bluuebunny/crossref_metadata_2025 huggingface dataset:
Family Typology and 6-Year All-Cause Mortality Among U.S. Chinese Older Adults
Authors: Li Mengting , Dong XinQi
Published: August 2022

Objectives

Previous research focused on the individual risk factors of mortality, while little is known about how family environment could influence mortality in later life. This study aims to examine mortality risks in different family types and what family type may increase mortality risk for older adults with medical comorbidities or functional impairment.

Methods

Data were derived from the Population Study of Chinese Elderly (PINE) in Chicago. The baseline interview was conducted from 2011 to 2013. The outcome was 6-year all-cause mortality. Family typology included tight-knit, unobligated-ambivalent, commanding-conflicted, and detached types. Cox proportional hazards models were used.

Results

The study sample consisted of 3,019 older adults and 372 participants passed away during 6 years follow-up. Older adults in the detached type had higher risks of mortality than those in the tight-knit type (hazard ratio: 1.45 [95% confidence interval, 1.02–2.07]). Regarding the interaction effect between family typology and functional impairment, older adults with higher levels of physical impairment (1.29 [1.07–1.56]) and cognitive impairment (1.07 [1.01–1.14]) nested in the commanding-conflicted type had higher mortality risks than their counterparts nested in the tight-knit type.

Discussion

In this longitudinal cohort study with a 6-year follow-up, older adults nested in the detached family type had higher 6-year mortality risks than those nested in the tight-knit family type. Living in the commanding-conflicted family increased the 6-year mortality risks for older adults with physical impairment or cognitive impairment compared with their counterparts residing in the tight-knit family type.
On the Use of Encomiastic Topoi in Hebrews
Authors: Martin Michael Wade , Whitlark Jason A
Published: August 2022

This study examines the debated questions of whether and to what extent the author of Hebrews employs Greco-Roman rhetorical topoi of praise in the speech’s various theological portraits. The study compares and contrasts five epideictic pieces in Hebrews, demonstrating the common topical template employed in their composition, the compositional tendencies evident among them, and the conformity of these tendencies to Greco-Roman rhetorical convention. The evidence points to a writer who is consciously following rhetorical convention at every turn. In the light of these findings, the study then addresses several questions that collectively contribute to scholarly doubt about the author’s use of topoi.
Exposure to the Organophosphate Pesticide Fenitrothion Directly Induced Defects in Mouse Embryonic External Genitalia
Authors: Acebedo Alvin R , Alcantara Mellissa C , Nakanishi Tsuyoshi , Ogawa Takehiko , Yamada Gen , Suzuki Kentaro
Published: August 2022

Many industrial chemicals have been reported as antiandrogenic substances. Exposure to these substances represents a potential risk to human health, particularly to the development of reproductive organs such as embryonic external genitalia (eExG). Currently, there is a need for more assay systems that can elucidate the toxicological actions and mechanisms of endocrine-disrupting chemicals. In this study, we show that the eExG slice culture assay is useful for the evaluation of the differing modes of action of endocrine-disrupting chemicals on urethra formation. We assessed the possible endocrine-disrupting activity of 3 chemicals with reported antiandrogenic function, diazinon, dibutyl phthalate, and fenitrothion (FNT) on eExG slices. Exposure to FNT, but not diazinon and dibutyl phthalate, induced defects of androgen-induced urethral masculinization and reduced expression of the androgen-target gene Mafb. Live imaging analyses showed that FNT treatment inhibited androgen-dependent MAFB induction within 12 h. Furthermore, FNT-treated tissue slices showed reduced expression of the androgen receptor. These results indicate that FNT disrupts androgen signaling by reduction of androgen receptor expression during androgen-induced eExG masculinization. This study thus highlights the importance of animal models, which allow for the effective assessment of tissue-specific endocrine-disrupting activity to further reveal the etiology of chemical-induced congenital anomalies.
Remote blood pressure monitoring with a wearable photoplethysmographic device in patients undergoing coronary angiography: the senbiosys substudy
Authors: Schukraft Sara , Haddad Serj , Faucherre Yannick , Arroyo Diego , Togni Mario , Barison Anthony , Boukhayma Assim , Cook Stéphane , Caizzone Antonino
Published: August 2022

Aims

The purpose of this study is to evaluate the accuracy of the Senbiosys device in measuring blood pressure (BP) by photoplethysmography (PPG) in patients undergoing coronary angiography.

Methods

This is a substudy within the Senbiosys trial, which is a prospective, single-arm, single-center study, evaluating the accuracy of BP estimation of the Senbiosys device compared to invasive BP. Patients referred for coronary angiography underwent invasive BP measurement and simultaneously wore the Senbiosys ring. SBP and DBP estimations measured by the Senbiosys device were compared with invasive measurements.

Results

A total of 25 patients were included. Overall, 708 epochs with adequate PPG signal belonging to 17 patients were analyzed. A total of 84% of the SBP estimates and 99% of the DBP estimates have an absolute error of less than 10 mmHg compared with the invasive measurements. Mean difference was 2.3 ± 7.0 mmHg and 0.5 ± 3.5 mmHg for SBP and DBP, respectively.

Conclusion

The Senbiosys device is accurate enough to determine BP in a selected population undergoing coronary angiography.
Emerging strategies for antibody-mediated rejection
Authors: Malvezzi Paolo
Published: August 2022

Purpose of the review

Antibody-mediated rejection (AMR) is the leading cause of kidney graft loss. Very few treatment options are available to the clinician to counter this disease process. In this review we describe the available therapeutics and the novel approaches that are being currently developed.

Recent findings

AMR treatment requires a multidrug approach. Imlifidase, a new immunoglobulin G cleaving agent, may prove to be the perfect replacement of apheresis. New complement blockers other than eculizumab are in development in order to block acute kidney damage in the delicate phase following antibody removal. Plasma cell depletion is being explored in chronic AMR: studies are in progress with daratumumab and felzartamab. Interleukin 6 inhibition is generating enthusiasm in the chronic setting with preliminary encouraging results.

In acute AMR, the clinicians will have to remove the antibodies, avoid rebound and block specific damage effectors. In chronic AMR they will need to reduce the inflammatory response induced by donor specific antibodies. New drugs are available and transplant physicians are starting to develop effective multidrug strategies to counter the complex disease mechanisms. Safety of these drugs needs to be further explored especially when used together with other potent immunosuppressive drugs.
Study Protocol
Authors: Klingman Karen J. , Skufca Joseph D. , Duncan Pamela W. , Wang Dongliang , Fulk George D.
Published: August 2022

Background

A range of sleep disturbances and disorders are problematic in people after stroke; they interfere with recovery of function during poststroke rehabilitation. However, studies to date have focused primarily on the effects of one sleep disorder—obstructive sleep apnea (OSA)—on stroke recovery.

Objectives

The study protocol for the SLEep Effects on Poststroke Rehabilitation (SLEEPR) Study is presented with aims of characterizing proportion of non-OSA sleep disorders in the first 90 days after stroke, evaluating the effect of non-OSA sleep disorders on poststroke recovery, and exploring the complex relationships between stroke, sleep, and recovery in the community setting.

Methods

SLEEPR is a prospective cohort observational study across multiple study sites following individuals from inpatient rehabilitation through 90 days poststroke, with three measurement time points (inpatient rehabilitation; i.e., ~15 days poststroke, 60 days poststroke, and 90 days poststroke). Measures of sleep, function, activity, cognition, emotion, disability, and participation will be obtained for 200 people without OSA at the study’s start through self-report, capacity assessments, and performance measures. Key measures of sleep include wrist actigraphy, sleep diaries, overnight oximetry, and several sleep disorders screening questionnaires (Insomnia Severity Index, Cambridge-Hopkins Restless Legs Questionnaire, Epworth Sleepiness Scale, and Sleep Disorders Screening Checklist). Key measures of function and capacity include the 10-meter walk test, Stroke Impact Scale, Barthel index, and modified Rankin scale. Key performance measures include leg accelerometry (e.g., steps/day, sedentary time, upright time, and sit-to-stand transitions) and community trips via GPS data and activity logs.

Discussion

The results of this study will contribute to understanding the complex interplay between non-OSA sleep disorders and poststroke rehabilitation; they provide insight regarding barriers to participation in the community and return to normal activities after stroke. Such results could lead to strategies for developing new stroke recovery interventions.
Sociodemographic Factors Associated With Gonorrhea and Chlamydia Infection in Pregnancy
Authors: Gulersen Moti , Lenchner Erez , Eliner Yael , Grunebaum Amos , Chervenak Frank A. , Bornstein Eran
Published: August 2022

Background

We explored the impact of maternal sociodemographic parameters on the prevalence of chlamydial and gonorrheal infection in pregnancy in a large United States population of live births.

Methods

Retrospective analysis of the Centers for Disease Control and Prevention Natality Live Birth database (2016–2019). We compared pregnancies complicated by maternal infection with either gonorrhea or chlamydia to those without gonorrheal or chlamydial infection, separately. Both analyses included assessment of multiple maternal sociodemographic factors, which were compared between the 2 groups. Multivariable logistic regression was performed to evaluate the association of these factors with gonorrheal or chlamydial infection in pregnancy.

Results

Of the 15,341,868 included live births, 45,639 (0.30%) were from patients who had gonorrheal infection, and 282,065 (1.84%) were from patients who had chlamydial infection during pregnancy. Concurrent infection with chlamydia and gonorrhea was associated with the highest risk of gonorrhea and chalmydia in pregnancy (adjusted odds ratio, 26.28; 95% confidence interval, 25.74–26.83, and adjusted odds ratio, 26.03; 95% confidence interval, 25.50–26.58, respectively). Young maternal age, low educational attainment, non-Hispanic Black race/ethnicity, concurrent infection with syphilis, and tobacco use were also associated with a substantial increase in the risk of gonorrheal and chlamydial infection in pregnancy.

Conclusions

Several sociodemographic factors including young maternal age, low educational attainment, Medicaid insurance, and non-Hispanic Black race/ethnicity, are associated with a marked increase in the risk for gonorrheal and chlamydial infection in current US pregnancies. These data may be used to better screen, educate, and treat pregnancies of vulnerable populations at risk for such infections.
Intravenous Smart Pumps at the Point of Care: A Descriptive, Observational Study
Authors: Giuliano Karen K. , Blake Jeannine W.C. , Bittner Nancy Phoenix , Gamez Vicki , Butterfield Robert
Published: August 2022

Objective

This study was conducted to advance understanding of intravenous (IV) smart pump medication administration practices using the Baxter Spectrum IQ. The primary objective was to observe adherence with manufacturer required IV smart pump system setup at the point of care during actual clinical use.

Methods

The study was conducted in a 285-bed acute care community hospital near Boston, Massachusetts. The study design was observational and noninterventional, and all data were collected by a single observer. Observations included measurement and documentation of adherence with the Baxter Spectrum IQ system setup requirements.

Results

A total of 200 primary and secondary IV medication administration observations were included: 101 in critical care and 99 in medical-surgical. Overall adherence was found to be: 6.5% with IV smart pump position relative to the patient (aim 1); 6.5% with required position of the primary infusion bag (aim 2); and 69.5% adherence with required position of the secondary medication infusion bag (aim 3). Additional exploratory data were also collected.

Conclusions

These results add to the emerging body of knowledge, which support that adherence to required system setup for head-height dependent IV smart pumps is low and difficult to achieve during actual clinical use. Consideration of alternative human factors–designed technology to replace the current manual setup requirements is needed to improve the process of acute care IV medication administration in this very important area of patient safety.
Enhancing the use of pain assessment at emergency department: a best practice implementation project
Authors: Ubierna-Prieto Joana Aintzane , Ballesteros-Peña Sendoa , Casbas Mayte Moreno , Klugarová Jitka , Klugar Miloslav
Published: August 2022

Objectives:

The main aim of the best practice implementation project was to enhance the use of pain assessment and the compliance with evidence-based criteria regarding pain assessment among incoming patients to emergency department.

Introduction:

Adequate approaches to pain assessment and documentation have been demonstrated beneficial for emergency department patients. Evidence-based recommendations establish a focus on education about the implications for evaluating and recording pain in order to improve outcome strategies and quality of care.

Methods:

The implementation project was undertaken in the emergency department following JBI Implementation framework in order to seek whether pain assessment was taken and registered as per protocols. Random selection for 100 anonymized emergency department admission episodes, which had to meet the specified inclusion criteria, was carried out.

Results:

The baseline audit showed low compliance in criterion 3 (C3) ‘Pain was documented in each assessment’ (6%), C4 ‘Pain was assessed after treatment’ (9%) and C5 ‘Pain was assessed prior to discharge’ (10%). In the follow-up audit, noticeable improvement was shown for four of the criteria; C3 (14%), C4 (22%) and for C5 (41%). C1 ‘Pain was assessed in a timely manner’ improved from 81% up to 95%. C2 ‘Use of a validated scoring tool’ had a compliance of 100% as the hospital's assessing system default has NRS-11 scale set up.

Conclusion:

We performed an audit of pain assessment documentation. Enhancing the use of pain assessment among emergency department nurses by means of specific training emphasizing the importance of documentation showed a positive impact on practice. Follow-up audit results justify the continuity of the implemented strategies.
Centuries of genome instability and evolution in soft-shell clam transmissible cancer
Authors: Hart Samuel F.M. , Yonemitsu Marisa A. , Giersch Rachael M. , Beal Brian F. , Arriagada Gloria , Davis Brian W. , Ostrander Elaine A. , Goff Stephen P. , Metzger Michael J.
Published: August 2022

Transmissible cancers are infectious parasitic clones of malignant cells that metastasize to new hosts, living past the death of the founder animal in which the cancer initiated. Several lineages of transmissible cancer have recently been identified in bivalves, including one that has spread through the soft-shell clam (Mya arenaria) population along the east coast of North America. To investigate the evolutionary history of this transmissible cancer lineage, we assembled a highly contiguous 1.2 Gb soft-shell clam reference genome and characterized somatic mutations from cancer sequences. We show that all cancer cases observed descend from a single founder and cluster into two geographically distinct sub-lineages. We discover a previously unreported clock-like mutational signature that predicts the cancer lineage to be 344 to 877 years old, indicating that it spread undetected long before it was first observed in the 1970s. We observe high mutation density, widespread copy number gain, structural rearrangement, loss of heterozygosity, variable telomere lengths, mitochondrial genome expansion, and transposable element activity, all indicative of an unstable cancer genome. Our study reveals the ability for an invertebrate cancer lineage to survive for centuries while its genome continues to structurally mutate, likely contributing to the ability of this lineage to adapt as a parasitic cancer.

The genome of a contagious cancer in clams reveals structural instability of multiple types throughout the ∼500 years since its origin.
State and trait dimensions of subjective memory concerns: Genetic influences across 30 years
Authors: Bell Tyler , Beck Asad , Gillespie Nathan , Reynolds Chandra , Williams McKenna E. , Gustavson Daniel E. , Lyons Michael J. , Neale Michael , Kremen William S. , Franz Carol E.
Published: August 2022

INTRODUCTION

Genetic influences on the stability of subjective memory concerns (SMC) may confound its interpretation as a state-related risk indicator.

METHODS

We estimated genetic influences on SMC and SMC change from average ages 38 to 67, genetic correlations of SMC with memory and depressive symptoms at average ages 56, 62, and 67, and correlations of SMC with polygenic scores for Alzheimer’s disease and neuroticism, APOE genotype, and parental history or dementia.

RESULTS

SMC was highly stable over this 30-year period. Heritability was .51. Phenotypically and genetically, SMC was more strongly related to depressive symptoms than to objective memory. It was also correlated with parental history of dementia and polygenic risk for neuroticism.

DISCUSSION

SMC’s heritability and stability indicate a substantial trait-like component that is related more to depression and personality than objective memory. Improving it as an indicator of impending cognitive decline or dementia will require isolating its state-related component.
Fibrillarin-1 and Fibrillarin-2 are required for divergent cell lineage development in planarian homeostasis and regeneration
Authors: Chen Jiajia , Pan Xue , Xu Hao , Zhang Yuhong , Lei Kai
Published: August 2022

Ribosome heterogeneity has been revealed to exist in different cell types during development. However, the function and regulatory mechanisms of ribosome heterogeneity in missing tissue regeneration have yet to be reported. We used the planarian Schmidtea mediterranea with whole-body regenerative capability as a model and revealed the function of the rRNA modification protein fibrillarin in cell lineage development and tissue regeneration. We identified two fibrillarin homologs in planarian, Smed-fbl-1 (fbl-1) and Smed-fbl-2 (fbl-2), with distinct expression patterns. While fbl-2 regulates stem cell proliferation and multiple progenitor cell differentiation, fbl-1 participates in epidermal lineage late-stage specification and wound response. This study indicates that fibrillarin, a nucleolar protein, can respond to wounds and function in distinct cell types, suggesting the existence and critical roles of ribosome heterogeneity in stem cells and tissue regeneration.
A comparative analysis of the ontogeny of syngnathids (pipefishes & seahorses) reveals how heterochrony contributed to their diversification
Authors: Schneider Ralf Friedrich , Woltering Joost Marten , Adriaens Dominique , Roth Olivia
Published: August 2022

Background

Syngnathids are a highly derived and diverse fish clade comprising the pipefishes, pipe-horses and seahorses. They are characterized by a plethora of iconic traits that increasingly capture the attention of biologists, including geneticists, ecologists and developmental biologists. The current understanding of the origins of their derived body plan is, however, hampered by incomplete and limited descriptions of the early syngnathid ontogeny.

Results

We provide a comprehensive description of the development of Nerophis ophidion, Syngnathus typhle, Hippocampus erectus from early cleavage stages to release from the male brooding organ and beyond, including juvenile development. We comparatively describe skeletogenesis with a particular focus on dermal bony plates, the snout-like jaw morphology, and appendages.

Conclusions

This most comprehensive and detailed account of syngnathid development to date suggests that convergent phenotypes (e.g. reduction and loss of the caudal fins), likely arose by distinct ontogenetic means in pipefish and seahorses. Comparison of the ontogenetic trajectories of S. typhle and H. erectus provides indications that characteristic features of the seahorse body plan result from developmental truncation. Altogether this work provides a valuable resource and framework for future research to understand the evolution of the outlandish syngnathid morphology from a developmental perspective.

Bullet points

Syngnathids (pipefish, pipe-horses and seahorses) are a highly derived and diverse fish taxon and many of their most iconic traits – and these traits’ variation across species - develop during their early ontogeny.

This study provides a detailed description and staging table of the entire pre-release development (and beyond) of three distinct syngnathids (two phylogenetically distinct pipefishes and a seahorse) with a focus on the skeletal elements forming the cranium, axial skeleton, appendages and the plate armor.

The data provided in this study suggests that developmental heterochrony, i.e. alterations in the rate and timing of developmental processes between lineages, might be a central evolutionary process shaping the morphological diversity found in syngnathids today.
In vivo reduction of age-dependent neuromelanin accumulation mitigates features of Parkinson’s disease
Authors: Gonzalez-Sepulveda Marta , Compte Joan , Cuadros Thais , Nicolau Alba , Guillard-Sirieix Camille , Peñuelas Núria , Lorente-Picon Marina , Parent Annabelle , Romero-Giménez Jordi , Cladera-Sastre Joana M. , Laguna Ariadna , Vila Miquel
Published: August 2022

Humans accumulate with age the dark-brown pigment neuromelanin inside specific neuronal groups. Neurons with the highest neuromelanin levels are particularly susceptible to degeneration in Parkinson’s disease, especially dopaminergic neurons of the substantia nigra (SN), the loss of which leads to characteristic motor Parkinson’s disease symptoms. In contrast to humans, neuromelanin does not appear spontaneously in most animals, including rodents, and Parkinson’s disease is an exclusively human condition. Using humanized neuromelanin-producing rodents, we recently found that neuromelanin can trigger Parkinson’s disease pathology when accumulated above a specific pathogenic threshold.

Here, by taking advantage of this newly developed animal model, we assessed whether the intracellular buildup of neuromelanin that occurs with age can be slowed down in vivo to prevent or attenuate Parkinson’s disease. Because neuromelanin derives from the oxidation of free cytosolic dopamine, we enhanced dopamine vesicular encapsulation in the SN of neuromelanin-producing rats by viral vector-mediated overexpression of vesicular monoamine transporter 2 (VMAT2). This strategy reduced the formation of potentially toxic oxidized dopamine species that can convert into neuromelanin and maintained intracellular neuromelanin levels below their pathogenic threshold. Decreased neuromelanin production was associated with an attenuation of Lewy body-like inclusion formation and a long-term preservation of dopamine homeostasis, nigrostriatal neuronal integrity and motor function in these animals.

Our results demonstrate the feasibility and therapeutic potential of modulating age-dependent intracellular neuromelanin production in vivo, thereby opening an unexplored path for the treatment of Parkinson’s disease and, in a broader sense, brain aging.
Pattern Of Some Inflammatory Mediators Among Adult Patients With Bronchial Asthma On Corticosteroids Attending Aminu Kano Teaching Hospital, Kano, Nigeria
Authors: Saidu H , Ismail M , Lawal U , Mannir H , Gwarzo MY , Rogo LD , Ibrahim A , Garba N , Danladi SB , Aliyu IA , Bala JA , Yahya IS
Published: August 2022

Background

Bronchial asthma in adults is typified by lingering allergic inflammation associated with elevation in the levels of certain acute phase reactants and indicators of mast cell activation. This study investigated the effect of corticosteroid treatment on the levels of C reactive protein (CRP), serum baseline tryptase (sBT), erythrocyte sedimentation rate (ESR) and granulocyte monocyte colony stimulating factor (GM-CSF) among asthmatics.

Method

Forty five adult patients with bronchial asthma on treatment with inhaled corticosteroids were enrolled. Forty five blood donors were used as control. Serum levels of CRP, sBT, ESR and GM-CSF were measured using sandwich ELISA.

Result

The GM-CSF, CRP, ESR and sBT were significantly elevated among asthmatics on treatment compared to normal healthy control. Significant difference in the level of GM-CSF, ESR and CRP was observed between asthmatics with mild and moderate disease severity.

Conclusion

Treatment with inhaled corticosteroids doesn’t restore the levels of GM-CSF, CRP, sBT and ESR to normalcy among asthmatics.
Developmental exposure to domoic acid targets reticulospinal neurons and leads to aberrant myelination in the spinal cord
Authors: Panlilio Jennifer M. , Hammar Katherine M. , Aluru Neelakanteswar , Hahn Mark E.
Published: August 2022

Harmful algal blooms (HABs) produce neurotoxins that affect human health. Developmental exposure of zebrafish embryos to the HAB toxin domoic acid (DomA) causes myelin defects, loss of reticulospinal neurons, and behavioral deficits. However, it is unclear whether DomA primarily targets myelin sheaths, leading to the loss of reticulospinal neurons, or reticulospinal neurons, causing myelin defects. Here, we show that while exposure to DomA at 2 dpf did not reduce the number of oligodendrocyte precursors prior to myelination, it led to fewer myelinating oligodendrocytes that produced shorter myelin sheaths and aberrantly wrapped neuron cell bodies. DomA-exposed larvae lacked Mauthner neurons prior to the onset of myelination, suggesting that axonal loss is not secondary to myelin defects. The loss of the axonal targets may have led oligodendrocytes to inappropriately myelinate neuronal cell bodies. Consistent with this, GANT61, which reduces oligodendrocyte number, caused a reduction in aberrantly myelinated neuron cell bodies in DomA-exposed fish. Together, these results suggest that DomA initially alters reticulospinal neurons and the loss of axons causes aberrant myelination of nearby cell bodies. The identification of initial targets and perturbed cellular processes provides a mechanistic understanding of how DomA alters neurodevelopment, leading to structural and behavioral phenotypes.
Steroidal glycoalkaloids contribute to anthracnose resistance in Solanum lycopersicum
Authors: Fabian Matthew L. , Zhang Chong , Sun Jianghao , Price Neil P. , Chen Pei , Clarke Christopher R. , Jones Richard W. , Stommel John R.
Published: August 2022

Anthracnose is a widespread plant disease caused by various species of the fungal pathogen Colletotrichum. In solanaceous plants such as tomato (Solanum lycoperiscum), Colletotrichum infections exhibit a quiescent, asymptomatic state in developing fruit, followed by a transition to necrotrophic infections in ripe fruit. Through analysis of fruit tissue extracts of 95L368, a tomato breeding line that yields fruit with enhanced anthracnose resistance, we identified a role for steroidal glycoalkaloids (SGAs) in anthracnose resistance. The SGA α-tomatine and several of its derivatives accumulated at higher levels, in comparison to fruit of the susceptible tomato cultivar US28, 95L368 fruit extracts with fungistatic activity against Colletotrichum. Correspondingly, ripe and unripe 95L368 fruit displayed enhanced expression of glycoalkaloid metabolic enzyme (GAME) genes, which encode key enzymes in SGA biosynthesis. Metabolomics analysis incorporating recombinant inbred lines (RILs) generated from 95L368 and US28 yielded strong positive correlations between anthracnose resistance and accumulation of α-tomatine and several derivatives. Lastly, transient silencing of expression of the GAME genes GAME31 and GAME5 in anthracnose-susceptible tomato fruit yielded enhancements to anthracnose resistance. Together, our data support a role for SGAs in anthracnose defense in tomato, with a distinct SGA metabolomic profile conferring resistance to virulent Colletotrichum infections in ripe fruit.

Highlight

This work describes an important role for steroidal glycoalkaloids (SGAs), abundant secondary metabolites in tomato fruit, in defense against anthracnose, a widespread fungal disease that impacts diverse crop species.
LinguaPhylo: a probabilistic model specification language for reproducible phylogenetic analyses
Authors: Drummond Alexei J. , Chen Kylie , Mendes Fábio K. , Xie Dong
Published: August 2022

Phylogenetic models have become increasingly complex, and phylogenetic data sets have expanded in both size and richness. However, current inference tools lack a model specification language that can concisely describe a complete phylogenetic analysis while remaining independent of implementation details. We introduce a new lightweight and concise model specification language, ‘LPhy’, which is designed to be both human and machine-readable. A graphical user interface accompanies ‘LPhy’, allowing users to build models, simulate data, and create natural language narratives describing the models. These narratives can serve as the foundation for manuscript method sections. Additionally, we present a command-line interface for converting LPhy-specified models into analysis specification files (in XML format) compatible with the BEAST2 software platform. Collectively, these tools aim to enhance the clarity of descriptions and reporting of probabilistic models in phylogenetic studies, ultimately promoting reproducibility of results.
Sodium-glucose cotransporter-2 inhibitors and the risk of lung cancer among patients with type 2 diabetes: a retrospective cohort study
Authors: Shapiro Samantha B. , Yin Hui , Yu Oriana H.Y. , Azoulay Laurent
Published: August 2022

Objective

To determine whether the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, compared to dipeptidyl peptidase 4 (DPP-4) inhibitors, is associated with a decreased risk of incident lung cancers among patients with type 2 diabetes.

Methods

We assembled a new-user, active comparator cohort of SGLT-2 inhibitor and DPP-4 inhibitor users using the United Kingdom Clinical Practice Research Datalink. We fit Cox proportional hazards models with propensity score fine stratification weighting to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for incident lung cancers.

Results

Crude lung cancer incidence rates were 0.92 and 1.37 per 1,000 person-years among 47,517 SGLT-2 inhibitor and 129,807 DPP-4 inhibitor users, respectively. No reduced risk of lung cancer was observed among SGLT-2 inhibitor users after weighting (HR 1.08, 95% CI 0.78–1.48). Conclusions: In this large cohort study, the use of SGLT-2 inhibitors was not associated with a decreased risk of lung cancer.
FGF21 Counteracts Alcohol Intoxication by Activating Noradrenergic Neurons
Authors: Choi Mihwa , Schneeberger Marc , Fan Wei , Bugde Abhijit , Gautron Laurent , Vale Kevin , Zhang Yuan , Friedman Jeffrey M. , Mangelsdorf David J. , Kliewer Steven A.
Published: August 2022

Animals that consume fermenting fruit or nectar are exposed to ethanol, thus increasing their risk of injury or predation. This risk is heightened in humans, who have actively imbibed alcohol for thousands of years. In this report, we show that the hormone FGF21, which is strongly induced by ethanol in murine and human liver, exerts sobering or “amethystic” effects on both arousal and motor coordination without changing ethanol catabolism. Mice lacking FGF21 take longer than wild-type littermates to recover their righting reflex and balance following ethanol exposure. Conversely, pharmacologic FGF21 administration reduces the time needed for mice to recover from ethanol-induced unconsciousness and ataxia. FGF21 mediates it amethystic effects by directly activating the noradrenergic nervous system, which regulates arousal and alertness. These results indicate that this FGF21 liver-brain pathway evolved to protect against ethanolinduced intoxication and that it might be targeted pharmaceutically for treating acute alcohol poisoning.
Sex differences in inter-individual gene expression variability across human tissues
Authors: Khodursky Samuel , Jiang Caroline S. , Zheng Eric B. , Vaughan Roger , Schrider Daniel R. , Zhao Li
Published: August 2022

Understanding phenotypic sex differences has long been a goal of biology from both a medical and evolutionary perspective. Although much attention has been paid to mean differences in phenotype between the sexes, little is known about sex differences in phenotypic variability. To gain insight into sex differences in inter-individual variability at the molecular level, we analyzed RNA-seq data from 43 tissues from the Genotype-Tissue Expression project (GTEx). Within each tissue, we identified genes that show sex differences in gene expression variability. We found that these sex-differentially variable (SDV) genes are associated with various important biological functions, including sex hormone response, immune response, and other signaling pathways. By analyzing single-cell RNA sequencing data collected from breast epithelial cells, we found that genes with sex differences in gene expression variability in breast tissue tend to be expressed in a cell-type-specific manner. We looked for an association between SDV expression and Graves’ disease, a well-known heavily female-biased disease, and found a significant enrichment of Graves’ associated genes among genes with higher variability in females in thyroid tissue. This suggests a possible role for SDV expression in the context of sex-biased disease. We then examined the evolutionary constraints acting on genes with sex differences in variability and found that they exhibit evidence of increased selective constraint. Through analysis of sex-biased eQTL data, we found evidence that SDV expression may have a genetic basis. Finally, we propose a simple evolutionary model for the emergence of sex-differentially variable expression from sex-specific constraints.
Urp1 and Urp2 act redundantly to maintain spine shape in zebrafish larvae
Authors: Gaillard Anne-Laure , Mohamad Teddy , Quan Feng B. , de Cian Anne , Mosiman Christian , Tostivint Hervé , Pézeron Guillaume
Published: August 2022

Urp1 and Urp2 are two neuropeptides, members of the Urotensin 2 family, that have been recently involved in the control of body axis morphogenesis in zebrafish. They are produced by a population of sensory spinal neurons, called cerebrospinal fluid contacting neurons (CSF-cNs), under the control of signals relying on the Reissner fiber, an extracellular thread bathing in the CSF. Here, we have investigated further the function of Urp1 and Urp2 (Urp1/2) in body axis formation and maintenance. We showed that urp1;urp2 double mutants develop strong body axis defects during larval growth, revealing the redundancy between the two neuropeptides. These defects were similar to those previously reported in uts2r3 mutants. We observed that this phenotype is not associated with bone formation defects nor with increased inflammation status but, by using specific inhibitors, we found that the action of Urp1/2 depends on myosin II contraction. Finally, we provide evidence that while the Urp1/2 signaling is functioning during larval growth but is dispensable for embryonic development. Taken together, our results show that Urp1/2 signaling is required in larvae to promote correct vertebral body axis, most likely by regulating muscle tone.
Spindle F-actin coordinates the first metaphase-anaphase transition in Drosophila meiosis
Authors: Wood Benjamin W. , Weil Timothy T.
Published: August 2022

Meiosis is a highly conserved feature of sexual reproduction that ensures germ cells have the correct number of chromosomes prior to fertilization. A subset of microtubules, known as the spindle, are essential for accurate chromosome segregation during meiosis. Building evidence in mammalian systems has recently highlighted the unexpected requirement of the actin cytoskeleton in chromosome segregation; a network of spindle actin filaments appear to regulate many aspects of this process. Here we show that Drosophila oocytes also have a spindle population of actin that regulates the formation of the microtubule spindle and chromosomal movements throughout meiosis. We demonstrate that genetic and pharmacological disruption of the actin cytoskeleton has a significant impact on spindle morphology, dynamics, and chromosome alignment and segregation during the metaphase-anaphase transition. We further reveal the requirement of calcium in maintaining the microtubule spindle and spindle actin. Together, our data highlights the significant conservation of morphology and mechanism of the spindle actin during meiosis.
Urine-based multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS
Authors: Batra Richa , Uni Rie , Akchurin Oleh M. , Alvarez-Mulett Sergio , Gómez-Escobar Luis G. , Patino Edwin , Hoffman Katherine L. , Simmons Will , Chetnik Kelsey , Buyukozkan Mustafa , Benedetti Elisa , Suhre Karsten , Schenck Edward , Cho Soo Jung , Choi Augustine M.K. , Schmidt Frank , Choi Mary E. , Krumsiek Jan
Published: August 2022

Acute respiratory distress syndrome (ARDS), a life-threatening condition during critical illness, is a common complication of COVID-19. It can originate from various disease etiologies, including severe infections, major injury, or inhalation of irritants. ARDS poses substantial clinical challenges due to a lack of etiology-specific therapies, multisystem involvement, and heterogeneous, poor patient outcomes. A molecular comparison of ARDS groups holds the potential to reveal common and distinct mechanisms underlying ARDS pathogenesis. In this study, we performed a comparative analysis of urine-based metabolomics and proteomics profiles from COVID-19 ARDS patients (n = 42) and bacterial sepsis-induced ARDS patients (n = 17). The comparison of these ARDS etiologies identified 150 metabolites and 70 proteins that were differentially abundant between the two groups. Based on these findings, we interrogated the interplay of cell adhesion/extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis through a multi-omic network approach. Moreover, we identified a proteomic signature associated with mortality in COVID-19 ARDS patients, which contained several proteins that had previously been implicated in clinical manifestations frequently linked with ARDS pathogenesis. In summary, our results provide evidence for significant molecular differences in ARDS patients from different etiologies and a potential synergy of extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis. The proteomic mortality signature should be further investigated in future studies to develop prediction models for COVID-19 patient outcomes.
Public relations strategies employed by healthcare organizations to address vaccine hesitancy: the case of the Ghana Health Service
Authors: McCarthy Ruth , Donkoh Emmanuel Timmy , De Graft Arthur Dominic , Dassah Edward Tieru , Boadu Kwame Ofori , Otoo John Ekow , Ofori Boadu Ivy Wina , Fosu-Gyasi Samuel
Published: August 2022

Background

Strategies for developing and advancing good public relations can be recognized in nearly all fields of life without making an exception for the healthcare industry. In the wake of the COVID-19 pandemic, matters of public health have gathered more force. The importance of effective public relations for improving healthcare is highlighted by the position that immediate access to reliable health information should be the hallmark of a just society. However, the strategies available for addressing major threats to the uptake of public health services such as mass vaccination campaigns are not properly studied and documented in the Ghanaian context.

Methods

Semi-structured interviews were conducted with officials of the Ghana Health Service (GHS). Participants were recruited through purposive sampling. Data collected included demographic characteristics, perspectives on public relations strategies used in the past year to improve vaccine uptake as well as successes and pitfalls. Thematic content analysis was performed on data collected using the NVIVO software.

Results

Healthcare workers perceived vaccine hesitancy to be a threat with the potential to undermine an important strategic organizational goal related to COVID-19 illness. A combination of informative, motivational, persuasive and coercive public relations strategies was employed by the Ghana Health Service to address the challenge of vaccine hesitancy. These strategies were deployed across both traditional (print, radio, TV) and emerging/social media networks. Officials were optimistic that the strategies would produce results but were uncertain whether they could attribute current successes or failures to the PR strategies used.

Conclusion

Since the onset of the COVID-19 pandemic, several public relations strategies have been evidently employed by the Ghana Health Service to address vaccine hesitancy. The nature of the audience and PR strategies employed suggests that the effect of these strategies may be short-lived unless they are constantly reinforced by the GHS.
Humoral immune responses remain quantitatively impaired but improve qualitatively in anti-CD20 treated patients with multiple sclerosis after three or four COVID-19 vaccinations
Authors: Otto Carolin , Schwarz Tatjana , Jeworowski Lara M. , Schmidt Marie L. , Walper Felix , Pache Florence , Schindler Patrick , Niederschweiberer Moritz , Krumbholz Andi , Rose Ruben , Drosten Christian , Ruprecht Klemens , Corman Victor M
Published: August 2022

Background

Humoral immune responses to COVID-19 vaccination are diminished in anti-CD20 treated patients with multiple sclerosis (pwMS). In healthy individuals, neutralizing antibodies against the SARS-CoV-2 Omicron variant are only detected after three COVID-19 vaccinations. It was hitherto unknown whether a third or fourth COVID-19 vaccination of anti-CD20 treated pwMS improves SARS-CoV-2 specific humoral immune responses, including neutralizing antibodies against Omicron.

Methods

Anti-CD20 treated pwMS vaccinated two (n=61), three (n=57) or four (n=15) times and healthy controls (n=10) vaccinated thrice were included in a prospective cohort study. Anti-SARS-CoV-2 spike S1 IgG and IgA levels, maturation of SARS-CoV-2 IgG avidity, neutralizing capacity against the SARS-CoV-2 Omicron BA.2 variant and SARS-CoV-2 specific T cell responses were analyzed.

Results

The proportion of anti-CD20 treated pwMS with detectable SARS-CoV-2 S1 IgG was similar after the second (31/61, 50.8%), third (31/57, 54.4%) and fourth (8/15, 53.3%) vaccination. In pwMS with detectable SARS-CoV-2 IgG, the proportion with high affinity antibodies increased from the second (6/31, 19.4%) to the third (17/31, 54.8%) and fourth (6/8, 75%) vaccination. While none (0/10) of the anti-CD20 treated pwMS vaccinated twice had Omicron specific neutralizing antibodies, 3/10 (30%) pwMS vaccinated thrice and 3/5 (60%) pwMS vaccinated four times generated Omicron specific neutralizing antibodies.

Conclusion

Although SARS-CoV-2 specific humoral immune responses remain quantitatively impaired, in those anti-CD20 treated pwMS who do develop SARS-CoV-2 antibodies, the functionality of SARS-CoV-2 antibodies, including neutralizing antibodies against Omicron, improves after three and four SARS-CoV-2 vaccinations, supporting current recommendations for one or two booster vaccination in anti-CD20 treated pwMS.
Defining and phenotyping gastric abnormalities in long-term type 1 diabetes using body surface gastric mapping
Authors: Xu William , Gharibans Armen A. , Calder Stefan , Schamberg Gabriel , Walters Anthony , Jang Jia , Varghese Chris , Carson Daniel , Daker Charlotte , Waite Stephen , Andrews Christopher N , Cundy Tim , O’Grady Gregory
Published: August 2022

Objective

To define phenotypes of gastric myoelectrical abnormalities and relation to symptoms in people with longstanding T1D, compared to matched healthy controls, using a novel non-invasive body surface gastric mapping (BSGM) device.

Research design and methods

BSGM was performed on people with T1D of >10 years duration and matched controls, employing Gastric Alimetry (Alimetry, New Zealand), comprising a high-resolution 64-channel array, validated symptom logging App, and wearable reader.

Results

32 people with T1D were recruited (15 with a high symptom burden), and 32 controls. Those with symptoms showed more unstable gastric myoelectrical activity, (Gastric Alimetry Rhythm Index 0.39 vs 0.51, p=0.017; and lower average spatial covariance 0.48 vs 0.51, p=0.009) compared with controls. Those with T1D and symptoms also had higher prevalence of peripheral neuropathy (67% vs 6%, p=0.001), anxiety/depression diagnoses (27% vs 0%, p=0.001), and mean HbA1c levels (76 vs 56 mmol/mol, p<0.001). BSGM defined distinct phenotypes in participants including those with markedly unstable gastric rhythms (4/32, 12.5%), and abnormally high gastric frequencies (10/32, 31%). Deviation in gastric frequency was positively correlated with symptoms of bloating, upper gut pain, nausea and vomiting, and fullness and early satiation (r>0.35, p<0.05)

Conclusion

Gastroduodenal symptoms in people with longstanding T1D correlate with gastric myoelectrical abnormalities on BSGM evaluation, in addition to glycemic control, psychological comorbidities, and peripheral neuropathy. BSGM using the Gastric Alimetry device identified a range of myoelectrical phenotypes, representing both myogenic and neurogenic mechanisms, which represent targets for diagnosis, monitoring and therapy.