bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study.
Authors: Brown Landon Carter , Halabi Susan , Humeniuk Michael Sandon , Wu Yuan , Oyekunle Taofik , Huang Jiaoti , Anand Monika , Davies Catrin , Zhang Tian , Harrison Michael Roger , George Daniel J. , Armstrong Andrew J.
Published: March 2021

89

Background: Men with metastatic neuroendocrine/small cell and aggressive variant prostate cancer (NEPC/AVPC) have poor outcomes despite platinum and taxane chemotherapy. These tumors share common features with small cell lung cancer, including higher tumor mutational burden and genomic alterations, and thus may be responsive to immunotherapy. Methods: We conducted a single arm, 2-stage phase II investigator-sponsored trial, (PICK-NEPC, NCT03179410) with the PD-L1 inhibitor avelumab in patients with NEPC/AVPC. NEPC/AVPC was defined either by histologic criteria (neuroendocrine or small cell features) by central pathology review or by aggressive variant clinical criteria (prior progression on abiraterone or enzalutamide with liver metastasis, bulky radiographic progression and low PSA, or high serum LDH). Prior chemotherapy or hormonal therapy was allowed. Avelumab 10 mg/kg IV every 2 weeks was administered until progression or unacceptable toxicity with ongoing ADT. The primary endpoint was overall response rate (ORR) defined by modified PCWG3 and iRECIST criteria. Results: We consented 19 men with AVPC/NEPC, and 15 initiated treatment with avelumab. The median age was 71 (range 51-85), and 27% had neuroendocrine or small cell histology, while 73% met AVPC clinical criteria with adenocarcinoma histology. Men had received a median of two prior systemic therapies (range 1-3) including carboplatin (27%), docetaxel (73%), enzalutamide (67%), and abiraterone (47%). Median PSA was 54 ng/mL (range 0-393) and 73% had liver metastasis. The ORR by iRECIST was 6.7% (95% CI 0-32%) with 1 CR, 0 PRs, 3 (20%) with stable disease, and 11 (73%) with progressive disease. The patient with a CR had NEPC with a CNS metastasis that was found to be MSI-high/TMB-high due to a somatic MSH2 alteration; he finished 12 months of avelumab and maintains a durable CR and undetectable PSA 6 months after completing all therapy including ADT. Median radiographic progression free survival was 1.8 months (95% CI 1.6-2.0 mo) and median time on therapy was 56 days (range 28-356). Median overall survival was 7.4 mo (85% CI 2.8-12.5 mo). Two grade 3 adverse events (abdominal pain due to hepatic disease progression versus immune hepatitis and pericarditis), and one grade 4 (immune hepatitis) adverse event were attributed to avelumab with no grade 5 adverse events. Grade 1 or 2 infusion-related reactions were experienced by 9 (60%). Conclusions: PD-L1 inhibition with avelumab demonstrated limited clinical efficacy in men with metastatic NEPC/AVPC other than in those with MSI-high disease. Further research is needed into mechanisms of immune evasion in NEPC/AVPC to develop novel immunotherapies. Clinical trial information: NCT03179410.
Anaplastic features (AnaF) and DNA-damage repair pathway (DDR) mutations in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Chau Vincent , Madan Ravi Amrit , Bilusic Marijo , Cordes Lisa M. , Marte Jennifer L. , Owens Helen , Hankin Amy , Gulley James L. , Lee Jung-Min , Dahut William L. , Karzai Fatima
Published: March 2021

92

Background: Anaplastic prostate cancer displays features of small-cell carcinoma, a type of neuroendocrine tumor. Treatments for anaplastic prostate cancer are based on small cell lung cancer regimens. Both AnaF and mutations in DDR pathways, including BRCA2 confer an aggressive phenotype. For patients (pts) with certain DDR mutations, olaparib (O) was recently FDA approved, and an ongoing study is evaluating whether the addition of durvalumab (D) confers additional benefit in mCRPC (NCT02484404). We evaluate a potential preliminary relationship between DDR mutations, treatment with D and O, and AnaF. Methods: This is a phase II study of O plus D in pts with mCRPC with disease that is amenable to biopsy. On-study core biopsies undergo mutational analysis. Prior treatment with enzalutamide (enza) and/or abiraterone (abi) is required. D is given at 1500 mg iv q28 days + O 300 mg tablets po q12 hours. The primary endpoint is PFS. Pts were categorized into those with and without AnaF as defined by Aparicio et al. (2013). AnaF include small-cell histology; exclusively visceral metastases; predominantly lytic bone metastases; bulky lymphadenopathy (≥5 cm) or high-grade (Gleason ≥8) mass in prostate/pelvis; low PSA (≤10 ng/mL) at initial presentation with high volume (≥20) bone metastases; neuroendocrine markers in histology or serum plus elevated LDH, malignant hypercalcemia, or elevated serum CEA; or short interval (≤6 months) to androgen-independent progression. Results: Of 55 pts accrued, 24 had prior abi and enza; 19 pts had prior taxane. Common adverse events include anemia, fatigue, and nausea. Also, 11 pts (20.0%) displayed clear AnaF (Table) and 43 pts lacked AnaF, including 8 (14.5%) with partial AnaF that did not meet the full criteria, 4 (7.3%) who likely did not have AnaF due to difficulty in quantifying disease burden, 29 (52.7%) who did not have AnaF, and 2 (3.6%) had unknown status. Four pts (36.4%) with clear AnaF had DDR aberrations, including 3 (27.3%) with BRCA2, 1 (9.1%) with both BRCA2 and CHEK2, and 1 (9.1%) with ATM. Conclusions: Pts with mCRPC with DDR mutations can also have AnaF. This preliminary data demonstrates that pts with anaplastic prostate cancer and pts with DDR mutations are two distinct populations with some degree of overlap. O+D is well-tolerated, and future studies should focus on finding optimal treatments for pts with AnaF without and without DDR mutations. Clinical trial information: NCT02484404. [Table: see text]
Phase I study of entinostat in combination with enzalutamide for treatment of patients with castration-resistant prostate cancer.
Authors: Lin Jianqing , Elkon Jacob Matt , Ricart Brittany , Burgess Brooke , Palmer Erica , Siegel Robert S. , Ma Yan , Villagra Alejandro
Published: March 2021

96

Background: Entinostat (SNDX-275, MS-275) is an oral histone deacetylase (HDAC) inhibitor with selectivity towards class I and IV HDACs. Entinostat inhibits prostate cancer (PCa) growth and suppresses Treg cell function in vitro and in vivo. The primary objective of this study was to determine the safe dose of Entinostat in combination with Enzalutamide in prostate cancer patients (PCa). Methods: Phase I, 2 cohorts "3+3", dose-escalation study to explore the safety and preliminary efficacy of Entinostat in combination with Enzalutamide in castration-resistant PCa (CRPC). The planned dose level of Entinostat was 3 and 5 mg orally per week. CRPC Patients progressed on Enzalutamide or eligible for Enzalutamide, able to tolerate 160 mg daily dose (in the initial run-in phase if Enzalutamide naïve), ECOG 0-1, and acceptable organ functions were enrolled in the study. The safety profile of the combination therapy, PSA, pharmacokinetics of Enzalutamide post-Entinostat administration, and peripheral T cell subtype (including Treg), mononuclear cell (PBMC) histone 3 acetylation were analyzed. Results: Total 6 mCRPC patients were enrolled. There was no dose limiting toxicity related to Entinostat in these patients. No obvious increased fatigue related to Entinostat. Toxicities possibly or probably related to Entinostat or the combination therapy included G3 anemia 1/6 (17%), G2 WBC decrease 1/6 (17%), All other toxicities were grade 1 only (Nausea 2/6, anorexia 1/6, emesis 1/6, constipation 1/6, headache 1/6, platelet count decrease 1/6, hypokalemia 1/6, hypoalbuminemia 1/6, hypermagnesemia 1/6). The median duration of treatment with Entinostat was 18 weeks. For patients already progressed on Enzalutamide there was no PSA response after Entinostat was added. Entinostat did not affect the steady plasma concentration of Enzalutamide. Increased PBMC H3 acetylation was observed (up to 3.6 fold from baseline) in the tested samples. No evident T cell subtype, including Treg, changes from these sample analysis. Phase II part of the trial was terminated because of sponsor withdrawal. Conclusions: Entinostat at the selected dose levels in combination with standard dose of enzalutamide showed promising safety profile in this small phase I study. Clinical trial information: NCT03829930.
18F-fluciclovine positron emission tomography (PET) in metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate.
Authors: Barata Pedro C. , Manogue Charlotte , Jaeger Ellen , Light Malcolm , Cotogno Patrick , Ledet Elisa Marie , Goffin Janeiro , Layton Jodi Lyn , Lewis Brian E. , Sartor A. Oliver
Published: March 2021

TPS171

Background: Conventional imaging of prostate cancer has limitations in staging, restaging after biochemical relapse, and response assessment. Functional imaging with positron emission tomography (PET) can target various aspects of tumor biology and has shown to be superior in the detection of prostate cancer compared with conventional computed tomography (CT) and bone scans. 18F-Fluciclovine, a synthetic amino acid transported across mammalian cell membranes by amino acid transporters that is upregulated to a greater extent in prostate cancer cells than in surrounding tissue, is currently approved for PET imaging for patients with biochemical recurrence. The role of 18F-Fluciclovine PET scans in monitoring response to novel hormonal therapies such as abiraterone acetate is unclear. We hypothesize that 1) using 18F-Fluciclovine PET scanning will allow a more sensitive assessment of mCRPC patients at the initiation of systemic therapy with abiraterone acetate and 2) the changes observed in 18F-Fluciclovine PET will correlate better with the serologic changes in PSA, allowing superior disease monitoring, than conventional imaging modalities. Methods: This single-arm, pilot study (NCT04158245) will describe the changes in 18F-Fluciclovine PET scan and compare these results with PSA and conventional computerized tomography (CT) and bone scans, in mCRPC patients treated with abiraterone acetate plus prednisone. Patients must have a detectable baseline PSA of ≥ 2 ng/mL and metastatic disease detected on conventional CT and bone scans. The use of docetaxel in the hormone-sensitive setting is allowed. Twelve patients will be treated with abiraterone 1000 mg daily plus prednisone 5 mg (or dexamethasone 0.5 mg) daily for mCRPC and get 18F-Fluciclovine PET and conventional CT and bone scans at baseline and 12 weeks after starting abiraterone therapy or at disease progression. PSA progression will be defined as a repeated increase in PSA of at least 2 ng/dL and 25% from nadir values, at least 1 week apart, according to PCWG3 criteria and clinical or radiographic progression by RECIST version 1.1. The co-primary objectives of the study include the 18F-Fluciclovine PET changes at baseline and 12 weeks after abiraterone acetate for mCRPC and the comparison between 18F-Fluciclovine PET and conventional scans. Secondary and exploratory endpoints include PSA response, PSA progression and genomic alterations by next-generation sequencing. As of 12 September 2020, this trial is actively enrolling. Clinical trial information: NCT04158245.
Treatment of aggressive prostate cancers in real life: Initiation, schedule, and management of triptorelin treatment (TALISMAN)—Design of the study.
Authors: Lebret Thierry , Rigaud Jerome , Crehange Gilles , Pello Leprince Ringuet Nathalie , Grandoulier Anne-Sophie , Thiery-Vuillemin Antoine
Published: March 2021

TPS173

Background: Prostate cancer (PCa) treatment management mostly depends on tumor aggressiveness and patient frailty. Guidelines recommend an intensification of treatment in high risk PCa, with a longer duration of androgen deprivation therapy (ADT), and, for more advanced cases, an administration for life, on top of which additional treatments may be proposed. This implies a holistic management of the patient, including management of comorbidities and ADT side effects. Triptorelin is a widely used gonadotropin-releasing hormone agonist (GnRHa). Generating data on the use of triptorelin in real life will help physicians to analyze the parameters influencing the choice of the planned duration of treatment. Methods: This prospective, multicenter, non-interventional study is conducted in France. Patients are recruited by urologists, radiation oncologists and medical oncologists. Main inclusion criteria are a histologically confirmed PCa, eligible for triptorelin therapy in its label, with a planned total duration of triptorelin treatment of at least 12 months. Decision of triptorelin treatment is made before the inclusion in the study, in the routine practice. 3 visits are planned: V1 (baseline), V2 (at 6 months), V3 (at 12 months). Primary objective of the study is to describe the proportion of patients treated continuously with triptorelin during 12 months following treatment initiation. 786 patients are planned to be enrolled, this will allow to estimate the proportion of patients treated continuously with triptorelin during 12 months following treatment initiation for an expected proportion of 80% with a precision of 3 % taking into account a drop out rate of 15%. Main secondary objectives are to describe the planned total duration of triptorelin treatment and main reason of choice, to identify parameters (tumor aggressiveness criteria, patient frailty...) associated with this planned duration, to describe the formulation and route of administration of triptorelin and reasons of choice, to identify parameters associated with this choice, to describe the change from baseline in quality of life evaluated through QLQ-PR25 questionnaire, and to describe the safety of triptorelin in the real world setting. An interim analysis on baseline data will be performed once 50% of patients are enrolled. It will focus on planned total duration of triptorelin at initiation, main reasons of choice according to circumstances of prescription, formulation and route of administration, and their reasons of choice. Clinical trial information: NCT04593420.
Study of the dosimetry, safety, and potential benefit of 177Lu-PSMA-617 radionuclide therapy prior to radical prostatectomy in men with high-risk localized prostate cancer (LuTectomy study).
Authors: Alghazo Omar , Eapen Renu , Dhiantravan Nattakorn , Violet John A. , Jackson Price , Scalzo Mark , Keam Simon P. , Mitchell Catherine , Neeson Paul J. , Sandhu Shahneen Kaur , Williams Scott , Moon Daniel , Lawrentschuk Nathan , Azad Arun , Hofman Michael S , Murphy Declan G.
Published: March 2021

TPS264

Background: High-risk localised prostate cancer (HRCaP) is treated by radical prostatectomy (RP) or radiotherapy. Despite curative intent, a significant number of men will progress with metastatic disease or local recurrence. Lutetium-177 radiolabelled to the small molecule PSMA-617 targeting prostate-specific membrane antigen (Lu-PSMA) has proven efficacious in men with metastatic castration-resistant prostate cancer who have progressed after standard-of-care. The LuTectomy trial evaluates whether administration of Lu-PSMA before radical prostatectomy in men with HRCaP will deliver high doses of radiation to the prostate and involved lymph nodes. It also aims to assess the feasibility, safety profile and oncological efficacy of Lu-PSMA. Methods: Lutectomy is an open-label, phase I/II non-randomised clinical trial. 20 men with HRCaP defined by European Association of Urology who are scheduled for RP and pelvic lymph node dissection (PLND) will be recruited. All men will have high PSMA-avidity with a standardised uptake value (SUVmax) of ≥ 20 on 68Ga-PSMA PET/CT. The initial 10 participants will receive one cycle of 5GBq Lu-PSMA intravenously and the latter 10 men will receive two cycles of 5GBq Lu-PSMA per cycle six weeks apart. RP with PLND will be performed six weeks later. Participants will be followed up for three years. The primary outcome is to determine the radiation absorbed dose in the prostate and involved lymph nodes. Three-time point quantitative single-photon emission computed tomography (SPECT/CT) will be used to estimate radiation dosimetry using a voxelated technique incorporating partial volume correction. Marrow absorbed dose will also be evaluated using serial blood measures to model pharmacokinetic clearance with a multi-phase exponential model. Translational research samples will include the original biopsy, prostatectomy specimen and plasma/whole blood samples. Secondary objectives include evaluation of the PSMA PET/CT imaging response (defined by SUVmax decline >30%), PSA response, pathological response following Lu-PSMA, adverse effects of Lu-PSMA, surgical safety, and health-related quality of life. Post estimates for time-to-event endpoints will be estimated using the Kaplan-Meier method. The first patient was recruited in July 2020 and recruitment is expected to take up to two years. ClinicalTrials.gov Identifier: NCT04430192. Funding: Movember and Medical Research Future Fund (MRFF), Endocyte Inc., a Novartis Company, E.J. Whitten Foundation. Clinical trial information: NCT04430192.
CONTACT-03: Randomized, open-label phase III study of atezolizumab plus cabozantinib versus cabozantinib monotherapy following progression on/after immune checkpoint inhibitor (ICI) treatment in patients with advanced/metastatic renal cell carcinoma.
Authors: Pal Sumanta K. , Albiges Laurence , Suarez Rodriguez Cristina , Liu Bo , Doss Jennifer , Khurana Sudha , Scheffold Christian , Voss Martin H , Choueiri Toni K.
Published: March 2021

TPS370

Background: Combining anti-angiogenic drugs with immune checkpoint inhibitors (ICI) after progression on ICIs presents a promising therapeutic approach in renal cell carcinoma (RCC). Atezolizumab (anti-PD-L1 mAb) has shown activity in combination with anti-angiogenic therapy after prior progression with ICI. Cabozantinib (VEGFR-TAM-TKI), a standard of care therapy in RCC, promotes an immune-permissive environment and may enhance atezolizumab activity. In phase Ib COSMIC-021, cabozantinib + atezolizumab safety and efficacy was favorable in clear-cell(cc) RCC and non(n)-ccRCC (Pal et al [702O] and McGregor et al [709P], ESMO 2020). The phase III CONTACT-03 study is further evaluating cabozantinib + atezolizumab vs cabozantinib in second-line/third-line RCC after prior ICC therapy. Methods: CONTACT-03 (NCT04338269) is a phase III, open-label, randomized, multicenter study that will enroll ≈500 patients across more than 150 sites globally. The trial opened in July 2020 and is actively recruiting adult patients with RCC. Key inclusion criteria include histologically confirmed locally advanced or metastatic ccRCC or nccRCC (papillary or unclassified); radiographic disease progression during or following first-line/second-line ICI treatment; measurable disease (RECIST 1.1); KPS score ≥70%; and availability of an archival tumor specimen and fresh biopsy (if clinically feasible). Patients must have adequate hematological and end organ function. Prior ICI therapy must be a PD-1/PD-L1 inhibitor (mono- or combination therapy) and must be in the immediate preceding line of therapy. Key exclusion criteria include prior treatment with cabozantinib or a mTOR inhibitor. Patients with symptomatic, untreated, or actively progressing CNS metastases or significant other intercurrent illness are not eligible. Stratification factors are IMDC risk group (0 vs 1-2 vs ≥3); line of most recent prior ICI therapy (first vs second); and histology (dominant cc without sarcomatoid vs dominant non-cc [papillary or unclassified] without sarcomatoid vs any sarcomatoid component [cc or ncc]). Patients will be randomized 1:1 to receive atezolizumab (1200 mg/IV/q3w) plus cabozantinib (60 mg/oral/qd) or cabozantinib alone (60 mg/oral/qd) until unacceptable toxicity or loss of clinical benefit. Patients will not be allowed to crossover from the control arm to the experimental arm. Multiple primary endpoints are independent review facility (IRF)-assessed PFS and OS. Additional endpoints include investigator-assessed PFS, IRF- and investigator-assessed ORR and DOR; HRQOL, biomarkers and safety. Radiographic efficacy will be assessed per RECIST 1.1. Clinical trial information: NCT04338269 .
Progresses on topological phenomena, time-driven phase transitions, and unconventional superconductivity
Authors: Guarcello C. , Citro R.
Published: March 2021

In this perspective we discuss three emerging fields of condensed matter physics which in recent years have attracted considerable attention. In particular, we consider the recent challenging topics on time-dependent phase transitions, topological phenomena, and unconventional superconductivity, with the aim to foster the community towards new applications and technological advancements. As for the time-dependent phase transitions, in recent years the experiments have shown light-induced phase transitions and new fields of application are emerging, including material design. Regarding topological materials, new challenges have arisen to detect the Majorana origin of quantized conductance in superconducting hybrid structures, as well as the effect of interaction on edge channels. Finally, concerning superconductivity, non-conventional pairing and correlation effects dominate the physics of a vast class of two-dimensional materials and novel devices were recently conceived. This work offers a comprehensive overview on these topics for promoting new ideas in these fertile fields of research.
Evidence of the Zakharov-Kolmogorov spectrum in numerical simulations of inertial wave turbulence
Authors: Le Reun T. , Favier B. , Le Bars M.
Published: March 2021

Rotating turbulence is commonly known for being dominated by geostrophic vortices that are invariant along the rotation axis and undergo an inverse cascade. Yet, it has recently been shown to sustain fully three-dimensional states with a downscale energy cascade. In this letter, we investigate the statistical properties of three-dimensional rotating turbulence by the means of direct numerical simulations in a triply periodic box where geostrophic vortices are specifically damped. The resulting turbulent flow is an inertial wave turbulence that verifies the Zakharov-Kolmogorov spectrum derived analytically by Galtier (Galtier S., Phys. Rev. E, 68 (2003) 015301), thus offering numerical proof of the relevance of wave turbulence theory for three-dimensional, anisotropic waves. Lastly, we show that the same forcing leads to either geostrophic or wave turbulence depending on the initial conditions. Our results thus bring further evidence for bi-stability in rotating turbulent flows at low Rossby numbers.
CRISPR/Cas9 mutagenesis reveals a role for ABCB1 in gut immune responses toVibrio diazotrophicusin sea urchin larvae
Authors: Fleming Travis J. , Schrankel Catherine S. , Vyas Himanshu , Rosenblatt Hannah D. , Hamdoun Amro
Published: March 2021

The ABC transporter ABCB1 plays an important role in the disposition of xenobiotics. Embryos of most species express high levels of this transporter in early development as a protective mechanism, but its native substrates are not known. Here, we used larvae of the sea urchin Strongylocentrotus purpuratus to characterize the early life expression and role of Sp-ABCB1a, a homolog of ABCB1. The results indicate that while Sp-ABCB1a is initially expressed ubiquitously, it becomes enriched in the developing gut. Using optimized CRISPR/Cas9 gene editing methods to achieve high editing efficiency in the F0 generation, we generated ABCB1a crispant embryos with significantly reduced transporter efflux activity. When infected with the opportunistic pathogen Vibrio diazotrophicus, Sp-ABCB1a crispant larvae demonstrated significantly stronger gut inflammation, immunocyte migration and cytokine Sp-IL-17 induction, as compared with infected control larvae. The results suggest an ancestral function of ABCB1 in host–microbial interactions, with implications for the survival of invertebrate larvae in the marine microbial environment.
Progeny ofXenopus laevisfrom altitudinal extremes display adaptive physiological performance
Authors: Wagener Carla , Kruger Natasha , Measey John
Published: March 2021

Environmental temperature variation generates adaptive phenotypic differentiation in widespread populations. We used a common garden experiment to determine whether offspring with varying parental origins display adaptive phenotypic variation related to different thermal conditions experienced in parental environments. We compared burst swimming performance and critical thermal limits of African clawed frog (Xenopus laevis) tadpoles bred from adults captured at high (∼2000 m above sea level) and low (∼ 5 m above sea level) altitudes. Maternal origin significantly affected swimming performance. Optimal swimming performance temperature (Topt) had a >9°C difference between tadpoles with low altitude maternal origins (pure- and cross-bred, 35.0°C) and high-altitude maternal origins (pure-bred, 25.5°C; cross-bred, 25.9°C). Parental origin significantly affected critical thermal (CT) limits. Pure-bred tadpoles with low-altitude parental origins had higher CTmax (37.8±0.8°C) than pure-bred tadpoles with high-altitude parental origins and all cross-bred tadpoles (37.0±0.8 and 37.1±0.8°C). Pure-bred tadpoles with low-altitude parental origins and all cross-bred tadpoles had higher CTmin (4.2±0.7 and 4.2±0.7°C) than pure-bred tadpoles with high-altitude parental origins (2.5±0.6°C). Our study shows that the varying thermal physiological traits of Xenopus laevis tadpoles are the result of adaptive responses to their parental thermal environments. This study is one of few demonstrating potential intraspecific evolution of critical thermal limits in a vertebrate species. Multi-generation common garden experiments and genetic analyses would be required to further tease apart the relative contribution of plastic and genetic effects to the adaptive phenotypic variation observed in these tadpoles.
Auditory perception of self and others in zebra finches: evidence from an operant discrimination task
Authors: Geberzahn Nicole , Zsebők Sándor , Derégnaucourt Sébastien
Published: March 2021

Vocal communication is essential for social interactions in many animal species. For this purpose, an animal has to perceive vocal signals of conspecifics and is often also required to discriminate conspecifics. The capacity to discriminate conspecifics is particularly important in social species in which individuals interact repeatedly. In addition, auditory perception of self plays an important role for vocal learners. A vocal learner has to memorise vocalisations of conspecifics and to subsequently modify its own vocalisations in order to match the memorised vocalisations. Here, we investigated auditory perception of self and others in zebra finches (Taeniopygia guttata), a highly gregarious songbird species and vocal learner. We used laboratory colonies in which founder males had been previously trained to produce the same song type. This resulted in artificial dialects in the song of founders and their offspring. We investigated whether those birds would be able to discriminate between familiar and unfamiliar conspecifics based on song. Furthermore, we examined whether they would classify their own song as familiar or unfamiliar. We found that birds were able to discriminate between songs of familiar versus unfamiliar conspecifics, despite the fact that all songs were imitations of the same song type. This suggests that such discrimination is possible even based on songs with a high acoustic similarity. None of the subjects classified their own song as unfamiliar. Three out of eight males classified their own song as familiar. Thus zebra finches might recognise their own song. Further experiments are needed to confirm such self-recognition.
Multiple behavior-specific cancellation signals contribute to suppressing predictable sensory reafference in a cerebellum-like structure
Authors: Lai Nicole Y. , Bell Jordan M. , Bodznick David
Published: March 2021

Movement induces sensory stimulation of an animal's own sensory receptors, termed reafference. With a few exceptions, notably vestibular and proprioception, this reafference is unwanted sensory noise and must be selectively filtered in order to detect relevant external sensory signals. In the cerebellum-like electrosensory nucleus of elasmobranch fish, an adaptive filter preserves novel signals by generating cancellation signals that suppress predictable reafference. A parallel fiber network supplies the principal Purkinje-like neurons (called ascending efferent neurons, AENs) with behavior-associated internal reference signals, including motor corollary discharge and sensory feedback, from which predictive cancellation signals are formed. How distinct behavior-specific cancellation signals interact within AENs when multiple behaviors co-occur and produce complex, changing patterns of reafference is unknown. Here, we show that when multiple streams of internal reference signals are available, cancellation signals form that are specific to parallel fiber inputs temporally correlated with, and therefore predictive of, sensory reafference. A single AEN has the capacity to form more than one cancellation signal, and AENs form multiple cancellation signals simultaneously and modify them independently during co-occurring behaviors. Cancellation signals update incrementally during continuous behaviors, as well as episodic bouts of behavior that last minutes to hours. Finally, individual AENs, independently of their neighbors, form unique AEN-specific cancellation signals that depend on the particular sensory reafferent input it receives. Together, these results demonstrate the capacity of the adaptive filter to utilize multiple cancellation signals to suppress dynamic patterns of reafference arising from complex co-occurring and intermittently performed behaviors.
Heat hardening in a pair of Anolis lizards: constraints, dynamics and ecological consequences
Authors: Deery Sean W. , Rej Julie E. , Haro Daniel , Gunderson Alex. R.
Published: March 2021

Heat tolerance plasticity is predicted to be an important buffer against global warming. Nonetheless, basal heat tolerance often correlates negatively with tolerance plasticity (‘trade-off hypothesis’), a constraint that could limit plasticity benefits. We tested the trade-off hypothesis at the individual level with respect to heat hardening in two lizard species, Anolis carolinensis and Anolis sagrei. Heat hardening is a rapid increase in heat tolerance after heat shock that is rarely measured in reptiles but is generally considered to be a first line of physiological defense against heat. We also employed a biophysical model of operative habitat temperatures to estimate the performance consequences of hardening under ecologically relevant conditions. Anolis carolinensis hardened by 2 h post-heat shock and maintained hardening for several hours. However, A. sagrei did not harden. Biophysical models showed that hardening in A. carolinensis reduces their overheating risk in the field. Therefore, while not all lizards heat harden, hardening has benefits for species that can. We initially found a negative relationship between basal tolerance and hardening within both species, consistent with the trade-off hypothesis. However, permutation analyses showed that the apparent trade-offs could not be differentiated from statistical artifact. We found the same result when we re-analyzed published data supporting the trade-off hypothesis in another lizard species. Our results show that false positives may be common when testing the trade-off hypothesis. Statistical approaches that account for this are critical to ensure that the hypothesis, which has broad implications for thermal adaptation and responses to warming, is assessed appropriately.
Catalytic Studies of Complexes of Organic Compounds. Part-4: Synthesis, Characterization, Catalytic activity of Cd (II) Complex of Chiral Schiff base
Authors: Patil C. J. , Salve S. B.
Published: March 2021

Chiral Schiff base ligand from 3,5-Diiodo-salicylaldehyde with a chiral amine (1S,2S)- (+)-1,2-Diaminocyclohexane is synthesized, and its Cd (II) complex was synthesized. These were analysed by the physical constant, TLC, colour, UV-Vis, FTIR and 1H NMR method. Also, efforts were made to study the catalytic activity of Cd (II) chiral schiff base complex. The oxidation of benzyl alcohol was used as model reaction using acetonitrile as solvent. The present reaction system was heterogeneous system of catalysis.
Activity of Laccase Enzyme Present in the Phenol-Contaminated Sediments of the Marilao-Meycauayan-Obando River System, Philippines
Authors: Martin King Dave G. , Astrero Maria Fatima T. , Mallari Laurence Anthony N. , Hipol Roland M.
Published: March 2021

Laccases are enzymes produced by different microbes like bacteria and fungi. These enzymes are members of the family of oxidases and are capable of oxidizing phenolics into non-toxic forms. Sediments were collected from the Marilao-Meycauayan-Obando River System, specifically from the sampling area connected to leather tanneries, which directly dump their effluents into the river. This study aimed to determine the presence of laccase activity of sediments of Meycauayan River where effluents of leather factories and tanneries are directly dumped. Concentration of the phenolic compounds from five collection sites were measured. Collected phenol - contaminated sediments were tested for laccase activity using ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)). Laccase was extracted from the collected sediments and used for the degradation of phenol. Reduction of phenol concentration by the extracted laccase reached 79.82% to as high as90.84%with a starting phenol concentration of 27.5 mmol per sample. Three strains of phenol-degrading ligninolytic bacteria closely related to Lysinibacillus xylanilyticus, Lysinibacillus fusiformisss, and Lysinibacillus sphaericuswere identified to be present in the river’s sediment which could produce laccase and facilitate degradation of phenol.
Synthesis, Structure and Reactivity of Schiff Base Transition Metal Mixed Ligand Complexes Derived from Isatin and Salal
Authors: S P Sridevi , C R Girija , Satish C D
Published: March 2021

A series of Isatin derivative Schiff Base ligands have been prepared by the nucleophilic addition of 5-Bromo Isatin with various amine derivatives and characterized by CHNS analysis and spectral data. Similarly, two of Salicylaldehyde ligand have been prepared by the nucleophilic addition of Salal with amine derivatives. In order to investigate the coordination behavior of these ligands and their metal complexes of the type M(acac)x, L [M = Cu(II), Ni(II); L = Schiff base ligands; x = 0 or 2] mixed ligand (chelate) have been prepared from the reaction of these ligands with their corresponding metal (Ni, Cu) acetylacetonates. The present paper was an approach to understand the chelating mixed ligand formation in complexes. All the isolated Shiff base ligands and mixed acac metal complexes were characterized by using IR, 1H NMR, UV-VIS, molar conductance and TGA/DTA analysis. The biological activities of all the isolated ligands and their corresponding mixed acac metal complexes have been used to screening against the microorganisms both gram positive and gram negative bacteria such as E.coli and S.sureus respectively, fungi A.niger and C.albicans and the results have been compared with standard and control. The main idea of these types of biological screening is to understand the role of these isolated compounds in pharmaceutical industries for drug development.
Associations Between Emotional Competence and Prosocial Behaviors With Peers Among Children With Autism Spectrum Disorder
Authors: Jahromi Laudan B. , Kirkman Katherine S. , Friedman Morgan A. , Nunnally Amanda Dimachkie
Published: March 2021

Children with autism spectrum disorder (ASD) are at risk for disrupted peer interactions. This study contributes to our understanding of how multiple foundational elements of emotional competence are related to children's prosocial behaviors with peers. Children with ASD demonstrated significantly lower non-stereotypical affective perspective taking, had lower ratings of emotion regulation, and showed differences from their typical peers in the use of discrete coping strategies during peer interactions. Children's emotion regulation and use of discrete coping strategies in the context of peers were associated with their prosocial behaviors one year later. The findings add to our understanding of how emotional development contributes to individual differences in the social-emotional behaviors of children with ASD. Implications for intervention are discussed.
Exploring Expressive Communication Skills in a Cross-Sectional Sample of Individuals With a Dual Diagnosis of Autism Spectrum Disorder and Down Syndrome
Authors: Cook Alexandria , Quinn Emily D. , Rowland Charity
Published: March 2021

Individuals with a comorbid diagnosis of Down syndrome (DS) and autism spectrum disorder (ASD) have been found to exhibit greater deficits in expressive communication than individuals with DS only. We hypothesized that individuals with a comorbid diagnosis (n = 430) would have significantly lower Communication Matrix scores and specifically social communication scores than individuals with DS alone (n = 4,352). In a sample of 4,782 individuals with DS, scores for individuals with a comorbid diagnosis were on average 18.01 points and 7.26 points lower for total score and social score respectively as compared to individuals with DS. Comorbid diagnosis accounted for 10.5% of the variance in communication scores. Between-group differences in referential gestures and symbolic communication behaviors were also observed.
Light-shift comparison of electromagnetically induced transparency and coherent population trapping in continuous-wave and Ramsey spectroscopies
Authors: Liu Xiaoyan , Zhao Xu , Xu Zhen , Hu Zhengfeng
Published: March 2021

In the atomic frequency standard, the light shift inevitably affects the long-term stability of the atomic clock. In this work, we accurately calculated the light shifts of electromagnetically induced transparency (EIT) and coherent population trapping (CPT) clocks operating under continuum and pulse sequence regimes by numerically solving the Liouville density matrix equation, including all the relaxation terms of a three-level system. The results show that the light shifts under pulse excitation are smaller than those under continuous excitation and the light shifts of the CPT process are much smaller than those of the EIT process under both excitations. It is also found that the light shifts in the continuous excitation increase and those in the pulse excitation decrease with an increase in the Rabi frequency. The light shifts will increase with an increase of the relaxations of the ground states for both the processes under both regimes. Compared to all process atomic clocks, the light shift of pulse-excited atomic clocks is the smallest, which will be suitable for many applications.
All-optical RF spectrum analyzer with a 5 THz bandwidth based on CMOS-compatible high-index doped silica waveguides
Authors: Li Yuhua , Kang Zhe , Zhu Kun , Ai Shiqi , Wang Xiang , Davidson Roy R. , Wu Yan , Morandotti Roberto , Little Brent E. , Moss David J. , Chu Sai Tak
Published: March 2021

We report an all-optical radio-frequency (RF) spectrum analyzer with a
bandwidth greater than 5 THz, based on a 50 cm long spiral waveguide
in a CMOS-compatible high-index doped silica platform. By carefully
mapping out the dispersion profile of the waveguides for different
thicknesses, we identify the optimal design to achieve near-zero
dispersion in the C-band. To demonstrate the capability of the RF
spectrum analyzer, we measure the optical output of a femtosecond
fiber laser with an ultrafast optical RF spectrum in the terahertz
regime.
Environment-friendly antisolvent tert-amyl alcohol modified hybrid perovskite photodetector with high responsivity
Authors: Li Tengteng , Li Qingyan , Tang Xin , Chen Zhiliang , Li Yifan , Zhao Hongliang , Wang Silei , Ding Xin , Zhang Yating , Yao Jianquan
Published: March 2021

The preparation of high-quality perovskite films with optimal morphologies is important for achieving high-performance perovskite photodetectors (PPDs). An effective strategy to optimize the morphologies is to add antisolvents during the spin-coating steps. In this work, a novel environment-friendly antisolvent tert-amyl alcohol (TAA) is employed first to improve the quality of perovskite films, which can effectively regulate the formation of an intermediate phase staged in between a liquid precursor phase and a solid perovskite phase due to its moderate polarity and further promote the homogeneous nucleation and crystal growth, thus leading to the formation of high-quality perovskite films and enhanced photodetector performance. As a result, the responsivity of the PPD reaches 1.56 A/W under the illumination of 532 nm laser with the power density of

6.37
  
μW
/

cm

2

at a bias voltage of

−
2
  
V

, which is good responsivity for PPDs with the vertical structure and only

CH

3

NH

3

PbI

3

perovskite as the photosensitive material. The corresponding detectivity reaches

1.47
×

10

12

Jones, while the linear dynamic range reaches 110 dB. These results demonstrate that our developed green antisolvent TAA has remarkable advantages for the fabrication of high-performance PPDs and can provide a reference for similar research work.
Using neural networks to mine text and predict metabolic traits for thousands of microbes
Authors: Hackmann Timothy J. , Zhang Bo
Published: March 2021

Microbes can metabolize more chemical compounds than any other group of organisms. As a result, their metabolism is of interest to investigators across biology. Despite the interest, information on metabolism of specific microbes is hard to access. Information is buried in text of books and journals, and investigators have no easy way to extract it out. Here we investigate if neural networks can extract out this information and predict metabolic traits. For proof of concept, we predicted two traits: whether microbes carry one type of metabolism (fermentation) or produce one metabolite (acetate). We collected written descriptions of 7,021 species of bacteria and archaea fromBergey’s Manual. We read the descriptions and manually identified (labeled) which species were fermentative or produced acetate. We then trained neural networks to predict these labels. In total, we identified 2,364 species as fermentative, and 1,009 species as also producing acetate. Neural networks could predict which species were fermentative with 97.3% accuracy. Accuracy was even higher (98.6%) when predicting species also producing acetate. Phylogenetic trees of species and their traits confirmed that predictions were accurate. Our approach with neural networks can extract information efficiently and accurately. It paves the way for putting more metabolic traits into databases, providing easy access of information to investigators.
Evaluating the effects of embedded self-massage practice on strength performance: A randomized crossover pilot trial
Authors: Kerautret Yann , Guillot Aymeric , Di Rienzo Franck
Published: March 2021

Background

Self-administered massage interventions with a roller massager are commonly used as part of warm-ups and post-workout recovery routines. There is yet no clear consensus regarding the practical guidelines for efficient embedded interventions.

Objectives

The present randomized crossover pilot trial aimed at examining the effects of a rolling intervention with a roller massager embedded within the rests periods of a resistance training protocol. The rolling intervention targeted quadriceps muscles.

Setting

Participants (n = 14) performed two resistance training protocols expected to elicit momentary muscle failure. The protocol consisted in 10 sets of 10 rest-pause repetitions of back squats, with a poundage set up at 50% of the maximal one-repetition. Two min were allocated to recovery between sets. During the recovery periods, participants completed a rolling routine with a roller massager for 60 s (Roller-massager), or underwent passive recovery (Control). The total workload, concentric power, thigh circumference rate of perceived exertion (RPE) and delayed onset of muscle soreness (DOMS) from 24 h to 120 h after completion of the protocol were the dependent variables.

Results

Roller-massager was associated with a reduction in total workload (-11.6%), concentric power (-5.1%) and an increase in perceived exertion compared to Control (p < 0.05). Roller-massager was also associated with reduced thigh circumference after the resistance training protocol, indicating reduced muscle swelling, and reduced DOMS 24 h to 120 h post-workout (p < 0.001).

Conclusion

These findings support that embedded rolling with a roller massager hinders performance and increases effort perception. Embedded interventions may not be suitable during conditioning periods designed to maximize training intensity.
Clinical Profile of Foot Gangrene and Its Outcome in a Rural Medical College
Authors: Murugiah Brinda Maheswari , Abdul Haium Anvar Ali , Govindarajan Ashok Swaminathan , Prakash Ravisankar , Mariappan Prema , Thirusangu Prem Kumar , Avwar Basha Mohamed Fazal
Published: March 2021

BACKGROUND Gangrene refers to the dead or dying body tissue (s) that occurs because the local blood supply to the tissue is either lost or is inadequate to keep the tissue alive. Foot gangrene is becoming a major concern which changes the quality of life, and also the social and economic point of view. We wanted to study the clinical profile of foot gangrene, determine the most common aetiology, distribution of age and sex, presentation, associated risk factors, commonest organisms involved, ways to find and manage the complications, and study the outcomes of foot gangrene in a rural medical college. METHODS Clinical profiles of all 50 patients with foot gangrene were studied as a prospective observational study in a rural medical college from October 2018 to October 2020. All cases were evaluated by history, clinical examination, investigations, management and follow up. RESULTS Our study involved 50 patients; youngest patient was 33 years and oldest was 70 years. Majority of patients with foot gangrene were in the age group of 41 - 50 years, (22 cases) and highest number were males, (37 cases). Diabetes mellitus is the commonest aetiology accounting for 30 cases and commonest risk factor that confounds the disease process is smoking (17 cases). The commonest presentation was blackish discoloration of toe (s) along with cellulitis and ulceration (30 cases). The commonest organism isolated from culture is methicillin resistant Staphylococcal aureus (MRSA) (13 cases). Majority of the patients underwent Ray’s amputation (16 cases) in our study and majority had no post-operative wound complication (28 cases) within the minimum follow up period of 6 months. CONCLUSIONS We have therefore attempted in our study, to analyse the gangrene of the foot since diabetic cases and trauma cases are more in the rural setup and treatment of these gangrene cases is a challenging task as well. KEY WORDS Foot Gangrene, Amputation, Diabetes Mellitus
A dcf-modellcsalád védelmében
Authors: Ulbert József
Published: March 2021

A gyakorlati adaptáció szempontjait szem előtt tartva a vállalatértékelési módszerek alkalmazhatóságát leginkább befolyásoló tényezők viszonylag jól beazonosíthatók. Ezeknek csak kisebb része vezethető vissza közvetlenül a módszertani feltételekre, nagyobb részük sokkal inkább az alkalmazás mikro- és makrogazdasági környezetrendszeréből táplálkozik. E tekintetben még ilyen halmozottan hátrányos közegben is, mint a mai hazai kkv-szektor, a klasszikus DCF-modellcsalád, véleményem szerint, semmivel nem rosszabb alkalmazkodási mechanizmusokat kelt életre, mint bármely más eljárás. Az egyedi értékelési esetekből általánosítható ajánlások fogalmazhatók meg a hazai terepen gyakorló értékelők számára.