bluuebunny/crossref_metadata_2025 huggingface dataset:
The Evolution of Whistler Hiss‐Like Waves Across Plasmapause: Hiss to Exohiss
Authors: Feng Bopu , Li Haimeng , Yu Xiongdong , Yuan Zhigang , Tang Rongxin , Wang Dedong , Ouyang Zhihai , Deng Xiaohua
Published: April 2023

The exohiss waves are hiss‐like whistler mode waves that occur outside plasmapause. Although these waves can cause the loss of radiation belt electrons ∼<MeV through resonant scattering, the formation and evolution processes of exohiss waves remain incompletely covered yet. In this letter, by virtue of measurement from Van Allen Probes and ray tracing simulation, we provide a direct observational evidence for the origin of exohiss waves. We analyze the evolution of power spectrum density of hiss‐like whistler waves during their propagation. The results suggest that exohiss waves originate from mixed result of hiss waves leaked out from different L shells inside the plasmapause. Additionally, we found that frequencies of exohiss waves are primarily below 700 Hz, it is probably because the hiss waves with higher frequencies experience more severe Landau damping. Our results significantly improve understanding of the evolution of whistler waves in radiation belts.
Palliative Care Interventions Among Adolescents and Young Adults With Serious Illness: A Scoping Review
Authors: Newman Amy R. , Kenney Ansley E. , Witkowski Elizabeth , Karst Jeffrey , Lerret Stacee , Davies W. Hobart , Rothschild Charles B.
Published: April 2023

Objective:

To map the range of multidisciplinary palliative care interventions that are available to adolescents and young adults (AYAs) with serious illness.

Methods:

Scoping review methodology as outlined by Arksey and O’Malley.

Results:

Twenty-two articles describing nine specific AYA-focused, multidisciplinary palliative care interventions were included in this review. Interventions focused on supporting advance care planning, facilitating treatment decision making, managing pain, and promoting resilience, psychosocial well-being, and quality of life. Interventions were delivered face-to-face and via different eHealth platforms and were targeted to AYAs with cancer, HIV/AIDS, and cystic fibrosis in both inpatient and outpatient settings.

Conclusions:

Few evidence-based multidisciplinary palliative care interventions have documented benefits for AYAs with serious illness. The limited work that has been done demonstrates that AYAs are open to engaging in palliative care interventions and suggests that individual members of the multidisciplinary team can implement these different interventions to support enhanced patient outcomes.

Implications for Impact Statement

Adolescents and young adults with serious illness benefit from palliative care interventions, yet only a limited number of interventions have been developed to meet their unique physical, psychological, and developmental needs. Pediatric psychologists can contribute to the development and implementation of interventions aimed to enhance the quality of life and illness experience among these patients.
Adapter CAR T cells to counteract T-cell exhaustion and enable flexible targeting in AML
Authors: Nixdorf D. , Sponheimer M. , Berghammer D. , Engert F. , Bader U. , Philipp N. , Kazerani M. , Straub T. , Rohrbacher L. , Wange L. , Dapa S. , Atar D. , Seitz C. M. , Brandstetter K. , Linder A. , von Bergwelt M. , Leonhardt H. , Mittelstaet J. , Kaiser A. , Bücklein V. , Subklewe M.
Published: April 2023

Although the landscape for treating acute myeloid leukemia (AML) patients has changed substantially in recent years, the majority of patients will eventually relapse and succumb to their disease. Allogeneic stem cell transplantation provides the best anti-AML treatment strategy, but is only suitable in a minority of patients. In contrast to B-cell neoplasias, chimeric antigen receptor (CAR) T-cell therapy in AML has encountered challenges in target antigen heterogeneity, safety, and T-cell dysfunction. We established a Fab-based adapter CAR (AdCAR) T-cell platform with flexibility of targeting and control of AdCAR T-cell activation. Utilizing AML cell lines and a long-term culture assay for primary AML cells, we were able to demonstrate AML-specific cytotoxicity using anti-CD33, anti-CD123, and anti-CLL1 adapter molecules in vitro and in vivo. Notably, we show for the first time the feasibility of sequential application of adapter molecules of different specificity in primary AML co-cultures. Importantly, using the AML platform, we were able to demonstrate that chronic T-cell stimulation and exhaustion can be counteracted through introduction of treatment-free intervals. As T-cell exhaustion and target antigen heterogeneity are well-known causes of resistance, the AdCAR platform might offer effective strategies to ameliorate these limitations.
3D Printing and processing of miniaturized transducers with near-pristine piezoelectric ceramics for localized cavitation
Authors: Lu Haotian , Cui Huachen , Lu Gengxi , Jiang Laiming , Hensleigh Ryan , Zeng Yushun , Rayes Adnan , Panduranga Mohanchandra K. , Acharya Megha , Wang Zhen , Irimia Andrei , Wu Felix , Carman Gregory P. , Morales José M. , Putterman Seth , Martin Lane W. , Zhou Qifa , Zheng Xiaoyu
Published: April 2023

The performance of ultrasonic transducers is largely determined by the piezoelectric properties and geometries of their active elements. Due to the brittle nature of piezoceramics, existing processing tools for piezoelectric elements only achieve simple geometries, including flat disks, cylinders, cubes and rings. While advances in additive manufacturing give rise to free-form fabrication of piezoceramics, the resultant transducers suffer from high porosity, weak piezoelectric responses, and limited geometrical flexibility. We introduce optimized piezoceramic printing and processing strategies to produce highly responsive piezoelectric microtransducers that operate at ultrasonic frequencies. The 3D printed dense piezoelectric elements achieve high piezoelectric coefficients and complex architectures. The resulting piezoelectric charge constant, d33, and coupling factor, kt, of the 3D printed piezoceramic reach 583 pC/N and 0.57, approaching the properties of pristine ceramics. The integrated printing of transducer packaging materials and 3D printed piezoceramics with microarchitectures create opportunities for miniaturized piezoelectric ultrasound transducers capable of acoustic focusing and localized cavitation within millimeter-sized channels, leading to miniaturized ultrasonic devices that enable a wide range of biomedical applications.
Expression-based subtypes define pathologic response to neoadjuvant immune-checkpoint inhibitors in muscle-invasive bladder cancer
Authors: Robertson A. Gordon , Meghani Khyati , Cooley Lauren Folgosa , McLaughlin Kimberly A. , Fall Leigh Ann , Yu Yanni , Castro Mauro A. A. , Groeneveld Clarice S. , de Reyniès Aurélien , Nazarov Vadim I. , Tsvetkov Vasily O. , Choy Bonnie , Raggi Daniele , Marandino Laura , Montorsi Francesco , Powles Thomas , Necchi Andrea , Meeks Joshua J.
Published: April 2023

Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced-stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling. We identify five distinctive genetic and transcriptomic programs and validate these in an independent neoadjuvant CPI trial to identify the features of response or resistance to CPI. By modeling the regulatory network, we identify the histone demethylase KDM5B as a repressor of tumor immune signaling pathways in one resistant subtype (S1, Luminal-excluded) and demonstrate that inhibition of KDM5B enhances immunogenicity in FGFR3-mutated BCa cells. Our study identifies signatures associated with response to CPI that can be used to molecularly stratify patients and suggests therapeutic alternatives for subtypes with poor response to neoadjuvant immunotherapy.
What the geological past can tell us about the future of the ocean’s twilight zone
Authors: Crichton Katherine A. , Wilson Jamie D. , Ridgwell Andy , Boscolo-Galazzo Flavia , John Eleanor H. , Wade Bridget S. , Pearson Paul N.
Published: April 2023

Paleontological reconstructions of plankton community structure during warm periods of the Cenozoic (last 66 million years) reveal that deep-dwelling ‘twilight zone’ (200–1000 m) plankton were less abundant and diverse, and lived much closer to the surface, than in colder, more recent climates. We suggest that this is a consequence of temperature’s role in controlling the rate that sinking organic matter is broken down and metabolized by bacteria, a process that occurs faster at warmer temperatures. In a warmer ocean, a smaller fraction of organic matter reaches the ocean interior, affecting food supply and dissolved oxygen availability at depth. Using an Earth system model that has been evaluated against paleo observations, we illustrate how anthropogenic warming may impact future carbon cycling and twilight zone ecology. Our findings suggest that significant changes are already underway, and without strong emissions mitigation, widespread ecological disruption in the twilight zone is likely by 2100, with effects spanning millennia thereafter.
Exploiting synergistic effect of CO/NO gases for soft tissue transplantation using a hydrogel patch
Authors: Tang Xiaoduo , Ren Jingyan , Wei Xin , Wang Tao , Li Haiqiu , Sun Yihan , Liu Yang , Chi Mingli , Zhu Shoujun , Lu Laijin , Zhang Junhu , Yang Bai
Published: April 2023

Autologous skin flap transplantation is a common method for repairing complex soft tissue defects caused by cancer, trauma, and congenital malformations. Limited blood supply range and post-transplantation ischemia-reperfusion injury can lead to distal necrosis of the flap and long-term functional loss, which severely restricts the decision-making regarding the optimal surgical plan. To address this issue, we develop a hydrogel patch that releases carbon monoxide and nitric oxide gases on demand, to afford a timely blood supply for skin flap transplantation during surgery. Using an ischemia-reperfusion dorsal skin flap model in rats, we show that the hydrogel patch maintains the immediate opening of blood flow channels in transplanted tissue and effective blood perfusion throughout the perioperative period, activating perfusion of the hemodynamic donor site. We demonstrate that the hydrogel patch promotes distal vascularization and long-term functional reconstruction of transplanted tissues by inhibiting inflammatory damage and accelerating blood vessel formation.
Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction
Authors: Sülzen Hagen , Began Jakub , Dhillon Arun , Kereïche Sami , Pompach Petr , Votrubova Jitka , Zahedifard Farnaz , Šubrtova Adriana , Šafner Marie , Hubalek Martin , Thompson Maaike , Zoltner Martin , Zoll Sebastian
Published: April 2023

African Trypanosomes have developed elaborate mechanisms to escape the adaptive immune response, but little is known about complement evasion particularly at the early stage of infection. Here we show that ISG65 of the human-infective parasite Trypanosoma brucei gambiense is a receptor for human complement factor C3 and its activation fragments and that it takes over a role in selective inhibition of the alternative pathway C5 convertase and thus abrogation of the terminal pathway. No deposition of C4b, as part of the classical and lectin pathway convertases, was detected on trypanosomes. We present the cryo-electron microscopy (EM) structures of native C3 and C3b in complex with ISG65 which reveal a set of modes of complement interaction. Based on these findings, we propose a model for receptor-ligand interactions as they occur at the plasma membrane of blood-stage trypanosomes and may facilitate innate immune escape of the parasite.
Giant dynamic electromechanical response via field driven pseudo-ergodicity in nonergodic relaxors
Authors: Qi He , Hu Tengfei , Deng Shiqing , Liu Hui , Fu Zhengqian , Chen Jun
Published: April 2023

Enhanced electromechanical response can commonly be found during the crossover from normal to relaxor ferroelectric state, making relaxors to be potential candidates for actuators. In this work, (Pb0.917La0.083)(Zr0.65Ti0.35)0.97925O3 ceramic was taken as a case study, which shows a critical nonergodic state with both double-like P-E loop and irreversible relaxor-normal ferroelectric phase after poling at room temperature. The low-hysteresis linear-like S-P2 loop, in-situ synchrotron X-ray diffraction and transmission electron microscope results suggest that the nonpolar relaxor state acts as a bridge during polarization reorientation process, accompanying which lattice strain contributes to 61.8% of the total strain. In other words, the transformation from normal ferroelectric to nonergodic relaxor state could be triggered by electric field through polarization contraction, which could change to be spontaneously with slightly increasing temperature in the nonergodic relaxor zone. Therefore, pseudo-ergodicity in nonergodic relaxors (i.e. reversible nonergodic-normal ferroelectric phase transition) driven by periodic electric field should be the main mechanism for obtaining large electrostrain close to the nonergodic-ergodic relaxor boundary. This work provides new insights into polarization reorientation process in relaxor ferroelectrics, especially phase instability in nonergodic relaxor zone approaching to freezing temperature.
Coherent hexagonal platinum skin on nickel nanocrystals for enhanced hydrogen evolution activity
Authors: Liu Kai , Yang Hao , Jiang Yilan , Liu Zhaojun , Zhang Shumeng , Zhang Zhixue , Qiao Zhun , Lu Yiming , Cheng Tao , Terasaki Osamu , Zhang Qing , Gao Chuanbo
Published: April 2023

Metastable noble metal nanocrystals may exhibit distinctive catalytic properties to address the sluggish kinetics of many important processes, including the hydrogen evolution reaction under alkaline conditions for water-electrolysis hydrogen production. However, the exploration of metastable noble metal nanocrystals is still in its infancy and suffers from a lack of sufficient synthesis and electronic engineering strategies to fully stimulate their potential in catalysis. In this paper, we report a synthesis of metastable hexagonal Pt nanostructures by coherent growth on 3d transition metal nanocrystals such as Ni without involving galvanic replacement reaction, which expands the frontier of the phase-replication synthesis. Unlike noble metal substrates, the 3d transition metal substrate owns more crystal phases and lower cost and endows the hexagonal Pt skin with substantial compressive strains and programmable charge density, making the electronic properties particularly preferred for the alkaline hydrogen evolution reaction. The energy barriers are greatly reduced, pushing the activity to 133 mA cmgeo–2 and 17.4 mA μgPt–1 at –70 mV with 1.5 µg of Pt in 1 M KOH. Our strategy paves the way for metastable noble metal catalysts with tailored electronic properties for highly efficient and cost-effective energy conversion.
A computational analysis of mouse behavior in the sucrose preference test
Authors: Verharen Jeroen P. H. , de Jong Johannes W. , Zhu Yichen , Lammel Stephan
Published: April 2023

The sucrose preference test (SPT) measures the relative preference of sucrose over water to assess hedonic behaviors in rodents. Yet, it remains uncertain to what extent the SPT reflects other behavioral components, such as learning, memory, motivation, and choice. Here, we conducted an experimental and computational decomposition of mouse behavior in the SPT and discovered previously unrecognized behavioral subcomponents associated with changes in sucrose preference. We show that acute and chronic stress have sex-dependent effects on sucrose preference, but anhedonia was observed only in response to chronic stress in male mice. Additionally, reduced sucrose preference induced by optogenetics is not always indicative of anhedonia but can also reflect learning deficits. Even small variations in experimental conditions influence behavior, task outcome and interpretation. Thus, an ostensibly simple behavioral task can entail high levels of complexity, demonstrating the need for careful dissection of behavior into its subcomponents when studying the underlying neurobiology.
Pathway choice in the alternative telomere lengthening in neoplasia is dictated by replication fork processing mediated by EXD2’s nuclease activity
Authors: Broderick Ronan , Cherdyntseva Veronica , Nieminuszczy Jadwiga , Dragona Eleni , Kyriakaki Maria , Evmorfopoulou Theodora , Gagos Sarantis , Niedzwiedz Wojciech
Published: April 2023

Telomerase-independent cancer proliferation via the alternative lengthening of telomeres (ALT) relies upon two distinct, largely uncharacterized, break-induced-replication (BIR) processes. How cancer cells initiate and regulate these terminal repair mechanisms is unknown. Here, we establish that the EXD2 nuclease is recruited to ALT telomeres to direct their maintenance. We demonstrate that EXD2 loss leads to telomere shortening, elevated telomeric sister chromatid exchanges, C-circle formation as well as BIR-mediated telomeric replication. We discover that EXD2 fork-processing activity triggers a switch between RAD52-dependent and -independent ALT-associated BIR. The latter is suppressed by EXD2 but depends specifically on the fork remodeler SMARCAL1 and the MUS81 nuclease. Thus, our findings suggest that processing of stalled replication forks orchestrates elongation pathway choice at ALT telomeres. Finally, we show that co-depletion of EXD2 with BLM, DNA2 or POLD3 confers synthetic lethality in ALT cells, identifying EXD2 as a potential druggable target for ALT-reliant cancers.
Engineering protein-based therapeutics through structural and chemical design
Authors: Ebrahimi Sasha B. , Samanta Devleena
Published: April 2023

Protein-based therapeutics have led to new paradigms in disease treatment. Projected to be half of the top ten selling drugs in 2023, proteins have emerged as rivaling and, in some cases, superior alternatives to historically used small molecule-based medicines. This review chronicles both well-established and emerging design strategies that have enabled this paradigm shift by transforming protein-based structures that are often prone to denaturation, degradation, and aggregation in vitro and in vivo into highly effective therapeutics. In particular, we discuss strategies for creating structures with increased affinity and targetability, enhanced in vivo stability and pharmacokinetics, improved cell permeability, and reduced amounts of undesired immunogenicity.
Compositing effects for high thermoelectric performance of Cu2Se-based materials
Authors: Zhou Zhifang , Huang Yi , Wei Bin , Yang Yueyang , Yu Dehong , Zheng Yunpeng , He Dongsheng , Zhang Wenyu , Zou Mingchu , Lan Jin-Le , He Jiaqing , Nan Ce-Wen , Lin Yuan-Hua
Published: April 2023

Thermoelectric materials can realize direct conversion between heat and electricity, showing excellent potential for waste heat recovery. Cu2Se is a typical superionic conductor thermoelectric material having extraordinary ZT values, but its superionic feature causes poor service stability and low mobility. Here, we reported a fast preparation method of self-propagating high-temperature synthesis to realize in situ compositing of BiCuSeO and Cu2Se to optimize the service stability. Additionally, using the interface design by introducing graphene in these composites, the carrier mobility could be obviously enhanced, and the strong phonon scatterings could lead to lower lattice thermal conductivity. Ultimately, the Cu2Se-BiCuSeO-graphene composites presented excellent thermoelectric properties with a ZTmax value of ~2.82 at 1000 K and a ZTave value of ~1.73 from 473 K to 1000 K. This work provides a facile and effective strategy to largely improve the performance of Cu2Se-based thermoelectric materials, which could be further adopted in other thermoelectric systems.
BICD2 phosphorylation regulates dynein function and centrosome separation in G2 and M
Authors: Gallisà-Suñé Núria , Sànchez-Fernàndez-de-Landa Paula , Zimmermann Fabian , Serna Marina , Regué Laura , Paz Joel , Llorca Oscar , Lüders Jens , Roig Joan
Published: April 2023

The activity of dynein is regulated by a number of adaptors that mediate its interaction with dynactin, effectively activating the motor complex while also connecting it to different cargos. The regulation of adaptors is consequently central to dynein physiology but remains largely unexplored. We now describe that one of the best-known dynein adaptors, BICD2, is effectively activated through phosphorylation. In G2, phosphorylation of BICD2 by CDK1 promotes its interaction with PLK1. In turn, PLK1 phosphorylation of a single residue in the N-terminus of BICD2 results in a structural change that facilitates the interaction with dynein and dynactin, allowing the formation of active motor complexes. Moreover, modified BICD2 preferentially interacts with the nucleoporin RanBP2 once RanBP2 has been phosphorylated by CDK1. BICD2 phosphorylation is central for dynein recruitment to the nuclear envelope, centrosome tethering to the nucleus and centrosome separation in the G2 and M phases of the cell cycle. This work reveals adaptor activation through phosphorylation as crucial for the spatiotemporal regulation of dynein activity.
Mesolimbic dopamine release precedes actively sought aversive stimuli in mice
Authors: Yawata Yosuke , Shikano Yu , Ogasawara Jun , Makino Kenichi , Kashima Tetsuhiko , Ihara Keiko , Yoshimoto Airi , Morikawa Shota , Yagishita Sho , Tanaka Kenji F. , Ikegaya Yuji
Published: April 2023

In some models, animals approach aversive stimuli more than those housed in an enriched environment. Here, we found that male mice in an impoverished and unstimulating (i.e., boring) chamber without toys sought aversive air puffs more often than those in an enriched chamber. Using this animal model, we identified the insular cortex as a regulator of aversion-seeking behavior. Activation and inhibition of the insular cortex increased and decreased the frequencies of air-puff self-stimulation, respectively, and the firing patterns of insular neuron ensembles predicted the self-stimulation timing. Dopamine levels in the ventrolateral striatum decreased with passive air puffs but increased with actively sought puffs. Around 20% of mice developed intense self-stimulation despite being offered toys, which was prevented by administering opioid receptor antagonists. This study establishes a basis for comprehending the neural underpinnings of usually avoided stimulus-seeking behaviors.
DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing MYC
Authors: Wang Yejinpeng , Ju Lingao , Wang Gang , Qian Kaiyu , Jin Wan , Li Mingxing , Yu Jingtian , Shi Yiliang , Wang Yongzhi , Zhang Yi , Xiao Yu , Wang Xinghuan
Published: April 2023

To date, most studies on the DNA polymerase, POLD1, have focused on the effect of POLD1 inactivation mutations in tumors. However, the implications of high POLD1 expression in tumorigenesis remains elusive. Here, we determine that POLD1 has a pro-carcinogenic role in bladder cancer (BLCA) and is associated to the malignancy and prognosis of BLCA. Our studies demonstrate that POLD1 promotes the proliferation and metastasis of BLCA via MYC. Mechanistically, POLD1 stabilizes MYC in a manner independent of its’ DNA polymerase activity. Instead, POLD1 attenuates FBXW7-mediated ubiquitination degradation of MYC by directly binding to the MYC homology box 1 domain competitively with FBXW7. Moreover, we find that POLD1 forms a complex with MYC to promote the transcriptional activity of MYC. In turn, MYC increases expression of POLD1, forming a POLD1-MYC positive feedback loop to enhance the pro-carcinogenic effect of POLD1-MYC on BLCA. Overall, our study identifies POLD1 as a promotor of BCLA via a MYC driven mechanism and suggest its potential as biomarker for BLCA.
HMGN1 enhances CRISPR-directed dual-function A-to-G and C-to-G base editing
Authors: Yang Chao , Ma Zhenzhen , Wang Keshan , Dong Xingxiao , Huang Meiyu , Li Yaqiu , Zhu Xiagu , Li Ju , Cheng Zhihui , Bi Changhao , Zhang Xueli
Published: April 2023

C-to-G base editors have been successfully constructed recently, but limited work has been done on concurrent C-to-G and A-to-G base editing. In addition, there is also limited data on how chromatin-associated factors affect the base editing. Here, we test a series of chromatin-associated factors, and chromosomal protein HMGN1 was found to enhance the efficiency of both C-to-G and A-to-G base editing. By fusing HMGN1, GBE and ABE to Cas9, we develop a CRISPR-based dual-function A-to-G and C-to-G base editor (GGBE) which is capable of converting simultaneous A and C to G conversion with substantial editing efficiency. Accordingly, the HMGN1 role shown in this work and the resulting GGBE tool further broaden the genome manipulation capacity of CRISPR-directed base editors.
Resurgence of Omicron BA.2 in SARS-CoV-2 infection-naive Hong Kong
Authors: Xie Ruopeng , Edwards Kimberly M. , Adam Dillon C. , Leung Kathy S. M. , Tsang Tim K. , Gurung Shreya , Xiong Weijia , Wei Xiaoman , Ng Daisy Y. M. , Liu Gigi Y. Z. , Krishnan Pavithra , Chang Lydia D. J. , Cheng Samuel M. S. , Gu Haogao , Siu Gilman K. H. , Wu Joseph T. , Leung Gabriel M. , Peiris Malik , Cowling Benjamin J. , Poon Leo L. M. , Dhanasekaran Vijaykrishna
Published: April 2023

Hong Kong experienced a surge of Omicron BA.2 infections in early 2022, resulting in one of the highest per-capita death rates of COVID-19. The outbreak occurred in a dense population with low immunity towards natural SARS-CoV-2 infection, high vaccine hesitancy in vulnerable populations, comprehensive disease surveillance and the capacity for stringent public health and social measures (PHSMs). By analyzing genome sequences and epidemiological data, we reconstructed the epidemic trajectory of BA.2 wave and found that the initial BA.2 community transmission emerged from cross-infection within hotel quarantine. The rapid implementation of PHSMs suppressed early epidemic growth but the effective reproduction number (Re) increased again during the Spring festival in early February and remained around 1 until early April. Independent estimates of point prevalence and incidence using phylodynamics also showed extensive superspreading at this time, which likely contributed to the rapid expansion of the epidemic. Discordant inferences based on genomic and epidemiological data underscore the need for research to improve near real-time epidemic growth estimates by combining multiple disparate data sources to better inform outbreak response policy.
Sensory perception relies on fitness-maximizing codes
Authors: Schaffner Jonathan , Bao Sherry Dongqi , Tobler Philippe N. , Hare Todd A. , Polania Rafael
Published: April 2023

Sensory information encoded by humans and other organisms is generally presumed to be as accurate as their biological limitations allow. However, perhaps counterintuitively, accurate sensory representations may not necessarily maximize the organism’s chances of survival. To test this hypothesis, we developed a unified normative framework for fitness-maximizing encoding by combining theoretical insights from neuroscience, computer science, and economics. Behavioural experiments in humans revealed that sensory encoding strategies are flexibly adapted to promote fitness maximization, a result confirmed by deep neural networks with information capacity constraints trained to solve the same task as humans. Moreover, human functional MRI data revealed that novel behavioural goals that rely on object perception induce efficient stimulus representations in early sensory structures. These results suggest that fitness-maximizing rules imposed by the environment are applied at early stages of sensory processing in humans and machines.
Nano-DMS-MaP allows isoform-specific RNA structure determination
Authors: Bohn Patrick , Gribling-Burrer Anne-Sophie , Ambi Uddhav B. , Smyth Redmond P.
Published: April 2023

Genome-wide measurements of RNA structure can be obtained using reagents that react with unpaired bases, leading to adducts that can be identified by mutational profiling on next-generation sequencing machines. One drawback of these experiments is that short sequencing reads can rarely be mapped to specific transcript isoforms. Consequently, information is acquired as a population average in regions that are shared between transcripts, thus blurring the underlying structural landscape. Here, we present nanopore dimethylsulfate mutational profiling (Nano-DMS-MaP)—a method that exploits long-read sequencing to provide isoform-resolved structural information of highly similar RNA molecules. We demonstrate the value of Nano-DMS-MaP by resolving the complex structural landscape of human immunodeficiency virus-1 transcripts in infected cells. We show that unspliced and spliced transcripts have distinct structures at the packaging site within the common 5′ untranslated region, likely explaining why spliced viral RNAs are excluded from viral particles. Thus, Nano-DMS-MaP is a straightforward method to resolve biologically important transcript-specific RNA structures that were previously hidden in short-read ensemble analyses.
PediCXR: An open, large-scale chest radiograph dataset for interpretation of common thoracic diseases in children
Authors: Pham Hieu H. , Nguyen Ngoc H. , Tran Thanh T. , Nguyen Tuan N. M. , Nguyen Ha Q.
Published: April 2023

Computer-aided diagnosis systems in adult chest radiography (CXR) have recently achieved great success thanks to the availability of large-scale, annotated datasets and the advent of high-performance supervised learning algorithms. However, the development of diagnostic models for detecting and diagnosing pediatric diseases in CXR scans is undertaken due to the lack of high-quality physician-annotated datasets. To overcome this challenge, we introduce and release PediCXR, a new pediatric CXR dataset of 9,125 studies retrospectively collected from a major pediatric hospital in Vietnam between 2020 and 2021. Each scan was manually annotated by a pediatric radiologist with more than ten years of experience. The dataset was labeled for the presence of 36 critical findings and 15 diseases. In particular, each abnormal finding was identified via a rectangle bounding box on the image. To the best of our knowledge, this is the first and largest pediatric CXR dataset containing lesion-level annotations and image-level labels for the detection of multiple findings and diseases. For algorithm development, the dataset was divided into a training set of 7,728 and a test set of 1,397. To encourage new advances in pediatric CXR interpretation using data-driven approaches, we provide a detailed description of the PediCXR data sample and make the dataset publicly available on https://physionet.org/content/vindr-pcxr/1.0.0/.
Multi-modal brain magnetic resonance imaging database covering marmosets with a wide age range
Authors: Hata Junichi , Nakae Ken , Tsukada Hiromichi , Woodward Alexander , Haga Yawara , Iida Mayu , Uematsu Akiko , Seki Fumiko , Ichinohe Noritaka , Gong Rui , Kaneko Takaaki , Yoshimaru Daisuke , Watakabe Akiya , Abe Hiroshi , Tani Toshiki , Hamda Hiro Taiyo , Gutierrez Carlos Enrique , Skibbe Henrik , Maeda Masahide , Papazian Frederic , Hagiya Kei , Kishi Noriyuki , Ishii Shin , Doya Kenji , Shimogori Tomomi , Yamamori Tetsuo , Tanaka Keiji , Okano Hirotaka James , Okano Hideyuki
Published: April 2023

Magnetic resonance imaging (MRI) is a non-invasive neuroimaging
technique that is useful for identifying normal developmental and aging processes
and for data sharing. Marmosets have a relatively shorter life expectancy than other
primates, including humans, because they grow and age faster. Therefore, the common
marmoset model is effective in aging research. The current study investigated the
aging process of the marmoset brain and provided an open MRI database of marmosets
across a wide age range. The Brain/MINDS Marmoset Brain MRI Dataset contains brain
MRI information from 216 marmosets ranging in age from 1 and 10 years. At the time
of its release, it is the largest public dataset in the world. It also includes
multi-contrast MRI images. In addition, 91 of 216 animals have corresponding
high-resolution ex vivo MRI datasets. Our MRI
database, available at the Brain/MINDS Data Portal, might help to understand the
effects of various factors, such as age, sex, body size, and fixation, on the brain.
It can also contribute to and accelerate brain science studies worldwide.
De novo transcriptomes of six calanoid copepods (Crustacea): a resource for the discovery of novel genes
Authors: Hartline Daniel K. , Cieslak Matthew C. , Castelfranco Ann M. , Lieberman Brandon , Roncalli Vittoria , Lenz Petra H.
Published: April 2023

This study presents eight new high-quality de novo transcriptomes from six co-occurring species of calanoid copepods, the first published for Neocalanus plumchrus, N. cristatus, Eucalanus bungii and Metridia pacifica and additional ones for N. flemingeri and Calanus marshallae. They are ecologically-important members of sub-arctic North Pacific marine zooplankton communities. ‘Omics data for this diverse and numerous taxonomic group are sparse and difficult to obtain. Total RNA from single individuals was used to construct gene libraries that were sequenced on an Illumina Next-Seq platform. Quality filtered reads were assembled with Trinity software and validated using multiple criteria. The study’s primary purpose is to provide a resource for gene expression studies. The integrated database can be used for quantitative inter- and intra-species comparisons of gene expression patterns across biological processes. An example of an additional use is provided for discovering novel and evolutionarily-significant proteins within the Calanoida. A workflow was designed to find and characterize unannotated transcripts with homologies across de novo assemblies that have also been shown to be eco-responsive.
Generating Detailed Spectral Libraries for Canine Proteomes Obtained from Serum and Urine
Authors: Ahn Hee-Sung , Yeom Jeonghun , Yu Jiyoung , Oh Yumi , Hong JeongYeon , Kim Minjung , Kim Kyunggon
Published: April 2023

Domestic dogs (Canis lupus familiaris) are popular companion animals. Increase in medical expenses associated with them and demand for extending their lifespan in a healthy manner has created the need to develop new diagnostic technology. Companion dogs also serve as important animal models for non-clinical research as they can provide various biological phenotypes. Proteomics have been increasingly used on dogs and humans to identify novel biomarkers of various diseases. Despite the growing applications of proteomics in liquid biopsy in veterinary medicine, no publicly available spectral assay libraries have been created for the proteome of canine serum and urine. In this study, we generated spectral assay libraries for the two-representative liquid-biopsy samples using mid-pH fractionation that allows in-depth understanding of proteome coverage. The resultant canine serum and urine spectral assay libraries include 1,132 and 4,749 protein groups and 5,483 and 25,228 peptides, respectively. We built these complimentary accessible resources for proteomic biomarker discovery studies through ProteomeXchange with the identifier PXD034770.
Land-use change is associated with multi-century loss of elephant ecosystems in Asia
Authors: de Silva Shermin , Wu Tiffany , Nyhus Philip , Weaver Ashley , Thieme Alison , Johnson Josiah , Wadey Jamie , Mossbrucker Alexander , Vu Thinh , Neang Thy , Chen Becky Shu , Songer Melissa , Leimgruber Peter
Published: April 2023

Understanding historic patterns of land use and land cover change across large temporal and spatial scales is critical for developing effective biodiversity conservation management and policy. We quantify the extent and fragmentation of suitable habitat across the continental range of Asian elephants (Elephas maximus) based on present-day occurrence data and land-use variables between 850 and 2015 A.D. We found that following centuries of relative stability, over 64% (3.36 million km2) of suitable elephant habitat across Asia was lost since the year 1700, coincident with colonial-era land-use practices in South Asia and subsequent agricultural intensification in Southeast Asia. Average patch size dropped 83% from approximately 99,000–16,000 km2and the area occupied by the largest patch decreased 83% from ~ 4 million km2(45% of area) to 54,000 km2(~ 7.5% of area). Whereas 100% of the area within 100 km of the current elephant range could have been considered suitable habitat in the year 1700, over half was unsuitable by 2015, driving potential conflict with people. These losses reflect long-term decline of non-forested ecosystems, exceeding estimates of deforestation within this century. Societies must consider ecological histories in addition to proximate threats to develop more just and sustainable land-use and conservation strategies.
Aphanothece sp. as promising biostimulant to alleviate heavy metals stress in Solanum lycopersicum L. by enhancing physiological, biochemical, and metabolic responses
Authors: Fal Soufiane , Aasfar Abderrahim , Ouhssain Ali , Choukri Hasnae , Smouni Abelaziz , El Arroussi Hicham
Published: April 2023

Heavy metals (H.M) are a major environmental concern around the world. They have harmful impact on plant productivity and pose a serious risk to humans and animals health. In the present study, we investigated the effect of Aphanothece crude extract (ACE) on physiological, biochemical, and metabolic responses of tomato plant exposed to 2 mM Pb and Cd. The results showed a significant reduction of tomato plant weights and perturbation in nutrients absorption under 2 mM Pb and Cd conditions. Moreover, ACE treatment showed a significant enhancement of plant biomass compared to plants under Pb and Cd. On the other hand, ACE application favoured H.M accumulation in root and inhibited their translocation to shoot. In addition, ACE treatment significantly enhanced several stress responses in plant under Pb and Cd stress such as scavenging enzymes and molecules: POD, CAT, SOD, proline, and polyphenols etc. Furthermore, ACE treatment showed remodulation of metabolic pathways related to plant tolerance such as wax construction mechanism, particularly SFA, UFA, VLFA, alkanes, alkenes, and sterols biosynthesis to enhance tolerance and resistance to H.M stress. In the present study, we emphasized that ACE alleviates H.M stress by minimizing metal translocation to above-part of plant and enhancing plant growth, nutrients absorption, and biochemical responses.
Excess mortality in Ukraine during the course of COVID-19 pandemic in 2020–2021
Authors: Shishkin Aleksandr , Lhewa Pema , Yang Chen , Gankin Yuriy , Chowell Gerardo , Norris Michael , Skums Pavel , Kirpich Alexander
Published: April 2023

In this work, the COVID-19 pandemic burden in Ukraine is investigated retrospectively using the excess mortality measures during 2020–2021. In particular, the epidemic impact on the Ukrainian population is studied via the standardized both all-cause and cause-specific mortality scores before and during the epidemic. The excess mortality counts during the pandemic were predicted based on historic data using parametric and nonparametric modeling and then compared with the actual reported counts to quantify the excess. The corresponding standardized mortality P-score metrics were also compared with the neighboring countries. In summary, there were three “waves” of excess all-cause mortality in Ukraine in December 2020, April 2021 and November 2021 with excess of 32%, 43% and 83% above the expected mortality. Each new “wave” of the all-cause mortality was higher than the previous one and the mortality “peaks” corresponded in time to three “waves” of lab-confirmed COVID-19 mortality. The lab-confirmed COVID-19 mortality constituted 9% to 24% of the all-cause mortality during those three peak months. Overall, the mortality trends in Ukraine over time were similar to neighboring countries where vaccination coverage was similar to that in Ukraine. For cause-specific mortality, the excess observed was due to pneumonia as well as circulatory system disease categories that peaked at the same times as the all-cause and lab-confirmed COVID-19 mortality, which was expected. The pneumonias as well as circulatory system disease categories constituted the majority of all cases during those peak times. The seasonality in mortality due to the infectious and parasitic disease category became less pronounced during the pandemic. While the reported numbers were always relatively low, alcohol-related mortality also declined during the pandemic.
Population-specific facial traits and diagnosis accuracy of genetic and rare diseases in an admixed Colombian population
Authors: Echeverry-Quiceno Luis M. , Candelo Estephania , Gómez Eidith , Solís Paula , Ramírez Diana , Ortiz Diana , González Alejandro , Sevillano Xavier , Cuéllar Juan Carlos , Pachajoa Harry , Martínez-Abadías Neus
Published: April 2023

Up to 40% of rare disorders (RD) present facial dysmorphologies, and visual assessment is commonly used for clinical diagnosis. Quantitative approaches are more objective, but mostly rely on European descent populations, disregarding diverse population ancestry. Here, we assessed the facial phenotypes of Down (DS), Morquio (MS), Noonan (NS) and Neurofibromatosis type 1 (NF1) syndromes in a Latino-American population, recording the coordinates of 18 landmarks in 2D images from 79 controls and 51 patients. We quantified facial differences using Euclidean Distance Matrix Analysis, and assessed the diagnostic accuracy of Face2Gene, an automatic deep-learning algorithm. Individuals diagnosed with DS and MS presented severe phenotypes, with 58.2% and 65.4% of significantly different facial traits. The phenotype was milder in NS (47.7%) and non-significant in NF1 (11.4%). Each syndrome presented a characteristic dysmorphology pattern, supporting the diagnostic potential of facial biomarkers. However, population-specific traits were detected in the Colombian population. Diagnostic accuracy was 100% in DS, moderate in NS (66.7%) but lower in comparison to a European population (100%), and below 10% in MS and NF1. Moreover, admixed individuals showed lower facial gestalt similarities. Our results underscore that incorporating populations with Amerindian, African and European ancestry is crucial to improve diagnostic methods of rare disorders.
Contact lens embedded holographic pointer
Authors: Robert François-Maël , Abiven Bernard , Sinou Maïna , Heggarty Kevin , Adam Laure , Nourrit Vincent , de Bougrenet de la Tocnaye Jean-Louis
Published: April 2023

In this paper we present an infrared laser pointer, consisting of a vertical-cavity surface-emitting laser (VCSEL) and a diffractive optical element (DOE), encapsulated into a scleral contact lens (SCL). The VCSEL is powered remotely by inductive coupling from a primary antenna embedded into an eyewear frame. The DOE is used either to collimate the laser beam or to project a pattern image at a chosen distance in front of the eye. We detail the different SCL constitutive blocks, how they are manufactured and assembled. We particularly emphasize the various technological challenges related to their encapsulation in the reduced volume of the SCL, while keeping the pupil free. Finally, we describe how the laser pointer operates, what are its performances (e.g. collimation, image formation) and how it can be used efficiently in various application fields such as visual assistance and augmented reality.
A spectral preserved model based on spectral contribution and dependence with detail injection for pansharpening
Authors: Wu Lei , Jiang Xunyan , Peng Jia , Wu Guangsheng , Xiong Xiaozhen
Published: April 2023

Pansharpening integrates the high spectral content of multispectral (MS) images and the fine spatial information of the corresponding panchromatic (PAN) images to produce a high spectral-spatial resolution image. Traditional pansharpening methods compensate for the spatial lack of the MS image using the PAN image details, which easily causes spectral distortion. To achieve spectral fidelity, a spectral preservation model based on spectral contribution and dempendence with detail injection for pansharpening is proposed. In the proposed model, first, an efficacy coefficient (CE) based on the spatial difference between the MS and PAN images is designed to suppress the impact of the detail injection on the spectra. Second, the spectral contribution and dependence (SCD) between the MS bands and pixels are considered to strengthen the internal adaptation of the spectra. Finally, a spectrally preserved model based on CE and SCD is designed to force the fused image fidelity in spectra when the MS image is pansharpened with the details of the PAN image. Experimental results show that the proposed model is effective.
Bone-patellar tendon-bone versus two- and four-strand hamstring tendon autografts for ACL reconstruction in young adults: a Bayesian network meta-analysis
Authors: Migliorini Filippo , Torsiello Ernesto , Trivellas Andromahi , Eschweiler Jörg , Hildebrand Frank , Maffulli Nicola
Published: April 2023

Bone-patellar tendon-bone (BPTB), two- and four-strand hamstring tendon (4SHT and 2SHT, respectively) are the most common autografts used for anterior cruciate ligament (ACL) reconstruction. The present study compared BPTB, 2SHT, and 4SHT for ACL reconstruction in terms of joint laxity, patient reported outcome measures (PROMs), rate of failure and anterior knee pain (AKP). The time to return to sport and the peak torque between the autografts were also compared. Finally, prognostic factors leading to worse outcomes were also investigated. It was hypothesized that all grafts yield similar proprieties in terms of joint laxity, patient reported outcome measures (PROMs) and rate of failure, but that the BPTB autograft causes a greater rate of anterior knee pain (AKP). The literature search was conducted. All clinical trials comparing BTPB and/or 2SHT, and/or 4SHT were accessed. Grafts other than BTPB and/or 4SHT and/or 2SHT were not considered. Articles reporting outcomes of allografts or synthetic grafts were not eligible, nor were those concerning revision settings. Articles reporting ACL reconstruction in patients with multi-ligament damage were also not eligible. Data from 95,575 procedures were retrieved. The median length of follow-up was 36 months. The median age of the patients was 27.5 years. With regard to joint laxity, similarity was found in terms of Lachman and Pivot shift tests between all three autografts. The BPTB demonstrated the greatest stability in terms of instrumental laxity. BPTB demonstrated the greatest PROMs. BPTB demonstrated the greatest rate of AKP, while AKP in 2SHT and 4SHT was similar. Concerning failure, statistically significant inconsistency was found (P = 0.008). The 4SHT demonstrated the quickest return to sport, followed by BPTB, and 2SHT. There was evidence of a negative association between the time span between injury to surgery, Lysholm score (P = 0.04), and Tegner scale (P = 0.04). Furthermore, there was evidence of a weak positive association between the time span between injury to surgery and return to sport (P = 0.01). BPTB may result in lower joint laxity, greater PROMs, and greater peak flexion torque compared to 2SHT and 4SHT autografts. On the other hand, BPTB reported the lowest peak extension torque and the greatest rate of AKP. Finally, a longer time span between injury and surgery negatively influences outcome.