Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor Primary Site and Histology Subtypes Role in Radiotherapeutic Management of Brain Metastases

Randomized controlled trials have failed to report any survival advantage for WBRT combined with SRS in the management of brain metastases, despite the enhanced local and distant control in comparison to each treatment alone. Literature review have revealed important role of primary histology of the tumor when dealing with brain metastases. NSCLC responds better to combined approach even when there was only single brain metastasis present while breast cancer has registered better survival with SRS alone probably due to better response of primary tumor to advancement in surgical and chemotherapeutic agents. Furthermore, mutation status (EGFR/ALK) in lung cancer and receptor status (ER/PR/HER2) in breast cancer also exhibit diversity in their response to radiotherapy. Radioresistant tumors like renal cell carcinoma and melanoma brain metastases have achieved better results when treated with SRS alone. Secondly, single brain metastasis may benefit from local and distant brain control achieved with combined treatment. These diverse outcomes suggest a primary histology-based analysis of the radiotherapy regimens (WBRT, SRS, or their combination) would more ideally establish the role of radiotherapy in the management of brain metastases. Molecularly targeted therapeutic and immunotherapeutic agents have revealed synergism with radiation therapy particularly SRS in treating cancer patients with brain metastases. Clinical updates in this regard have also been reviewed.
A new early Carboniferous crustacean from the Forest of Dean, England

Crustacean remains collected from quarries in Mitcheldean and the Great Doward in the Forest of Dean were originally thought to represent a species of Tealliocaris. Comparisons made with other Carboniferous crustaceans suggest that this material belongs to a new genus and species of eumalacostracan crustacean. The erection of this new genus and species is supported by morphometric and cladistic analyses. The new crustacean, Schramocaris gilljonesorum gen. et sp. nov., appears to exhibit more similarities to Tealliocaris and the Scottish and northern English crustacean Pseudogalathea. There are, however, some significant differences in the shape of the carapace, and the ornamentation of the carapace and pleon. The broad, squat telson is more akin to that of Pseudogalathea, but the length of the pleon and the lack of elongated sharp posterolateral angles to the carapace are more like those of Tealliocaris. The apparent lack of a scaphocerite and the lack of an enlarged third pleomere are more suggestive of affinities with Pseudogalathea. principal coordinate analysis on 12 landmarks of the carapace indicate that this new crustacean is distinct from both Tealliocaris and Pseudogalathea. A cladistic comparison with other Devonian and Carboniferous crustaceans from around the world also suggests that it is distinct, but morphologically similar to a grouping that includes Chaocaris, Tylocaris, Fujianocaris, Pseudogalathea and Tealliocaris. http://zoobank.org/urn:lsid:zoobank.org:pub:7B8D687C-B09D-4198-B234-6F74C55C0E3B
An in situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva

We previously developed ophthalmic formulations containing tranilast nanopartaicles (ophthalmic TL-NPs formulations), and found them to show high uptake into ocular tissues. In this study, we aimed to design an in situ gel incorporating TL-NPs with 0.5–3% methylcellulose (MC, type SM-4) to ensure long residence time of the drug at the ocular surface. The ophthalmic TL-NPs formulations were prepared by the bead mill method, which yielded a mean particle size of ~93 nm with or without MC (0.5–3%). Although the dispersibility of TL particles in ophthalmic formulations increased with the MC content, the diffusion behavior of TL particles in the dispersion medium decreased with MC content. In an in vivo study using rats, the TL content in the lacrimal fluid was enhanced with MC content in the ophthalmic TL-NPs formulations, and the optimum amount of MC (0.5–1.5%) enhanced the TL content in the cornea and conjunctiva, and an anti-inflammatory effect of TL in rats instilled with ophthalmic TL-NPs formulations was observed. On the other hand, excessive MC (3%) prevented the corneal uptake of TL-NPs after instillation, and the anti-inflammation effect of TL was lower than that of ophthalmic TL-NPs formulations with optimum MC (0.5–1.5%). In conclusion, we found that gel formulations of TL-NPs with 0.5 and 1.5% MC provided a prolonged pre-corneal and pre-conjunctival contact time of TL, and resulted in higher TL contents in the cornea and conjunctiva following instillation in comparison with TL-NPs with or without 3% MC. This is probably due to the balance between the higher residence time and faster diffusion of TL-NPs on the ocular surface. These findings provide significant information that can be used to design further studies aimed at developing ophthalmic nanomedicines.
Isolating Human Monoclonal Antibodies Against Adeno-Associated Virus From Donors With Pre-existing Immunity

With the advent of single B-cell cloning technology, we can isolate antibodies against virtually any antigen to study the interaction of a given pathogen with the immune system and develop novel therapeutic strategies. Antibodies directed against the capsid of adeno-associated viruses (AAV) are a significant obstacle to effectively leveraging AAV as a gene-delivery vector in seropositive individuals. In order to design next-generation vectors that can evade neutralization by these antibodies, studies have mapped the epitopes of mouse monoclonal antibodies generated by immunization with AAV. Although these studies provide critical information regarding capsid immunogenicity, they cannot address (1) differences in the antibody repertoire generated in humans following AAV natural infection; or (2) how reactions can vary when generated in response to vector administration. Here, we isolated and evaluated a panel of novel, fully human anti-AAV antibodies by cloning single memory B cells from a seropositive normal donor. We have validated the utility of this approach to study AAV immunology. Our goal is to leverage this knowledge to design novel AAV variants that can effectively transduce target tissues in individuals with AAV-neutralizing antibodies.
Mapping the Contrast Sensitivity of the Visual Field With Bayesian Adaptive qVFM

Current clinical evaluation, which focuses on central vision, could be improved through characterization of residual vision with peripheral testing of visual acuity, contrast sensitivity, color vision, crowding, and reading speed. Assessing visual functions in addition to light sensitivity, a comprehensive visual field map (VFM) would be valuable for detecting and managing eye diseases. In a previous study, we developed a Bayesian adaptive qVFM method that combines a global module for preliminary assessment of the VFM's shape and a local module for assessment at individual retinal locations. The method was validated in measuring the light sensitivity VFM. In this study, we extended the qVFM method to measure contrast sensitivity across the visual field. In both simulations and psychophysics, we sampled 64 visual field locations (48 x 48 deg) and compared the qVFM method with a procedure that tested each retinal location independently (qFC; Lesmes et al., 2015). In each trial, subjects were required to identify a single optotype (size: 2.5 x 2.5 deg), one of 10 filtered Sloan letters. To compare the accuracy and precision of the two methods, three simulated eyes were tested in 1,280 trials with each method. In addition, data were collected from 10 eyes (5 OS, 5 OD) of five normal observers. For simulations, the average RMSE of the estimated contrast sensitivity with the qVFM and qFC methods were 0.057 and 0.100 after 320 trials, and 0.037 and 0.041 after 1,280 trials [all in log10 units, represent as log(sensitivity)], respectively. The average SD of the qVFM and qFC estimates were 0.054 and 0.096 after 320 trials, and 0.032 and 0.041 after 1,280 trials, respectively. The within-run variability (68.2% HWCIs) were comparable to the cross-run variability (SD). In the psychophysics experiment, the average HWCI of the estimated contrast sensitivity from the qVFM and qFC methods across the visual field decreased from 0.33 on the first trial to 0.072 and 0.16 after 160, and to 0.060 and 0.10 after 320 trials. The RMSE between the qVFM and qFC estimates started at 0.26, decreased to 0.12 after 160 and to 0.11 after 320 qVFM trials. The qVFM provides an accurate, precise, and efficient mapping of contrast sensitivity across the entire visual field. The method might find potential clinical applications in monitoring vision loss, evaluating therapeutic interventions, and developing effective rehabilitation for visual diseases.
Gender Comparison of Psychological Comorbidities in Tinnitus Patients – Results of a Cross-Sectional Study

Background In the last decades, research focused on gender-related features in patients with tinnitus has often led to controversial results. The complex clinical picture of tinnitus patients often consists of an interdependent relationship between audiological symptoms and co-occurrent psychological disorders, which can complicate the diagnostic evaluation. Methods Therefore, we studied 107 patients with tinnitus, investigating their psychological comorbidities in the light of gender differences. All patients were evaluated with ENT/audiological and psychological examination to consider presence/absence, type and gender distribution of psychopathological comorbidities. Patients completed questionnaires on tinnitus distress (Tinnitus Handicap Inventory, THI), anxiety (Beck Anxiety Inventory, BAI), depression (Beck Depression Inventory, BDI), metacognition (Metacognition Questionnaire-30, MCQ-30) and worry (Penn State Worry Questionnaire). The influence of gender on the relationship between tinnitus distress and psychological comorbidities was investigated with simple moderation analyses using the SPSS PROCESS macro. Results The total sample included 65 male and 42 female patients (60.7 vs. 39.3%), matched for age and duration of tinnitus. We found no significant differences for tinnitus distress (THI total score, THI subscales) and MCQ-30 subscales, except for the control over thoughts, where men showed significantly higher scores than women (p = 0.045). Also, in our sample women showed significantly higher values for depression (BDI total score, p = 0.019), anxiety (BAI total score, p = 0.010) and worries (PSQW total score, p = 0.015). Moderation analyses revealed a significant influence of gender on the relationship of tinnitus distress with depression: higher scores of tinnitus distress were associated with significantly elevated levels of depression amongst men. No further gender influences could be observed in our sample. Discussion In conclusion, our results indicate general gender differences for psychological comorbidities in tinnitus patients, with women reporting more depression, anxiety and worries. Men, on the other hand, showed a higher need to control their thoughts. Additionally, our results indicate that men might have more coping problems with increasing levels of tinnitus distress, leading to increased depressive symptoms. Nevertheless, several gender related aspects in tinnitus patients remain unclear, thus warranting the need future studies in this field.
Language networks in aphasia and health: a 1000 participant Activation Likelihood Estimate analysis

Aphasia recovery post-stroke is classically and most commonly hypothesised to rely on regions that were not involved in language premorbidly, through ‘neurocomputational invasion’ or engagement of ‘quiescent homologues’. Contemporary accounts have suggested, instead, that recovery might be supported by under-utilised areas of the premorbid language network, which are downregulated in health to save neural resources (‘variable neurodisplacement’). Despite the importance of understanding the neural bases of language recovery clinically and theoretically, there is no consensus as to which specific regions are activated more consistently in post-stroke aphasia (PSA) than healthy individuals. Accordingly, we performed an Activation Likelihood Estimation analysis of language functional neuroimaging studies in PSA and linked control data. We obtained coordinate-based functional neuroimaging data for 481 individuals with aphasia following left hemisphere stroke (one third of which was previously unpublished) and for 530 healthy controls. Instead of the language network expanding by activating novel right hemisphere regions ‘de novo’ post-stroke, as would be predicted by neurocomputational invasion/quiescent homologue engagement mechanisms of recovery, we found that multiple regions throughout both hemispheres were consistently activated during language tasks in PSA and controls. Multiple undamaged regions were less consistently activated in PSA than controls, including domain-general regions of medial superior frontal cortex and right fronto-temporal cortex. In the reverse direction, the right anterior insula and inferior frontal gyrus were more consistently activated in PSA than controls, particularly for executively-demanding comprehension tasks. These regions overlap with control networks known to be recruited during difficult tasks in healthy individuals and were more consistently activated by patients during higher than lower demand tasks in this meta-analysis. Overall, these findings run counter to neurocomputational invasion of the language network into new territory or engagement of quiescent homologues. Instead, many parts of the pre-existing language network are less consistently activated in PSA, except for more consistent use of spare capacity within right hemisphere executive-control related regions (cf. variable neurodisplacement). This study provides novel insights into the language network changes that occur post-stroke. Such knowledge is essential if we are to design neurobiologically-informed therapeutic interventions to facilitate language recovery.
Sedentary Behaviors and Physical Activity Habits Independently Affect Fat Oxidation in Fasting Conditions and Capillary Glucose Levels After Standardized Glucose-Rich Meal in Healthy Females

Purpose Sedentary behaviors and muscle inactivity are being growingly recognized as important risk factors for health, adjunctively and independently from a scarce physical activity (PA), although the metabolic mechanism underneath is barely clear. To explore the relation between sedentary behaviors (SBs) and metabolism, we measured the metabolic profile in fasting condition and after oral glucose overload in a group of women, along with objective monitoring of their PA/sedentary lifestyle habits. Subjects and Methods Thirteen women (age: 32.5 ± 16.1 years; BMI: 24.0 ± 3.3 kg/m2), recruited among university students and research staff, underwent indirect calorimetry to assess fat and carbohydrate contribution to energy metabolism, in fasting conditions and after a glucose-rich standard meal (about 45 g of glucose). Glucose concentration in capillary blood was determined in fasting state and 15 and 30 min after meal. Habitual PA and SBs in the previous week were continuously monitored with Actigraph accelerometers. Results After adjustment for age, the contribution of fat oxidation to metabolic energy sources, normalized for fat-free mass, in fasting conditions was significantly correlated with time spent in sitting/lying position during wake hours (p < 0.001), independent from PA habits, whereas capillary blood peak and change of glucose concentration after the meal were significantly and inversely correlated with average daily moderate to vigorous PA (p = 0.025 and p = 0.019, respectively), independent from average daily sitting/lying time. Conclusions Here, we report for the first time a direct effect of muscle inactivity on increased fat oxidation in fasting conditions, which can be hypothesized as a preliminary condition for the development of insulin resistance. We also report the direct independent effect of PA on the capacity to respond to a glycemic load, so that SBs and reduced PA appear to concur, although independently, to the increased health risk, as elsewhere observed on an epidemiological ground.
A New Species of the Deep-Sea Sponge-Associated Genus Eiconaxius (Crustacea: Decapoda: Axiidae), With New Insights Into the Distribution, Speciation, and Mitogenomic Phylogeny of Axiidean Shrimps

Eiconaxius Bate, 1888 is a genus of axiid shrimps exclusively associated with deep-sea hexactinellid sponges. Due to its special morphology and habitat, Eiconaxius is taxonomically and ecologically controversial. Based on material recently collected from seamounts in the northwestern Pacific, a new species of Eiconaxius is described. Intraspecific morphological and genetic variation and host specificity were evaluated. The complete mitochondrial genome of the new species was sequenced to explore the systematic status of Eiconaxius and some other axiidean taxa. Our analyses showed that differentiation of the new species occurs both allopatrically and sympatrically, probably resulting from the interaction of geographical isolation and deep water current movement, rather than from adaptation to different hosts. In addition, species of Eiconaxius are suggested to have wider ranges of distribution and host than expected. The reconstructed mitogenomic phylogeny supported merging Eiconaxius into Axiidae, and recognized most axiidean families, except that Strahlaxiidae was suggested to be paraphyletic. However, more comprehensive taxon sampling is still needed to resolve the explicit internal relationships among Axiidea.
Multidrug-Resistant Avian Pathogenic Escherichia coli Strains and Association of Their Virulence Genes in Bangladesh

The avian pathogenic Escherichia coli (APEC) strains are the chief etiology of avian colibacillosis worldwide. The present study investigated the circulating phylotypes, existence of virulence genes (VGs) and antimicrobial resistance (AMR) in 392 APEC isolates, obtained from 130 samples belonged to six farms using both phenotypic and PCR-based molecular approaches. Congo red binding (CRB) assay confirmed 174 APEC isolates which were segregated into 10, 9 and 8 distinctive genotypes by RAPD assay (discriminatory index, D=0.8707), BOX-PCR (D=0.8591) and ERIC-PCR (D=0.8371), respectively. The combination of three phylogenetic markers (chuA, yjaA and DNA fragment TspE4.C2) classified APEC isolates into B23 (37.36%), A1 (33.91%), D2 (11.49%), B22 (9.20%) and B1 (8.05%) phylotypes. Majority of the APEC isolates (75-100%) harbored VGs (ial, fimH, crl, papC and cjrC), and of them, VGs (papC and cjrC) and phylotypes (D2 and B2) of APEC had significant (p=0.004) association with colibacillosis. Phylogenetic analysis showed two distinct clades (Clade A and Clade B) of APEC where Clade A had 98-100.0% similarity with E. coli APEC O78 and E. coli EHEC strains, and Clade B had closest relationship with E. coli O169:H41 strain. Interestingly, phylogroups B2 and D2 were found in the APEC strains of both clades while the strains from phylogroups A1 and B1 were found in clade A only. In this study, 81.71% of the isolates were biofilm formers and possessed plasmids of varying ranges (1.0 to 54 kb). In vitro antibiogram profiling revealed that 100.0% isolates were resistant to ≥3 antibiotics, of which61.96%, 55.24, 53.85, 51.16 and 45.58 % isolates in phylotypes B1, D2, B22, B23 and A1, respectively were these antimicrobials. The resistance patterns varied among different phylotypes, notably in phylotype B22 showing the highest resistance to ampicillin (90.91%), nalidixic acid (90.11%), tetracycline (83.72%) and nitrofurantoin (65.12%). Correspondence analysis also showed significant correlation of phylotypes with CRB (p=0.008), biofilm formation (p=0.02), drug resistance (p=0.03) and VGs (p=0.06). This report demonstrated that B2 and A1 phylotypes are dominantly circulating APEC phylotypes in Bangladesh; however, B2 and D2 are strongly associated with the pathogenicity. A high prevalence of antibiotic resistant APEC strains from different phylotypes suggest to use of organic antimicrobial compounds, and/or metals, and the rotational use of antibiotics in the poultry farms in Bangladesh.
Predictive Neural Computations Support Spoken Word Recognition: Evidence from MEG and Competitor Priming

Human listeners achieve quick and effortless speech comprehension through computations of conditional probability using Bayes rule. However, the neural implementation of Bayesian perceptual inference remains unclear. Competitive-selection accounts (e.g., TRACE) propose that word recognition is achieved through direct inhibitory connections between units representing candidate words that share segments (e.g., hygiene and hijack share /haidʒ/). Manipulations that increase lexical uncertainty should increase neural responses associated with word recognition when words cannot be uniquely identified. In contrast, predictive-selection accounts (e.g., Predictive-Coding) propose that spoken word recognition involves comparing heard and predicted speech sounds and using prediction error to update lexical representations. Increased lexical uncertainty in words, such as hygiene and hijack, will increase prediction error and hence neural activity only at later time points when different segments are predicted. We collected MEG data from male and female listeners to test these two Bayesian mechanisms and used a competitor priming manipulation to change the prior probability of specific words. Lexical decision responses showed delayed recognition of target words (hygiene) following presentation of a neighboring prime word (hijack) several minutes earlier. However, this effect was not observed with pseudoword primes (higent) or targets (hijure). Crucially, MEG responses in the STG showed greater neural responses for word-primed words after the point at which they were uniquely identified (after /haidʒ/ in hygiene) but not before while similar changes were again absent for pseudowords. These findings are consistent with accounts of spoken word recognition in which neural computations of prediction error play a central role. SIGNIFICANCE STATEMENT Effective speech perception is critical to daily life and involves computations that combine speech signals with prior knowledge of spoken words (i.e., Bayesian perceptual inference). This study specifies the neural mechanisms that support spoken word recognition by testing two distinct implementations of Bayes perceptual inference. Most established theories propose direct competition between lexical units such that inhibition of irrelevant candidates leads to selection of critical words. Our results instead support predictive-selection theories (e.g., Predictive-Coding): by comparing heard and predicted speech sounds, neural computations of prediction error can help listeners continuously update lexical probabilities, allowing for more rapid word identification.