bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes and safety of atezolizumab plus bevacizumab in the treatment of hepatocellular carcinoma: treatment prognosis and comparison with tyrosine kinase inhibitors in a French multicenter matched real-life study
Authors: Adhoute Xavier , Gonzalez Alexia , Levi-strauss Thomas , Mineur Laurent , Pénaranda Guillaume , Sellier Floriane , Toullec Clémence , Pietri Olivia , Castellani Paul , Tran Albert , Perrier Hervé , Bourliere Marc , Anty Rodolphe
Published: July 2024

Background and aims

The combination of atezolizumab plus bevacizumab (Atz/Bev) has radically changed the treatment strategy for advanced hepatocellular carcinoma (HCC) but raises questions. Our objectives were to determine survival outcomes and safety in a real-life multicenter French cohort, to investigate the on-treatment prognostic value of the bioinflammatory RECA score, and to perform a matched comparison with patients who previously received tyrosine kinase inhibitors (TKIs).

Methodology

A retrospective analysis of 109 consecutive patients enrolled from September 2020 to January 2023 and a post matched comparison with a TKI cohort (n = 79) by the propensity score matching method.

Results

The Atz/Bev population was mainly nonviral disease patients (69%) with Child–Pugh grade A (90%), performance status 0/1 (90%), and Barcelona Clinic Liver Cancer stage B (38%) or stage C (62%) classification. After a median follow-up of 6.5 months (3.6–11.7), overall survival (OS) was 13.0 (5.1–28.7) months. OS was independently associated with metastasis, increased alkaline phosphatase, and serum bilirubin levels. Treatment-related adverse events were reported in 78% of patients, mostly grade 1 or 2. The RECA score clearly revealed two different prognosis groups after three cycles. No difference in OS was observed after matching between sequential treatment with TKIs and Atz/Bev.

Conclusion

This real-life study highlights the importance of liver function when using Atz/Bev combination and the necessity of identifying predictive markers of response to HCC therapies. Our findings suggest a change in practices, with a marked proportion of intermediate stages, and support the on-treatment prognostic value of an inflammatory score.
Fetal, neonatal, and infant death among offspring of pregnant women with HIV in Tanzania
Authors: Manji Karim P. , Muhihi Alfa , Duggan Christopher P. , Alwy Al-beity Fadhlun M. , Perumal Nandita , Ulenga Nzovu , Fawzi Wafaie W. , Sudfeld Christopher R.
Published: July 2024

Objective:

Assess the risk of death for offspring of pregnant women with HIV (PWHIV) and the association with sociodemographic, pregnancy, HIV-related, and birth factors.

Design:

We conducted a prospective cohort study of PWHIV on antiretroviral therapy (ART) and their offspring in urban Tanzania who were enrolled in a vitamin D trial conducted from June 2015 to October 2019.

Methods:

We described rates of fetal, neonatal, and infant death and assessed risk factors for these outcomes with generalized estimating equations. We also estimated population-attributable risk percentages for the contribution of prematurity and small-for-gestational age (SGA) to neonatal and infant mortality.

Results:

Among 2299 PWHIV, there were a total of 136 fetal deaths (5.6%) and the stillbirth rate was 42.0 per 1000 total births. Among 2167 livebirths, there were 57 neonatal deaths (26.3 per 1000 livebirths) and 114 infant deaths (52.6 per 1000 livebirths). Twin birth was associated with neonatal death, while maternal CD4+ T-cell count <350 cells/μl in pregnancy was associated with infant death (P-values < 0.05). As compared to term-appropriate-for-gestational age (AGA) births, the relative risks for neonatal mortality for term-SGA, preterm-AGA, and preterm-SGA infants were 2.07 [95% confidence interval (CI): 1.00–4.28], 2.87 (95% CI 1.54–5.35), and 7.15 (95% CI: 2.11–24.30), respectively. We estimated that 42.7% of neonatal and 29.4% of infant deaths were attributable to prematurity and SGA in the cohort.

Conclusions:

The risk of death is high for offspring of PWHIV in Tanzania and the combination of prematurity and fetal growth restriction may account for nearly half of neonatal deaths.
Joint Damage and Low Lean Body Mass in a Cohort of Peruvian Patients With Rheumatoid Arthritis
Authors: Velarde-Mejía Yelitza , Gamboa-Cárdenas Rocío , Ugarte-Gil Manuel F. , Pimentel-Quiroz Victor R. , Reátegui-Sokolova Cristina , Rodriguez-Bellido Zoila , Perich-Campos R. A. , Pastor-Asurza Cesar , Alarcón Graciela S.
Published: July 2024

Objectives

To determine the association between radiologic joint damage (JD) and a lower lean body mass (LBM) in rheumatoid arthritis (RA) patients.

Methods

A cross-sectional study from a single center established RA cohort. JD and appendicular LBM (arms and legs) were measured with the Sharp/van der Heijde (SvdH) score and dual x-ray absorptiometry expressed as kg/m2, respectively. A univariable analysis was used to determine the association between JD an LBM; then, a multivariable regression model was performed to evaluate the persistence of this association, adjusted by age, gender, disease duration, socioeconomic status (by the Graffar method), tobacco use, anticitrullinated protein antibody levels, Disease Activity Score in 28 joints for RA with erythrocyte sedimentation rate, glucocorticoid use (as prednisone equivalent), disease-modifying antirheumatic drug use, body mass index, and disability (by the multidimensional Health Assessment Questionnaire).

Results

Two hundred forty-seven patients were included; the average (SD) age was 63.0 (12.8) years, disease duration 20 (15.00) years, the total SvdH was 66 (86.75), and the aLBM was 13.6 (3.82) kg/m2. In the univariable analysis, a lower appendicular LBM was associated with higher SvdH score on the female population, in terms of the total (B= −8.6,p< 0.01), bone erosion (−4.4,p< 0.01), and joint space narrowing (−4.2,p< 0.01) scores; this correlation remained in the multivariable analysis in terms of total SvdH (B= −9.5,p< 0.01), bone erosion (−5.2,p< 0.01), and joint space narrowing (−4.3,p< 0.01).

Conclusions

A lower LBM in female patients was associated with more severe JD independently of other variables examined. Strategies aimed at preserving LBM could have a favorable impact on the course of disease.
Family Planning in Genetic Optic Atrophies in Israel, a Case Series and a Discussion of Ethical Considerations
Authors: Rozanes Eliane , Ben-Arzi Assaf , Boas Hagai , Ehrenberg Miriam , Bialer Omer , Stiebel-Kalish Hadas
Published: July 2024

Background:

Patients with genetic optic atrophies must navigate all stages of life with their visual impairment, including the important milestone of family planning. Advances in genetic testing now allows physicians and affected families to consider medical help with the aim of preventing blindness through preconception, preimplantation, and perinatal methods.

Methods:

This case series presents 4 patients with different genetic optic atrophies (Leber hereditary optic neuropathy [LHON], autosomal dominant optic atrophy, Wolfram syndrome, and papillorenal syndrome) who were followed by the Neuro-Ophthalmology Unit at a tertiary medical center between 2010 and 2023 and were of child-bearing age. The aim of this study was to increase understanding in family planning options for patients with optic atrophies, raise awareness of the solutions available, and provide guidance for clinicians to support their patients.

Results:

Advances in medicine, genetics, and medical technology allow multidisciplinary teams to assist patients in fulfilling their desire for a genetically healthy offspring. Customized solutions can be designed to meet the specific challenges posed by each type of genetic optic atrophy. The solutions proposed in this series are based on genetic testing done in the parents, which then allows to plan medical and genetic intervention individually. The solutions opted for in this series range from the decision to not have another child until PGD (Preimplantation genetic diagnosis).

Conclusion:

We describe how genetic advancements have made it possible for patients with the 4 most common hereditary optic atrophies to fulfill their wish to have children without visually threatening genetic mutations. We also review the recent literature on the penetrance of optic atrophy in OA-mutation carriers and raise 2 significant ethical considerations: the reduction of a future life to a non–life-threatening impairment and that of public expenditure for non–life-threatening conditions.
From fibres to adhesives: evolution of spider capture threads from web anchors by radical changes in silk gland function
Authors: Wolff Jonas O. , Ashley Leah J. , Schmitt Clemens , Heu Celine , Denkova Denitza , Jani Maitry , Řezáčová Veronika , Blamires Sean J. , Gorb Stanislav N. , Garb Jessica , Goodacre Sara L. , Řezáč Milan
Published: July 2024

Spider webs that serve as snares are one of the most fascinating and abundant type of animal architectures. In many cases they include an adhesive coating of silk lines—so-called viscid silk—for prey capture. The evolutionary switch from silk secretions forming solid fibres to soft aqueous adhesives remains an open question in the understanding of spider silk evolution. Here we functionally and chemically characterized the secretions of two types of silk glands and their behavioural use in the cellar spider,
Pholcus phalangioides.
Both being derived from the same ancestral gland type that produces fibres with a solidifying glue coat, the two types produce respectively a quickly solidifying glue applied in thread anchorages and prey wraps, or a permanently tacky glue deployed in snares. We found that the latter is characterized by a high concentration of organic salts and reduced spidroin content, showing up a possible pathway for the evolution of viscid properties by hygroscopic-salt-mediated hydration of solidifying adhesives. Understanding the underlying molecular basis for such radical switches in material properties not only helps to better understand the evolutionary origins and versatility of ecologically impactful spider web architectures, but also informs the bioengineering of spider silk-based products with tailored properties.
wQFM-TREE: highly accurate and scalable quartet-based species tree inference from gene trees
Authors: Rafi Abdur , Rumi Ahmed Mahir Sultan , Hakim Sheikh Azizul , Sohaib  , Tahmid Md. Toki , Momin Rabib Jahin Ibn , Zaman Tanjeem Azwad , Reaz Rezwana , Bayzid Md. Shamsuzzoha
Published: July 2024

Summary methods are becoming increasingly popular for species tree estimation from multi-locus data in the presence of gene tree discordance. ASTRAL, a leading method in this class, solves the Maximum Quartet Support Species Tree problem within a constrained solution space constructed from the input gene trees. In contrast, alternative heuristics such as wQFM and wQMC operate by taking a set of weighted quartets as input and employ a divide-and-conquer strategy to construct the species tree. Recent studies showed wQFM to be more accurate than ASTRAL and wQMC, though its scalability is hindered by the computational demands of explicitly generating and weighting Θ(n4) quartets. Here, we introduce wQFM-TREE, a novel summary method that enhances wQFM by circumventing the need for explicit quartet generation and weighting, thereby enabling its application to large datasets. Unlike wQFM, wQFM-TREE can also handle polytomies. Extensive simulations under diverse and challenging model conditions, with hundreds or thousands of taxa and genes, consistently demonstrate that wQFM-TREE matches or improves upon the accuracy of ASTRAL. Specifically, wQFM-TREE outperformed ASTRAL in 25 of 27 model conditions analyzed in this study involving 200-1000 taxa, with statistically significant differences in 20 of these conditions. Moreover, we applied wQFM-TREE to re-analyze the green plant dataset from the One Thousand Plant Transcriptomes Initiative. Its remarkable accuracy and scalability position wQFM-TREE as a highly competitive alternative to leading methods in the field. Additionally, the algorithmic and combinatorial innovations introduced in this study will benefit various quartet-based computations, advancing the state-of-the-art in phylogenetic estimations.
Metabolic alterations drive inflammatory phenotypes in CHIP-associated heart failure
Authors: Mansouri Siavash , Hemmerling Inga , Hesami Golnaz , Cremer Sebastian , Kirschbaum Klara , Klatt Stephan , Behjati Fatemeh , Schulz Marcel H. , Li Xue , Scheller Marina , Müller-Tidow Carsten , Arndt Philipp Friedrich , Günther Stefan , Padmasekar Manju , Looso Mario , Rieger Michael A. , Kuhnert Stefan , Vogelmeier Claus F. , Bals Robert , Fleming Ingrid , Zeiher Andreas , Seeger Werner , Leuschner Florian , Savai Rajkumar , Dimmeler Stefanie , Pullamsetti Soni S
Published: July 2024

Mutations in DNA methyltransferase 3 alpha(DNMT3A)are the most frequent driver of clonal hematopoiesis of indeterminate potential (CHIP), and associated with higher risk of cardiovascular disease and pro-inflammatory activation of immune cells. Here, we investigated the mechanisms underlying DNMT3A CHIP-associated inflammatory phenotypes in macrophages. We show that monocytes ofDNMT3ACHIP-driver mutation carriers are associated with DNA hypomethylation of succinate dehydrogenase A (SDHA) and an altered tricarboxylic acid cycle metabolite profile. Silencing of DNMT3A in monocytes increased SDHA and elevated mitochondria complex II activity. The secreted complex II product, malate, further increased inflammatory activation in wild type monocytes to further augment inflammation in a paracrine manner. Pharmacological inhibition of SDHA (using dimethyl malonate) in mice harboringDNMT3Amutations in hematopoietic stem cells ameliorated the inflammatory response and improved cardiac function after myocardial infarction. Thus, interfering with the altered metabolic state may provide a new therapeutic option to dampen inflammatory activation in DNMT3A CHIP carrying patients.
Harnessing Community Science and Open Research-based Data to Track Distributions of Invasive Species in Japan
Authors: Sakai Shoko , Atsumi Keisuke , Genroku Takanori , Goka Koichi , Fujiki Shogoro
Published: July 2024

At the forefront of invasive alien species (IAS) control, information gaps about the latest IAS distribution can hinder the required actions of local governments. In Japan, many prefectural governments still lack a list of invasive species despite the request stipulated in the Invasive Alien Species Management Action Plan enacted in 2015. Here, we examined to what extent open research-based data deposited by museums and herbaria (ORD) and community science data deposited by volunteers (CSD) can fill the gaps. We focused on 145 plant and 38 insect invasive species, and updated their distribution maps using ORD and CSD. We found complementarity as well as common limitations between ORD and CSD. While taxonomic biases were weaker in ORD, CSD had better prefectural coverage. In addition, some important taxa have rarely been captured by CSD or ORD. Mixed strategies of facilitating community science, supporting local museums, and taxon-specific monitoring by experts are necessary.
Effects of selection for early dispersal on the ambrosia beetleXyleborinus saxeseniiand its fungal symbionts
Authors: Melet Antoine , Biedermann Peter
Published: July 2024

Overlapping generations is a defining characteristic of advanced social life. In cooperative breeding societies, for example, temporary groups of mature offspring are formed that assist in the rearing of additional brood before the offspring disperse and reproduce independently. It is hypothesized that the number of helpers and their delayed dispersal period will determine the number of siblings that can be reared, thus resulting in an indirect fitness gain. The objective of this study, was to investigate the effect of artificial selection for early dispersal of mature offspring on the life history, behaviour and fungal symbionts in the cooperatively breeding ambrosia beetleXyleborinus saxesenii. Two lineages of beetles were bred in the laboratory for five successive generations. In one group, dispersing females were selected at random to initiate the next generation, while in the other group, only early dispersers were selected. A number of life-history traits exhibited a pronounced response in the initial generation, subsequently recuperating to levels approximating those observed at the outset of the experiment. The laboratory rearing resulted in an increasing proportion of successful nests in both lineages. Additionally, the control lineage exhibited a reduction in lifespan and in productivity. Furthermore, significant differences were observed in the fungal communities from the third generation onwards. The results suggest thatX. saxeseniihas limited potential to respond to this selection pressure, potentially due to sibmating and resulting low genetic variability. Furthermore, the correlation between nest lifespan and productivity is a crucial factor in explaining philopatry and altruism in this species.
Creation of a novel zebrafish model with low DHA status to study the role of maternal nutrition during neurodevelopment
Authors: Ranard Katherine M. , Appel Bruce
Published: July 2024

Docosahexaenoic acid (DHA), a dietary omega-3 fatty acid, is a major building block of brain cell membranes. Offspring rely on maternal DHA transfer to meet their neurodevelopmental needs, but DHA sources are lacking in the American diet. Low DHA status is linked to altered immune responses, white matter defects, impaired vision, and an increased risk of psychiatric disorders during development. However, the underlying cellular mechanisms involved are largely unknown, and advancements in the field have been limited by the existing tools and animal models. Zebrafish are an excellent model for studying neurodevelopmental mechanisms. Embryos undergo rapid external development and are optically transparent, enabling direct observation of individual cells and dynamic cell-cell interactions in a way that is not possible in rodents. Here, we create a novel DHA-deficient zebrafish model by 1) disruptingelovl2,a key gene in the DHA biosynthesis pathway, via CRISPR-Cas9 genome editing, and 2) feeding mothers a DHA-deficient diet. We show that low DHA status during development is associated with a small eye morphological phenotype and demonstrate that even the morphologically normal siblings exhibit dysregulated gene pathways related to vision and stress response. Future work using our zebrafish model could reveal the cellular and molecular mechanisms by which low DHA status leads to neurodevelopmental abnormalities and provide insight into maternal nutritional strategies that optimize infant brain health.
A laboratory method for simulating the effects of subsequent fires on pyrogenic organic matter at different exposure depths in a sand matrix
Authors: Luo Mengmeng , Yedinak Kara , Bourne Keith , Whitman Thea
Published: July 2024

Background

Across a variety of anthropogenic and natural contexts, fire can reoccur in a previously burned location. However, effects of subsequent fire on preexisting pyrogenic organic matter (PyOM) stocks are difficult to discern. Laboratory experiments offer a powerful approach to investigating how subsequent fire impacts the preexisting PyOM.

Aims

We aimed to design a highly repeatable laboratory method to effectively measure the impacts of subsequent fires on PyOM at different soil depths while addressing key limitations of previous methods.

Methods

Jack pine (Pinus banksianaLamb.) log burns were used to parameterize realistic heat flux profiles. Using a cone calorimeter, these profiles were applied to buried jack pine PyOM to simulate variable reburn fire intensities.

Key results

In general, higher heat flux and shallower depths led to more mass loss of PyOM from combustion and more heat exposure.

Conclusions

Our reburn method offers a highly replicable way to simulate specific fire scenarios. Conditions that result in more heat exposure (higher heat fluxes, shallower depths) are likely to lead to more loss of PyOM in subsequent fires.

Implications

The customizable method could simulate different fire scenarios to investigate spatial variability within a given fire event, or to study the effects of fire on different types of biomass or organisms, such as microbes.

Summary text

Our paper illustrates a laboratory method to better quantify loss of preexisting PyOM in soil after a fire.
An effective model for community-based conservation around authorized fishing settlements inside a devolved Wildlife Management Area in southern Tanzania
Authors: Duggan Lily M , Tarimo Lucia J , Walsh Katrina A , Kavishe Deogratius Roman , Crego Ramiro D , Elisa Manase , Mombo Felister , Butler Fidelma , Killeen Gerry
Published: July 2024

Wildlife Management Areas (WMAs) represent a relatively new institutional model for devolved, locally-led conservation in Tanzania, in which local villages set aside part of their land for wildlife conservation and manage that resource collectively, so that their stakeholder communities can collectively leverage economic and social benefits from income-generating activities like tourism. This study examines the relationship between community-defined land use plans andde factoland use practices, and the influence of the latter on the relative abundance and distribution of large wild mammals in a across the Ifakara-Lupiro-Mangula (ILUMA) WMA, which acts as a key buffer zone between Nyerere National Park (NNP) to the east and adjacent stakeholder villages to the north and west. All observed signs of wildlife and human activity were recorded across 32 locations inside ILUMA and in the permanent settlements and national park that respectively border it to the west and east. Across much of ILUMA WMA, in areas where agreed land use plans were not adhered to, rampant cattle herding and land clearing for agriculture were associated with reductions in wildlife richness and biodiversity, as well as overall ecosystem integrity. Although human settlement was also generally associated with reduced natural ecosystem integrity, some important exceptions to this rule illustrate how sustainable livelihoods for local people that are based on well-managed natural resource harvesting practices may actually enhance conservation effectiveness: Three authorised human settlements within the WMA, where fishing was the primary permitted livelihood and local communities collaborated with the WMA management, were surrounded by pristine land cover with thriving terrestrial wildlife populations. Correspondingly, the best conserved parts of the WMA not only included those closest to the boundary with the national park to the east, but also these fishing villages along the riverbank to the north, where compliance with agreed land use plans was most rigorous. Overall, this study documents a useful example of how a devolved conservation area may conditionally host resident local communities undertaking selective natural resource extraction activities and collaborate with them to achieve effectivede factoconservation practices.
CRISPR-mediated chromosome deletion facilitates genetic mapping of Vip3Aa resistance gene within complex genomic region in an invasive global pest
Authors: Jin Minghui , Shan Yinxue , Peng Yan , Chen Senlin , Zhou Xuanhe , Liu Kaiyu , Xiao Yutao
Published: July 2024

Connecting genetic variation to phenotypes and understanding the underlying biological mechanisms has been a fundamental goal of biological genetics. Here, we used the association analysis to identify a Vip3Aa resistance-associated genomic region in a strain of fall armyworm, JC-R, which exhibits >5000-fold resistance to the Bt toxin Vip3Aa. However, through various analytical approaches and fine-scale mapping across different populations, we demonstrated that this genomic region exhibits strong genetic linkage. The chromosome-level genome of JC-R and its parent strain JC-S were assembled, and extensive structural variations in the linkage regions were identified, which could be responsible for maintaining the linkage. To identify the causal variation within this linked region, a chromosome fragment stepwise knockout strategy based on CRISPR/Cas9 was developed. By crossing with the resistant strain and phenotyping segregating offspring on Vip3Aa-containing diet, we identified a chromosomal segment, KO8, containing the resistant gene. Subsequently, we conducted a comprehensive analysis of the variations in the KO8 region using multi-omics approaches, including genomic data, RNA-seq, proteomic, PacBio long read Iso-seq, and phosphoproteomic data. This analysis identified multiple variations in the chitin synthase geneCHS2, including amino acid substitution, alternative splicing, and changes in phosphorylation sites. After knocking out theCHS2, larvae exhibited over 6777-fold resistance to Vip3Aa. These results demonstrate that the chromosome fragment stepwise knockout strategy is a viable approach for studying complex genomic regions, and highlight the value of comprehensive analysis of genetic variations using multi-omics data. The identified candidate gene could potentially advance monitoring and management of pest resistance to Vip3Aa.
A Bayesian Hierarchical Model of Trial-To-Trial Fluctuations in Decision Criterion
Authors: Vloeberghs Robin , Urai Anne E. , Desender Kobe , Linderman Scott W.
Published: July 2024

Classical decision models assume that the parameters giving rise to choice behavior are stable, yet emerging research suggests these parameters may fluctuate over time. Such fluctuations, observed in neural activity and behavioral strategies, have significant implications for understanding decision-making processes. However, empirical studies on fluctuating human decision-making strategies have been limited due to the extensive data requirements for estimating these fluctuations. Here, we introduce hMFC (Hierarchical Model for Fluctuations in Criterion), a Bayesian framework designed to estimate slow fluctuations in the decision criterion from limited data. We first showcase the importance of considering fluctuations in decision criterion: incorrectly assuming a stable criterion gives rise to apparent history effects and underestimates perceptual sensitivity. We then present a hierarchical estimation procedure capable of reliably recovering the underlying state of the fluctuating decision criterion with as few as 500 trials per participant, offering a robust tool for researchers with typical human datasets. Critically, hMFC does not only accurately recover the state of the underlying decision criterion, it also effectively deals with the confounds caused by criterion fluctuations. Lastly, we provide code and a comprehensive demo atwww.github.com/robinvloeberghs/hMFCto enable widespread application of hMFC in decision-making research.
A novel and potent MICA/B antibody is therapeutically effective inKRAS LKB1mutant lung cancer models
Authors: Kowash Ryan R , Sabnani Manoj , Gray Laura T , Deng Qing , Girard Luc , Naito Yujiro , Masuhiro Kentaro , Minna John D , Gerber David E , Koyama Shohei , Liu Zhiqian Lucy , Baruah Hemanta , Akbay Esra A
Published: July 2024

ConcurrentKRAS LKB1(STK11, KL) mutant Non-Small Cell Lung Cancers (NSCLC) is particularly difficult to treat and does not respond well to current immune checkpoint blockade (ICB) therapies. This is due to numerous mechanisms including low antigen presentation limiting T cell mediated killing. To activate anti-tumor immunity, we targeted tumor cell – natural killer (NK) cell interactions. We tested whether a novel antibody based therapeutic strategy that predominantly activates natural killer (NK) cells demonstrates efficacy in pre-clinical mouse models of KL NSCLC. NK cells rely on binding of ligands, such as Major Histocompatibility Complex (MHC) class I-related chain A or B (MICA/B), to the activating receptor NKG2D. Importantly MICA and MICB are widely expressed in elevated levels across NSCLC subtypes including KL lung cancers. Proteases with the tumor microenvironment (TME) can cleave these proteins rendering tumor cells less visible to NK cells. We therefore developed a MICA monoclonal antibody, AHA-1031, which utilizes two NK cell activating receptors. AHA1031 prevents ligand shedding without interfering with binding to NKG2D while targeting cancer cells to antibody mediated cell dependent cytotoxicity (ADCC). Our therapeutic novel antibody has significant monotherapy activity in KL cancer models including xenografts of human cell lines and patient derived xenografts. Activating NK cells through MICA/B stabilization and inducing ADCC offers an alternative and potent therapy option in KL tumors. MICA/B are shed across different tumors making this therapeutic strategy universally applicable.
Origin and development of uniparental and polyploid blastomeres
Authors: Zhao Yan , Fernández-Montoro Andrea , Peeters Greet , Jatsenko Tatjana , De Coster Tine , Angel-Velez Daniel , Lefevre Thomas , Voet Thierry , Tšuiko Olga , Kurg Ants , Smits Katrien , Van Soom Ann , Vermeesch Joris Robert
Published: July 2024

Whole-genome (WG) abnormalities, such as uniparental diploidy and triploidy, cause fetal death. Occasionally, they coexist with biparental diploid cells in live births. Understanding the origin and early development of WG abnormal blastomeres is crucial for explaining the formation of androgenotes, gynogenotes, triploidy, chimerism, and mixoploidy. By haplotyping 118 blastomeres from first cleavages, we identified various mechanisms of heterogoneic divisions that lead to WG abnormal blastomeres or their coexistence with normal blastomeres in both multipolar and bipolar cleaving zygotes. After culturing the totipotent blastomeres to three preimplantation stages and performing transcriptome profiling on over 600 cells, we discovered that stress responses contribute to developmental impairment in WG abnormal cells, resulting in either cell arrest or blastocyst formation. Some first-cleavage-derived WG abnormal blastomeres can survive early development and progress to blastocysts. Their potential dominance in preimplantation embryos represents an overlooked cause of abnormal development. Haplotype based screening could further increase pregnancy rates.
The integrated stress response regulates 18S nonfunctional rRNA decay in mammals
Authors: Coria Aaztli R. , Shah Akruti , Shafieinouri Mohammad , Taylor Sarah J. , Guiblet Wilfried , Miller Jennifer T. , Mani Sharma Indra , Wu Colin Chih-Chien
Published: July 2024

18S nonfunctional rRNA decay (NRD) detects and eliminates translationally nonfunctional 18S rRNA. While this process is critical for ribosome quality control, the mechanisms underlying nonfunctional 18S rRNA turnover remain elusive. NRD was originally identified and has exclusively been studied inSaccharomyces cerevisiae.Here, we show that 18S NRD is conserved in mammals. Using genome-wide CRISPR genetic interaction screens, we find that mammalian NRD acts through the integrated stress response (ISR) via GCN2 and ribosomal protein ubiquitination by RNF10. Selective ribosome profiling reveals nonfunctional 18S rRNA induces translational arrest at start sites. Indeed, biochemical analyses demonstrate that ISR activation limits translation initiation and attenuates collisions between scanning 43S preinitiation complexes and nonfunctional 80S ribosomes arrested at start sites. Overall, the ISR promotes nonfunctional 18S rRNA and 40S ribosomal protein turnover by RNF10-mediated ubiquitination. These findings establish a dynamic feedback mechanism by which the GCN2-RNF10 axis surveils ribosome functionality at translation initiation.
Loss ofRREB1reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes
Authors: Yu Grace Z. , Krentz Nicole A. J. , Bentley Liz , Zhao Meng , Paphiti Keanu , Sun Han , Honecker Julius , Nygård Marcus , Dashti Hesam , Bai Ying , Reid Madeleine , Thaman Swaraj , Wabitsch Martin , Rajesh Varsha , Yang Jing , Mattis Katia K , Abaitua Fernando , Casero Ramon , Hauner Hans , Knowles Joshua W , Wu Joy Y , Mandrup Susanne , Claussnitzer Melina , Svensson Katrin J , Cox Roger D. , Gloyn Anna L.
Published: July 2024

There are multiple independent genetic signals at theRas-responsive element binding protein 1(RREB1) locus associated with type 2 diabetes risk, fasting glucose, ectopic fat, height, and bone mineral density. We have previously shown that loss ofRREB1in pancreatic beta cells reduces insulin content and impairs islet cell development and function. However, RREB1 is a widely expressed transcription factor and the metabolic impact of RREB1 lossin vivoremains unknown. Here, we show that male and female global heterozygous knockout (Rreb1+/-) mice have reduced body length, weight, and fat mass on high-fat diet.Rreb1+/-mice have sex- and diet-specific decreases in adipose tissue and adipocyte size; male mice on high-fat diet had larger gonadal adipocytes, while males on standard chow and females on high-fat diet had smaller, more insulin sensitive subcutaneous adipocytes. Mouse and human precursor cells lacking RREB1 have decreased adipogenic gene expression and activated transcription of genes associated with osteoblast differentiation, which was associated withRreb1+/-mice having increased bone mineral densityin vivo. Finally, human carriers ofRREB1T2D protective alleles have smaller adipocytes, consistent with RREB1 loss-of-function reducing diabetes risk.
ERGA-BGE genome ofValencia hispanica(Valenciennes, 1826): a critically endangered Iberian toothcarp
Authors: Ventura Marc , Franch Nati , Fernández Rosa , Palma-Guerrero Javier , Böhne Astrid , Monteiro Rita , Aguilera Laura , Gut Marta , Alioto Tyler S. , Câmara Ferreira Francisco , Cruz Fernando , Gómez-Garrido Jèssica , Haggerty Leanne , Martin Fergal , Brown Thomas
Published: July 2024

The reference genome ofValencia hispanica, a critically endangered actinopterygian species endemic to the Iberian Peninsula, is key to unravelling its genetic architecture and adaptation to freshwater ecosystems. This genomic resource will enable targeted conservation efforts and shed light on the species’ essential role in ecological dynamics, including its contributions to algal biomass regulation and role in the aquatic food web while also highlighting the challenges it faces from habitat degradation and invasive species. Furthermore, it offers opportunities to gain valuable insights into the evolutionary paths within the Valenciidae family, significantly advancing our comprehension of genetic diversity and adaptability in aquatic ecosystems. The entirety of the genome sequence was assembled into 24 contiguous chromosomal pseudomolecules. This chromosome-level assembly encompasses 1.29Gb, composed of 99 contigs and 28 scaffolds, with contig and scaffold N50 values of 38.3Mb and 56.9Mb, respectively.
Probing the Quark Orbital Angular Momentum at Electron-Ion Colliders Using Exclusive
π0
Production
Authors: Bhattacharya Shohini , Zheng Duxin , Zhou Jian
Published: July 2024

We propose to detect signals from quark orbital angular momentum (OAM) through exclusive π0 production in electron- (longitudinally polarized) proton collisions. Our analysis demonstrates that the sin2ϕ azimuthal angular correlation between the transverse momentum of the scattered electron and the recoil proton serves as a sensitive probe of quark OAM. Additionally, we present a numerical estimate of the asymmetry associated with this correlation for the kinematics accessible at the Electron-Ion Colliders in the U.S. and China. This study aims to pave the way for the first experimental study of quark OAM in relation to the Jaffe-Manohar spin sum rule.

Published by the American Physical Society
2024
RMCProfile7: reverse Monte Carlo for multiphase systems
Authors: Sławiński Wojciech A. , Kerr Christopher J. , Zhang Yuanpeng , Playford Helen Y. , Dove Martin T. , Phillips Anthony E. , Tucker Matthew G.
Published: July 2024

This work introduces a completely rewritten version of the program RMCProfile (version 7), big-box, reverse Monte Carlo modelling software for analysis of total scattering data. The major new feature of RMCProfile7 is the ability to refine multiple phases simultaneously, which is relevant for many current research areas such as energy materials, catalysis and engineering. Other new features include improved support for molecular potentials and rigid-body refinements, as well as multiple different data sets. An empirical resolution correction and calculation of the pair distribution function as a back-Fourier transform are now also available. RMCProfile7 is freely available for download at https://rmcprofile.ornl.gov/.
AutoRefl: active learning in neutron reflectometry for fast data acquisition
Authors: Hoogerheide David P. , Heinrich Frank
Published: July 2024

Neutron reflectometry (NR) is a powerful technique for interrogating the structure of thin films at interfaces. Because NR measurements are slow and instrument availability is limited, measurement efficiency is paramount. One approach to improving measurement efficiency is active learning (AL), in which the next measurement configurations are selected on the basis of information gained from the partial data collected so far. AutoRefl, a model-based AL algorithm for neutron reflectometry measurements, is presented in this manuscript. AutoRefl uses the existing measurements of a function to choose both the position and the duration of the next measurement. AutoRefl maximizes the information acquisition rate in specific model parameters of interest and uses the well defined signal-to-noise ratio in counting measurements to choose appropriate measurement times. Since continuous measurement is desirable for practical implementation, AutoRefl features forecasting, in which the optimal positions of multiple future measurements are predicted from existing measurements. The performance of AutoRefl is compared with that of well established best practice measurements for supported lipid bilayer samples using realistic digital twins of monochromatic and polychromatic reflectometers. AutoRefl is shown to improve NR measurement speeds in all cases significantly.
Crystal structures of seven gold(III) complexes of the form LAuX
3 (L = substituted pyridine, X = Cl or Br)
Authors: Döring Cindy , Jones Peter G.
Published: July 2024

The structures of seven gold(III) halide derivatives of general formula LAuX
3 (L = methylpyridines or dimethylpyridines, X = Cl or Br) are presented: trichlorido(2-methylpyridine)gold(III), [AuCl3(C6H7N)], 1 (as two polymorphs 1a and 1b); tribromido(2-methylpyridine)gold(III), [AuBr3(C6H7N)], 2; tribromido(3-methylpyridine)gold(III), [AuBr3(C6H7N)], 3; tribromido(2,4-dimethylpyridine)gold(III), [AuBr3(C7H9N)], 4; trichlorido(3,5-dimethylpyridine)gold(III), [AuCl3(C7H9N)], 5; tribromido(3,5-dimethylpyridine)gold(III), [AuBr3(C7H9N)], 6, and trichlorido(2,6-dimethylpyridine)gold(III), [AuCl3(C7H9N)], 7. Additionally, the structure of 8, the 1:1 adduct of 2 and 6, [AuBr3(C6H7N)]·[AuBr3(C7H9N)], is included. All the structures crystallize solvent-free, and all have Z′ = 1 except for 5 and 7, which display crystallographic twofold rotation symmetry, and 4, which has Z′ = 2. 1a and 2 are isotypic. The coordination geometry at the gold(III) atoms is, as expected, square-planar. Four of the crystals (1a, 1b, 2 and 8) were non-merohedral twins, and these structures were refined using the ‘HKLF 5’ method. The largest interplanar angles between the pyridine ring and the coordination plane are observed for those structures with a 2-methyl substituent of the pyridine ring. The Au—N bonds are consistently longer trans to Br (average 2.059 Å) than trans to Cl (average 2.036 Å). In the crystal packing, a frequent feature is the offset-stacked and approximately rectangular dimeric moiety (Au—X)2, with antiparallel Au—X bonds linked by Au...X contacts at the vacant positions axial to the coordination plane. The dimers are connected by further secondary interactions (Au...X or X...X contacts, `weak' C—H...X hydrogen bonds) to form chain, double chain (`ladder') or layer structures, and in several cases linked again in the third dimension. Only 1b and 7 contain no offset dimers; these structures instead involve C—H...Cl hydrogen bonds combined with Cl...Cl contacts (1b) or Cl...π contacts (7). The packing patterns of seven further complexes LAuX
3 involving simple pyridines (taken from the Cambridge Structural Database) are compared with those of 1–8.
Fixed-time fault-tolerant attitude tracking control for UAV based on fixed-time extended state observer
Authors: Wu Qilong , Zhu Qidan
Published: July 2024

Purpose

To improve the robustness of carrier-based unmanned aerial vehicle (UAV) with actuator faults attitude tracking control system, this paper aims to propose a fixed-time backstepping (FXTBSC) fault-tolerant control based on a fixed-time extended state observer.

Design/methodology/approach

A fixed-time extended state observer (FXTESO) is designed to estimate the total disturbance including nonlinear, coupling, actuator faults and external disturbances. The integration of backstepping control and fixed-time technology ensures fixed-time convergence.

Findings

The simulation results of tracking the desired attitude angle show that the anti-interference, fault tolerance and tracking accuracy of FXTBSC-FXTESO are better than the BSC-ESO control method.

Originality/value

Different from the traditional BSC-ESO, the convergence speed and convergence accuracy of FXTBSC-FXTESO proposed in this paper are better than conventional extended state observer. And the fixed time controller has the advantages of high tracking accuracy, fault tolerance and anti-interference ability.
Human rights health care measures reporting physical fitness test for ages 6 to 17 with 10-year follow-up
Authors: Fujimori Satomi , Ashida Kazuki , Watanabe Noriaki , Nishino Tomoyuki , Sasamori Fumihito , Okuhara Masao , Tabuchi Hisaaki , Terasawa Koji
Published: July 2024

Purpose

This study aims to compare the physical fitness test results of Japanese children in 2008 and 2018 to narrow the gap between life expectancy and healthy life expectancy and extend healthy life expectancy. In addition, this paper sought to explore the potential of implementing health education programs as a new social context to promote race equality and human rights in health and social care.

Design/methodology/approach

This study was conducted in 2008 and 2018 in Nagano Prefecture, Japan. Physical fitness tests related to growth and development were administered to participants aged 6–17 years.

Findings

Physical fitness measurements in 2018, specifically those for walking ability and endurance, were significantly inferior to those in 2008. In a gender-specific analysis, boys outperformed girls in muscle strength, muscle endurance, walking ability and endurance tests, while girls outperformed boys in the balance test.

Research limitations/implications

Most of the junior and senior high school students who participated in the EO test exceeded the upper limit of 120 s, suggesting that the load of the measurement method is low and improvement is necessary. In 2018, a large variation in 6M results was observed among participants, possibly due to the differences in the level of seriousness during the 6M test. Therefore, to ensure that junior and senior high school students properly perform the EO and 6M tests, it is necessary to devise an effective method of implementation, such as changing the physical fitness test load.

Originality/value

Mere health education is ineffective to address health inequalities. Addressing structural factors is essential to avoid unintended consequences such as increasing the gap between groups of people. However, one way to extend healthy life expectancy is to improve overall health, including differences in the health status of groups due to differences in region and socioeconomic status.
The impact of sustainable design and construction upon FM: four case studies
Authors: Lavy Sarel , Deshpande Rahul , Jadhav Tushar
Published: July 2024

Purpose

This paper aims to analyze the impact of sustainability measures taken during the design and construction phases, by examining two categories of sustainability: energy efficiency and reducing carbon emissions and material selection and waste management. These aspects are examined from the perspectives of long-term building performance and maintenance practices, as well as user/tenant satisfaction.

Design/methodology/approach

This study includes a literature review related to the two topics under consideration, followed by a comparative case study analysis of four projects to determine practical validity. All case studies in this paper used a semi-structured survey with various project stakeholders, which helped the authors identify measures taken as well as obstacles and challenges during the process.

Findings

According to the four case studies, adequate attention should be paid to the two areas of interest during a project’s design and construction phases. Including case studies from around the world (four case studies from three different countries) offers insights into effective sustainability practices in building design and construction, providing instances of successful implementation and emphasizing the obstacles and potential when incorporating sustainability into the design and construction phases.

Research limitations/implications

The findings also show that design and construction participants and companies should reduce waste generation and carbon emissions. In addition, they should make decisions on material selection to enhance projects’ sustainability and to contribute to creating a habitable planet for the future.

Originality/value

The influence of the design and construction phases on long-term project sustainability is of major importance and concern to users, owners, designers, contractors and facility managers. This study illustrates the necessity of including sustainability measures in the design and construction phases, highlighting the importance of sustainability in building design and construction through effective implementation techniques and interdisciplinary teamwork to realize sustainable goals.
Health service requirements of mHealth app users: evidence from Hangzhou, China
Authors: Xu Zhongyang , Meng Zhiqian
Published: July 2024

Purpose

China’s healthcare system is being burdened by the increasing prevalence of chronic diseases. Therefore, this study investigated the health service requirements of mobile health applications (mHealth apps) users in Hangzhou, China. This study aimed to propose suggestions and theoretical references to improve mHealth apps and promote their development, thereby meeting public medical and health needs and creating an efficient medical service system.

Design/methodology/approach

We constructed a model of health service demands using a literature review, network survey, and semi-structured interviews. We analyzed the demand attributes using the Kano model and Better-Worse index and obtained the priority ranking of demands.

Findings

The results revealed 25 demand elements in four dimensions: must-be (M), one-dimensional (O), attractive (A), and indifferent (I) requirements. The findings suggest that mHealth app developers can optimize health services by categorizing and managing health services, focusing on middle-aged users, enhancing the professionalism of health service providers, and improving the feedback mechanism.

Originality/value

Studies on mHealth apps user demands, particularly on health service needs, remain scarce. This study employed a mixed-methods approach, integrating both qualitative and quantitative research techniques, to establish a priority ranking of user health service needs for mHealth apps. The study offers recommendations and theoretical references to optimize and improve mHealth app services.

Highlights

Construct a better health service requirements model for mHealth app users.

Obtain the prioritization of demand elements in the model.

Propose some management suggestions to improve mHealth apps.