bluuebunny/crossref_metadata_2025 huggingface dataset:
A pan-variant miniprotein inhibitor protects against SARS-CoV-2 variants
Authors: Lee Jimin , Case James Brett , Ravichandran Rashmi , Asarnow Daniel , Tortorici M. Alejandra , Brown Jack T , Sanapala Shilpa , Carter Lauren , Baker David , Diamond Michael S , Veesler David
Published: August 2024

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised neutralizing antibody responses elicited by prior infection or vaccination and abolished the utility of most monoclonal antibody therapeutics. We previously described a computationally-designed, homotrimeric miniprotein inhibitor, designated TRI2-2, that protects mice against pre-Omicron SARS-CoV-2 variants. Here, we show that TRI2-2 exhibits pan neutralization of variants that evolved during the 4.5 years since the emergence of SARS-CoV-2 and protects mice against BQ.1.1, XBB.1.5 and BA.2.86 challenge when administered post-exposure by an intranasal route. The resistance of TRI2-2 to viral escape and its direct delivery to the upper airways rationalize a path toward clinical advancement.
Eosinophils protect against SARS-CoV-2 following a vaccine breakthrough infection
Authors: Moore Kathryn M. , Foster Stephanie L. , Kar Meenakshi , Floyd Katharine A. , Elrod Elizabeth J. , Williams M. Elliott , Velden Jacob Vander , Ellis Madison , Malik Ansa , Wali Bushra , Lapp Stacey , Metz Amanda , Bosinger Steven E. , Menachery Vineet D. , Seder Robert A. , Amara Rama Rao , Kohlmeier Jacob E. , Grakoui Arash , Suthar Mehul S.
Published: August 2024

Waning immunity and the emergence of immune evasive SARS-CoV-2 variants jeopardize vaccine efficacy leading to breakthrough infections. We have previously shown that innate immune cells play a critical role in controlling SARS-CoV-2. To investigate the innate immune response during breakthrough infections, we modeled breakthrough infections by challenging low-dose vaccinated mice with a vaccine-mismatched SARS-CoV-2 Beta variant. We found that low-dose vaccinated infected mice had a 2-log reduction in lung viral burden, but increased immune cell infiltration in the lung parenchyma, characterized by monocytes, monocyte-derived macrophages, and eosinophils. Single cell RNA-seq revealed viral RNA was highly associated with eosinophils that corresponded to a unique IFN-γ biased signature. Antibody-mediated depletion of eosinophils in vaccinated mice resulted in increased virus replication and dissemination in the lungs, demonstrating that eosinophils in the lungs are protective during SARS-CoV-2 breakthrough infections. These results highlight the critical role for the innate immune response in vaccine mediated protection against SARS-CoV-2.
Optimized methods for mapping DNA double-strand-break ends and resection tracts and application to meiotic recombination in mouse spermatocytes
Authors: Kim Soonjoung , Yamada Shintaro , Maekawa Kaku , Keeney Scott
Published: August 2024

DNA double-strand breaks (DSBs) made by SPO11 protein initiate homologous recombination during meiosis. Subsequent to DNA strand breakage, endo- and exo-nucleases process the DNA ends to resect the strands whose 5’ termini are at the DSB, generating long 3’-terminal single-stranded tails that serve as substrates for strand exchange proteins. DSB resection is essential for meiotic recombination, but a detailed understanding of its molecular mechanism is currently lacking. Genomic approaches to mapping DSBs and resection endpoints, e.g., S1-sequencing (S1-seq) and similar methods, play a critical role in studies of meiotic DSB processing. In these methods, nuclease S1 or other enzymes that specifically degrade ssDNA are used to trim resected DSBs, allowing capture and sequencing of the ends of resection tracts. Here, we present optimization of S1-seq that improves its signal:noise ratio and allows its application to analysis of spermatocyte meiosis in adult mice. Furthermore, quantitative features of meiotic resection are evaluated for reproducibility, and we suggest approaches for analysis and interpretation of S1-seq data. We also compare S1-seq to variants that use exonuclease T and/ or exonuclease VII fromEscherichia coliinstead of nuclease S1. Detailed step-by-step protocols and suggestions for troubleshooting are provided.
Long-read transcriptomic identification of synaptic adaptation to amyloid pathology in theAppNL-G-Fknock-in mouse model of the earliest phase of Alzheimer’s disease
Authors: Yaman Umran , Banks Gareth , Gustavsson Emil K. , Mumford Paige , Magusali Naciye , Taso Orjona Stella , Macpherson Hannah , Carmona Susana , Murray Malgorzata , Bains Rasneer Sonia , Forrest Hamish , Stewart Michelle , Scott Connor , Lipina Tatiana V. , Cheng Zhao , Tierney Anna L. , Unwin Richard D. , Botia Juan A. , Frigerio Carlo Sala , Wells Sara E. , Hardy John , Soreq Lilach , Wiseman Frances K. , Salih Dervis A.
Published: August 2024

Genome-wide association studies (GWAS) have identified a transcriptional network of Alzheimer’s disease (AD) risk genes that are primarily expressed in microglia and are associated with AD pathology. However, traditional short-read sequencers have limited our ability to fully characterize how GWAS variants exert their effects on gene expression regulation or alternative splicing in response to the pathology, particularly resulting in inaccurate detection of splicing. To address this gap, we utilized long-read RNA-sequencing (RNA-seq) in theAppNL-G-Fknock-in mouse model to identify changes in splicing and novel transcript isoforms in response to amyloid-β. We show that long-read RNA-seq can recapitulate the expected induction of microglial expressed risk genes such asTrem2in response to amyloid-β at 9 months of age associated with ageing-dependent deficiencies in spatial short-term memory in theAppNL-G-Fknock-in mice. Our results not only identified novel splicing events and transcript isoform abundance in genes associated with AD, but also revealed the complex regulation of gene expression through splicing in response to amyloid plaques. Surprisingly, the regulation of alternative splicing in response to amyloid was seen in genes previously not identified as AD risk genes, expressed in microglia, neurons and oligodendrocytes, and included genes such asSyngr1that modulate synaptic physiology. We saw alternative splicing in genes such asCtsa,Clta,Dennd2a,Irf9andSmad4in mice in response to amyloid, and the orthologues of these genes also showed transcript usage changes in human AD brains. Our data suggests a model whereby induction of AD risk gene expression associated with microglial proliferation and activation is concomitant with alternative splicing in a different class of genes expressed by microglia and neurons, which act to adapt or preserve synaptic activity in response to amyloid-β during early stages of the disease. Our study provides new insights into the mechanisms and effects of the regulation of genes associated with amyloid pathology, which may ultimately enable better disease diagnosis, and improved tracking of disease progression. Additionally, our findings identify new therapeutic avenues for treatment of AD.
MyVivarium: A cloud-based lab animal colony management application with realtime ambient sensing
Authors: Vidva Robinson , Raza Mir Abbas , Prabhakaran Jaswant , Sheikh Ayesha , Sharp Alaina , Ott Hayden , Moore Amelia , Fleisher Christopher , Netherton Hailey , Goldstein Evan , Pitychoutis Pothitos M. , Nguyen Tam V. , Sathyanesan Aaron
Published: August 2024

Management of research-animal colonies is vital for lab productivity in preclinical research. Labs often rely on inefficient paper-based or spreadsheet-based methods to manage animal colonies. Dedicated software-based solutions are generally expensive and many lack remote access. Currently available open-source alternatives are difficult to implement and deploy. These solutions also do not have the capability to track ambient variables that affect colony well-being. We builtMyVivarium, an open-source database management web application to address these gaps. MyVivarium can be easily deployed to the cloud and sustained for a cost comparable to starting and maintaining a lab website. Using MyVivarium, lab members can collaboratively track individual animals within a database. Physical identities of cages map onto the database using QR codes, enabling quick and easy record-keeping on mobile devices. Lab administrators can assign tasks to users with reminders for experiments or cage maintenance. Finally, we designed a low-cost system to sense ambient humidity, temperature, vivarium worker activity, and room illuminance. These data are then sent to MyVivarium in realtime providing information relevant to colony well-being. Taken together, MyVivarium is a novel, open-source, cloud-based application template that provides a low-cost, simple, and efficient way to digitally manage research-animal colonies.
Weber’s law and natural inference
Authors: Beck Jeffrey , Kanitscheider Ingmar , Dehaene Guillaume , Pouget Alexandre
Published: August 2024

For most extensive sensory variables such as speed or numerosity, the discrimination thresholds of human subjects are proportional to the value around which the discrimination is performed, a scaling known as Weber’s law. Many theories have been proposed for this law, which all rely on the assumption that neurons are noisy. By contrast, we argue here that noisy neurons are not required to explain Weber’s law. Instead, we propose that it is the unavoidable consequence of the statistics of natural sensory inputs. In natural environments, sensory measurements are typically scaled by global variables such as contrast in vision or loudness in audition. These global scaling parameters induce positive correlations among measurements which in turn lead to Weber’s scaling. This theory makes testable experimental predictions and accounts for the fact that tuning curves to speed and numerosity in vivo are approximately log normal.
Genomic Study of Taste Perception Genes in African Americans Reveals SNPs Linked to Alzheimer’s Disease
Authors: Joseph Paule Valery , Abbas Malak , Goodney Gabriel , Diallo Ana , Gaye Amadou
Published: August 2024

Background

While previous research has shown the potential links between taste perception pathways and brain-related conditions, the area involving Alzheimer’s disease remains incompletely understood. Taste perception involves neurotransmitter signaling, including serotonin, glutamate, and dopamine. Disruptions in these pathways are implicated in neurodegenerative diseases. The integration of olfactory and taste signals in flavor perception may impact brain health, evident in olfactory dysfunction as an early symptom in neurodegenerative conditions. Shared immune response and inflammatory pathways may contribute to the association between altered taste perception and conditions like neurodegeneration, present in Alzheimer’s disease.

Methods

This study consists of an exploration of expression-quantitative trait loci (eQTL), utilizing whole-blood transcriptome profiles, of 28 taste perception genes, from a combined cohort of 475 African American subjects. This comprehensive dataset was subsequently intersected with single-nucleotide polymorphisms (SNPs) identified in Genome-Wide Association Studies (GWAS) of Alzheimer’s Disease (AD). Finally, the investigation delved into assessing the association between eQTLs reported in GWAS of AD and the profiles of 741 proteins from the Olink Neurological Panel.

Results

The eQTL analysis unveiled 3,547 statistically significant SNP-Gene associations, involving 412 distinct SNPs that spanned all 28 taste genes. In 17 GWAS studies encompassing various traits, a total of 14 SNPs associated with 12 genes were identified, with three SNPs consistently linked to Alzheimer’s disease across four GWAS studies. All three SNPs demonstrated significant associations with the down-regulation ofTAS2R41, and two of them were additionally associated with the down-regulation ofTAS2R60. In the subsequent pQTL analysis, two of the SNPs linked toTAS2R41andTAS2R60genes (rs117771145 and rs10228407) were correlated with the upregulation of two proteins, namely EPHB6 and ADGRB3.

Conclusions

Our investigation introduces a new perspective to the understanding of Alzheimer’s disease, emphasizing the significance of bitter taste receptor genes in its pathogenesis. These discoveries set the stage for subsequent research to delve into these receptors as promising avenues for both intervention and diagnosis. Nevertheless, the translation of these genetic insights into clinical practice requires a more profound understanding of the implicated pathways and their pertinence to the disease’s progression across diverse populations.
Self-organizing ovarian somatic organoids preserve cellular heterogeneity and reveal cellular contributions to ovarian aging
Authors: Dipali Shweta S. , Gowett Madison Q. , Kamat Pratik , Converse Aubrey , Zaniker Emily J. , Fennell Abigail , Chou Teresa , Pritchard Michele T. , Zelinski Mary , Phillip Jude M. , Duncan Francesca E.
Published: August 2024

Ovarian somatic cells are essential for reproductive function, but no existingex vivomodels recapitulate the cellular heterogeneity or interactions within this compartment. We engineered a novel ovarian somatic organoid model by culturing a stroma-enriched fraction of mouse ovaries in scaffold-free agarose micromolds. Ovarian somatic organoids self-organized, maintained diverse cell populations, produced extracellular matrix, and secreted hormones. Organoids generated from reproductively old mice exhibited reduced aggregation and growth compared to young counterparts, as well as differences in cellular composition. Interestingly, matrix fibroblasts from old mice demonstrated upregulation of pathways associated with the actin cytoskeleton and downregulation of cell adhesion pathways, indicative of increased cellular stiffness which may impair organoid aggregation. Cellular morphology, which is regulated by the cytoskeleton, significantly changed with age and in response to actin depolymerization. Moreover, actin depolymerization rescued age-associated organoid aggregation deficiency. Overall, ovarian somatic organoids have advanced fundamental knowledge of cellular contributions to ovarian aging.
The limitation of lipidation: conversion of semaglutide from once-weekly to once-monthly dosing
Authors: Schneider Eric L. , Hangasky John A. , del Valle Fernandez Rocio , Ashley Gary W. , Santi Daniel V.
Published: August 2024

The objective of this work was to develop a long-acting form of the lipidated peptide semaglutide that can be administered to humans once-monthly. Semaglutide was attached to 50 μ diameter hydrogel microspheres by a cleavable linker with an expected in vivo release half-life of about one-month. After a single subcutaneous dose, the pharmacokinetic parameters of released semaglutide were determined in normal mice and the bodyweight loss was determined in diet induced obese mice. The results were used to simulate the pharmacokinetics of semaglutide released from the microspheres in humans.Semaglutide tethered to microspheres by a cleavable linker could be completely released with an in vitro half-life of ∼55 days at pH 7.4. The in vivo half-life of released semaglutide was ∼30 days, and a single dose in diet-induced obese mice resulted in a lean-sparing body weight loss of 20% over 1 month, statistically the same as semaglutide dosed twice daily. Simulations indicated the microsphere-semaglutide would permit once-monthly administration in humans. The microsphere-semaglutide conjugate described here should be suitable for once-monthly dosing in humans, and the same approach should enable conversion of other lipidated peptides from once-weekly to once-monthly administration.
Differential Drug Susceptibility Across Trichomonasvirus Species Allows for Generation of Varied Isogenic Clones ofTrichomonas vaginalis
Authors: Hetzel Carrie A. , Appah-Sampong Akua A. , Hurst-Manny Austin R. , Nibert Max L.
Published: August 2024

Trichomonas vaginalis(Tvag) is a sexually transmitted human pathogen that is commonly infected with strains of one or more of five known species of Trichomonas vaginalis viruses (TVVs), members of genusTrichomonasvirus. TVVs are thought not to have an extracellular phase to their lifecycle and instead to be transmitted vertically from mother to daughter cells. As a result, generation of isogenic virus-positive and virus-negative sets of Tvag clones has been a major barrier to study interactions between TVVs and their host. Nucleoside analog 2’-C-methylcytidine (2CMC) has been recently reported to clear trichomonads of infections with TVV1, TVV2, and TVV3. We used 2CMC to treat a panel of Tvag isolates that collectively harbor at least one representative strain of each TVV species and thereby provided evidence that infections with TVV4 and TVV5 can also be cleared by 2CMC. Furthermore, our results suggest a newly identified difference in drug susceptibility between TVV species. We took advantage of these susceptibility difference to generate isogenic sets of Tvag clones harboring different combinations of the five TVV species. These results provide both new insight into differences between these species and new avenues for generating tools to study the potential roles of TVVs in Tvag biology.
Primary care-based approaches to reduce readmissions: older patients’ perspectives on the transition of care from secondary care to primary care
Authors: Sheeran-Purcell Luke , McCombe Geoff , Broughan John , Sietins Emils , Fawsitt Ronan , Queally Martina , Lynch Timothy , Cullen Walter
Published: August 2024

Purpose

Readmissions to the hospital are expensive and can have negative health consequences for patients. Older adults are at greater risk of readmission. Patient perspectives are valuable in identifying areas for improvement in the transition of care. The purpose of this qualitative study is to increase our understanding of patients’ perspectives on the transition of care from hospital to primary care.

Design/methodology/approach

This study employs a qualitative methodology to conduct semi-structured interviews with patients who have been discharged from hospitals in the Ireland East Hospital Group region. Remote interviews were conducted with 18 participants from eight general practices. Transcripts were analysed using thematic analysis as described by Braun and Clarke.

Findings

The three main themes identified were communication, outpatient supports and patient education. Gaps in communication do occur, but patients are often too external to comment. Patients benefit from a wide variety of outpatient supports including general practice, family, carers, allied health professionals and voluntary organisations. Access and cost are barriers to these supports. Participants were generally positive towards proposed primary care-based interventions such as follow-up appointments with general practitioners (GPs) and education sessions.

Originality/value

This study highlights a number of areas for improvement in the transition of care in current practice including communication between services and access to outpatient care. It also suggests directions for further research, such as explorations of healthcare provider perspectives and pilot studies of readmission reduction interventions.
Analysing policy success and failure in Australia: Pink batts and set‐top boxes
Authors: Casey Daniel
Published: August 2024

This article examines two Australian government programs from the Rudd/Gillard Labor government, the Home Insulation Program (HIP) and the Digital Switchover Household Assistance Scheme (HAS). Both became shibboleths of the Labor government's perceived waste and incompetence. Using key informant interviews and documents obtained under freedom of information (FOI), I analyse these programs against the multiple ‘dimensions’ of success proposed by Newman and common narrative frames around programme failure. I argue that the HAS was broadly successful across most dimensions of success, notwithstanding the adverse media attention. The study identifies four key factors driving HIP's failure: scheme design, installer training, demand control, and departmental expertise. All of these came back to the timeline pressures, driven by conflicting priorities, which in turn gave the Department of the Prime Minister and Cabinet (PM&C) more influence than would usually be the case. In comparison, HAS's success is attributed to crucial design choices, like the phased rollout and head contractor model. The article identifies the danger of ignoring subject matter expertise and poor policy/Cabinet processes, which have been reinforced by the recent Royal Commission into the Robodebt Scheme.

Points for practitioners

Demand‐driven programmes need to have demand‐side control techniques built into them.

The role of central agencies needs to be carefully considered, particularly in relation to areas that are not their expertise, such as detailed programme development and implementation.

Lessons about poor policy and Cabinet processes, as well as cultural change from the Pink Batts Royal Commission, do not appear to have been sufficiently embedded in the culture of the APS, as there are ongoing echoes of the same problems evident in the Robodebt Royal Commission.
Microwave detection technique combined with deep learning algorithm facilitates quantitative analysis of heavy metal Pb residues in edible oils
Authors: Deng Jihong , Zhao Xinke , Luo Wangfei , Bai Xue , Xu Leijun , Jiang Hui
Published: August 2024

The heavy metal content in edible oils is intricately associated with their suitability for human consumption. In this study, standard soybean oil was used as a sample to quantify the specified concentration of heavy metals using microwave sensing technique. In addition, an attention‐based deep residual neural network model was developed as an alternative to traditional modeling methods for predicting heavy metals in edible oils. In the process of microwave data processing, this work continued to discuss the impact of depth on convolutional neural networks. The results demonstrated that the proposed attention‐based residual network model outperforms all other deep learning models in all metrics. The performance of this model was characterized by a coefficient of determination (R2) of 0.9605, a relative prediction deviation (RPD) of 5.0479, and a root mean square error (RMSE) of 3.1654 mg/kg. The research findings indicate that the combination of microwave detection technology and chemometrics holds significant potential for assessing heavy metal levels in edible oils.
Bipolar disorder and oxidative stress: A bibliometric perspective
Authors: Gui Zhen , Zhang Qinge , Sha Sha , Li Xiao‐Hong , Su Zhaohui , Cheung Teris , Cui Xi‐Ling , Ungvari Gabor S. , Wong Katrine K. , Ng Chee H. , Yuan Feng , Xiang Yu‐Tao
Published: August 2024

Objective

Accumulating evidence indicates that oxidative stress and the disruption of antioxidant defenses play an important role in the neurobiology of bipolar disorder (BD). Studies have found that increased oxidative stress may be associated with cell apoptosis and neuronal damage in BD patients. Hence, this study explored the research field related to BD and oxidative stress from a bibliometrics perspective.

Methods

Literature search and relevant data retrieval based on the Web of Sciences Core Collection (WoSCC). R software (version 4.2.2), VOSviewer software (version 1.6.18), and CiteSpace (version 6.1.6) were used in this bibliometric analysis.

Results

A total of 2081 publications related to BD and oxidative stress were published between 1986 and 2024. Bipolar Disorders was the journal that had the most publications in this area (72; 3.46%; IF = 5.9), while the United States (1285; 61.7%) and the University of Toronto (377; 18.1%) were the most productive country and institution, respectively. Apart from “oxidative stress” and “bipolar disorder,” the most frequently used keywords were “schizophrenia,” “prefrontal cortex,” and “nitric oxide.”

Conclusions

The growing number of publications related to BD and oxidative stress in recent years highlights the importance of this research field. Hot topics in research related to BD and oxidative stress included animal experiments and molecular mechanisms, psychiatric‐related inflammation and biomarkers, neurodegenerative diseases, and metabolism. Furthermore, the biological mechanisms of BD, particularly biomarkers and inflammation, may be the emerging research priority area in the future.
Myokines are associated with progression, course and mortality in alcohol‐associated liver disease
Authors: Kaur Parminder , Verma Nipun , Garg Pratibha , Ralmilay Samonee , Wadhawan Aishani , Nadda Rohit , Prajapati Jiya , Sharma Gaurav , Rathi Sahaj , De Arka , Premkumar Madhumita , Taneja Sunil , Singal Ashwani K. , Duseja Ajay
Published: August 2024

Background and Aims

Myokines are the muscle‐derived hormones orchestrating muscle and systemic health. Their role in the progression of alcohol‐associated liver disease (ALD) remains elusive.

Methods

Three‐hundred‐one patients across the spectrum of ALD including fatty liver (FL, N = 13), compensated cirrhosis (CC, N = 17), non‐acute decompensation (NAD, N = 95), acute decompensation (AD, N = 51) and acute‐on‐chronic liver failure (ACLF, N = 125) were recruited between 2021 and 2023. Plasma myostatin, decorin levels, nutritional status, handgrip strength (HGS), systemic inflammation, infection, ammonia, disease course and 30‐day mortality were recorded.

Results

Patients aged 48 years (IQR: 38–52) and 97.7% of males were enrolled. Myostatin was elevated while decorin was reduced in cirrhosis compared to without cirrhosis, and further in DC compared to CC (p < 0.001). A step‐wise increase in myostatin and reduction in decorin was observed transitioning from NAD to AD to ACLF (p < 0.001). Myostatin was further increased and decorin was reduced along with the grades and organ failures in AD and ACLF (p < 0.001, each). Baseline decorin (AUC: 0.797) and its combination with MELD (AUC: 0.814) predicted disease resolution in AD and ACLF. Although, both myostatin (aOR: 18.96) and decorin (aOR: 0.02) could predict mortality, decorin was independent (aOR: 0.04) and additive to MELD (AUC of MELD+logDecorin + logTLC + HE‐grade:0.815); p < 0.05 each. Myostatin increased and decorin reduced with inflammation, hyperammonaemia, malnutrition and HGS in AD and ACLF (p < 0.05, each).

Conclusion

Myokines are linked with malnutrition, fibrosis, systemic inflammation, organ failures, disease course and mortality in ALD. Decorin enhances the risk estimation of mortality of MELD in AD and ACLF. Therapeutic modulation of myokines is a potentially disease‐modifying target in ALD.
Editorial: Quantity is important! Authors' reply
Authors: Rudler Marika , Thabut Dominique
Published: August 2024

LINKED CONTENT

This article is linked to Sultanik et al papers. To view these articles, visit https://doi.org/10.1111/apt.18165 and https://doi.org/10.1111/apt.18181
Iron metabolism in sickle cell disease patients undergoing chronic red blood cell exchange: A delicate homeostasis in balance
Authors: Valentini Caterina Giovanna , Teofili Luciana , Gehrie Eric
Published: August 2024

Sickle cell disease (SCD) is an inherited haemoglobinopathy associated with significant morbidity and mortality. Automated red blood cell exchange (aRCE) plays a key role in managing SCD, eliciting both therapeutic and prophylactic effects. The ideal post‐apheresis Ht target for chronic aRCE treatment is not yet unanimously recognized, as well as iron homeostasis can be different among patients. Ross et al. reported their experience on the chronic management of SCD patients undergoing aRCE with a final post‐exchange Ht higher than the value commonly adopted, analysing red blood cell transfusion requirements and iron‐related outcomes in the study population.

Commentary on: Ross et al. Automated red blood cell exchange with a post‐procedure haematocrit targeted at 34% in the chronic management of sickle cell disease. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19674.
Manipulating mannose metabolism as a potential anticancer strategy
Authors: Harada Yoichiro
Published: August 2024

Cancer cells acquire metabolic advantages over their normal counterparts regarding the use of nutrients for sustained cell proliferation and cell survival in the tumor microenvironment. Notable among the metabolic traits in cancer cells is the Warburg effect, which is a reprogrammed form of glycolysis that favors the rapid generation of ATP from glucose and the production of biological macromolecules by diverting glucose into various metabolic intermediates. Meanwhile, mannose, which is the C‐2 epimer of glucose, has the ability to dampen the Warburg effect, resulting in slow‐cycling cancer cells that are highly susceptible to chemotherapy. This anticancer effect of mannose appears when its catabolism is compromised in cancer cells. Moreover, de novo synthesis of mannose within cancer cells has also been identified as a potential target for enhancing chemosensitivity through targeting glycosylation pathways. The underlying mechanisms by which alterations in mannose metabolism induce cancer cell vulnerability are just beginning to emerge. This review summarizes the current state of our knowledge of mannose metabolism and provides insights into its manipulation as a potential anticancer strategy.
Soil organic carbon formation efficiency from straw/stover and manure input and its drivers: Estimates from long‐term data in global croplands
Authors: Yin Yulong , Chen Zhong , Gong Haiqing , He Kai , Miao Qi , Tian Xingshuai , Wang Zihan , Wang Yingcheng , Zheng Huifang , Cui Zhenling
Published: August 2024

New soil organic carbon (SOC) formation in cropland from straw/stover or manure input is a vital source of SOC for climate change mitigation. However, location and variations in the efficiency, specifically the ratio of new SOC formation to organic C input (NCE), remain unquantified globally. In this study, the spatial variability of cropland NCE from straw/stover or manure input and explanatory factors were determined by analyzing 897 pairs of long‐term field measurements from 404 globally distributed sites and by mapping grid‐level cropland NCEs. The global NCE for paddy and upland averaged 13.8% (8.7%–25.1%, 5th–95th percentile) and 10.9% (6.8%–17.3%), respectively. The initial SOC and the clay content of soil, rather than temperature, were the most important factors regulating NCE. A parabola with an apex at approximately 17 g kg−1 between the initial SOC and NCE was resolved, and a positive correlation between soil clay content and NCE was observed. High‐resolution mapping of the global NCE derived from manure/straw and insight into NCE dynamics provide a benchmark for diagnosing cropland soil C dynamics under climate change and identifying priority regions and actions for C management.
Interaction between magnetite and inoculum characteristics in accelerating methane production kinetics
Authors: Al‐Essa Ethar M. , Bello‐Mendoza Ricardo , Wareham David G.
Published: August 2024

Magnetite nanoparticles can boost methane production via direct interspecies electron transfer. However, the combined effect of inoculum and particle characteristics on magnetite's methanogenesis stimulation is poorly understood. Here, the influence of inoculum type, particle size, and particle concentration on the ability of magnetite to accelerate methanogenesis was studied in batch anaerobic digestion experiments. Fresh and degassed mesophilic digester sludge was used as inoculum, representing methanogenic communities in the exponential or stationary growth and endogenous decay phases, respectively. Three magnetite particle size ranges, small (50–150 nm), medium (168–490 nm), and large (800 nm–4.5 μm), at two different concentrations (2 and 7 mM) were used. With degassed sludge, the effect of magnetite on the methane production rate was weak and depended on the particle size and concentration. Only magnetite of medium size at both 2 and 7 mM significantly increased the methane production rate by 12% compared to the control with no magnetite. The lag phase was reduced by 17% compared to the control, only with 2 mM of both small and medium size magnetite. Conversely, adding magnetite into fresh sludge significantly increased the methane production rate by an average of 32% while simultaneously decreasing the lag phase by 15%–40%, as compared to the control, independently of the magnetite's size and concentration. The stimulation of methane production depends on magnetite and inoculum characteristics.
Clinical outcomes and risk factors in patients with COVID‐19 and autoimmune rheumatic diseases: insights from a major Australian hospital study
Authors: Ling Zhi , Guy Stephen , Fong Christopher
Published: August 2024

Background and Aim

Patients with autoimmune inflammatory rheumatic disease (AIIRD) are at higher risk of severe infections because of their underlying diseases and immunosuppression. Our objective was to elucidate the epidemiological and clinical characteristics of patients with AIIRD presenting with COVID‐19 and their relation to disease severity. We explored whether variables, including underlying diagnosis, disease‐modifying antirheumatic drugs (DMARDs) and COVID‐19 vaccine status, were associated with more severe forms of COVID‐19 infection.

Methods

Between 1 January 2020 and 30 June 2022, 151 patients with AIIRD and COVID‐19 infection were analysed using a binary regression model and a multinomial regression model.

Results

The average age was 61.5 years, and average Charlson Comorbidity Index (CCI) was 2.1; 106 (70.2%) patients were diagnosed with rheumatoid arthritis (RA), and 70 (46.4%) patients were receiving prednisolone. In the multivariable logistic regression model, ages between 50 and 69 years (odds ratio (OR) = 5.85; 95% confidence interval (CI) = 1.35–25.25) and older than 70 years (OR = 5.29; 95% CI = 1.21–23.14), prior prednisolone treatment (OR = 7.09; 95% CI = 2.63–19.11) and vaccination status including one and two doses (OR = 0.19; 95% CI = 0.05–0.69) and three and four doses (OR = 0.09; 95% CI = 0.02–0.35) were all statistically significant factors related to changes in the severity level of COVID‐19.

Conclusion

Severity of COVID‐19 infection in patients with AIIRD is affected by age, background steroid use and vaccination status. Factors including sex, comorbidity, diagnosis of AIIRDs and use of DMARDs, including conventional synthetic, biologics and targeted DMARDs, were not significantly associated with COVID‐19 severity.
Procreative Obligations and the Directed Duty of Care
Authors: Brandt Reuven
Published: August 2024

There is much dispute about what we owe the children we are responsible for creating. Some argue that so long as we provide offspring with lives worth living we do no wrong. Others argue that our procreative obligations are weightier and oblige us to provide (or attempt to provide) our offspring with a reasonable opportunity to thrive, or meet some other standard beyond merely providing a life worth living. Our practices and intuitions on this matter are inconsistent. For example, gamete donors who intentionally participate in the project of creating a child are thought to have few obligations to their offspring, but those who create a child accidentally are thought to have weighty obligations. Furthermore, a justification for why we are obliged to provide offspring with more than a life worth living has been elusive. To resolve this puzzle I argue that an under‐theorized element of morality, the directed duty of care, explains why we owe our offspring more than a life worth living.
Ocean warming and novel species interactions boost growth and persistence of range‐extending tropical fishes but challenge that of sympatric temperate species in temperate waters
Authors: Sasaki Minami , Monaco Cristián J. , Booth David J. , Nagelkerken Ivan
Published: August 2024

Aim

Climate change can have a broad range of impacts on the physiology and behaviour of animals. These effects can be mediated by the presence of other species in the community, but current forecasts of species responses to climate change largely ignore biological interactions. This is particularly true for novel interactions between range‐extending and native species, as this is often considered as noise and excluded from predictive models. Here we simulate how a tropical range‐extending and a local temperate fish species respond to the independent and combined effects of future ocean warming (RCPs 4.5 and 8.5) and novel ecological interactions in temperate ecosystems.

Location

East coast of Australia, along a ~ 2,000 km latitudinal gradient in a global climate warming hotspot.

Taxon

Abudefduf vaigiensis (tropical) and Atypicthys strigatus (temperate) fishes.

Methods

We use a dynamic energy budget model to simulate the length growth (i.e., increases in body length of individuals over time) and population persistence of juveniles of a tropical and a temperate fish species that form mixed‐species shoals, under different climate scenarios with and without the effects of novel ecological interactions.

Results

Our model forecasts that length growth of the juvenile tropical species will increase under ocean warming across subtropical to temperate regions. This increased length growth will be more drastic in temperate regions than in the subtropics, as winter warming will allow the tropical species to overwinter more frequently and show positive growth throughout the year. In contrast, warmer summer temperatures in the subtropics will likely exceed the optimal temperature of the juvenile temperate species at their trailing edge, resulting in reduced length growth under climate warming. Novel species interactions increased length growth of the juvenile tropical species but did not affect its winter or summer survival. In contrast, novel species interactions with tropical species were forecast to reduce length growth of the juvenile temperate species.

Main Conclusions

Our study suggests that for some coastal fish species future warming will likely reverse body size dominance between temperate and tropical fish species, with increased novel interactions in temperate ecosystems (due to range extensions) but decreased novel interactions in the subtropics (due to range contractions). Novel species interactions and warming effects on body size and species survival are likely to reshuffle temperate fish communities and their competitive interactions.
Fitness consequences of population bottlenecks in an invasive blowfly
Authors: Croft Lilly , Matheson Paige , Butterworth Nathan J. , McGaughran Angela
Published: August 2024

Invasive species often undergo demographic bottlenecks that cause a decrease in genetic diversity and associated reductions in population fitness. Despite this, they manage to thrive in novel environments. Investigating the effects of inbreeding and genetic bottlenecks on population fitness for invasive species is, therefore, key to understanding how they may survive in new environments. We used the blowfly Calliphora vicina (Sciences, Mathématiques et Physique, 1830, 2, 1), which is native to Europe and was introduced to Australia and New Zealand, to examine the effects of genetic diversity on population fitness. We first collected 59 samples from 15 populations across New Zealand and one in Australia, and used 20,501 biallelic SNPs to investigate population genomic diversity, structure and admixture. We then explored the impacts of repeated experimental bottlenecks on population fitness by creating inbred and outbred lines of C. vicina and measuring a variety of fitness traits. In wild‐caught samples, we found low overall genetic diversity, signals of genetic admixture and limited (<3%) genetic differentiation between North and South Island populations, with genetic links between the South Island and Australia. Following experimental bottlenecks, we found significant reductions in fitness for inbred lines. However, fitness effects were not felt equally across all phenotypic traits. Moreover, they were not enough to cause population collapse in any experimental line, suggesting that C. vicina (when under relaxed selection, as in laboratory settings) may be able to compensate for population bottlenecks even when highly inbred. Our results demonstrate the value of a tractable experimental system for investigating processes that may facilitate or hamper biological invasion.
Anti‐Ri‐antibodies associated paraneoplastic myelopathy revealing a woman's breast cancer: A case report
Authors: Zouari Rania , Ben Hmid Ahlem , Abdellatif Jihen , Zamali Imen , Saeid Mohamed Zakaria , Sassi Samia Ben , Ben Ahmed Melika
Published: August 2024

Paraneoplastic myelopathy (PM) is an enigmatic immune‐mediated disorder rarely associated with breast cancer (BC) and anti‐Ri antibodies. Sometimes diagnosis is difficult due to the heterogeneity of symptoms and the timing of their onset. Herein, we report the case of a woman presenting with cervical myelopathy causing spastic left hemiplegia and painful spasms. Diagnosis of PM was confirmed through the positivity of well‐characterized onconeural antibodies (anti‐Ri) and the discovery of BC after a clinical examination and multiple investigations. We highlight, through this case, the importance of onconeural antibodies in the diagnosis of paraneoplastic neurological syndromes and associated cancer.
Biomodulation effects induced by ultrasound stimulation in periodontal cells implicated in orthodontic tooth movement: A systematic review
Authors: Pascoal Selma , Monteiro Francisca , Oliveira Sofia , Simoni Arianna , Carvalho Óscar , Pinho Teresa
Published: August 2024

Accelerating orthodontic tooth movement (OTM) is increasingly important for shorter treatment times, which reduces periodontal risks, root resorption and dental caries. Techniques to accelerate OTM focus on stimulating bone remodelling by enhancing osteoclast and osteoblast activity and include both surgical and non‐surgical methods. The therapeutic potential of ultrasounds is highly recognized among many medical areas and has shown promising results in modulating bone remodelling and inflammation phenomena. This systematic review aims to collect and analyse the current scientific in vitro and ex vivo evidence on ultrasound stimulation (US) bioeffects in cells implicated in tooth movement. This review was conducted according to PRISMA 2020 guidelines. A bibliographic search was carried out in the PubMed, Scopus and Web of Science databases. Sixteen articles were selected and included in this review. The revised studies suggest that US of 1.0 and 1.5 MHz, delivered at 30 mW/cm2, 10 to 30 min daily over three to 14 days seems to be effective in promoting osteoclastogenic activity, while US of 1.5 MHz, 30 to 90 mW/cm2, in 5‐ to 20‐min sessions delivered daily for 5 to 14 days exhibits the potential to stimulate osteogenic activity and differentiation. Previous research yielded varied evidence of the effectiveness of US in orthodontics. Future animal studies should employ the recommended US parameters and investigate how distinct protocols can differentially impact tissue remodelling pathways. The knowledge arising from this review will ultimately potentiate the application of US to accelerate OTM in the clinical setting.
Food allergy in a changing dietary landscape: A focus on the Asia Pacific region
Authors: Leung Agnes Sze‐Yin , Pacharn Punchama , Tangvalelerd Supaluk , Sato Sakura , Pitt Erin , Wong Gary , Koplin Jennifer J.
Published: August 2024

Recent studies have provided compelling evidence to suggest that various environmental factors play a significant role in the development of food allergies. As our society experiences rapid economic growth, increased urbanization, and a shift towards a more Westernized diet, the incidence of food allergies is also on the rise and the pattern is gradually evolving. This review will delve into the changes in the epidemiology of food allergies within the Asia‐Pacific region and the various dietary practices and factors that are postulated to play a role in the rise in food allergies over the years. Although there have been important advancements in the field of food allergies, there are still numerous uncertainties regarding the intricate relationship between diet and food allergies. Specifically, the role of epigenetic factors in influencing the susceptibility to food allergies, as evidenced by studies that assessed the impact of migration and rural–urban dynamics, is not fully understood. Addressing this knowledge gap presents an opportunity to develop more effective prevention and treatment strategies that could greatly benefit individuals living with food allergies.

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Relationship sustainability: Exploring the idea of sustainable marriages among Indian married couples
Authors: Barman Jeshmeen D. , Maheshwari Saurabh
Published: August 2024

The present study adopted the concept of sustainability to understand Indian marriages and proposed a new concept of relationship sustainability. Employing an exploratory sequential mixed‐method design, Study 1 involved 30 interviews with long‐term married couples (Mage = 44.70; Mmarriage years = 19.48) to understand their marital experiences. Thematic analysis identified three major factors that lead to sustainability in marital relationships: couple bonding (a close connection that binds two partners together), personal well‐being (partner's contributions toward one's well‐being), and partner's well‐being (one's contribution to the partner's well‐being). Findings from Study 1 were used to develop a relationship sustainability scale, which was then used in Study 2, a survey study. A survey was conducted on 415 long‐term married individuals (Male: 221, Female: 194; Mage = 43.55; Mmarriage years = 17.74) that included information about relationship commitment, satisfaction, and happiness, along with other variables. Data from 415 long‐term married individuals were collected. The results confirmed the applicability of the concept of relationship sustainability and also showed that relationship sustainability predicted marital outcomes, such as happiness and satisfaction. Overall, the results showed that to achieve marital well‐being, one needs to move toward a sustainable model of relationship where partners both together strive for long‐term relationship and personal goals.
The effects of spiritual wellbeing on life satisfaction in hematologic cancer patients aged 65 and older in Turkey: mediating role of hope
Authors: Bahcecioglu Turan Gülcan , Özer Zülfünaz , YanmıŞ Safiye
Published: August 2024

Background

The mediating role of hope in the effects of spiritual wellbeing on life satisfaction in elderly haematologic cancer patients in Turkey was investigated in the present study.

Methods

The study was conducted in a descriptive, cross‐sectional and correlational design. The study was conducted with 150 patients aged 65 and older who were diagnosed with haematologic cancer and who were referred to a university hospital haematology clinic and outpatient clinic. Research data were collected with Descriptive Information Form, Dispositional Hope Scale (DHS), Spiritual Well‐being Scale (FACIT‐Sp‐12) and Satisfaction with Life Scale (SWLS).

Results

FACIT‐Sp‐12 score was 37.25 ± 7.29; DHS score was 40.42 ± 8.29, SWLS score was 16.24 ± 8.79. FACIT‐Sp‐12 (β = 0.668) and DHS (β = 0.226) were found to affect SWLS positively. In terms of the effect of FACIT‐Sp‐12 on SWLS, DHS has a mediating role and makes the positive effect of FACIT‐Sp‐12 on SWLS stronger (β = 0.771).

Conclusions

Spiritual wellbeing levels of the participants in our study were found to be high, while their levels of satisfaction with life and hope were found to be moderate. It was also concluded that spiritual wellbeing had a direct effect on satisfaction with life and an indirect effect through the mediating role of hope.