bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elastic and collapsible: current understanding of cell walls in succulent plants
Authors: Fradera-Soler Marc , Grace Olwen M , Jørgensen Bodil , Mravec Jozef 
Published: February 2022

AbstractSucculent plants represent a large functional group of drought-resistant plants that store water in specialized tissues. Several co-adaptive traits accompany this water-storage capacity to constitute the succulent syndrome. A widely reported anatomical adaptation of cell walls in succulent tissues allows them to fold in a regular fashion during extended drought, thus preventing irreversible damage and permitting reversible volume changes. Although ongoing research on crop and model species continuously reports the importance of cell walls and their dynamics in drought resistance, the cell walls of succulent plants have received relatively little attention to date, despite the potential of succulents as natural capital to mitigate the effects of climate change. In this review, we summarize current knowledge of cell walls in drought-avoiding succulents and their effects on tissue biomechanics, water relations, and photosynthesis. We also highlight the existing knowledge gaps and propose a hypothetical model for regulated cell wall folding in succulent tissues upon dehydration. Future perspectives of methodological development in succulent cell wall characterization, including the latest technological advances in molecular and imaging techniques, are also presented.
Moss transcription factors regulating development and defense responses to stress
Authors: Reboledo Guillermo , Agorio Astrid , Ponce De León Inés 
Published: February 2022

AbstractTranscription factors control gene expression, leading to regulation of biological processes that determine plant development and adaptation to the environment. Land colonization by plants occurred 450–470 million years ago and was accompanied by an increase in the complexity of transcriptional regulation associated to transcription factor gene expansions. AP2/ERF, bHLH, MYB, NAC, GRAS, and WRKY transcription factor families increased in land plants compared with algae. In angiosperms, they play crucial roles in regulating plant growth and responses to environmental stressors. However, less information is available in bryophytes and only in a few cases is the functional role of moss transcription factors in stress mechanisms known. In this review, we discuss current knowledge of the transcription factor families involved in development and defense responses to stress in mosses and other bryophytes. By exploring and analysing the Physcomitrium patens public database and published transcriptional profiles, we show that a high number of AP2/ERF, bHLH, MYB, NAC, GRAS, and WRKY genes are differentially expressed in response to abiotic stresses and during biotic interactions. Expression profiles together with a comprehensive analysis provide insights into relevant transcription factors involved in moss defenses, and hint at distinct and conserved biological roles between bryophytes and angiosperms.
The role of Gentiana lutea extracts in reducing UV-induced DNA damage
Authors: Cvetković Stefana , Vuletić Stefana , Vunduk Jovana , Klaus Anita , Mitić-Ćulafić Dragana , Nikolić Biljana 
Published: February 2022

Abstract
Ultraviolet (UV) radiation can result in DNA damage, mainly through direct formation of pyrimidine dimers and generation of reactive oxygen species, which can lead to the skin disorders including cancer. In accordance with this, the use of natural antigenotoxins and/or antioxidants could contribute to human health protection. Considering that plants are rich in both, the aim of this study was to investigate UV-protective and antioxidative properties of yellow gentian (Gentiana lutea), being well established in pharmacopeias and traditional medicine. Tested extracts were derived from root and shoot of the in vitro cultivated plants. Prescreening of the genotoxic properties of UVC, UVA, and the extracts, as well as the extracts’ antigenotoxicity were estimated by applying alkaline comet assay on normal fetal lung fibroblast (MRC-5) and human melanoma cells (Hs 294T). Antioxidant potential was tested in ferrous ions chelating ferric reducing antioxidant power and cupric reducing antioxidant capacity assays. Genotoxicity testing, which revealed moderate DNA-damaging potential of root extract on MRC-5 cells and high genotoxicity of shoot extract on both cell lines, pointed out nongenotoxic concentrations that could be used in antigenotoxicity assay. Doses of 63 and 3 J/cm2 for UVC and UVA, respectively, were established for antigenotoxicity study, since they induced sufficient DNA damage without notable cytotoxicity. Results of antigenotoxicity revealed strong protective effect of both extracts against UVC (the highest inhibitions 58% and 47%) and UVA (the highest inhibitions 69% and 60%), in Hs 294T and MRC-5 cells, respectively. Study of the antioxidative properties demonstrated stronger activity of shoot extract. Results obtained proved to be encouraging but further research of the UV-protective role of Gentiana lutea extracts and underlying molecular mechanisms is recommended.
Characterizing mobile element insertions in 5675 genomes
Authors: Niu Yiwei , Teng Xueyi , Zhou Honghong , Shi Yirong , Li Yanyan , Tang Yiheng , Zhang Peng , Luo Huaxia , Kang Quan , Xu Tao , He Shunmin 
Published: February 2022

Abstract
Mobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36 699 non-reference MEIs constructed from 5675 genomes, comprising 2998 Chinese samples (∼26.2×, NyuWa) and 2677 samples from the 1000 Genomes Project (∼7.4×, 1KGP). We discovered that LINE-1 insertions were highly enriched in centromere regions, implying the role of chromosome context in retroelement insertion. After functional annotation, we estimated that MEIs are responsible for about 9.3% of all protein-truncating events per genome. Finally, we built a companion database named HMEID for public use. This resource represents the latest and largest genomewide study on MEIs and will have broad utility for exploration of human MEI findings.
Single-cell genome-wide concurrent haplotyping and copy-number profiling through genotyping-by-sequencing
Authors: Masset Heleen , Ding Jia , Dimitriadou Eftychia , Ardeshirdavani Amin , Debrock Sophie , Tšuiko Olga , Smits Katrien , Peeraer Karen , Moreau Yves , Voet Thierry , Zamani Esteki Masoud , Vermeesch Joris R 
Published: February 2022

Abstract
Single-cell whole-genome haplotyping allows simultaneous detection of haplotypes associated with monogenic diseases, chromosome copy-numbering and subsequently, has revealed mosaicism in embryos and embryonic stem cells. Methods, such as karyomapping and haplarithmisis, were deployed as a generic and genome-wide approach for preimplantation genetic testing (PGT) and are replacing traditional PGT methods. While current methods primarily rely on single-nucleotide polymorphism (SNP) array, we envision sequencing-based methods to become more accessible and cost-efficient. Here, we developed a novel sequencing-based methodology to haplotype and copy-number profile single cells. Following DNA amplification, genomic size and complexity is reduced through restriction enzyme digestion and DNA is genotyped through sequencing. This single-cell genotyping-by-sequencing (scGBS) is the input for haplarithmisis, an algorithm we previously developed for SNP array-based single-cell haplotyping. We established technical parameters and developed an analysis pipeline enabling accurate concurrent haplotyping and copy-number profiling of single cells. We demonstrate its value in human blastomere and trophectoderm samples as application for PGT for monogenic disorders. Furthermore, we demonstrate the method to work in other species through analyzing blastomeres of bovine embryos. Our scGBS method opens up the path for single-cell haplotyping of any species with diploid genomes and could make its way into the clinic as a PGT application.
Imipridones affect tumor bioenergetics and promote cell lineage differentiation in diffuse midline gliomas
Authors: Przystal Justyna M , Cianciolo Cosentino Chiara , Yadavilli Sridevi , Zhang Jie , Laternser Sandra , Bonner Erin R , Prasad Rachna , Dawood Adam A , Lobeto Nina , Chin Chong Wai , Biery Matt C , Myers Carrie , Olson James M , Panditharatna Eshini , Kritzer Bettina , Mourabit Sulayman , Vitanza Nicholas A , Filbin Mariella G , de Iuliis Geoffry N , Dun Matthew D , Koschmann Carl , Cain Jason E , Grotzer Michael A , Waszak Sebastian M , Mueller Sabine , Nazarian Javad 
Published: February 2022

Abstract

Background
Pediatric diffuse midline gliomas (DMGs) are incurable childhood cancers. The imipridone ONC201 has shown early clinical efficacy in a subset of DMGs. However, the anticancer mechanisms of ONC201 and its derivative ONC206 have not been fully described in DMGs.

Methods
DMG models including primary human in vitro (n = 18) and in vivo (murine and zebrafish) models, and patient (n = 20) frozen and FFPE specimens were used. Drug-target engagement was evaluated using in silico ChemPLP and in vitro thermal shift assay. Drug toxicity and neurotoxicity were assessed in zebrafish models. Seahorse XF Cell Mito Stress Test, MitoSOX and TMRM assays, and electron microscopy imaging were used to assess metabolic signatures. Cell lineage differentiation and drug-altered pathways were defined using bulk and single-cell RNA-seq.

Results
ONC201 and ONC206 reduce viability of DMG cells in nM concentrations and extend survival of DMG PDX models (ONC201: 117 days, P = .01; ONC206: 113 days, P = .001). ONC206 is 10X more potent than ONC201 in vitro and combination treatment was the most efficacious at prolonging survival in vivo (125 days, P = .02). Thermal shift assay confirmed that both drugs bind to ClpP, with ONC206 exhibiting a higher binding affinity as assessed by in silico ChemPLP. ClpP activation by both drugs results in impaired tumor cell metabolism, mitochondrial damage, ROS production, activation of integrative stress response (ISR), and apoptosis in vitro and in vivo. Strikingly, imipridone treatment triggered a lineage shift from a proliferative, oligodendrocyte precursor-like state to a mature, astrocyte-like state.

Conclusion
Targeting mitochondrial metabolism and ISR activation effectively impairs DMG tumorigenicity. These results supported the initiation of two pediatric clinical trials (NCT05009992, NCT04732065).
Distinct metabolic hallmarks of WHO classified adult glioma subtypes
Authors: Björkblom Benny , Wibom Carl , Eriksson Maria , Bergenheim A Tommy , Sjöberg Rickard L , Jonsson Pär , Brännström Thomas , Antti Henrik , Sandström Maria , Melin Beatrice 
Published: February 2022

AbstractBackgroundGliomas are complex tumors with several genetic aberrations and diverse metabolic programs contributing to their aggressive phenotypes and poor prognoses. This study defines key metabolic features that can be used to differentiate between glioma subtypes, with potential for improved diagnostics and subtype targeted therapy.MethodsCross-platform global metabolomic profiling coupled with clinical, genetic, and pathological analysis of glioma tissue from 224 tumors—oligodendroglioma (n = 31), astrocytoma (n = 31) and glioblastoma (n = 162)—were performed. Identified metabolic phenotypes were evaluated in accordance with the WHO classification, IDH-mutation, 1p/19q-codeletion, WHO-grading 2–4, and MGMT promoter methylation.ResultsDistinct metabolic phenotypes separate all six analyzed glioma subtypes. IDH-mutated subtypes, expressing 2-hydroxyglutaric acid, were clearly distinguished from IDH-wildtype subtypes. Considerable metabolic heterogeneity outside of the mutated IDH pathway were also evident, with key metabolites being high expression of glycerophosphates, inositols, monosaccharides, and sugar alcohols and low levels of sphingosine and lysoglycerophospholipids in IDH-mutants. Among the IDH-mutated subtypes, we observed high levels of amino acids, especially glycine and 2-aminoadipic acid, in grade 4 glioma, and N-acetyl aspartic acid in low-grade astrocytoma and oligodendroglioma. Both IDH-wildtype and mutated oligodendroglioma and glioblastoma were characterized by high levels of acylcarnitines, likely driven by rapid cell growth and hypoxic features. We found elevated levels of 5-HIAA in gliosarcoma and a subtype of oligodendroglioma not yet defined as a specific entity, indicating a previously not described role for the serotonin pathway linked to glioma with bimorphic tissue.ConclusionKey metabolic differences exist across adult glioma subtypes.
A Cold-Blooded Tiptoer: Nonresolving Cellulitis in an Immunocompromised Patient
Authors: Kitaura Satoshi , Okamoto Koh , Wakabayashi Yoshitaka , Okada Yuta , Okazaki Aiko , Ikeda Mahoko , Okugawa Shu , Fujimoto Fumie , Bujo Chie , Minatsuki Shun , Tsushima Kensuke , Chikamatsu Kinuyo , Mitarai Satoshi , Moriya Kyoji 
Published: February 2022

Abstract
Mycobacterium haemophilum is a nontuberculous mycobacteria (NTM) with a predilection for skin and soft tissue infection (SSTI) in the immunocompromised host. We report a case of disseminated M haemophilum infection initially presenting as a nonresolving subacute cellulitis of bilateral lower extremities. Genetic sequencing was used for final identification, while a commercially available polymerase chain reaction test returned a false-positive result for Mycobacterium intracellulare. Consequently, we highlight the importance of M haemophilum as a major differential diagnosis of SSTI in the immunocompromised host and the need for careful interpretation of rapid diagnostic tests.
Early seed development requires the A-type ATP-binding cassette protein ABCA10
Authors: Shin Seungjun , Chairattanawat Chayanee , Yamaoka Yasuyo , Yang Qianying , Lee Youngsook , Hwang Jae-Ung 
Published: February 2022

AbstractA-type ATP-binding cassette (ABCA) proteins transport lipids and lipid-based molecules in humans, and their malfunction is associated with various inherited diseases. Although plant genomes encode many ABCA transporters, their molecular and physiological functions remain largely unknown. Seeds are rapidly developing organs that rely on the biosynthesis and transport of large quantities of lipids to generate new membranes and storage lipids. In this study, we characterized the Arabidopsis (Arabidopsis thaliana) ABCA10 transporter, which is selectively expressed in female gametophytes and early developing seeds. By 3 d after flowering (DAF), seeds from the abca10 loss-of-function mutant exhibited a smaller chalazal endosperm than those of the wild-type. By 4 DAF, their endosperm nuclei occupied a smaller area than those of the wild-type. The endosperm nuclei of the mutants also failed to distribute evenly inside the seed coat and stayed aggregated instead, possibly due to inadequate expansion of abca10 endosperm. This endosperm defect might have retarded abca10 embryo development. At 7 DAF, a substantial portion of abca10 embryos remained at the globular or earlier developmental stages, whereas wild-type embryos were at the torpedo or later stages. ABCA10 is likely involved in lipid metabolism, as ABCA10 overexpression induced the overaccumulation of triacylglycerol but did not change the carbohydrate or protein contents in seeds. In agreement, ABCA10 localized to the endoplasmic reticulum (ER), the major site of lipid biosynthesis. Our results reveal that ABCA10 plays an essential role in early seed development, possibly by transporting substrates for lipid metabolism to the ER.
Early Intervention Services for Schizophrenia: Looking Back and Looking Ahead
Authors: Srihari Vinod H , Keshavan Matcheri S 
Published: February 2022

Abstract
This invited commentary provides a conceptual history of modern early intervention services, briefly reviews the accomplishments of an international clinical and research community, and offers proposals for how such services might participate in the next generation of progress. In keeping with the theme of this column, we make the argument that such services should orient around bi-directional knowledge translation across basic, clinical and policy domains.
Ambiguities in Action Ascription
Authors: Stivers Tanya , Rossi Giovanni , Chalfoun Andrew 
Published: February 2022

Abstract
In everyday interactions with one another, speakers not only say things but also do things like offer, complain, reject, and compliment. Through observation, it is possible to see that much of the time people unproblematically understand what others are doing. Research on conversation has further documented how speakers’ word choice, prosody, grammar, and gesture all help others to recognize what actions they are performing. In this study, we rely on spontaneous naturally occurring conversational data where people have trouble making their actions understood to examine what leads to ambiguous actions, bringing together prior research and identifying recurrent types of ambiguity that hinge on different dimensions of social action. We then discuss the range of costs and benefits for social actors when actions are clear versus ambiguous. Finally, we offer a conceptual model of how, at a microlevel, action ascription is done. Actions in interaction are building blocks for social relations; at each turn, an action can strengthen or strain the bond between two individuals. Thus, a unified theory of action ascription at a microlevel is an essential component for broader theories of social action and of how social actions produce, maintain, and revise the social world.
Outcomes After Targeted Treatment Based on Somatic Tumor Genetic Testing for Women With Gynecologic Cancers
Authors: Somasegar Sahana , Hoppenot Claire , Kuchta Kristine , Sereika Annette , Khandekar Janardan , Rodriguez Gustavo , Moore Elena , Hurteau Jean , Vogel Tilley Jenkins 
Published: February 2022

(Abstracted from Gynecol Oncol 2021;163:220–228)
Molecular tumor profiling with next-generation sequencing (NGS) has become increasingly used in the evaluation and treatment planning for primary and recurrent gynecologic cancer. This is driven by studies demonstrating that NGS-guided treatment results in longer time to treatment failure and overall survival while also being better tolerated than conventional chemotherapy.
Performance of Six Birth-Weight and Estimated-Fetal-Weight Standards for Predicting Adverse Perinatal Outcome: A 10-Year Nationwide Population-Based Study
Authors: Choi S. K. Y. , Gordon A. , Hilder L. , Henry A. , Hyett J. A. , Brew B. K. , Joseph F. , Jorm L. , Chambers G. M. 
Published: February 2022

(Abstracted from Ultrasound Obstet Gynecol 2021;58:264–277)
One of the risk factors for perinatal mortality and morbidity is abnormal fetal growth. The goal of this study was to study the prediction of adverse perinatal outcomes in preterm and term babies based on 3 birth weight (BW) standards (Australian population-based, Fenton, and INTERGROWTH-21st) and 3 estimated fetal weight (EFW) standards (Hadlock, INTERGROWTH-21st, and World Health Organization [WHO]) to classify small-for-gestational age (SGA) and large-for-gestational age (LGA).
Prenatal exposure to insecticides and child cardiometabolic risk factors in the VHEMBE birth cohort
Authors: Kim Joanne , Yang Seungmi , Moodie Erica EM , Obida Muvhulawa , Bornman Riana , Eskenazi Brenda , Chevrier Jonathan 
Published: February 2022

Background:
As part of malaria control programs, many countries spray dichlorodiphenyltrichloroethane (DDT) or pyrethroid insecticides inside dwellings in a practice called indoor residual spraying that results in high levels of exposure to local populations. Gestational exposure to these endocrine- and metabolism-disrupting chemicals may influence child cardiometabolic health.

Methods:
We measured the serum concentration of DDT and dichlorodiphenyldichloroethylene (DDE) and urinary concentration of pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA) in peripartum samples collected between August 2012 and December 2013 from 637 women participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), a birth cohort study based in Limpopo, South Africa. We applied marginal structural models to estimate the relationship between biomarker concentrations and child-size (height and weight), adiposity (body mass index [BMI], body fat percentage, waist circumference) and blood pressure at 5 years of age.

Results:
Maternal concentrations of all four pyrethroid metabolites were associated with lower adiposity including reduced BMI z-scores, smaller waist circumferences, and decreased body fat percentages. Reductions in BMI z-score were observed only among children of mothers with sufficient energy intake during pregnancy (βcis-DCCA,
trans
-DCCA=−0.4, 95% confidence interval (CI) = −0.7,−0.1; pinteraction=0.03 and 0.04, respectively) but there was no evidence of effect modification for the other measures of adiposity. Maternal p,p’-DDT concentrations were associated with a reduction in body fat percentage (β = −0.4%, 95% CI = −0.8,−0.0).

Conclusions:
Gestational exposure to pyrethroids may reduce adiposity in children at 5 years of age.
Case Report
Authors: Park Hiromichi , Bhagat Hita , Messer William , Maier Marissa 
Published: February 2022

Abstract
A case of a 56-year-old man with severe COVID-19 infection who later developed septic shock because of disseminated cryptococcemia. This is the first published case of culture proven non-human immunodeficiency virus nontransplant COVID-associated Cryptococcus neoformans meningitis. Profound immunological impact of COVID-19 has been observed with associated increased risk of developing opportunistic infections.
A Pain in the Flank
Authors: Masood Maryam , Panek David , Butler-Wu Susan , Spellberg Brad 
Published: February 2022

Abstract
Culture-negative endocarditis is rarely encountered and that caused by Bartonella quintana has been very rarely described. Virtually, all such cases in the literature have been related to human body louse exposure due to homelessness or living in refugee camps or similar environments. We describe a case of B. guintana endocarditis in a healthy adult with no exposure to body lice and no other risk factors. The patient also presented without fevers, which is also very uncommon. Rather, she presented with isolated flank pain due to a renal infarction, which led to an investigation for an endovascular source for emboli. The diagnosis was confirmed by a combination of serology and polymerase chain reaction from the excised valve. This case highlights the potentially atypical nature of culture-negative endocarditis and the power of multiplex polymerase chain reaction to make diagnoses that likely would not have been established in the past.
Human Immunodeficiency Virus–Related Infection in the Hand
Authors: Scarborough Alexander , Wharton Rupert M. H. , Nelson Mark , Horwitz Maxim D. 
Published: February 2022

Abstract
Chronic HIV infection is increasingly common in clinical practice, and it is necessary for clinicians to have an understanding of specific infections and know how to treat them in this patient cohort. Delayed or incomplete treatment of infection in the hand may cause irreversible stiffness and loss of function. A literature review was conducted using the databases MEDLINE, Embase, EmCare, and CINAHL. Nineteen full-text articles were used to assimilate current evidence on the nature and implications of hand and upper extremity infection in HIV individuals. The HIV patients commonly require multiple surgical episodes to establish control of infection, prolonged hospital stay, and prolonged antimicrobial therapy to establish cure. Prompt referral to the hand surgery team is vital in HIV patients with hand infections to avoid long-lasting sequelae.