bluuebunny/crossref_metadata_2025_split huggingface dataset:
ONE21 technique for an individualized assessment and treatment of upper face wrinkles in five pairs of identical twins with IncobotulinumtoxinA
Authors: de Sanctis Pecora Carla , Ventura Ferreira Karin , Amante Miot Hélio 
Published: February 2022

AbstractBackgroundFacial aging is a complex process, which, beyond a genetic predisposition, involves both physical and environmental factors. Even identical twins with the same genetic load may differ substantially in facial wrinkles and aging, demanding a personalized treatment approach.ObjectiveTo demonstrate the ONE21 technique as an excellent tool to a customized assessment and IncobotulinuntoxinA treatment to address phenotype discordances and epigenetic drifts in identical twins, expressed by different patterns of upper face muscle contractions and wrinkles intensity.Patients/MethodsFive pairs of identical Caucasian twin sisters, from 30 to 45 years of age, were evaluated for hyperfunctional upper facial wrinkles (forehead, glabella, and periorbital), assessing the individual anatomy, muscle function and habitual facial movements of each patient. All the subjects were treated with the ONE21 technique using IncobotulinumtoxinA and reevaluated 30 days after the procedure.ResultsThough the clinical‐anatomical pattern of the forehead contraction was similar between the pairs, the strength of the muscles, the number and depth of wrinkles differed. This varied presentation demanded distinct points of distribution and dosages of incobotulinumtoxinA for all the twins, according to the ONE21 approach. The results 30 days after treatment were satisfactory in all the subjects.ConclusionThe ONE21 technique allows an objective and careful evaluation of the wrinkles of the upper face, based on an individualized assessment, which may vary even in identical twins.
Fire stimulates grass flowering in the Cerrado independent of season
Authors: Fidelis Alessandra , Zirondi Heloiza L. , Rossatto Davi R. , Zanzarini Vagner 
Published: February 2022

AbstractQuestionsPost‐fire flowering is an underestimated plant trait of many fire‐prone ecosystems and is rarely considered for tropical savannas. Therefore, we analyzed the effects of fire season and history on post‐fire flowering of grass species in a tropical savanna (Cerrado), by evaluating the number of species, frequency of individuals and number of reproductive tillers after wet‐ and dry‐season fires, and under different fire histories.LocationsOpen savannas (campo sujo) of the Cerrado in central Brazil (Reserva Natural Serra do Tombador [RNST], 13°35–13°38′ S, 47°45′–47°51′ W).MethodsWe sampled flowering individuals in 10 Poaceae species and counted flowering/vegetative tillers of grass species in 1 m × 1 m plots after wet‐ and dry‐season fires and under different fire histories (3, 18 and 72 months post fire).ResultsSome of the studied species responded differently to fire according to season but most flowered after fire events. Moreover, the exclusion of fire led to a decrease in the number of flowering individuals and reproductive tillers of grass species.ConclusionsWe describe a unique event for tropical savannas: beside rapid resprout after fire events, grasses can allocate resources for both vegetative and reproductive tiller production, even during the dry season. If fire is excluded from the system, fewer grass species and individuals will flower and there will be a lower percentage of reproductive tillers, showing the importance of fire for grass flowering in these tropical savannas, independently of fire season.
Transmissible cancer influences immune gene expression in an endangered marsupial, the Tasmanian devil (Sarcophilus harrisii)
Authors: Raven Nynke , Klaassen Marcel , Madsen Thomas , Thomas Frédéric , Hamede Rodrigo K. , Ujvari Beata 
Published: February 2022

AbstractUnderstanding the effects of wildlife diseases on populations requires insight into local environmental conditions, host defence mechanisms, host life‐history trade‐offs, pathogen population dynamics, and their interactions. The survival of Tasmanian devils (Sarcophilus harrisii) is challenged by a novel, fitness limiting pathogen, Tasmanian devil facial tumour disease (DFTD), a clonally transmissible, contagious cancer. In order to understand the devils’ capacity to respond to DFTD, it is crucial to gain information on factors influencing the devils’ immune system. By using RT‐qPCR, we investigated how DFTD infection in association with intrinsic (sex and age) and environmental (season) factors influences the expression of 10 immune genes in Tasmanian devil blood. Our study showed that the expression of immune genes (both innate and adaptive) differed across seasons, a pattern that was altered when infected with DFTD. The expression of immunogbulins IgE and IgM:IgG showed downregulation in colder months in DFTD infected animals. We also observed strong positive association between the expression of an innate immune gene, CD16, and DFTD infection. Our results demonstrate that sampling across seasons, age groups and environmental conditions are beneficial when deciphering the complex ecoevolutionary interactions of not only conventional host‐parasite systems, but also of host and diseases with high mortality rates, such as transmissible cancers.
The cross‐cultural adaptation and factor analysis of the Turkish version of Iconographical Falls Efficacy Scale Long Version
Authors: Yağci Şentürk Aysun , Livanelioğlu Ayşe 
Published: February 2022

AbstractBackgroundIconographical Falls Efficacy Scale (Icon‐FES) is the first visual scale for fear of falling. Unlike the others, Icon‐FES, including 30 items offers a unique perspective to assess the fear of falling by providing more precise contexts.ObjectivesThe study aimed to introduce the 30‐item Icon‐FES, the first visual content fear of falling scale, into Turkish and to explore its psychometric properties.MethodsFirst, the Turkish language validity of Icon‐FES was ensured by following the forward‐backward translation protocol. A total of 150 older adults independent in their daily living activities were included in the study. Falls Efficacy Scale International (FES‐I) and Activities Specific Balance and Confidence Scale (ABC), which are frequently preferred in the literature for the same purpose, were used to provide the criterion validity of the scale. The exploratory factor analysis method was utilised for the construct validity of the scale.ResultsFactor analysis revealed a two‐factor structure. 52.22% of the total variance was explained with single‐factor analysis. In the criterion validity analysis, while there was a strong positive correlation between Icon‐FES and FES‐I (r = 0.910, p < 0.01), a strong negative correlation was found between Icon‐FES and ABC (r = −0.887, p < 0.01). The Cronbach Alpha value for the internal consistency of the scale was calculated as 0.965. The intraclass correlation coefficient between two measurements performed one‐week interval was found to be 0.985 (p < 0.001).ConclusionThe study showed that Icon‐FES is a valid, reliable and rapid result assessment tool for community‐dwelling older adults without cognitive dysfunction.
Discovery and Characterization of Intercondylar Transphyseal Complexes and their Oncological Significance in Transphyseal Extension of Pediatric Osteosarcoma
Authors: Shao Xian‐hao , Li Jian‐min , Zhang Ai‐lin , Yao Yuan , Sun Fei‐fei , Li Zhen‐zhong , Liu Tao , Cheng Kun 
Published: February 2022

ObjectiveTo explore whether there exist undiscovered transphyseal vasculature‐canal compound structures in immature femurs and tibias, and reveal their potential oncological impact.MethodsThis investigation was divided into a morphological study and a clinical study. In the morphological part, a new‐identified anatomic structure was investigated by using radiographical, anatomical, and histological methodologies. Twenty‐eight 1‐mm‐slice thickness magnetic resonance images of pediatric knees were generated and 10 pediatric knees were dissected to verify the existence and universality, observe the radiographic and anatomic characteristics, and determined the located region of this structure. Hematoxylin–eosin staining, immunofluorescence, and angiography procedures were performed to illustrate its histological feature, molecular identification, and vascular origination, respectively. In the clinical part, 38 pediatric osteosarcoma patients were enrolled from January 2014 to December 2020. A descriptive clinical study including 13 typical participants was conducted to investigate the oncological significance of this new‐identified structure. Meanwhile, the discrepancy in transphyseal osteosarcoma extension between different physeal regions was evaluated in a cross‐sectional study.ResultsIn the morphological study, we discovered a new‐found vasculature‐canal compound structure, intercondylar transphyseal complex (ITC), which originated from the middle genicular vessels, traversed the whole epiphysis, and breached the intact open physis in the immature proximal tibia or distal femur. The components of ITC included the juxta‐articular, epiphyseal, and transphyseal segments of vessels, the canals that traverse the entire epiphysis and physis and enclosed the vessels, vascular foramina on articular facet and foramina‐covered synovium. Depending on the location, ITCs can be divided into three types: femoral ITC, anterior tibial ITC, and posterior tibial ITC. Clinically, the ITC may facilitate intercondylar transphyseal sarcomatous dissemination without damaging the adjacent physeal cartilage. Compared to bilateral condylar physes, more osteosarcomas transgressed the open growth plates through intercondylar regions in which ITC was located (P = 0.022).ConclusionAs the “gap” on intact open physis, ITC, which is a new‐identified compound structure in intercondylar regions of immature femur or tibia, may promote intercondylar transphyseal tumor extension. Moreover, the identification and characterization of ITC subvert some traditional comprehensions about physis and may provide novel perspectives for pediatric osteosarcomas.
Upregulation of C4 characteristics does not consistently improve photosynthetic performance in intraspecific hybrids of a grass
Authors: Bianconi Matheus E. , Sotelo Graciela , Curran Emma V. , Milenkovic Vanja , Samaritani Emanuela , Dunning Luke T. , Bertolino Lígia T. , Osborne Colin P. , Christin Pascal‐Antoine 
Published: February 2022

AbstractC4 photosynthesis is thought to have evolved via intermediate stages, with changes towards the C4 phenotype gradually enhancing photosynthetic performance. This hypothesis is widely supported by modelling studies, but experimental tests are missing. Mixing of C4 components to generate artificial intermediates can be achieved via crossing, and the grass Alloteropsis semialata represents an outstanding study system since it includes C4 and non‐C4 populations. Here, we analyse F1 hybrids between C3 and C4, and C3+C4 and C4 genotypes to determine whether the acquisition of C4 characteristics increases photosynthetic performance. The hybrids have leaf anatomical characters and C4 gene expression profiles that are largely intermediate between those of their parents. Carbon isotope ratios are similarly intermediate, which suggests that a partial C4 cycle coexists with C3 carbon fixation in the hybrids. This partial C4 phenotype is associated with C4‐like photosynthetic efficiency in C3+C4 × C4, but not in C3 × C4 hybrids, which are overall less efficient than both parents. Our results support the hypothesis that the photosynthetic gains from the upregulation of C4 characteristics depend on coordinated changes in anatomy and biochemistry. The order of acquisition of C4 components is thus constrained, with C3+C4 species providing an essential step for C4 evolution.
Exploring Climate Change Perspectives. An Analysis of Undergraduate Students' Place‐Based Attachment in Appalachia, USA
Authors: Caretta Martina Angela , Rothrock Brandon Anthony , Zegre Nicolas P. 
Published: February 2022

AbstractDespite global scientific consensus, climate change is a highly controversial and politicized issue in the United States. Grounded in two quantitative survey iterations with approximately 446 responses, 28 semi‐structured interviews, and 4 focus groups with 60 undergraduate students from six state universities in the Appalachian region, this five‐year study explores the role of place‐based attachment and emotions in framing undergraduate students' climate change perspectives. Results show that the rural, socioeconomic status of Appalachia affects students' perspectives toward climate change and the barrage of information they are exposed to—whether scientific or media or from family—triggers uncertainty and inaction in them. They, in fact, think that climate change is happening elsewhere and will not necessarily affect them. We consider the importance, particularly in natural resource, extraction‐dependent areas of the US, to better understand students' perspectives of climate change, given their role as current and future voters and policymakers. We argue that an emotional and place‐based analysis of students' identities helps to frame climate change as an issue impacting themselves and their communities, prompting students to better articulate their perspectives on climate change.
Rattle Dynamic Model and Vibration Behaviors of Noncircular Face Gear
Authors: Liu Dawei , Zhao Guohao , Fu Zhanglei , Jin Xin 
Published: February 2022

Abstract
Noncircular face gear (NFG) is a new type of variable transmission ratio gear mechanism. Based on nonlinear dynamic theory of gear, the rattling behavior of the NFG under multifrequency excitation was studied. The generalized transmission ratio function of the NFG with closed pitch curve was constructed by Fourier series. The nonlinear relative displacement between teeth was described by an analytical expression during the process of time-varying transmission. Considering the factors of time-varying instantaneous center, meshing stiffness, transmission error, and backlash, a nonlinear dynamic model of the gear was established with the rotational angle as the independent variable. The dynamical responses were calculated by Runge–Kutta method to analyze the effects of the input speed, load torque, transmission ratio coefficient, and error on rattling behaviors. The results show that under the action of combined excitation of time-varying instantaneous center and meshing stiffness, the rattle of noncircular gear is more likely to occur. As the increase in input speed, error, and range of transmission ratio variation or the decrease of load, the NFG appears no rattling, unilateral, and bilateral rattle successively and the rattling intensity increases accordingly. The rattling threshold speed can be improved by increasing the accuracy and load of gear or decreasing the range of the transmission ratio.
Effects of SiO2/Al2O3 Ratio in ZSM-5 Zeolite on the Activity and Selectivity of a Bifunctional Cobalt Catalyst for Synthesis of Low-Pour-Point Diesel Fuels from CO and H2
Authors: Yakovenko R. E. , Zubkov I. N. , Bakun V. G. , Papeta O. P. , Savostyanov A. P. 
Published: February 2022

Abstract
This study investigates the production of diesel fuels by integrated
Fischer–Tropsch synthesis over a bifunctional cobalt catalyst consisting of a
cobalt component
(Co–Al2O3/SiO2)
and a zeolite-containing component (ZSM-5). The catalytic properties were tested
in a continuous-flow reactor with a stationary catalyst bed at 240–250°C, 2 MPa,
and gas WHSV 1000 h–1. The effects of the
SiO2/Al2O3
ratio in a HZSM-5 zeolite on the catalytic performance, catalyst deactivation
rate, and hydrocarbon and fractional compositions of the synthetic product were
identified. The low-temperature properties of the synthesized diesel fuel
satisfy the current requirements for winter fuels.
Targeting of the alphavbeta3integrin complex by CAR-T cells leads to rapid regression of diffuse intrinsic pontine glioma and glioblastoma
Authors: Cobb Dustin A , de Rossi Jacopo , Liu Lixia , An Erin , Lee Daniel W 
Published: February 2022

BackgroundDiffuse intrinsic pontine glioma (DIPG) and glioblastoma (GBM) are two highly aggressive and generally incurable gliomas with little therapeutic advancements made in the past several decades. Despite immense initial success of chimeric antigen receptor (CAR) T cells for the treatment of leukemia and lymphoma, significant headway into the application of CAR-T cells against solid tumors, including gliomas, is still forthcoming. The integrin complex alphavbeta3(αvβ3) is present on multiple and diverse solid tumor types and tumor vasculature with limited expression throughout most normal tissues, qualifying it as an appealing target for CAR-T cell-mediated immunotherapy.MethodsPatient-derived DIPG and GBM cell lines were evaluated by flow cytometry for surface expression of αvβ3. Second-generation CAR-T cells expressing an anti-αvβ3single-chain variable fragment were generated by retroviral transduction containing either a CD28 or 4-1BB costimulatory domain and CD3zeta. CAR-T cells were evaluated by flow cytometry for CAR expression, memory phenotype distribution, and inhibitory receptor profile. DIPG and GBM cell lines were orthotopically implanted into NSG mice via stereotactic injection and monitored with bioluminescent imaging to evaluate αvβ3CAR-T cell-mediated antitumor responses.ResultsWe found that patient-derived DIPG cells and GBM cell lines express high levels of surface αvβ3by flow cytometry, while αvβ3is minimally expressed on normal tissues by RNA sequencing and protein microarray. The manufactured CAR-T cells consisted of a substantial frequency of favorable early memory cells and a low inhibitory receptor profile. αvβ3CAR-T cells demonstrated efficient, antigen-specific tumor cell killing in both cytotoxicity assays and in in vivo models of orthotopically and stereotactically implanted DIPG and GBM tumors into relevant locations in the brain of NSG mice. Tumor responses were rapid and robust with systemic CAR-T cell proliferation and long-lived persistence associated with long-term survival. Following tumor clearance, TCF-1+αvβ3CAR-T cells were detectable, underscoring their ability to persist and undergo self-renewal.ConclusionsThese results highlight the potential of αvβ3CAR-T cells for immunotherapeutic treatment of aggressive brain tumors with reduced risk of on-target, off-tumor mediated toxicity due to the restricted nature of αvβ3expression in normal tissues.
Safety and efficacy of nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carcinoma: results from the phase 3b/4 CheckMate 920 trial
Authors: Tykodi Scott S , Gordan Lucio N , Alter Robert S , Arrowsmith Edward , Harrison Michael R , Percent Ivor , Singal Rakesh , Van Veldhuizen Peter , George Daniel J , Hutson Thomas , Zhang Joshua , Zoco Jesus , Johansen Jennifer L , Rezazadeh Kalebasty Arash 
Published: February 2022

BackgroundCheckMate 920 (NCT02982954) is a multicohort, phase 3b/4 clinical trial of nivolumab plus ipilimumab treatment in predominantly US community-based patients with previously untreated advanced renal cell carcinoma (RCC) and clinical features mostly excluded from phase 3 trials. We report safety and efficacy results from the advanced non-clear cell RCC (nccRCC) cohort of CheckMate 920.MethodsPatients with previously untreated advanced/metastatic nccRCC, Karnofsky performance status ≥70%, and any International Metastatic Renal Cell Carcinoma Database Consortium risk received up to four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks followed by nivolumab 480 mg every 4 weeks for ≤2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥3 immune-mediated adverse events (AEs) within 100 days of last dose of study drug. Key secondary endpoints included objective response rate (ORR), progression-free survival (PFS; both investigator-assessed), time to response (TTR), and duration of response (DOR), all using RECIST V.1.1. Overall survival (OS) was exploratory.ResultsFifty-two patients with nccRCC (unclassified histology, 42.3%; papillary, 34.6%; chromophobe, 13.5%; translocation-associated, 3.8%; collecting duct, 3.8%; renal medullary, 1.9%) received treatment. With 24.1 months minimum study follow-up, median duration of therapy (range) was 3.5 (0.0–25.8) months for nivolumab and 2.1 (0.0–3.9) months for ipilimumab. Median (range) number of doses received was 4.5 (1–28) for nivolumab and 4.0 (1–4) for ipilimumab. Grade 3–4 immune-mediated AEs were diarrhea/colitis (7.7%), rash (5.8%), nephritis and renal dysfunction (3.8%), hepatitis (1.9%), adrenal insufficiency (1.9%), and hypophysitis (1.9%). No grade 5 immune-mediated AEs occurred. ORR (n=46) was 19.6% (95% CI 9.4 to 33.9). Two patients achieved complete response (papillary, n=1; unclassified, n=1), seven achieved partial response (papillary, n=4; unclassified, n=3), and 17 had stable disease. Median TTR was 2.8 (range 2.1–14.8) months. Median DOR was not reached (range 0.0+−27.8+); eight of nine responders remain without reported progression. Median PFS (n=52) was 3.7 (95% CI 2.7 to 4.6) months. Median OS (n=52) was 21.2 (95% CI 16.6 to not estimable) months.ConclusionsNivolumab plus ipilimumab for previously untreated advanced nccRCC showed no new safety signals and encouraging antitumor activity.Trial registration numberNCT02982954.
Impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis
Authors: Kawai Taketo , Taguchi Satoru , Nakagawa Tohru , Kamei Jun , Nakamura Yu , Obinata Daisuke , Yamaguchi Kenya , Kaneko Tomoyuki , Kakutani Shigenori , Tokunaga Mayuko , Uemura Yukari , Sato Yusuke , Enomoto Yutaka , Nishimatsu Hiroaki , Fujimura Tetsuya , Fukuhara Hiroshi , Takahashi Satoru , Kume Haruki 
Published: February 2022

BackgroundSeveral studies have reported the incidence of immune-related adverse events (irAEs) as a predictor of the efficacy of anti-programmed cell death protein 1 antibodies in patients with cancer. However, immortal time bias has not always been fully addressed in these studies. In this retrospective multicenter study, we assessed the association between the incidence of irAEs and the efficacy of pembrolizumab in urothelial carcinoma (UC) using time-dependent analysis, an established statistical method to minimize immortal time bias.MethodsThe study included 176 patients with advanced UC who underwent pembrolizumab treatment at seven affiliated institutions between January 2018 and July 2020. Patients with irAEs were compared with those without irAEs in terms of overall survival (OS) and cancer-specific survival (CSS). Immortal time bias was eliminated by using time-dependent analysis.ResultsOf the 176 patients, irAEs occurred in 77 patients (43.8%), with a median of 60 days. The irAEs (+) cohort showed significantly favorable OS and CSS compared with the irAEs (−) cohort (p=0.018 and p=0.005, respectively), especially in the cohort with grade 1–2 irAEs (OS and CSS; p=0.003 and p=0.002, respectively). Multivariate analyses identified any irAEs and grade 1–2 irAEs as independent favorable prognostic factors for OS and CSS.ConclusionEven after minimizing immortal time bias by time-dependent analysis, the incidence of irAEs, especially grade 1–2 irAEs, could be a significant predictor of favorable prognoses in patients with UC who have undergone pembrolizumab treatment.