bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multidisciplinary Method to Support the Evolution of NWS Weather Radar Technology
Authors: Boettcher Jami , Torres Sebastián , Nai Feng , Curtis Christopher , Schvartzman David 
Published: February 2022

Abstract
The highly successful fleet of Weather Surveillance Radar-1988 Doppler (WSR-88D) radars is approaching its end of service, and research efforts are under way to inform a decision toward a possible WSR-88D replacement. A methodology to link radar design characteristics to impacts on how radar data are used to diagnose hazardous weather was developed through a unique partnership between radar-engineering innovations in radar simulations and National Weather Service (NWS) radar data interpretation expertise. Deep commitment to two-way learning across disciplines resulted in a methodology that is both efficient and highly relevant to the NWS hazardous weather warning program. The methodology presented in this paper is a model for revealing complex trade-offs between weather radar characteristics and their resultant impact on NWS data interpretation for threat identification. This qualitative methodology is presented in the context of a broader proof-of-concept study from which it was developed. Adapted for further research, it can support the crucial role of deriving quantitative radar design criteria that balance the trade-offs among radar capabilities, cost, and impact to users. That is, the proposed methodology supports the evaluation of candidates for a potential WSR-88D replacement and any necessary major system upgrades in the interim.

Significance Statement
Defining the requirements for an operational weather radar system is ideally achieved with clearly identified trade-offs among cost, radar design characteristics, and impacts on user data interpretation. This work is an advancement of the historic evolution of weather radar development to support the U.S. National Weather Service (NWS) mission, based on collaboration among researchers, radar engineers, and NWS forecasters. The methodology presented here is an adaptable tool for revealing these essential, but complex trade-offs, providing a roadmap for further studies toward the next-generation NWS weather radar fleet.
Deletion of platelet CLEC-2 decreases GPIbα-mediated integrin αIIbβ3 activation and decreases thrombosis in TTP
Authors: Shao Bojing , Hoover Christopher , Shi Huiping , Kondo Yuji , Lee Robert H. , Chen Junmei , Shan Xindi , Song Jianhua , McDaniel J. Michael , Zhou Meixiang , McGee Samuel , Vanhoorelbeke Karen , Bergmeier Wolfgang , López José A. , George James N. , Xia Lijun 
Published: February 2022

Abstract
Microvascular thrombosis in patients with thrombotic thrombocytopenic purpura (TTP) is initiated by GPIbα-mediated platelet binding to von Willebrand factor (VWF). Binding of VWF to GPIbα causes activation of the platelet surface integrin αIIbβ3. However, the mechanism of GPIbα-initiated activation of αIIbβ3 and its clinical importance for microvascular thrombosis remain elusive. Deletion of platelet C-type lectin-like receptor 2 (CLEC-2) did not prevent VWF binding to platelets but specifically inhibited platelet aggregation induced by VWF binding in mice. Deletion of platelet CLEC-2 also inhibited αIIbβ3 activation induced by the binding of VWF to GPIbα. Using a mouse model of TTP, which was created by infusion of anti-mouse ADAMTS13 monoclonal antibodies followed by infusion of VWF, we found that deletion of platelet CLEC-2 decreased pulmonary arterial thrombosis and the severity of thrombocytopenia. Importantly, prophylactic oral administration of aspirin, an inhibitor of platelet activation, and therapeutic treatment of the TTP mice with eptifibatide, an integrin αIIbβ3 antagonist, reduced pulmonary arterial thrombosis in the TTP mouse model. Our observations demonstrate that GPIbα-mediated activation of integrin αIIbβ3 plays an important role in the formation of thrombosis in TTP. These observations suggest that prevention of platelet activation with aspirin may reduce the risk for thrombosis in patients with TTP.
MRD in adult Ph/BCR-ABL-negative ALL: how best to eradicate?
Authors: Gökbuget Nicola 
Published: February 2022

Abstract
Evaluation of minimal residual disease (MRD) during first-line treatment and after salvage therapy is part of the standard management of acute lymphoblastic leukemia (ALL). Persistent or recurrent MRD is one of the most relevant prognostic factors and identifies a group of patients with resistance to standard chemotherapy. These patients have a high risk of relapse despite continued first-line therapy. Although stem cell transplantation (SCT) is an appropriate strategy, patients with high MRD show an increased relapse rate even after SCT. Approximately one-quarter of adult ALL patients develop an MRD failure, defined as MRD above 0.01% after standard induction and consolidation. The best time point and level of MRD for treatment modification are matters of debate. In order to eradicate MRD and thereby improve chances for a cure, new targeted compounds with different mechanisms of action compared to chemotherapy are being utilized. These compounds include monoclonal antibodies, chimeric antigen receptor T cells, and molecular targeted compounds. Essential factors for decision-making, available compounds, and follow-up therapies are discussed.
Multi-objective Trajectory Planning Method based on the Improved Elitist Non-dominated Sorting Genetic Algorithm
Authors: Wang Zesheng , Li Yanbiao , Shuai Kun , Zhu Wentao , Chen Bo , Chen Ke 
Published: February 2022

AbstractRobot manipulators perform a point-point task under kinematic and dynamic constraints. Due to multi-degree-of-freedom coupling characteristics, it is difficult to find a better desired trajectory. In this paper, a multi-objective trajectory planning approach based on an improved elitist non-dominated sorting genetic algorithm (INSGA-II) is proposed. Trajectory function is planned with a new composite polynomial that by combining of quintic polynomials with cubic Bezier curves. Then, an INSGA-II, by introducing three genetic operators: ranking group selection (RGS), direction-based crossover (DBX) and adaptive precision-controllable mutation (APCM), is developed to optimize travelling time and torque fluctuation. Inverted generational distance, hypervolume and optimizer overhead are selected to evaluate the convergence, diversity and computational effort of algorithms. The optimal solution is determined via fuzzy comprehensive evaluation to obtain the optimal trajectory. Taking a serial-parallel hybrid manipulator as instance, the velocity and acceleration profiles obtained using this composite polynomial are compared with those obtained using a quintic B-spline method. The effectiveness and practicability of the proposed method are verified by simulation results. This research proposes a trajectory optimization method which can offer a better solution with efficiency and stability for a point-to-point task of robot manipulators.
Programmed death-ligand 1 signaling and expression are reversible by lycopene via PI3K/AKT and Raf/MEK/ERK pathways in tongue squamous cell carcinoma
Authors: Peng Mingjing , Fan Songqing , Li Junjun , Zhou Xiao , Liao Qianjin , Tang Faqing , Liu Wei 
Published: February 2022

Abstract
Background
Cancer therapy targeting programmed death receptor-1 (PD-1 or CD279) or programmed death-ligand 1 (PD-L1 or CD274) gives hope to Tongue Squamous Cell Carcinoma (TSCC) treatment. However, the tumor-intrinsic mechanism of PD-L1 is not fully elucidated in TSCC. On the other hand, lycopene showed antitumor effects and chemotherapy/radiotherapy-enhancing effects by mechanisms closely correlated with PD-L1.

Purpose
We aimed to explore whether the mechanisms of PD-L1 signaling and regulation are reversible by lycopene treatment in TSCC.

Methods
We collected TSCC tissues and normal tissues for assessment of PD-L1 expression by immunohistochemical technique and western blotting. We measured the expression of PD-L1 in three TSCC cell lines and constructed cell lines with knockdown and overexpression of PD-L1. Then, we measured the proliferation by CCK-8 assay, migration and invasion by Transwell assay, and apoptosis by TUNEL assay in five groups with treatment of blank control, negative control with vector transfection, PD-L1 knockdown/overexpression, 4 μM lycopene, and combined 4 μM lycopene and PD-L1 knockdown/overexpression. We also systematically analyzed the PD-L1 constitutive signaling pathways and their effect EMT pathways. In order to bring out the mechanism underlying PI3K/AKT depressing Raf/MEK/ERK, we used PI3K inhibitor LY294002.

Results
We detected significant PD-L1 upregulation in biopsies by western blot and immunohistochemistry. Our study demonstrated that PD-L1 upregulation elevated IGF-1R to activate the PI3K/AKT pathway but inactivated the Raf/MEK/ERK pathway in TSCC cell line CAL27, while PD-L1 knockdown decreased IGF-1R to inactivate both PI3K/AKT and Raf/MEK/ERK pathways in cell line SCC9, to increase/decrease p-FOXOs and decrease/increase p-GSK-3β, producing further changes in EMT, proliferation, migration, invasion, and apoptosis. Lycopene reversed PD-L1 signaling and expression by mechanisms opposite to PD-L1 upregulation but similar to PD-L1 knockdown.

Conclusion
Taken together, this study firstly confirmed PD-L1 expression and signaling are reversible by lycopene via PI3K/AKT and Raf/MEK/ERK pathways in TSCC. Our study provides a sounder basis for comprehending PD-L1 signaling and expression and prevention and treatment of TSCC.
Ontogenetic drivers of morphological evolution in monitor lizards and allies (Squamata: Paleoanguimorpha), a clade with extreme body size disparity
Authors: Pavón-Vázquez Carlos J. , Esquerré Damien , Keogh J. Scott 
Published: February 2022

AbstractBackgroundHeterochrony, change in the rate or timing of development, is thought to be one of the main drivers of morphological evolution, and allometry, trait scaling patterns imposed by size, is traditionally thought to represent an evolutionary constraint. However, recent studies suggest that the ontogenetic allometric trajectories describing how organisms change as they grow may be labile and adaptive. Here we investigated the role of postnatal ontogenetic development in the morphological diversification of Paleoanguimorpha, the monitor lizards and allies, a clade with extreme body size disparity. We obtained linear and geometric morphometric data for more than 1,600 specimens belonging to three families and 60 species, representing ~ 72% of extant paleoanguimorph diversity. We used these data to undertake one of the largest comparative studies of ontogenetic allometry to date.ResultsHeterochrony is likely dictating morphological divergence at shallow evolutionary scales, while changes in the magnitude and direction of ontogenetic change are found mainly between major clades. Some patterns of ontogenetic variation and morphological disparity appear to reflect ontogenetic transitions in habitat use. Generally, juveniles are more similar to each other than adults, possibly because species that differ in ecology as adults are arboreal as juveniles. The magnitude of ontogenetic change follows evolutionary models where variation is constrained around an optimal value. Conversely, the direction of ontogenetic change may follow models with different adaptive optima per habitat use category or models where interspecific interactions influence its evolution. Finally, we found that the evolutionary rates of the ontogenetic allometric trajectories are phylogenetically variable.ConclusionsThe attributes of ontogenetic allometric trajectories and their evolutionary rates are phylogenetically heterogeneous in Paleoanguimorpha. Both allometric constraints and ecological factors have shaped ontogeny in the group. Our study highlights the evolutionary lability and adaptability of postnatal ontogeny, and teases apart how different evolutionary shifts in ontogeny contribute to the generation of morphological diversity at different evolutionary scales.
Genome-wide localization of histone variants in Toxoplasma gondii implicates variant exchange in stage-specific gene expression
Authors: Nardelli Sheila C. , Silmon de Monerri Natalie C. , Vanagas Laura , Wang Xiaonan , Tampaki Zoi , Sullivan William J. , Angel Sergio O. , Kim Kami 
Published: February 2022

Abstract
Background
Toxoplasma gondii is a protozoan parasite that differentiates from acute tachyzoite stages to latent bradyzoite forms in response to environmental cues that modify the epigenome. We studied the distribution of the histone variants CenH3, H3.3, H2A.X, H2A.Z and H2B.Z, by genome-wide chromatin immunoprecipitation to understand the role of variant histones in developmental transitions of T. gondii parasites.

Results
H3.3 and H2A.X were detected in telomere and telomere associated sequences, whereas H3.3, H2A.X and CenH3 were enriched in centromeres. Histones H2A.Z and H2B.Z colocalize with the transcriptional activation mark H3K4me3 in promoter regions surrounding the nucleosome-free region upstream of the transcription start site. The H2B.Z/H2A.Z histone pair also localizes to the gene bodies of genes that are silent but poised for activation, including bradyzoite stage-specific genes. The majority of H2A.X and H2A.Z/H2B.Z loci do not overlap, consistent with variant histones demarcating specific functional regions of chromatin. The extent of enrichment of H2A.Z/H2B.Z (and H3.3 and H2A.X) within the entire gene (5’UTR and gene body) reflects the timing of gene expression during the cell cycle, suggesting that dynamic turnover of H2B.Z/H2A.Z occurs during the tachyzoite cell cycle. Thus, the distribution of the variant histone H2A.Z/H2B.Z dimer defines active and developmentally silenced regions of the T. gondii epigenome including genes that are poised for expression.

Conclusions
Histone variants mark functional regions of parasite genomes with the dynamic placement of the H2A.Z/H2B.Z dimer implicated as an evolutionarily conserved regulator of parasite and eukaryotic differentiation.
Genion, an accurate tool to detect gene fusion from long transcriptomics reads
Authors: Karaoglanoglu Fatih , Chauve Cedric , Hach Faraz 
Published: February 2022

Abstract
Background
The advent of next-generation sequencing technologies empowered a wide variety of transcriptomics studies. A widely studied topic is gene fusion which is observed in many cancer types and suspected of having oncogenic properties. Gene fusions are the result of structural genomic events that bring two genes closely located and result in a fused transcript. This is different from fusion transcripts created during or after the transcription process. These chimeric transcripts are also known as read-through and trans-splicing transcripts. Gene fusion discovery with short reads is a well-studied problem, and many methods have been developed. But the sensitivity of these methods is limited by the technology, especially the short read length. Advances in long-read sequencing technologies allow the generation of long transcriptomics reads at a low cost. Transcriptomic long-read sequencing presents unique opportunities to overcome the shortcomings of short-read technologies for gene fusion detection while introducing new challenges.

Results
We present Genion, a sensitive and fast gene fusion detection method that can also detect read-through events. We compare Genion against a recently introduced long-read gene fusion discovery method, LongGF, both on simulated and real datasets. On simulated data, Genion accurately identifies the gene fusions and its clustering accuracy for detecting fusion reads is better than LongGF. Furthermore, our results on the breast cancer cell line MCF-7 show that Genion correctly identifies all the experimentally validated gene fusions.

Conclusions
Genion is an accurate gene fusion caller. Genion is implemented in C++ and is available at https://github.com/vpc-ccg/genion.
Differential gene expression associated with a floral scent polymorphism in the evening primrose Oenothera harringtonii (Onagraceae)
Authors: Bechen Lindsey L. , Johnson Matthew G. , Broadhead Geoffrey T. , Levin Rachel A. , Overson Rick P. , Jogesh Tania , Fant Jeremie B. , Raguso Robert A. , Skogen Krissa A. , Wickett Norman J. 
Published: February 2022

Abstract
Background
Plant volatiles play an important role in both plant-pollinator and plant-herbivore interactions. Intraspecific polymorphisms in volatile production are ubiquitous, but studies that explore underlying differential gene expression are rare. Oenothera harringtonii populations are polymorphic in floral emission of the monoterpene (R)-(−)-linalool; some plants emit (R)-(−)-linalool (linalool+ plants) while others do not (linalool- plants). However, the genes associated with differential production of this floral volatile in Oenothera are unknown. We used RNA-Seq to broadly characterize differential gene expression involved in (R)-(−)-linalool biosynthesis. To identify genes that may be associated with the polymorphism for this trait, we used RNA-Seq to compare gene expression in six different Oenothera harringtonii tissues from each of three linalool+ and linalool- plants.

Results
Three clusters of differentially expressed genes were enriched for terpene synthase activity: two were characterized by tissue-specific upregulation and one by upregulation only in plants with flowers that produce (R)-(−)-linalool. A molecular phylogeny of all terpene synthases identified two putative (R)-(−)-linalool synthase transcripts in Oenothera harringtonii, a single allele of which is found exclusively in linalool+ plants.

Conclusions
By using a naturally occurring polymorphism and comparing different tissues, we were able to identify candidate genes putatively involved in the biosynthesis of (R)-(−)-linalool. Expression of these genes in linalool- plants, while low, suggests a regulatory polymorphism, rather than a population-specific loss-of-function allele. Additional terpene biosynthesis-related genes that are up-regulated in plants that emit (R)-(−)-linalool may be associated with herbivore defense, suggesting a potential economy of scale between plant reproduction and defense.
Maternal diabetes-mediated RORA suppression contributes to gastrointestinal symptoms in autism-like mouse offspring
Authors: Xiao Li , Wang Min , Zhang Wanhua , Song Yuan , Zeng Jiaying , Li Huilin , Yu Hong , Li Ling , Gao Pingming , Yao Paul 
Published: February 2022

Abstract
Background
Retinoic acid-related orphan receptor alpha (RORA) has been reported to be suppressed in autistic patients and is associated with autism spectrum disorders (ASD), although the potential role and mechanism of RORA on gastrointestinal (GI) symptoms in ASD patients is still not reported. In this study, we aim to investigate the contribution of RORA to GI symptoms through a maternal diabetes-mediated autism-like mouse model.

Results
Male offspring of diabetic dams were treated with either superoxide dismutase (SOD) mimetic MnTBAP or RORA agonist SR1078, or were crossbred with intestine epithelial cells (IEC)-specific RORA knockout (RORA−/−) mouse. Gene expression, oxidative stress and inflammation were measured in brain tissues, peripheral blood mononuclear cells (PBMC) and IEC, and GI symptoms were evaluated. Our results showed that SOD mimetic MnTBAP completely, while RORA agonist SR1078 partly, reversed maternal diabetes-mediated oxidative stress and inflammation in the brain, PBMC and IEC, as well as GI symptoms, including intestine permeability and altered gut microbiota compositions. IEC-specific RORA deficiency either mimicked or worsened maternal diabetes-mediated GI symptoms as well as oxidative stress and inflammation in IEC, while there was little effect on maternal diabetes-mediated autism-like behaviors.

Conclusions
We conclude that RORA suppression contributes to maternal diabetes-mediated GI symptoms in autism-like mouse offspring, this study provides a potential therapeutical target for maternal diabetes-mediated GI symptoms in offspring through RORA activation.
Lobaplatin hyperthermic intraperitoneal chemotherapy plus cytoreduction and rechallenge using cetuximab for wild-type RAS peritoneal metastatic colon cancer: a case report and literature review
Authors: Dai Peilin , Ye Zaisheng , Cai Zhai , Luo Zeyu , Qiu Enming , Lin Yu , Cai Jian , Wang Hui , Li Zhou , Han Shuai 
Published: February 2022

Abstract
Background
Synchronous peritoneal metastasis of colorectal cancer usually predicts a bleak prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) have brought a glimmer of hope to the treatment of peritoneal cancer. Few cases treated with lobaplatin have been reported in the literature and the regimen is controversial. In this case, the comprehensive treatment scheme of lobaplatin-based HIPEC plus CRS and rechallenge using cetuximab plus systemic chemotherapy is effective, especially for the patients with left colon cancer (wild-type RAS).

Case presentation
A 49 year-old man with signet ring cell carcinoma of sigmoid colon with extensive abdominal metastasis (wild-type RAS) was hospitalized with prolonged abdominal pain, distention and abdominal mass. After receiving HIPEC with lobaplatin and XELOX regimen combined with cetuximab for eight cycles, the patient had been treated with the FOLFIRI regimen and cetuximab for 24 cycles, which discontinued due to myelosuppression. Because the disease recurred unfortunately 4 months later, the FOLFIRI + cetuximab regimen was initiated again and stopped after two cycles. Intestinal obstruction occurred 1 month later, so open total colectomy, CRS + HIPEC and ileorectal anastomosis were performed. Capecitabine adjuvant chemotherapy was administered, followed by the maintenance therapy with FOLFIRI + cetuximab regimen. After that, the patient has been in relatively stable condition. By August 2021, the overall survival is more than 45 months, which displays significant curative effect.

Conclusion
For peritoneal metastasis from left colon cancer, the management with CRS + lobaplatin HIPEC and rechallenge of systemic chemotherapy plus targeted medicine based on gene detection can dramatically improve prognosis and extend the overall survival.
Family caregiving during the COVID-19 pandemic: factors associated with anxiety and depression of carers for community-dwelling older adults in Hong Kong
Authors: Chiu Marcus Y. L. , Leung Cyrus L. K. , Li Ben K. K. , Yeung Dannii , Lo T. W. 
Published: February 2022

Abstract
Background
The COVID-19 pandemic disrupts the daily routine and increases the caregiving load of the family carers of older adults. This study examined how the pandemic may impact mental health and investigated the prevalence of anxiety and depressive symptoms in family carers of older people.

Methods
Two hundred and thirty-six family carers of older adults participated in this cross-sectional survey study. Outcome measures included their symptoms of anxiety and depression, pandemic-related psychosocial factors, external factors, and the practice of preventive behaviours.

Results
Caseness prevalence of anxiety and depression among family carers was 25 and 56% respectively. Working carers were more depressed than non-working, while younger carers reported more anxiety and depression symptoms than older. Hand hygiene and getting drugs from the hospital positively predicted depression while healthy lifestyle negatively predicted depression. These variables, together with perceived risk and severity and the worry of getting infected, predicted anxiety.

Conclusions
The prevalence of mental health symptoms was alarming. Telemedicine practice, including online pharmaceutical services and the Internet Hospital plus Drug Delivery platform, could be a solution in alleviating the burden and worry of infection of family carers. Tailored-made interventions by age and working status of the family carers are recommended.