bluuebunny/crossref_metadata_2025 huggingface dataset:
Population Pharmacokinetic Model and Dosing Simulation of Meropenem Using Measured Creatinine Clearance for Patients with Sepsis
Authors: Fukumoto Shiori , Ohbayashi Masayuki , Okada Akira , Kohyama Noriko , Tamatsukuri Tatsuro , Inoue Hideki , Kato Akihito , Kotani Toru , Sagara Hironori , Dohi Kenji , Kogo Mari
Published: October 2022

Purpose:

Creatinine clearance (CCr) and pharmacokinetic parameters are markedly affected by pathophysiological changes in patients with sepsis. However, only a few reports have assessed renal function in patients with sepsis using the measured CCr. Furthermore, the administration regimen has not been sufficiently evaluated using a population PK (PPK) model across renal function broad ranges. Therefore, this study was performed to construct a meropenem PPK model for patients with sepsis using the measured CCr and evaluate the optimized meropenem dosing regimen based on the CCr.

Methods:

Patients with sepsis who received intravenous meropenem at the Showa University Hospital were enrolled in this prospective observational study. The PPK model was constructed using blood samples and clinical information of patients. The probability of target attainment (PTA) indicates the likelihood of achieving 50% time above the minimum inhibitory concentration (% T > MIC) based on 10,000 virtual patients using Monte Carlo simulations. The PTA for each meropenem regimen was 50% T > MIC based on different renal functions using the Monte Carlo simulation.

Results:

One hundred samples were collected from 31 patients. The final PPK model incorporating the measured CCr as a covariate in CL displayed the best fit. The recommended dosing regimen to achieve a PTA of 50% T > MIC of 4 mcg/mL was 1 g every 8 hours as a 3-hour prolonged infusion for patients with CCr 85–130 mL/min and 1 g every 8 hours as an 8-hour continuous infusion for patients with CCr ≥ 130 mL/min.

Conclusions:

This model precisely predicted meropenem concentrations in patients with sepsis by accurately evaluating renal function using the measured CCr. Extended dosing was demonstrated to be necessary to achieve a PTA of 50% T > MIC for patients with CCr ≥ 85 mL/min. Meropenem effectiveness can be maximized in patients with sepsis by selecting the appropriate dosing regimen based on renal function and the MIC.
A dietary intervention for vasomotor symptoms of menopause: a randomized, controlled trial
Authors: Barnard Neal D. , Kahleova Hana , Holtz Danielle N. , Znayenko-Miller Tatiana , Sutton Macy , Holubkov Richard , Zhao Xueheng , Galandi Stephanie , Setchell Kenneth D. R.
Published: October 2022

Objective

Postmenopausal vasomotor symptoms disrupt quality of life. This study tested the effects of a dietary intervention on vasomotor symptoms and menopause-related quality of life.

Methods

Postmenopausal women (n = 84) reporting at least two moderate-to-severe hot flashes daily were randomly assigned, in two successive cohorts, to an intervention including a low-fat, vegan diet and cooked soybeans (½ cup [86 g] daily) or to a control group making no dietary changes. During a 12-week period, a mobile application was used to record hot flashes (frequency and severity), and vasomotor, psychosocial, physical, and sexual symptoms were assessed with the Menopause-Specific Quality of Life questionnaire. Between-group differences were assessed for continuous (t tests) and binary (χ
2/McNemar tests) outcomes. In a study subsample, urinary equol was measured after the consumption of ½ cup (86 g) of cooked whole soybeans twice daily for 3 days.

Results

In the intervention group, moderate-to-severe hot flashes decreased by 88% (P < 0.001) compared with 34% for the control group (P < 0.001; between-group P < 0.001). At 12 weeks, 50% of completers in the intervention group reported no moderate-to-severe hot flashes at all. Among controls, there was no change in this variable from baseline (χ
2 test, P < 0.001). Neither seasonality nor equol production status was associated with the degree of improvement. The intervention group reported greater reductions in the Menopause-Specific Quality of Life questionnaire vasomotor (P = 0.004), physical (P = 0.01), and sexual (P = 0.03) domains.

Conclusions

A dietary intervention consisting of a plant-based diet, minimizing oils, and daily soybeans significantly reduced the frequency and severity of postmenopausal hot flashes and associated symptoms.
Isolated vitamin D supplementation improves the adipokine profile of postmenopausal women: a randomized clinical trial
Authors: Schmitt Eneida B. , Orsatti Claudio L. , Cangussu Luciana , Bueloni-Dias Flavia N. , Poloni Priscila F. , Spadoto-Dias Daniel , Nahas Eliana A. P.
Published: October 2022

Objective

The aim of the study is to evaluate the effect of vitamin D supplementation alone on the adipokine profile of postmenopausal women.

Methods

In this randomized clinical trial, 160 women were randomized to 2 groups: oral supplementation with 1,000 IU cholecalciferol/d (vitamin D, n = 80) or placebo (PL, n = 80). Women with amenorrhea 12 months or more and aged 50 to 65 years were included. Women with established cardiovascular disease, insulin-dependent diabetes, renal failure, liver diseases, and previous use of menopausal hormone therapy and vitamin D were excluded. The intervention lasted 9 months and serum adiponectin, resistin, and adipsin levels were determined at the start and end of treatment. Intention to treat was adopted as the statistical method using a repeated measures design, followed by Wald's multiple comparison test adjusted for group × time interaction.

Results

After 9 months, 25-hydroxyvitamin D concentrations increased from 15.0 ± 7.5 to 27.5 ± 10.4 ng/mL (+45.4%) in the vitamin D group and decreased from 16.9 ± 6. to 13.8 ± 6.0 ng/mL (−18.5%) in the PL group (P < 0.001). In the vitamin D group, there was an increase in adiponectin (+18.6%) and a decrease in resistin (−32.4%, P < 0.05). At the end point, a difference was observed between the PL and vitamin D groups in mean adiponectin and resistin levels (11.5 ± 5.5 vs 18.5 ± 21.8 ng/mL, P = 0.047, and 16.5 ± 3.5 vs 11.7 ± 3.3 ng/mL, P = 0.027, respectively). There were no significant intervention effects on serum adipsin levels.

Conclusions

Daily supplementation with 1,000 IU of vitamin D alone was associated with an increase in adiponectin and a decrease in resistin, suggesting a beneficial effect on the adipokine profile of postmenopausal women with vitamin D deficiency.
Menopause hormone therapy and complementary alternative medicine, quality of life, and racial/ethnic differences: the Study of Women's Health Across the Nation (SWAN)
Authors: Christmas Monica , Janssen Imke , Joffe Hadine , Upchurch Dawn , Santoro Nanette , Kravitz Howard M.
Published: October 2022

Objective

We hypothesized that, among midlife women with vasomotor and/or genitourinary symptoms of menopause, (1) hormone therapy (HT) compared with complementary alternative medicine (CAM) will be associated with higher quality of life (QoL), and (2) race/ethnicity would modify associations of HT and CAM with QoL.

Methods

Cross-sectional and longitudinal analyses of QoL in the Study of Women's Health Across the Nation participants using HT, CAM, or both. Women (n = 2,514) completed a CAM use questionnaire and QoL assessments at baseline and every 1 to 2 years from 2002 to 2013. Associations between QoL and treatment, adjusted for covariates, and race/ethnicity-by-treatment interactions were analyzed using linear and mixed effects regression models.

Results

During 7.8 (SD, 2.9) years of follow-up, 732 women (29%) reported HT of 2.4 (SD, 1.7) years, and 798 women (32%) reported CAM use of 2.1 (SD, 1.4) years. Overall, neither HT nor CAM was associated with QoL. However, the treatment-by-race/ethnicity interaction was significant for self-reported QoL (P = 0.034 at baseline, P = 0.044 longitudinal). Among White women, self-reported QoL was higher in HT-only users than in those who used neither (P = 0.030; d = 0.11; 95% confidence interval, 0.01-0.21). In contrast, Black women using HT only had lower self-reported QoL compared with Black women using neither (P = 0.027; d = −0.21; 95% confidence interval, −0.40 to −0.02).

Conclusion

Comparisons between treatment type within each racial/ethnic group yielded significant differences in self-reported QoL. Clinicians should be aware of racial/ethnic differences in treatment preferences when counseling patients on treatment options for menopausal symptoms to provide optimal care.

Video Summary

http://links.lww.com/MENO/B33.
Autoantibodies Against Trisulfated Heparin Disaccharide and Fibroblast Growth Factor Receptor-3 May Play a Role in the Pathogenesis of Neuropathic Corneal Pain
Authors: Bayraktutar Betul N. , Atocha Vanessa , Farhad Khosro , Soto Oscar , Hamrah Pedram
Published: October 2022

Purpose:

The aim of this study was to describe cases of patients with presumable dysimmune small-fiber neuropathy (SFN)-related neuropathic corneal pain (NCP), presenting with autoantibodies against trisulfated heparin disaccharide (TS-HDS) or fibroblast growth factor receptor-3 (FGFR-3).

Methods:

This study was a case series of 3 patients with NCP with positive anti-TS-HDS and/or anti-FGFR-3 autoantibodies and systemic SFN as confirmed by positive skin biopsy results.

Results:

All 3 patients were women with a mean age of 34.3± 6.1 years. They suffered from moderate to severe persistent chronic ocular discomfort (10/10, 10/10, and 9/10 on a visual analogue scale, respectively). Although 1 patient suffered from ocular pain and photophobia alone, the other 2 patients experienced additional non-ocular pain. One of the patients had pain on her face and head, and 1 patient reported neck and lower back pain. Two patients had high anti-TS-HDS IgM titers, whereas 1 patient had both high anti-TS-HDS IgM and anti-FGFR-3 IgG titers. Skin biopsy confirmed the presence of SFN in all patients by demonstrating decreased intraepidermal nerve fiber density.

Conclusions:

The presence of anti-TS-HDS and anti-FGFR-3 autoantibodies in patients with NCP with positive skin biopsy findings for SFN highlights the potential role of dysimmune SFN in the pathogenesis of this disease.
Promoting understanding of medical decision-making coding for nurse practitioner students
Authors: Shanahan Tonya D. , Gurley Lisa E. , Chatman Sherri H. , Cunningham Jill L.
Published: October 2022

Nurse practitioners (NPs) are often responsible for coding patient encounters for reimbursement. Students should learn the basics of this skill during their educational preparation. On January 1, 2021, the American Medical Association and the Centers for Medicare & Medicaid Services implemented new guidelines to the evaluation and management office appointment documentation and coding. The new medical decision-making (MDM) guidelines created a learning curve for NP students, faculty, and preceptors. An additional obstacle was encountered when on-campus preclinical intensives, which included a coding practice session, were canceled due to the COVID-19 pandemic. The faculty of an NP program identified MDM coding as a difficult concept to teach in an asynchronous learning environment. In response, the faculty developed and implemented synchronous online case study sessions that incorporated active student participation and real-time feedback, thus increasing engagement with peers, faculty, and the MDM concepts. The purpose of this article was to present a synchronous method for teaching MDM coding to NP students, and the outcomes, lessons learned, and implications for nursing education and practice.
Coronavirus disease 2019 vaccine effectiveness among a population-based cohort of people living with HIV
Authors: Chambers Catharine , Samji Hasina , Cooper Curtis L. , Costiniuk Cecilia T. , Janjua Naveed Z. , Kroch Abigail E. , Arbess Gordon , Benoit Anita C. , Buchan Sarah A. , Chung Hannah , Kendall Claire E. , Kwong Jeffrey C. , Langlois Marc-André , Lee Samantha M. , Mbuagbaw Lawrence , McCullagh John , Moineddin Rahim , Nambiar Devan , Walmsley Sharon , Anis Aslam H. , Burchell Ann N.
Published: October 2022

Objective:

People with HIV were underrepresented in coronavirus disease 2019 (COVID-19) vaccine clinical trials. We estimated vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for the BNT162b2, mRNA-1273, and ChAdOx1 vaccines among a population-based cohort of people with HIV in Ontario, Canada.

Design:

Test-negative design

Methods:

We identified people with HIV aged ≥19 years who were tested for SARS-CoV-2 by RT-PCR between December 14, 2020 (first availability of COVID-19 vaccines) and November 21, 2021 (pre-Omicron circulation). Outcomes included any infection, symptomatic infection, and COVID-19-related hospitalization/death. We compared the odds of vaccination between test-positive cases and test-negative controls using multivariable logistic regression with adjustment for age, sex, region, calendar time, SARS-CoV-2 test histories, influenza vaccination, comorbidities, and neighborhood-level socio-economic status. VE was derived as (1 – adjusted odds ratio) × 100%.

Results:

Among 21 023 adults living with HIV, there were 801 (8.3%) test-positive cases and 8,879 (91.7%) test-negative controls. 20.1% cases and 47.8% of controls received ≥1 COVID-19 vaccine dose; among two-dose recipients, 93.4% received ≥1 mRNA dose. Two-dose VE ≥7 days before specimen collection was 82% (95% confidence interval [CI] = 74–87%) against any infection, 94% (95% CI = 82–98%) against symptomatic infection, and 97% (95% CI = 85–100%) against hospitalization/death. Against any infection, VE declined from 86% (95% CI = 77–92%) within 7–59 days after the second dose to 66% (95% CI = −15–90%) after ≥180 days; we did not observe evidence of waning protection for other outcomes.

Conclusion:

Two doses of COVID-19 vaccine offered substantial protection against symptomatic illness and hospitalization/death in people with HIV prior to the emergence of the Omicron variant. Our findings do not support a broad conclusion that COVID-19 VE is lower among people with HIV in populations that, for the most part, are attending HIV care, taking antiretroviral medication, and are virally suppressed.
A “Leopard Man” Aspect on 18F-FDG PET/CT Revealing a VEXAS Syndrome
Authors: Fagart Alexandre , Quemeneur Thomas , Collet Guillaume , Demailly Franck , Rousselin Clementine
Published: October 2022

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset autoinflammatory disease caused by somatic UBA1 mutations first described in 2020. Most of these patients met clinical criteria for an inflammatory syndrome (relapsing polychondritis, Sweet syndrome, polyarteritis nodosa, or giant-cell arteritis) or a hematologic condition (myelodysplastic syndrome or multiple myeloma) or both. We described here an FDG PET/CT “leopard man” appearance, with abnormal marrow recruitment the findings, in a 70-year-old man diagnosed with a VEXAS syndrome.
Isolated Liver Metastasis Detected by 68Ga-PSMA PET/CT in Newly Diagnosed Prostate Cancer
Authors: Önner Hasan , Özer Halil , Çelik Ahmet Volkan , Yilmaz Farise , Kara Gedik Gonca
Published: October 2022

Lymph nodes, bones, and liver are the most typical metastatic sites for prostate cancer. However, isolated liver metastasis from prostate cancer is extremely rare. Here, we report a 75-year-old man with newly diagnosed prostate adenocarcinoma, with isolated liver metastasis detected by 68Ga-PSMA (68Ga–prostate-specific membrane antigen) PET/CT. There was no sign of regional or distant metastases elsewhere. This case highlights the value of 68Ga-PSMA PET/CT in detecting a very uncommon solitary liver metastasis from prostate cancer.
POSTINJURY FECAL MICROBIOME TRANSPLANT DECREASES LESION SIZE AND NEUROINFLAMMATION IN TRAUMATIC BRAIN INJURY
Authors: Davis Booker T , Chen Zhangying , Islam Mecca B.A.R. , Timken Madeline E. , Procissi Daniele , Schwulst Steven J.
Published: October 2022

Background: Traumatic brain injury (TBI) is an underrecognized public health threat. The constitutive activation of microglia after TBI has been linked to long-term neurocognitive deficits and the progression of neurodegenerative disease. Evolving evidence indicates a critical role for the gut-brain axis in this process. Specifically, TBI has been shown to induce the depletion of commensal gut bacteria. The resulting gut dysbiosis is associated with neuroinflammation and disease. Hypothesis: We hypothesized that fecal microbiota transplantation would attenuate microglial activation and improve neuropathology after TBI. Methods: C57Bl/6 mice were subjected to severe TBI (n = 10) or sham injury (n = 10) via an open-head controlled cortical impact. The mice underwent fecal microbiota transplantation (FMT) or vehicle alone via oral gavage once weekly for 4 weeks after injury. At 59 days after TBI, mice underwent three-dimensional, contrast-enhanced magnetic resonance imaging. Following imaging, mice were killed, brains harvested at 60 DPI, and CD45+ cells isolated via florescence-activated cell sorting. cDNA libraries were prepared using the 10x Genomics Chromium Single Cell 3′ Reagent kit followed by sequencing on a HiSeq4000 instrument, and computational analysis was performed. Results: Fecal microbiota transplantation resulted in a >marked reduction of ventriculomegaly (P < 0.002) and preservation of white matter connectivity at 59 days after TBI (P < 0.0001). In addition, microglia from FMT-treated mice significantly reduced inflammatory gene expression and enriched pathways involving the heat-shock response compared with mice treated with vehicle alone. Conclusions: We hypothesized that restoring gut microbial community structure via FMT would attenuate microglial activation and reduce neuropathology after TBI. Our data demonstrated significant preservation of cortical volume and white matter connectivity after an injury compared with mice treated with vehicle alone. This preservation of neuroanatomy after TBI was associated with a marked reduction in inflammatory gene expression within the microglia of FMT-treated mice. Microglia from FMT-treated mice enriched pathways in the heat-shock response, which is known to play a neuroprotective role in TBI and other neurodegenerative disease processes.
No Stone Left Unturned: Utilization of an Organ Procurement Organization Donor Surgeon at Procurement Reduces Discards of Marginal Liver Allografts
Authors: Shubin Andrew D. , MacConmara Malcolm P. , Patel Madhukar S. , Wang Benjamin K. , Feizpour Cyrus A. , Reese Jeffrey , Niles Patricia A. , Shah Jigesh A. , Desai Dev M. , De Gregorio Lucia , Hanish Steven I. , Vagefi Parsia A. , Hwang Christine S.
Published: October 2022

Background.

The recent trend of organ procurement organizations (OPOs) employing independent surgeons for organ procurement has been developed with the goal of improving the supply of suitable organs for transplantation. We investigated the effects that the addition of an OPO-employed, organ-procurement specialist has on liver allograft discard rate, marginal organ utilization, and graft survival.

Methods.

Organ Procurement and Transplant Network and OPO data were retrospectively studied between April 1, 2014‚ and July 31, 2019‚ within the Southwest Transplant Alliance donor service area. Liver procurements with an OPO-surgeon present (OPO-Present) were compared to those without the involvement of an OPO surgeon (OPO-Absent). Donor and recipient characteristics as well as outcomes were analyzed across groups using propensity score matching.

Results.

In total 869 OPO-Present liver allografts had similar rates of discard (5.2%) compared to 771 OPO-Absent livers (5.8%). However, after adjusting for donor risk, OPO-Present livers had a lower propensity of discard compared to OPO-Absent (3.4% versus 7.6%, P < 0.05). OPO-Present livers were more likely to be shared nationally (11.0% versus 4.8%, P < 0.001). Outcome analysis showed allograft survival of OPO-Present livers at 5 y was comparable to OPO-Absent livers (79.5% versus 80%, P = 0.34).

Conclusions.

The presence of an OPO surgeon was associated with decreased liver allograft discard and increased utilization of marginal donor organs. The OPO surgeon’s presence represents a potential strategy to increase organ utilization nationally.
Image-based quantification of histological features as a function of spatial location using the Tissue Positioning System
Authors: Wang Yunguan , Rong Ruichen , Wei Yonglong , Wang Tao , Xiao Guanghua , Zhu Hao
Published: October 2022

Tissues such as the liver lobule, kidney nephron, and intestinal gland exhibit intricate patterns of zonated gene expression corresponding to distinct cell types and functions. To quantitatively understand zonation, it would be important to measure cellular or genetic features as a function of position along a zonal axis. While it is possible to manually count, characterize, and locate features in relation to the zonal axis, it is very difficult to do this for more than a few hundred instances. We addressed this challenge by developing a deep-learning-based quantification method called the “Tissue Positioning System” (TPS), which can automatically analyze zonation in the liver lobule as a model system. By using algorithms that identified vessels, classified vessels, and segmented zones based on the relative position along the portal vein to central vein axis, TPS was able to spatially quantify gene expression in mice with zone specific reporters. TPS could discern expression differences between zonal reporter strains, ages, and disease states. TPS could also reveal the zonal distribution of cells previously thought to be randomly distributed. The design principles of TPS could be generalized to other tissues to explore the biology of zonation.

The software is available athttps://github.com/yunguan-wang/Tissue_positioning_system.
Improved breeding forFusarium pseudograminarium(Fusarium crown rot) using qPCR measurement of infection in multi-species winter cereal experiments
Authors: Milgate Andrew , Baxter Brad , Simpfendorfer Steven , Yang Nannan , Orchard Beverly , Ovenden Ben
Published: October 2022

Fusarium crown rot (FCR) causes significant grain yield loss in winter cereals around the world. Breeding for resistance and/or tolerance to FCR has been slow with relatively limited success. In this study, multi-species experiments were used to demonstrate an improved method to quantify FCR infection levels at plant maturity using qPCR, as well as the genotype yield retention using residual regression deviation. Using qPCR to measure FCR infection allowed a higher degree of resolution between genotypes than traditional visual stem basal browning assessments. The results were consistent across three environments with different levels of disease expression. The improved measure of FCR infection along with genotype yield retention allows for partitioning of both tolerance and partial resistance. Together these methods offer new insights to FCR partial resistance and its relative importance to tolerance in bread wheat and barley. This new approach offers a more robust, cost-effective way to select for both FCR traits within breeding programs.

Key message

Genetic gain for tolerance and partial resistance against Fusarium crown rot (FCR) in winter cereals has been impeded by laborious and variable visual measures of infection severity. This paper presents results of an improved method to quantify FCR infection that are strongly correlated to yield loss and reveal previously unrecognised partial resistance in barley and wheat varieties.
Refphase: Multi-sample reference phasing reveals haplotype-specific copy number heterogeneity
Authors: Watkins Thomas BK , Colliver Emma C , Huska Mathew R , Kaufmann Tom L , Lim Emilia L , Haase Kerstin , Van Loo Peter , Swanton Charles , McGranahan Nicholas , Schwarz Roland F
Published: October 2022

Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patient’s disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample reference phasing. We demonstrate Refphase’s ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours.
Quartile coefficient of variation is more robust than CV for traits calculated as a ratio1
Authors: Botta-Dukát Zoltán
Published: October 2022

Comparing within-species variations of traits can be used in testing ecological theories. In these comparisons, it is useful to remove the effect of the difference in mean trait values, therefore measures of relative variation, most often the coefficient of variation (CV), are used. The studied traits are often calculated as the ratio of the size or mass of two organs: e.g. SLA is the ratio of leaf size and leaf mass. Often the inverse of these ratios is also meaningful; for example, the inverse of SLA is often referred to as LMA (leaf mass per area). Relative variation of a trait and its inverse should not considerably differ. However, it is illustrated that using the coefficient of variation may result in differences that could influence the interpretation, especially if there are outlier trait values. The alternative way for estimating CV from the standard deviation of log-transformed data assuming log-normal distribution and Kirkwood’s geometric coefficient of variation free from this problem, but they proved to be sensitive to outlier values. Quartile coefficient of variation performed best in the tests: it gives the same value for a trait and its inverse and it is not sensitive to outliers.
A chromosome-scale assembly ofBrassica carinata(BBCC) accession HC20 containing resistance to multiple pathogens and an early generation assessment of introgressions intoB. juncea(AABB)
Authors: Paritosh Kumar , Rajarammohan Sivasubramanian , Yadava Satish Kumar , Sharma Sarita , Verma Rashmi , Mathur Shikha , Mukhopadhyay Arundhati , Gupta Vibha , Pradhan Akshay K , Kaur Jagreet , Pental Deepak
Published: October 2022

Brassica carinata(BBCC) commonly referred to as Ethiopian mustard is a natural allotetraploid containing the genomes ofBrassica nigra(BB) andBrassica oleracea(CC). It is an oilseed crop endemic to the Northeastern regions of Africa. Although it is grown in a limited manner,B. carinatais of value as it is resistant/highly tolerant to most of the pathogens affecting cultivated Brassica species of the U’s triangle that are grown worldwide as oilseed and vegetable crops. We report a chromosome-scale genome assembly ofB. carinataaccession HC20 using long-read Oxford Nanopore and Illumina sequencing and BioNano optical maps. The assembly has a scaffold N50 of ~39.8 Mb and covers ~1.11 Gb of the genome. We compared the available long-read genome assemblies of the six species of the U’s triangle and found a highly conserved gene number and collinearity suggesting thatB. juncea(AABB),B. napus(AACC), andB. carinataare strict allopolyploids. We cataloged the nucleotide-binding and leucine-rich repeat immune receptor (NLR) repertoire ofB. carinataresulting in the identification of 465 NLRs. We investigated the extent and nature of early generation genomic interactions between the subgenomes ofB. carinataandB. junceain interspecific crosses between the two species. We found that C chromosome additions are well tolerated, with homoeologous exchanges occurring between the A and C genomes. Based on the genomic interactions, we propose strategies to utilize the interspecific crosses for transferring disease resistance fromB. carinatatoB. junceaand other Brassica species.
Environmental drivers of earthworm communities along an altitudinal gradient in the French Alps
Authors: Gabriac Quentin , Ganault Pierre , Barois Isabelle , Aranda-Delgado Eduardo , Cimetière Elisa , Cortet Jérôme , Gautier Montan , Hedde Mickaël , Marchán Daniel F. , Pimentel Reyes José Carlos , Stokes Alexia , Decaëns Thibaud
Published: October 2022

The study of elevational diversity gradients is a central topic in biodiversity research. In this study, we tested for the effect of climate, resource quality and habitat heterogeneity on earthworm communities along an altitudinal gradient and around the treeline in the French Alps. Earthworm communities and environmental properties (i.e. climate, soil properties and vegetation structure and composition) were sampled in six altitudinal stages from 1400 to 2400 m. Results were analysed through multi-table factorial analyses and structural equation modelling. We found average density, biomass and species richness in the range of what is usually reported in comparable ecosystems. We found no monotonic decrease in species richness along the altitudinal gradient, which we explain by the species pool being dominated by taxa with high environmental tolerance and dispersal capacities. Instead, we highlighted the ecotone associated with the treeline as the primary driving factor of earthworm communities: at 1800-2000m altitude, communities were more abundant and diverse, and had a greater variability in body mass. This result was largely explained by the structure and composition of the vegetation, whereas soil and climate appeared to have only indirect effects. Therefore, the treeline effect on earthworm communities can be explained both by the effect of environmental heterogeneity and of trophic resource quality which increases at the ecotone level.
Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation
Authors: Ahmed Faraz , Vu Luyen Tien , Zhu Hongya , Iu David Shing Huk , Fogarty Elizabeth A. , Kwak Yeonui , Chen Weizhong , Franconi Carl J. , Munn Paul R. , Levine Susan M. , Stevens Jared , Mao Xiangling , Shungu Dikoma C. , Moore Geoffrey E. , Keller Betsy A. , Hanson Maureen R. , Grenier Jennifer K. , Grimson Andrew
Published: October 2022

ME/CFS is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we used single-cell RNA-seq (scRNA-seq) to examine immune cells in cohorts of patients and controls. Post-exertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. Thus, to detect changes coincident with PEM, we also performed scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients displayed dysregulation of classical monocytes suggestive of inappropriate differentiation and migration to tissue. We were able to identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlated with metrics of disease severity. Comparing the transcriptome at baseline and post-exercise challenge, we discovered patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation following exercise.

Highlights

ME/CFS is a debilitating disease with unknown causes. Here, we provide, for the first time, an extensive single cell resolution dataset detailing the gene expression programs of circulating immune cells of ME/CFS cases at baseline and after symptom provocation. We were able to detect robust dysregulation in certain immune cells from patients, with dysregulation of classical monocytes manifesting the strongest signal. Indeed, the fraction of aberrant monocytes in ME/CFS patients correlated with the degree of disease severity. Surprisingly, platelet transcriptomes were also altered in ME/CFS, and they were the only component of the immune system that showed large-scale changes following symptom provocation.
Nitrogen uptake pattern of dry direct-seeding rice and its contribution to yield in northeastern Japan
Authors: Namikawa Mari , Yabiku Takayuki , Matsunami Maya , Matsunami Toshinori , Hasegawa Toshihiro
Published: October 2022

Dry direct-seeding rice (DDSR) cultivation is expected to reduce production costs compared with transplanted rice (TPR); however, its low nitrogen (N) use efficiency (NUE) has hindered cost reduction. Additionally, polymer-coated urea application in rice cultivation is reduced for plastic pollution regulation. The split application of urea can be an alternative, but it has not been used in northeastern Japan, hence needs to be investigated. We conducted DDSR and TPR field experiments for three years using two cultivars and three or two N regimes to determine factors limiting yield and NUE using a standard cultivar (‘Akitakomachi’) and a high-yielding cultivar (‘Yumiazusa’) grown under different N regimes. The yield, yield components, and N uptake of DDSR were analyzed, and examined the contribution of N uptake until panicle initiation and heading for spikelet number by multiple regression compared to that of TPR. Additionally, we investigated the detailed N uptake pattern on DDSR until PI using the two parameters, which were calculated by exponential regression of N uptake during the vegetative period. DDSR yield was lower than that of TPR by 11% and revealed that both fertilizer recovery rate and crop NUE (yield per unit N uptake) contributed to the lower yield. N uptake until the fifth leaf age significantly influenced the N uptake until panicle initiation. DDSR yield with normal urea in this study proportion was not significantly different compared to coated urea application, indicating the possibility to be an alternative N application method.
Immunofilaments Provide a Nanoscale Platform for In Vivo T Cell Expansion and Cancer Immunotherapy
Authors: Weiss Lea , Weiden Jorieke , Dölen Yusuf , Grad Emilia M. , van Dinther Eric A.W. , Schluck Marjolein , Eggermont Loek J. , van Mierlo Guido , Gileadi Uzi , Bartoló-Ibars Ariadna , Raavé René , Gorris Mark A.J. , Verrijp Kiek , Valente Michael , Deplancke Bart , Verdoes Martijn , Benitez-Ribas Daniel , Cerundolo Vincenzo , Heskamp Sandra , van Spriel Annemiek B. , Figdor Carl G. , Hammink Roel
Published: October 2022

Adoptive T cell therapy has successfully been implemented for the treatment of cancer. Nevertheless, the precarious ex vivo expansion of T cells by artificial antigen-presenting cells (aAPCs) remains cumbersome and can compromise T cell functionality, thereby limiting their therapeutic potential. Here, we propose a radically different approach aiming at direct expansion of T cells in vivo, thereby omitting the need for large-scale ex vivo T cell production. We engineered nanosized immunofilaments (IFs), consisting of a soluble semiflexible polyisocyanopeptide polymer backbone that presents peptide-loaded major histocompatibility complexes and co-stimulatory molecules in a multivalent fashion. We demonstrate that IFs readily activate and expand antigen-specific T cells in a manner highly similar to natural APCs, as evidenced by transcriptomic analyses of T cells. Upon intravenous injection, IFs reach lymphoid organs including spleen and lymph nodes and induce antigen-specific T cell responses in vivo. Moreover, IFs display remarkable anti-tumor efficacy resulting in inhibition of melanoma metastases formation and reduction of primary tumor growth in synergy with immune checkpoint blockade. In conclusion, nanosized IFs represent a powerful new type of aAPC that provide a modular platform for direct activation and expansion of antigen-specific T cells in vivo, which can greatly contribute to cancer immunotherapy.
Identifying dynamic reproducible brain states using a predictive modelling approach
Authors: O’Connor D , Horien C , Mandino F , Constable RT
Published: October 2022

Conceptually brain states reflect some combination of the internal mental process of a person, and the influence of their external environment. Importantly, for neuroimaging, brain states may impact brain-behavior modeling of a person’s traits, which should be independent of moment-to-moment changes in behavior. A common way to measure both brain states and traits is to use functional connectivity based on functional MRI data. Brain states can fluctuate in time periods shorter than a typical fMRI scan, and a family of methods called dynamic functional connectivity analyses, have been developed to capture these short time estimates of brain states. There has been a rise in the use of dynamic functional connectivity in order to find temporally specific spatial patterns of connectivity which reflect brain states, that can yield further insight into traits and behaviors. It has previously been shown that brain state can be manipulated through the use of continuous performance tasks that put the brain in a particular configuration while the task is performed. Here we focus on moment-to-moment changes in brain state and test the hypothesis that there are particular brain-states that maximize brain-trait modeling performance. We use a regression-based brain-behavior modelling framework, Connectome-based Predictive Modelling, allied to a resample aggregating approach, to identify behavior and trait related short time brain states, as represented by dynamic functional connectivity maps. We find that there is not a particular brain state that is optimal for trait-based prediction, and drawing data from across the scan is better. We also find that this not the case for in-magnet behavioral prediction where more isolated and temporally specific parts of the scan session are better for building predictive models of behavior. The resample aggregated dynamic functional connectivity models of behavior replicated within sample using unseen HCP data. The modelling framework also showed success in the estimating variance behavior in the ABCD dataset when using data from that dataset. The method detailed here may prove useful for both the study of behaviorally related brain states, and for short time predictive modelling.
Field dependent deep learning enables high-throughput whole-cell 3D super-resolution imaging
Authors: Fu Shuang , Shi Wei , Luo Tingdan , He Yingchuan , Zhou Lulu , Yang Jie , Yang Zhichao , Liu Jiadong , Liu Xiaotian , Guo Zhiyong , Yang Chengyu , Liu Chao , Huang Zhen-li , Ries Jonas , Zhang Mingjie , Xi Peng , Jin Dayong , Li Yiming
Published: October 2022

Single-molecule localization microscopy (SMLM) in a typical wide-field setup has been widely used for investigating sub-cellular structures with super resolution. However, field-dependent aberrations restrict the field of view (FOV) to only few tens of micrometers. Here, we present a deep learning method for precise localization of spatially variant point emitters (FD-DeepLoc) over a large FOV covering the full chip of a modern sCMOS camera. Using a graphic processing unit (GPU) based vectorial PSF fitter, we can fast and accurately model the spatially variant point spread function (PSF) of a high numerical aperture (NA) objective in the entire FOV. Combined with deformable mirror based optimal PSF engineering, we demonstrate high-accuracy 3D SMLM over a volume of ~180 × 180 × 5 μm3, allowing us to image mitochondria and nuclear pore complex in the entire cells in a single imaging cycle without hardware scanning - a 100-fold increase in throughput compared to the state-of-the-art.
Weekly dance training over eight months reduces depression and correlates with fMRI brain signals in subcallosal cingulate gyrus (SCG) for people with Parkinson’s Disease: An observational study
Authors: Barnstaple Rebecca E , Bearss Karolina , Bar Rachel J , DeSouza Joseph F
Published: October 2022

Depression affects 280 million people globally and is considered a prodromal feature for increasingly prevalent neurodegenerative conditions including Parkinson’s disease (PD). With age-related neurodegeneration on the rise, it’s important to consider non-invasive, inexpensive interventions such as dance. Dance has emerged as a complementary treatment that may support adaptive neuroplasticity while diminishing motor and non-motor symptoms including depression. Although dance has been shown to impact brain structures and functions with improvements in motor and psychological symptoms, the neural mechanisms underlying depression/mood remain elusive. Our observational study tracks the relationship between depression scores and functional neuroimaging measures for subgenual cingulate gyrus (SCG). While learning choreography over an 8-month period, 34 dancers [23 people with PD] completed GDS questionnaires before and after their community dance classes. Seventeen of these dancers had BOLD fMRI scans conducted using learning-related protocols to examine underlying neural mechanisms for moving to music over 4 times points of learning. A significant decrease in depression scores correlated with a reduced BOLD signal from SCG, a putative node in the neural network of depression. Conclusions: This is the first study to clearly find a correlation with a neural substrate involved in mood changes as a function of dance for PD. Not only do the results contribute to understanding neural mechanisms involved in adaptive plasticity with a learning task, but they also uncover reduced activity within SCG during longitudinal therapeutic dance interventions. These results are especially illuminating since SCG is a controversial target in deep brain stimulation (DBS) used in the treatment of major depressive disorder (MDD).
Herb-paths, a network and statistical model to explore health-beneficial effects of herbs and herbal constituents
Authors: van der Voet Monique , Xu Zhiyi , van Rijnberk Lotte , Wu Huihui , Liang Wen , Sun Pengyue , Wang Mei , Wildwater Marjolein , Poppelaars Eefje S.
Published: October 2022

Predictions on bioactivities of herbs and herbal compounds could greatly aid drug development, but require integration of available information on herb and compound effects from various databases. We present Herb-paths, an integrated network connecting information on health-beneficial effects of herbs and herbal constituents. The statistical models included in Herb-paths allow for the calculation of the association strength of herbal (constituents) with health-beneficial effects, for both known and novel effects, and give insight into the major bioactive compounds and molecular mechanisms driving the effects.

Herb-paths’ predictions were tested and validated using a case-study ofPanax notoginsengand its derived medicinal extract of Panaxatriol saponins (PTS), used in traditional Chinese medicine to treat stroke and other cardiovascular and cerebrovascular thromboembolic (CCT) disorders.

Results showed that Herb-paths predicted known and novel associations between PTS/Notoginsengand CCT phenotypes and diseases, including stroke. Predicted novel associations, such as MoyaMoya disease, are promising putative leads for treatment with PTS/Notoginseng, to be tested in further studies.
Tracking the behavioral and neural dynamics of semantic representations through negation
Authors: Zuanazzi Arianna , Ripollés Pablo , Lin Wy Ming , Gwilliams Laura , King Jean-Rémi , Poeppel David
Published: October 2022

Combinatoric linguistic operations underpin human language processes, but how meaning is composed and refined in the mind of the reader is not well understood. We address this puzzle by exploiting the ubiquitous function of negation. We track the online effects of negation (“not”) and intensifiers (“really”) on the representation of scalar adjectives (e.g., “good”) in parametrically designed behavioral and neurophysiological (MEG) experiments. The behavioral data show that participants first interpret negated adjectives as affirmative and later modify their interpretation towards, but never exactly as, the opposite meaning. Decoding analyses of neural activity further reveal significant above chance decoding accuracy for negated adjectives within 600 ms from adjective onset, suggesting that negation does not invert the representation of adjectives (i.e., “not bad” represented as “good”); furthermore, decoding accuracy for negated adjectives is found to be significantly lower than that for affirmative adjectives. Overall, these results suggest that negation mitigates rather than inverts the neural representations of adjectives. This putative suppression mechanism of negation is supported by increased synchronization of beta-band neural activity in sensorimotor areas. The analysis of negation provides a steppingstone to understand how the human brain represents changes of meaning over time.
Inference of gene-environment interaction from heterogeneous case-parent trios
Authors: Ratnasekera Pulindu , Graham Jinko , McNeney Brad
Published: October 2022

In genetic epidemiology, log-linear models of population risk may be used to study the effect of genotypes and exposures on the relative risk of a disease. Such models may also include gene-environment interaction terms that allow the genotypes to modify the effect of the exposure, or equivalently, the exposure to modify the effect of genotypes on the relative risk. When a measured test locus is in linkage disequilibrium with an unmeasured causal locus, exposure-related genetic structure in the population can lead to spurious gene-environment interaction; that is, to apparent gene-environment interaction at the test locus in the absence of true gene-environment interaction at the causal locus. Exposure-related genetic structure occurs when the distributions of exposures and of haplotypes at the test and causal locus both differ across population strata. A case-parent trio design can protect inference of genetic main effects from confounding bias due to genetic structure in the population. Unfortunately, when the genetic structure is exposure-related, the protection against confounding bias for the genetic main effect does not extend to the gene-environment interaction term. We show that current methods to reduce the bias in estimated gene-environment interactions from case-parent trio data can only account for simple population structure involving two strata. To fill this gap, we propose to directly accommodate multiple population strata by adjusting for genetic principal components. We evaluate our approach through simulation and illustrate it on data from a study of genetic modifiers of cleft palate.