bluuebunny/crossref_metadata_2025 huggingface dataset:
The ProtoDUNE Photon Detection System: technology validation and performance
Authors: Brizzolari C. ,   the DUNE collaboration
Published: March 2024

DUNE is a long-baseline accelerator experiment currently in construction at Fermilab and SURF (South Dakota). The science objectives of DUNE include the search for CP violation
in the leptonic sector and the identification of the neutrino mass hierarchy, along with the
observation of supernova neutrino bursts and proton decay.
The Far Detector consists of four modules located deep underground, three of those instrumented with Liquid Argon TPCs and equipped with the DUNE Photon Detection System (PDS). The PDS is based on a novel
light trapping technology that greatly enhances the DUNE physics reach,
improving vertex identification, energy resolution and providing the trigger for non-beam events.
Following a first run of data taking (from 2018 to 2020), the PDS of the two prototypes of the Far Detector located at CERN Neutrino Platform, ProtoDUNE-HD and ProtoDUNE-VD, is currently being reinstalled in order to implement the final design of the first (Horizontal Drift) and second (Vertical Drift) module.
This paper presents the latest results of the PDS from test facilities and the status of the installation in ProtoDUNE in view of its second run. The most important achievements of the Vertical Drift PDS are reported, with emphasis on the new SiPM configuration and cold electronics, the custom WaveLength Shifting bars, and the latest generation of the dichroic filter designed for ProtoDUNE-VD.
Chemical and green synthesis of gold nanoparticles for mRNA delivery in vitro
Authors: Venkatas Jeaneen , Singh Moganavelli
Published: March 2024

Nanotechnology has paved the way for novel treatment strategies for diseases such as cancer. While chemical synthesis of nanoparticles (NPs) can introduce toxic and expensive reducing reagents, green synthesis offers an alternative with dual reducing and capping properties. Curcumin exhibits favourable pharmacological properties, enabling synergism with the therapeutic cargo. This study aimed to compare green and chemically synthesised gold NPs for the delivery of FLuc-mRNA in vitro. Chemical and green synthesised AuNPs were produced using trisodium citrate and curcumin, respectively, and functionalised with poly-L-lysine (PLL) and polyethylene glycol (PEG). The NP:mRNA nanocomplexes were characterised using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and UV–visible spectroscopy. Various mRNA binding studies assessed the optimal mRNA binding, compaction, and protection of the mRNA. All AuNPs were small (<150 nm) and had good colloidal stability, mRNA binding, and protection. The MTT (3-[4,5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide) assay showed favourable cell viability, with significant transgene expression noted using the luciferase reporter gene assay. Higher transfection was achieved in the human cervical carcinoma (HeLa) than in the breast adenocarcinoma (MCF-7) and embryonic kidney (HEK293) cells. Both chemically and curcumin-synthesised AuNPs displayed similar activity in all cells, with curcumin-capped AuNPs marginally better at the same concentration.
The Noether–Lefschetz theorem in arbitrary characteristic
Authors: Ji Lena
Published: March 2024

We show that if

X
⊂

P

k
N

X\subset \mathbb P^N_k

is a normal variety of dimension

≥
3

\geq 3

and

H
⊂

P

k
N

H\subset \mathbb P^N_k

a very general hypersurface of degree

d
=
4

d=4

or

≥
6

\geq 6

, then the restriction map

Cl
⁡
(
X
)
→
Cl
⁡
(
X
∩
H
)

\operatorname {Cl}(X)\to \operatorname {Cl}(X\cap H)

is an isomorphism up to torsion. If

dim
⁡
X
≥
4

\dim X\geq 4

, the result holds for

d
≥
2

d\geq 2

. The proof uses the relative Jacobian of a curve fibration, together with a specialization argument, and the result holds over fields of arbitrary characteristic.
Dual-channel hypergraph convolutional network for predicting herb–disease associations
Authors: Hu Lun , Zhang Menglong , Hu Pengwei , Zhang Jun , Niu Chao , Lu Xueying , Jiang Xiangrui , Ma Yupeng
Published: March 2024

Herbs applicability in disease treatment has been verified through experiences over thousands of years. The understanding of herb–disease associations (HDAs) is yet far from complete due to the complicated mechanism inherent in multi-target and multi-component (MTMC) botanical therapeutics. Most of the existing prediction models fail to incorporate the MTMC mechanism. To overcome this problem, we propose a novel dual-channel hypergraph convolutional network, namely HGHDA, for HDA prediction. Technically, HGHDA first adopts an autoencoder to project components and target protein onto a low-dimensional latent space so as to obtain their embeddings by preserving similarity characteristics in their original feature spaces. To model the high-order relations between herbs and their components, we design a channel in HGHDA to encode a hypergraph that describes the high-order patterns of herb-component relations via hypergraph convolution. The other channel in HGHDA is also established in the same way to model the high-order relations between diseases and target proteins. The embeddings of drugs and diseases are then aggregated through our dual-channel network to obtain the prediction results with a scoring function. To evaluate the performance of HGHDA, a series of extensive experiments have been conducted on two benchmark datasets, and the results demonstrate the superiority of HGHDA over the state-of-the-art algorithms proposed for HDA prediction. Besides, our case study on Chuan Xiong and Astragalus membranaceus is a strong indicator to verify the effectiveness of HGHDA, as seven and eight out of the top 10 diseases predicted by HGHDA for Chuan-Xiong and Astragalus-membranaceus, respectively, have been reported in literature.
Agreeing that maps can disagree: Moving away from map confusion in conservation
Authors: Dreiss Lindsay M , Anderson Mark G , Bateman Brooke L , Belote R Travis , Michalak Julia L , Rice Mindy B
Published: March 2024

Deciding where to implement actions for biodiversity conservation remains challenging for many reasons, including the increase in maps aimed at prioritizing locations for conservation efforts. Although a growing numbers of maps can create the perception of uncertainty and competing science, a shared set of principles underlie many mapping initiatives. We overlaid the priority areas identified by a subset of maps to assess the extent to which they agree. The comparison suggests that when maps are used without understanding their origin, confusion seems justified: The union of all maps covers 73% of the contiguous United States, whereas the intersection of all maps is at least 3.5%. Our findings support the need to place a strong focus on the principles and premises underpinning the maps and the end users’ intentions. We recommend developing a science-based guidance to aid scientists, policymakers, and managers in selecting and applying maps for supporting on-the-ground decisions addressing biodiversity loss and its interconnected crises.
Daily handover in surgery: systematic review and a novel taxonomy of interventions and outcomes
Authors: Ryan Jessica M , McHugh Fiachra , Simiceva Anastasija , Eppich Walter , Kavanagh Dara O , McNamara Deborah A
Published: March 2024

Background

Poor-quality handovers lead to adverse outcomes for patients; however, there is a lack of evidence to support safe surgical handovers. This systematic review aims to summarize the interventions available to improve end-of-shift surgical handover. A novel taxonomy of interventions and outcomes and a modified quality assessment tool are also described.

Methods

Ovid MEDLINE®, PubMed, Embase, and Cochrane databases were searched for articles up to April 2023. Comparative studies describing interventions for daily in-hospital surgical handovers between doctors were included. Studies were grouped according to their interventions and outcomes.

Results

In total, 6139 citations were retrieved, and 41 studies met the inclusion criteria. The total patient sample sizes in the control and intervention groups were 11 946 and 11 563 patients, respectively. Most studies were pre-/post-intervention cohort studies (92.7%), and most (73.2%) represented level V evidence. The mean quality assessment score was 53.4% (17.1). A taxonomy of handover interventions and outcomes was developed, with interventions including handover tools, process standardization measures, staff education, and the use of mnemonics. More than 25% of studies used a document as the only intervention. Overall, 55 discrete outcomes were assessed in four categories including process (n = 27), staff (n = 14), patient (n = 12) and system-level (n = 2) outcomes. Significant improvements were seen in 51.8%, 78.5%, 58.3% (n = 9761 versus 9312 patients) and 100% of these outcomes, respectively.

Conclusions

Most publications demonstrate that good-quality surgical handover improves outcomes and many interventions appear to be effective; however, studies are methodologically heterogeneous. These novel taxonomies and quality assessment tool will help standardize future studies.
Differential associations of fetuin-A and calcification propensity with cardiovascular events and subsequent mortality in patients undergoing hemodialysis
Authors: Mori Katsuhito , Shoji Tetsuo , Nakatani Shinya , Uedono Hideki , Ochi Akinobu , Yoshida Hisako , Imanishi Yasuo , Morioka Tomoaki , Tsujimoto Yoshihiro , Kuro-o Makoto , Emoto Masanori
Published: March 2024

Background

Fetuin-A inhibits precipitation of calcium-phosphate crystals by forming calciprotein particles (CPP). A novel T50 test, which measures transformation time from primary to secondary CPP, is an index for calcification propensity. Both lower fetuin-A and shorter T50 levels were associated with cardiovascular disease (CVD) risk in patients with chronic kidney disease (CKD). Extremely high risk for CVD death in advanced CKD patients consists of high-incidental CVD event and high mortality after CVD event. To date, it is unclear whether fetuin-A and/or T50 can equally predict each CVD outcome.

Methods

This prospective cohort study examined patients undergoing maintenance hemodialysis. The exposures were fetuin-A and T50. The outcomes of interests were new CVD events and subsequent deaths. The patients were categorized into tertiles of fetuin-A or T50 (T1 to T3).

Results

We identified 190 new CVD events during the 5-year follow-up of the 513 patients and 59 deaths subsequent to the CVD events during 2.5-year follow-up. A lower fetuin-A but not T50 was significantly associated with new CVD events [subdistribution hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.15–2.61, P = .009 for T1 vs T3]. In contrast, a shorter T50 but not fetuin-A was a significant predictor of deaths after CVD events (HR 3.31, 95% CI 1.42–7.74, P = .006 for T1 + T2 vs T3). A lower fetuin-A was predictive of new CVD events, whereas a shorter T50 was more preferentially associated with subsequent death.

Conclusion

These results indicate that fetuin-A and T50 are involved in cardiovascular risk in different manners.
Exposure to Synthetic Psychoactive Substances: A Potential Cause for Increased Human Hepatotoxicity Markers
Authors: Balloni Aurora , Tini Anastasio , Prospero Emilia , Busardò Francesco Paolo , Huestis Marilyn Ann , Lo Faro Alfredo Fabrizio
Published: March 2024

Background

Approximately 30 million people worldwide consume new psychoactive substances (NPS), creating a serious public health issue due to their toxicity and potency. Drug-induced liver injury is the leading cause of liver disease, responsible for 4% of global deaths each year.

Content

A systematic literature search revealed 64 case reports, in vitro and in vivo studies on NPS hepatotoxicity. Maximum elevated concentrations of aspartate aminotransferase (136 to 15 632 U/L), alanine transaminase (121.5 to 9162 U/L), total bilirubin (0.7 to 702 mg/dL; 0.04 to 39.03 mmol/L), direct (0.2–15.1 mg/dL; 0.01–0.84 mmol/L) and indirect (5.3 mg/dL; 0.29 mmol/L) bilirubin, alkaline phosphatase (79–260 U/L), and gamma-glutamyltransferase (260 U/L) were observed as biochemical markers of liver damage, with acute and fulminant liver failure the major toxic effects described in the NPS case reports. In vitro laboratory studies and subsequent in vivo NPS exposure studies on rats and mice provide data on potential mechanisms of toxicity. Oxidative stress, plasma membrane stability, and cellular energy changes led to apoptosis and cell death. Experimental studies of human liver microsome incubation with synthetic NPS, with and without specific cytochrome P450 inhibitors, highlighted specific enzyme inhibitions and potential drug–drug interactions leading to hepatotoxicity.

Mild to severe hepatotoxic effects following synthetic NPS exposure were described in case reports. In diagnosing the etiology of liver damage, synthetic NPS exposure should be considered as part of the differential diagnosis. Identification of NPS toxicity is important for educating patients on the dangers of NPS consumption and to suggest promising treatments for observed hepatotoxicity.
Outcomes of thoracic endovascular aortic repair using fenestrated stent grafts in patients with thoracic aortic distal arch aneurysms
Authors: Okamoto Takeshi , Yokoi Yoshihiko , Sato Noriaki , Suzuki Shuhei , Enomoto Takashi , Onishi Ryo , Nakamura Norihito , Okubo Yuka , Nagasawa Ayako , Mishima Takehito , Shiraishi Shuichi , Tsuchida Masanori
Published: March 2024

OBJECTIVES

Thoracic endovascular aortic repair (TEVAR) for aortic arch aneurysms is challenging because of anatomical restrictions and the presence of cervical branches. Revascularization of the cervical branch is required when conventional commercial stent grafts are used. TEVAR using fenestrated stent grafts (FSG) often does not require additional procedures to revascularize cervical branches. This study aimed to evaluate the features and initial and midterm outcomes of TEVAR using fenestrated stent grafts.

METHODS

From April 2007 to December 2016, 101 consecutive patients underwent TEVAR using fenestrated stent grafts for distal aortic arch aneurysms at a single centre. Technical success, complications, freedom from aneurysm-related death, secondary intervention and aneurysm progression were retrospectively investigated.

RESULTS

All the patients underwent TEVAR using fenestrated stent grafts. The 30-day mortality rate was zero. Cerebral infarction, access route problems and spinal cord injury occurred in 4, 3 and 2 patients, respectively. Each type of endoleak was observed in 38 of the 101 patients during the course of the study; 20/38 patients had minor type 1 endoleaks at the time of discharge. The endoleak disappeared in 2 patients and showed no significant change in 8 patients; however, the aneurysm expanded over time in 10 patients. Additional treatment was performed in 8 of the 10 patients with type 1 endoleaks and dilatation of the aneurysm. The rate of freedom from aneurysm-related death during the observation period was 98%.

CONCLUSIONS

TEVAR with FSG is a simple procedure, with few complications. Additional treatment has been observed to reduce aneurysm-related deaths, even in patients with endoleaks and enlarged aneurysms. Based on this study, the outcomes of endovascular repair of aortic arch aneurysms using a fenestrated stent graft seem acceptable.
Major improvement in thyroid cancer survival of elderly patients in the Nordic countries
Authors: Zitrický František , Koskinen Anni , Liska Vaclav , Försti Asta , Hemminki Akseli , Hemminki Kari
Published: March 2024

Objectives

We describe age-specific survival in thyroid cancer (TC) from Denmark, Finland, Norway, and Sweden over a 50-year period.

Design

Population-based survival study.

Methods

Relative 5-year survival data were obtained from the NORDCAN database for the years 1972-2021.

Results

In the first period 1972-1976, 5-year survival in TC in Finland, Norway, and Sweden was 90% or higher, but a strong negative step-wise age gradient was observed, which was worse for men than women. Over time, survival increased, and in the final period, 2017-2021, survival for all women and Danish men up to age 69 years was about 90% or higher and, for men from the other countries, only marginally lower. Even for older women survival reached 80%, for older men somewhat less.

Conclusions

Age disadvantage in TC survival was for the most part corrected over the 50-year period, and the remaining task is to boost survival for the oldest patients.
Arm and ankle blood pressure indices, and peripheral artery disease, and mortality: a cohort study
Authors: Mohammedi Kamel , Pigeyre Marie , Bosch Jackie , Yusuf Salim , Gerstein Hertzel C
Published: March 2024

Background and Aims

Few studies have compared arm and ankle blood pressures (BPs) with regard to peripheral artery disease (PAD) and mortality. These relationships were assessed using data from three large prospective clinical trials.

Methods

Baseline BP indices included arm systolic BP (SBP), diastolic BP (DBP), pulse pressure (arm SBP minus DBP), ankle SBP, ankle–brachial index (ABI, ankle SBP divided by arm SBP), and ankle–pulse pressure difference (APPD, ankle SBP minus arm pulse pressure). These measurements were categorized into four groups using quartiles. The outcomes were PAD (the first occurrence of either peripheral revascularization or lower-limb amputation for vascular disease), the composite of PAD or death, and all-cause death.

Results

Among 40 747 participants without baseline PAD (age 65.6 years, men 68.3%, diabetes 50.2%) from 53 countries, 1071 (2.6%) developed PAD, and 4955 (12.2%) died during 5 years of follow-up. Incident PAD progressively rose with higher arm BP indices and fell with ankle BP indices. The strongest relationships were noted for ankle BP indices. Compared with people whose ankle BP indices were in the highest fourth, adjusted hazard ratios (95% confidence interval) for each lower fourth were 1.64 (1.31–2.04), 2.59 (2.10–3.20), and 4.23 (3.44–5.21) for ankle SBP; 1.19 (0.95–1.50), 1.66 (1.34–2.05), and 3.34 (2.75–4.06) for ABI; and 1.41 (1.11–1.78), 2.04 (1.64–2.54), and 3.63 (2.96–4.45) for APPD. Similar patterns were observed for mortality. Ankle BP indices provided the highest c-statistics and classification indices in predicting future PAD beyond established risk factors.

Conclusions

Ankle BP indices including the ankle SBP and the APPD best predicted PAD and mortality.
Employment outcomes of people with Long Covid symptoms: community-based cohort study
Authors: Ayoubkhani Daniel , Zaccardi Francesco , Pouwels Koen B , Walker A Sarah , Houston Donald , Alwan Nisreen A , Martin Josh , Khunti Kamlesh , Nafilyan Vahé
Published: March 2024

Background

Evidence on the long-term employment consequences of SARS-CoV-2 infection is lacking. We used data from a large, community-based sample in the UK to estimate associations between Long Covid and employment outcomes.

Methods

This was an observational, longitudinal study using a pre–post design. We included survey participants from 3 February 2021 to 30 September 2022 when they were aged 16–64 years and not in education. Using conditional logit modelling, we explored the time-varying relationship between Long Covid status ≥12 weeks after a first test-confirmed SARS-CoV-2 infection (reference: pre-infection) and labour market inactivity (neither working nor looking for work) or workplace absence lasting ≥4 weeks.

Results

Of 206 299 participants (mean age 45 years, 54% female, 92% white), 15% were ever labour market inactive and 10% were ever long-term absent during follow-up. Compared with pre-infection, inactivity was higher in participants reporting Long Covid 30 to <40 weeks [adjusted odds ratio (aOR): 1.45; 95% CI: 1.17–1.81] or 40 to <52 weeks (aOR: 1.34; 95% CI: 1.05–1.72) post-infection. Combining with official statistics on Long Covid prevalence, and assuming a correct statistical model, our estimates translate to 27 000 (95% CI: 6000–47 000) working-age adults in the UK being inactive because of Long Covid in July 2022.

Conclusions

Long Covid is likely to have contributed to reduced participation in the UK labour market, though it is unlikely to be the sole driver. Further research is required to quantify the contribution of other factors, such as indirect health effects of the pandemic.
Building conceptual and methodological bridges between SSE’s diversity, equity, and inclusion statement and educational actions in evolutionary biology
Authors: Sbeglia Gena C , Nehm Ross H
Published: March 2024

The field of evolutionary biology must bridge the gap between its diversity, equity, and inclusion (DEI) commitments and data-driven educational actions in the nation’s undergraduate classrooms and degree programs. In this article, we discuss the urgent need for the adoption of equity frameworks and why they are centrally important to data-driven DEI efforts in evolutionary biology. We describe why equity indicators (e.g., measures) must be anchored in and aligned with equity frameworks. We introduce a specific equity framework for learning (the enhanced educational debt framework) and illustrate how it may be leveraged to document, interpret, and improve outcomes in evolutionary biology. We apply the equity framework and associated indicators to >3,500 students’ first college-level experience with evolutionary biology at a public, 4-year institution in the Northeastern United States to demonstrate how these conceptual tools and empirical perspectives may be used by faculty, departments, and degree programs to better understand their roles in mitigating or perpetuating inequities. We end by discussing how this framework may be applied to a range of evolution concepts and courses in the educational hierarchy and used to help evolutionary biologists better understand the extent to which a core aspect of SSE’s diversity statement is being realized.
Effects of integrated care with case management and nutritional counselling for frail older adults with nutritional risk in the primary care setting
Authors: Hsiao Mei-Lan , Su Chen-Ying , Loh Ching-Hui , Kao Sheng-Lun
Published: March 2024

Background

The effects of integrated care with case management and nutritional counselling for frail patients with nutritional risk are unclear.

Objectives

To assess the impact of the integrated care model for frail patients with nutritional risk in the primary care setting.

Methods

This was a retrospective observational study. We enrolled 100 prefrail or frail patients according to Clinical Frailty Scale (CFS) aged ≥ 60 years with nutritional risk from the geriatric clinic. We implemented the frailty intervention model, including integrated care with comprehensive geriatric assessments (CGA), case management, and nutritional counselling by the dietitian. We obtained measures of CGA components, physical performance, body mass index (BMI), and daily caloric intake before and after the 2-month care program. We used the Wilcoxon signed-rank test to analyse differences after the care program and applied multiple linear regression to determine the predictive factors for CFS improvement.

Results

Among the 100 patients (mean age, 75.0 ± 7.2 years; females, 71.0%; frail patients, 26%), 93% improved their CFS status, and 91% achieved > 80% of recommended daily caloric intake after the care program. The Mini Nutritional Assessment Short-Form significantly improved after the program. BMI and daily caloric intake increased significantly after nutritional counselling. The post-test short physical performance battery (SPPB) significantly increased with a faster 4 m gait speed. Baseline poor CFS was a significant predictor for CFS improvement.

Conclusions

Integrated care with case management and nutritional counselling for prefrail and frail patients with nutritional risk in the primary care setting may improve physical performance and nutritional status.
Genetic variation for sexual dimorphism in developmental traits in Drosophila melanogaster
Authors: Li Tianyu , Zhang Rebecca S , True John R
Published: March 2024

Sexual dimorphism in traits of insects during the developmental stages could potentially be the direct or indirect result of sex-specific selection provided that genetic variation for sexual dimorphism is present. We investigated genetic variation in sexual dimorphism in a set of Drosophila melanogaster inbred lines for 2 traits: egg to adult development time and pupation site preference. We observed considerable genetic variation in sexual dimorphism among lines in both traits. The sexual dimorphic patterns remained relatively consistent across multiple trials, despite both traits being sensitive to environmental conditions. Additionally, we measured 2 sexually dimorphic adult morphological traits in 6 sampled lines and investigated correlations in the sexual dimorphism patterns with the 2 developmental traits. The abundance of genetic variation in sexual dimorphism for D. melanogaster developmental traits demonstrated in this study provides evidence for a high degree of evolvability of sex differences in preadult traits in natural populations.
Investigating genomic prediction strategies for grain carotenoid traits in a tropical/subtropical maize panel
Authors: LaPorte Mary-Francis , Suwarno Willy Bayuardi , Hannok Pattama , Koide Akiyoshi , Bradbury Peter , Crossa José , Palacios-Rojas Natalia , Diepenbrock Christine Helen
Published: March 2024

Vitamin A deficiency remains prevalent on a global scale, including in regions where maize constitutes a high percentage of human diets. One solution for alleviating this deficiency has been to increase grain concentrations of provitamin A carotenoids in maize (Zea mays ssp. mays L.)—an example of biofortification. The International Maize and Wheat Improvement Center (CIMMYT) developed a Carotenoid Association Mapping panel of 380 inbred lines adapted to tropical and subtropical environments that have varying grain concentrations of provitamin A and other health-beneficial carotenoids. Several major genes have been identified for these traits, 2 of which have particularly been leveraged in marker-assisted selection. This project assesses the predictive ability of several genomic prediction strategies for maize grain carotenoid traits within and between 4 environments in Mexico. Ridge Regression-Best Linear Unbiased Prediction, Elastic Net, and Reproducing Kernel Hilbert Spaces had high predictive abilities for all tested traits (β-carotene, β-cryptoxanthin, provitamin A, lutein, and zeaxanthin) and outperformed Least Absolute Shrinkage and Selection Operator. Furthermore, predictive abilities were higher when using genome-wide markers rather than only the markers proximal to 2 or 13 genes. These findings suggest that genomic prediction models using genome-wide markers (and assuming equal variance of marker effects) are worthwhile for these traits even though key genes have already been identified, especially if breeding for additional grain carotenoid traits alongside β-carotene. Predictive ability was maintained for all traits except lutein in between-environment prediction. The TASSEL (Trait Analysis by aSSociation, Evolution, and Linkage) Genomic Selection plugin performed as well as other more computationally intensive methods for within-environment prediction. The findings observed herein indicate the utility of genomic prediction methods for these traits and could inform their resource-efficient implementation in biofortification breeding programs.
COP9 signalosome component CSN-5 stabilizes PUF proteins FBF-1 and FBF-2 in Caenorhabditis elegans germline stem and progenitor cells
Authors: Osterli Emily , Ellenbecker Mary , Wang Xiaobo , Terzo Mikaya , Jacobson Ketch , Cuello DeAnna , Voronina Ekaterina
Published: March 2024

RNA-binding proteins FBF-1 and FBF-2 (FBFs) are required for germline stem cell maintenance and the sperm/oocyte switch in Caenorhabditis elegans, although the mechanisms controlling FBF protein levels remain unknown. We identified an interaction between both FBFs and CSN-5), a component of the constitutive photomorphogenesis 9 (COP9) signalosome best known for its role in regulating protein degradation. Here, we find that the Mpr1/Pad1 N-terminal metalloprotease domain of CSN-5 interacts with the Pumilio and FBF RNA-binding domain of FBFs and the interaction is conserved for human homologs CSN5 and PUM1. The interaction between FBF-2 and CSN-5 can be detected in vivo by proximity ligation. csn-5 mutation results in the destabilization of FBF proteins, which may explain previously observed decrease in the numbers of germline stem and progenitor cells, and disruption of oogenesis. The loss of csn-5 does not decrease the levels of a related PUF protein PUF-3, and csn-5(lf) phenotype is not enhanced by fbf-1/2 knockdown, suggesting that the effect is specific to FBFs. The effect of csn-5 on oogenesis is largely independent of the COP9 signalosome and is cell autonomous. Surprisingly, the regulation of FBF protein levels involves a combination of COP9-dependent and COP9-independent mechanisms differentially affecting FBF-1 and FBF-2. This work supports a previously unappreciated role for CSN-5 in the stabilization of germline stem cell regulatory proteins FBF-1 and FBF-2.
Analysing the impact of SWOT observation errors on marine gravity recovery
Authors: Sun Mingzhi , Feng Wei , Yu Daocheng , Chen Xiaodong , Liang Weixuan , Zhong Min
Published: March 2024

The wide-swath altimeter satellite Surface Water and Ocean Topography (SWOT) will provide high spatiotemporal resolution sea surface heights (SSHs), which is crucial for studying the impact of observation errors on marine gravity recovery. This study uses simulated SWOT data to derive deflection of the vertical (DOV) and gravity anomalies in the northern South China Sea. We quantified the impact of SWOT errors on DOV and gravity anomalies, and analysed the contributions from different directions of geoid gradient. The results show that the geoid gradient in the cross-track direction significantly improves gravity field recovery by enhancing the precision of east component of DOV. For one-cycle SWOT observations, phase errors emerge as the most impactful error affecting both DOV and gravity anomalies, followed by random errors. 2-D Gaussian filtering and the tilt correction proposed in this study could effectively mitigate their impact. Using the corrected data for DOV computation, the precision in the east and north components improves by 75.32 and 46.80 per cent, respectively, while enhancing the accuracy of the gravity field by 70.23 per cent. For 17-cycle data, phase errors and random errors remain the predominant factors affecting DOV and gravity anomalies, but their impact diminishes with an increase in SWOT observations. Our results indicate that marine gravity accuracy improves by approximately 70 per cent compared to a single cycle. Whether for single-cycle or multicycle data, the impact of phase errors is roughly twice that of random errors. These data processing strategies can serve as valuable references for wide-swath altimeter data processing, aiming to advance the precision and resolution of marine gravity field recovery.
BLUPmrMLM: A Fast mrMLM Algorithm in Genome-wide Association Studies
Authors: Li Hong-Fu , Wang Jing-Tian , Zhao Qiong , Zhang Yuan-Ming
Published: March 2024

Multilocus genome-wide association study has become the state-of-the-art tool for dissecting the genetic architecture of complex and multiomic traits. However, most existing multilocus methods require relatively long computational time when analyzing large datasets. To address this issue, in this study, we proposed a fast mrMLM method, namely, best linear unbiased prediction multilocus random-SNP-effect mixed linear model (BLUPmrMLM). First, genome-wide single-marker scanning in mrMLM was replaced by vectorized Wald tests based on the best linear unbiased prediction (BLUP) values of marker effects and their variances in BLUPmrMLM. Then, adaptive best subset selection (ABESS) was used to identify potentially associated markers on each chromosome to reduce computational time when estimating marker effects via empirical Bayes. Finally, shared memory and parallel computing schemes were used to reduce the computational time. In simulation studies, BLUPmrMLM outperformed GEMMA, EMMAX, mrMLM, and FarmCPU as well as the control method (BLUPmrMLM with ABESS removed), in terms of computational time, power, accuracy for estimating quantitative trait nucleotide positions and effects, false positive rate, false discovery rate, false negative rate, and F1 score. In the reanalysis of two large rice datasets, BLUPmrMLM significantly reduced the computational time and identified more previously reported genes, compared with the aforementioned methods. This study provides an excellent multilocus model method for the analysis of large-scale and multiomic datasets. The software mrMLM v5.1 is available at BioCode (https://ngdc.cncb.ac.cn/biocode/tool/BT007388) or GitHub (https://github.com/YuanmingZhang65/mrMLM).
Risk of Infection in Patients With Inflammatory Bowel Disease Treated With Interleukin-Targeting Agents: A Systematic Review and Meta-Analysis
Authors: Ouranos Konstantinos , Saleem Hira , Vassilopoulos Stephanos , Vassilopoulos Athanasios , Mylona Evangelia K , Shehadeh Fadi , Kalligeros Markos , Abraham Bincy P , Mylonakis Eleftherios
Published: March 2024

Background

Patients with inflammatory bowel disease (IBD) are at increased risk of infection. The aim of this study was to assess the cumulative incidence and risk of infection in patients with IBD treated with interleukin (IL)-targeting agents.

Methods

We searched PubMed, EMBASE, and Web of Science for randomized controlled trials including patients with IBD receiving IL-targeting agents compared with patients receiving placebo or treatment that only differed from the intervention arm in the absence of an IL-targeting agent. The primary outcome of interest was the relative risk (RR) of any-grade and severe infection during the induction phase.

Results

There was no difference in risk of any-grade (RR, 0.98; 95% confidence interval [CI], 0.89-1.09) or severe (RR, 0.64; 95% CI, 0.38-1.10) infection in patients receiving any IL-targeting agent compared with the control group. During the maintenance period, the cumulative incidence of any-grade infection in patients receiving IL-12/23p40–targeting agents (mean follow-up 29 weeks) was 34.82% (95% CI, 26.78%-43.32%), while the cumulative incidence of severe infection was 3.07% (95% CI, 0.93%-6.21%). The cumulative incidence of any-grade infection in patients receiving IL-23p19–targeting agents (mean follow-up 40.9 weeks) was 32.16% (95% CI, 20.63%-44.88%), while the cumulative incidence of severe infection was 1.75% (95% CI, 0.60%-3.36%). During the maintenance phase of the included studies, the incidence of infection was 30.66% (95% CI, 22.12%-39.90%) for any-grade and 1.59% (95% CI, 0.76%-2.63%) for severe infection in patients in the control group.

Conclusions

There was no difference in risk of infection between patients with IBD who received IL-targeting agents compared with the control group. Case registries and randomized controlled trials reporting the safety of IL inhibitors should provide detailed information about the risk of specific infectious complications in patients with IBD receiving IL-targeting agents.
Comprehensive analysis and optimization of a low-carbon multi-generation system driven by municipal solid waste and solar thermal energy integrated with a microbial fuel cell
Authors: Wang Hanning , Song Mingxiao , Taghavi Mohammad
Published: March 2024

In this article, a novel multi-generation plant is addressed and assessed from the energy, exergy, exergoenvironmental and exergoeconomic points of view. The multi-generation plant is composed of two main units: one unit for energy production and another unit for carbon capture and methanol synthesis. Biomass fuel, solar energy and seawater are the main nutrients in the plant. Steam, Brayton, organic Rankine and Kalina cycles have been employed to generate electricity. A linear Fresnel collector-driven solar farm is considered as an auxiliary heat source. In addition, an integrated desalination unit based on a multi-effect desalination unit, a microbial fuel cell and a reverse osmosis unit has been installed in the multi-generation plant. The proposed structure for the offered multi-generation plant is designed under a new configuration and layout that had not been reported in the publications. From the outcomes, the multi-generation plant can produce 69.6 MW of net electricity, 0.53 kg/s of methanol, 0.81 kg/s of oxygen gas, 73.8 kg/s of fresh water and ~0.015 kg/s of hydrogen gas. Under such performance, the offered multi-generation plant can be 51.72 and 27.5% efficient from the points of view of energy and exergy, respectively. Further, the total cost rate and environmental impact of the plant are ~3378 US$/h and 294.1 mPts/s, respectively. A comparative analysis is developed to exhibit the superiority of the planned multi-generation plant. A five-objective optimization is also developed to achieve the optimum design data and outcomes of the plant.
Assessment of renewable energy hosting capacity in distribution networks considering demand-side management and network reconfiguration
Authors: Ye Gaoxiang , Yang Jie , Xia Fangzhou , Shao Feifan , Xu Jingyou , Chen Ke , Tang Jing , Zhou Yujie
Published: March 2024

A renewable energy carrying capacity assessment method for distribution grids considering demand-side management (DSM) and network reconfiguration (NR) was proposed. First, a DSM and NR model applicable to the renewable energy carrying capacity (NECC) assessment of the distribution network (DN) was established; second, an NECC evaluation model for DN considering DSM and NR was established with the aim of maximizing the access capacity of distributed new energies; second, the second-order conical relaxation method was applied to convex solve the model; third, the simulation example adopts an improved IEEE 33-node DN to evaluate the NECC of system with various scenarios. Finally, the simulation experiment based on improved IEEE 33-node DN was conducted to assess the distributed NECC of the system in some scenarios.
Unrecognizing Refugees: The Inadmissibility Scheme Replacing Article 1F Decisions in Canada
Authors: Doğar Didem
Published: March 2024

This article examines the interwoven relationship between article 1F (the exclusion provision) of the 1951 Refugee Convention and the inadmissibility scheme based on the grounds of security, violation of human or international rights, serious criminality, or organized criminality (SHSO) in Canada. Incorporating evidence from a literature review, case law, statistics, and interviews conducted with practitioners in Canada, this research demonstrates that Canada deliberately chooses to review the cases of refugee claimants about whom there are serious reasons to consider that they have committed grave crimes under the inadmissibility scheme rather than under article 1F. Accordingly, the article argues that the exclusion provision in Canada, through practice and with an intentional design, has turned into the inadmissibility proceeding. This shift from the exclusion provision to the inadmissibility scheme is problematic since using the broader SHSO grounds instead of article 1F violates Canada’s international obligations under the Refugee Convention.
Could Less Be More? Accounting for Fractional-Dose Regimens and Different Number of Vaccine Doses When Measuring the Impact of the RTS,S/AS01E Malaria Vaccine
Authors: Westercamp Nelli , Osei-Tutu Lawrence , Schuerman Lode , Kariuki Simon K , Bollaerts Anne , Lee Cynthia K , Samuels Aaron M , Ockenhouse Christian , Bii Dennis K , Adjei Samuel , Oneko Martina , Lievens Marc , Attobrah Sarfo Maame Anima , Atieno Cecilia , Bakari Ashura , Sang Tony , Kotoh-Mortty Maame Fremah , Otieno Kephas , Roman François , Buabeng Patrick Boakye Yiadom , Ntiamoah Yaw , Ansong Daniel , Agbenyega Tsiri , Ofori-Anyinam Opokua
Published: March 2024

Background

The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya.

Methods

In total, 1500 children aged 5–17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine. RTS,S groups received 2 full RTS,S doses at months 0 and 1 and either full (groups R012-20, R012-14-26) or fractional doses (one-fifth; groups Fx012-14-26, Fx017-20-32).

Results

At month 32 post-dose 1, vaccine efficacy against clinical malaria (all episodes) ranged from 38% (R012-20; 95% confidence interval [CI]: 24%–49%) to 53% (R012-14-26; 95% CI: 42%–62%). Vaccine impact (cumulative number of cases averted/1000 children vaccinated) was 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), and 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional vs full dose; post hoc analysis), we estimated cases averted/1000 RTS,S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), and 880 (Fx017-20-32).

Conclusions

Vaccine efficacy was similar across RTS,S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If maintained through trial end, these observations underscore the means to reduce cost per regimen thus maximizing impact and optimizing supply.

Clinical Trials Registration

NCT03276962 (ClinicalTrials.gov).
Potential for functional divergence in ectomycorrhizal fungal communities across a precipitation gradient
Authors: Pellitier Peter T , Van Nuland Michael , Salamov Asaf , Grigoriev Igor V , Peay Kabir G
Published: March 2024

Functional traits influence the assembly of microbial communities, but identifying these traits in the environment has remained challenging. We studied ectomycorrhizal fungal (EMF) communities inhabiting Populus trichocarpa roots distributed across a precipitation gradient in the Pacific Northwest, USA. We profiled these communities using taxonomic (meta-barcoding) and functional (metagenomic) approaches. We hypothesized that genes involved in fungal drought-stress tolerance and fungal mediated plant water uptake would be most abundant in drier soils. We were unable to detect support for this hypothesis; instead, the abundance of genes involved in melanin synthesis, hydrophobins, aquaporins, trehalose-synthases, and other gene families exhibited no significant shifts across the gradient. Finally, we studied variation in sequence homology for certain genes, finding that fungal communities in dry soils are composed of distinct aquaporin and hydrophobin gene sequences. Altogether, our results suggest that while EMF communities exhibit significant compositional shifts across this gradient, coupled functional turnover, at least as inferred using community metagenomics is limited. Accordingly, the consequences of these distinct EMF communities on plant water uptake remain critically unknown, and future studies targeting the expression of genes involved in drought stress tolerance are required.
Chromatin accessibility profiling reveals that human fibroblasts respond to mechanical stimulation in a cell-specific manner
Authors: Logan Niall J , Broda Krystyna L , Pantelireis Nikolaos , Williams Greg , Higgins Claire A
Published: March 2024

Fibroblasts in the skin are highly heterogeneous, both in vivo and in vitro. One difference between follicular (dermal papilla fibroblasts [DP]) and interfollicular fibroblasts (papillary fibroblasts [PFi]) in vitro is their ability to differentiate in response to osteogenic media (OM), or mechanical stimulation. Here, we asked whether differences in the ability of DP and PFi to respond to differentiation stimuli are due to differences in chromatin accessibility. We performed chromatin accessibility and transcriptional profiling of DP and PFi in human skin, which arise from a common progenitor during development, yet display distinct characteristics in adult tissue and in vitro. We found that cells cultured in growth media had unique chromatin accessibility profiles; however, these profiles control similar functional networks. Upon introduction of a chemical perturbation (OM) to promote differentiation, we observed a divergence not only in the accessible chromatin signatures but also in the functional networks controlled by these signatures. The biggest divergence between DP and PFi was observed when we applied 2 perturbations to cells: growth in OM and mechanical stimulation (a shock wave [OMSW]). DP readily differentiate into bone in OMSW conditions, while PFi lack differentiation capability in vitro. In the DP we found a number of uniquely accessible promoters that controlled osteogenic interaction networks associated with bone and differentiation functions. Using ATAC-seq and RNA-seq we found that the combination of 2 stimuli (OMSW) could result in significant changes in chromatin accessibility associated with osteogenic differentiation, but only within the DP (capable of osteogenic differentiation). De novo motif analysis identified enrichment of motifs bound by the TEA domain (TEAD) family of transcription factors, and inter-cell comparisons (UpSet analysis) displayed large groups of genes to be unique to single cell types and conditions. Our results suggest that these 2 stimuli (OMSW) elicit cell-specific responses by modifying chromatin accessibility of osteogenic-related gene promoters.
A homozygous SP7/OSX mutation causes osteogenesis and dentinogenesis imperfecta with craniofacial anomalies
Authors: Al-Mutairi Dalal A , Jarragh Ali A , Alsabah Basel H , Wein Marc N , Mohammed Wasif , Alkharafi Lateefa
Published: March 2024

Osteogenesis imperfecta (OI) is a heterogeneous spectrum of hereditary genetic disorders that cause bone fragility, through various quantitative and qualitative defects of type 1 collagen, a triple helix composed of two α1 and one α2 chains encoded by COL1A1 and COL1A2, respectively. The main extra–skeletal manifestations of OI include blue sclerae, opalescent teeth, and hearing impairment. Moreover, multiple genes involved in osteoblast maturation and type 1 collagen biosynthesis are now known to cause recessive forms of OI. In this study a multiplex consanguineous family of two affected males with OI was recruited for genetic screening. To determine the causative, pathogenic variant(s), genomic DNA from two affected family members were analyzed using whole exome sequencing, autozygosity mapping, and then validated with Sanger sequencing. The analysis led to the mapping of a homozygous variant previously reported in SP7/OSX, a gene encoding for Osterix, a transcription factor that activates a repertoire of genes involved in osteoblast and osteocyte differentiation and function. The identified variant (c.946C > T; p.Arg316Cys) in exon 2 of SP7/OSX results in a pathogenic amino acid change in two affected male siblings and develops OI, dentinogenesis imperfecta, and craniofacial anomaly. On the basis of the findings of the present study, SP7/OSX:c. 946C > T is a rare homozygous variant causing OI with extra–skeletal features in inbred Arab populations.