bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeat radiofrequency catheter ablation of atrial tachycardias in patients with congenital heart disease
Authors: Klehs Sophia , Schneider Heike E. , Backhoff David , Müller Matthias J. , Paul Thomas , Krause Ulrich
Published: February 2022

Introduction

Atrial tachycardias (AT) in patients with congenital heart disease (CHD) are significantly contributing to morbidity and mortality. Aim of this study was to evaluate the long‐term course of CHD patients requiring repeat ablation procedures (RAP) of AT.

Patients and Methods

All 144 patients with CHD who had undergone ablation of AT at our center between January 2003 and October 2018 were enrolled. Patients were classified according to the complexity of CHD: complex CHD (cCHD), moderate CHD (mCHD), and simple CHD (sCHD).

Results

A total of 101 RAP were performed in 64 patients. One RAP was performed in n = 40, two in n = 13, three in n = 10, and five in n = 1. Acute success rate was 82% (83/101) and was not associated with the complexity of CHD (p = 1.0). Number of procedures was lower in patients with sCHD than in patients with mCHD and cCHD (sCHD 1.3 ± 0.6, mCHD 1.8 ± 1.0, and cCHD 1.8 ± 1.1, p = .04). RAP were most frequent in patients after Fontan palliation or Atrial switch procedure (2.0 ± 1.1 [n = 41] vs. 1.6 ± 0.9 all others, p = .016) and in patients with multiple unstable AT's (2.5 ± 1.1 [n = 11] vs. 1.7 ± 1.0, p = .008). Major complications occurred in 4/101 procedures. Complete follow‐up was available in 125 patients. Since last RAP 73% of the patients were in sinus/atrial rhythm and 34/125 patients (27%) with AT recurrence did not require re‐ablation with mean follow‐up of 52 ± 40 months.

Conclusions

Recurrences after ablation of AT in CHD patients were frequent. After RAP promising long‐term results could be achieved. Data encourage repetitive ablation procedures in this patient population.
Responses of cyprinid (Ancherythroculter nigrocauda) to flow with a semi‐circular cylinder patch
Authors: Yang Fan , Zeng Yuhong , Huai Wenxin , Zha Wei , Wan Yunjiao
Published: February 2022

Flows in river habitats are characterized by unsteady turbulence due to the existence of woody debris, boulders and vegetation. As a representative aquatic species, fish is important for the riverine ecosystems, with its complex behavioural responses to turbulent flows. Previous studies investigated the fish–vortices interaction with vortex streets by placing objects with simplified geometries centred at the flow. Nonetheless, complex river morphology in natural rivers results in much more spatially heterogeneous flows due to randomly distributed obstructions. Thus, a semi‐circular cylinder patch located on one side of the flume is used to mimic a vegetation patch at the riverbank. The patch varies in diameter (D0 = 16, 20 and 24 cm) and density (φ = 0.04 and 0.1), whereas the flow velocity is fixed at 25 cm s−1. Fish are observed to swim in three typical patterns, which are “swim around” (pattern 1), “spill” (pattern 2) and “swim through” (pattern 3). For flow with a dense patch, all three patterns are recorded, but only patterns 1 and 2 are observed in sparse patches. It is noticed that in patterns 1 and 2, fish prefer to hold place in zones of low velocity and low turbulence. Moreover, variations in patch diameter have little influence on pattern selection. Results showed that tail beat amplitude (TBA*) in each zone displayed more variations compared with tail beat frequency (TBF). In addition, Spearman's rank tests revealed that TBA* is affected by none of the four hydrodynamic variables (), whereas flow velocity imposes the most influence on TBF. Both diameter and density of the patch displayed no significant influence on TBA* and TBF.
The immunophilin CYCLOPHILIN28 affects PSII‐LHCII supercomplex assembly and accumulation in Arabidopsis thaliana
Authors: Zhu Weining , Xu Linqing , Yu Xiaoxia , Zhong Ying
Published: February 2022

In plant chloroplasts, photosystem II (PSII) complexes, together with light‐harvesting complex II (LHCII), form various PSII‐LHCII supercomplexes (SCs). This process likely involves immunophilins, but the underlying regulatory mechanisms are unclear. Here, by comparing Arabidopsis thaliana mutants lacking the chloroplast lumen‐localized immunophilin CYCLOPHILIN28 (CYP28) to wild‐type and transgenic complemented lines, we determined that CYP28 regulates the assembly and accumulation of PSII‐LHCII SCs. Compared to the wild type, cyp28 plants showed accelerated leaf growth, earlier flowering time, and enhanced accumulation of high molecular weight PSII‐LHCII SCs under normal light conditions. The lack of CYP28 also significantly affected the electron transport rate. Blue native‐polyacrylamide gel electrophoresis analysis revealed more Lhcb6 and less Lhcb4 in M‐LHCII‐Lhcb4‐Lhcb6 complexes in cyp28 versus wild‐type plants. Peptidyl‐prolyl cis/trans isomerase (PPIase) activity assays revealed that CYP28 exhibits weak PPIase activity and that its K113 and E187 residues are critical for this activity. Mutant analysis suggested that CYP28 may regulate PSII‐LHCII SC accumulation by altering the configuration of Lhcb6 via its PPIase activity. Furthermore, the Lhcb6‐P139 residue is critical for PSII‐LHCII SC assembly and accumulation. Therefore, our findings suggest that CYP28 likely regulates PSII‐LHCII SC assembly and accumulation by altering the configuration of P139 of Lhcb6 via its PPIase activity.
MdbHLH3 modulates apple soluble sugar content by activating phosphofructokinase gene expression
Authors: Yu Jian‐Qiang , Gu Kai‐Di , Zhang Li‐Li , Sun Cui‐Hui , Zhang Quan‐Yan , Wang Jia‐Hui , Wang Chu‐Kun , Wang Wen‐Yan , Du Meng‐Chi , Hu Da‐Gang
Published: February 2022

Sugars are involved in plant growth, fruit quality, and signaling perception. Therefore, understanding the mechanisms involved in soluble sugar accumulation is essential to understand fruit development. Here, we report that MdPFPβ, a pyrophosphate‐dependent phosphofructokinase gene, regulates soluble sugar accumulation by enhancing the photosynthetic performance and sugar‐metabolizing enzyme activities in apple (Malus domestica Borkh.). Biochemical analysis revealed that a basic helix‐loop‐helix (bHLH) transcription factor, MdbHLH3, binds to the MdPFPβ promoter and activates its expression, thus promoting soluble sugar accumulation in apple fruit. In addition, MdPFPβ overexpression in tomato influenced photosynthesis and carbon metabolism in the plant. Furthermore, we determined that MdbHLH3 increases photosynthetic rates and soluble sugar accumulation in apple by activating MdPFPβ expression. Our results thus shed light on the mechanism of soluble sugar accumulation in apple leaves and fruit: MdbHLH3 regulates soluble sugar accumulation by activating MdPFPβ gene expression and coordinating carbohydrate allocation.
Symplastic communication in the root cap directs auxin distribution to modulate root development
Authors: Li Meng , Wang Mengxue , Lin Qingyun , Wang Mengyao , Niu Xufang , Cheng Jie , Xu Meizhi , Qin Yaxin , Liao Xinyi , Xu Jian , Wu Shuang
Published: February 2022

Root cap not only protects root meristem, but also detects and transduces the signals of environmental changes to affect root development. The symplastic communication is an important way for plants to transduce signals to coordinate the development and physiology in response to the changing enviroments. However, it is unclear how the symplastic communication between root cap cells affects root growth. Here we exploit an inducible system to specifically block the symplastic communication in the root cap. Transient blockage of plasmodesmata (PD) in differentiated collumella cells severely impairs the root development in Arabidopsis, in particular in the stem cell niche and the proximal meristem. The neighboring stem cell niche is the region that is most sensitive to the disrupted symplastic communication and responds rapidly via the alteration of auxin distribution. In the later stage, the cell division in proximal meristem is inhibited, presumably due to the reduced auxin level in the root cap. Our results reveal the essential role of the differentiated collumella cells in the root cap mediated signaling system that directs root development.
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

Background

Facial 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.

Objective

To 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/Methods

Five 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.

Results

Though 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.

Conclusion

The 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

Questions

Post‐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.

Locations

Open 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).

Methods

We 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).

Results

Some 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.

Conclusions

We 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

Understanding 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

Background

Iconographical 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.

Objectives

The 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.

Methods

First, 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.

Results

Factor 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).

Conclusion

The 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

Objective

To explore whether there exist undiscovered transphyseal vasculature‐canal compound structures in immature femurs and tibias, and reveal their potential oncological impact.

Methods

This 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.

Results

In 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).

Conclusion

As 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

C4 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

Despite 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

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.
Optimization of the variational quantum eigensolver for quantum chemistry applications
Authors: de Keijzer R. J. P. T. , Colussi V. E. , Škorić B. , Kokkelmans S. J. J. M. F.
Published: February 2022

This work studies the variational quantum eigensolver (VQE) algorithm, which is designed to determine the ground state of a quantum mechanical system by combining classical and quantum hardware. Two methods of reducing the number of required qubit manipulations, prone to induce errors, for the variational quantum eigensolver are studied. First, we formally justify the multiple ℤ2 symmetry qubit reduction scheme first sketched by Bravyi et al. [arXiv:1701.08213 (2017)]. Second, we show that even in small, but non-trivial systems such as H2, LiH, and H2O, the choice of entangling methods (gate based or native) gives rise to varying rates of convergence to the ground state of the system. Through both the removal of qubits and the choice of entangler, the demands on the quantum hardware can be reduced. We find that in general, analyzing the VQE problem is complex, where the number of qubits, the method of entangling, and the depth of the search space all interact. In specific cases however, concrete results can be shown, and an entangling method can be recommended over others as it outperforms in terms of difference from the ground state energy.
Streamlining ethics review for international health research
Authors: Rothstein Mark A. , Zawati Ma’n H. , Thorogood Adrian , Beauvais Michael J. S. , Joly Yann , Brothers Kyle B. , Lang Michael , Andanda Pamela , Ho Calvin , Isasi Rosario , Kaye Jane , Lee Won Bok , Nnamuchi Obiajulu , Saltzman Andrea , Knoppers Bartha Maria
Published: February 2022

Single-site review means protection and efficiency
A crooked spinning black hole
Authors: Patat Ferdinando , Mapelli Michela
Published: February 2022

New observations challenge the current understanding of black hole formation
One antibody to treat them all
Authors: Biering Scott B.
Published: February 2022

Conserved flavivirus protein holds potential as target for versatile vaccines and therapies
Anticipating antibiotic resistance
Authors: Lugagne Jean-Baptiste , Dunlop Mary J.
Published: February 2022

Machine learning can use clinical history to lower the risk of infection recurrence
Inferring human evolutionary history
Authors: Rees Jasmin , Andrés Aida
Published: February 2022

Unified genetic genealogy improves our understanding of how humans evolved
Biden gets pans and praise for dividing top science positions
Authors: Mervis Jeffrey
Published: February 2022

Francis Collins named as science adviser and Alondra Nelson as head of White House science office
Oldest genomes from Africa offer glimpse of complex past
Authors: Price Michael
Published: February 2022

Signs of ice age isolation match archaeological clues
Novel viruses highlight risks of Asia’s wild animal trade
Authors: Cohen Jon
Published: February 2022

Sampling of game in China reveals many viral threats
Supplemental Material: Reconstructing source-to-sink systems from detrital zircon core and rim ages
Authors: Liu Li , al. et
Published: February 2022

Methodologies and Figure S1, sample details (Table S1), and zircon U-Pb age data of individual analyses in this study (Table S2).
Supplemental Material: Deformation and metasomatism recorded by single-grain apatite petrochronology
Authors: Odlum Margo , al. et
Published: February 2022

Detailed SEM and LA-ICP-MS methodologies, U-Pb and TREE data tables, and supplemental figures.
Supplemental Material: The Indian Ocean, its supra-subduction history, and implications for ophiolites
Authors: Moores E.M. , al. et
Published: February 2022

Figures S1-S7: Additional rare earth element plots of individual ophiolites.
Supplemental Material: Sedimentary provenance of Silurian basins in western Ireland during Iapetus closure
Authors: Riggs Nancy
Published: February 2022

Figure S1: Histograms of detrital zircon ages
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

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

Background

Diffuse 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.

Methods

Patient-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.

Results

We 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.

Conclusions

These 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

Background

CheckMate 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.

Methods

Patients 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.

Results

Fifty-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.

Conclusions

Nivolumab plus ipilimumab for previously untreated advanced nccRCC showed no new safety signals and encouraging antitumor activity.

Trial registration number

NCT02982954.
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

Background

Several 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.

Methods

The 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.

Results

Of 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.

Conclusion

Even 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.
Night work, chronotype and risk of endometrial cancer in the Screenwide case–control study
Authors: Costas Laura , Frias-Gomez Jon , Benavente Moreno Yolanda , Peremiquel-Trillas Paula , Carmona Álvaro , de Francisco Javier , Caño Victor , Paytubi Sonia , Pelegrina Beatriz , Martínez José Manuel , Pineda Marta , Brunet Joan , Vidal August , Matias-Guiu Xavier , Bosch Xavier , Ponce Jordi , Kogevinas Manolis , De Sanjosé Silvia , Alemany Laia
Published: February 2022

Background

Circadian disruption caused by night work has been associated with hormonal-related cancers such as breast and prostate cancer. Data on the role of circadian factors in the aetiology of endometrial cancer, an oestrogen-associated cancer, are scarce.

Methods

We examined the association between endometrial cancer and night shift work, chronotype (a characteristic correlating with preference for morning or evening activity) and sleep duration, in 180 incident cases and 218 hospital controls. Participants were interviewed face-to-face by trained interviewers to collect information on sociodemographic factors, familial, medical, occupational history (including work shifts), sleep duration and chronotype, and other lifestyle factors. We used logistic regression models adjusted for potential confounders to estimate ORs and 95% CIs.

Results

After adjustment by potential confounders, we found an inverse not statistically significant association between ever worked in night shifts and endometrial cancer (OR=0.64; 95% CI=0.35 to 1.16). Associations were irrespective of shift type (permanent or rotating nights) or duration of night work. We did not observe any statistically significant association between endometrial cancer and sleep duration, while inconsistent patterns were observed for chronotype and endometrial cancer risk.

Conclusions

These data do not support a role for circadian disruption in the carcinogenesis of endometrial cancer.
Strongly Connected Orientation with Minimum Lexicographic Order of Indegrees
Authors: Zhou Hongyu , Hou Xinmin
Published: February 2022

Given a simple undirected graph [Formula: see text], an orientation of [Formula: see text] is to assign every edge of [Formula: see text] a direction. Borradaile et al gave a greedy algorithm SC-Path-Reversal (in polynomial time) which finds a strongly connected orientation that minimizes the maximum indegree, and conjectured that SC-Path-Reversal is indeed optimal for the ”minimizing the lexicographic order” objective as well. In this note, we give a positive answer to the conjecture, which is that we show that the algorithm SC-PATH-REVERSAL finds a strongly connected orientation that minimizes the lexicographic order of indegrees.
Computational Argumentation for Medical Device Regulatory Classification
Authors: Almpani Sofia , Kiouvrekis Yiannis , Stefaneas Petros , Frangos Panayiotis
Published: February 2022

This work implements argumentation as the basis for modeling the relevant EU legislation concerning medical devices classification. Stakeholders can consult a web application for determining the risk-based class of a medical device based on the relevant legislation. The described approach is generally applicable to any other analogous cases of decision-making based on legislative regulations. One of the main advantages of using argumentation is the explainability and the high modularity of software permitting the extension and/or modification of the code when new relevant regulations become available.
Forty years in mathematics: Personal perspective (Part I)
Authors: Przytycki Józef H.
Published: February 2022

Conference like this in Dallas is a perfect occasion to give some reminiscences of my 40 years of work as a mathematician, and to muse a little about my mathematical past. It is a rare occasion to be a little sentimental. In this essay, I summarize and expand my birthday talk given at University of Texas at Dallas conference. There, I mostly covered the early years of my mathematical career ending with a detailed description about the smallest volume hyperbolic 3-manifold and the HOMFLYPT polynomial. Thus I seldom venture to the time after 1984 (for example to mention skein modules constructed in April 1987) and only occasionally after 1995 when I settled to work at George Washington University and have had several successful PhD students.
Nonlinear absorption in phthalocyanine thin films and solutions using a continuous wave laser
Authors: Morrison Nathaniel , Gredig Thomas
Published: February 2022

The nonlinear absorption of nanoscale thin films of iron phthalocyanine, zinc phthalocyanine, and metal-free phthalocyanine fabricated via thermal evaporation at various deposition temperatures was studied using the open-aperture z-scan method with a continuous wave laser. A solution of tetra-tert-butyl-phthalocyanine in chloroform was also studied via z-scan. The thin films exhibit pronounced saturable absorption, with the degree of nonlinearity highly dependent on the type of metal complex. No significant correlation was found between deposition temperature and nonlinear absorption. The liquid sample exhibits a transition from saturable absorption to reverse saturable absorption at high irradiance.
A Unified Transient Vibration Analysis of FGM Sandwich Plates in Thermal Environment Based on a Further Refined Zigzag Plate Theory
Authors: Shao Dong , Liang Weige , Wu Wei , Tao YongQiang
Published: February 2022

In this study, a simple and unified process is established for transient vibration analysis of functionally graded material (FGM) sandwich plates in thermal environment. The temperature field, considered constant in the plane, is distributed along the thickness with uniform, linear and nonlinear profiles. For the material properties, both temperature and position dependence are taken into account. A further refined zigzag plate theory accounting for partitioned transverse displacements and piecewise-continuous in-plane displacements is developed within the framework of Hamilton’s principle including thermal effects. Appropriately and simplicity representation of the deformation states is provided in the governing equations. A spectral analysis technique, namely, method of reverberation ray matrix (MRRM), is employed to calculate the transient vibration responses of FGM sandwich plates with general boundary conditions and arbitrary external loadings. The artificial spring technology and the equivalent wave source vector are introduced to improve the numerical stability and parametric adjustability of MRRM. The accuracy, flexibility and efficiency of the proposed process are discussed using many numerical examples. On this basis, the effects of the boundary parameters, FGM gradient index, core-to-facesheet thickness ratio, thermal properties and external loadings on the transient vibration behaviors of FGM sandwich plates are thoroughly investigated.
Generalizations of UU-rings, UJ-rings and UNJ-rings
Authors: Zhou Yiqiang
Published: February 2022

A unit-picker is a map [Formula: see text] that associates to every ring [Formula: see text] a well-defined set [Formula: see text] of central units in [Formula: see text] which contains [Formula: see text], is invariant under isomorphisms of rings, is closed under taking inverses, and which satisfies certain set containment conditions for quotient rings, corner rings and matrix rings. Let [Formula: see text] be a unit-picker. A ring [Formula: see text] is called [Formula: see text] if [Formula: see text] and [Formula: see text] if [Formula: see text] and [Formula: see text] if [Formula: see text]. An extensive study of these rings is conducted, and their connections with strongly nil [Formula: see text]-clean rings and semi [Formula: see text]-Boolean rings are investigated. When [Formula: see text] is specified, known results of [Formula: see text]-rings, [Formula: see text]-rings and [Formula: see text]-rings are obtained and new results are proved.
Discriminant and integral basis of quintic fields defined by x5 + ax + b
Authors: Jakhar Anuj , Kaur Sumandeep , Khanduja Sudesh K.
Published: February 2022

Let [Formula: see text] be an algebraic number field with [Formula: see text] a root of an irreducible trinomial [Formula: see text] belonging to [Formula: see text]. In this paper, we compute the highest power of each prime [Formula: see text] dividing the discriminant of [Formula: see text] in terms of powers of [Formula: see text] dividing [Formula: see text] and the discriminant of [Formula: see text] besides explicitly constructing a [Formula: see text]-integral basis of [Formula: see text]. These [Formula: see text]-integral bases lead to the construction of an integral basis of [Formula: see text] which is illustrated with examples.
Lie symmetry analysis and exact solutions of space-time fractional cubic Schrödinger equation
Authors: Yu Jicheng , Feng Yuqiang
Published: February 2022

In this paper, the Lie symmetry analysis method is applied to the space-time fractional cubic Schrödinger equation. The group generators are obtained for the system of space-time fractional differential equations. They are utilized to reduce the system of fractional partial differential equations with Riemann–Liouville fractional derivative to the system of fractional ordinary differential equations with Erdélyi–Kober fractional derivative. Then, the power series method is applied to derive explicit solutions for the reduced systems. Furthermore, the traveling wave solutions of the integer-order cubic Schrödinger equation is obtained.
A hyperextension assemblage, imbricated in Archean–Paleoproterozoic crust, at the base of the Kalak Nappe Complex in the northern Scandinavian Caledonides
Authors: Corfu Fernando , Andersen Torgeir B.
Published: February 2022

The break-up of continents generates dyke swarms, basins and hyperextension assemblages. Once incorporated into new orogens, the latter can provide crucial information about origins and tectonic processes. The Nålfjell Complex in the Caledonian Skillefjord Nappe of northern Norway has many of the characteristics of a hyperextension assemblage, notably the presence of solitary serpentinite bodies exposed by the exhumation of serpentinized mantle and now embedded in schists, amphibolites, mylonites, marbles and felsic gneisses. The Skillefjord Nappe is a lithologically diverse, imbricated and discontinuous allochthon. It consists of felsic gneisses and dykes dated by zircon U–Pb to
c.
3100, 2940, 2830, 2510 and 1800–1750 Ma. These rocks yield titanite ages of 2810–2700, 1750, 1660–1590 and 430–420 Ma. Metagabbro intruded at 1995 Ma. The ages and evolution of the Skillefjord Nappe are distinct from those of the structurally higher Svaertholt Terrane (>1030 Ma sediments deformed and intruded by granite at 980–950 Ma) and the Sørøy Terrane (characterized by a multi-stage 900–500 Ma evolution). The assembly of these disparate elements was completed at 420 Ma. The timing of hyperextension is uncertain. The serpentinites have a primitive Pb isotopic composition indicating old depleted mantle lithosphere. Extensional processes from the Paleoproterozoic to Ediacaran are considered.

Thematic collection:
This article is part of the Caledonian Wilson cycle collection available at:
https://www.lyellcollection.org/cc/caledonian-wilson-cycle
The Distance Function Optimization for the Near Neighbors-Based Classifiers
Authors: Jiřina Marcel , Krayem Said
Published: February 2022

Based on the analysis of conditions for a good distance function we found four rules that should be fulfilled. Then, we introduce two new distance functions, a metric and a pseudometric one. We have tested how they fit for distance-based classifiers, especially for the IINC classifier. We rank distance functions according to several criteria and tests. Rankings depend not only on criteria or nature of the statistical test, but also whether it takes into account different difficulties of tasks or whether it considers all tasks as equally difficult. We have found that the new distance functions introduced belong among the four or five best out of 23 distance functions. We have tested them on 24 different tasks, using the mean, the median, the Friedman aligned test, and the Quade test. Our results show that a suitable distance function can improve behavior of distance-based classification rules.