Hit Score Research Articles

Potential Bioactive Compounds in Java Cardamom Fruit (Amomum compactum) As Candidate COX-2 Targeted Anti-Inflammatory Agents: In Silico Study

Inflammation is the defense mechanism of the body against harmful stimuli, such as pathogens, damaged cells, toxic compounds, or irradiation. Javanese cardamom (Amomum compactum) has pharmacological activity that has potential as an anti-inflammatory based on in vitro tests. This study aims to assess the physico-chemical characteristics of bioactive compounds contained in Java cardamom and molecular interactions on cyclooxygenase-2 (COX-2) as a target of inflammatory processes through a computational study. This study used molecular docking and pharmacophore modeling with structure-based drug design principles aimed at simulating how the binding interaction and fit score between bioactive compounds in Java cardamom toward COX-2. In addition, drug-likeness evaluation of the secondary metabolite compounds of Java cardamom was also carried out based on Lipinski rules-of-five and ADMET profiles. Our results demonstrated that trans-nerolidol B from Java cardamom showed the most potential activity against COX-2 based on molecular tethering in the form of Gibbs free energy of -7.11 kcal/mol and inhibition constant of 6.13 μM, as well as its interaction on amino acid residues at HIS75, VAL509, MET508, LEU370, VAL335, TRP373, and pharmacophore hit score of 35.99 in pharmacophore modeling with AUC score of 0.73 and 337 hits. Overall, this study is useful for the future development of Java cardamom and trans-nerolidol B as candidate natural substance-based COX-2 targeted anti-inflammatory agents.

The Efficacy of a Food Supplement in the Treatment of Tinnitus with Comorbid Headache: A Statistical and Machine Learning Analysis with a Literature Review

Introduction: Tinnitus, the perception of sound without an external auditory stimulus, affects approximately 10–15% of the population and is often associated with significant comorbidities such as headaches. These conditions can severely impact the quality of life. The aim of this study was to evaluate the efficacy of a food supplement in reducing the symptoms of both tinnitus and headache in patients experiencing these conditions concurrently. Methods: This prospective study included 32 patients (21 males and 11 females) aged between 23 and 68 years (mean age 49.38 years) who were experiencing both tinnitus and headache. The study assessed the impact of a food supplement on tinnitus and headache over a 90-day treatment period using three main instruments: the Tinnitus Handicap Inventory (THI), the Headache Impact Test (HIT-6), and a Visual Analog Scale (VAS) for discomfort. Statistical analyses, including paired t tests, were conducted to compare pre- and posttreatment scores. In the same dataset, Ridge Regression, a linear regression model with L2 regularization, was used to predict posttreatment scores (THI90, HIT90, VAS90). Results: The results indicated a statistically significant reduction in all three measures after 90 days of treatment. The mean THI score decreased from 29.81 to 27.06 (p = 0.011), the mean HIT-6 score decreased from 50.41 to 48.75 (p = 0.019), and the mean VAS score for discomfort decreased from 7.63 to 7.13 (p = 0.033). The optimal Ridge Regression model was found with an “alpha” value of approximately 3.73. The performance metrics on the test set were as follows: Mean Squared Error (MSE) of 13.91 and an R-squared score of 0.61, indicating that the model explains approximately 61% of the variance in the posttreatment scores. These results indicate that pretreatment scores are significant predictors of posttreatment outcomes, and gender plays a notable role in predicting HIT and VAS scores posttreatment. Conclusion: This study demonstrates that a food supplement is effective in reducing the symptoms of tinnitus and headache in patients suffering from both conditions. The significant improvements in THI, HIT-6, and VAS scores indicate a positive impact on patient quality of life. Further research with larger sample sizes and more detailed subgroup analyses is recommended to fully understand the differential impacts of treatment across various demographics.

Vocal Emotion Perception in Children Using Cochlear Implant.

The significance of emotional prosody in social communication is well-established, yet research on emotion perception among cochlear implant (CI) users is less extensive. This study aims to explore vocal emotion perception in children using CI and bimodal hearing devices and compare them with their normal hearing (NH) peers. The study involved children aged 4-10 years with unilateral CI and contralateral hearing aid (HA), matched with NH peers by gender and listening age. Children were selected using snowball sampling for the CI group and purposive sampling for the NH group. Vocal emotion perception was assessed for semantically neutral sentences in "happy," "sad," and "angry" emotions using a 3 alternate forced choice test. The NH group demonstrated significantly superior emotion perception (P=.002) compared to the CI group. Both groups accurately identified the "happy" emotion. However, the NH group had higher scores for the "angry" emotion compared to the "sad" emotion, while the CI group showed better scores for "sad" than "angry" emotion. Bimodal hearing devices improved recognition of "sad"and "angry" emotions, with a decrease in confusion percentages. The unbiased hit (Hu) value provided more substantial insight than the hit score. Bimodal hearing devices enhance the perception of "sad" and "angry" vocal emotions compared to using a CI alone, likely due to the HA providing the temporal fine structure cues, thereby better representing fundamental frequency variations. Children with unilateral CI benefit significantly in the perception of emotions by using a HA in the contralateral ear, aiding in better socio-emotional development.

Repetitive transcranial magnetic stimulation in new daily persistent headache patients: a single arm open label study

BackgroundNew daily persistent headache (NDPH) is a continuous, unremitting headache from onset that yields suboptimal results with traditional medicines. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive treatment for other headache disorders, such as migraine, and neuromodulation has not been well-studied in NDPH. The objective of the study was to evaluate the efficacy of rTMS in reducing the frequency and severity of headaches, and associated anxiety and depressive symptoms in NDPH patients.MethodsThis was an open label prospective, single arm, interventional pilot study conducted between October 2022 and September 2023. All eligible participants received 10 Hz rTMS (600 pulses, 10 trains), delivered to the left prefrontal cortex for three consecutive days. The post-rTMS headache severity was recorded weekly for four weeks and headache free days/functional disability, PHQ-9, and GAD-7 scores at the end of four weeks and compared with pre-rTMS parameters. The primary outcome was defined by ≥ 50% reduction in headache severity on Visual Analogue Scale (VAS) score, decrease in headache days from the baseline and secondary outcome was ≥ 6 point reduction in HIT-6 score at 4 weeks.ResultsFifty NDPH patients (mean [SD] age, 35.06 [13.91] years; 31 females [62%]) participated in this study. Thirty-five patients (70%) reported ≥ 50% improvement in pain severity (p-value < 0.001), with a mean reduction of 10.84 (4.88) headache days per 28 days from a baseline of 28 headache days (p-value < 0.001). Thirty-eight patients (76%) reported a ≥ 6 point’s reduction in HIT score at 4 weeks. Maximum improvement in the above parameters was observed in NDPH patients with chronic migraine. Two patients reported intolerance to the sound of the rTMS. The median (IQR) PHQ-9 and GAD-7 scores reduced from 11.5(3.75,20) to 7(2,15) (p-value < 0.001) and 10(3,14) to 5.5(0,9) (p-value < 0.001) respectively.ConclusionrTMS was well tolerated and effective in reducing pain severity, headache days and headache related disability, depressive and anxiety symptoms.Trial registrationCTRI/2023/05/053247.

A THREE MONTHS YOGA PROGRAM ON COGNITIVE VARIABLES OF DEMENTIA RISK PARTICIPANTS: A PILOT STUDY

Background: Dementia refers to symptoms that affect memory, thinking, orientation, judgment, speech, and social abilities significantly enough to interfere with daily activities. Dementia is the second most prevalent disease worldwide. Materials &amp; Methods: A total of thirty individuals, with an average age of 52.4 years (± 7.68 years), were enrolled and then assigned at random to either the yoga group (average age 50.9 years ± 7.23 years) or the control group (average age 52.2 years ± 7.73 years). For a duration of three months, the control group participated in brisk walking sessions lasting thirty minutes five days a week, whereas the yoga group endured sixty-minute yoga sessions five days a week. Before and after the three-month intervention period for both groups, working memory was evaluated using the N back task, and executive function was examined using the Trail Making Test (TMT). Results: A significant difference was observed in all four parameters of N back test in yoga group as compared to the control group (P &lt; 0.05) after 12 weeks [ H1( P = 0.01), E1( P = 0.009), H2 (P = 0.0007), E2 ( P = 0.006 ]. There was improvement in the Trail Making Test, but did not observe the significant difference in the yoga group as compared to the control group ( P &gt; 0.05), [ A ( P = 0.096), B ( P = 0.569)]. Conclusion: The result of this pilot study suggests that yoga practices for dementia risk participants improves the Hit score of the N back test and reduces errors, similarly this improves the executive functions of the brain. Larger studies are needed to confirm these findings.

Impact of intimate partner violence on quality of life and disease activity in women with systemic lupus erythematosus.

Stress and trauma are psychosocial factors with an impact on the course of systemic lupus erythematosus (SLE). The influence of violence on SLE has not been entirely explored, even though women (including patients with rheumatic diseases) are a vulnerable population to any form of violence. This study aims to assess the prevalence and impact of intimate partner violence (IPV) on health-related quality of life in women with SLE. An observational, cross-sectional, and analytical study was conducted at a rheumatology clinic of a university hospital from September 2022 and September 2023. We evaluated the presence of IPV in 85 women with SLE with the Hurt, Insulted, Threatened with Harm and Screamed at (HITS) questionnaire and the Index of Spouse Abuse (ISA), and quality of life with LupusQoL. The prevalence by HITS score of past-year IPV was 24.4% and of lifetime IPV was 36.5%. Past-year non-physical violence was present in 17.1% of patients by ISA, and 27.1% were victims in their lifetime. While in physical violence, 7.3% were victims in the previous year and 21.2% in their lifetime. The total quality of life and the emotional domain by LupusQoL were diminished in victims of past-year IPV, compared to those who weren't exposed (p = .018 and p = .036, respectively). Past-year HITS score correlated with the Physician Global Assessment (PGA) (rho = 0.301, p = .006), while lifetime HITS score correlated with PGA (rho = 0.329, p = .002) and SLEDAI-2K (rho = 0.277, p = .010). We found that one in four women suffered IPV in the previous year, and those who were exposed had diminished quality of life. Also, the severity of the abuse correlated with disease activity. Our findings emphasize the importance of comprehensive care for patients with SLE.

EPID-04. CAUSES AND LONG-TERM COURSE OF OTOTOXICITY IN PEDIATRIC MEDULLOBLASTOMA AND EPENDYMOMA PATIENTS – CUMULATIVE PLATINUM AND COCHLEAR IRRADIATION DOSE MATTER

Abstract BACKGROUND Ototoxicity is a well-known side effect of treatment with platinum-containing chemotherapy and radiotherapy (RT). Nevertheless, precise dose-effect relationships are still lacking. METHODS Patients from the HIT2000 trial receiving first-line treatment for medulloblastoma (MB) or ependymoma (EPN) who were alive at last follow-up and had at least one audiogram prior to and after administration of chemotherapy with cisplatinum and radiotherapy were included into this study. Treatment details (incl. cochlear irradiation dose [CID]) and audiological outcome were analyzed. The ototoxicity was graded using the HIT scoring. RESULTS Courses of 101 patients were analyzed. Median audiology follow-up was 6 years [range: 1.0–18.1 years]. Ototoxicity grade ≥1 was documented for n=66 patients (65.4%). For n=27 this resulted in treatment modification. Univariable analyses revealed different proportions of ototoxicity (grade ≥1) regarding histology (CMB: 50/65, LCAMB: 3/3, DMB/MBEN: 8/12, EPN: 5/21; p&amp;lt;0.001), tumor location (supratentorial: 3/9, infratentorial: 63/92; p&amp;lt;0.001), metastatic status at diagnosis (M0: 46/77, M+: 20/24; p=0.003), radiation field (CSI: 59/75, local RT: 6/21, no RT: 1/5; p&amp;lt;0.001), CID (continuous variable, p=0.001) and cumulative cisplatinum dose (continuous variable, p&amp;lt;0.001). Certainly, disease specific parameters (histology/staging) were related to treatment intensity (cisplatinum/irradiation dose). Multivariable analyses confirmed the impact of cumulative cisplatinum dose (p=0.01) and CID (p=0.04). ROC-analyses allowed the definition of cut-offs for high risk of ototoxicity grade ≥1 (cisplatinum: 70mg/m2 BSA, CID: 37.5 Gy) and ototoxicity risk estimation, when applying doses above the respective cut-offs (cisplatinum dose increase by 1mg/m2 BSA results in 4% higher risk for ototoxicity grade ≥1; CID dose increase by 1 Gy results in 4.6% higher risk for ototoxicity grade ≥1). CONCLUSIONS Ototoxicity affects a majority of children receiving adjuvant treatment for MB and EPN. To avoid disabilities and negative effect on quality of live, dosage of cisplatinum and radiotherapy should be scrutinized and reduced whenever possible.

Headache alleviation with nasal irrigation following endoscopic endonasal surgery for pituitary adenomas

BackgroundHeadache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES.MethodsA retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache.ResultsIn Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16–13.03, p = 0.028) and Hardy’s grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups.ConclusionsPostoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis.

Inverse problem solver for epidemiological geographic profiling

This work studies machine-learning-based inverse problem solvers for a reaction–diffusion process. The study focus is on the performance of a state-of-the-art convolutional neural network in discovering the source of disease spreading. This problem is called epidemiological geographic profiling. The performance is investigated with synthetic datasets for SIR epidemiological compartments on a square grid geo-space. The convolutional neural network works effectively in discovering a single source and achieves the largest time average of accuracy for growing infection in a heterogeneous geo-space. The hit score remains near the lower bound over time. Discovering multiple sources is feasible potentially as well by learning the dataset for a single source.

Assessment of Executive Functioning in School-Age Children With And Without Stuttering: A case-control study

Background: Stuttering is defined as a neurodevelopmental disorder, with disruptions in the normal fluency and time patterning of speech that are inappropriate for the individual's age and language skills. Executive functions (EF) include various cognitive skills, such as directing the attention required for planning and maintaining thoughts and behaviors, suppressing inappropriate stimuli, keeping the processed information active, and providing the transition between the information. This study was aimed at investigating whether there is a difference between school-age children with and without stuttering about executive functions (EF) skills and attention. Method: Twenty-six children with stuttering (14 boys; mean age=10.1±2.88) and twenty-five children without stuttering (14 boys; mean age=10.2±2.77) aged between 7 and 12 were admitted to the study. The participants were administered the Visual Aural Digit Span Test-B Form (VADS-B), which evaluates working memory and audiovisual attention, and the Cancellation Tests (CT), which evaluates sustained attention. The Parents of the participants were applied the Behavior Rating Inventory of Executive Function (BRIEF), which was developed to evaluate executive functions, problem-solving skills and adaptive behaviors. Differences in mean subscores of VADS-B, CT, and BRIEF were analyzed using univariate analysis of covariance (ANCOVA) with participant group as the factor and VADS-B, CT, and BRIEF subscores as the dependent variable; Chronological age (years) was designated as a covariate. Results: This study was conducted between two groups that were equal in terms of age, gender, developmental steps (walking, talking, toilet training), family structure, and socioeconomic status (p&gt;0.05). All subscales of VADS-B (aural-verbal, aural-written, visual-verbal, visual-written) were found to be significantly lower in children with stuttering (p&lt;0.05). In cancellation test results, there was a significant difference between the groups in terms of hit scores and total number of errors in organized letter and random letter forms (p&lt;0.05). No difference was found between the two groups in the BRIEF scale completed by the parents (p&gt;0.05). Conclusion: This study demonstrated that school-aged children with stuttering had weaker working memory and sustained attention performance in performance-based tests. Thus, we believe that in the evaluation and treatment of stuttering, comprehensive approaches should be adopted to evaluate attention and executive functions and to improve these functions. In this area, studies with larger samples are needed in which stuttering, attention, and executive functions are evaluated more comprehensively with different tasks (computer-based performance tests, parent-teacher scales, etc.) and neuroimaging (magnetic resonance imaging [MRI]). Lastly, the tasks used in our study (VADS-B, CT, and BRIEF) were applied to Turkish-speaking school-age children with stuttering for the first time. In this regard, we think that our study will contribute to the literature.

Celeritas: Accelerating Geant4 with GPUs

Celeritas: Accelerating Geant4 with GPUs

EVALUATING THE EFFICACY OF BRIHAT DASHAMOOLA TAILA NASYA AND RASNA DASHAMOOLA KASHAYA WITH VARUNAADI KSHEERA GHRITA NASYA AND MUNDITAKA KASHAYA IN THE MANAGEMENT OF ARDHAVABHEDAKA VIS-A-VIS MIGRAINE

Introduction: Ardhavabedhaka is a condition characterized by severe pain in half of the head, such as bheda, toda, bhrama, shula appearing in interval of either 15 or 10 days or spontaneously without any cause1. This disease shows close resemblance to migraine. Migraine is a neural condition characterized by severe recurrent headache usually on one side of the head often accompanied by nausea, vomiting and photophobia2. Migraine affects globally 12% of the population. In India 14.12%-25.2% population and it is a disease predominantly seen in females, with male to female ratio of 1.7:2.6 and among those from urban than rural areas 1.3:1.83. Currently, migraines are managed by usage of analgesics and triptans. Chronic usage of these drugs may cause renal and hepatotoxicity. Therefore, it is necessary to explore ayurvedic approaches that can combat the disease. In Ayurevda this disease is managed by usage of uttama matra of chatuhsneha, shirokaya virechana, nadi sweda, niruha basti, anuvasana basti and shamanaoushadi. As Nasya karma is the prime treatment modality for the management of urdhwa jatrugata vikaras, it is considered appropriate for management of Ardhavabedhaka4. Materials and Methods: The study was conducted using Brihat dashamoola taila as nasya for 8 days and Rasna dashamooladi Kashaya as shamanoushadhi for 23 days post nasya in group 1 and Varunadi ksheera ghrita nasya for 8 days and Munditaka Kashaya as shamanoushadhi for 23 days post nasya in group 2. The assessments were done on the domains of intensity of pain, frequency of attacks and duration of pain, along with the Headache impact score, on the 0th, 8th and 31st days, before and after the treatment. Result: It showed that there was significant decrease in intensity, frequency, duration of pain and Hit score, post nasya karma in both group 1 and 2, also the reduction in pain was significant in both group 1 and 2 post shamanoushadhi. With the overall treatment, it was seen that the reduction in Hit score was highly significant with a p value of 0.000. On comparing the results obtained in both groups, it was observed that group 1 had significant results compared to group 2. Conclusion: Nasya karma works as a treatment of choice in Ardhavabhedaka, due to its ability to eliminate the accumulated doshas from the shiras. The present study showed that Brihat dashamoola taila nasya along with Rasna dashamoola kashaya gives better results in vatakapha pradhana Ardhavabhedaka, and Varunadi ksheera ghrita nasya along with Munditaka Kashaya works better in vatapitta pradhana Ardhavabhedaka.

A new European coastal flood database for low–medium intensity events

Abstract. Coastal flooding is recognized as one of the most devastating natural disasters, resulting in significant economic losses. Therefore, hazard assessment is crucial to support preparedness and response to such disasters. Toward this, flood map databases and catalogues are essential for the analysis of flood scenarios, and furthermore they can be integrated into disaster risk reduction studies. In this study and in the context of the European Coastal Flood Awareness System (ECFAS) project (GA 101004211), which aimed to propose the European Copernicus Coastal Flood Awareness System, a catalogue of flood maps was produced. The flood maps were generated from flood models developed with LISFLOOD-FP for defined coastal sectors along the entire European coastline. For each coastal sector, 15 synthetic scenarios were defined focusing on high-frequency events specific to the local area. These scenarios were constructed based on three distinct storm durations and five different total-water-level (TWL) peaks incorporating tide, mean sea level, surge and wave setup components. The flood model method was extensively validated against 12 test cases for which observed data were collated using satellite-derived flood maps and in situ flood markers. Half of the test cases represented well the flooding with hit scores higher than 80 %. The synthetic-scenario approach was assessed by comparing flood maps from real events and their closest identified scenarios, producing a good agreement and global skill scores higher than 70 %. Using the catalogue, flood scenarios across Europe were assessed, and the biggest flooding occurred in well-known low-lying areas. In addition, different sensitivities to the increase in the duration and TWL peak were noted. The storm duration impacts a few limited flood-prone areas such as the Dutch coast, for which the flooded area increases more than twice between 12 and 36 h storm scenarios. The influence of the TWL peak is more global, especially along the Mediterranean coast, for which the relative difference between a 2- and 20-year return period storm is around 80 %. Finally, at a European scale, the expansion of flood areas in relation to increases in TWL peaks demonstrated both positive and negative correlations with the presence of urban and wetland areas, respectively. This observation supports the concept of storm flood mitigation by wetlands.

Remote Viewing: A 1974-2022 Systematic Review and Meta-Analysis

This is the first meta-analysis of all studies related to remote-viewing tasks conducted up to December 2022. After applying our inclusion criteria, we selected 36 studies with a total of 40 effect sizes. Both frequentist and Bayesian meta-analyses revealed a strong average effect size of .34; 95% confidence interval: .22 -.45, after the exclusion of outliers, without signs of publication bias and a minimal decline effect. In terms of raw scores, these average results correspond to a difference in hits score of 19.3%; 95% confidence intervals:13.6%–25%, above the expected chance. Among the meta-analyses of moderators, a small nonstatistical difference emerged between the precognitive and clairvoyance tasks, particularly for those with an outbound agent. A comparison among meta-analyses results observed with other experimental protocols testing extrasensory perception showed the clear superiority of remote viewing. After more than 50 years of investigation into extrasensory perception, remote-viewing experimental protocols appear to be the most efficient for both experimental and practical applications.

The first shot counts the most: Tactical breathing as an intervention to increase marksmanship accuracy in student officers

ABSTRACT In this study, we investigated the effect of tactical breathing (breath-based stress management) on marksmanship performance in a randomized between-subjects design. The total of n = 100 participants (18% female) were all student soldiers and randomly assigned to the intervention group (tactical breathing) or the control group. In the German Armed Forces shooting simulator, participants shot ten rounds at ten meters with the P8 (Heckler and Koch). In addition, the effect of neuroticism, fear of failure, and resilience on shooting performance and the interaction of those traits with the experimental condition were examined. Overall, the total hit score showed a strong ceiling effect, so the more difficult initial hit was primarily used as a performance criterion. None of the personality traits significantly affected the initial hit, and there were no interactions between the experimental condition and the personality traits. However, there was a significant difference in initial hit between the control and experimental group, as the tactical breathing group shot an average of 1.9 points better, t(98) = 8.489, p < .001, d = 1.698. Considering the initial shot, which was more difficult due to the uncocked trigger, tactical breathing proved to be an effective method for increasing marksmanship performance.

P05.03.B METHYLOME PROFILING OF GLIOBLASTOMAS WITH FGFR3/TACC3 FUSION

Abstract BACKGROUND Glioblastomas (GBMs) with the FGFR3-TACC3 (F3T3) gene fusion have histological, molecular, metabolic, and clinicoradiological characteristics. They have a better prognosis compared to other GBMs. Recent findings suggest that methylome profiling could further stratify these patients identifying a subgroup (defined as “outlier” F3T3+ GBMs, or GBM-F3T3-O) with a methylation profile resembling gangliogliomas (GGs), low-grade histological appearance, and a better outcome. MATERIAL AND METHODS We performed DNA methylation profiling (Infinium MethylationEPIC Array v1.0) of 32 adult diffuse gliomas with FGFR3 gene fusions (30 FGFR3-TACC3, one FGFR3-ACLY, and one FGFR3-MYO18A), plus two paired samples of a diffuse glioma with two distinct contingents (one with positive FGFR3 staining and FGFR3-TACC3 gene fusion, the other with intense EGFR staining and EGFR gene amplification). All cases corresponded to “glioblastoma, IDH-wildtype” according to the WHO CNS5. Methylation data were submitted to the DFKZ brain tumor classifier (molecularneuropathology.org), versions 11b4 and 12.5 and to dimensionality reduction with t-distributed stochastic neighbor embedding (tSNE). Copy-number variation (CNV) estimation based on conumee package was obtained from DFKZ website. RESULTS With the brain tumor classifier v11b4, most cases (26/34, 76%) were classified as methylation class (MC) GBM (17/26 with a significant score ≥0.9). Out of them, 23/26 (88%) were significantly (score ≥0.5) classified in the “GBM, mesenchymal” (16/26, 62%) or in the “GBM, RTK II” methylation families (7/26, 27%). With the classifier v12.5, again most tumors were classified as “GBM, mesenchymal” (18/34, 53%) or “GBM, RTK II” (9/34, 26%), of which twelve (12/34, 35%) with a score ≥0.9. Two were classifed as GG (score 0.69 and 0.39), both having “GBM, mesenchymal” as a second hit (score 0.19 and 0.33, respectively). Five had GG as a second hit, although with low scores (range &amp;lt;0.01-0.25). After tSNE dimensionality reduction of our and literature cases, most tumors clustered together with other GBM, mesenchymal and GBM, RTK II cases. Only two cases fell within a distinct cluster corresponding to GBM-F3T3-O tumors from the literature. These included two histologically defined GBMs with a survival of 26 and 100 months. Recurrent inferred CNV included chromosome (chr) 7 gain (96%) and chr10 loss (85%), followed by chr20 gain (46%), chr22q loss (46%), and chr19 gain (33%). The presence of chr19 gain (alone or associated with chr20 gain) was associated with increased survival (p=0.01). CONCLUSION Glioblastomas with FGFR3 fusions (mostly F3T3) have an epigenomic profile close to other mesenchymal and RTK II GBMs. Methylation analysis identifies methylation (GBM-F3T3-O) and CNV (chr19 gain) profiles associated with better survival.

Rainfall forecasting in the Barak river basin, India using a LSTM network based on various climate indices

The proposed study employs a long short-term memory (LSTM) neural network (NN) to forecast monthly rainfall in the Barak river basin in the northeastern region of India for a prediction horizon up to 4 months in advance. Out of nine significant climate variables, sea surface temperature (SST), sea level pressure (SLP), Nino 3.4 index, the Indian summer monsoon rainfall (ISMR) anomalies and dipole mode index (DMI) were identified to be the best-suited predictors and were introduced as the inputs in the NN. The LSTM is a special kind of recurrent neural network (RNN) which specializes in feature extraction and storing memory in its cell state cumulatively. The model results display strong correlations between the potential predictor sets and the rainfall distribution across the basin. The obtained forecast results were scrutinized in terms of various statistical measures and the predictions were found to be at par with the real time observations (correlations greater than 0.90 and hit score greater than 85%). The testing phase of model produced root mean square errors in the range of 12.45% to 15.65% highlighting satisfactory model performance. The proposed method of incorporating different climate indices form a novel approach to forecast rainfall in the region which may lead to timely and effective management of water resources.

Correlation between Germinal Center Differentiation and Double/Triple Hit Score in the Classification of Diffuse Large B Cell Non-Hodgkin Lymphoma: A Clinicopathological Approach

Background: Diffuse large B cell lymphoma (DLBCL) is considered the most common type of non-Hodgkin lymphoma. The global incidence of DLBCL has been doubled in the past decades, highlighting the need for more effective treatment regimens. The curability of DLBCL is heavily influenced by a number of factors, such as the age, the international prognostic index (IPI) score, the molecular cell of origin (COO) subtype, and presence/ absence of specific chromosomal rearrangements or protein expression. Recent gene profiling studies have classified DLBCL into two main categories, germinal center B-cell type (GCB) and activated B-cell type (ABC). Validation of these subtypes has become more applicable after the immunohistochemical algorithm suggested by Hans, which included three commercially available markers, CD10, BCL6, and MUM-1/IRF4. In addition to this classification, DLBCL prognostic models based on different sets of genes or immunohistochemical markers have been proposed. More recently, DLBCLs with translocations of MYC, along with a B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangement, are now called double-hit lymphoma (DHL) or triple-hit lymphoma (THL), respectively. Furthermore, the co-expre sion of MYC and BCL2 proteins without underlying rearrangements is considered a new adverse prognostic indicator termed double-expressor lymphoma (DEL). The present study is aiming to combine morphological, immunophenotypical, and genetic features of DLBCLs to reach a more reproducible subtyping. Aim: To identify the relation between clinicopathological features as patient age, sex, site of tumor, clinical presentation and tumor stage and the germinal center differentiation in DLBCL (germinal center B-cell (GCB) or activated B-cell (ABC)) and the double/triple genetic hits status.Material and Methods: The material of this study comprised 52 formalin-fixed paraffin- embedded blocks representative of diffuse large B cell lymphoma cases retrieved from the archival material available at the Pathology Department, Faculty of Medicine, Alexandria University. Subclassification of cases into (germinal center / and post-germinal center types) using a panel of immunohistochemical markers including CD10, BCL6 and MUM1 was done and scoring of double/triple hit expression using a panel of immunohistochemical markers including c-MYC, BCL6 and BCL2 was also done and correlation with their subtypes and clinical data was performed.Results: there was significant association between germinal center differentiation and tumor stage (MCp= 0.018).Conclusion: Germinal center differentiation status is a valid method to evaluate the prognosis of DLBCL.

Identification of novel human nicotinamide N-methyltransferase inhibitors: a structure-based pharmacophore modeling and molecular dynamics approach

Human nicotinamide N-methyltransferase (hNNMT) is a cytosolic enzyme associated in the phase-II metabolism, belonging to the S-adenosyl-L-methionine (SAM)-dependent methyltransferases family. Overexpression of hNNMT was observed in diseases such as metabolic disorders and different types of cancers, which suggest NNMT as a prospective therapeutic target. In this study we propose a structure-based pharmacophore model to understand the structural features responsible for the pharmacological activity. The generated model was validated using the ROC curve (AUC), goodness of hit score (GH), specificity, sensitivity and enrichment factor (EF). The pharmacophore was employed to retrieve active molecules from the ZINC database, followed by virtual-screening and molecular docking. Six molecules with the best pharmfit score, binding energy and ADMET properties were identified in this study. A 150 ns molecular dynamics simulation was performed on the selected molecules complexed with hNNMT protein to validate the results. The molecules ZINC35464499, ZINC13311192, ZINC31159282, ZINC14650833, ZINC14819515 and ZINC00303881 were identified, which could be act as the potential hNNMT inhibitors and can also be used as direct hits for developing novel hNNMT antagonists. Communicated by Ramaswamy H. Sarma

HyperVR: a hybrid deep ensemble learning approach for simultaneously predicting virulence factors and antibiotic resistance genes.

Infectious diseases emerge unprecedentedly, posing serious challenges to public health and the global economy. Virulence factors (VFs) enable pathogens to adhere, reproduce and cause damage to host cells, and antibiotic resistance genes (ARGs) allow pathogens to evade otherwise curable treatments. Simultaneous identification of VFs and ARGs can save pathogen surveillance time, especially in situ epidemic pathogen detection. However, most tools can only predict either VFs or ARGs. Few tools that predict VFs and ARGs simultaneously usually have high false-negative rates, are sensitive to the cutoff thresholds and can only identify conserved genes. For better simultaneousprediction of VFs and ARGs, we propose a hybrid deep ensemble learning approach called HyperVR. By considering both best hit scores and statistical gene sequence patterns, HyperVR combines classical machine learning and deep learning to simultaneously and accurately predict VFs, ARGs and negative genes (neither VFs nor ARGs). For the prediction of individual VFs and ARGs, insilico spike-in experiment (the VFs and ARGs in real metagenomic data), and pseudo-VFs and -ARGs (gene fragments), HyperVR outperforms the current state-of-the-art prediction tools. HyperVR uses only gene sequence information without strict cutoff thresholds, hence making prediction straightforward and reliable.