bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue-location-specific transcription programs drive tumor dependencies in colon cancer
Authors: Yang Lijing , Tu Lei , Bisht Shilpa , Mao Yiqing , Petkovich Daniel , Thursby Sara-Jayne , Liang Jinxiao , Patel Nibedita , Yen Ray-Whay Chiu , Largent Tina , Zahnow Cynthia , Brock Malcolm , Gabrielson Kathy , Salimian Kevan J. , Baylin Stephen B. , Easwaran Hariharan
Published: February 2024

Cancers of the same tissue-type but in anatomically distinct locations exhibit different molecular dependencies for tumorigenesis. Proximal and distal colon cancers exemplify such characteristics, with BRAFV600E predominantly occurring in proximal colon cancers along with increased DNA methylation phenotype. Using mouse colon organoids, here we show that proximal and distal colon stem cells have distinct transcriptional programs that regulate stemness and differentiation. We identify that the homeobox transcription factor, CDX2, which is silenced by DNA methylation in proximal colon cancers, is a key mediator of the differential transcriptional programs. Cdx2-mediated proximal colon-specific transcriptional program concurrently is tumor suppressive, and Cdx2 loss sufficiently creates permissive state for BRAFV600E-driven transformation. Human proximal colon cancers with CDX2 downregulation showed similar transcriptional program as in mouse proximal organoids with Cdx2 loss. Developmental transcription factors, such as CDX2, are thus critical in maintaining tissue-location specific transcriptional programs that create tissue-type origin specific dependencies for tumor development.
PheWAS-based clustering of Mendelian Randomisation instruments reveals distinct mechanism-specific causal effects between obesity and educational attainment
Authors: Darrous Liza , Hemani Gibran , Davey Smith George , Kutalik Zoltán
Published: February 2024

Mendelian Randomisation (MR) estimates causal effects between risk factors and complex outcomes using genetic instruments. Pleiotropy, heritable confounders, and heterogeneous causal effects violate MR assumptions and can lead to biases. To alleviate these, we propose an approach employing a Phenome-Wide association Clustering of the MR instruments (PWC-MR) and apply this method to revisit the surprisingly large apparent causal effect of body mass index (BMI) on educational attainment (EDU): $$\widehat{\alpha }$$

α

̂

= −0.19 [−0.22, −0.16]. First, we cluster 324 BMI-associated genetic instruments based on their association with 407 traits in the UK Biobank, which yields six distinct groups. Subsequent cluster-specific MR reveals heterogeneous causal effect estimates on EDU. A cluster enriched for socio-economic indicators yields the largest BMI-on-EDU causal effect estimate ($$\widehat{\alpha }$$

α

̂

= −0.49 [−0.56, −0.42]) whereas a cluster enriched for body-mass specific traits provides a more likely estimate ($$\widehat{\alpha }$$

α

̂

= −0.09 [−0.13, −0.05]). Follow-up analyses confirms these findings: within-sibling MR ($$\widehat{\alpha }$$

α

̂

= −0.05 [−0.09, −0.01]); MR for childhood BMI on EDU ($$\widehat{\alpha }$$

α

̂

= −0.03 [−0.06, −0.002]); step-wise multivariable MR ($$\widehat{\alpha }$$

α

̂

= −0.05 [−0.07, −0.02]) where socio-economic indicators are jointly modelled. Here we show how the in-depth examination of the BMI-EDU causal relationship demonstrates the utility of our PWC-MR approach in revealing distinct pleiotropic pathways and confounder mechanisms.
Computational redesign of a hydrolase for nearly complete PET depolymerization at industrially relevant high-solids loading
Authors: Cui Yinglu , Chen Yanchun , Sun Jinyuan , Zhu Tong , Pang Hua , Li Chunli , Geng Wen-Chao , Wu Bian
Published: February 2024

Biotechnological plastic recycling has emerged as a suitable option for addressing the pollution crisis. A major breakthrough in the biodegradation of poly(ethylene terephthalate) (PET) is achieved by using a LCC variant, which permits 90% conversion at an industrial level. Despite the achievements, its applications have been hampered by the remaining 10% of nonbiodegradable PET. Herein, we address current challenges by employing a computational strategy to engineer a hydrolase from the bacterium HR29. The redesigned variant, TurboPETase, outperforms other well-known PET hydrolases. Nearly complete depolymerization is accomplished in 8 h at a solids loading of 200 g kg−1. Kinetic and structural analysis suggest that the improved performance may be attributed to a more flexible PET-binding groove that facilitates the targeting of more specific attack sites. Collectively, our results constitute a significant advance in understanding and engineering of industrially applicable polyester hydrolases, and provide guidance for further efforts on other polymer types.
Trabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes
Authors: Son Kook , Takhaveev Vakil , Mor Visesato , Yu Hobin , Dillier Emma , Zilio Nicola , Püllen Nikolai J. L. , Ivanov Dmitri , Ulrich Helle D. , Sturla Shana J. , Schärer Orlando D.
Published: February 2024

Most genotoxic anticancer agents fail in tumors with intact DNA repair. Therefore, trabectedin, anagent more toxic to cells with active DNA repair, specifically transcription-coupled nucleotide excision repair (TC-NER), provides therapeutic opportunities. To unlock the potential of trabectedin and inform its application in precision oncology, an understanding of the mechanism of the drug’s TC-NER-dependent toxicity is needed. Here, we determine that abortive TC-NER of trabectedin-DNA adducts forms persistent single-strand breaks (SSBs) as the adducts block the second of the two sequential NER incisions. We map the 3’-hydroxyl groups of SSBs originating from the first NER incision at trabectedin lesions, recording TC-NER on a genome-wide scale. Trabectedin-induced SSBs primarily occur in transcribed strands of active genes and peak near transcription start sites. Frequent SSBs are also found outside gene bodies, connecting TC-NER to divergent transcription from promoters. This work advances the use of trabectedin for precision oncology and for studying TC-NER and transcription.
The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation
Authors: Nelson Christopher B. , Rogers Samuel , Roychoudhury Kaushik , Tan Yaw Sing , Atkinson Caroline J. , Sobinoff Alexander P. , Tomlinson Christopher G. , Hsu Anton , Lu Robert , Dray Eloise , Haber Michelle , Fletcher Jamie I. , Cesare Anthony J. , Hegde Rashmi S. , Pickett Hilda A.
Published: February 2024

The Eyes Absent proteins (EYA1-4) are a biochemically unique group of tyrosine phosphatases known to be tumour-promoting across a range of cancer types. To date, the targets of EYA phosphatase activity remain largely uncharacterised. Here, we identify Polo-like kinase 1 (PLK1) as an interactor and phosphatase substrate of EYA4 and EYA1, with pY445 on PLK1 being the primary target site. Dephosphorylation of pY445 in the G2 phase of the cell cycle is required for centrosome maturation, PLK1 localization to centrosomes, and polo-box domain (PBD) dependent interactions between PLK1 and PLK1-activation complexes. Molecular dynamics simulations support the rationale that pY445 confers a structural impairment to PBD-substrate interactions that is relieved by EYA-mediated dephosphorylation. Depletion of EYA4 or EYA1, or chemical inhibition of EYA phosphatase activity, dramatically reduces PLK1 activation, causing mitotic defects and cell death. Overall, we have characterized a phosphotyrosine signalling network governing PLK1 and mitosis.
High-spin Co3+ in cobalt oxyhydroxide for efficient water oxidation
Authors: Zhang Xin , Zhong Haoyin , Zhang Qi , Zhang Qihan , Wu Chao , Yu Junchen , Ma Yifan , An Hang , Wang Hao , Zou Yiming , Diao Caozheng , Chen Jingsheng , Yu Zhi Gen , Xi Shibo , Wang Xiaopeng , Xue Junmin
Published: February 2024

Cobalt oxyhydroxide (CoOOH) is a promising catalytic material for oxygen evolution reaction (OER). In the traditional CoOOH structure, Co3+ exhibits a low-spin state configuration ($${t}_{2{{{{{\rm{g}}}}}}}^{6}{e}_{{{{{{\rm{g}}}}}}}^{0}$$

t

2
g

6

e

g

0

), with electron transfer occurring in face-to-face $${t}_{2{{{{{\rm{g}}}}}}}^{*}$$

t

2
g

*

orbitals. In this work, we report the successful synthesis of high-spin state Co3+ CoOOH structure, by introducing coordinatively unsaturated Co atoms. As compared to the low-spin state CoOOH, electron transfer in the high-spin state CoOOH occurs in apex-to-apex $${e}_{{{{{{\rm{g}}}}}}}^{*}$$

e

g

*

orbitals, which exhibits faster electron transfer ability. As a result, the high-spin state CoOOH performs superior OER activity with an overpotential of 226 mV at 10 mA cm−2, which is 148 mV lower than that of the low-spin state CoOOH. This work emphasizes the effect of the spin state of Co3+ on OER activity of CoOOH based electrocatalysts for water splitting, and thus provides a new strategy for designing highly efficient electrocatalysts.
Electrocatalytic water oxidation with manganese phosphates
Authors: Yang Shujiao , Yue Kaihang , Liu Xiaohan , Li Sisi , Zheng Haoquan , Yan Ya , Cao Rui , Zhang Wei
Published: February 2024

As inspired by the Mn4CaO5 oxygen evolution center in nature, Mn-based electrocatalysts have received overwhelming attention for water oxidation. However, the understanding of the detailed reaction mechanism has been a long-standing problem. Herein, homologous KMnPO4 and KMnPO4•H2O with 4-coordinated and 6-coordinated Mn centers, respectively, are prepared. The two catalysts constitute an ideal platform to study the structure-performance correlation. The presence of Mn(III), Mn(IV), and Mn(V) intermediate species are identified during water oxidation. The Mn(V)=O species is demonstrated to be the substance for O−O bond formation. In KMnPO4•H2O, the Mn coordination structure did not change significantly during water oxidation. In KMnPO4, the Mn coordination structure changed from 4-coordinated [MnO4] to 5-coordinated [MnO5] motif, which displays a triangular biconical configuration. The structure flexibility of [MnO5] is thermodynamically favored in retaining Mn(III)−OH and generating Mn(V)=O. The Mn(V)=O species is at equilibrium with Mn(IV)=O, the concentration of which determines the intrinsic activity of water oxidation. This study provides a clear picture of water oxidation mechanism on Mn-based systems.
Adipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape
Authors: Reinisch Isabel , Michenthaler Helene , Sulaj Alba , Moyschewitz Elisabeth , Krstic Jelena , Galhuber Markus , Xu Ruonan , Riahi Zina , Wang Tongtong , Vujic Nemanja , Amor Melina , Zenezini Chiozzi Riccardo , Wabitsch Martin , Kolb Dagmar , Georgiadi Anastasia , Glawitsch Lisa , Heitzer Ellen , Schulz Tim J. , Schupp Michael , Sun Wenfei , Dong Hua , Ghosh Adhideb , Hoffmann Anne , Kratky Dagmar , Hinte Laura C. , von Meyenn Ferdinand , Heck Albert J. R. , Blüher Matthias , Herzig Stephan , Wolfrum Christian , Prokesch Andreas
Published: February 2024

In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, the impact of fasting regimens on the regulation of AT immune infiltration is still elusive. Here we show that intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, this increase in LAM abundance is strongly p53 dependent and partly mediated by p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation during IF, increases the catabolic state of adipocytes, and enhances systemic metabolic flexibility and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to efficacy of a fasting-mimicking diet and that the expression of p53 and TREM2 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signalling in adipocytes dictates LAM accumulation in AT under IF and modulates fasting effectiveness in mice and humans.
High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing
Authors: Wu Haojia , Dixon Eryn E. , Xuanyuan Qiao , Guo Juanru , Yoshimura Yasuhiro , Debashish Chitnis , Niesnerova Anezka , Xu Hao , Rouault Morgane , Humphreys Benjamin D.
Published: February 2024

Emerging spatially resolved transcriptomics technologies allow for the measurement of gene expression in situ at cellular resolution. We apply direct RNA hybridization-based in situ sequencing (dRNA HybISS, Cartana part of 10xGenomics) to compare male and female healthy mouse kidneys and the male kidney injury and repair timecourse. A pre-selected panel of 200 genes is used to identify cell state dynamics patterns during injury and repair. We develop a new computational pipeline, CellScopes, for the rapid analysis, multi-omic integration and visualization of spatially resolved transcriptomic datasets. The resulting dataset allows us to resolve 13 kidney cell types within distinct kidney niches, dynamic alterations in cell state over the course of injury and repair and cell-cell interactions between leukocytes and kidney parenchyma. At late timepoints after injury, C3+ leukocytes are enriched near pro-inflammatory, failed-repair proximal tubule cells. Integration of snRNA-seq dataset from the same injury and repair samples also allows us to impute the spatial localization of genes not directly measured by dRNA HybISS.
Evaluation of single-sample network inference methods for precision oncology
Authors: Deschildre Joke , Vandemoortele Boris , Loers Jens Uwe , De Preter Katleen , Vermeirssen Vanessa
Published: February 2024

A major challenge in precision oncology is to detect targetable cancer vulnerabilities in individual patients. Modeling high-throughput omics data in biological networks allows identifying key molecules and processes of tumorigenesis. Traditionally, network inference methods rely on many samples to contain sufficient information for learning, resulting in aggregate networks. However, to implement patient-tailored approaches in precision oncology, we need to interpret omics data at the level of individual patients. Several single-sample network inference methods have been developed that infer biological networks for an individual sample from bulk RNA-seq data. However, only a limited comparison of these methods has been made and many methods rely on ‘normal tissue’ samples as reference, which are not always available. Here, we conducted an evaluation of the single-sample network inference methods SSN, LIONESS, SWEET, iENA, CSN and SSPGI using transcriptomic profiles of lung and brain cancer cell lines from the CCLE database. The methods constructed functional gene networks with distinct network characteristics. Hub gene analyses revealed different degrees of subtype-specificity across methods. Single-sample networks were able to distinguish between tumor subtypes, as exemplified by node strength clustering, enrichment of known subtype-specific driver genes among hubs and differential node strength. We also showed that single-sample networks correlated better to other omics data from the same cell line as compared to aggregate networks. We conclude that single-sample network inference methods can reflect sample-specific biology when ‘normal tissue’ samples are absent and we point out peculiarities of each method.
Intranasal vaccine for Lyme disease provides protection against tick transmitted Borrelia burgdorferi beyond one year
Authors: Gingerich Maria Cristina , Nair Nisha , Azevedo Jose F. , Samanta Kamalika , Kundu Suman , He Biao , Gomes-Solecki Maria
Published: February 2024

Strategies for disease control are necessary to reduce incidence of Lyme Disease (LD) including development of safe vaccines for human use. Parainfluenza virus 5 (PIV5) vector has an excellent safety record in animals and PIV5-vectored vaccines are currently under clinical development. We constructed PIV5-vectored LD vaccine candidates expressing OspA from B. burgdorferi (OspAB31) and a chimeric protein containing sequences from B. burgdorferi and B. afzelii (OspABPBPk). Immunogenicity and vaccine efficacy were analyzed in C3H-HeN mice after prime-boost intranasal vaccination with live PIV5-OspAB31 or PIV5-OspABPBPk, subcutaneous (s.c.) vaccination with rOspAB31+Alum, and the respective controls. Mice vaccinated intranasally with live PIV5-AB31 or PIV5-ABPBPk had higher endpoint titers of serum antibody against OspAB31 at 6- and 12- months post vaccination, compared to mice vaccinated s.c. with rOspAB31. Neutralization activity of antibody was maintained up to 18-months post-immunization, with the response greater in live PIV5-delivered OspA vaccines, than that induced by s.c. rOspAB31. Challenge with infected ticks carrying 10-19 strains of B. burgdorferi performed at 4-, 9- or 15-months post-immunization showed increased breakthrough infections in mice vaccinated with s.c. rOspAB31 compared to intranasal PIV5-AB31 or PIV5-ABPBPk at 9- and 15-months, as determined by quantification of serologic antibodies to B. burgdorferi proteins as well as flaB DNA in tissues, and by visualization of motile B. burgdorferi in culture of tissues under dark field microscope. These findings indicate that immunization of mice with PIV5 delivered OspA generates immune responses that produce longer-lasting protection ( > 1 year) against tick-transmitted B. burgdorferi than a parenteral recombinant OspA vaccine.
Zika purified inactivated virus (ZPIV) vaccine reduced vertical transmission in pregnant immunocompetent mice
Authors: Kim In-Jeong , Tighe Michael P. , Lanthier Paula A. , Clark Madeline J. , De La Barrera Rafael A. , Dussupt Vincent , Mendez-Rivera Letzibeth , Krebs Shelly J. , Travis Kelsey L. , Low-Beer Timothy C. , Cookenham Tres S. , Lanzer Kathleen G. , Bernacki Derek T. , Szaba Frank M. , Schneck Amanda A. , Ward Jerrold , Thomas Stephen J. , Modjarrad Kayvon , Blackman Marcia A.
Published: February 2024

Zika virus (ZIKV) is a significant threat to pregnant women and their fetuses as it can cause severe birth defects and congenital neurodevelopmental disorders, referred to as congenital Zika syndrome (CZS). Thus, a safe and effective ZIKV vaccine for pregnant women to prevent in utero ZIKV infection is of utmost importance. Murine models of ZIKV infection are limited by the fact that immunocompetent mice are resistant to ZIKV infection. As such, interferon-deficient mice have been used in some preclinical studies to test the efficacy of ZIKV vaccine candidates against lethal virus challenge. However, interferon-deficient mouse models have limitations in assessing the immunogenicity of vaccines, necessitating the use of immunocompetent mouse pregnancy models. Using the human stat2 knock-in (hSTAT2KI) mouse pregnancy model, we show that vaccination with a purified formalin-inactivated Zika virus (ZPIV) vaccine prior to pregnancy successfully prevented vertical transmission. In addition, maternal immunity protected offspring against postnatal challenge for up to 28 days. Furthermore, passive transfer of human IgG purified from hyper-immune sera of ZPIV vaccinees prevented maternal and fetal ZIKV infection, providing strong evidence that the neutralizing antibody response may serve as a meaningful correlate of protection.
Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression
Authors: Hu Junyi , Wang Shao-Gang , Hou Yaxin , Chen Zhaohui , Liu Lilong , Li Ruizhi , Li Nisha , Zhou Lijie , Yang Yu , Wang Liping , Wang Liang , Yang Xiong , Lei Yichen , Deng Changqi , Li Yang , Deng Zhiyao , Ding Yuhong , Kuang Yingchun , Yao Zhipeng , Xun Yang , Li Fan , Li Heng , Hu Jia , Liu Zheng , Wang Tao , Hao Yi , Jiao Xuanmao , Guan Wei , Tao Zhen , Ren Shancheng , Chen Ke
Published: February 2024

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.
RANKL blockade for erosive hand osteoarthritis: a randomized placebo-controlled phase 2a trial
Authors: Wittoek Ruth , Verbruggen Gust , Vanhaverbeke Tine , Colman Roos , Elewaut Dirk
Published: February 2024

Erosive hand osteoarthritis (OA) is a prevalent and disabling disease with limited treatment options. Here we present the results of a monocentric, placebo-controlled, double-blind, randomized phase 2a clinical trial with denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, evaluating the effects on structure modification in erosive hand OA. Patients were randomized to 48 weeks treatment with denosumab 60 mg every 3 months (n = 51, 41 females) or placebo (n = 49, 37 females). The primary (radiographic) endpoint was the change in the total Ghent University Scoring System (GUSS) at week 24, where positive changes correspond to remodeling and negative changes to erosive progression. Secondary endpoints were the change in the GUSS at week 48 and the number of new erosive joints at week 48 by the anatomical phase scoring system. Baseline mean GUSS (standard deviation) of target joints was 155.9 (69.3) in the denosumab group and 158.7 (46.8) in the placebo group. The primary endpoint was met with an estimated difference between groups of 8.9 (95% confidence interval (CI) 1.0 to 16.9; P = 0.024) at week 24. This effect was confirmed at week 48 (baseline adjusted GUSS (standard error of the mean) denosumab and placebo were 163.5 (2.9) and 149.2 (3.9), respectively; with an estimated difference between groups of 14.3 (95% CI 4.6 to 24.0; P = 0.003)). At patient level, more new erosive joints were developed in the placebo group compared with denosumab at week 48 (odds ratio 0.24 (95% CI 0.08 to 0.72); P = 0.009). More adverse events occurred in the placebo group (125 events in 44 patients (90%)) compared with the denosumab group (97 events in 41 patients (80%)). These results demonstrate that denosumab has structure modifying effects in erosive hand OA by inducing remodeling and preventing new erosive joints. EU Clinical Trials Register identifier 2015-003223-53.
Transitioning from MODIS to VIIRS Global Water Reservoir Product
Authors: Shah Deep , Zhang Shuai , Sarkar Sudipta , Davidson Carol , Zhang Rui , Zhao Maosheng , Devadiga Sadashiva , Noojipady Praveen , Román Miguel O. , Gao Huilin
Published: February 2024

Reservoirs play a crucial role in regulating water availability and enhancing water security. Here, we develop NASA’s Visible Infrared Imaging Radiometer Suite (VIIRS) based Global Water Reservoir (GWR) product, consisting of measurements of reservoir area, elevation, storage, evaporation rate, and evaporation loss for 164 large global reservoirs. The dataset is available at 8-day and monthly temporal resolutions. Since the Moderate Resolution Imaging Spectroradiometer (MODIS) is close to the end of its life, we further evaluated the consistency between MODIS and VIIRS-based GWR to ensure continuity to the 20+ year MODIS GWR product. Independent assessment of VIIRS reservoir storage (8-day) retrievals against in-situ measurements shows an average of R2 = 0.84, RMSE = 0.47 km3, and NRMSE = 16.45%. The evaporation rate has an average of R2 = 0.56, RMSE = 1.32 mm/day, and NRMSE = 28.14%. Furthermore, results show good consistency (R2 ≥ 0.90) between the VIIRS and MODIS-based product components, confirming that long-term data continuity can be achieved. This dataset can provide valuable insights for long-term trend analysis, hydrological modeling, and understanding hydroclimatic extremes in the context of reservoirs.
Assessment of Self-report, Palpation, and Surface Electromyography Dataset During Isometric Muscle Contraction
Authors: Lim Jihoon , Lu Lei , Goonewardena Kusal , Liu Jefferson Zhe , Tan Ying
Published: February 2024

Measuring muscle fatigue involves assessing various components within the motor system. While subjective and sensor-based measures have been proposed, a comprehensive comparison of these assessment measures is currently lacking. This study aims to bridge this gap by utilizing three commonly used measures: participant self-reported perceived muscle fatigue scores, a sports physiotherapist’s manual palpation-based muscle tightness scores, and surface electromyography sensors. Compensatory muscle fatigue occurs when one muscle group becomes fatigued, leading to the involvement and subsequent fatigue of other muscles as they compensate for the workload. The evaluation of compensatory muscle fatigue focuses on nine different upper body muscles selected by the sports physiotherapist. With a cohort of 30 male subjects, this study provides a valuable dataset for researchers and healthcare practitioners in sports science, rehabilitation, and human performance. It enables the exploration and comparison of diverse methods for evaluating different muscles in isometric contraction.
Metabolism Regimes in Regulated Rivers of the Illinois River Basin, USA
Authors: Harvey Judson W. , Choi Jay , Quion Katherine
Published: February 2024

Metabolism estimates organic carbon accumulation by primary productivity and removal by respiration. In rivers it is relevant to assessing trophic status and threats to river health such as hypoxia as well as greenhouse gas fluxes. We estimated metabolism in 17 rivers of the Illinois River basin (IRB) for a total of 15,176 days, or an average of 2.5 years per site. Daily estimates of gross primary productivity (GPP), ecosystem respiration (ER), net ecosystem productivity (NEP), and the air-water gas exchange rate constant (K600) are reported, along with ancillary data such as river temperature and saturated dissolved oxygen concentration, barometric pressure, and river depth and discharge. Workflows for metabolism estimation and quality assurance are described including a new method for estimating river depth. IRB rivers are dominantly heterotrophic; however, autotrophy was common in river locations coinciding with reported harmful algal blooms (HABs) events. Metabolism of these regulated Midwestern U.S. rivers can help assess the causes and consequences of excessive algal blooms in rivers and their role in river ecological health.
High-resolution Annual Dynamic dataset of Curve Number from 2008 to 2021 over Conterminous United States
Authors: Wu Qiong , Ramirez Avila John J. , Yang Jia , Ji Cunxiong , Fang Shanmin
Published: February 2024

The spatial distribution and data quality of curve number (CN) values determine the performance of hydrological estimations. However, existing CN datasets are constrained by universal-applicability hypothesis, medium resolution, and imbalance between specificity CN tables to generalized land use/land cover (LULC) maps, which hinder their applicability and predictive accuracy. A new annual CN dataset named CUSCN30, featuring an enhanced resolution of 30 meters and accounting for temporal variations in climate and LULC in the continental United States (CONUS) between 2008 and 2021, was developed in this study. CUSCN30 demonstrated good performance in surface runoff estimation using CN method when compared to observed surface runoff for the selected watersheds. Compared with existing CN datasets, CUSCN30 exhibits the highest accuracy in runoff estimation for both normal and extreme rainfall events. In addition, CUSCN30, with its high spatial resolution, better captures the spatial heterogeneity of watersheds. This developed CN dataset can be used as input for hydrological models or machine learning algorithms to simulate rainfall-runoff across multiple spatiotemporal scales.
Detection of prions from spiked and free-ranging carnivore feces
Authors: Inzalaco H. N. , Brandell E. E. , Wilson S. P. , Hunsaker M. , Stahler D. R. , Woelfel K. , Walsh D. P. , Nordeen T. , Storm D. J. , Lichtenberg S. S. , Turner W. C.
Published: February 2024

Chronic wasting disease (CWD) is a highly contagious, fatal neurodegenerative disease caused by infectious prions (PrPCWD) affecting wild and captive cervids. Although experimental feeding studies have demonstrated prions in feces of crows (Corvus brachyrhynchos), coyotes (Canis latrans), and cougars (Puma concolor), the role of scavengers and predators in CWD epidemiology remains poorly understood. Here we applied the real-time quaking-induced conversion (RT-QuIC) assay to detect PrPCWD in feces from cervid consumers, to advance surveillance approaches, which could be used to improve disease research and adaptive management of CWD. We assessed recovery and detection of PrPCWD by experimental spiking of PrPCWD into carnivore feces from 9 species sourced from CWD-free populations or captive facilities. We then applied this technique to detect PrPCWD from feces of predators and scavengers in free-ranging populations. Our results demonstrate that spiked PrPCWD is detectable from feces of free-ranging mammalian and avian carnivores using RT-QuIC. Results show that PrPCWD acquired in natural settings is detectable in feces from free-ranging carnivores, and that PrPCWD rates of detection in carnivore feces reflect relative prevalence estimates observed in the corresponding cervid populations. This study adapts an important diagnostic tool for CWD, allowing investigation of the epidemiology of CWD at the community-level.
Selection and validation of reference genes suitable for gene expression analysis by Reverse Transcription Quantitative real-time PCR in Acinetobacter baumannii
Authors: de Oliveira Paloma Aparecida Alves , Baboghlian Juliana , Ramos Clarissa Orandina Aparecida , Mançano Alquiandra Stefani Ferreira , Porcari Andréia de Melo , Girardello Raquel , Ferraz Lúcio Fábio Caldas
Published: February 2024

Acinetobacter baumannii is a Gram-negative bacterium considered an emerging multi-drug-resistant pathogen. Furthermore, this bacterium can survive in extreme environmental conditions, which makes it a frequent cause of nosocomial infection outbreaks. Gene expression analyses by Reverse Transcription Quantitative real-time PCR (RT-qPCR) depend on a reference gene, also called an endogenous gene, which is used to normalize the generated data and thus ensure an accurate analysis with minimal errors. Currently, gene expression analyses in A. baumannii are compromised, as there are no reports in the literature describing the identification of validated reference genes for use in RT-qPCR analyses. For this reason, we selected twelve candidate reference genes of A. baumannii and assessed their expression profile under different experimental and culture conditions. The expression stability of the candidate genes was evaluated by using statistical algorithms such as BestKeeper, geNorm, NormFinder, Delta CT, and RefFinder, in order to identify the most suitable candidate reference genes for RT-qPCR analyses. The statistical analyses indicated rpoB, rpoD, and fabD genes as the most adequate to ensure accurate normalization of RT-qPCR data in A. baumannii. The accuracy of the proposed reference genes was validated by using them to normalize the expression of the ompA gene, encoding the outer membrane protein A, in A. baumannii sensible and resistant to the antibiotic polymyxin. The present work provides suitable reference genes for precise RT-qPCR data normalization on future gene expression studies with A. baumannii.
People do change their beliefs about conspiracy theories—but not often
Authors: Williams Matt N. , Ling Mathew , Kerr John R. , Hill Stephen R. , Marques Mathew D. , Mawson Hollie , Clarke Edward J. R.
Published: February 2024

Recent research has produced a significant body of knowledge about the antecedents and consequences of individual differences in belief in conspiracy theories. What is less clear, however, is the extent to which individuals’ beliefs in conspiracy theories vary over time (i.e., within-person variation). In this descriptive and exploratory study, we therefore aimed to describe within-person variability in belief in conspiracy theories. We collected data from 498 Australians and New Zealanders using an online longitudinal survey, with data collected at monthly intervals over 6 months (March to September 2021). Our measure of conspiracy theories included items describing ten conspiracy theories with responses on a 5-point Likert scale. While there was substantial between-person variance, there was much less within-person variance (intraclass r = 0.91). This suggests that beliefs in conspiracy theories were highly stable in our sample. This stability implies that longitudinal studies testing hypotheses about the causes and consequences of belief in conspiracy theories may require large samples of participants and time points to achieve adequate power. It also implies that explanations of belief in conspiracy theories need to accommodate the observation that beliefs in such theories vary much more between people than within people.
Pheromonal variation and mating between two mitotypes of fall armyworm (Spodoptera frugiperda) in Africa
Authors: Sisay Birhanu , Tamiru Amanuel , Subramanian Sevgan , Weldon Christopher W. , Khamis Fathiya , Green Kristina Karlsson , Anderson Peter , Torto Baldwyn
Published: February 2024

In the Americas, the fall armyworm (Spodoptera frugiperda) exists in two genetically distinct strains, the corn (C) and rice (R) strains. Despite their names, these strains are not associated with host plant preferences but have been shown to vary in pheromone composition and male responses. Recently, S. frugiperda was detected in Africa as an invasive species, but knowledge about variation in strain types, pheromone composition and inter-strain mating of populations of the pest in the continent has not been fully examined. Therefore, this study aimed to investigate variations, if any in the pheromone composition of female moths, male moth responses, and mating between C and R mitotypes of S. frugiperda populations in Kenya, as well as their geographic distribution. Strains (mitotypes) of S. frugiperda were identified using mitochondrial DNA (mtDNA) markers, and their pheromonal composition determined by coupled gas chromatography–mass spectrometric (GC–MS) analysis. Male moth responses to these compounds were evaluated using GC-electroantennographic detection (EAD), electroantennogram (EAG), and wind tunnel assays. Oviposition assays were used to determine whether R and C mitotype moths could mate and produce eggs. The results showed that both the R and C mitotypes were present, and there were no statistically significant differences in their distribution across all sampled locations. Five pheromone compounds including (Z)-7-dodecenyl acetate (Z7-12:OAc), (Z)-7-tetradecenyl acetate (Z7-14:OAc), (Z)-9-tetradecenyl acetate (Z9-14:OAc), (Z)-11-tetradecenyl acetate (Z11-14:OAc) and (Z)-11-hexadecenyl acetate (Z11-16:OAc), were detected in the pheromone glands of female moths of both mitotypes, with Z9-14:OAc being the most abundant. The relative percentage composition of Z9-14:OAc was similar in both mitotypes. However, the R mitotype had a 2.7 times higher relative percentage composition of Z7-12:OAc compared to the C mitotype moth, while the C mitotype moth had a 2.4 times higher relative percentage composition of Z11-16:OAc than the R mitotype moth. Male moths of both mitotypes exhibited similar responses to the pheromone compounds, showing the strongest responses to Z9-14:OAc and Z7-12:OAc in electrophysiological and behavioural assays. There was mating between R and C mitotypes with egg production comparable to mating within the same mitotype. Our results revealed that differences between the two S. frugiperda mitotypes are characterized by female moth pheromone composition rather than male moth responses to the pheromones, and that this does not prevent hybridisation between the mitotypes, which may have implications for their management.
Exploring the therapeutic mechanisms and prognostic targets of Biochanin A in glioblastoma via integrated computational analysis and in vitro experiments
Authors: Ge Wanwen , Yuan Guoqiang , Wang Dongping , Dong Li
Published: February 2024

Glioblastoma (GBM) is the most aggressive brain tumor and is characterized by a poor prognosis and high recurrence and mortality rates. Biochanin A (BCA) exhibits promising clinical anti-tumor effects. In this study, we aimed to explore the pharmacological mechanisms by which BCA acts against GBM. Network pharmacology was employed to identify overlapping target genes between BCA and GBM. Differentially expressed genes from the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database were visualized using VolcaNose. Interactions among these overlapping genes were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins database. Protein–protein interaction networks were constructed using Cytoscape 3.8.1. The Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology enrichment analyses were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Survival analyses for these genes were performed using the GEPIA2 database. The Chinese Glioma Genome Atlas database was used to study the correlations between key prognostic genes. Molecular docking was confirmed using the DockThor database and visualized with PyMol software. Cell viability was assessed via the CCK-8 assay, apoptosis and the cell cycle stages were examined using flow cytometry, and protein expression was detected using western blotting. In all, 63 genes were initially identified as potential targets for BCA in treating GBM. Enrichment analysis suggested that the pharmacological mechanisms of BCA primarily involved cell cycle inhibition, induction of cell apoptosis, and immune regulation. Based on these findings, AKT1, EGFR, CASP3, and MMP9 were preliminarily predicted as key prognostic target genes for BCA in GBM treatment. Furthermore, molecular docking analysis suggested stable binding of BCA to the target protein. In vitro experiments revealed the efficacy of BCA in inhibiting GBM, with an IC50 value of 98.37 ± 2.21 μM. BCA inhibited cell proliferation, induced cell apoptosis, and arrested the cell cycle of GBM cells. Furthermore, the anti-tumor effects of BCA on U251 cells were linked to the regulation of the target protein. We utilized integrated bioinformatics analyses to predict targets and confirmed through experiments that BCA possesses remarkable anti-tumor activities. We present a novel approach for multi-target treatment of GBM using BCA.
Symptom burden and follow-up of patients with neck and back complaints in specialized outpatient care: a national register study
Authors: Bjørneboe John , Bratsberg Andrea , Brox Jens Ivar , Skatteboe Sigrid , Wilhelmsen Maja , Samuelsen Kjetil Magne , Marchand Gunn Hege , Flørenes Tonje , Kielland Maja Garnaas , Røe Cecilie
Published: February 2024

Back and neck pain are common in the population, especially among immigrants. In Norway's specialist care system, treating these patients typically involves a multidisciplinary approach based on the biopsychosocial model. However, language and cultural differences may create barriers to participation. Immigrants are often underrepresented in clinical studies, but a register-based approach can enhance their participation in research. This study aimed to compare both the symptom burden, and treatment, among Norwegians, non-Norwegians, and patients requiring translator service for back and neck pain within the Norwegian specialist care system. The Norwegian neck and back registry is a National Quality Register, established in 2012 and fully digitized in late 2020. The baseline data includes demographics and patient recorded outcome measures including Oswestry Disability Index, Fear-Avoidance Beliefs, pain rating on a numeric rating scale, Hopkins Symptom Checklist and EuroQol five-dimensional questionnaire on health related quality of life. During the two-year study period, a total of 14,124 patients were invited, and 10,060 (71%) participated. Norwegian patients reported less pain, better function assessed by Oswestry Disability Index, lower fear avoidance beliefs, less emotional distress, and higher health related quality of life compared to non-Norwegians. We found that patients with female gender, who were younger, more educated and exhibited fear-avoidance behavior were significantly more likely to receive multidisciplinary treatment. We found no difference in the proportion of Norwegian and non-Norwegian patients receiving multidisciplinary treatment [odds ratio (OR) 1.02 (95% confidence interval (CI) 0.90–1.16)]. However, patients needing a translator were less likely to receive multidisciplinary treatment compared to those who didn't require translation [OR 0.41 (95% CI (0.25–0.66)]. We found that non-Norwegian patients experience a higher symptom burden compared to Norwegian. We found that both non-Norwegians and patient in need of translator were to a greater extent recommended treatment in primary health care. The proportion of non-Norwegians patients receiving multidisciplinary treatment was similar to Norwegians, but those needing a translator were less likely to receive such treatment.
Wide-angle non-uniform optical phased array using compact and efficient antenna design
Authors: Elsheikh Omar E. , Swillam Mohamed A.
Published: February 2024

In the need for a more compact and efficient optical phased array with a wide steering beam for LIDAR applications, a wide steering array with high resolution is desirable. However, in the published work, a trade-off is often made for one over another. Apodized grating antennas have shown good efficiency with a compact size and wide beam profile, which improve optical phased array beam steering capability and are also compatible with the CMOS silicon photonics process. A promising studies shows enhancement in steering range with good resolution utilizing a non-uniform optical phased array. In this work, we present two highly efficient optical antennas with 94% and 93.5% upward power at the center frequency for the first and second antenna respectively, exceeding state-of-the-artwork to the best of our knowledge, and wide full-width half maximum of 8.88° x 78.05° and 7.53° x 69.85° in elevation and azimuthal planes, respectively. Both antennas provide a broad bandwidth across the 1400–1700 nm wavelength range with more than 80% efficiency in the S, C, and L bands. To overcome the limited scan ranges and small aperture size, a two-dimensional non-uniform array of 10 × 10 elements is utilized to increase the beam steering capability. A genetic algorithm is used to optimize the position of array elements, resulting in an aliasing-free array with a wide steering range of 160° with beam width 0.5° and consistent −11 dB maximum side lobe level across the steering range.
Intersectional inequalities in somatic symptom severity in the adult population in Germany found within the SOMA.SOC study
Authors: Barbek Rieke , Toussaint Anne , Löwe Bernd , von dem Knesebeck Olaf
Published: February 2024

Somatic symptoms are common in a wide range of medical conditions. In severe cases, they are associated with high individual and economic burden. To explore social inequalities in somatic symptom severity (SSS) and to identify social groups with highest SSS, we applied an intersectional research approach. Analyses are based on cross-sectional data of the adult population living in Germany (N = 2413). SSS was assessed with the Somatic Symptom Scale-8. A multiple linear regression model with three-way interaction of gender, income and history of migration and post-hoc pairwise comparison of estimated marginal means was conducted. Analyses revealed intersectional inequalities in SSS along the axis of gender, income, and history of migration. Highest SSS was found in males with low income whose parent(s) immigrated, females with low income who immigrated themselves, and females with low income and no history of migration. Intersectional approaches contribute to a more comprehensive understanding of health disparities. To reduce disparities in SSS, proportionate universal interventions combining universal screening and targeted treatment seem promising.
Prognostic value of the expression and localization of cell proliferation and apoptosis markers in unicystic ameloblastomas
Authors: Vieira Costa Rebeca , Balbinot Karolyny Martins , da Silveira Gabriela Cristina Avertano Rocha , Kataoka Maria Sueli da Silva , de Menezes Silvio Augusto Fernandes , Freitas Vanessa Morais , Vasconcelos Ana Carolina Uchoa , Etges Adriana , Martins Montalli Victor Angelo , Santos Fabricio Passador , Alves Júnior Sérgio de Melo , Jaeger Ruy Gastaldoni , Pinheiro João de Jesus Viana
Published: February 2024

The aim of this study was to verify whether the expression of cell proliferation and apoptosis markers in different types of unicystic ameloblastoma (UA) is associated with the location of neoplastic cells. Immunohistochemical study with a sample of 32 cases of UA, 11 cases of conventional ameloblastoma (CAM) and ten dental follicles (DF) cases was performed. Cell proliferation was assessed using Ki-67 status, and apoptosis by caspase-3 expression. Mural UA (MUA) showed a higher immunostaining of Ki-67 (p < 0.05) and a lower immunostaining of Caspase-3 (p < 0.05) compared with luminal and intraluminal subtypes of UA and CAM. The neoplastic cells of the MUA’s cystic capsule showed a higher expression of Ki-67 protein (p < 0.0001) and a lower expression of Caspase-3 (p < 0.0001) compared with the lumen. DF showed lower Ki-67 and Caspase-3 immunostaining (p < 0.05) than neoplasms. The higher immunoexpression of Ki-67 and the lower immunoexpression of Caspase-3 in MUA, in the parenchyma cells within the cystic capsule, suggest an association between the biological behaviour and location of neoplastic cells in a tumour.
Investigating the impacts of airborne dust on herbicide performance on Amaranthus retroflexus
Authors: Sharifi Kalyani Firouzeh , Babaei Sirwan , Zafarsohrabpour Yasin , Nosratti Iraj , Gage Karla , Sadeghpour Amir
Published: February 2024

Dust pollution poses environmental hazards, affecting agriculture through reduced sunlight exposure, photosynthesis, crop yields, and food security. This study explores the interference of dust pollution on herbicide efficacy to control weeds in a semi-arid region. In a factorial experiment conducted in 2019 and replicated in 2020, the interaction of dust and various herbicide applications, including bentazon, sulfosulfuron, tribenuron-methyl, aminopyralid + florasulam, foramsulfuron + iodosulfuron + thiencarbazone, 2,4-D + MCPA, and acetochlor, in controlling Amaranthus retroflexus L. were assessed. Dust induced a 9.2% reduction in the total chlorophyll content of A. retroflexus, while herbicide application independently led to a 67.5% decrease. Contrary to expectations, herbicides performed better in dust, except bentazon, which caused a 28% drop in plant height and a 29% decrease in total biomass compared to non-dust conditions. Both herbicides and dust exerted suppressive effects on A. retroflexus's leaf and stem weights and overall biomass. Despite dust presence, tribenuron-methyl (95.8%), aminopyralid + florasulam (95.7%), sulfosulfuron (96.5%), and foramsulfuron + iodosulfuron + thiencarbazone (97.8%) effectively controlled A. retroflexus. These findings indicate that dust's effect on herbicide efficacy is herbicide-dependent but except bentazon, dust generally increased herbicide efficacy and amplified the control of A. retroflexus.