bluuebunny/crossref_metadata_2025 huggingface dataset:
Multinucleated tumor cells in clear cell renal cell carcinoma
Authors: Pacheco Richard R , Binboga Kurt Busem , Kosemehmetoglu Kemal , Rothrock Aimi T , Lightle Andrea , Akgul Mahmut
Published: August 2023

Objectives

Multinucleated tumor cells (MTCs) in clear cell renal cell carcinoma (ccRCC) are not well understood.

Methods

Our study included ccRCC cases in a single institution between 2010 and 2019. We classified MTC as MTC with degenerative atypia (MTCD), MTC with no anaplasia (MTCNA), and MTC with anaplasia (MTCA). Clinicopathologic characteristics and outcomes were compared between MTC groups.

Results

In all, 92 of 256 people (36%) with ccRCC had MTC. People with ccRCC with MTCD and those with ccRCC but no MTC had similar clinicopathologic characteristics and outcomes. Also, MTCNA and MTCA were associated with larger tumor size, advanced pathologic tumor stage, higher World Health Organization/International Society of Urologic Pathologists nuclear grade, and higher metastatic potential (P < .001 for each parameter). Overall, MTCA was associated with an increased rate of recurrence (P = .004), higher metastatic potential (P < .001), and shorter time to metastasis (P = .033), regardless of tumor stage. Univariate Cox regression revealed MTCNA as a significant predictor of metastasis at 5 years (hazard ratio [HR], 4.171; 95% CI, 1.934-8.998); moreover, MTCA was a significant predictor of recurrence (HR, 5.723; 95% CI, 2.495-13.124), metastasis (HR, 12.024; 5.966-24.232), and death (HR, 5.661; 95% CI, 2.688-11.924) at 5 years.

Conclusions

Although MTCD may not be relevant in tumor grading, MTCNA and MTCA are associated with adverse outcomes.
The effect of exogenous dihydroxyacetone and methylglyoxal on growth, anthocyanin accumulation, and the glyoxalase system in Arabidopsis
Authors: Zhao Maoxiang , Nakamura Toshiyuki , Nakamura Yoshimasa , Munemasa Shintaro , Mori Izumi C , Murata Yoshiyuki
Published: August 2023

Dihydroxyacetone (DHA) occurs in wide-ranging organisms, including plants, and can undergo spontaneous conversion to methylglyoxal (MG). While the toxicity of MG to plants is well-known, the toxicity of DHA to plants remains to be elucidated. We investigated the effects of DHA and MG on Arabidopsis. Exogenous DHA at up to 10 mm did not affect the radicle emergence, the expansion of green cotyledons, the seedling growth, or the activity of glyoxalase II, while DHA at 10 mm inhibited the root elongation and increased the activity of glyoxalase I. Exogenous MG at 1.0 mm inhibited these physiological responses and increased both activities. Dihydroxyacetone at 10 mm increased the MG content in the roots. These results indicate that DHA is not so toxic as MG in Arabidopsis seeds and seedlings and suggest that the toxic effect of DHA at high concentrations is attributed to MG accumulation by the conversion to MG.
MLNGCF: circRNA–disease associations prediction with multilayer attention neural graph-based collaborative filtering
Authors: Wu Qunzhuo , Deng Zhaohong , Zhang Wei , Pan Xiaoyong , Choi Kup-Sze , Zuo Yun , Shen Hong-Bin , Yu Dong-Jun
Published: August 2023

Motivation

CircRNAs play a critical regulatory role in physiological processes, and the abnormal expression of circRNAs can mediate the processes of diseases. Therefore, exploring circRNAs–disease associations is gradually becoming an important area of research. Due to the high cost of validating circRNA–disease associations using traditional wet-lab experiments, novel computational methods based on machine learning are gaining more and more attention in this field. However, current computational methods suffer to insufficient consideration of latent features in circRNA–disease interactions.

Results

In this study, a multilayer attention neural graph-based collaborative filtering (MLNGCF) is proposed. MLNGCF first enhances multiple biological information with autoencoder as the initial features of circRNAs and diseases. Then, by constructing a central network of different diseases and circRNAs, a multilayer cooperative attention-based message propagation is performed on the central network to obtain the high-order features of circRNAs and diseases. A neural network-based collaborative filtering is constructed to predict the unknown circRNA–disease associations and update the model parameters. Experiments on the benchmark datasets demonstrate that MLNGCF outperforms state-of-the-art methods, and the prediction results are supported by the literature in the case studies.

Availability and implementation

The source codes and benchmark datasets of MLNGCF are available at https://github.com/ABard0/MLNGCF.
Distinct tau folds initiate templated seeding and alter the post-translational modification profile
Authors: Tarutani Airi , Kametani Fuyuki , Tahira Marina , Saito Yuko , Yoshida Mari , Robinson Andrew C , Mann David M A , Murayama Shigeo , Tomita Taisuke , Hasegawa Masato
Published: August 2023

Pathological tau accumulates in the brain in tauopathies such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration, and forms amyloid-like filaments incorporating various post-translational modifications (PTMs). Cryo-electron microscopic (cryo-EM) studies have demonstrated that tau filaments extracted from tauopathy brains are characteristic of the disease and share a common fold(s) in the same disease group. Furthermore, the tau PTM profile changes during tau pathology formation and disease progression, and disease-specific PTMs are detected in and around the filament core. In addition, templated seeding has been suggested to trigger pathological tau amplification and spreading in vitro and in vivo, although the molecular mechanisms are not fully understood. Recently, we reported that the cryo-EM structures of tau protofilaments in SH-SY5Y cells seeded with patient-derived tau filaments show a core structure(s) resembling that of the original seeds. Here, we investigated PTMs of tau filaments accumulated in the seeded cells by liquid chromatography/tandem mass spectrometry and compared them with the PTMs of patient-derived tau filaments. Examination of insoluble tau extracted from SH-SY5Y cells showed that numerous phosphorylation, deamidation and oxidation sites detected in the fuzzy coat in the original seeds were well reproduced in SH-SY5Y cells. Moreover, templated tau filament formation preceded both truncation of the N-/C-terminals of tau and PTMs in and around the filament core, indicating these PTMs may predominantly be introduced after the degradation of the fuzzy coat.
p53 promotes the expansion of regulatory T cells via DNMT3a- and TET2- mediated Foxp3 expression in sepsis
Authors: Zhang Hui , Wu Tiantian , Ren Chao , Dong Ning , Wu Yao , Yao Yongming
Published: August 2023

Background

Immunosuppression is an important characteristic of sepsis and is closely related to poor outcomes. Regulatory T cells (Tregs) contribute to immune suppression by inhibiting effector T cell (Teff) proliferation and differentiation. We aimed to investigate the role of p53 in Treg expansion after sepsis.

Methods

We constructed a sepsis model in wild-type (WT) and p53f/f/CD4-Cre+ mice by cecal ligation and puncture (CLP) and evaluated the proportions of CD4+CD25+ Foxp3+ Tregs by flow cytometry. The expression levels of forkhead/winged helix transcription factor p3 (Foxp3), DNA methyltransferase enzyme (DMNT)3a and ten–eleven translocation (TET)2 were examined using quantitative real-time PCR and Western blot analysis. Treg-specific demethylation region (TSDR) methylation sites in cells were analyzed by bisulfite-sequencing PCR. Furthermore, the direct binding of p53 to the Dnmt3a and TET2 promoters was illustrated using a luciferase assay. The suppressive ability of Tregs was indicated by enzyme-linked immunosorbent assay analysis of cytokine levels and the proliferation of cocultured Teffs. Finally, mortality rates after CLP were compared among WT and p53f/f/CD4-Cre+ mice.

Results

The proportion of CD4+CD25+ Foxp3+ Tregs was significantly reduced in p53f/f/CD4-Cre+ mice compared to WT mice after CLP. The enhanced expression of Foxp3 in WT mice was downregulated in the p53f/f/CD4-Cre+ group. We found decreased DMNT3a and increased TET2 levels after CLP. However, the dysregulation of DNMT3a and TET2 was significantly reversed in p53f/f/CD4-Cre+ mice. TSDR underwent increased demethylation in p53f/f/CD4-Cre+ mice. Luciferase activity indicated direct binding of p53 to the promoter regions of DNMT3a and TET2 to regulate their transcription. Consequently, Tregs from p53f/f/CD4-Cre+ CLP mice exhibited limited suppressive ability, as indicated by the reduced production of transforming growth factor-β and interleukin 10 (IL-10). In the coculture system, Teffs showed preserved production of IL-2, differentiation into Th1 cells and proliferation in the presence of Tregs isolated from p53f/f/CD4-Cre+ CLP mice. Finally, the mortality rate of the p53f/f/CD4-Cre+ group after CLP was significantly reduced in comparison to that of the WT group.

Conclusion

p53 appears to be critical for Foxp3 expression and consequent Treg expansion by regulating the induction of DNMT3a and TET2, thereby resulting in Foxp3-TSDR demethylation in the context of sepsis.
Development of human hippocampal subfield microstructure and relation to associative inference
Authors: Vinci-Booher Sophia , Schlichting Margaret L , Preston Alison R , Pestilli Franco
Published: August 2023

The hippocampus is a complex brain structure composed of subfields that each have distinct cellular organizations. While the volume of hippocampal subfields displays age-related changes that have been associated with inference and memory functions, the degree to which the cellular organization within each subfield is related to these functions throughout development is not well understood. We employed an explicit model testing approach to characterize the development of tissue microstructure and its relationship to performance on 2 inference tasks, one that required memory (memory-based inference) and one that required only perceptually available information (perception-based inference). We found that each subfield had a unique relationship with age in terms of its cellular organization. While the subiculum (SUB) displayed a linear relationship with age, the dentate gyrus (DG), cornu ammonis field 1 (CA1), and cornu ammonis subfields 2 and 3 (combined; CA2/3) displayed nonlinear trajectories that interacted with sex in CA2/3. We found that the DG was related to memory-based inference performance and that the SUB was related to perception-based inference; neither relationship interacted with age. Results are consistent with the idea that cellular organization within hippocampal subfields might undergo distinct developmental trajectories that support inference and memory performance throughout development.
Box–Behnken Design-Aided Validation and Optimization of a Stability-Indicating Reverse Phase-HPLC Method for the Estimation of Tamoxifen Citrate in Lipidic Nano-Vesicles
Authors: Kumar Gautam , Mullick Prashansha , Nandakumar Krishnadas , Mutalik Srinivas , Chamallamudi Mallikarjuna Rao
Published: August 2023

Stability indicating a reverse-phase HPLC analytical method for the quantification of tamoxifen citrate (TMX) in the bulk and lipidic nano-vesicles (LNVs) was developed. The optimized method was validated according to the ICH Q2 (R1) guidelines by following a three-factor interaction Box–Behnken design using Design-Expert® software. The responses measured at 236 nm were retention time (Rt), peak area, tailing factor (TF) and the number of theoretical plates. TMX was eluted best using the Luna® C18 LC Column along with a mobile phase of methanol (MeOH) and ammonium acetate buffer (AAB pH 4.5) 80:20 v/v mixture at 25 ± 2°C temperature. The currently developed method was linear in 100-5,000 ng/mL range with a detection limit of 4.55 ng/mL and a quantification limit of 13.78 ng/mL. The optimized method was utilized to evaluate the stability of TMX in different stress conditions by performing forced degradation studies. The results from the degradation study stipulated that on exposure to various stressors namely acid, alkali, oxidative, thermal and UV light, the TMX did not show considerable degradation except for UV light exposure. Further, the method was successfully used for the quantification of TMX in LNVs.
Cost-Effectiveness of Universal Asymptomatic Preoperative SARS-CoV-2 Polymerase Chain Reaction Screening: A Cost-Utility Analysis
Authors: Uno Shunsuke , Goto Rei , Honda Kimiko , Uchida Sho , Uwamino Yoshifumi , Namkoong Ho , Yoshifuji Ayumi , Mikita Kei , Takano Yaoko , Matsumoto Morio , Kitagawa Yuko , Hasegawa Naoki
Published: August 2023

Background

An early report has shown the clinical benefit of the asymptomatic preoperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening test, and some clinical guidelines recommended this test. However, the cost-effectiveness of asymptomatic screening was not evaluated. We aimed to investigate the cost-effectiveness of universal preoperative screening of asymptomatic patients for SARS-CoV-2 using polymerase chain reaction (PCR) testing.

Methods

We evaluated the cost-effectiveness of asymptomatic screening using a decision tree model from a payer perspective, assuming that the test-positive rate was 0.07% and the screening cost was 8500 Japanese yen (JPY) (approximately 7601 US dollars [USD]). The input parameter was derived from the available evidence reported in the literature. A willingness-to-pay threshold was set at 5 000 000 JPY/quality-adjusted life-year (QALY).

Results

The incremental cost of 1 death averted was 74 469 236 JPY (approximately 566 048 USD) and 291 123 368 JPY/QALY (approximately 2 212 856 USD/QALY), which was above the 5 000 000 JPY/QALY willingness-to-pay threshold. The incremental cost-effectiveness ratio fell below 5 000 000 JPY/QALY only when the test-positive rate exceeded 0.739%. However, when the probability of developing a postoperative pulmonary complication among SARS-CoV-2–positive patients was below 0.22, asymptomatic screening was never cost-effective, regardless of how high the test-positive rate became.

Conclusions

Asymptomatic preoperative universal SARS-CoV-2 PCR screening is not cost-effective in the base case analysis. The cost-effectiveness mainly depends on the test-positive rate, the frequency of postoperative pulmonary complications, and the screening costs; however, no matter how high the test-positive rate, the cost-effectiveness is poor if the probability of developing postoperative pulmonary complications among patients positive for SARS-CoV-2 is sufficiently reduced.
Why do we keep ignoring sex in kidney disease?
Authors: Jankowska Magdalena , Soler María José , Stevens Kate I , Torra Roser
Published: August 2023

Throughout the history of nephrology, little attention has been paid to the sex and gender differences in kidney disease. This lack of awareness prevents optimal diagnosis and management of kidney disease. In today's world of precision medicine, it is imperative to appreciate the differential factors regarding gender and kidney disease.

This editorial summarizes the up-to-date literature regarding sex and gender differences in kidney disease and considers areas where knowledge is incomplete and where further research is needed. We address sex-specific effects on chronic kidney disease epidemiology; risks of dialysis underdosing and medication overdosing in women; unexplained loss of female sex advantage in life expectancy during dialysis, and impact of sex on diagnosis and management of genetic kidney disease. We also aim to highlight the impact of gender on kidney health and raise awareness of disparities that may be faced by women, and transgender and gender-diverse persons when a male-model approach is used by healthcare systems. By understanding the link between sex and kidney disease, kidney specialists can improve the care and outcomes of their patients. In addition, research on this topic can inform the development of targeted prevention and intervention strategies that address the specific needs and risk factors of different populations.
TRGdb: a universal resource for the exploration of taxonomically restricted genes in bacteria
Authors: Zielezinski Andrzej , Dobrychlop Wojciech , Karlowski Wojciech M
Published: August 2023

The TRGdb database is a resource dedicated to taxonomically restricted genes (TRGs) in bacteria. It provides a comprehensive collection of genes that are specific to different genera and species, according to the latest release of bacterial taxonomy. The user interface allows for easy browsing and searching as well as sequence similarity exploration. The website also provides information on each TRG protein sequence, including its level of disorder, complexity and tendency to aggregate. TRGdb is a valuable resource for gaining a deeper understanding of the TRG-associated, unique features, and characteristics of bacterial organisms.

Database URL www.combio.pl/trgdb
Disorder, Riot and Governance in Early Tudor London: Evil May Day, 1517
Authors: McSheffrey Shannon
Published: August 2023

On the eve of the May Day festival in 1517, a night of anti-immigrant violence broke out in London. Though pre-modern English historians have frequently invoked Evil May Day, as it came to be called, it has only recently been given concerted scholarly attention. The riot itself was ordinary, one amongst dozens in the first decades of the sixteenth century; it reveals, as a reflection of endemic grievance, a constellation of tensions surrounding labour, immigration, masculine identities, and governance in early Tudor London. More extraordinary, and heretofore not much noticed, was the Crown reaction to the Evil May Day disturbances, on which this article focuses. The insurrectionists were prosecuted for high treason rather than the minor charge of riot; a multi-day pageant of severe justice punctuated by theatrical reprieves followed. At least fifteen were put to death within London’s city walls and there are indications that the final execution toll was much greater, perhaps as high as forty-three. Such a toll following a mild riot could only have been unexpected and shocking, even if in fact ‘only’ fifteen rather than forty or more were executed. This was a message from the Crown both strategically conceived and emotionally driven by the king’s own rage, fury and fear. Though it was the youthful rioters who constituted most of those put to death in the aftermath, the message was meant primarily for the London civic elite, who had dared to question Crown policy and had failed to control the violence in their city.
Birth cohort changes in fertility ideals: evidence from repeated cross-sectional surveys in Finland
Authors: Golovina Kateryna , Nitsche Natalie , Berg Venla , Miettinen Anneli , Rotkirch Anna , Jokela Markus
Published: August 2023

Fertility has declined in developed countries but whether there is a similar pattern in the number of children individuals wish to have (henceforth an ideal number of children) remains unclear. Using repeated cross-sectional survey data from the Finnish Family Barometers, we examine birth cohort changes in the ideal number of children among men and women from five birth cohorts (1970–1974, 1975–1979, 1980–1984, 1985–1989, and 1990–1994). We also investigate whether associations between socioeconomic factors and the ideal number of children differ across birth cohorts, and whether there are any gender differences in these associations. We find that the ideal number of children is lower among more recent than earlier birth cohorts and that this shift is driven by substantially higher child-free ideals among recent cohorts. While the ideal number of children among men and women is associated with socioeconomic factors, birth cohort differences remain significant after controlling for these characteristics. These findings suggest that large birth cohort differences in child-free ideals are not due to the individual socioeconomic circumstances of more recent birth cohorts. Rather, it appears that the childbearing attitudes of Finns have changed and may have contributed to the recent fertility decline.
The association between daily step count and all-cause and cardiovascular mortality: a meta-analysis
Authors: Banach Maciej , Lewek Joanna , Surma Stanisław , Penson Peter E , Sahebkar Amirhossein , Martin Seth S , Bajraktari Gani , Henein Michael Y , Reiner Željko , Bielecka-Dąbrowa Agata , Bytyçi Ibadete
Published: August 2023

Aims

There is good evidence showing that inactivity and walking minimal steps/day increase the risk of cardiovascular (CV) disease and general ill-health. The optimal number of steps and their role in health is, however, still unclear. Therefore, in this meta-analysis, we aimed to evaluate the relationship between step count and all-cause mortality and CV mortality.

Methods and results

We systematically searched relevant electronic databases from inception until 12 June 2022. The main endpoints were all-cause mortality and CV mortality. An inverse-variance weighted random-effects model was used to calculate the number of steps/day and mortality. Seventeen cohort studies with a total of 226 889 participants (generally healthy or patients at CV risk) with a median follow-up 7.1 years were included in the meta-analysis. A 1000-step increment was associated with a 15% decreased risk of all-cause mortality [hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.81–0.91; P < 0.001], while a 500-step increment was associated with a 7% decrease in CV mortality (HR 0.93; 95% CI 0.91–0.95; P < 0.001). Compared with the reference quartile with median steps/day 3867 (2500–6675), the Quartile 1 (Q1, median steps: 5537), Quartile 2 (Q2, median steps 7370), and Quartile 3 (Q3, median steps 11 529) were associated with lower risk for all-cause mortality (48, 55, and 67%, respectively; P < 0.05, for all). Similarly, compared with the lowest quartile of steps/day used as reference [median steps 2337, interquartile range 1596–4000), higher quartiles of steps/day (Q1 = 3982, Q2 = 6661, and Q3 = 10 413) were linearly associated with a reduced risk of CV mortality (16, 49, and 77%; P < 0.05, for all). Using a restricted cubic splines model, we observed a nonlinear dose–response association between step count and all-cause and CV mortality (Pnonlineraly < 0.001, for both) with a progressively lower risk of mortality with an increased step count.

Conclusion

This meta-analysis demonstrates a significant inverse association between daily step count and all-cause mortality and CV mortality with more the better over the cut-off point of 3867 steps/day for all-cause mortality and only 2337 steps for CV mortality.
Stability of clustering of lifestyle risk factors in the Dutch adult population and the association with mental health
Authors: Dorsman Hannah , de Hollander Ellen , Wendel-Vos Wanda , van Rossum Caroline , Kemler Ellen , Hupkens Christianne , Hosper Karen , de Beurs Derek , Hiemstra Marieke
Published: August 2023

Background

Lifestyle factors often co-occur in clusters. This study examines whether clusters of lifestyle risk factors, such as smoking, alcohol use, physical inactivity, poor diet, sexual risk behaviour, cannabis and other drug use, change over time in a representative sample of Dutch adults. Additionally, the association between mental health and self-reported depression of lifestyle clusters was examined.

Methods

Each year cross-sectional data of approximately 7500 individuals of 18 years and older from the annual Dutch Health Survey of 2014–2019 were used. Clusters were determined by a two-step cluster analysis. Furthermore, regression analyses determined the association between clusters of lifestyle risk factors and mental health.

Results

Results show six clusters composed of one, multiple or no lifestyle risk factors. The clusters remained relatively stable over time: in some clusters, the number of people slightly changed between 2014 and 2019. More specifically, clusters that increased in size were the cluster with no lifestyle risk factors and the cluster with multiple lifestyle risk factors. Furthermore, results show that clusters with none to a few lifestyle risk factors were associated with better mental health and a lower prevalence of self-reported depression compared with clusters with multiple lifestyle risk factors.

Conclusions

The clustering of lifestyle risk factors remained stable over time. People with multiple lifestyle risk factors had poorer mental health than those without risk factors. These findings may emphasize the need for intervention strategies targeting this subgroup with multiple lifestyle risk factors.
Adaptation versus plastic responses to temperature, light, and nitrate availability in cultured snow algal strains
Authors: Broadwell Emily L M , Pickford Rachel E , Perkins Rupert G , Sgouridis Fotis , Williamson Christopher J
Published: August 2023

Snow algal blooms are widespread, dominating low temperature, high light, and oligotrophic melting snowpacks. Here, we assessed the photophysiological and cellular stoichiometric responses of snow algal genera Chloromonas spp. and Microglena spp. in their vegetative life stage isolated from the Arctic and Antarctic to gradients in temperature (5 – 15°C), nitrate availability (1 – 10 µmol L−1), and light (50 and 500 µmol photons m−2 s−1). When grown under gradients in temperature, measured snow algal strains displayed Fv/Fm values increased by ∼115% and electron transport rates decreased by ∼50% at 5°C compared to 10 and 15°C, demonstrating how low temperatures can mimic high light impacts to photophysiology. When using carrying capacity as opposed to growth rate as a metric for determining the temperature optima, these snow algal strains can be defined as psychrophilic, with carrying capacities ∼90% higher at 5°C than warmer temperatures. All strains approached Redfield C:N stoichiometry when cultured under nutrient replete conditions regardless of temperature (5.7 ± 0.4 across all strains), whereas significant increases in C:N were apparent when strains were cultured under nitrate concentrations that reflected in situ conditions (17.8 ± 5.9). Intra-specific responses in photophysiology were apparent under high light with Chloromonas spp. more capable of acclimating to higher light intensities. These findings suggest that in situ conditions are not optimal for the studied snow algal strains, but they are able to dynamically adjust both their photochemistry and stoichiometry to acclimate to these conditions.
Activity of root-knot nematodes associated with composition of a nematode-attached microbiome and the surrounding soil microbiota
Authors: Topalović Olivera , Bak Frederik , Santos Susana , Sikder Md Maniruzzaman , Sapkota Rumakanta , Ekelund Flemming , Nicolaisen Mette Haubjerg , Vestergård Mette
Published: August 2023

We investigated if activity of the pre-infective juveniles (J2s) of root-knot nematodes is linked to the recruitment of a specific microbiome on the nematode surface and/or to the composition of the surrounding microbiota. For this, we determined the J2 activity (active vs. non-motile, which referred to dead and immobile J2s) upon a 3-day incubation in soil suspensions and studied the composition of bacteria, protists, and fungi present on the nematode surface and in the suspensions using amplicon sequencing of the 16S/18S rRNA genes, and ITS region. We also amended suspensions with Pseudomonas protegens strain CHA0 to study its effects on J2 activity and microbial composition. The J2 activity was suppressed in soil suspensions, but increased when suspensions were amended with P. protegens CHA0. The active and non-motile J2s differed in the composition of surface-attached bacteria, which was altered by the presence of P. protegens CHA0 in the soil suspensions. The bacterial genera Algoriphagus, Pedobacter, and Bdellovibrio were enriched on active J2s and may have protected the J2s against antagonists. The incubation time appeared short for attachment of fungi and protists. Altogether, our study is a step forward in disentangling the complex nematode-microbe interactions in soil for more successful nematode control.
Magnitude and Mechanism of Phrenic Long-term Facilitation Shift Between Daily Rest Versus Active Phase
Authors: Marciante Alexandria B , Seven Yasin B , Kelly Mia N , Perim Raphael R , Mitchell Gordon S
Published: August 2023

Plasticity is a fundamental property of the neural system controlling breathing. One key example of respiratory motor plasticity is phrenic long-term facilitation (pLTF), a persistent increase in phrenic nerve activity elicited by acute intermittent hypoxia (AIH). pLTF can arise from distinct cell signaling cascades initiated by serotonin versus adenosine receptor activation, respectively, and interact via powerful cross-talk inhibition. Here, we demonstrate that the daily rest/active phase and the duration of hypoxic episodes within an AIH protocol have profound impact on the magnitude and mechanism of pLTF due to shifts in serotonin/adenosine balance. Using the historical “standard” AIH protocol (3, 5-min moderate hypoxic episodes), we demonstrate that pLTF magnitude is unaffected by exposure in the midactive versus midrest phase, yet the mechanism driving pLTF shifts from serotonin-dominant (midrest) to adenosine-dominant (midactive). This mechanistic “flip” results from combined influences of hypoxia-evoked adenosine release and daily fluctuations in basal spinal adenosine. Since AIH evokes less adenosine with shorter (15, 1-min) hypoxic episodes, midrest pLTF is amplified due to diminished adenosine constraint on serotonin-driven plasticity; in contrast, elevated background adenosine during the midactive phase suppresses serotonin-dominant pLTF. These findings demonstrate the importance of the serotonin/adenosine balance in regulating the amplitude and mechanism of AIH-induced pLTF. Since AIH is emerging as a promising therapeutic modality to restore respiratory and nonrespiratory movements in people with spinal cord injury or ALS, knowledge of how time-of-day and hypoxic episode duration impact the serotonin/adenosine balance and the magnitude and mechanism of pLTF has profound biological, experimental, and translational implications.
The Effect of the Human Brainstem Myelination on Gait Speed in Normative Aging
Authors: Akhonda Mohammad A B S , Faulkner Mary E , Gong Zhaoyuan , Laporte John P , Church Sarah , D’Agostino Jarod , Bergeron Jan , Bergeron Christopher M , Ferrucci Luigi , Bouhrara Mustapha
Published: August 2023

The brainstem functions as a relay and integrative brain center and plays an essential role in motor function. Whether brainstem tissue deterioration, including demyelination, affects motor function has not been studied. Understanding the potential relationship between brainstem demyelination and motor function may be useful for the early diagnosis of neurodegenerative diseases and to understand age-related gait impairments that have no apparent cause. In this work, we investigated the associations between rapid or usual gait speeds, as integrative measures of motor function, and cerebral myelin content. In 118 individuals (age 22–94 years) free of neurodegenerative diseases or cognitive impairment, myelin content was assessed as the myelin water fraction, a direct magnetic resonance imaging measure of myelin content, and longitudinal and transverse relaxation rates (R1 and R2), which are sensitive magnetic resonance imaging measures of myelin content. Our results indicate that participants with lower usual or rapid gait speed exhibited lower values of myelin water fraction and R1 in the main brainstem regions, which were more evident and statistically significant in the midbrain. In contrast, we found no significant associations between gait speeds and R2, an expected result because various physiological factors confound R2. These original findings provide evidence that the level of brainstem myelination may affect gait performance among cognitively unimpaired adults who are free from any clinically detectable neurodegenerative diseases. Further studies are needed to understand the longitudinal changes in brainstem myelination with aging and neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease.
Immigration, Racialization, and Asian American Older Adults’ Cognitive Difficulties
Authors: Nguyen Duy , Liu Rui , Lee Yookyong
Published: August 2023

Objectives

The sociohistorical experiences of Asian American older adults (AAOA) vary, but limited research has examined how immigration status operates as social determinants. This study builds on an existing framework to examine the relationship among social determinants and the differential effects of immigration status on cognitive difficulties among AAOA.

Methods

Using 5-year estimate data from the 2019 American Community Survey, the study sample consisted of AAOA aged 65 years and older identifying as Chinese, Filipino, Indian, Japanese, Korean, or Vietnamese (N = 100,584). AAOA were categorized as noncitizens, naturalized, or U.S. born for their immigration status. Participants who indicated having difficulty concentrating, remembering, or making decisions were categorized as having cognitive difficulties.

Results

Chinese were the most prevalent ethnic group (30%). Over 70% were naturalized citizens. About 8% endorsed having cognitive difficulties. According to bivariate analyses, there were considerable differences in AAOA’s characteristics (e.g., age, gender, marital status, medical insurance, employment status) by their immigration status. The results from the logistic regressions showed that immigration status was independently associated with poor cognitive difficulties. By AAOA’s immigration status, unique protective and risk factors were presented for cognitive difficulties.

Discussion

The differential pattern of cognitive difficulties among AAOA reveals a fuller picture of variations within AAOA by immigration status. The results imply that more research is needed to develop culturally sensitive practices that account for the racialized differences by AAOA’s immigration status. Further research into the interplay between structural determinants is necessary to formulate practice and policy interventions to address better successful aging for AAOA.
Polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) isozyme surface charge governs charge substrate preferences to modulate mucin type O-glycosylation
Authors: Ballard Collin J , Paserba Miya R , Paul Daniel Earnest James , Hurtado-Guerrero Ramón , Gerken Thomas A
Published: August 2023

A large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) initiate mucin type O-glycosylation transferring α-GalNAc from a UDP-GalNAc donor to the hydroxyl groups of Ser and Thr residues of peptides and proteins, thereby defining sites of O-glycosylation. Mutations and differential expression of several GalNAc-Ts are associated with many disease states including cancers. The mechanisms by which these isozymes choose their targets and their roles in disease are not fully understood. We previously showed that the GalNAc-Ts possess common and unique specificities for acceptor type, peptide sequence and prior neighboring, and/or remote substrate GalNAc glycosylation. In the present study, the role of flanking charged residues was investigated using a library of charged peptide substrates containing the central -YAVTPGP- acceptor sequence. Eleven human and one bird GalNAc-T were initially characterized revealing a range of preferences for net positive, net negative, or unique combinations of flanking N- and/or C-terminal charge, correlating to each isozyme’s different electrostatic surface potential. It was further found that isoforms with high sequence identity (>70%) within a subfamily can possess vastly different charge specificities. Enzyme kinetics, activities obtained at elevated ionic strength, and molecular dynamics simulations confirm that the GalNAc-Ts differently recognize substrate charge outside the common +/−3 residue binding site. These electrostatic interactions impact how charged peptide substrates bind/orient on the transferase surface, thus modulating their activities. In summary, we show the GalNAc-Ts utilize more extended surfaces than initially thought for binding substrates based on electrostatic, and likely other hydrophobic/hydrophilic interactions, furthering our understanding of how these transferases select their target.
Methodological reflections: developing the WHO database of violence against women policies
Authors: Watson Katherine , Burke Eva , Gold Judy , Eva Gillian , Amin Avni
Published: August 2023

This paper presents methodological reflections from the development of the World Health Organization (WHO) Violence against Women (VAW) Policies Database (hereinafter referred to as ‘the Database’) to inform future efforts to create similar public health policy databases for government accountability. Using the WHO Global Plan of Action on Violence accountability measures as a starting point, the Database was developed over a 2-year period in consultation with a reference group. A subset of indicators was piloted before finalization of a full list and the structure of the Database. Available VAW policies from 194 WHO Member States were reviewed by a team of consultants, who conducted content analysis and data entry. A ‘Manual and User Guide’ was developed to record decisions related to the processes for developing the Database. This guide was used to draw out key reflections in relation to policy indicators, inclusion criteria for policy documents, languages and analysis, quality assurance and sustainability. The process of developing the Database evolved iteratively in response to many factors, including the content of policies and the specificities of policy-making in each jurisdiction. Pragmatic decisions about the number of indicators and the types of policies to review were informed by pilot tests across a range of geographies. Standardization of analysis and data entry was ensured through the provision of in-depth guidance for researchers, and regular and open communication within the team was key to quality assurance. Online translation services enabled a review of policy documents in most languages. Documentation of the methodology ensured that others could replicate processes with fidelity in the future. Despite complexities, it is possible to develop a sound methodology for analysing the content of policy documents in a manner that yields findings that are useful in holding governments accountable for the commitments to address VAW and other public health issues in policy.
Characteristics of sows’ milk and piglet nutrient utilization during a 28-d lactation period
Authors: Chisoro Prince , Krogh Uffe , Theil Peter Kappel , Eskildsen Maria
Published: August 2023

The present study aimed to characterize the performance of suckling piglets from high prolific sows and investigate the impact of milk composition on piglet growth during a 4-wk lactation period. Piglet performance included weight gain (WG), milk intake, nutrients and energy in milk, and piglet energy metabolism in weeks 1 to 4 of lactation. Data from six previous experiments were used with a total of 2,047 piglets and 604 milk samples collected from 151 sows. Piglet body weight linearly increased (P < 0.001) as lactation progressed, with the piglet WG being low in week 1 (132 g/d) and relatively constant from weeks 2 to 4 (248 g/d; P < 0.001). The metabolizable energy (ME) intake of the piglets increased (P < 0.001) from weeks 1 to 3; however, with lower values in week 4 than for week 3. The heat energy production and energy required for maintenance (MEm) linearly increased (P < 0.001) from weeks 1 to 4. In addition, the retained energy and ME to MEm ratio only increased from weeks 1 to 2 (P < 0.001) and then declined through week 4. Pearson correlation coefficients were used to examine the relations between the milk nutrient composition and the WG in weeks 1 to 4. The results showed that WG was negatively correlated with the milk protein concentration at all stages of lactation (P < 0.001). In contrast, the WG was positively correlated with milk fat and lactose concentrations in weeks 2 and 4, respectively (P < 0.001). In conclusion, the stage of lactation influenced WG, milk intake, nutrients in milk, energy in milk, and the energy metabolism of the suckling piglets. Moreover, maximizing milk protein concentration does not optimize piglet growth.
A wavefield reconstruction method using sparse representation and dictionary learning for RTM
Authors: Pei Chunyang , Shi Linge , Li Shiheng , Zhou Xiaohua , Long Yun , Chen Zubin
Published: August 2023

Reverse time migration (RTM) is a well-established imaging technique that uses the two-way wave equation to achieve high-resolution imaging of complex subsurface media. However, when using RTM for reverse time extrapolation, a source wavefield needs to be stored for cross-correlation with the backward wavefield. This requirement results in a significant storage burden on computer memory. This paper introduces a wavefield reconstruction method that combines sparse representation to compress a substantial amount of crucial information in the source wavefield. The method uses the K-SVD algorithm to train an adaptive dictionary, learned from a training dataset consisting of wavefield image patches. For each timestep, the source wavefield is divided into image patches, which are then transformed into a series of sparse coefficients using the trained dictionary via the batch-orthogonal matching pursuit algorithm, known for its accelerated sparse coding process. This novel method essentially attempts to transform the wavefield domain into the sparse domain to reduce the storage burden. We used several evaluation metrics to explore the impact of parameters on performance. We conducted numerical experiments using acoustic RTM and compared two RTM methods using checkpointing techniques with two strategies from our proposed method. Additionally, we extended the application of our method to elastic RTM. The conducted tests demonstrate that the method proposed in this paper can efficiently compress wavefield data, while considering both computational efficiency and reconstruction accuracy.
The impact of osteosarcopenia in patients with unresectable or recurrent biliary tract cancer receiving palliative chemotherapy
Authors: Takeda Tsuyoshi , Okamoto Takeshi , Sasaki Takashi , Hirai Tatsuki , Ishitsuka Takahiro , Yamada Manabu , Nakagawa Hiroki , Mie Takafumi , Furukawa Takaaki , Kasuga Akiyoshi , Ozaka Masato , Sasahira Naoki
Published: August 2023

Background

Osteosarcopenia is a newly described syndrome that has been reported to be associated with worse outcomes in various types of cancer. However, its impact on survival in biliary tract cancer remains unclear. This study evaluated the impact of osteosarcopenia on survival in patients with unresectable or recurrent biliary tract cancer.

Methods

A total of 306 patients with unresectable or recurrent biliary tract cancer who initiated chemotherapy at our institution between 2015 and 2021 were retrospectively investigated. Skeletal muscle index and bone mineral density were measured using pretreatment cross-sectional computed tomography images. Baseline characteristics and survival outcomes were compared between patients with osteosarcopenia and those without. The Cox proportional hazards regression model was used to identify factors associated with survival.

Results

Osteosarcopenia was present in 66 patients (22%) and was associated with older age (74 vs. 69 years, P < 0.001) and female sex (58 vs. 37%, P = 0.003). Patients with osteosarcopenia tended to have worse performance status (P = 0.098), higher modified Glasgow prognostic score (P = 0.082), higher neutrophil to lymphocyte ratio (P = 0.058) and were significantly less likely to receive combination chemotherapy (68 vs. 80%, P = 0.044) than those without. Osteosarcopenia was associated with reduced survival (8.9 vs. 14.0 months, P < 0.001) and was identified as an independent factor predicting shorter survival in multivariate analysis.

Conclusions

Osteosarcopenia was associated with poor survival in unresectable or recurrent biliary tract cancer treated with chemotherapy. This study highlights the potential importance of screening for osteosarcopenia in patients with biliary tract cancer.
Proliferation of monocytes and macrophages in homeostasis, infection, injury, and disease
Authors: Pang Jingbo , Koh Timothy J
Published: August 2023

Monocytes (Mo) and macrophages (Mφ) play important roles in the function of tissues, organs, and systems of all animals during homeostasis, infection, injury, and disease. For decades, conventional wisdom has dictated that Mo and Mφ are end-stage cells that do not proliferate and that Mφ accumulation in tissues is the result of infiltration of Mo from the blood and subsequent differentiation to Mφ. However, reports from the early 1900s to the present describe evidence of Mo and Mφ proliferation in different tissues and contexts. The purpose of this review is to summarize both historical and current evidence for the contribution of Mφ proliferation to their accumulation in different tissues during homeostasis, infection, injury, and disease. Mφ proliferate in different organs and tissues, including skin, peritoneum, lung, heart, aorta, kidney, liver, pancreas, brain, spinal cord, eye, adipose tissue, and uterus, and in different species including mouse, rat, rabbit, and human. Mφ can proliferate at different stages of differentiation with infiltrating Mo-like cells proliferating in certain inflammatory contexts (e.g. skin wounding, kidney injury, bladder and liver infection) and mature resident Mφ proliferating in other inflammatory contexts (e.g. nematode infection, acetaminophen liver injury) and during homeostasis. The pathways involved in stimulating Mφ proliferation also may be context dependent, with different cytokines and transcription factors implicated in different studies. Although Mφ are known to proliferate in health, injury, and disease, much remains to be learned about the regulation of Mφ proliferation in different contexts and its impact on the homeostasis, injury, and repair of different organs and tissues.
A study of Anopheles monticola of the Baileyi Complex, Culex sasai, and Lutzia vorax (Diptera: Culicidae) in Yunnan Province, China
Authors: Zhou Li , Phanitchakun Thanari , Saingamsook Jassada , Harbach Ralph E , Somboon Pradya
Published: August 2023

This article deals with the morphological and molecular assessments of 3 species of mosquitoes collected in Yunnan Province, China, i.e Anopheles monticola Somboon, Namgay & Harbach, the only species of the Baileyi Complex identified, Culex sasai Kano, Nitahara & Awaya, and Lutzia vorax Edwards. Interestingly, some adult specimens of An. monticola exhibited a variant form in having pale fringe spots, as found in An. simlensis James, another species of the Baileyi Complex. Culex sasai was recorded for the first time in Yunnan and mainland China. The prevalence of Lt. vorax was confirmed, and previous records of Lt. halifaxii in China are regarded as misidentifications of Lt. vorax.