Naïve chicks do not prefer objects with stable body orientation, though they may prefer behavioural variability

Domestic chicks (Gallus gallus domesticus) have been widely used as a model to study the motion cues that allow visually naïve organisms to detect animate agents shortly after hatching/birth. Our previous work has shown that chicks prefer to approach agents whose main body axis and motion direction are aligned (a feature typical of creatures whose motion is constrained by a bilaterally symmetric body plan). However, it has never been investigated whether chicks are also sensitive to the fact that an agent maintains a stable front–back body orientation in motion (i.e. consistency in which end is leading and which trailing). This is another feature typical of bilateria, which is also associated with the detection of animate agents in humans. The aim of the present study was to fll this gap. Contrary to our initial expectations, after testing 300 chicks across 3 experimental conditions, we found a recurrent preference for the agent which did not maintain a stable front–back body orientation. Since this preference was limited to female chicks, the results are discussed also in relation to sex diferences in the social behaviour of this model. Overall, we show for the frst time that chicks can discriminate agents based on the stability of their front–back orientation. The unexpected direction of the efect could refect a preference for agents’ whose behaviour is less predictable. Chicks may prefer agents with greater behavioural variability, a trait which has been associated with animate agents, or have a tendency to explore agents performing “odd behaviours”

Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma

BET inhibitors; Glioblastoma; PharmacokineticsInhibidores de BET; Glioblastoma; FarmacocinéticaInhibidors de BET; Glioblastoma; FarmacocinèticaBackground Standard-of-care treatment for newly diagnosed glioblastoma (ndGBM), consisting of surgery followed by radiotherapy (RT) and temozolomide (TMZ), has improved outcomes compared with RT alone; however, prognosis remains poor. Trotabresib, a novel bromodomain and extraterminal inhibitor, has demonstrated antitumor activity in patients with high-grade gliomas. Methods In this phase Ib, dose-escalation study (NCT04324840), we investigated trotabresib 15, 30, and 45 mg combined with TMZ in the adjuvant setting and trotabresib 15 and 30 mg combined with TMZ+RT in the concomitant setting in patients with ndGBM. Primary endpoints were to determine safety, tolerability, maximum tolerated dose, and/or recommended phase II dose (RP2D) of trotabresib. Secondary endpoints were assessment of preliminary efficacy and pharmacokinetics. Pharmacodynamics were investigated as an exploratory endpoint. Results The adjuvant and concomitant cohorts enrolled 18 and 14 patients, respectively. Trotabresib in combination with TMZ or TMZ+RT was well tolerated; most treatment-related adverse events were mild or moderate. Trotabresib pharmacokinetics and pharmacodynamics in both settings were consistent with previous data for trotabresib monotherapy. The RP2D of trotabresib was selected as 30 mg 4 days on/24 days off in both settings. At last follow-up, 5 (28%) and 6 (43%) patients remain on treatment in the adjuvant and concomitant settings, respectively, with 1 patient in the adjuvant cohort achieving complete response. Conclusions Trotabresib combined with TMZ in the adjuvant setting and with TMZ+RT in the concomitant setting was safe and well tolerated in patients with ndGBM, with encouraging treatment durations. Trotabresib 30 mg was established as the RP2D in both settings.This study was sponsored by Celgene, a Bristol Myers Squibb company

Metal artefact reduction in computed tomography images by a fourth-order total variation flow

Permanent metallic implants, such as dental fillings and cardiac devices, generate streaks-like artefacts in computed tomography (CT) images. In this article, we propose a strategy to perform metal artefact reduction (MAR) that relies on the total variation-H-1 inpainting, a variational approach based on a fourth-order total variation (TV) flow. This approach has never been used to perform MAR, although it has been profitably employed in other branches of image processing. A systematic evaluation of the performance is carried out. Comparisons are made with the results obtained using classical linear interpolation and two other partial differential equation-based approaches relying, respectively, on the Fourier's heat equation and on a second order TV flow. Visual inspection of both synthetic and real CT images, as well as computation of similarity indexes, suggests that our strategy for MAR outperforms the others considered here, as it provides best image restoration, highest similarity indexes and for being the only one able to recover hidden structures, a task of primary importance in the medical field

ULTRASONOGRAPHIC FEATURES OF ADRENAL GLAND LESIONS IN DOGS CAN AID IN DIAGNOSIS

BACKGROUND: Ultrasonography to visualize adrenal gland lesions and evaluate incidentally discovered adrenal masses in dogs has become more reliable with advances in imaging techniques. However, correlations between sonographic and histopathological changes have been elusive. The goal of our study was to investigate which ultrasound features of adrenal gland abnormalities could aid in discriminating between benign and malignant lesions. To this end, we compared diagnosis based on ultrasound appearance and histological findings and evaluated ultrasound criteria for predicting malignancy. RESULTS: Clinical records of 119 dogs that had undergone ultrasound adrenal gland and histological examination were reviewed. Of these, 50 dogs had normal adrenal glands whereas 69 showed pathological ones. Lesions based on histology were classified as cortical adrenal hyperplasia (n = 67), adenocarcinoma (n = 17), pheochromocytoma (n = 10), metastases (n = 7), adrenal adenoma (n = 4), and adrenalitis (n = 4). Ultrasonographic examination showed high specificity (100%) but low sensitivity (63.7%) for identifying the adrenal lesions, which improved with increasing lesion size. Analysis of ultrasonographic predictive parameters showed a significant association between lesion size and malignant tumors. All adrenal gland lesions >20 mm in diameter were histologically confirmed as malignant neoplasms (pheochromocytoma and adenocarcinoma). Vascular invasion was a specific but not sensitive predictor of malignancy. As nodular shape was associated with benign lesions and irregular enlargement with malignant ones, this parameter could be used as diagnostic tool. Bilaterality of adrenal lesions was a useful ultrasonographic criterion for predicting benign lesions, as cortical hyperplasia. CONCLUSIONS: Abnormal appearance of structural features on ultrasound images (e.g., adrenal gland lesion size, shape, laterality, and echotexture) may aid in diagnosis, but these features alone were not pathognomic. Lesion size was the most direct ultrasound predictive criterion. Large and irregular masses seemed to be better predictors of malignant neoplasia and lesions <20 mm in diameter and nodular in shape were often identified as cortical hyperplastic nodules or adenomas

Somatic variants for seed and fruit set in grapevine

Background: Grapevine reproductive development has direct implications on yield. It also impacts on berry and wine quality by affecting traits like seedlessness, berry and bunch size, cluster compactness and berry skin to pulp ratio. Seasonal fluctuations in yield, fruit composition and wine attributes, which are largely driven by climatic factors, are major challenges for worldwide table grape and wine industry. Accordingly, a better understanding of reproductive processes such as gamete development, fertilization, seed and fruit set is of paramount relevance for managing yield and quality. With the aim of providing new insights into this field, we searched for clones with contrasting seed content in two germplasm collections. Results: We identified eight variant pairs that seemingly differ only in seed-related characteristics while showing identical genotype when tested with the GrapeReSeq_Illumina_20K_SNP_chip and several microsatellites. We performed multi-year observations on seed and fruit set deriving from different pollination treatments, with special emphasis on the pair composed by Sangiovese and its seedless variant locally named Corinto Nero. The pollen of Corinto Nero failed to germinate in vitro and gave poor berry set when used to pollinate other varieties. Most berries from both open- and cross-pollinated Corinto Nero inflorescences did not contain seeds. The genetic analysis of seedlings derived from occasional Corinto Nero normal seeds revealed that the few Corinto Nero functional gametes are mostly unreduced. Moreover, three genotypes, including Sangiovese and Corinto Nero, were unexpectedly found to develop fruits without pollen contribution and occasionally showed normal-like seeds. Five missense single nucleotide polymorphisms were identified between Corinto Nero and Sangiovese from transcriptomic data. Conclusions: Our observations allowed us to attribute a seedlessness type to some variants for which it was not documented in the literature. Interestingly, the VvAGL11 mutation responsible for Sultanina stenospermocarpy was also discovered in a seedless mutant of Gouais Blanc. We suggest that Corinto Nero parthenocarpy is driven by pollen and/or embryo sac defects, and both events likely arise from meiotic anomalies. The single nucleotide polymorphisms identified between Sangiovese and Corinto Nero are suitable for testing as traceability markers for propagated material and as functional candidates for the seedless phenotype

Embryonic Exposure to Valproic Acid Affects Social Predispositions for Dynamic Cues of Animate Motion in Newly-Hatched Chicks

Early predispositions to preferentially orient towards cues associated with social partners have been documented in several vertebrate species including human neonates and domestic chicks. Human newborns at high familiar risk of Autism Spectrum Disorder (ASD) show differences in their attention toward these predisposed stimuli, suggesting potential impairments in these social-orienting mechanisms in ASD. Using embryonic exposure to valproic acid (VPA) we modelled ASD behavioural deficits in domestic chicks. To investigate social predispositions towards animate motion in domestic chicks, we focused on self-propulsion, using two video-animations representing a simple red circle moving at constant speed (speed-constant) or one that was changing its speed (accelerating and decelerating; speed-change). Using a six minutes spontaneous choice test for the two stimuli, we compared unlearned preferences for stimuli that autonomously change speed between VPA- and vehicle-injected chicks. We found that the preference for speed changes was abolished in VPA-injected chicks compared to vehicle-injected controls. These results add to previous findings indicating similar impairments for static social stimuli and suggest a specific effect of VPA on the development of mechanisms that enhance orienting towards animate stimuli. These findings strengthen the hypothesis of an early impairment of predispositions in the early development of ASD. Hence, early predispositions are a potentially useful tool to detect early ASD symptoms in human neonates and to investigate the molecular and neurobiological mechanisms underlying the onset of this neurodevelopmental disorder

DMRT1 regulates human germline commitment

Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo. Moreover, the induction of DMRT1 and SOX17 in PGC-like cells promoted epigenetic resetting with striking global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites and the expression of DAZL representing DNA methylation-sensitive genes, a hallmark of the germline commitment programme. We provide insight into the unique role of DMRT1 in germline development for advances in human germ cell biology and in vitro gametogenesis

Differential Associations Between Sensory Response Patterns and Language, Social, and Communication Measures in Children With Autism or Other Developmental Disabilities

Examine patterns of sensory responsiveness (i.e., hyperresponsiveness, hyporesponsiveness, and sensory seeking) as factors that may account for variability in social-communicative symptoms of autism and variability in language, social, and communication skill development in children with autism or other developmental disabilities

Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma

Standard-of-care treatment for newly diagnosed glioblastoma (ndGBM), consisting of surgery followed by radiotherapy (RT) and temozolomide (TMZ), has improved outcomes compared with RT alone; however, prognosis remains poor. Trotabresib, a novel bromodomain and extraterminal inhibitor, has demonstrated antitumor activity in patients with high-grade gliomas. In this phase Ib, dose-escalation study (NCT04324840), we investigated trotabresib 15, 30, and 45 mg combined with TMZ in the adjuvant setting and trotabresib 15 and 30 mg combined with TMZ+RT in the concomitant setting in patients with ndGBM. Primary endpoints were to determine safety, tolerability, maximum tolerated dose, and/or recommended phase II dose (RP2D) of trotabresib. Secondary endpoints were assessment of preliminary efficacy and pharmacokinetics. Pharmacodynamics were investigated as an exploratory endpoint. The adjuvant and concomitant cohorts enrolled 18 and 14 patients, respectively. Trotabresib in combination with TMZ or TMZ+RT was well tolerated; most treatment-related adverse events were mild or moderate. Trotabresib pharmacokinetics and pharmacodynamics in both settings were consistent with previous data for trotabresib monotherapy. The RP2D of trotabresib was selected as 30 mg 4 days on/24 days off in both settings. At last follow-up, 5 (28%) and 6 (43%) patients remain on treatment in the adjuvant and concomitant settings, respectively, with 1 patient in the adjuvant cohort achieving complete response. Trotabresib combined with TMZ in the adjuvant setting and with TMZ+RT in the concomitant setting was safe and well tolerated in patients with ndGBM, with encouraging treatment durations. Trotabresib 30 mg was established as the RP2D in both setting