bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of a population of leaf-eared micePhyllotis vaccarumabove 6,000 m in the Andes and a survey of high-elevation mammals
Authors: Steppan Scott J , Bowen Thomas , Bangs Max R , Farson Matthew , Storz Jay F , Quiroga-Carmona Marcial , D’Elía Guillermo , Vimercati Lara , Dorador Ortiz Cristina , Zimmerman Graham , Schmidt Steve K
Published: February 2022

Biologists have long pondered the extreme limits of life on Earth, including the maximum elevation at which species can live and reproduce. Here we review evidence of a self-sustaining population of mice at an elevation that exceeds that of all previously reported for mammals. Five expeditions over 10 years to Volcán Llullaillaco on the Argentina/Chile border observed and collected mice at elevations ranging from 5,070 m at the mountain’s base to the summit at 6,739 m (22,110 feet). Previously unreported evidence includes observations and photographs of live animals and mummified remains, environmental DNA, and a soil microbial community reflecting animal activity that are evaluated in combination with previously reported video recordings and capture of live mice. All of the evidence identifies the mouse as the leaf-eared mouse Phyllotis vaccarum, and it robustly places the population within a haplotype group containing individuals from the Chilean Atacama Desert and nearby regions of Argentina. A critical review of the literature affirms that this population is not only an elevational record for mammals but for all terrestrial vertebrates to date, and we further find that many extreme elevations previously reported for mammals are based on scant or dubious evidence.
Ground-Truthing Forest Change Detection Algorithms in Working Forests of the US Northeast
Authors: Desrochers Madeleine L , Tripp Wayne , Logan Stephen , Bevilacqua Eddie , Johnson Lucas , Beier Colin M
Published: February 2022

The need for reliable landscape-scale monitoring of forest disturbance has grown with increased policy and regulatory attention to promoting the climate benefits of forests. Change detection algorithms based on satellite imagery can address this need but are largely untested for the forest types and disturbance regimes of the US Northeast, including management practices common in northern hardwoods and mixed hardwood-conifer forests. This study ground-truthed the “off-the-shelf” outputs of three satellite-based change detection algorithms using detailed harvest records and maps covering 43,000 ha of working forests in northeastern New York.
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

Succulent 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

Transcription 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

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

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

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

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

Background

Gliomas 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.

Methods

Cross-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.

Results

Distinct 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.

Conclusion

Key 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

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

A-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

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

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

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

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

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.
Disseminated Tuberculosis in an Immunocompetent Patient Associated With the Use of Contaminated Bone Matrix Graft in Spine Surgery
Authors: Cullen Grace D. , Tabaja Hussam , Ogbonna Chioma P. , Menze Anna K. , Escalante Patricio , Wilson John W.
Published: February 2022

Miliary tuberculosis (TB) is a rare and potentially fatal form of disseminated TB. Disseminated TB involving the central nervous system (CNS) may be seen in up to nearly a third of miliary TB cases. We describe a case of miliary TB with CNS involvement and suspected hepatobiliary involvement in an immunocompetent patient after an elective spine surgery. Given the patient's unusual presentation in the absence of risk factors for TB, diagnosis was delayed. We were later informed that the bone graft he received during spine surgery, FiberCel (“FiberCel”) Fiber Viable Bone Matrix (Aziyo Biologics, Inc, Richmond, Calif), was contaminated with TB. This patient is 1 of almost 2 dozens reported to be affected. This case represents a novel presentation of TB due to contaminated cadaveric bone allograft matrix implantation, with notable rapid dissemination and CNS involvement.
Impact of a Social Justice Course in Graduate Nursing Education
Authors: Crawford Daniel , Jacobson Diana , McCarthy Marianne
Published: February 2022

Background:

Social justice and health equity are foundational concepts to the graduate-prepared nurse's role. However, the integration of these concepts into graduate nursing education has been unclear.

Purpose:

This study examined the impact of a newly created social justice course in a graduate nursing program.

Methods:

The impact of the Health Equity and Social Justice course on students' values and attitudes toward social justice was investigated through analysis of quantitative and qualitative data generated in the course.

Results:

Data were collected from 41 graduate nursing students. Findings demonstrated that students who completed the course had an increased endorsement of social justice values, goals, and behaviors. Students universally found the course to be transformational.

Conclusions:

A social justice course in graduate education can be transformational in shaping students' values and attitudes toward health equity and social justice.
Enhanced Recovery Protocol Enhances Postdischarge Recovery After Laparoscopic Sacrocolpopexy
Authors: Pan Christine , Hale Douglass , Heit Michael
Published: February 2022

(Abstracted from Female Pelvic Med Reconstr Surg 2021;27:667–671)

ERAS (enhanced recovery after surgery) guidelines were published in the United States for multiple surgical specialties, including gynecology in 2016. Previous studies on ERAS have focused on the immediate perioperative period.
Sexual coercion in a natural mandrill population
Authors: Smit Nikolaos , Baniel Alice , Roura-Torres Berta , Amblard-Rambert Paul , Charpentier Marie J. E. , Huchard Elise
Published: February 2022

Increasing evidence indicates that sexual coercion is widespread. While some coercive strategies are conspicuous, such as forced copulation or sexual harassment, less is known about the ecology and evolution of intimidation, where repeated male aggression promotes future rather than immediate mating success with targeted females. Although known in humans, intimidation was recently reported in chimpanzees (Pan troglodytes) and chacma baboons (Papio ursinus), where males are regularly violent against females. Here, we investigate the nature of male coercive strategies in wild mandrills (Mandrillus sphinx), a primate living in large polygynandrous groups where severe male aggression towards females is rare and females can form coalitions against males. Yet, we found support for all three predictions of the sexual coercion hypothesis, namely that male aggression (1) specifically targets sexually receptive females, (2) inflicts costs to these females, and (3) increases male mating success in the long-term. These results hold true when considering only non-physical threats, or only severe aggression. Finally, we show that high-ranking females are most targeted by males, probably because of their higher reproductive performances, while high-ranking males are most coercive. These results indicate that sexual intimidation is widespread in sexually dimorphic and group-living mammals, and that males and females vary in their propensities to use, and to be exposed to sexual coercion, respectively.
Novel AlphasynucleinPAN in human Mesenchymal Stem Cells-derived neurons masks SNCA140 and creates dissociation of deleterious SNCA98 in astrocytoma stem cells
Authors: Owoola Akeem G. , Okolicsanyi Rachel K. , Griffiths Lyn R. , Haupt Larisa M.
Published: February 2022

This manuscript has been withdrawn by the authors as it was submitted and made public without the full consent of all the authors. If you have any questions, please contact the corresponding author.
DNA Aptamer Gold Nanoparticle Colorimetric Diagnostic Test Kit of Saliva Samples for SARS_Cov2 Virus Linked to Mobile Phone Application (Aptamex™)
Authors: Chotimah Siska Nurul , Putra Yudhistira Eka , Ng Jocelyn H. , Tijptaningrum Agustyas , Sahara Nabilla Sonia , Arfianti  , Amaliah Ridha , Edel Michael J. , Rodriguez Mayreli Ortiz , Llerga Teresa Mairal , O’Sullivan Ciara K. , Goh Steven
Published: February 2022

The development of the use of DNA aptamers for clinical applications to detect human diseases is at the forefront of research. Synthetic DNA aptamers are easy to generate, inexpensive, highly specific and have been postulated to replace antibodies for research and clinical use. Despite the considerable amount of published work on the use of DNA aptamers for research use, to date they have not been exploited for clinical diagnostics. SARS-CoV-2 virus is a pandemic causing a global disruptive event preventing people from travel, work and leisure activities resulting in a major health crisis, hospital overloads and a high death rate. The detection of SARS-CoV-2 virus in communities is therefore very important, especially for returning normality of life. The current gold standard for detection of SARS-CoV-2 virus is RT-PCR, a technique that is relatively expensive and most importantly with a slow turnaround time between sample procurement and result. This paper describes the development of a rapid, accurate, low-cost, facile to use assay for the detection of the SARS-CoV-2 spike protein in saliva. The assay exploits a simple system based on the use of a gold nanoparticle-aptamer complex, that can be easily produced and distributed, facilitating its deployment to the point-of-need, potentially reaching millions of individuals in resource-limited settings. The proposed colorimetric diagnostic test kit uses a SARS-CoV-2 DNA aptamer adsorbed on gold nanoparticles and salt-induced aggregation to detect the presence of SARS-CoV-2 Spike protein in saliva samples indicated by a color change of the gold absorbance spectrum that can be quantified by a spectrophotometer, linked to a mobile phone for data processing and analysis. The assay parameters were optimized and then tested in a field calibration clinical test in Indonesia. At a research level, a limit of detection of ca. 1.25 nM to synthetic spike protein (S1) was observed and a method to test human saliva samples developed. The DNA aptamer was specific to SARS-CoV-2, with minor cross-reactivity observed with MERS and SARS-CoV-1, but negligible cross-reactivity seen with common cold coronaviruses. A calibration clinical test of patients in Indonesia demonstrated a classification resulting in a > 97% sensitivity and a > 97% specificity compared with saliva RT-PCR test for SARS-CoV-2. Furthermore, the data indicates that anatomical location and sample type (swab vs saliva) can affect RT-PCR results. In conclusion, we have developed the use of a robust and reproducible aptamer-gold nanoparticle assay for clinical diagnostic use based on a colorimetric system that is cheap, simple, rapid, sensitive and can be employed for large scale testing of human populations for SARS-CoV-2 virus.
Ethnic disparities in immunisation: analyses of zero-dose prevalence in 64 low- and middle-income countries
Authors: Cata-Preta Bianca O , Santos Thiago M , Wendt Andrea , Hogan Daniel R , Mengistu Tewodaj , Barros Aluísio JD , Victora Cesar G
Published: February 2022

Background

The Sustainable Development Goals (SDGs) recommend stratification of health indicators by ethnic group, yet there are few studies that have assessed if there are ethnic disparities in childhood immunisation in low- and middle-income countries (LMICs).

Methods

We identified 64 LMICs with standardized national surveys carried out since 2010, which provided information on ethnicity or a proxy variable and on vaccine coverage; 339 ethnic groups across the 64 countries were identified after excluding those with fewer than 50 children in the sample and countries with a single ethnic group. Lack of vaccination with diphtheria-pertussis-tetanus (DPT) vaccine – a proxy for no access to routine vaccination or ‘zero-dose’ status – was the outcome of interest. Differences among ethnic groups were assessed using a chi-squared test for heterogeneity. Additional analyses controlled for household wealth, maternal education and urban-rural residence.

Findings

The median gap between the highest and lowest zero-dose prevalence ethnic groups in all countries was equal to 10 percentage points (interquartile range 4-22; range 1 to 84) and the median ratio was 3.3 (interquartile range 1.8-6.7; range 1.1-30.4). In 35 of the 64 countries, there was significant heterogeneity in zero-dose prevalence among the ethnic groups. In most countries, adjustment for wealth, education and residence made little difference to the ethnic gaps, but in four countries (Angola, Benin, Nigeria, and Philippines) the high-low ethnic gap decreased by over 15 pp after adjustment. Children belonging to a majority group had 29% lower prevalence of zero-dose compared to the rest of the sample.

Interpretation

Statistically significant ethnic disparities in child immunisation were present in over half of the countries studied. Such inequalities have been seldom described in the published literature. Regular analyses of ethnic disparities are essential for monitoring trends, targeting resources and assessing the impact of health interventions to ensure zero-dose children are not left behind in the Sustainable Development Goals era.

Funding

Bill & Melinda Gates Foundation, Gavi, the Vaccine Alliance, Wellcome Trust, and Associação Brasileira de Saúde Coletiva.
SARS-CoV-2 neutralization after mRNA vaccination and variant breakthrough infection
Authors: Gaebler Christian , DaSilva Justin , Bednarski Eva , Muecksch Frauke , Schmidt Fabian , Weisblum Yiska , Millard Katrina G. , Turroja Martina , Cho Alice , Wang Zijun , Caskey Marina , Nussenzweig Michel C. , Bieniasz Paul D. , Hatziioannou Theodora
Published: February 2022

Vaccination and infection by viral variants are shaping population immunity to SARS-CoV-21 and breakthrough infections of vaccinated or previously infected individuals have become common as variants evade preexisting immunity. Omicron (B.1.1.529) is highly resistant to plasma neutralizing antibodies elicited by infection with prior variants and the 2-dose mRNA vaccination regimens. However, vaccination after infection or a third mRNA vaccine dose elicit high levels of neutralizing antibodies that can also neutralize omicron to a degree2-4. We compared neutralizing antibody titers in 54 individuals that had received 2 or 3 doses of mRNA vaccines and had experienced breakthrough infection with SARS-CoV-2 variants.
The isoforms of pyruvate kinase act as nutrient sensors for the β-cell KATP channel
Authors: Foster Hannah R. , Ho Thuong , Potapenko Evgeniy , Sdao Sophia M. , Lewandowski Sophie L. , VanDeusen Halena R. , Davidson Shawn M. , Cardone Rebecca L. , Prentki Marc , Kibbey Richard G. , Merrins Matthew J.
Published: February 2022

Pyruvate kinase (PK) and the phosphoenolpyruvate (PEP) cycle play key roles in nutrient-stimulated KATP channel closure and insulin secretion. To identify the PK isoforms involved, we generated mice lacking β-cell PKm1, PKm2, and mitochondrial PEP carboxykinase (PCK2) that generates mitochondrial PEP. Glucose metabolism generates both glycolytic and mitochondrially-derived PEP, which triggers KATP closure through local PKm1 and PKm2 signaling at the plasma membrane. Amino acids, which generate mitochondrial PEP without producing glycolytic fructose 1,6-bisphosphate to allosterically activate PKm2, signal through PKm1 to raise ATP/ADP, close KATP channels, and stimulate insulin secretion. Raising cytosolic ATP/ADP with amino acids is insufficient to close KATP channels in the absence of PK activity or PCK2, indicating that KATP channels are regulated by mitochondrially-derived PEP that provides ATP via plasma membrane-associated PK, but not via mitochondrially-derived ATP. Following membrane depolarization, the PEP cycle is also involved in an “off-switch” that facilitates KATP channel reopening and Ca2+ extrusion, as shown by PK activation experiments and β-cell PCK2 deletion that prolonged Ca2+ oscillations and increased insulin secretion. In conclusion, the differential response of PKm1 and PKm2 to the glycolytic and mitochondrial sources of PEP influences the β-cell nutrient response, and controls the oscillatory cycle regulating insulin secretion.
Simultaneous therapeutic targeting of inflammation and virus ameliorates influenza pneumonia and protects from morbidity and mortality
Authors: Pandey Pratikshya , Al Rumaih Zahrah , Kels Ma. Junaliah Tuazon , Ng Esther , Rajendra KC , Malley Roslyn , Chaudhri Geeta , Karupiah Gunasegaran
Published: February 2022

Pneumonia is a severe complication caused by inflammation of the lungs following infection with seasonal and pandemic strains of influenza A virus (IAV) that can result in lung pathology, respiratory failure and death. There is currently no treatment available for severe disease and pneumonia caused by IAV. Antivirals are available, but they are far from satisfactory if treatment is not initiated within 48 hours of symptoms onset. Influenza complications and mortality are often associated with high viral load and excessive lung inflammatory cytokine response. Therefore, we simultaneously targeted IAV with the antiviral drug oseltamivir and inflammation with the anti-inflammatory drug etanercept, targeting TNF after the onset of clinical signs to treat IAV pneumonia effectively. The combined treatment effectively reduced lung viral load, lung pathology, morbidity and mortality during respiratory IAV infection in mice, contemporaneous with significant downregulation of the inflammatory cytokines TNF, IL-1β, IL-6, IL-12p40, chemokines CCL2, CCL5 and CXCL10 and dampened STAT3 activation. Consequently, combined therapy with oseltamivir and a STAT3 inhibitor also effectively reduced clinical disease and lung pathology. Combined treatment using either of the anti-inflammatory drugs and oseltamivir dampened an overlapping set of cytokines. Thus, combined therapy targeting a specific cytokine or cytokine signaling pathway plus an antiviral drug provides an effective treatment strategy for ameliorating IAV pneumonia. Effective treatment of IAV pneumonia required multiple doses of etanercept and a high dose of oseltamivir. This approach might apply to the treatment of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Significance Statement

Antivirals against influenza A virus (IAV) are ineffective in treating pneumonia if administered 48 h after onset of disease symptoms. The host inflammatory response and tissue damage caused by IAV are responsible for lung pathology. We reasoned that targeting both virus and inflammation would be more effective in reducing lung pathology and pneumonia, morbidity and mortality. The simultaneous treatment with an anti-inflammatory drug targeting TNF or STAT3, combined with the anti-IAV antiviral drug, oseltamivir, significantly improved clinical disease, reduced lung viral load and pathology, and protected mice from severe pneumonia. The combined treatment suppressed multiple pro-inflammatory cytokines and cytokine signaling pathways. Thus, after the onset of disease symptoms, both virus and inflammation must be targeted to treat IAV pneumonia effectively.
Tongue immune compartment analysis reveals spatial macrophage heterogeneity
Authors: Lyras Ekaterini Maria , Zimmermann Karin , Wagner Lisa Katharina , Dörr Dorothea , Fischer Cornelius , Jung Steffen , Yona Simon , Hovav Avi-Hai , Stenzel Werner , Dommerich Steffen , Conrad Thomas , Leutz Achim , Mildner Alexander
Published: February 2022

The tongue is a unique muscular organ situated in the oral cavity where it is involved in taste sensation, mastication and articulation. As a barrier organ, which is constantly exposed to environmental pathogens, the tongue is expected to host an immune cell network ensuring local immune defence. However, the composition and the transcriptional landscape of the tongue immune system are currently not completely defined. Here we characterised the tissue-resident immune compartment of the murine tongue during development, health and disease, combining single cell RNA-sequencing with in situ immunophenotyping. We identified distinct local immune cell populations and described two specific subsets of tongue-resident macrophages occupying discrete anatomical niches. Cx3cr1+ macrophages were located specifically in the highly innervated lamina propria beneath the tongue epidermis and at times in close proximity to fungiform papillae. Folr2+ macrophages were detected in deeper muscular tissue. The two macrophage subsets originate from a common proliferative precursor during early postnatal development and responded differently to systemic LPS in vivo. Our description of the under-investigated tongue immune system sets a starting point to facilitate research on tongue immune-physiology and pathology including cancer and taste disorders.
InfoMuNet: Information-theory-based Functional Muscle Network Tracks Sensorimotor Integration Post-stroke
Authors: O’Keeffe Rory , Shirazi Seyed Yahya , Bilaloglu Seda , Jahed Shayan , Bighamian Ramin , Raghavan Preeti , Atashzar S. Farokh
Published: February 2022

Sensory information is critical for motor coordination. However, understanding sensorimotor integration is complicated, especially in individuals with nervous system impairment. This research presents a novel functional biomarker, based on a nonlinear network graph of muscle connectivity, called InfoMuNet, to quantify the role of sensory information in motor performance. Thirty-two individuals with post-stroke hemiparesis performed a grasp-and-lift task while muscle activities were measured using eight surface electromyography (sEMG) sensors. Subjects performed the task with their affected hand before and after exposure to the sensory stimulation elicited by performing the task with the less-affected hand. For the first time, this work shows that InfoMuNet robustly quantifies functional muscle connectivity improvements in the affected hand after exposure of the less-affected side to sensory information. >90% of the subjects conformed with the improvement resulting from this sensory exposure. InfoMuNet also shows high sensitivity to tactile, kinesthetic, and visual input alterations at the subject level, highlighting the potential use in precision rehabilitation interventions.
Aryl hydrocarbon receptor-dependent and -independent pathways mediate curcumin anti-aging effects
Authors: Brinkmann Vanessa , Romeo Margherita , Larigot Lucie , Hemmers Anne , Tschage Lisa , Kleinjohann Jennifer , Schiavi Alfonso , Steinwachs Swantje , Esser Charlotte , Menzel Ralph , Tagliabue Sara Giani , Bonati Laura , Cox Fiona , Ale-Agha Niloofar , Jakobs Philipp , Altschmied Joachim , Haendeler Judith , Coumoul Xavier , Ventura Natascia
Published: February 2022

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose activity can be modulated by polyphenols such as curcumin. AhR and curcumin have evolutionarily conserved effects on aging. Here, we investigated whether and how the AhR mediates the anti-aging effects of curcumin across species. Using a combination ofin vivo, in vitro, andin silicoanalyses, we demonstrated that curcumin has AhR-dependent or -independent effects in a context-specific manner. We found that inCaenorhabditis elegans, AhR mediates curcumin-induced lifespan extension, most likely through a ligand-independent inhibitory mechanism related to its antioxidant activity. Curcumin also showed AhR-independent anti-aging activities such as protection against aggregation-prone proteins and oxidative stress inC. elegansand promotion of the migratory capacity of human primary endothelial cells. These AhR-independent effects are largely mediated by the Nrf2/SKN-1 pathway.

Graphical Abstract