bluuebunny/crossref_metadata_2025 huggingface dataset:
Roadmap: helium ion therapy
Authors: Mairani Andrea , Mein Stewart , Blakely Eleanor , Debus Jürgen , Durante Marco , Ferrari Alfredo , Fuchs Hermann , Georg Dietmar , Grosshans David R , Guan Fada , Haberer Thomas , Harrabi Semi , Horst Felix , Inaniwa Taku , Karger Christian P , Mohan Radhe , Paganetti Harald , Parodi Katia , Sala Paola , Schuy Christoph , Tessonnier Thomas , Titt Uwe , Weber Ulrich
Published: April 2022

Helium ion beam therapy for the treatment of cancer was one of several developed and studied particle treatments in the 1950s, leading to clinical trials beginning in 1975 at the Lawrence Berkeley National Laboratory. The trial shutdown was followed by decades of research and clinical silence on the topic while proton and carbon ion therapy made debuts at research facilities and academic hospitals worldwide. The lack of progression in understanding the principle facets of helium ion beam therapy in terms of physics, biological and clinical findings persists today, mainly attributable to its highly limited availability. Despite this major setback, there is an increasing focus on evaluating and establishing clinical and research programs using helium ion beams, with both therapy and imaging initiatives to supplement the clinical palette of radiotherapy in the treatment of aggressive disease and sensitive clinical cases. Moreover, due its intermediate physical and radio-biological properties between proton and carbon ion beams, helium ions may provide a streamlined economic steppingstone towards an era of widespread use of different particle species in light and heavy ion therapy. With respect to the clinical proton beams, helium ions exhibit superior physical properties such as reduced lateral scattering and range straggling with higher relative biological effectiveness (RBE) and dose-weighted linear energy transfer (LETd) ranging from ∼4 keV μm−1 to ∼40 keV μm−1. In the frame of heavy ion therapy using carbon, oxygen or neon ions, where LETd increases beyond 100 keV μm−1, helium ions exhibit similar physical attributes such as a sharp lateral penumbra, however, with reduced radio-biological uncertainties and without potentially spoiling dose distributions due to excess fragmentation of heavier ion beams, particularly for higher penetration depths. This roadmap presents an overview of the current state-of-the-art and future directions of helium ion therapy: understanding physics and improving modeling, understanding biology and improving modeling, imaging techniques using helium ions and refining and establishing clinical approaches and aims from learned experience with protons. These topics are organized and presented into three main sections, outlining current and future tasks in establishing clinical and research programs using helium ion beams—A. Physics B. Biological and C. Clinical Perspectives.
Design and performance of a compact stick-slip type piezoelectric actuator based on right triangle flexible stator
Authors: Wang Liang , Wang Heran , Cheng Tinghai
Published: April 2022

In the field of stick-slip type piezoelectric actuators, the actuator with simple and compact structure has been given significant research and design value. A compact stick-slip piezoelectric actuator based on right triangle flexible stator is proposed and evaluated in this work. The proposed actuator only includes a right triangular type stator inserted with a PZT stack and it has the merit of simple structure. The PZT stack is excited under a sawtooth waveform voltage, and the elongation deformation of the PZT stack makes the driving foot move obliquely due to the right triangular stator. The slider is pressed under the vertical component of the oblique movement, while the slider is actuated under the horizontal component simultaneously. The working principle of the proposed actuator is illustrated by theoretical and simulation methods in detail. The proposed actuator is fabricated and its output characteristics are measured. The experimental results show that the maximum output speed of the developed actuator is 4.6 mm s−1 when the voltage and frequency are 100 V and 720 Hz. It has the merit of simple design and relatively better performance by series of comparisons with some existing works.
Systematic study of α decay half-lives for even–even nuclei within a deformed two-potential approach
Authors: Gui Hai-Feng , Liu Hong-Ming , Wu Xi-Jun , Chu Peng-Cheng , He Biao , Li Xiao-Hua
Published: April 2022

In this work, we systematically study the α decay half-lives of 196 even–even nuclei using a two-potential approach improved by considering nuclear deformation. The results show that the accuracy of this model has been improved after considering nuclear deformation. In addition, we extend this model to predict the α decay half-lives of Z = 118 and 120 isotopes by inputting the α decay energies extracted from the Weizsacker–Skyrme-type (WS-type) mass model, a simple nuclear mass formula, relativistic continuum Hartree–Bogoliubov theory and Duflo-Zuker-19 (DZ19) mass model. It is useful for identifying the new superheavy elements or isotopes for future experiments. Finally, the predicted α decay energies and half-lives of Z = 118 and 120 isotopes are analyzed, and the shell structure of superheavy nuclei is discussed. It shows that the shell effect is obvious at N = 184, while the shell effect at N = 178 depends on the nuclear mass model.
Erratum to “Accurate GW
0 band gaps and their phonon-induced renormalization in solids”
Authors: Shen Tong , Zhang Xiao-Wei , Zhang Min-Ye , Jiang Hong , Li Xin-Zheng
Published: April 2022

The derivation of Eq. (28) in the original paper [Chin. Phys. B
30 117101 (2021)] is corrected.
Enhanced photoluminescence of monolayer MoS2 on stepped gold structure
Authors: Liu Yu-Chun , Tan Xin , Shen Tian-Ci , Gu Fu-Xing
Published: April 2022

Different MoS2/Au heterostructures can play an important role in tuning the photoluminescence (PL) and optoelectrical properties of monolayer MoS2. Previous studies of PL of MoS2/Au heterostructures were mainly limited to the PL enhancement by using different Au nanostructures and PL quenching of monolayer MoS2 on flat Au surfaces. Here, we demonstrate the enhanced excitonic PL emissions of monolayer MoS2/Au heterostructures on Si/SiO2 substrates. By transferring the continuous monolayer MoS2 onto a stepped Au structure consisting of 60-nm and 100-nm Au films, the MoS2/Au-60 and MoS2/Au-100 heterostructures exhibit enhanced PL emissions, each with a blue-shifted PL peak in comparison with the MoS2/SiO2. Furthermore, the PL intensity of MoS2/Au-60 is about twice larger than that of MoS2/Au-100. The different enhanced excitonic PL emissions in MoS2/Au heterostructures can be attributed to the different charge transfer effects modified by the stepped Au structure. This work may provide an insight into the excitonic PL and charge transfer effect of MoS2 on Au film and yield novel phenomena in MoS2/Au heterostructures for further study of PL tuning and optoelectrical properties.
Synthesis of hexagonal boron nitride films by dual temperature zone low-pressure chemical vapor deposition
Authors: Zhu Zhi-Fu , Wang Shao-Tang , Zou Ji-Jun , Huang He , Sun Zhi-Jia , Xiu Qing-Lei , Zhang Zhong-Ming , Yue Xiu-Ping , Zhang Yang , Qu Jin-Hui , Gan Yong
Published: April 2022

Hexagonal boron nitride (h-BN) films are synthesized by dual temperature zone low-pressure chemical vapor deposition (LPCVD) through using a single ammonia borane precursor on non-catalytic c-plane Al2O3 substrates. The grown films are confirmed to be h-BN films by various characterization methods. Meanwhile, the growth rates and crystal quality of h-BN films at different positions in the dual temperature zone are studied. It is found that the growth rates and crystal quality of the h-BN films at different positions on the substrate are significantly different. The growth rates of the h-BN thin films show their decreasing trends with the rearward position, while the crystal quality is improved. This work provides an experimental basis for the preparation of large area wafer thick h-BN films by LPCVD.
Evidence of rapid adaptation integrated into projections of temperature-related excess mortality
Authors: Huber Veronika , Peña Ortiz Cristina , Gallego Puyol David , Lange Stefan , Sera Francesco
Published: April 2022

Few studies have used empirical evidence of past adaptation to project temperature-related excess mortality under climate change. Here, we assess adaptation in future projections of temperature-related excess mortality by employing evidence of shifting minimum mortality temperatures (MMTs) concurrent with climate warming of recent decades. The study is based on daily non-external mortality and daily mean temperature time-series from 11 Spanish cities covering four decades (1978–2017). It employs distributed lag non-linear models (DLNMs) to describe temperature-mortality associations, and multivariate mixed-effect meta-regression models to derive city- and subperiod-specific MMTs, and subsequently MMT associations with climatic indicators. We use temperature projections for one low- and one high-emission scenario (ssp126, ssp370) derived from five global climate models. Our results show that MMTs have closely tracked mean summer temperatures (MSTs) over time and space, with meta-regression models suggesting that the MMTs increased by 0.73 °C (95%CI: 0.65, 0.80) per 1 °C rise in MST over time, and by 0.84 °C (95%CI: 0.76, 0.92) per 1 °C rise in MST across cities. Future projections, which include adaptation by shifting MMTs according to observed temporal changes, result in 63.5% (95%CI: 50.0, 81.2) lower heat-related excess mortality, 63.7% (95%CI: 30.2, 166.7) higher cold-related excess mortality, and 11.2% (95%CI: −5.5, 39.5) lower total temperature-related excess mortality in the 2090s for ssp370 compared to estimates that do not account for adaptation. For ssp126, assumptions on adaptation have a comparatively small impact on excess mortality estimates. Elucidating the adaptive capacities of societies can motivate strengthened efforts to implement specific adaptation measures directed at reducing heat stress under climate change.
Navigating tensions between rapid and just low-carbon transitions
Authors: Newell Peter J , Geels Frank W , Sovacool Benjamin K
Published: April 2022

In this Perspective, we suggest that research on just transitions and energy justice needs to better attend to the increasingly important trade-offs arising from issues related to speed and acceleration of low-carbon transitions. We identify and elaborate two important tensions that policymakers face when they want to simultaneously achieve both just and rapid low-carbon transitions. First, the way in which participatory processes may increase justice but slow the speed of action; and second the way in which incumbent mobilization can accelerate transitions but entrench injustices. Such an analysis shifts the focus from mapping justice dimensions to acknowledging the inevitable trade-offs and winners and losers produced by transition processes as a first step to better navigating them.
Mapping and modeling the impact of climate change on recreational ecosystem services using machine learning and big data
Authors: Manley Kyle , Egoh Benis N
Published: April 2022

The use of recreational ecosystem services is highly dependent on the surrounding environmental and climate conditions. Due to this dependency, future recreational opportunities provided by nature are at risk from climate change. To understand how climate change will impact recreation we need to understand current recreational patterns, but traditional data is limited and low resolution. Fortunately, social media data presents an opportunity to overcome those data limitations and machine learning offers a tool to effectively use that big data. We use data from the social media site Flickr as a proxy for recreational visitation and random forest to model the relationships between social, environmental, and climate factors and recreation for the peak season (summer) in California. We then use the model to project how non-urban recreation will change as the climate changes. Our model shows that current patterns are exacerbated in the future under climate change, with currently popular summer recreation areas becoming more suitable and unpopular summer recreation areas becoming less suitable for recreation. Our model results have land management implications as recreation regions that see high visitation consequently experience impacts to surrounding ecosystems, ecosystem services, and infrastructure. This information can be used to include climate change impacts into land management plans to more effectively provide sustainable nature recreation opportunities for current and future generations. Furthermore, our study demonstrates that crowdsourced data and machine learning offer opportunities to better integrate socio-ecological systems into climate impacts research and more holistically understand climate change impacts to human well-being.
Non-Markovianity criteria for mixtures of noninvertible Pauli dynamical maps
Authors: Siudzińska Katarzyna
Published: April 2022

We analyze the connections between the non-Markovianity degree of the most general phase-damping qubit maps and their legitimate mixtures. Using the results for image non-increasing dynamical maps, we formulate the necessary and sufficient conditions for the Pauli maps to satisfy specific divisibility criteria. Next, we examine how the non-Markovianity properties for (in general noninvertible) Pauli dynamical maps influence the properties of their convex combinations. Our results are illustrated with instructive examples. For P-divisible maps, we propose a legitimate time-local generator whose all decoherence rates are temporarily infinite.
Backflow in relativistic wave equations
Authors: Bialynicki-Birula Iwo , Bialynicka-Birula Zofia , Augustynowicz Szymon
Published: April 2022

We show that, contrary to the statements made by many authors, the backflow is not a nonclassical effect. The backflow is a characteristic feature of solutions of the wave equations: quantum and classical. We present simple solutions of the Dirac equation, Maxwell equations and equations of linearized gravity where the backflow phenomenon is clearly seen. In this work we describe backflow in relativistic theories but this phenomenon can occur in the solutions of all kinds of wave equations: quantum and classical.
Critical time-dependent branching process modelling epidemic spreading with containment measures*
Authors: Sun Hanlin , Kryven Ivan , Bianconi Ginestra
Published: April 2022

During the COVID pandemic, periods of exponential growth of the disease have been mitigated by containment measures that in different occasions have resulted in a power-law growth of the number of cases. The first observation of such behaviour has been obtained from 2020 late spring data coming from China by Ziff and Ziff in reference Ziff and Ziff (2020 Fractal kinetics of COVID-19 pandemic MedRxiv). After this important observation the power-law scaling (albeit with different exponents) has also been observed in other countries during periods of containment of the spread. Early interpretations of these results suggest that this phenomenon might be due to spatial effects of the spread. Here we show that temporal modulations of infectivity of individuals due to containment measures can also cause power-law growth of the number of cases over time. To this end we propose a stochastic well-mixed susceptible-infected-removed model of epidemic spreading in presence of containment measures resulting in a time dependent infectivity and we explore the statistical properties of the resulting branching process at criticality. We show that at criticality it is possible to observe power-law growth of the number of cases with exponents ranging between one and two. Our asymptotic analytical results are confirmed by extensive Monte Carlo simulations. Although these results do not exclude that spatial effects might be important in modulating the power-law growth of the number of cases at criticality, this work shows that even well-mixed populations may already feature non trivial power-law exponents at criticality.
Effects of InGaN-interlayer on closed stripes of GaN grown by serpentine channel patterned sapphire substrate
Authors: Khan Muhammad Saddique Akbar , Lei Menglai , Chen Huanqing , Yu Guo , Lang Rui , Li Shukun , Hu Xiaodong
Published: April 2022

Gallium nitride (GaN) is a widely investigated semiconductor owing to its fascinating features suitable for a plethora of optoelectronic applications; nevertheless, high-quality growth of this material remains a challenge. In this work, the crystal quality of GaN grown by serpentine channel patterned sapphire substrates (SCPSS) is improved via introducing indium gallium nitride (InGaN) as an interlayer (IL). The closed stripes of GaN are grown by the modified design of SCPSS. Our results show that the crystal quality of GaN grown in the form of closed stripes is superior than conventionally grown counterpart. Transmission electron microscopy (TEM) revealed that the design of SCPSS controls all threading dislocations (TDs) while cathodoluminescence (CL) analysis showed that the closed stripes are relaxed and produce many TDs. Therefore, further control over the TDs was achieved by InGaN-IL. During the growth process, the temperature of GaN was reduced and 20 nm thick InGaN-IL was added at 800

°
C
.

The detailed characterization of our developed samples indicated that the additional use of InGaN-IL in SCPSS is very effective for improving the crystal quality of GaN. We anticipate that our findings will improve the current understanding about the growth of high-quality GaN towards efficient optoelectronic devices.
Development of the pellet injection system on the J-TEXT tokamak
Authors: JIANG Yingzhou , CHEN Zhongyong , LI You , YAN Wei , LUKIN A , VINYAR I , LI Feng , XU Xin , CHEN Zhipeng , YANG Zhoujun , WANG Nengchao , DING Yonghua , PAN Yuan
Published: April 2022

Pellet injection is an attractive technology for core-fueling and magnetohydrodynamic study in magnetic-confinement fusion devices like tokamaks and stellarators. It can inject solid hydrogen/deuterium pellets into the plasma with deeper density deposition compared with other fueling methods, such as gas puffing. A three-barrel H2 pellet injection system was installed on the J-TEXT tokamak and experiments were carried out. The pellets are formed in three barrels cooled by a cryocooler and compressor system at around 9 K, and are 0.8 mm/1 mm diameter and 0.8 mm length. The pellet is launched by helium propellant gas and injected from the low-field side of the plasma. The normal range of pellet speed is 210–310 m s−1 for different propellant gas pressures. Due to the three-barrel structure, the number of injected pellets can be adjusted between one and three. Pellets can be launched sequentially with arbitrary time intervals, which enables flexible applications. The results of the experiments show that pellet fueling efficiency can reach 50%. The energy confinement time increased by about 7.5‒10 ms after pellet injection.
Field-free approaches for deterministic spin–orbit torque switching of the perpendicular magnet
Authors: Wu Hao , Zhang Jing , Cui Baoshan , Razavi Seyed Armin , Che Xiaoyu , Pan Quanjun , Wu Di , Yu Guoqiang , Han Xiufeng , Wang Kang L
Published: April 2022

All-electrical driven magnetization switching attracts much attention in next-generation spintronic memory and logic devices, particularly in magnetic random-access memory (MRAM) based on the spin–orbit torque (SOT), i.e. SOT-MRAM, due to its advantages of low power consumption, fast write/read speed, and improved endurance, etc. For conventional SOT-driven switching of the magnet with perpendicular magnetic anisotropy, an external assisted magnetic field is necessary to break the inversion symmetry of the magnet, which not only induces the additional power consumption but also makes the circuit more complicated. Over the last decade, significant effort has been devoted to field-free magnetization manipulation by using SOT. In this review, we introduce the basic concepts of SOT. After that, we mainly focus on several approaches to realize the field-free deterministic SOT switching of the perpendicular magnet. The mechanisms mainly include mirror symmetry breaking, chiral symmetry breaking, exchange bias, and interlayer exchange coupling. Furthermore, we show the recent progress in the study of SOT with unconventional origin and symmetry. The final section is devoted to the industrial-level approach for potential applications of field-free SOT switching in SOT-MRAM technology.
findPC: An R package to automatically select the number of principal components in single-cell analysis
Authors: Zhuang Haotian , Wang Huimin , Ji Zhicheng
Published: April 2022

Principal component analysis is widely used in analyzing single-cell genomic data. Selecting the optimal number of principal components (PCs) is a crucial step for downstream analyses. The elbow method is most commonly used for this task, but it requires one to visually inspect the elbow plot and manually choose the elbow point. To address this limitation, we developed six methods to automatically select the optimal number of PCs based on the elbow method. We evaluated the performance of these methods on real single-cell RNA-seq data from multiple human and mouse tissues and cell types. The perpendicular line method with 30 PCs has the best overall performance, and its results are highly consistent with the numbers of PCs identified manually. We implemented the six methods in an R package, findPC, that objectively selects the number of PCs and can be easily incorporated into any automatic analysis pipeline.

Availability and Implementation

findPC R package is freely available at https://github.com/haotian-zhuang/findPC.

Supplementary information

Supplementary data are available at Bioinformatics online.
Maturation of hiPSC-derived cardiomyocytes promotes adult alternative splicing of SCN5A and reveals changes in sodium current associated with cardiac arrhythmia
Authors: Campostrini Giulia , Kosmidis Georgios , Ward-van Oostwaard Dorien , Davis Richard Paul , Yiangou Loukia , Ottaviani Daniele , Veerman Christiaan Cornelis , Mei Hailiang , Orlova Valeria Viktorovna , Wilde Arthur Arnold Maria , Bezzina Connie Rose , Verkerk Arie Otto , Mummery Christine Lindsay , Bellin Milena
Published: April 2022

Aims

Human-induced pluripotent stem cell-cardiomyocytes (hiPSC-CMs) are widely used to study arrhythmia-associated mutations in ion channels. Among these, the cardiac sodium channel SCN5A undergoes foetal-to-adult isoform switching around birth. Conventional hiPSC-CM cultures, which are phenotypically foetal, have thus far been unable to capture mutations in adult gene isoforms. Here, we investigated whether tri-cellular cross-talk in a three-dimensional (3D) cardiac microtissue (MT) promoted post-natal SCN5A maturation in hiPSC-CMs.

Methods and results

We derived patient hiPSC-CMs carrying compound mutations in the adult SCN5A exon 6B and exon 4. Electrophysiological properties of patient hiPSC-CMs in monolayer were not altered by the exon 6B mutation compared with isogenic controls since it is not expressed; further, CRISPR/Cas9-mediated excision of the foetal exon 6A did not promote adult SCN5A expression. However, when hiPSC-CMs were matured in 3D cardiac MTs, SCN5A underwent isoform switch and the functional consequences of the mutation located in exon 6B were revealed. Up-regulation of the splicing factor muscleblind-like protein 1 (MBNL1) drove SCN5A post-natal maturation in microtissues since its overexpression in hiPSC-CMs was sufficient to promote exon 6B inclusion, whilst knocking-out MBNL1 failed to foster isoform switch.

Conclusions

Our study shows that (i) the tri-cellular cardiac microtissues promote post-natal SCN5A isoform switch in hiPSC-CMs, (ii) adult splicing of SCN5A is driven by MBNL1 in these tissues, and (iii) this model can be used for examining post-natal cardiac arrhythmias due to mutations in the exon 6B.

Translational perspective

The cardiac sodium channel is essential for conducting the electrical impulse in the heart. Postnatal alternative splicing regulation causes mutual exclusive inclusion of fetal or adult exons of the corresponding gene, SCN5A. Typically, immature hiPSCCMs fall short in studying the effect of mutations located in the adult exon. We describe here that an innovative tri-cellular three-dimensional cardiac microtissue culture promotes hiPSC-CMs maturation through upregulation of MBNL1, thus revealing the effect of a pathogenic genetic variant located in the SCN5A adult exon. These results help advancing the use of hiPSC-CMs in studying adult heart disease and for developing personalized medicine applications.
Eosinophils protect pressure overload- and β-adrenoreceptor agonist-induced cardiac hypertrophy
Authors: Yang Chongzhe , Li Jie , Deng Zhiyong , Luo Songyuan , Liu Jing , Fang Wenqian , Liu Feng , Liu Tianxiao , Zhang Xian , Zhang Yuanyuan , Meng Zhaojie , Zhang Shuya , Luo Jianfang , Liu Conglin , Yang Dafeng , Liu Lijun , Sukhova Galina K , Sadybekov Anastasiia , Katritch Vsevolod , Libby Peter , Wang Jing , Guo Junli , Shi Guo-Ping
Published: April 2022

Aims

Blood eosinophil (EOS) counts and EOS cationic protein (ECP) levels associate positively with major cardiovascular disease (CVD) risk factors and prevalence. This study investigates the role of EOS in cardiac hypertrophy.

Methods and results

A retrospective cross-section study of 644 consecutive inpatients with hypertension examined the association between blood EOS counts and cardiac hypertrophy. Pressure overload- and β-adrenoreceptor agonist isoproterenol-induced cardiac hypertrophy was produced in EOS-deficient ΔdblGATA mice. This study revealed positive correlations between blood EOS counts and left ventricular (LV) mass and mass index in humans. ΔdblGATA mice showed exacerbated cardiac hypertrophy and dysfunction, with increased LV wall thickness, reduced LV internal diameter, and increased myocardial cell size, death, and fibrosis. Repopulation of EOS from wild-type (WT) mice, but not those from IL4-deficient mice ameliorated cardiac hypertrophy and cardiac dysfunctions. In ΔdblGATA and WT mice, administration of ECP mEar1 improved cardiac hypertrophy and function. Mechanistic studies demonstrated that EOS expression of IL4, IL13, and mEar1 was essential to control mouse cardiomyocyte hypertrophy and death and cardiac fibroblast TGF-β signalling and fibrotic protein synthesis. The use of human cardiac cells yielded the same results. Human ECP, EOS-derived neurotoxin, human EOS, or murine recombinant mEar1 reduced human cardiomyocyte death and hypertrophy and human cardiac fibroblast TGF-β signalling.

Conclusion

Although blood EOS counts correlated positively with LV mass or LV mass index in humans, this study established a cardioprotective role for EOS IL4 and cationic proteins in cardiac hypertrophy and tested a therapeutic possibility of ECPs in this human CVD.
Phenome-wide screening of the putative causal determinants of depression using genetic data
Authors: Aman Asma M , García-Marín Luis M , Thorp Jackson G , Campos Adrian I , Cuellar-Partida Gabriel , Martin Nicholas G , Rentería Miguel E
Published: April 2022

Depression is one of the most common mental health disorders and one of the top causes of disability throughout the world. The present study sought to identify putative causal associations between depression and hundreds of complex human traits through a genome-wide screening of genetic data and a hypothesis-free approach. We leveraged genome-wide association studies summary statistics for depression and 1504 complex traits and investigated potential causal relationships using the latent causal variable method. We identified 559 traits genetically correlated with depression risk at FDR < 5%. Of these, 46 were putative causal genetic determinants of depression, including lifestyle factors, diseases of the nervous system, respiratory disorders, diseases of the musculoskeletal system, traits related to the health of the gastrointestinal system, obesity, vitamin D levels and the use of prescription medications, among others. No phenotypes were identified as potential outcomes of depression. Our results suggest that genetic liability to multiple complex traits may contribute to a higher risk for depression. In particular, we show a putative causal genetic effect of pain, obesity and inflammation on depression. These findings provide novel insights into the potential causal determinants of depression and should be interpreted as testable hypotheses for future studies to confirm, which may facilitate the design of new prevention strategies to reduce depression’s burden.
Autoclaving time-related reduction in metabolizable energy of poultry meal is greater in growing pigs compared with broiler chickens
Authors: Sung Jung Yeol , Wiltafsky-Martin Markus K , Caroline González-Vega J , Adeola Olayiwola
Published: April 2022

The objective of this study was to determine the energy utilization responses of growing pigs and broiler chickens to poultry meal that was autoclaved at 134 °C for 0 to 180 min. Poultry meal from the same batch was autoclaved at 134 °C for 7 autoclaving times of 0, 30, 60, 90, 120, 150, or 180 min to generate 7 samples. Eight experimental diets consisting of a basal diet based on corn and soybean meal, and seven test diets in which 15% of energy-contributing ingredients in the basal diet were replaced with each of the seven poultry meal samples were used. In experiment 1, there were 64 barrows (initial body weight = 19.4 ± 1.0 kg) allotted to 8 experimental diets in a randomized complete block design with body weight as a blocking factor. Each pig received an experimental diet during 5 d of adaptation followed by 5 d of quantitative total, but separate, collection of urine and feces. In experiment 2, a total of 512 male broiler chickens at day 17 post-hatching (initial body weight = 660 ± 80 g) in 8 replicate cages were allotted to 8 experimental diets in a randomized complete block design with body weight as a blocking factor. Excreta were collected from days 20 to 22 post-hatching, and birds were euthanized by CO2 asphyxiation for ileal digesta collection. Data from experiments 1 and 2 were pooled together for statistical analysis as a 2 × 7 factorial treatment arrangement with the effect of species (pigs or broiler chickens) and autoclaving time of poultry meal (7 autoclaving times between 0 and 180 min). An interaction between species and their linear effect of autoclaving time was observed (P < 0.05) in metabolizable energy (ME) of poultry meal. Specifically, linear decrease in ME values in poultry meal with increasing autoclaving time was greater (P < 0.05) in growing pigs (4,792 to 3,897 kcal/kg dry matter) compared with broiler chickens (3,591 to 3,306 kcal/kg dry matter). The ME value of unautoclaved poultry meal was greater (P < 0.01) for pigs than broiler chickens at 4,792 vs. 3,591 kcal/kg dry matter. Although decrease in ME values with autoclaving time of poultry meal was greater in growing pigs than in broiler chickens, the ME in autoclaved poultry meal fed to pigs was greater than ME in non-autoclaved poultry meal fed to broiler chickens. Furthermore, the ratio of cysteine to crude protein concentration is a potential indicator for estimating the ratio of ME to gross energy in poultry meal for growing pigs (r2 = 0.81) and broiler chickens (r2 = 0.84).
Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG)
Authors: Desai Ami V , Robinson Giles W , Gauvain Karen , Basu Ellen M , Macy Margaret E , Maese Luke , Whipple Nicholas S , Sabnis Amit J , Foster Jennifer H , Shusterman Suzanne , Yoon Janet , Weiss Brian D , Abdelbaki Mohamed S , Armstrong Amy E , Cash Thomas , Pratilas Christine A , Corradini Nadège , Marshall Lynley V , Farid-Kapadia Mufiza , Chohan Saibah , Devlin Clare , Meneses-Lorente Georgina , Cardenas Alison , Hutchinson Katherine E , Bergthold Guillaume , Caron Hubert , Chow Maneval Edna , Gajjar Amar , Fox Elizabeth
Published: April 2022

Background

Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non–small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors.

Methods

STARTRK-NG (NCT02650401) is a phase 1/2 trial. Phase 1, dose-escalation of oral, once-daily entrectinib, enrolled patients aged <22 years with solid tumors with/without target NTRK1/2/3, ROS1, or ALK fusions. Phase 2, basket trial at the RP2D, enrolled patients with intracranial or extracranial solid tumors harboring target fusions or neuroblastoma. Primary endpoints: phase 1, RP2D based on toxicity; phase 2, objective response rate (ORR) in patients harboring target fusions. Safety-evaluable patients: ≥1 dose of entrectinib; response-evaluable patients: measurable/evaluable baseline disease and ≥1 dose at RP2D.

Results

At data cutoff, 43 patients, median age of 7 years, were response-evaluable. In phase 1, 4 patients experienced dose-limiting toxicities. The most common treatment-related adverse event was weight gain (48.8%). Nine patients experienced bone fractures (20.9%). In patients with fusion-positive tumors, ORR was 57.7% (95% CI 36.9-76.7), median duration of response was not reached, and median (interquartile range) duration of treatment was 10.6 months (4.2-18.4).

Conclusions

Entrectinib resulted in rapid and durable responses in pediatric patients with solid tumors harboring NTRK1/2/3 or ROS1 fusions.
Dichotomous Role of Jasmonic Acid in Modulating Sorghum Defense Against Aphids
Authors: Grover Sajjan , Puri Heena , Xin Zhanguo , Sattler Scott E. , Louis Joe
Published: April 2022

The precursors and derivatives of jasmonic acid (JA) contribute to plant protective immunity to insect attack. However, the role of JA in sorghum ( Sorghum bicolor) defense against sugarcane aphid (SCA) ( Melanaphis sacchari), which is considered a major threat to sorghum production, remains elusive. Sorghum SC265, previously identified as a SCA-resistant genotype among the sorghum nested association mapping founder lines, transiently increased JA at early stages of aphid feeding and deterred aphid settling. Monitoring of aphid feeding behavior using electropenetrography, a technique to unveil feeding process of piercing-sucking insects, revealed that SC265 plants restricted SCA feeding from the phloem sap. However, exogenous application of JA attenuated the resistant phenotype and promoted improved aphid feeding and colonization on SC265 plants. This was further confirmed with sorghum JA-deficient plants, in which JA deficiency promoted aphid settling, however, it also reduced aphid feeding from the phloem sap and curtailed SCA population. Exogenous application of JA caused enhanced feeding and aphid proliferation on JA-deficient plants, suggesting that JA promotes aphid growth and development. SCA feeding on JA-deficient plants altered the sugar metabolism and enhanced the levels of fructose and trehalose compared with wild-type plants. Furthermore, aphid artificial diet containing fructose and trehalose curtailed aphid growth and reproduction. Our findings underscore a previously unknown dichotomous role of JA, which may have opposing effects by deterring aphid settling during the early stage and enhancing aphid proliferative capacity during later stages of aphid colonization on sorghum plants.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Intramedullary Delivery of Autologous Bone Graft to Long Bone Defects Using Reamer Irrigator Aspirator 2 System: Technical Trick
Authors: Speirs Joshua N. , Wilson Matthew , Johnson Joey P.
Published: April 2022

Management of nonunions and bone defects remain a persistent orthopedic challenge. Traditional methods of autologous bone graft are complicated by donor site morbidity, limited graft availability, and local morbidity imposed from surgical dissection around the nonunion. This case demonstrates a method of autologous bone grafting which avoids many of these patient morbidities while delivering large volume bone graft to the nonunion site. The technique utilizes the Reamer Irrigator Aspirator 2 System to harvest and deliver ipsilateral autologous bone graft intramedullary to the distal tibia nonunion without the need for further surgical dissection. This technical trick successfully delivered a large volume of bone graft intramedullary to the nonunion site without additional surgical dissection or extra equipment. Using the Reamer Irrigator Aspirator 2 System equipment, a large volume of autologous bone graft can be delivered to the nonunion site intramedullary without additional fracture site dissection or additional harvest site morbidity.
Stereotactic Body Radiation Therapy (SBRT) for Spinal Metastases
Authors: Singh Raj , Valluri Anisha , Jenkins Jan , Davis Joanne , Vargo John A. , Sharma Sanjeev
Published: April 2022

Objective:

The objective of this study was to compare clinical outcomes following single fraction versus fractionated stereotactic body radiotherapy (SBRT) for spinal metastases.

Materials and Methods:

A multi-institutional registry was queried for patients with spinal metastases treated with single-fraction or fractionated SBRT. Potential predictive factors of local control (LC) and overall survival were evaluated. Pretreatment and posttreatment Visual Analog Scale scores were analyzed to examine initial and durable pain responses and complete response (CR) rates. Logistic regression was utilized to assess potential correlations between pain response, biologically effective dose (BED), and fractionation.

Results:

Four hundred sixty-six patients with 514 lesions treated with SBRT were identified; 209 and 104 lesions had information on LC and pain, respectively. The median pain score of patients with symptoms was 6 (range: 3 to 10). The median follow-up was 8.9 months (range: 0.4 to 125.5 mo). Utilizing Karnofsky Performance Score, age, and primary site (lung and/or nonbreast), 1-year overall survival rates were 76.1%, 59.1%, 54.9%, 37.2%, and 23.5% for patients with 0 to 4 of these factors, respectively (P<0.0001). One- and 2-year LC rates were 79.9% and 73.6%, respectively. Eighty-six patients (82.7%) had an initial pain response with a median decline of 3.5 and a CR rate of 47.1%. Sixty-five patients (62.5%) had a durable pain response with a median decline of 2 and a CR rate of 20.2%. Higher initial CR rates were observed with BED10 ≥51 Gy10 (58.7% vs. 37.9%; P=0.04).

Conclusions:

Following SBRT, encouraging palliative responses with >80% and 60% of patients having initial and durable pain responses, respectively. Dose escalation may result in improved initial CR rates. Performance status, age, and primary histology are factors to consider in the absence of pain.
Incretin-Based Drugs and the Incidence of Prostate Cancer Among Patients With Type 2 Diabetes
Authors: Lu Sally , Yin Hui , Yu Oriana H. Y. , Azoulay Laurent
Published: April 2022

Background:

There is some evidence that glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors have chemopreventive effects on prostate cancer cells but real-world evidence for this possible effect is lacking. Thus, the objective of this study was to estimate whether use of GLP-1 receptor agonists and DPP-4 inhibitors, separately, is associated with a decreased risk of prostate cancer among patients with type 2 diabetes.

Methods:

We assembled two new-user, active-comparator cohorts using the UK Clinical Practice Research Datalink (2007 to 2019). The first cohort included 5,063 initiators of GLP-1 receptor agonists and 112,955 of sulfonylureas. The second cohort included 53,529 initiators of DPP-4 inhibitors and 114,417 of sulfonylureas. We fit Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer. We weighted the models using propensity score fine stratification, which considered over 50 potential confounders.

Results:

GLP-1 receptor agonists were associated with a decreased risk of prostate cancer when compared with sulfonylureas (incidence rates = 156.4 vs. 232.0 per 100,000 person-years, respectively; HR = 0.65; 95% CI = 0.43, 0.99). DPP-4 inhibitors were also associated with a decreased risk of prostate cancer when compared with sulfonylureas (incidence rates = 316.2 vs. 350.5 events per 100,000 person-years, respectively; HR = 0.90; 95% CI = 0.81, 1.00).

Conclusions:

The results of this study are consistent with the hypothesis that the use of GLP-1 receptor agonists and DPP-4 inhibitors, separately, may decrease the risk of prostate cancer when compared with the use of sulfonylureas.
Effects of a Modified Chitosan Compound Combined with Lung Lavage after Inhalation of Depleted Uranium Dust
Authors: Xiao Yao , Zeng Feng , Fu Weilin , Zhang Yi , Chen Xiangyu , Liang Yi , Li Rong , Liu Minghua
Published: April 2022

When exposed to depleted uranium (DU), the respiratory tract is the main route for DU to enter the body. At present, lung lavage is considered to be a method for removing DU from the lung. However, there is still room for improvement in the efficiency of lung lavage. In this work, a model of DU dust inhalation injury was established in beagle dogs so that chitosan-diethylenetriaminepentaacetic nanoparticles (CS-DTPA NP) could be synthesized. The purpose of this work was to evaluate the removal efficiency of CS-DTPA NP combined with lung lavage in dogs. Results showed that 7 d after DU exposure, the diethylenetriaminepentaacetic (DTPA) and CS-DTPA NP groups showed lower U content in kidney tissue compared with the normal saline (NS) group. In the left lung tissue (lavage fluid and recovery rate of lavage fluid), the U content in the CS-DTPA NP group was higher than in the NS and DTPA groups. In terms of blood levels, the CS-DPTA NP group increased over time at 1, 3 and 7 d of DU exposure without lavage; however, the U levels in the 3 and 7 d lavage groups were significantly lower than in the non-lavage groups. IL-1 in the lavage fluid of the CS-DPTA NP and CS NPs group were lower than in the NS group. In summary, after respiratory exposure to DU, early inhalation of CS-DPTA NP may block insoluble DU particles in the lung, and if combined with lung lavage, the clearance efficiency of DU from lung tissue improves.
Outcome of COVID-19 in Patients With Mantle Cell Lymphoma—Report From the European MCL Registry
Authors: Tilch Marie-Kristin , Visco Carlo , Kinda Sandra , Hermine Olivier , Kohn Milena , Besson Caroline , Lamure Sylvain , Duléry Rémy , Ragaini Simone , Eyre Toby A. , Van Meerten Tom , Ohler Anke , Eckerle Steffen , Dreyling Martin , Hess Georg , Giné Eva , Gomes da Silva Maria
Published: April 2022

Data on outcome of patients with mantle cell lymphoma (MCL) and COVID-19 infection are limited. The European MCL (EMCL) registry is a centralized registry of the EMCL network, collecting real-world information about treatments and disease courses. During the COVID-19 pandemic, additional data on MCL patients with COVID-19 infection were collected, aiming to identify risk factors for mortality from COVID-19. In our retrospective, multicenter, international study, we collected data from 63 MCL patients with a median age of 64 years (range, 44–84) in 9 countries with evidence of a COVID-19 infection between February 2020 and October 2021. The overall mortality rate was high (44.4%), especially in hospitalized patients (61%) and in patients with need for intensive care unit care (94%). Patients receiving rituximab had significantly poorer survival than patients not receiving rituximab (P = 0.04). Our data highlight the importance of prevention strategies and underline the need for effective vaccination in this vulnerable cohort.
Endoscope-Assisted Carlevale Lens Implantation in Patients Without Capsular Support: A Novel Surgical Approach to Ensure Correct Lens Positioning
Authors: Dyrda Agnieszka , Pighin Maria S. , Jürgens Ignasi
Published: April 2022

Purpose:

To describe endoscope-assisted Carlevale intraocular lens (IOL) implantation.

Methods:

Twelve eyes underwent posterior vitrectomy combined with Carlevale IOL implantation and endoscopy in a single procedure, using a technique developed by the authors. Transscleral incisions were performed under direct visualization of the sulcus using the endoscope, and the final lens position was checked at the end of each intervention. The main outcome was to determine the exact position of all lens fixation points.

Results:

All plugs were correctly placed in the sulcus, but in seven eyes (58.3%), at least one of the closed-loop haptics was folded over the ciliary body. Repositioning was performed during the same procedure. Given that each IOL has four closed-loop haptics, the incidence of this complication was 23% (11/48).

Conclusion:

Blind implantation of Carlevale IOL may cause a high incidence of haptic malpositioning. Because the sulcus and the ciliary body are not visible under the microscope, endoscopy is the only way to ensure correct lens implantation. This new technique ensures that all lens fixation points are correctly placed by the end of surgery, avoiding complications such as decentration or tilting of the IOL, damage to the iris or the ciliary body, and uveitis.
Investigation of the Relationship Between the Alexithymic Characteristics of Secondary Students and Their Childhood Maltreatment Experiences
Authors: Özgün Hakkı , Kanak Mehmet
Published: April 2022

This research is a descriptive study aiming at revealing the difference between alexithymia levels and childhood period trauma experience levels according to variables discussed, of students who study in different high schools. In the study, quantitative method and relational survey model have been used. Five hundred ninety-nine students (57.3% female, 42.7% male) studying in 7 different high schools located in a city in the Southeastern Anatolian Region of Turkey in 2018–2019 school year constitutes the study group of the research. A proper sampling method has been used to determine the study group. In the scope of the study, Personal Information Form, Toronto Alexithymia Scale, and Childhood Trauma Questionnaire–Short Form have been used as data collection tools. In data analysis, IBM SPSS 23 Pack software has been used. In the study, it has been observed that according to multivariate analysis of variance test, which is used with the purpose of determining the effects of independent variables, difficulty in expressing feelings and childhood trauma experiences that are the lower dimension of alexithymia become drastically distinct according to school type-class level joint interaction variable. It has been observed that levels of expressing feelings, physical neglect, and emotional neglect become distinct according to school type and childhood trauma experiences, school type–age joint interaction variables.