radiation damage to cells. These are equally invaluable in radiation protection, both in intentional and unintentional radiation exposure. It is however, complex to use a universal radioprotector that could be beneficial in diverse contexts such as in radiotherapy, nuclear accidents, and space travel, as each of these circumstances have unique requirements. In a clinical setting such as in radiotherapy, a radioprotector is used to increase the efficacy of cancer treatment. The protective agent must act against radiation damage selectively in normal healthy cells while enhancing the radiation damage imparted on cancer cells. In the context of radiotherapy, plant-based compounds offer a more reliable solution over synthetic ones as the former are less expensive, less toxic, possess synergistic phytochemical activity, and are environmentally friendly. Phytochemicals with both radioprotective and anticancer properties may enhance the treatment efficacy by two-fold. Hence, plant based radioprotective agents offer a promising field to progress forward, and to expand the boundaries of radiation protection. This review is an account on radioprotective properties of phytochemicals and complications encountered in the development of the ideal radioprotector to be used as an adjunct in radiotherapy.