bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-genome resequencing reveals genomic variation and dynamics in Ethiopian indigenous goats
Authors: Sheriff Oumer , Ahbara Abulgasim M. , Haile Aynalem , Alemayehu Kefyalew , Han Jian-Lin , Mwacharo Joram M.
Published: May 2024

Ethiopia has about 52 million indigenous goats with marked phenotypic variability, which is the outcome of natural and artificial selection. Here, we obtained whole-genome sequence data of three Ethiopian indigenous goat populations (Arab, Fellata, and Oromo) from northwestern Ethiopia and analyzed their genome-wide genetic diversity, population structure, and signatures of selection. We included genotype data from four other Ethiopian goat populations (Abergelle, Keffa, Gumuz, and Woyto-Guji) and goats from Asia; Europe; and eastern, southern, western, and northern Africa to investigate the genetic predisposition of the three Ethiopian populations and performed comparative genomic analysis. Genetic diversity analysis showed that Fellata goats exhibited the lowest heterozygosity values (Ho = 0.288 ± 0.005 and He = 0.334 ± 0.0001). The highest values were observed in Arab goats (Ho = 0.310 ± 0.010 and He = 0.347 ± 4.35e−05). A higher inbreeding coefficient (FROH = 0.137 ± 0.016) was recorded for Fellata goats than the 0.105 ± 0.030 recorded for Arab and the 0.112 ± 0.034 recorded for Oromo goats. This indicates that the Fellata goat population should be prioritized in future conservation activities. The three goat populations showed the majority (∼63%) of runs of homozygosity in the shorter (100–150 Kb) length category, illustrating ancient inbreeding and/or small founder effects. Population relationship and structure analysis separated the Ethiopian indigenous goats into two distinct genetic clusters lacking phylogeographic structure. Arab, Fellata, Oromo, Abergelle, and Keffa represented one genetic cluster. Gumuz and Woyto-Guji formed a separate cluster and shared a common genetic background with the Kenyan Boran goat. Genome-wide selection signature analysis identified nine strongest regions spanning 163 genes influencing adaptation to arid and semi-arid environments (HOXC12, HOXC13, HOXC4, HOXC6, and HOXC9, MAPK8IP2), immune response (IL18, TYK2, ICAM3, ADGRG1, and ADGRG3), and production and reproduction (RARG and DNMT1). Our results provide insights into a thorough understanding of genetic architecture underlying selection signatures in Ethiopian indigenous goats in a semi-arid tropical environment and deliver valuable information for goat genetic improvement, conservation strategy, genome-wide association study, and marker-assisted breeding.
A novel locus in CSMD1 gene is associated with increased susceptibility to severe malaria in Malian children
Authors: Damena Delesa , Barry Amadou , Morrison Robert , Gaoussou Santara , Mahamar Almahamoudou , Attaher Oumar , Issiaka Djibrilla , Dicko Yahia , Dicko Alassane , Duffy Patrick , Fried Michal
Published: May 2024

Background

Plasmodium falciparum malaria is still a leading cause of child mortality in sub-Saharan Africa. The clinical manifestations of malaria range from asymptomatic infection to severe disease. The variation in clinical presentation is partly attributed to host genetic factors with estimated narrow-sense heritability of 23%. Here, we investigate the associations between candidate gene polymorphisms and the likelihood of severe malaria (SM) in a cohort of Malian children.

Methods

Based on our previous genome-wide association studies (GWAS) analysis, candidate genes were selected for in-depth analysis using several criteria including gene-level GWAS scores, functional overlap with malaria pathogenesis, and evidence of association with protection or susceptibility to other infectious or inflammatory diseases. Single Nucleotide Polymorphisms (SNPs) residing within these genes were selected mainly based on p-values from previous severe malaria susceptibility GWAS studies and minor allele frequency (MAF) in West African populations.

Results

Of 182 candidate genes reported in our previous study, 11 genes and 22 SNPs residing in these genes were selected. The selected SNPs were genotyped using KASP technology in 477 DNA samples (87 SM and 390 controls). Logistic regression analysis revealed that a common intron variant, rs13340578 in CUB and Sushi Multi Domain (CSMD1) gene, is associated with increased odds of SM in recessive mode of inheritance (MAF = 0.42, OR = 1.8, 95% CI = [1.78, 1.84], p = 0.029). The SNP is in linkage disequilibrium (LD) with multiple variants with regulatory features.

Conclusion

Taken together, the current study showed that an intron variant rs13340578, residing in CSMD1 gene, is associated with increased susceptibility to malaria. This finding suggests that modified regulation of complement may contribute to malaria disease severity. Further studies are needed to identify the causal variants and the underlying molecular mechanisms.
Barriers to help-seeking for postpartum depression mapped onto the socio-ecological model and recommendations to address barriers
Authors: Place Jean Marie S. , Renbarger Kalyn , Van De Griend Kristin , Guinn Maya , Wheatley Chelsie , Holmes Olivia
Published: May 2024

Postpartum depression affects nearly a quarter of women up to a year after childbirth. Although it is treatable, significant barriers to help-seeking prevent women from being treated. This paper assesses key literature on the barriers for help-seeking among women with postpartum depression. The barriers identified have been mapped onto the socio-ecological model in addition to potential recommendations that professionals can use to address barriers on individual, interpersonal, organizational, community and societal levels. The recommendations provided are meant to serve as leverage points for professionals in efforts to create appropriate support and interventions. As such, this paper serves as a mapping tool for healthcare and public health professionals to assess obstacles to women's help-seeking and to guide multi-pronged interventions on various levels of the socio-ecological model that may increase help-seeking among women with postpartum depression. Holistically and comprehensively providing support to women will require significant effort throughout all sectors of society as opposed to isolated, siloed interventions.
Simultaneous targeting of Tim3 and A2a receptors modulates MSLN-CAR T cell antitumor function in a human cervical tumor xenograft model
Authors: Soltantoyeh Tahereh , Akbari Behnia , Shahosseini Zahra , Mirzaei Hamid Reza , Hadjati Jamshid
Published: May 2024

Introduction

Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of hematological malignancies. However, its efficacy in solid tumors is limited by the immunosuppressive tumor microenvironment that compromises CAR T cell antitumor function in clinical settings. To overcome this challenge, researchers have investigated the potential of inhibiting specific immune checkpoint receptors, including A2aR (Adenosine A2 Receptor) and Tim3 (T cell immunoglobulin and mucin domain-containing protein 3), to enhance CAR T cell function. In this study, we evaluated the impact of genetic targeting of Tim3 and A2a receptors on the antitumor function of human mesothelin-specific CAR T cells (MSLN-CAR) in vitro and in vivo.

Methods

Second-generation anti-mesothelin CAR T cells were produced using standard cellular and molecular techniques. A2aR-knockdown and/or Tim3- knockdown anti-mesothelin-CAR T cells were generated using shRNA-mediated gene silencing. The antitumor function of CAR T cells was evaluated by measuring cytokine production, proliferation, and cytotoxicity in vitro through coculture with cervical cancer cells (HeLa cell line). To evaluate in vivo antitumor efficacy of manufactured CAR T cells, tumor growth and mouse survival were monitored in a human cervical cancer xenograft model.

Results

In vitro experiments demonstrated that knockdown of A2aR alone or in combination with Tim3 significantly improved CAR T cell proliferation, cytokine production, and cytotoxicity in presence of tumor cells in an antigen-specific manner. Furthermore, in the humanized xenograft model, both double knockdown CAR T cells and control CAR T cells could effectively control tumor growth. However, single knockdown CAR T cells were associated with reduced survival in mice

Conclusion

These findings highlight the potential of concomitant genetic targeting of Tim3 and A2a receptors to augment the efficacy of CAR T cell therapy in solid tumors. Nevertheless, caution should be exercised in light of our observation of decreased survival in mice treated with single knockdown MSLN-CAR T cells, emphasizing the need for careful efficacy considerations.
Interleukin-1 regulates follicular T cells during the germinal center reaction
Authors: Belbezier Aude , Engeroff Paul , Fourcade Gwladys , Vantomme Hélène , Vaineau Romain , Gouritin Bruno , Bellier Bertrand , Brocheriou Isabelle , Tchitchek Nicolas , Graff-Dubois Stephanie , Klatzmann David
Published: May 2024

Introduction

Antibody production and the generation of memory B cells are regulated by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in germinal centers. However, the precise role of Tfr cells in controlling antibody production is still unclear. We have previously shown that both Tfh and Tfr cells express the IL-1R1 agonist receptor, whereas only Tfr cells express the IL-1R2 decoy and IL-1Ra antagonist receptors. We aimed to investigate the role of IL-1 receptors in the regulation of B cell responses by Tfh and Tfr.

Methods

We generated mice with IL-1 receptors inactivated in Tfh or Tfr and measured antibody production and cell activation after immunisation.

Results

While IL-1β levels are increased in the draining lymph node after immunisation, antigen-specific antibody levels and cell phenotypes indicated that IL-1β can activate both Tfh and Tfr cells through IL-1R1 stimulation. Surprisingly, expression of IL-1R2 and IL-1Ra on Tfr cells does not block IL-1 activation of Tfh cells, but rather prevents IL-1/IL-1R1-mediated early activation of Tfr cells. IL-1Rs also regulate the antibody response to autoantigens and its associated pathophysiology in an experimental lupus model.

Discussion

Collectively, our results show that IL-1 inhibitory receptors expressed by Tfr cells prevent their own activation and suppressive function, thus licensing IL-1-mediated activation of Tfh cells after immunisation. Further mechanistic studies should unravel these complex interactions between IL-1β and follicular helper and regulatory T cells and provide new avenues for therapeutic intervention.
The 330 risk loci known for systemic lupus erythematosus (SLE): a review
Authors: Laurynenka Viktoryia , Harley John B.
Published: May 2024

An in-depth literature review of up to 2023 reveals 330 risk loci found by genetic association at p ≤ 5 × 10−8, with systemic lupus erythematosus (SLE) in at least one study of 160 pertinent publications. There are 225 loci found in East Asian (EAS), 106 in European (EU), 11 in African-American (AA), 18 Mixed American (MA), and 1 in Egyptian ancestries. Unexpectedly, most of these associations are found to date at p ≤ 5 × 10−8 in a single ancestry. However, the EAS and EU share 40 risk loci that are independently established. The great majority of the identified loci [250 (75.8%) of 330] do not contain a variant that changes an amino acid sequence. Meanwhile, most overlap with known regulatory elements in the genome [266 (80.6%) of 330], suggesting a major role for gene regulation in the genetic mechanisms of SLE. To evaluate the pathways altered by SLE-associated variants, we generated gene sets potentially regulated by SLE loci that consist of the nearest genes, published attributions, and genes predicted by computational tools. The most useful insights, at present, suggest that SLE genetic mechanisms involve (1) the regulation of both adaptive and innate immune responses including immune cell activation and differentiation; (2) the regulation of production and response to cytokines, including type I interferon; (3) apoptosis; (4) the sensing and removal of immune complexes and apoptotic particles; and (5) immune response to infections, including Epstein–Barr Virus, and symbiont microorganisms. These mechanisms affected by SLE genes involve multiple cell types, including B cells/plasma cells, T cells, dendritic cells, monocytes/macrophages, natural killer cells, neutrophils, and endothelial cells. The genetics of SLE from GWAS data reveal an incredibly complex profusion of interrelated molecular processes and interacting cells participating in SLE pathogenesis, mostly unified in the molecular regulation of inflammatory responses. These genetic associations in lupus and affected molecular pathways not only give us an understanding of the disease pathogenesis but may also help in drug discoveries for SLE treatment.
Spatial differences in recruit density, survival, and size structure prevent population growth of stony coral assemblages in southeast Florida
Authors: Jones Nicholas P. , Gilliam David S.
Published: May 2024

The size structure of stony coral populations can reveal underlying demographic barriers to population growth or recovery. Recent declines in coral cover from acute disturbances are well documented, but few studies have assessed size structure and the demographic processes that determine population growth. Vital rates, such as recruitment and survival, vary spatially and temporally in response to environmental conditions, in turn influencing assemblage composition. The Southeast Florida Coral Reef Ecosystem Conservation Area (Coral ECA) is a high-latitude reef system offshore of a heavily urbanized coastline. Consecutive heat stress events, stony coral tissue loss disease (SCTLD), and Hurricane Irma caused significant declines in stony coral cover and density from 2014 to 2018. The recovery potential of stony coral assemblages is influenced by their composition, the size structure of the remnant populations, and population growth during inter-disturbance periods. To assess the viability of the remaining stony coral assemblages in the Coral ECA, we quantified variation in stony coral recruit density, abundance, size structure, and assemblage composition across depth and latitude at permanent sites over 3 years (2019–2022) when no disturbances occurred. We found spatial decoupling in recruit density, adult colony density, and cover that maintains a preponderance of small colonies and skewed size structure. At sites close to shore where recruit density was higher, there was limited evidence of survival and growth of recruits, while at sites where large colonies were sampled or cover was relatively high, there was limited recruitment. The majority (>75%) of recruits sampled were Siderastrea siderea, but size frequency distributions were positively skewed and the coefficient of variation was high, suggesting high recruit/juvenile colony mortality and little growth into larger size classes. Porites astreoides size structure was generally lognormal and mesokurtic, particularly closer to shore, suggesting a transition between size classes. Skewness decreased moving offshore in Montastraea cavernosa and S. siderea, suggesting a transition between size classes. Recruit and adult diversity also increased moving offshore, but recruits of most species were uncommon throughout the study area. We suggest that low recruitment and high mortality, particularly in small colonies and inshore, even during inter-disturbance periods, limit the population growth of stony coral assemblages in southeast Florida.
Comparison of infrared thermography of the blowhole mucosa with rectal temperatures in killer whales (Orcinus orca)
Authors: Russell Jennifer P. , Germain Micah St. , Osborn Steve D. , Schmitt Todd L. , Herrick Kelsey E. S. , Robeck Todd
Published: May 2024

Killer whales are an important sentinel species and developing non-invasive methods of health assessments might provide insight for understanding how wildlife health is influenced by ecosystem change. Rectal temperature (RT) is a proxy for core body temperature in managed-care cetaceans, however, this measurement is impractical for free-ranging cetaceans and infrared imaging has been suggested as an alternative. The aim of the current study was to prospectively compare infrared thermography of the blowhole to rectal temperatures in killer whales, as well as establish a healthy range for rectal temperature using retrospective data. Infrared video was recorded from the blowhole of thirteen healthy killer whales in managed care, immediately followed by rectal temperature measurement. Repeated measures Bland-Altman analysis revealed blowhole temperature (BHT) had a bias of -1.28°C from RT. Considerable proportional bias was observed with agreement between measurements improving as mean temperature increased. RT positively associated with air temperature, and inversely associated with body mass. BHT was not significantly affected by sex or body mass but was significantly affected by water temperature and air temperature. Retrospective analysis from eighteen killer whales (n = 3591 observations) was performed to generate expected RT ranges, partitioning out for sex and body mass. Given the proportional bias observed with Bland Altman analysis, BHT cannot currently be recommended as a measurement for absolute core body temperature, however infrared thermography of the blowhole remains a promising tool for health assessment of free-ranging killer whale populations, as it may serve as a non-contact screening tool to detect pyrexic animals within a group.
Physical mechanisms, dynamics and interconnections of multiple estuarine turbidity maximum in the Pearl River estuary
Authors: Ma Mengyao , Porz Lucas , Schrum Corinna , Zhang Wenyan
Published: May 2024

The formation and dynamics of individual estuarine turbidity maximum (ETM) in the Pearl River estuary (PRE) have been investigated but the temporal variability of the ETMs and interconnections among them remain poorly understood. To address these open questions, the distribution and transport of suspended particulate matter (SPM) in the PRE for the period of 2017–2020 are investigated by numerical modeling. The simulated sediment transport flux is decomposed into several major components associated with specific physical processes. Then, the relative contribution of each component to the formation of the ETMs is evaluated. Results suggest the coexistence of three prominent ETMs in the Lingding Bay of the PRE. They are formed by different physical mechanisms and characterized by remarkable seasonality in the spatial extension. In the two ETMs located at the west shoal and middle shoal, advection dominates the sediment transport flux, whilst tidal pumping plays a crucial role in maintaining the ETMs. A sharp bathymetric gradient leads to an entrapment of sediment flux within the bottom layer in the west channel ETM, a phenomenon referred to as topographical trapping. The interconnection analysis shows that the sediment transport between the ETMs varies with seasons, which is attributed to the variation of stratification driven by the monsoon-mediated river runoff. Our results provide new insights into the physical dynamics and interconnections of the ETMs in the PRE, which can serve as scientific base for estuarine sediment management and engineering.
The role of Zip1 and Zip3 in cadmium accumulation in Fujian oyster (Crassostrea angulata)
Authors: Li Huanhuan , Liang Zhixiu , Wu Longping , Ke Yizhou , Que Huayong , Shi Bo
Published: May 2024

Oysters are notably susceptible to accumulating substantial amounts of cadmium (Cd), leading to food safety concerns, yet the molecular mechanisms are not fully understood. Previous study identified a significant correlation between polymorphisms in the Zip1 and Zip3 of Fujian oyster (Crassostrea angulata) and the levels of Cd accumulation. Zip1 and Zip3, belonging to the Zip family, are primarily responsible for the cellular transport of zinc and other metal ions. To delve deeper into their roles in Cd transport within oysters, this research cloned and analyzed the sequences of Fujian oyster Zip1 and Zip3. The open reading frames for Zip1 and Zip3 were 960 and 978 bp, respectively, encoding proteins of 319 and 325 amino acids. Following Cd exposure, the expression levels of these genes in the mantle, gills, and other tissues initially increased significantly before decreasing, demonstrating a dose-dependent response. The lowest expression levels were observed in the adductor muscle, with Zip1 reaching its highest expression in the mantle and Zip3 in the visceral mass. In vitro RNAi experiments revealed that silencing Zip1 led to a 1.26-fold decrease in new 113Cd accumulation in the mantle, whereas silencing Zip3 resulted in a 1.29-fold increase. Immunohistochemistry showed weak expression of Zip1 and Zip3 proteins in the connective tissue of the mantle. In summary, Zip1 and Zip3 in Fujian oyster can transport Cd as a substrate, and played different roles in the absorption and efflux of Cd.
Heterostructured Ti3C2Tx/carbon nanohorn-based gas sensor for NH3 detection at room temperature
Authors: Han Yutong , Ding Yuan , Yao Yu , Li Zhanhong , Zhu Zhigang
Published: May 2024

In this study, a two-dimensional Ti3C2Tx MXene compounded with carbon nanohorn (CNH) by an electrostatic self-assembly method was proposed and then fabricated as room temperature ammonia (NH3) gas sensors. The successful preparation of the Ti3C2Tx/CNH nanocomposite has been characterized in detail. The NH3 sensing performance based on Ti3C2Tx/CNH also has been tested at room temperature. The optimal Ti3C2Tx/CNH sensor has a response value of 21.6% to 100 ppm NH3 at room temperature, which is 10 times higher than that of the pure Ti3C2Tx sensor. Furthermore, this sensor is endowed with excellent selectivity, reliable long-term stability, and reproducibility. The enhanced sensing performance is associated with the interconnected structure and the synergistic effect of Ti3C2Tx and CNH. This work provides an effective way to prepare MXene-based sensitive materials for NH3 sensors, which shows excellent NH3 detection potential at room temperature.
Enhancing the DNA yield intended for microbial sequencing from a low-biomass chlorinated drinking water
Authors: Putri Ratna E. , Vrouwenvelder Johannes S. , Farhat Nadia
Published: May 2024

DNA extraction yield from drinking water distribution systems and premise plumbing is a key metric for any downstream analysis such as 16S amplicon or metagenomics sequencing. This research aimed to optimize DNA yield from low-biomass (chlorinated) reverse osmosis-produced tap water by evaluating the impact of different factors during the DNA extraction procedure. The factors examined are (1) the impact of membrane materials and their pore sizes; (2) the impact of different cell densities; and (3) an alternative method for enhancing DNA yield via incubation (no nutrient spiking). DNA from a one-liter sampling volume of RO tap water with varying bacterial cell densities was extracted with five different filter membranes (mixed ester cellulose 0.2 μm, polycarbonate 0.2 μm, polyethersulfone 0.2 and 0.1 μm, polyvinylidene fluoride 0.1 μm) for biomass filtration. Our results show that (i) smaller membrane pore size solely did not increase the DNA yield of low-biomass RO tap water; (ii) the DNA yield was proportional to the cell density and substantially dependent on the filter membrane properties (i.e., the membrane materials and their pore sizes); (iii) by using our optimized DNA extraction protocol, we found that polycarbonate filter membrane with 0.2 μm pore size markedly outperformed in terms of quantity (DNA yield) and quality (background level of 16S gene copy number) of recovered microbial DNA; and finally, (iv) for one-liter sampling volume, incubation strategy enhanced the DNA yield and enabled accurate identification of the core members (i.e., Porphyrobacter and Blastomonas as the most abundant indicator taxa) of the bacterial community in low-biomass RO tap water. Importantly, incorporating multiple controls is crucial to distinguish between contaminant/artefactual and true taxa in amplicon sequencing studies of low-biomass RO tap water.
Characterization of the preweaned Holstein calf fecal microbiota prior to, during, and following resolution of uncomplicated gastrointestinal disease
Authors: Claus-Walker Rachel A. , Slanzon Giovana S. , Elder Lily A. , Hinnant Holly R. , Mandella Chris M. , Parrish Lindsay M. , Trombetta Sophie C. , McConnel Craig S.
Published: May 2024

Little is known about shifts in the fecal microbiome of dairy calves preceding and following the incidence of gastrointestinal disease. The objective of this cohort study was to describe the fecal microbiome of preweaned dairy calves before, during, and after gastrointestinal disease. A total of 111 Holstein dairy calves were enrolled on 2 dairies (D1 and D2) and followed until 5 weeks old. Health assessments were performed weekly and fecal samples were collected every other week. Of the 111 calves, 12 calves from D1 and 12 calves from D2 were retrospectively defined as healthy, and 7 calves from D1 and 11 calves from D2 were defined as diarrheic. Samples from these calves were sequenced targeting the 16S rRNA gene and compared based on health status within age groups and farms: healthy (0–1 week old) vs. pre-diarrheic (0–1 week old), healthy (2–3 weeks old) vs. diarrheic (2–3 weeks old), and healthy (4–5 weeks old) vs. post-diarrheic (4–5 weeks old) calves. Healthy and diarrheic samples clustered together based on age rather than health status on both farms. Based on linear discriminant analysis, a few species were identified to be differently enriched when comparing health status within age groups and farm. Among them, Bifidobacterium sp. was differently enriched in pre-diarrheic calves at D1 (0–1 week old) whereas healthy calves of the same age group and farm showed a higher abundance of Escherichia coli. Bifidobacterium sp. was identified as a biomarker of fecal samples from healthy calves (2–3 weeks old) on D1 when compared with diarrheic calves of the same age group and farm. Feces from diarrheic calves on D2 (2–3 weeks old) were characterized by taxa from Peptostreptococcus and Anaerovibrio genera whereas fecal samples of age-matched healthy calves were characterized by Collinsella aerofaciens and Bifidobacterium longum. After resolution of uncomplicated diarrhea (4–5 weeks old), Collinsella aerofaciens was more abundant in D2 calves whereas Bacteriodes uniformis was more abundant in D1 calves. Taken together, these findings suggest that the age of the preweaned calf is the major driver of changes to fecal microbiome composition and diversity even in the face of uncomplicated gastrointestinal disease.
Causal links between gut microbiomes, cytokines and risk of different subtypes of epilepsy: a Mendelian randomization study
Authors: Qiu Youjia , Song Bingyi , Xie Minjia , Tao Yuchen , Yin Ziqian , Wang Menghan , Ma Chao , Chen Zhouqing , Wang Zhong
Published: May 2024

Objective

Recent research suggests a potential link between the gut microbiome (GM) and epilepsy. We undertook a Mendelian randomization (MR) study to determine the possible causal influence of GM on epilepsy and its various subtypes, and explore whether cytokines act as mediators.

Methods

We utilized Genome-Wide Association Study (GWAS) summary statistics to examine the causal relationships between GM, cytokines, and four epilepsy subtypes. Furthermore, we assessed whether cytokines mediate the relationship between GM and epilepsy. Significant GMs were further investigated using transcriptomic MR analysis with genes mapped from the FUMA GWAS. Sensitivity analyses and reverse MR were conducted for validation, and false discovery rate (FDR) correction was applied for multiple comparisons.

Results

We pinpointed causal relationships between 30 GMs and various epilepsy subtypes. Notably, the Family Veillonellaceae (OR:1.03, 95%CI:1.02–1.05, p = 0.0003) consistently showed a strong positive association with child absence epilepsy, and this causal association endured even after FDR correction (p-FDR < 0.05). Seven cytokines were significantly associated with epilepsy and its subtypes. A mediating role for cytokines has not been demonstrated. Sensitivity tests validated the primary MR analysis outcomes. Additionally, no reverse causality was detected between significant GMs and epilepsy. Of the mapped genes of notable GMs, genes like BLK, FDFT1, DOK2, FAM167A, ZSCAN9, RNGTT, RBM47, DNAJC21, SUMF1, TCF20, GLO1, TMTC1, VAV2, and RNF14 exhibited a profound correlation with the risk factors of epilepsy subtypes.

Conclusion

Our research validates the causal role of GMs and cytokines in various epilepsy subtypes, and there has been no evidence that cytokines play a mediating role between GM and epilepsy. This could provide fresh perspectives for the prevention and treatment of epilepsy.
Marine microalgae Schizochytrium demonstrates strong production of essential fatty acids in various cultivation conditions, advancing dietary self-sufficiency
Authors: Literáková Petra , Zavřel Tomáš , Búzová Diana , Kaštánek Petr , Červený Jan
Published: May 2024

Introduction

Polyunsaturated fatty acids (PUFAs) are essential nutrients that humans obtain from their diet, primarily through fish oil consumption. However, fish oil production is no longer sustainable. An alternative approach is to produce PUFAs through marine microalgae. Despite the potential of algae strains to accumulate high concentrations of PUFAs, including essential fatty acids (EFAs), many aspects of PUFA production by microalgae remain unexplored and their current production outputs are frequently suboptimal.

Methods

In this study, we optimized biomass and selected ω-3 PUFAs production in two strains of algae, Schizochytrium marinum AN-4 and Schizochytrium limacinum CO3H. We examined a broad range of cultivation conditions, including pH, temperature, stirring intensity, nutrient concentrations, and their combinations.

Results

We found that both strains grew well at low pH levels (4.5), which could reduce bacterial contamination and facilitate the use of industrial waste products as substrate supplements. Intensive stirring was necessary for rapid biomass accumulation but caused cell disruption during lipid accumulation. Docosahexaenoic acid (DHA) yield was independent of cultivation temperature within a range of 28–34°C. We also achieved high cell densities (up to 9 g/L) and stable DHA production (average around 0.1 g/L/d) under diverse conditions and nutrient concentrations, with minimal nutrients required for stable production including standard sea salt, glucose or glycerol, and yeast extract.

Discussion

Our findings demonstrate the potential of Schizochytrium strains to boost industrial-scale PUFA production and make it more economically viable. Additionally, these results may pave the way for smaller-scale production of essential fatty acids in a domestic setting. The development of a new minimal culturing medium with reduced ionic strength and antibacterial pH could further enhance the feasibility of this approach.
In vitro protein digestibility to replace in vivo digestibility for purposes of nutrient content claim substantiation in North America's context
Authors: Krul Elaine S. , Sá Amanda G. A. , Goldberg Erin M. , House James D.
Published: May 2024

The reliance by North American regulatory authorities on in vivo rodent bioassays—Protein Correct-Amino Acid Score (PDCAAS) in the U.S. and Protein Efficiency Ratio (PER) in Canada—to measure the protein quality for protein content claim substantiation represents a major barrier for innovation in the development and marketing of protein foods. Although FAO in 2013 proposed a new method (Digestible Indispensable Amino Acid Score, DIAAS), it is still not used for protein content claim substantiation in any jurisdiction. Together with public health efforts to increase the consumption of plant-based foods, removing hurdles is key to incentivizing the food industry to measure protein digestibility in making food formulation decisions as well as in claiming protein content on product labels. To address this issue, a pathway has been proposed to position alternative methods for in vitro protein digestibility in collaborative studies to generate the data necessary for method approval by a certifying body. The latter is critical to the potential recognition of these methods by both Health Canada and the US FDA. The purpose of this article is to briefly summarize the state-of-the-art in the field, to inform the research community of next steps, and to describe the path engaging collaborative laboratories in a proficiency test as the first step in moving forward toward acceptance of in vitro digestibility methods. Throughout, a consultative and iterative process will be utilized to ensure the program goals are met. Success will be achieved when the proposed path results in the acceptance of an in vitro methods for protein digestibility used for PDCAAS determinations, which will enable increased protein analyses and improved nutrition labeling of protein foods.
High serum klotho levels are inversely associated with the risk of low muscle mass in middle-aged adults: results from a cross-sectional study
Authors: Xie Yilian , Huang Kai , Li Hui , Kong Weiliang , Ye Jiayuan
Published: May 2024

Objective

Muscle mass gradually declines with advancing age, and as an anti-aging protein, klotho may be associated with muscle mass. This study aims to explore the relationship between klotho levels and muscle mass in the middle-aged population.

Methods

Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018, we conducted a cross-sectional analysis on a cohort of individuals aged 40–59. Weighted multivariable analysis was employed to assess the correlation between klotho and low muscle mass, with stratified and Restricted Cubic Spline (RCS) analyses.

Results

The cross-sectional investigation revealed a significant negative correlation between klotho levels and the risk of low muscle mass (Model 3: OR = 0.807, 95% CI: 0.712–0.915). A notable interaction between klotho and sex was observed, with a significant interaction effect (P for interaction = 0.01). The risk association was notably higher in females. The risk association was notably higher in females. Additionally, RCS analysis unveiled a significant linear relationship between klotho and low muscle mass (P for nonlinear = 0.9495, P for overall<0.0001).

Conclusion

Our observational analysis revealed a noteworthy inverse relationship between klotho and low muscle mass, particularly prominent among female participants. This discovery provides crucial insights for the development of more effective intervention strategies and offers a new direction for enhancing muscle quality in the middle-aged population.
Assessing the role of advanced artificial intelligence as a tool in multidisciplinary tumor board decision-making for primary head and neck cancer cases
Authors: Schmidl Benedikt , Hütten Tobias , Pigorsch Steffi , Stögbauer Fabian , Hoch Cosima C. , Hussain Timon , Wollenberg Barbara , Wirth Markus
Published: May 2024

Background

Head and neck squamous cell carcinoma (HNSCC) is a complex malignancy that requires a multidisciplinary approach in clinical practice, especially in tumor board discussions. In recent years, artificial intelligence has emerged as a tool to assist healthcare professionals in making informed decisions. This study investigates the application of ChatGPT 3.5 and ChatGPT 4.0, natural language processing models, in tumor board decision-making.

Methods

We conducted a pilot study in October 2023 on 20 consecutive head and neck cancer patients discussed in our multidisciplinary tumor board (MDT). Patients with a primary diagnosis of head and neck cancer were included. The MDT and ChatGPT 3.5 and ChatGPT 4.0 recommendations for each patient were compared by two independent reviewers and the number of therapy options, the clinical recommendation, the explanation and the summarization were graded.

Results

In this study, ChatGPT 3.5 provided mostly general answers for surgery, chemotherapy, and radiation therapy. For clinical recommendation, explanation and summarization ChatGPT 3.5 and 4.0 scored well, but demonstrated to be mostly an assisting tool, suggesting significantly more therapy options than our MDT, while some of the recommended treatment modalities like primary immunotherapy are not part of the current treatment guidelines.

Conclusions

This research demonstrates that advanced AI models at the moment can merely assist in the MDT setting, since the current versions list common therapy options, but sometimes recommend incorrect treatment options and in the case of ChatGPT 3.5 lack information on the source material.
Characterization of prostatic cancer lesion and gleason grade using a continuous-time random-walk diffusion model at high b-values
Authors: Sheng Yurui , Chang Huan , Xue Ke , Chen Jinming , Jiao Tianyu , Cui Dongqing , Wang Hao , Zhang Guanghui , Yang Yuxin , Zeng Qingshi
Published: May 2024

Background

Distinguishing between prostatic cancer (PCa) and chronic prostatitis (CP) is sometimes challenging, and Gleason grading is strongly associated with prognosis in PCa. The continuous-time random-walk diffusion (CTRW) model has shown potential in distinguishing between PCa and CP as well as predicting Gleason grading.

Purpose

This study aimed to quantify the CTRW parameters (α, β & Dm) and apparent diffusion coefficient (ADC) of PCa and CP tissues; and then assess the diagnostic value of CTRW and ADC parameters in differentiating CP from PCa and low-grade PCa from high-grade PCa lesions.

Study type

Retrospective (retrospective analysis using prospective designed data).

Population

Thirty-one PCa patients undergoing prostatectomy (mean age 74 years, range 64–91 years), and thirty CP patients undergoing prostate needle biopsies (mean age 68 years, range 46–79 years).

Field strength/Sequence

MRI scans on a 3.0T scanner (uMR790, United Imaging Healthcare, Shanghai, China). DWI were acquired with 12 b-values (0, 50, 100, 150, 200, 500, 800, 1200, 1500, 2000, 2500, 3000 s/mm2).

Assessment

CTRW parameters and ADC were quantified in PCa and CP lesions.

Statistical tests

The Mann-Whitney U test was used to evaluate the differences in CTRW parameters and ADC between PCa and CP, high-grade PCa, and low-grade PCa. Spearman’s correlation of the pathologic grading group (GG) with CTRW parameters and ADC was evaluated. The usefulness of CTRW parameters, ADC, and their combinations (Dm, α and β; Dm, α, β, and ADC) to differentiate PCa from CP and high-grade PCa from low-grade PCa was determined by logistic regression and receiver operating characteristic curve (ROC) analysis. Delong test was used to compare the differences among AUCs.

Results

Significant differences were found for the CTRW parameters (α, Dm) between CP and PCa (all P<0.001), high-grade PCa, and low-grade PCa (α:P=0.024, Dm:P=0.021). GG is correlated with certain CTRW parameters and ADC(α:P<0.001,r=-0.795; Dm:P<0.001,r=-0.762;ADC:P<0.001,r=-0.790). Moreover, CTRW parameters (α, β, Dm) combined with ADC showed the best diagnostic efficacy for distinguishing between PCa and CP as well as predicting Gleason grading. The differences among AUCs of ADC, CTRW parameters and their combinations were not statistically significant (P=0.051–0.526).

Conclusion

CTRW parameters α and Dm, as well as their combination were beneficial to distinguish between CA and PCa, low-grade PCa and high-grade PCa lesions, and CTRW parameters and ADC had comparable diagnostic performance.
Development and validation of nomogram to predict overall survival and disease-free survival after surgical resection in elderly patients with hepatocellular carcinoma
Authors: Tian Yuan , Wang Yaoqun , Wen Ningyuan , Lin Yixin , Liu Geng , Li Bei
Published: May 2024

Background

Hepatocellular carcinoma (HCC) is one of the common causes of tumor death in elderly patients. However, there is a lack of individualized prognostic predictors for elderly patients with HCC after surgery.

Method

We retrospectively analyzed HCC patients over 65 years old who underwent hepatectomy from 2015 to 2018, and randomly divided them into training cohort and validation cohort in a ratio of 3:1. Univariate Cox regression was used to screen the risk factors related to prognosis. Prognostic variables were further selected by least absolute shrinkage and selection operator regression model (LASSO) and multivariate Cox regression to identify the predictors of overall survival (OS) and disease-free survival (DFS). These indicators were then used to construct a predictive nomogram. The receiver operating characteristic curve (ROC curve), calibration curve, consistency index (C-index) and decision analysis curve (DCA) were used to test the predictive value of these independent prognostic indicators.

Result

A total of 188 elderly HCC patients who underwent hepatectomy were enrolled in this study. The independent prognostic indicators of OS included albumin (ALB), cancer embolus, blood loss, viral hepatitis B, total bilirubin (TB), microvascular invasion, overweight, and major resection. The independent prognostic indicators of DFS included major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion. In the training cohort, the ROC curve showed that the predictive values of these indicators for OS and DFS were 0.827 and 0.739, respectively, while in the validation cohort, they were 0.798 and 0.694. The calibration curve nomogram exhibited good prediction for 1-year, 2-year, and 3-year OS and DFS. Moreover, the nomogram models exhibited superior performance compared to the T-staging suggested by C-index and DCA.

Conclusion

The nomogram established in this study demonstrate commendable predictive efficacy for OS and DFS in elderly patients with HCC after hepatectomy.

Core Tip: The purpose of this retrospective study is to screen the risk factors of survival and recurrence in elderly patients with HCC after hepatectomy. The nomogram included cancer embolus, viral hepatitis B, overweight, major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion as predictors. The calibration curve of this nomogram was good, indicating credible predictive value and clinical feasibility.
Case report: Slipped capital femoral epiphysis: a rare adverse event associated with FGFR tyrosine kinase inhibitor therapy in a child
Authors: Brizini Meziane , Drimes Tina , Bourne Catherine , Streilein Jessica , Drapeau Annie , Wrogemann Jens , Archer Lori Anne , Del Bigio Marc , Vanan Magimairajan Issai
Published: May 2024

We report a case of slipped capital femoral epiphysis (SCFE), an on target skeletal toxicity of a pan-FGFR TKI inhibitor, erdafitinib. A 13-year-old boy was diagnosed to have an optic pathway/hypothalamic glioma with signs of increased intracranial pressure and obstructive hydrocephalus requiring placement of ventriculo-peritoneal (VP) shunt. Sequencing of the tumor showed FGFR1-tyrosine kinase domain internal tandem duplication (FGFR1-KD-ITD). He developed hypothalamic obesity with rapid weight gain and BMI >30. At 12 weeks of treatment with erdafitinib, he developed persistent knee pain. X-ray of the right hip showed SCFE. Erdafitinib was discontinued, and he underwent surgical pinning of the right hip. MRI at discontinuation of erdafitinib showed a 30% decrease in the size of the tumor, which has remained stable at 6 months follow-up. Our experience and literature review suggest that pediatric patients who are treated with pan-FGFR TKIs should be regularly monitored for skeletal side effects.
“It's more than just a conversation about the heart”: exploring barriers, enablers, and opportunities for improving the delivery and uptake of cardiac neurodevelopmental follow-up care
Authors: Abell Bridget , Rodwell David , Eagleson Karen J. , Parsonage William , Auld Ben , Bora Samudragupta , Kasparian Nadine A. , Justo Robert , McPhail Steven M.
Published: May 2024

Introduction

Surveillance, screening, and evaluation for neurodevelopmental delays is a pivotal component of post-surgical care for children with congenital heart disease (CHD). However, challenges exist in implementing such neurodevelopmental follow-up care in international practice. This study aimed to characterise key barriers, enablers, and opportunities for implementing and delivering outpatient cardiac neurodevelopmental follow-up care in Australia.

Methods

an exploratory descriptive qualitative study was conducted with healthcare professionals across Australia who had lived experience of designing, implementing, or delivering neurodevelopmental care for children with CHD. Online semi-structured interviews were conducted using a guide informed by the Consolidated Framework for Implementation Research to explore contextual influences. Interview transcripts were analysed using a rapid qualitative approach including templated summaries and hybrid deductive-inductive matrix analysis.

Results

fifty-two participants were interviewed. Perceived barriers and enablers were organised into six higher-order themes: factors in the broader environmental, economic, and political context; healthcare system factors; organisational-level factors; provider factors; patient and family factors; and care model factors. The largest number of barriers occurred at the healthcare system level (service accessibility, fragmentation, funding, workforce), while service providers demonstrated the most enabling factors (interprofessional relationships, skilled teams, personal characteristics). Strategies to improve practice included building partnerships; generating evidence; increasing funding; adapting for family-centred care; and integrating systems and data.

Discussion

Australia shares many similar barriers and enablers to cardiac neurodevelopmental care with other international contexts. However, due to unique geographical and health-system factors, care models and implementation strategies will require adaption to the local context to improve service provision.