bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary l-glutamic acid N,N-diacetic acid improves short-term maintenance of zinc homoeostasis in a model of subclinical zinc deficiency in weaned piglets
Authors: Boerboom Gavin , Ganslmaier Elena , Oeckl Josef , Busink Ronald , Martín-Tereso Javier , Windisch Wilhelm , Brugger Daniel
Published: January 2022

This study compared the Zn response in selected tissues of weaned piglets fed L-glutamic acid, N,N-diacetic acid (GLDA), while challenged with short-term subclinical Zn deficiency (SZD). During a total experimental period of eight days, 96 piglets were fed restrictively (450 g/d) a high phytate (9 g/kg) diet containing added Zn at 0, 5, 10, 15, 20, 25, 45 and 75 mg/kg with and without 200 mg/kg of GLDA. No animals showed signs of clinical Zn deficiency and no phenotypical differences were observed. Broken line analysis of Zn status parameters such as liver Zn and apparently absorbed Zn indicated that the gross Zn requirement threshold was around 55 mg/kg diet. Supplementation of Zn above this threshold led to a saturation of the response in apparently absorbed Zn and linear increase in liver Zn. Bone and serum Zn responded to the dose in a linear fashion, likely due to the time-frame of Zn homoeostatic adaptation. Inclusion of GLDA into the diets yielded a higher intercept for bone Zn (P < 0·05). Liver Zn accumulation and MT1A gene expression was higher for piglets receiving GLDA (P < 0·05), indicating higher Zn influx. This study indicates that a strong chelator such as GLDA mitigates negative effects of phytate in plant-based diets, by sustaining Zn solubility, thereby improving nutritional Zn availability.
Influence of crude protein content and flint maize processing methods on the performance of early-weaning Nellore calves
Authors: Godoi L. A. , Silva B. C. , Souza G. A. P. , Lage B. C. , Zanetti D. , Costa e Silva L. F. , Rennó L. N. , Paulino M. F. , Valadares Filho S. C.
Published: January 2022

This study aims to determine the effects of dietary crude protein (CP) content of early-weaned calves; and the influence of flint maize processing methods on intake, total tract nutrient digestibilities and performance of Nellore heifer calves. Fifteen early-weaned Nellore female calves (4 ± 0.5 months; 108 ± 13.1 kg) were used. In phase 1, animals were fed one of the following diets for 112 days: 130, 145 or 160 g CP/kg dry matter (DM). In phase 2, animals received one of the two diets for 84 days: 0.60 dry ground maize grain, 0.30 whole-plant maize silage plus 0.10 mineral-protein supplement or 0.90 snaplage plus 0.10 mineral-protein supplement. In phase 1, intake and digestibility of dietary components were not affected (P > 0.05) by increasing dietary CP content. Daily total urinary nitrogen (N) and urinary urea N increased (P < 0.05) in response to increasing dietary CP content. Animal performance was not affected (P > 0.05) by dietary CP content. In phase 2, maize processing methods did not affect (P > 0.05) intake and digestibility of dietary components as well as animal performance, carcase characteristics and carcase composition. Therefore, based on the current experimental condition, we conclude that dietary CP concentrations of 130 g/kg DM can be indicated for early-weaned Nellore calves. However, more studies are recommended to validate this result and to evaluate concentrations below 130 g CP/kg DM for early-weaned Nellore calves. Moreover, snaplage could be used as an exclusive fibre and energy source for finishing cattle in feedlot.
Critical medical ecology and intersectionality perspectives in schistosomiasis prevention and control in selected communities in Mindanao, the Philippines
Authors: Dalisay Soledad Natalia M. , Belizario Vicente Y. , Joe Joseph Aaron S. , Lumangaya Carlo R. , Cruz Reginaldo D.
Published: January 2022

Schistosomiasis japonica remains a public health concern in many areas of the Philippines. Periodic Mass Drug Administration (MDA) to at-risk populations is the main strategy for morbidity control of schistosomiasis. Attaining MDA coverage targets is important for the reduction of morbidity and prevention of complications due to the disease, and towards achieving Universal Health Care. The study employed a qualitative case study design. Key informant interviews and focus group discussions were conducted to provide in-depth and situated descriptions of the contexts surrounding the implementation of MDA in two selected villages in known schistosomiasis-endemic provinces in Mindanao in the Philippines. Data analysis was done using the Critical Ecology for Medical Anthropology (CEMA) model coupled with the intersectionality approach. It was found that within various areas in the CEMA model, enabling as well as constraining factors have been encountered in MDA in the study settings. The interplay of income class, geographical location, gender norms and faith-based beliefs may have led to key populations being missed during the conduct of MDA in the study sites. The constraints faced by the target beneficiaries of MDA, as well as programme implementers, must be addressed to enhance service delivery and to control morbidity due to schistosomiasis. Improving compliance with MDA also requires a holistic, integrated approach to addressing barriers to participation, which are shaped by wider socio-political and power structures.
Handmaidens of the legislature? Understanding regulatory timing
Authors: Haeder Simon F. , Yackee Susan Webb
Published: January 2022

When does legislation trigger regulation? The US Congress regularly passes laws that authorise government agencies to write legally binding regulations. Yet, when this occurs, agencies may take years to act – or, at times – may never act at all. We theorise that the breadth of the congressional statutory delegation drives the timing of agency policy production. In particular, when Congress expressly tells an agency to promulgate a rule, we expect agencies to do so quickly. Yet, when Congress provides greater policymaking discretion to agencies, we expect other factors – and especially, internal agency considerations – to drive regulatory timing. We use data from almost 350 statutes spanning four decades, which are then matched up with thousands of regulations, to assess the argument. Using innovative methods, we find support for our hypotheses. Overall, we produce a deeper understanding of the link between delegation and discretion: suggesting when it occurs, as well as, importantly, why.
Prevalence of anaemia and associated factors among people with pulmonary tuberculosis in Uganda
Authors: Baluku Joseph Baruch , Mayinja Ernest , Mugabe Pallen , Ntabadde Kauthrah , Olum Ronald , Bongomin Felix
Published: January 2022

Anaemia predicts delayed sputum conversion and mortality in tuberculosis (TB). We determined the prevalence and factors associated with anaemia among people with TB at the National Tuberculosis Treatment Centre in Uganda. People with bacteriologically confirmed TB were consecutively enrolled in a cross-sectional study between August 2017 and March 2018. Blood samples were tested for a full blood hemogram, HIV infection, and CD4+ and CD8+ T-cell counts. Anaemia was defined as a haemoglobin level of <13.0 grams per decilitre (g/dl) for males and <12.0 g/dl for females. Of 358 participants, 210 (58.7%, 95% confidence interval (CI) 53.4–63.8) had anaemia. Anaemia was associated with night sweats, a longer duration of fever, low body mass index (BMI), hyperthermia, high sputum bacillary loads, HIV co-infection, and low CD4 and CD8 counts at bivariate analysis. Factors associated with anaemia at multivariable analysis were low BMI (odds ratio (OR) 2.93, 95% CI 1.70–5.05, P < 0.001), low CD4:CD8 ratio (OR 2.54, 95% CI 1.07–6.04, P = 0.035) and microcytosis (OR 4.23, 95% CI 2.17–8.25, P < 0.001). Anaemia may be associated with the features of severe TB disease and should be considered in TB severity scores.
Beyond food swamps and food deserts: exploring urban Australian food retail environment typologies
Authors: Needham Cindy , Strugnell Claudia , Allender Steven , Orellana Liliana
Published: January 2022

Objective:

‘Food deserts’ and ‘food swamps’ are food retail environment typologies associated with unhealthy diet and obesity. The current study aimed to identify more complex food retail environment typologies and examine temporal trends.

Design:

Measures of food retail environment accessibility and relative healthy food availability were defined for small areas (SA2s) of Melbourne, Australia, from a census of food outlets operating in 2008, 2012, 2014 and 2016. SA2s were classified into typologies using a two-stage approach: (1) SA2s were sorted into twenty clusters according to accessibility and availability and (2) clusters were grouped using evidence-based thresholds.

Setting:

The current study was set in Melbourne, the capital city of the state of Victoria, Australia.

Subjects:

Food retail environments in 301 small areas (Statistical Area 2) located in Melbourne in 2008, 2012, 2014 and 2016.

Results:

Six typologies were identified based on access (low, moderate and high) and healthy food availability including one where zero food outlets were present. Over the study period, SA2s experienced an overall increase in accessibility and healthiness. Distribution of typologies varied by geographic location and area-level socio-economic position.

Conclusion:

Multiple typologies with contrasting access and healthiness measures exist within Melbourne and these continue to change over time, and the majority of SA2s were dominated by the presence of unhealthy relative to healthy outlets, with SA2s experiencing growth and disadvantage having the lowest access and to a greater proportion of unhealthy outlets.
Systematic review of metrics used to characterise dietary nutrient supply from household consumption and expenditure surveys
Authors: Tang Kevin , Adams Katherine P , Ferguson Elaine L , Woldt Monica , Yourkavitch Jennifer , Pedersen Sarah , Broadley Martin R , Dary Omar , Ander E Louise , Joy Edward JM
Published: January 2022

Objective:

To review existing publications using Household Consumption and Expenditure Survey (HCES) data to estimate household dietary nutrient supply to (1) describe scope of available literature, (2) identify the metrics reported and parameters used to construct these metrics, (3) summarise comparisons between estimates derived from HCES and individual dietary assessment data and (4) explore the demographic and socio-economic sub-groups used to characterise risks of nutrient inadequacy.

Design:

This study is a systematic review of publications identified from online databases published between 2000 to 2019 that used HCES food consumption data to estimate household dietary nutrient supply. Further publications were identified by ‘snowballing’ the references of included database-identified publications.

Setting:

Publications using data from low- and lower-middle income countries.

Results:

In total, fifty-eight publications were included. Three metrics were reported that characterised household dietary nutrient supply: apparent nutrient intake per adult-male equivalent per day (n35), apparent nutrient intake per capita per day (n24) and nutrient density (n5). Nutrient intakes were generally overestimated using HCES food consumption data, with several studies finding sizeable discrepancies compared with intake estimates based on individual dietary assessment methods. Sub-group analyses predominantly focused on measuring variation in household dietary nutrient supply according to socio-economic position and geography.

Conclusion:

HCES data are increasingly being used to assess diets across populations. More research is needed to inform the development of a framework to guide the use of and qualified interpretation of dietary assessments based on these data.
Osteoarthritis improvement effect of Chrysanthemum zawadskii var. latilobum extract in relation to genotype
Authors: Lee Taeheon , Na Chae-Bin , Kim Dasom , Han Hae Jung , Yun Jongbok , Park Sun Kyu , Cho Eunhae
Published: January 2022

Abstract: Objectives: To determine whether SNPs of osteoarthritis (OA)-related genes predict the effect of Chrysanthemum zawadskii var. latilobum (CZ) extract in OA patients with OA. Subjects/methods: To analyze correlations between CZ extract effects in humans and their genotypes, 121 Korean patients with OA were recruited. Patients ingested 600 mg/day of the CZ extract GCWB106 (one tablet daily), including 250-mg CZ, or placebo (one tablet daily) for 12 weeks. Twenty SNPs were genotyped in 11 genes associated with OA pathogenesis, including tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinases (MMPs), and 9 genes involved in OA-related dietary intervention. The Visual Analogue Scale (VAS) and Korean Western Ontario and McMaster Universities (K-WOMAC) were measured as indicators of GCWB106 effect. Statistical comparisons were performed using Kruskal-Wallis tests to identify associations between these scales and genotyped loci in patients with OA. Results: Three SNPs ( PPARG rs3856806, MMP13 rs2252070, and ZIP2 rs2234632) were significantly associated with the degree of change in VAS pain score. Homozygous CC genotype carriers of rs3856806, G allele carriers (GA or GG) of rs2252070, and T allele carriers (GT or TT) of rs2234632 showed lower VAS score (i.e., less severe symptoms) in the GCWB106 group (n=53) than the placebo group (n=57) (p=0.026, p=0.009, and p=0.025, respectively). Gene–gene interaction effects on GCWB106-mediated pain relief were then examined, and it was found that the addition of each genotype resulted in a greater decrease in VAS pain score in the GCWB106 group (p=0.0024) but not the placebo group (p=0.7734). Conclusions: These novel predictive markers for the pain-relieving effects of GCWB106 may be used in the personalized treatment of patients with OA.
Kognitives Training mit Kindern: Die Bedeutung von Need for Cognition
Authors: Ackermann A. Laura , Strobel Anja , Rindermann Heiner
Published: January 2022

Zusammenfassung. Die vorliegende Studie prüft, inwieweit Klauersche Trainings zur Förderung des (induktiven) Denkens und ihre Wirkung auf kognitive Fähigkeiten mit Need for Cognition (NFC; die Motivation und Freude, kognitive Anstrengungen zu erbringen) zusammenhängen. Es wurde bei 145 (121 final) Vorschul- und Erstklassenkindern (Alter 6 bis 7 Jahre) für das Klauersche Denktraining Keiner ist so schlau wie ich (KISSWI) untersucht, welcher Zusammenhang zwischen NFC sowie dem nachfolgenden kognitiven Trainingseffekt besteht und inwieweit sich die NFC-Ausprägung während des Trainings ändert. Insgesamt fand sich ein Zusammenhang von r = .22 zwischen der Prätestausprägung von NFC und kognitiver Fähigkeitssteigerung während des Trainings sowie ein kleiner positiver Effekt des Denktrainings auf die NFC-Entwicklung von Prä- zu Posttest ( d = 0.21). Auf Intelligenz (CFT-1) zeigte das Denktraining einen kleinen Effekt (Prä- zu Posttest d = 0.39). Die Ergebnisse liefern erste Hinweise auf Wechselwirkungen von NFC mit Klauerschen Denktrainings und damit auch auf die Bedeutung interindividueller Unterschiede von Trainierten für die Wirksamkeit kognitiver Trainings. >Σ: 150 Wörter.
Radiocarbon as a Dating Tool and Tracer in Paleoceanography
Authors: Skinner L. C. , Bard E.
Published: January 2022

Radiocarbon is an extremely useful carbon cycle tracer and radiometric dating tool. Here, we review the main principles and challenges involved in the use of radiocarbon in paleoceanography. First, we present a conceptual framework in which there are three possible uses of a radiocarbon measurement: (a) to obtain a calendar age interval, or a fossil entity's age; (b) to obtain an estimate of a carbon reservoir's past radiocarbon activity; or (c) to compare the relative radiocarbon activities of two contemporary carbon reservoirs. We discuss the analysis of marine fossil material, the generation of an atmospheric reference curve, and the interpretation of marine radiocarbon “ventilation metrics” in relation to this reference curve. It is emphasized that marine radiocarbon integrates the influences of: changing radiocarbon production; air‐sea gas exchange effects at the sea surface; transport times within the ocean interior; and the mixing of water parcels with different transit times from the sea surface, and different sea‐surface sources. These controls are what make radiocarbon such a powerful paleoceanographic tracer, though the difficulty of disentangling them is what makes marine radiocarbon dating and tracer studies so challenging. We discuss the implementation of radiocarbon in numerical models, and explore the theory linking ocean‐atmosphere partitioning of radiocarbon and CO2. Finally, we review existing records of marine radiocarbon variability over the last ∼25,000 years, which highlight the influence of ocean‐atmosphere carbon exchange on past atmospheric CO2 and climate, and point to emerging opportunities for resolving the global radiocarbon‐ and carbon budgets over the last glacial cycle.
Preferential Solute Transport in Low Permeability Zones During Spontaneous Imbibition in Heterogeneous Porous Media
Authors: Zahasky Christopher , Benson Sally M.
Published: January 2022

Multiphase flows in porous media, and the associated solute transport processes, are controlled by a combination of gravity, capillary, and viscous forces. Geologic heterogeneity influences flow and transport processes, yet gaps exist in our understanding of how heterogeneity impacts capillary‐driven transport, such as during spontaneous imbibition. Here we use positron emission tomography, combined with a newly developed method for conducting spontaneous imbibition experiments, to observe solute transport into low permeability regions during imbibition. Using an experimentally parameterized 2D numerical model, we demonstrate how capillary‐driven flow near the imbibition front can carry solutes into low permeability regions. This process displaces solutes from high permeability zones, while the cumulative amount of solute in low permeability zones increases, opposite of what is observed under fully saturated solute transport conditions. These results highlight the complex flow and solute transport behavior that arise during multiphase displacements in heterogeneous geologic porous media.
Association of Organic Carbon With Reactive Iron Oxides Driven by Soil pH at the Global Scale
Authors: Ye Chenglong , Huang Wenjuan , Hall Steven J. , Hu Shuijin
Published: January 2022

Association of organic carbon (C) with iron (Fe) minerals is one important mechanism for long‐term terrestrial C storage. Yet, specific edaphic variables that directly contribute to Fe‐associated C across diverse soil types are still unclear. Through analyzing soils from the National Ecological Observatory Network (NEON) and other published data, here we show that soil pH primarily controls Fe‐associated C across the globe. Fe‐associated C in most soils ranged from 0 to 20 g kg−1 soil, with a strong increase from pH 4.2 to 3.5, but a small change in soils with pH > 4.2. A microcosm experiment further showed that raising soil pH by liming reduced the formation of Fe‐associated C in an acidic Oxisol. Together, these findings demonstrate the dominant role of soil pH in controlling the abundance of Fe‐associated C.
Ion Dynamics at the Magnetopause of Ganymede
Authors: Fatemi S. , Poppe A. R. , Vorburger A. , Lindkvist J. , Hamrin M.
Published: January 2022

We study the dynamics of the thermal O+ and H+ ions at Ganymede's magnetopause when Ganymede is inside and outside of the Jovian plasma sheet using a three‐dimensional hybrid model of plasma (kinetic ions, fluid electrons). We present the global structure of the electric fields and power density (E ⋅ J) in the magnetosphere of Ganymede and show that the power density at the magnetopause is mainly positive and on average is +0.95 and +0.75 nW/m3 when Ganymede is inside and outside the Jovian plasma sheet, respectively, but locally it reaches over +20 nW/m3. Our kinetic simulations show that ion velocity distributions at the vicinity of the upstream magnetopause of Ganymede are highly non‐Maxwellian. We investigate the energization of the ions interacting with the magnetopause and find that the energy of those particles on average increases by a factor of 8 and 30 for the O+ and H+ ions, respectively. The energy of these ions is mostly within 1–100 keV for both species after interaction with the magnetopause, but a few percentages reach to 0.1–1 MeV. Our kinetic simulations show that a small fraction (25%) of the corotating Jovian plasma reach the magnetopause, but among those >50% cross the high‐power density regions at the magnetopause and gain energy. Finally, we compare our simulation results with Galileo observations of Ganymede's magnetopause crossings (i.e., G8 and G28 flybys). There is an excellent agreement between our simulations and observations, particularly our simulations fully capture the size and structure of the magnetosphere.
Listvenite Formation During Mass Transfer into the Leading Edge of the Mantle Wedge: Initial Results from Oman Drilling Project Hole BT1B
Authors: Kelemen Peter B. , Carlos de Obeso Juan , Leong James A. , Godard Marguerite , Okazaki Keishi , Kotowski Alissa J. , Manning Craig E. , Ellison Eric T. , Menzel Manuel D. , Urai Janos L. , Hirth Greg , Rioux Matthew , Stockli Daniel F. , Lafay Romain , Beinlich Andreas M. , Coggon Jude A. , Warsi Nehal H. , Matter Jürg M. , Teagle Damon A. H. , Harris Michelle , Michibayashi Katsuyoshi , Takazawa Eiichi , Al Sulaimani Zaher ,   The Oman Drilling Project Science Team
Published: January 2022

This paper provides an overview of research on core from Oman Drilling Project Hole BT1B and the surrounding area, plus new data and calculations, constraining processes in the Tethyan subduction zone beneath the Samail ophiolite. The area is underlain by gently dipping, broadly folded layers of allochthonous Hawasina pelagic sediments, the metamorphic sole of the Samail ophiolite, and Banded Unit peridotites at the base of the Samail mantle section. Despite reactivation of some faults during uplift of the Jebel Akdar and Saih Hatat domes, the area preserves the tectonic “stratigraphy” of the Cretaceous subduction zone. Gently dipping listvenite bands, parallel to peridotite banding and to contacts between the peridotite and the metamorphic sole, replace peridotite at and near the basal thrust. Listvenites formed at less than 200°C and (poorly constrained) depths of 25–40 km by reaction with CO2‐rich, aqueous fluids migrating from greater depths, derived from devolatilization of subducting sediments analogous to clastic sediments in the Hawasina Formation, at 400°–500°. Such processes could form important reservoirs for subducted CO2. Listvenite formation was accompanied by ductile deformation of serpentinites and listvenites—perhaps facilitated by fluid‐rock reaction—in a process that could lead to aseismic subduction in some regions. Addition of H2O and CO2to the mantle wedge, forming serpentinites and listvenites, caused large increases in the solid mass and volume of the rocks. This may have been accommodated by fractures formed as a result of volume changes, mainly at a serpentinization front.
When Will MISR Detect Rising High Clouds?
Authors: Aerenson Travis , Marchand Roger , Chepfer Hélène , Medeiros Brian
Published: January 2022

It is predicted by both theory and models that high‐altitude clouds will occur higher in the atmosphere as a result of climate warming. This produces a positive longwave feedback and has a substantial impact on the Earth's response to warming. This effect is well established by theory, but is poorly constrained by observations, and there is large spread in the feedback strength between climate models. We use the NASA Multi‐angle Imaging SpectroRadiometer (MISR) to examine changes in Cloud‐Top‐Height (CTH). MISR uses a stereo‐imaging technique to determine CTH. This approach is geometric in nature and insensitive to instrument calibration and therefore is well suited for trend analysis and studies of variability on long time scales. In this article we show that the current MISR record does have an increase in CTH for high‐altitude cloud over Southern Hemisphere (SH) oceans but not over Tropical or the Northern Hemisphere (NH) oceans. We use climate model simulations to estimate when MISR might be expected to detect trends in CTH, that include the NH. The analysis suggests that according to the models used in this study MISR should detect changes over the SH ocean earlier than the NH, and if the model predictions are correct should be capable of detecting a trend over the Tropics and NH very soon (3–10 years). This result highlights the potential value of a follow‐on mission to MISR, which no longer maintains a fixed equator crossing time and is unlikely to be making observations for another 10 years.
Reconstructing Terrestrial Paleoclimates: A Comparison of the Co‐Existence Approach, Bayesian and Probability Reconstruction Techniques Using the UK Neogene
Authors: Gibson M. E. , McCoy J. , O’Keefe J. M. K. , Nuñez Otaño N. B. , Warny S. , Pound M. J.
Published: January 2022

Neogene sediments in the UK are ideally situated for understanding the early development of hydrological dynamics and atmospheric circulation that led to the modern oceanic climate of northwest Europe. Onshore Neogene fossiliferous deposits in the UK are limited to the solution pipe fills at Trwyn y Parc in Anglesey (Middle Miocene), the Brassington Formation of Derbyshire (Serravallian‐Tortonian), and the Coralline Crag Formation (latest Zanclean‐earliest Piacenzian) and Red Crag Formation (Piacenzian‐Gelasian) in southeast England. Palynoflora from these localities can be used to provide snapshots into the climate at the time of deposition, however, palaeobotanical‐based reconstructions are typically lacking in their poor estimation of error. Therefore, we present the first pre‐Quaternary application of two terrestrial climate reconstruction techniques: CREST (Climate Reconstruction SofTware) and CRACLE (Climate Reconstruction Analysis using Coexistence Likelihood Estimation), that use Bayesian and likelihood estimation probability respectively to generate a new palaeoclimate reconstruction, and compare this to Co‐existence Approach reconstructions from the UK and continental Europe. Our study shows how Mean Annual Temperature (MAT) declines by 3°–6°C, Mean Annual Precipitation (MAP) declines by 480–600 mm and Precipitation Seasonality approximately halves throughout the Neogene. CREST and CRACLE reconstructions overlap with the Co‐exisence Approach and have the advantage of providing uncertainty, rather than ranges. The UK appears to have had a milder, wetter, and less seasonal climate than continental Europe. This is likely due to the buffering effects of the Atlantic Ocean and North Sea ameliorating the UK Neogene climate despite regional and global changes in atmospheric and oceanic circulation.
Cell-free DNA analysis in current cancer clinical trials: a review
Authors: Cisneros-Villanueva M. , Hidalgo-Pérez L. , Rios-Romero M. , Cedro-Tanda A. , Ruiz-Villavicencio C. A. , Page K. , Hastings R. , Fernandez-Garcia D. , Allsopp R. , Fonseca-Montaño M. A. , Jimenez-Morales S. , Padilla-Palma V. , Shaw J. A. , Hidalgo-Miranda A.
Published: January 2022

Cell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility and usefulness has been demonstrated, several issues related to standardisation and technical validation must be addressed for its routine clinical application in cancer. In this regard, most cfDNA clinical applications are still limited to clinical trials, proving its value in several settings. In this paper, we review the current clinical trials involving cfDNA/ctDNA analysis and highlight those where it has been useful for patient stratification, treatment follow-up or development of novel approaches for early diagnosis. Our query included clinical trials, including the terms ‘cfDNA’, ‘ctDNA’, ‘liquid biopsy’ AND ‘cancer OR neoplasm’ in the FDA and EMA public databases. We identified 1370 clinical trials (FDA = 1129, EMA = 241) involving liquid-biopsy analysis in cancer. These clinical trials show promising results for the early detection of cancer and confirm cfDNA as a tool for real-time monitoring of acquired therapy resistance, accurate disease-progression surveillance and improvement of treatment, situations that result in a better quality of life and extended overall survival for cancer patients.
Exosomal circRELL1 serves as a miR-637 sponge to modulate gastric cancer progression via regulating autophagy activation
Authors: Sang Huaiming , Zhang Weifeng , Peng Lei , Wei Shuchun , Zhu Xudong , Huang Keting , Yang Jiajia , Chen Meihong , Dang Yini , Zhang Guoxin
Published: January 2022

Circular RNAs (circRNAs) play a vital role in the occurrence and development of tumors, including gastric cancer (GC). However, there are still many circRNAs related to GC whose functions and molecular mechanisms remain undetermined. Herein, we discover circRNA RELL1, which has not been investigated in GC, and it is markedly downregulated in GC tissues, which is related with poor prognosis, more pronounced lymph node metastasis and poor TNM stage. After confirming the circular structure of circRELL1, we found that circRELL1 could block cell proliferation, invasion, migration, and anti-apoptosis in patients with GC by a series of in vivo and in vitro function-related studies. Further mechanism investigation demonstrated that circRELL1 could sponge miR-637 and indirectly unregulated the expression of EPHB3 via modulating autophagy activation in GC. Additionally, circRELL1 can be transmitted by exosomal communication, and exosomal circRELL1 suppressed the malignant behavior of GC in vivo and in vitro. Taken together, this study elucidates the suppressive roles of circRELL1/miR-637/EPHB3 axis through autophagy activation in GC progression, inspiring for further understanding of the underlying molecular mechanisms of GC and providing a promising novel diagnostic circulating biomarker and therapeutic target in GC.
ZC3H15 promotes glioblastoma progression through regulating EGFR stability
Authors: Hou Jianbing , Xu Minghao , Gu Hongyu , Pei Dakun , Liu Yudong , Huang Pan , Chang Hongbo , Cui Hongjuan
Published: January 2022

Zinc finger CCCH-type containing 15 (ZC3H15), a highly conserved protein involved in several cellular processes, which was responsible for tumorigenesis and may be a promising marker in myeloid leukemia (AML) and hepatocellular carcinoma (HCC). However, little is known about the biological significance and molecular mechanisms of ZC3H15 in GBM. In this study, we revealed that ZC3H15 was overexpressed in GBM and high ZC3H15 expression was associated with poor survival of patients with GBM. We found that ZC3H15 promoted the proliferation, migration, invasion, and tumorigenesis of GBM cells by activating the EGFR signaling pathway. We also revealed that ZC3H15 reduced EGFR ubiquitination, which was responsible for EGFR protein stabilization. In addition, we demonstrated that ZC3H15 inhibited the transcription of CBL, which was an E3 ubiquitin ligase for EGFR proteasomal degradation. And silencing of CBL could partly abrogate the inhibitory effects on cell proliferation, migration, and invasion of GBM cells induced by ZC3H15 knockdown. Thus, our research revealed the important roles of ZC3H15 in GBM development and provided a brand-new insight for improving the treatment of GBMs.
MiR-135b-5p is an oncogene in pancreatic cancer to regulate GPRC5A expression by targeting transcription factor KLF4
Authors: Liu Daren , Jin Yun , Wu Jinhong , Zhu Huanbing , Ye Dan
Published: January 2022

KLF4 is implicated in tumor progression of pancreatic cancer, but the molecular regulatory mechanism of KLF4 needs to be further specified. We aimed to probe molecular regulatory mechanism of KLF4 in malignant progression of pancreatic cancer. qRT-PCR or western blot was completed to test levels of predicted genes. Dual-luciferase and chromatin immunoprecipitation (ChIP) assays were designed to validate binding between genes. Cell viability and oncogenicity detection were used for in vitro and vivo functional assessment. KLF4 was a downstream target of miR-135b-5p. KLF4 could regulate GPRC5A level. MiR-135b-5p was notably increased in cancer cells, and overexpressing KLF4 functioned a tumor repressive role, which could be restored by miR-135b-5p. Besides, cell malignant phenotypes could be inhibited through reducing miR-135b-5p level, but they were restored by GPRC5A. Our results stressed that KLF4, as a vital target of miR-135b-5p, could influence promoter region of GPRC5A, thus affecting the malignant progression of pancreatic cancer.
USP15 and USP4 facilitate lung cancer cell proliferation by regulating the alternative splicing of SRSF1
Authors: Das Tanuza , Lee Eun-Young , You Hye Jin , Kim Eunice EunKyeong , Song Eun Joo
Published: January 2022

The deubiquitinating enzyme USP15 is implicated in several human cancers by regulating different cellular processes, including splicing regulation. However, the underlying molecular mechanisms of its functional relevance and the successive roles in enhanced tumorigenesis remain ambiguous. Here, we found that USP15 and its close paralog USP4 are overexpressed and facilitate lung cancer cell proliferation by regulating the alternative splicing of SRSF1. Depletion of USP15 and USP4 impair SRSF1 splicing characterized by the replacement of exon 4 with non-coding intron sequences retained at its C-terminus, resulting in an alternative isoform SRSF1-3. We observed an increased endogenous expression of SRSF1 in lung cancer cells as well, and its overexpression significantly enhanced cancer cell phenotype and rescued the depletion effect of USP15 and USP4. However, the alternatively spliced isoform SRSF1-3 was deficient in such aspects for its premature degradation through nonsense-mediated mRNA decay. The increased USP15 expression contributes to the lung adenocarcinoma (LUAD) development and shows significantly lower disease-specific survival of patients with USP15 alteration. In short, we identified USP15 and USP4 as key regulators of SRSF1 alternative splicing with altered functions, which may represent the novel prognostic biomarker as well as a potential target for LUAD.
Post translational modifications of Trifolitoxin: a blue fluorescent peptide antibiotic
Authors: Lethbridge Benjamin J. , Asenstorfer Robert E. , Bailey Laura S. , Breil Brenda T. , Johnson Jodie V. , Jones Graham P. , Rumjanek Victor , Sims James J. , Tate Max E. , Triplett Eric W.
Published: January 2022

Trifolitoxin (TFX, C41H63N15O15S) is a selective, ribosomally-synthesized, post-translationally modified, peptide antibiotic, produced by Rhizobium leguminosarum bv. trifolii T24. TFX specifically inhibits α-proteobacteria, including the plant symbiont Rhizobium spp., the plant pathogen Agrobacterium spp. and the animal pathogen Brucella abortus. TFX-producing strains prevent legume root nodulation by TFX-sensitive rhizobia. TFX has been isolated as a pair of geometric isomers, TFX1 and TFX2, which are derived from the biologically inactive primary amino acid sequence: Asp-Ile-Gly-Gly-Ser-Arg-Gln-Gly-Cys-Val-Ala. Gly-Cys is present as a thiazoline ring and the Arg-Gln-Gly sequence is extensively modified to a UV absorbing, blue fluorescent chromophore. The chromophore consists of a conjugated, 5-membered heterocyclic ring and side chain of modified glutamine.
Clinical and genetic diagnosis of thirteen Japanese patients with hereditary spherocytosis
Authors: Yamamoto Keiko Shimojima , Utshigisawa Taiju , Ogura Hiromi , Aoki Takako , Kawakami Takahiro , Ohga Shoichi , Ohara Akira , Ito Etsuro , Yamamoto Toshiyuki , Kanno Hitoshi
Published: January 2022

Hereditary spherocytosis is the most frequent cause of hereditary hemolytic anemia and is classified into five subtypes (SPH1-5) according to OMIM. Because the clinical and laboratory features of patients with SPH1-5 are variable, it is difficult to classify these patients into the five subtypes based only on these features. We performed target capture sequencing in 51 patients with hemolytic anemia associated with/without morphological abnormalities in red blood cells. Thirteen variants were identified in five hereditary spherocytosis-related genes (six inANK1[SPH1]; four inSPTB[SPH2]; and one in each ofSPTA1[SPH3],SLC4A1[SPH4], andEPB42[SPH5]). Among these variants, seven were novel. The distribution pattern of the variants was different from that reported previously in Japan but similar to those reported in other Asian countries. Comprehensive genomic analysis would be useful and recommended, especially for patients without a detailed family history and those receiving frequent blood transfusions due to chronic hemolytic anemia.
Towards practical quantum computers: transmon qubit with a lifetime approaching 0.5 milliseconds
Authors: Wang Chenlu , Li Xuegang , Xu Huikai , Li Zhiyuan , Wang Junhua , Yang Zhen , Mi Zhenyu , Liang Xuehui , Su Tang , Yang Chuhong , Wang Guangyue , Wang Wenyan , Li Yongchao , Chen Mo , Li Chengyao , Linghu Kehuan , Han Jiaxiu , Zhang Yingshan , Feng Yulong , Song Yu , Ma Teng , Zhang Jingning , Wang Ruixia , Zhao Peng , Liu Weiyang , Xue Guangming , Jin Yirong , Yu Haifeng
Published: January 2022

Here we report a breakthrough in the fabrication of a long lifetime transmon qubit. We use tantalum films as the base superconductor. By using a dry etching process, we obtained transmon qubits with a best T1 lifetime of 503 μs. As a comparison, we also fabricated transmon qubits with other popular materials, including niobium and aluminum, under the same design and fabrication processes. After characterizing their coherence properties, we found that qubits prepared with tantalum films have the best performance. Since the dry etching process is stable and highly anisotropic, it is much more suitable for fabricating complex scalable quantum circuits, when compared to wet etching. As a result, the current breakthrough indicates that the dry etching process of tantalum film is a promising approach to fabricate medium- or large-scale superconducting quantum circuits with a much longer lifetime, meeting the requirements for building practical quantum computers.
Terahertz pulse-driven collective mode in the nematic superconducting state of Ba1−xKxFe2As2
Authors: Grasset Romain , Katsumi Kota , Massat Pierre , Wen Hai-Hu , Chen Xian-Hui , Gallais Yann , Shimano Ryo
Published: January 2022

We investigate the collective mode response of the iron-based superconductor Ba1−xKxFe2As2 using intense terahertz (THz) light. In the superconducting state a THz Kerr signal is observed and assigned to nonlinear THz coupling to superconducting degrees of freedom. The polarization dependence of the THz Kerr signal is remarkably sensitive to the coexistence of a nematic order. In the absence of nematic order the C4 symmetric polarization dependence of the THz Kerr signal is consistent with a coupling to the Higgs amplitude mode of the superconducting condensate. In the coexisting nematic and superconducting state the signal becomes purely nematic with a vanishing C4 symmetric component, signaling the emergence of a superconducting collective mode activated by nematicity.
Structure of UBE2K–Ub/E3/polyUb reveals mechanisms of K48-linked Ub chain extension
Authors: Nakasone Mark A. , Majorek Karolina A. , Gabrielsen Mads , Sibbet Gary J. , Smith Brian O. , Huang Danny T.
Published: January 2022

Ubiquitin (Ub) chain types govern distinct biological processes. K48-linked polyUb chains target substrates for proteasomal degradation, but the mechanism of Ub chain synthesis remains elusive due to the transient nature of Ub handover. Here, we present the structure of a chemically trapped complex of the E2 UBE2K covalently linked to donor Ub and acceptor K48-linked di-Ub, primed for K48-linked Ub chain synthesis by a RING E3. The structure reveals the basis for acceptor Ub recognition by UBE2K active site residues and the C-terminal Ub-associated (UBA) domain, to impart K48-linked Ub specificity and catalysis. Furthermore, the structure unveils multiple Ub-binding surfaces on the UBA domain that allow distinct binding modes for K48- and K63-linked Ub chains. This multivalent Ub-binding feature serves to recruit UBE2K to ubiquitinated substrates to overcome weak acceptor Ub affinity and thereby promote chain elongation. These findings elucidate the mechanism of processive K48-linked polyUb chain formation by UBE2K.
Visualizing the native cellular organization by coupling cryofixation with expansion microscopy (Cryo-ExM)
Authors: Laporte Marine H. , Klena Nikolai , Hamel Virginie , Guichard Paul
Published: January 2022

Cryofixation has proven to be the gold standard for efficient preservation of native cell ultrastructure compared to chemical fixation, but this approach is not widely used in fluorescence microscopy owing to implementation challenges. Here, we develop Cryo-ExM, a method that preserves native cellular organization by coupling cryofixation with expansion microscopy. This method bypasses artifacts associated with chemical fixation and its simplicity will contribute to its widespread use in super-resolution microscopy.
A reverse transcription-cross-priming amplification method with lateral flow dipstick assay for the rapid detection of Bean pod mottle virus
Authors: Yang Qian-Qian , Zhao Xing-Xing , Wang Dao , Zhang Peng-Jun , Hu Xue-Nan , Wei Shuang , Liu Jing-Yuan , Ye Zi-Hong , Yu Xiao-Ping
Published: January 2022

Bean pod mottle virus(BPMV) is a destructive virus that causes serious economic losses in many countries every year, highlighting the importance of its effective detection. In this study, we developed a fast reverse transcription-cross-priming amplification (RT-CPA) coupled with lateral flow dipstick (LFD) diagnostic method for BPMV detection. The RT-CPA-LFD assay that targets the coat protein gene of BPMV was highly specific against diagnosing four other common viruses transmitted by soybean seeds, i.e.,Southern bean mosaic virus(SBMV),Tomato ringspot virus (ToRSV),Arabis mosaic virus (ArMV), andTobacco ringspot virus (TRSV). The sensitivities of the real-time fluorescent RT-CPA and the RT-CPA-LFD assay were at least 50 pg/μl and 500 pg/μl, respectively. Despite a compromise in the limit of detection of the RT-CPA method compared with TaqMan-MGB real-time RT-PCR, our results demonstrated a notably better performance in the detection of field samples of BPMV-infested soybean seeds. With the advantages of efficiency and convenience by visual determination, the RT-CPA-LFD assay presents a potential application for the rapid and accurate detection of BPMV in routine tests.
Synergy between an emerging monopartite begomovirus and a DNA-B component
Authors: Ouattara Alassane , Tiendrébéogo Fidèle , Becker Nathalie , Urbino Cica , Thébaud Gaël , Hoareau Murielle , Allibert Agathe , Chiroleu Frédéric , Vernerey Marie-Stéphanie , Traoré Edgar Valentin , Barro Nicolas , Traoré Oumar , Lefeuvre Pierre , Lett Jean-Michel
Published: January 2022

In recent decades, a legion of monopartite begomoviruses transmitted by the whitefly Bemisia tabaci has emerged as serious threats to vegetable crops in Africa. Recent studies in Burkina Faso (West Africa) reported the predominance of pepper yellow vein Mali virus (PepYVMLV) and its frequent association with a previously unknown DNA-B component. To understand the role of this DNA-B component in the emergence of PepYVMLV, we assessed biological traits related to virulence, virus accumulation, location in the tissue and transmission. We demonstrate that the DNA-B component is not required for systemic movement and symptom development of PepYVMLV (non-strict association), but that its association produces more severe symptoms including growth arrest and plant death. The increased virulence is associated with a higher viral DNA accumulation in plant tissues, an increase in the number of contaminated nuclei of the phloem parenchyma and in the transmission rate by B. tabaci. Our results suggest that the association of a DNA-B component with the otherwise monopartite PepYVMLV is a key factor of its emergence.
Lapatinib as first-line treatment for muscle-invasive urothelial carcinoma in dogs
Authors: Maeda Shingo , Sakai Kosei , Kaji Kenjiro , Iio Aki , Nakazawa Maho , Motegi Tomoki , Yonezawa Tomohiro , Momoi Yasuyuki
Published: January 2022

Epidermal growth factor receptors 1 and 2 (EGFR and HER2) are frequently overexpressed in various malignancies. Lapatinib is a dual tyrosine kinase inhibitor that inhibits both EGFR and HER2. Although a phase III trial failed to show the survival benefits of lapatinib treatment after first-line chemotherapy in patients with EGFR/HER2-positive metastatic urothelial carcinoma, the efficacy of lapatinib for untreated urothelial carcinoma is not well defined. Here, we describe the therapeutic efficacy of lapatinib as a first-line treatment in a canine model of muscle-invasive urothelial carcinoma. In this non-randomized clinical trial, we compared 44 dogs with naturally occurring urothelial carcinoma who received lapatinib and piroxicam, with 42 age-, sex-, and tumor stage-matched dogs that received piroxicam alone. Compared to the dogs treated with piroxicam alone, those administered the lapatinib/piroxicam treatment had a greater reduction in the size of the primary tumor and improved survival. Exploratory analyses showed that HER2 overexpression was associated with response and survival in dogs treated with lapatinib. Our study suggests that lapatinib showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use for untreated advanced urothelial carcinoma in dogs. The use of lapatinib as a first-line treatment may be investigated further in human patients with urothelial carcinoma.
Longer than 2 hours to antibiotics is associated with doubling of mortality in a multinational community-acquired bacterial meningitis cohort
Authors: Eisen Damon P. , Hamilton Elizabeth , Bodilsen Jacob , Køster-Rasmussen Rasmus , Stockdale Alexander J. , Miner James , Nielsen Henrik , Dzupova Olga , Sethi Varun , Copson Rachel K. , Harings Miriam , Adegboye Oyelola A.
Published: January 2022

To optimally define the association between time to effective antibiotic therapy and clinical outcomes in adult community-acquired bacterial meningitis. A systematic review of the literature describing the association between time to antibiotics and death or neurological impairment due to adult community-acquired bacterial meningitis was performed. A retrospective cohort, multivariable and propensity-score based analyses were performed using individual patient clinical data from Australian, Danish and United Kingdom studies. Heterogeneity of published observational study designs precluded meta-analysis of aggregate data (I2 = 90.1%, 95% CI 71.9–98.3%). Individual patient data on 659 subjects were made available for analysis. Multivariable analysis was performed on 180–362 propensity-score matched data. The risk of death (adjusted odds ratio, aOR) associated with treatment after two hours was 2.29 (95% CI 1.28–4.09) and increased substantially thereafter. Similarly, time to antibiotics of greater than three hours was associated with an increase in the occurrence of neurological impairment (aOR 1.79, 95% CI 1.03–3.14). Among patients with community-acquired bacterial meningitis, odds of mortality increase markedly when antibiotics are given later than two hours after presentation to the hospital.