bluuebunny/crossref_metadata_2025_split huggingface dataset:
LUNAR: a randomized Phase 2 study of 177Lutetium‐PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (clinical trial protocol)
Authors: Ma Ting Martin , Czernin Johannes , Felix Carol , Alano Rejah , Wilhalme Holly , Valle Luca , Steinberg Michael L. , Dahlbom Magnus , Reiter Robert E. , Rettig Matthew B. , Cao Minsong , Calais Jeremie , Kishan Amar U. 
Published: February 2023

ObjectiveTo assess the efficacy of 177Lu‐PNT2002, a novel radiolabelled small molecule that binds with high affinity to prostate‐specific membrane antigen (PSMA), in combination with stereotactic body radiotherapy (SBRT) to all sites of metastasis, vs SBRT alone, in men with oligorecurrent metastatic hormone‐sensitive prostate cancer (mHSPC).Patients and MethodsThe 177Lutetium‐PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR) trial is an open‐label, randomized, stratified, two‐arm, single‐centre, Phase 2 trial to compare the efficacy and safety of neoadjuvant 177Lu‐PNT2002 plus SBRT vs SBRT alone in men with oligorecurrent mHSPC. Key eligibility criteria include one to five lesions identified on a PSMA positron emission tomography (PET)/computed tomography (CT) scan centrally reviewed by a board‐certified nuclear medicine physician. Key exclusion criteria include castrate‐resistant disease, de novo oligometastatic disease and receipt of androgen deprivation therapy (ADT) within 6 months of trial enrolment. The trial aims to enrol 100 patients who will be centrally randomized to one of the two treatment arms, in a 1:1 ratio. Patients in the control arm receive SBRT to all sites of disease. Patients in the experimental arm receive two cycles of neoadjuvant 177Lu‐PNT2002 (6.8 GBq) 6–8 weeks apart, followed by an interval PSMA PET/CT in 4–6 weeks and dose‐adapted SBRT to all sites of disease 1–2 weeks later. The primary endpoint is progression‐free survival. Secondary endpoints are radiographic and prostate‐specific antigen‐based progression, acute and late physician‐scored toxicity, patient‐reported quality of life, ADT‐free survival, time to progression, overall survival, locoregional control, and duration of response. Enrolment in the study commenced in September 2022.Results and ConclusionsThe addition of 177Lu‐PNT2002 to metastasis‐directed therapy alone may potentially further forestall disease progression. The results of this Phase 2 trial will determine, for the first time in a randomized fashion, the added benefit of 177Lu‐PNT2002 to SBRT in patients with oligorecurrent mHSPC.
Safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel acetylcholinesterase inhibitor: A phase I study in healthy young and elderly Chinese subjects
Authors: Qian Hongjie , Yu Chengyin , Zhu Huijuan , Ding Qichen , Cai Yuting , Jing Jiao , Xu Xin , Guo Runcong , Zhang Haiyan , Liu Hong , Chen Xiaoyan , Liu Yun 
Published: February 2023

AbstractThe present study evaluated the safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel acetylcholinesterase inhibitor under development for the treatment of Alzheimer's disease (AD) in otherwise healthy young and elderly Chinese subjects. The study of young subjects included the multiple ascending dose (MAD) arm (2 and 6 mg, N = 24) and the food effect arm (4 mg, N = 12) and was followed by the study of elderly subjects who were given (2 and 4 mg, N = 11). The noncompartmental analysis method was used to determine the pharmacokinetic parameters. The pharmacokinetics of fed versus fasted dose administration in the same subjects was assessed by 90% confidence interval. In the MAD arm, the accumulation ratios of DC20 in vivo were 2.29 and 2.15, respectively. In the food effect arm, compared with fasting administration, an area under the concentration‐time curve from zero to t after a standard and high‐fat diet orally administered slightly increased by about 19% and 29%, and the time to maximum concentration (Tmax) was delayed by around 1 h. For elderly study subjects, Tmax was 1.5 and 1.25 h, and terminal half‐life (t1/2) was 77.1 and 74.2 h, respectively. There were no serious adverse events (AEs), whereas gastrointestinal reactions were the most common AEs associated with the study drug. We predicted the safety risks of DC20 in the clinical treatment of AD, which were well‐tolerated by the healthy young and elderly subjects. The elimination of DC20 from the body was slower in elderly subjects than in young subjects. This study was approved by the Center for Drug Evaluation, National Medical Products Administration (CTR20181428, CTR20190664, CTR20191878, and CTR20192724).
Influence of habitat on abundance, size and growth rate of pikeperch (Sander lucioperca) 0+ juveniles in a canyon‐shaped reservoir
Authors: Blabolil Petr , Peterka Jiří , Čech Martin , Jůza Tomáš 
Published: February 2023

AbstractAbundance, size (standard length, LS) and growth rate of early pikeperch (Sander lucioperca) 0+ juveniles were monitored in the epipelagic and bathypelagic layers near the dam, and in the middle and upper sections at the canyon‐shaped Římov Reservoir (Czech Republic) during the day on 26 and 29 May, and during the night on 5 and 11 June in 2008. The greatest abundance of 0+ fish was observed in the middle section of the reservoir and their LS increased upstream from the dam towards the reservoir's tributary. Moreover, larger and older pikeperch 0+ juveniles migrated to the bathypelagic layer during the day. The epilimnetic temperature and productivity (expressed as chlorophyll‐a concentration) gradients were suggested as the main drivers affecting the distribution and growth of the fish.
The effects of delta‐9‐tetrahydrocannabinol administration in the regulation of female rat sociosexual behaviour
Authors: Costa Flávia M. , Fonseca Bruno M. , Sá Susana I. 
Published: February 2023

AbstractBy targeting the endocannabinoid system, delta‐9‐tetrahydrocannabinol (THC) modulates female motivated behaviours, influenced by sex hormones. Both medial preoptic nucleus (MPN) and ventromedial nucleus of the hypothalamus (VMN) are involved in the modulation of female sexual responses. The first triggers proceptivity, whereas the ventrolateral division of the latter (VMNvl) triggers receptivity. These nuclei are modulated by glutamate, which inhibits female receptivity, and GABA, which has a dichotomous action in female sexual motivation. Here, we evaluated the action of THC on the modulation of social and sexual behaviours, on signalling pathways of MPN and VMNvl and how sex hormones influence these parameters. Young ovariectomized female rats, given sex hormones (oestradiol benzoate, EB, and progesterone, P) and THC were used for behavioural testing and for immunofluorescence analyses of vesicular glutamate transporter 2 (VGlut2) and GAD (glutamic acid decarboxylase)67 expression. Results showed that females given EB + P exhibited a higher preference for male partner, as well as higher proceptivity and a higher receptivity than control or females given only EB. Females treated with THC presented similar responses in control or EB + P female rats and even more facilitated behavioural responses in EB females than the ones that did not receive THC. Immunofluorescence results in the MPN exhibited a decreased expression of GAD67 and VGlut2 in EB + THC‐treated female rats. Within VMNvl of EB‐primed rats no changes in the expression of both proteins were observed after THC exposure. This study demonstrates how the possible outcomes of endocannabinoid system instability within hypothalamic neuron connectivity can modify female rat sociosexual behaviour.
From remotely sensed solar‐induced chlorophyll fluorescence to ecosystem structure, function, and service: Part I—Harnessing theory
Authors: Sun Ying , Gu Lianhong , Wen Jiaming , van der Tol Christiaan , Porcar‐Castell Albert , Joiner Joanna , Chang Christine Y. , Magney Troy , Wang Lixin , Hu Leiqiu , Rascher Uwe , Zarco‐Tejada Pablo , Barrett Christopher B. , Lai Jiameng , Han Jimei , Luo Zhenqi 
Published: February 2023

AbstractSolar‐induced chlorophyll fluorescence (SIF) is a remotely sensed optical signal emitted during the light reactions of photosynthesis. The past two decades have witnessed an explosion in availability of SIF data at increasingly higher spatial and temporal resolutions, sparking applications in diverse research sectors (e.g., ecology, agriculture, hydrology, climate, and socioeconomics). These applications must deal with complexities caused by tremendous variations in scale and the impacts of interacting and superimposing plant physiology and three‐dimensional vegetation structure on the emission and scattering of SIF. At present, these complexities have not been overcome. To advance future research, the two companion reviews aim to (1) develop an analytical framework for inferring terrestrial vegetation structures and function that are tied to SIF emission, (2) synthesize progress and identify challenges in SIF research via the lens of multi‐sector applications, and (3) map out actionable solutions to tackle these challenges and offer our vision for research priorities over the next 5–10 years based on the proposed analytical framework. This paper is the first of the two companion reviews, and theory oriented. It introduces a theoretically rigorous yet practically applicable analytical framework. Guided by this framework, we offer theoretical perspectives on three overarching questions: (1) The forward (mechanism) question—How are the dynamics of SIF affected by terrestrial ecosystem structure and function? (2) The inference question: What aspects of terrestrial ecosystem structure, function, and service can be reliably inferred from remotely sensed SIF and how? (3) The innovation question: What innovations are needed to realize the full potential of SIF remote sensing for real‐world applications under climate change? The analytical framework elucidates that process complexity must be appreciated in inferring ecosystem structure and function from the observed SIF; this framework can serve as a diagnosis and inference tool for versatile applications across diverse spatial and temporal scales.
Across‐model spread and shrinking in predicting peatland carbon dynamics under global change
Authors: Hou Enqing , Ma Shuang , Huang Yuanyuan , Zhou Yu , Kim Hyung‐Sub , López‐Blanco Efrén , Jiang Lifen , Xia Jianyang , Tao Feng , Williams Christopher , Williams Mathew , Ricciuto Daniel , Hanson Paul J. , Luo Yiqi 
Published: February 2023

AbstractLarge across‐model spread in simulating land carbon (C) dynamics has been ubiquitously demonstrated in model intercomparison projects (MIPs), and became a major impediment in advancing climate change prediction. Thus, it is imperative to identify underlying sources of the spread. Here, we used a novel matrix approach to analytically pin down the sources of across‐model spread in transient peatland C dynamics in response to a factorial combination of two atmospheric CO2 levels and five temperature levels. We developed a matrix‐based MIP by converting the C cycle module of eight land models (i.e., TEM, CENTURY4, DALEC2, TECO, FBDC, CASA, CLM4.5 and ORCHIDEE) into eight matrix models. While the model average of ecosystem C storage was comparable to the measurement, the simulation differed largely among models, mainly due to inter‐model difference in baseline C residence time. Models generally overestimated net ecosystem production (NEP), with a large spread that was mainly attributed to inter‐model difference in environmental scalar. Based on the sources of spreads identified, we sequentially standardized model parameters to shrink simulated ecosystem C storage and NEP to almost none. Models generally captured the observed negative response of NEP to warming, but differed largely in the magnitude of response, due to differences in baseline C residence time and temperature sensitivity of decomposition. While there was a lack of response of NEP to elevated CO2 (eCO2) concentrations in the measurements, simulated NEP responded positively to eCO2 concentrations in most models, due to the positive responses of simulated net primary production. Our study used one case study in Minnesota peatland to demonstrate that the sources of across‐model spreads in simulating transient C dynamics can be precisely traced to model structures and parameters, regardless of their complexity, given the protocol that all the matrix models were driven by the same gross primary production and environmental variables.
How does the modern home environment impact children's mathematics knowledge? Evidence from Canadian elementary children's digital home numeracy practice (DHNP)
Authors: Alam Sabrina Shajeen , Dubé Adam Kenneth 
Published: February 2023

AbstractBackgroundA strong knowledge of mathematics, beginning at the elementary level, is critical for participation in today's complex world. The home may be one way to facilitate individualized mathematics instruction, given that children spend more time at home than in an academic institution. Therefore, researchers are interested to see whether the home numeracy environment (HNE) can provide a solid foundation for children's mathematics understanding. Further, children's digital mathematics exploration at home is increasingly common (e.g., using math apps).ObjectivesThe present study evaluates the digital home numeracy practice (DHNP) model and explores its effect on children's mathematics knowledge across five domains (numeration, number operation, pattern recognition, spatial sense, and applied problem‐solving).MethodsTo conduct this study, 117 Canadian parents and their children from Grade 1 through 5 completed a DHNP survey and a range of in‐person mathematics measures.Results and ConclusionsThe results identified significant relations between parents and children's implicit mathematics factors (e.g., math anxiety, motivation). Children's mathematics anxiety and parents' academic estimations and expectations for their children positively predicted children's mathematics knowledge. In terms of DHNP components, parental involvement in DHNP predicted children's numeration and applied problem‐solving knowledge.ImplicationsTaken together, the results detail the contribution of parental and child factors to children's mathematics knowledge and suggest that parents adjust their role in DHNP according to their children's mathematics ability.
Changes in quality of life over time in patients diagnosed with oral leukoplakia: A prospective longitudinal study
Authors: Frydrych Agnieszka M. , van Schaijik Bede , Parsons Richard , Kujan Omar 
Published: February 2023

AbstractBackgroundOral leukoplakia (OL) is one of the most prevalent oral potentially malignant disorders (OPMD). Although there is emerging evidence that quality of life (QoL) is impaired in subjects with OL; studies to date are based on single and heterogenous point‐in‐time assessments. The aim of this study was to ascertain if QoL scores change over time in individuals diagnosed with OL.MethodsForty‐one individuals with OL were administered the Short Generic Health Questionnaire (SF‐12) and the discipline‐specific Oral Potentially Malignant Disorder Questionnaire (OPMDQ) at four points in time: at the time of clinical diagnosis, at the post‐biopsy review (confirmed diagnosis), and at 3‐ and 6‐month follow‐up appointments. Responses were compared between the four time points.ResultsNo significant differences were observed in the SF‐12 questionnaire scores over time. However, a general improvement in the participants' life quality was evident over the 6‐month period under investigation in the domains of psychological and social well‐being (p = 0.0027) and effect of treatment on daily life (p = 0.0317) as well as in the total score (p = 0.0005) of the OPMDQ. Age, gender, medical status, tobacco/alcohol use, lesion site, size, the presence of dysplasia and treatment did not impact QoL scores over time.ConclusionsQoL scores of OL subjects may improve with time. Our results suggest that studies examining QoL in individuals with OL should be controlled for time at which the participants are surveyed.
Biomechanical influence of narrow‐diameter implants placed at the crestal and subcrestal level in the maxillary anterior region. A 3D finite element analysis
Authors: Cruz Ronaldo S. , Fernandes e Oliveira Hiskell Francine , Lemos Cleidiel Aparecido Araújo , de Souza Batista Victor Eduardo , Capalbo da Silva Rodrigo , Verri Fellippo R. 
Published: February 2023

AbstractPurposeTo evaluate the tendency of movement, stress distribution, and microstrain of single‐unit crowns in simulated cortical and trabecular bone, implants, and prosthetic components of narrow‐diameter implants with different lengths placed at the crestal and subcrestal levels in the maxillary anterior region using 3D finite element analysis (FEA).Materials and methodsSix 3D models were simulated using Invesalius 3.0, Rhinoceros 4.0, and SolidWorks software. Each model simulated the right anterior maxillary region including a Morse taper implant of Ø2.9 mm with different lengths (7, 10, and 13 mm) placed at the crestal and subcrestal level and supporting a cement‐retained monolithic single crown in the area of tooth 12. The FEA was performed using ANSYS 19.2. The simulated applied force was 178 N at 0°, 30°, and 60°. The results were analyzed using maps of displacement, von Mises (vM) stress, maximum principal stress, and microstrain.ResultsModels with implants at the subcrestal level showed greater displacement. vM stress increased in the implant and prosthetic components when implants were placed at the subcrestal level compared with the crestal level; the length of the implants had a low influence on the stress distribution. Higher stress and strain concentrations were observed in the cortical bone of the subcrestal placement, independent of implant length. Non‐axial loading influenced the increased stress and strain in all the evaluated structures.ConclusionsNarrow‐diameter implants positioned at the crestal level showed a more favorable biomechanical behavior for simulated cortical bone, implants, and prosthetic components. Implant length had a smaller influence on stress or strain distribution than the other variables.
Examining the role of maternity benefit comparisons and pregnancy discrimination in women's turnover decisions
Authors: Paustian‐Underdahl Samantha C. , Little Laura M. , Mandeville Ashley M. , Hinojosa Amanda S. , Keyes Andrew 
Published: February 2023

AbstractRetaining pregnant women and mothers is a prevalent challenge for companies in the United States. In this paper, we highlight the importance of favorable maternity benefits. Specifically, we argue that maternity benefits can signal how pregnant workers are treated within the organization, particularly as women compare their own benefits to referent others'. Drawing from identity threat response theory, we propose a conceptual framework that explains the influence of maternity benefit comparisons on perceptions of discrimination and, subsequently, turnover. Upon evaluating two studies using multi‐wave survey data and two vignette studies, our results indicate that when women perceive their maternity benefits to be less favorable than referent others' benefits, they perceive more pregnancy discrimination. In turn, perceptions of pregnancy discrimination influence their subsequent turnover decisions. Consistent with identity threat response theory, our results also suggest that perceived supervisor support is a significant moderator, weakening the impact of maternity benefit comparisons on perceptions of pregnancy discrimination.
Continuity, change and new ways of being: An exploratory assessment of farmer's experiences and responses to public health restrictions during the COVID‐19 pandemic in a rural Irish community
Authors: O'Reilly Alexis , Meredith David , Foley Ronan , McCarthy Jack 
Published: February 2023

AbstractFarming occupations are, in the Global North, generally solitary, and a growing body of research identifies this as one of the factors that underpins low levels of wellbeing and poor mental health amongst farmers. The primary public health response to the coronavirus disease 2019 (COVID‐19) pandemic focused on reducing transmission of the virus by limiting interactions of people. This article seeks to assess the impact of these restrictions on farmer's experience of isolation and how it shaped their wellbeing. Applying a broad socio‐ecological framework, we analyse change, continuity and shifts in social and economic relations and their spatial reconfiguration during the COVID‐19 pandemic as recounted in semi‐structured, qualitative interviews. We found that while COVID‐19 has disrupted socio‐spatial relations, including key sites of socialisation for farmers and rural communities, occupational isolation was viewed as a positive feature of farming as was working in nature. Familial and informal networks of support were important throughout the pandemic, while novel engagements with communication technologies facilitated both change and continuity of social and economic interaction. Whilst these findings are broadly positive, the reconfiguration of, particularly, economic relations is viewed as accelerating the turn towards service delivery using technology and, consequently, further reducing opportunities for social interaction.
DNA methylation variation is crucial to restore adventitious rooting ability during in vitro shoot culture‐induced rejuvenation in apple rootstock
Authors: Wang Zhe , Li Zhengnan , Wu Dongchen , Tian Qiuye , Su Shenghui , Cheng Chenxia , Nie Jiyun , Yuan Yongbing , Wang Yongzhang , Xu Xiaozhao 
Published: February 2023

SUMMARYIn vitro shoot culture has been widely used for restoring adventitious rooting ability in rooting recalcitrant woody perennial species for the past few decades, but its molecular mechanism is largely uncovered. DNA methylation is an essential epigenetic mark that participates in many biological processes. Recent reports suggested a role of DNA methylation in vitro culture in plants. In this study, we characterized the single‐base resolution DNA methylome and transcriptome of adult and in vitro shoot culture‐induced rejuvenation cuttings of apple rootstock M9T337. We found a global decrease in DNA methylation during rejuvenation, which may be correlated with increased expression of DNA demethylase genes and decreased expression of DNA methyltransferase genes. We additionally documented DNA hypomethylation in ‘T337’_R in gene protomer associated with higher transcript levels of several adventitious rooting‐related genes. The application of a DNA methylation inhibitor (5‐azacytidine) enhanced the adventitious rooting ability and the expression level of adventitious rooting‐related genes, such as, MdANT, MdMPK3, MdABCB21, MdCDC48, MdKIN8B, pri‐MdMIR156a5 and pri‐MdMIR156a12. Together, the DNA hypomethylation is critical for the rejuvenation‐dependent adventitious rooting ability in apple rootstock. In addition, increased DNA methylation was also found in thousands of genes in ‘T337’_R. We additionally documented that DNA hypermethylation is required for inhibition of adventitious rooting‐repressed genes, such as MdGAD5a, encoding glutamate decarboxylase, which can catalyze glutamate decarboxylated to form γ‐aminobutyric acid (GABA). Our results revealed that in vitro shoot culture‐dependent DNA methylation variation plays important roles in adventitious rooting in apple rootstock.