bluuebunny/crossref_metadata_2025 huggingface dataset:
cGAS restricts colon cancer development by protecting intestinal barrier integrity
Authors: Hu Shuiqing , Fang Yan , Chen Xiang , Cheng Tianlei , Zhao Miaoqing , Du Mingjian , Li Tuo , Li Minghao , Zeng Zhiqun , Wei Yonglong , Gu Zhimin , Zhang Conggang , Sun Lijun , Chen Zhijian J.
Published: June 2021

Significance

Intestinal barrier plays a key role in maintaining organismal health. Here we find cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) deficiency compromises intestinal epithelial barrier and exacerbates inflammation. cGAS-deficient mice were highly susceptible to colitis-associated colon cancer (CAC) but not sporadic colon cancer. Surprisingly, the role of cGAS in this process appears to be independent of stimulator of interferon genes (STING)-induced type I interferon signaling, because mice lacking STING or type I interferon receptor were less susceptible to CAC than those lacking cGAS. cGAS but not STING is highly expressed in intestinal stem cells. These results suggest that cGAS has a unique role in protecting the intestinal epithelial barrier and preventing colon cancer development.
The difference between squat jump and countermovement jump in 770 male and female participants from different sports
Authors: Kozinc Žiga , Žitnik Jure , Smajla Darjan , Šarabon Nejc
Published: June 2021

Traditionally, a larger difference between countermovement (CMJ) and squat jump (SJ) was seen as beneficial, as it reflects the ability to utilize the stretch‐shortening cycle. However, strong arguments have been made that this might not always be the case, as larger differences between the jumps could also suggest higher muscle‐tendon slack, or poor capability to take this slack up quickly. The purpose of this study was to explore SJ and CMJ, as well as the CMJ to SJ difference (CMJSJDiff) in 9 groups of young athletes. In total, 712 athletes from various disciplines (mean age range: 15.7–36.3 years) and 58 physical education students (mean age: 19.6 years) participated in the study. The major finding of this study was that the groups that showed better SJ and CMJ performance did not show the larger CMJSJDiff. For instance, SJ and CMJ heights were highest in short‐distance runners and lowest in long‐distance runners, while the largest and smallest CMJSJDiff was shown in physical education students and speed skaters, respectively. Male athletes had a higher CMJSJDiff than female athletes, but the difference was very small. While a larger CMJSJDiff has been traditionally associated viewed as positive, our results could indicate both superior ability to utilize the stretch‐shortening cycle, as well as poor ability of rapid force development and excessive muscle slack. Further studies are needed to directly investigate the associations between CMJSJDiff and indicators of athletic performance.
Understanding detachment of the W7-X island divertor
Authors: Feng Y. , Jakubowski M. , König R. , Krychowiak M. , Otte M. , Reimold F. , Reiter D. , Schmitz O. , Zhang D. , Beidler C.D. , Biedermann C. , Bozhenkov S. , Brunner K.J. , Dinklage A. , Drewelow P. , Effenberg F. , Endler M. , Fuchert G. , Gao Y. , Geiger J. , Hammond K.C. , Helander P. , Killer C. , Knauer J. , Kremeyer T. , Pasch E. , Rudischhauser L. , Schlisio G. , Sunn Pedersen T. , Wenzel U. , Winters V. , W7-X team
Published: June 2021

The fundamental behavior of the W7-X island divertor under detached conditions, which has been theoretically predicted with the EMC3-Eirene code, is re-examined here under the experimental conditions achieved so far and compared with the first experimental results. Both simulations and experiments cover a range of divertor configurations and plasma parameters, and show the following common trends: (1) with rising impurity radiation, the target heat load decreases ‘uniformly’ over the entire target surface in the sense that both the peak and average heat loads can drop by an order of magnitude. Impurity radiation (mainly from intrinsic carbon) occurs primarily at the plasma edge and the resulting negative impact on the stored energy is less than 10%. (2) When the total radiation exceeds a critical level, the target particle flux (the recycling flux Γrecy) begins to fall and can drop by a factor of 3–5 at high radiation levels without an obvious indication of significant volume recombination. (3) While Γrecy decreases, the divertor neutral pressure continues to build up and reaches a maximum, at which point Γrecy has declined significantly. (4) During detachment, the electron temperature at the last closed flux surface falls in a way that is not quantitatively understandable from parallel classical heat conduction processes. This paper presents a physical explanation of the numerical/experimental results described above. Furthermore, using the EMC3-Eirene code as a diagnostic tool, we are able, apparently for the first time, to provide a full quantitative analysis of each transport channel in the island divertor, aiming to clarify how the island divertor plasma self-regulates to maintain particle, energy, and momentum balance under detached conditions.
Changes in regional wet heatwave in Eurasia during summer (1979–2017)
Authors: Yu Shuang , Tett Simon F B , Freychet Nicolas , Yan Zhongwei
Published: June 2021

Wet heatwaves can have more impact on human health than hot dry heatwaves. However, changes in these have received little scientific attention. Using the ECMWF Reanalysis v5 reanalysis dataset, wet-bulb temperatures (T
w) were used to investigate the spatial-temporal variation of wet heatwaves in Eurasia for 1979–2017. Wet heatwaves were defined as three day or longer periods when T
w was above the 90th percentile of the summer distribution and characterized by amplitude, duration and frequency. Maximum values of amplitude, close to 31 °C, occur in the Indus–Ganges plain, the lower Yangtze valley, and the coasts of the Persian Gulf and Red Sea. Significant positive trends in the frequency and amplitude of wet heatwaves have occurred over most of Eurasia though with regional variations. Changes in heatwave amplitude (HWA) are largely driven by changes in summer mean T
w. For Eurasia as a whole, increases in temperature contribute more than six times the impact of changes in relative humidity (RH) to changes in T
w HWA. Changes in T
w have a strong dependence on climatological RH with an increase in RH of 1% causing a T
w increase of 0.2 °C in arid regions, and only increasing T
w by 0.1 °C in humid regions. During T
w heatwaves in Europe, parts of Tibet, India, East Asia and parts of the Arabian Peninsula both temperature and humidity contribute to the increase in T
w, with temperature the dominant driver. During wet heatwaves in part of Russia, changes in humidity are weak and the increase in T
w is mainly caused by an increase in temperature. In the Mediterranean and Central Asia, RH has fallen reducing the increase in T
w from general warming.
A porous material of cross-linked adenine-polyethylene glycol diglycidyl ether for copper ion adsorption
Authors: Zhang Longfei , Zhang Shuai , Wang Cheng , Li Wa , Yang Lirong , Li Shanggeng , Hu Jiaming , Zhang Lin
Published: June 2021

A porous material (PEA) was prepared by the ring opening polymerization of polyethylene glycol diglycidyl ether with adenine in a simple sol-gel method. The structure and composition of PEA were characterized by SEM, FT-IR, BET and XRD. The adsorption experiments of copper ion by PEA at different pH, temperature, contact time and initial concentration were studied. The results show that the PEA is macroporous, the optimum adsorption pH is 5 and the saturated adsorption time is 180 min. The maximum equilibrium adsorption capacity of copper ion is 80.1 mg g−1 at 40 °C according to the Langmuir model and the competitive adsorption test shows that PEA has good adsorption on copper ion, but low effect on cobalt, cadmium and nickel. The repeated adsorption experiments show that PEA could still adsorb 82% of the first adsorption capacity after 5 times elution. These results indicate that the PEA can be used as a practical adsorbent for copper ion adsorption in aqueous solution.
Loading and sustained release of sodium alginate membranes on pyridirubicin chloride
Authors: Li Mengde , Li Yahua , Wang Xiaofeng , Chang Zhonghua , Jiang Yong-Chao , Han Shanshan , Cui Zhixiang , Han Xinwei , Li Qian
Published: June 2021

To develop diversified drug carriers for local treatment of cancer, three types of alginate membranes were fabricated by spin-coating, freeze drying and electrospinning. The uniaxial tensile test is shown that spin-coated membranes possess the maximum tensile strength. All the three types of membranes present excellent adsorption performance toward pyridirubicin chloride (THP) and the electrospinning membranes exhibit the maximum adsorption mass of 144.13 mg g−1. The pseudo-first order, pseudo-second order, and intra-particle diffusion equation were used to evaluate the kinetic data and the drug adsorption process followed the pseudo-first-order model well. The drug releasing mechanism was studied by using different release medium, and it shows that the release process was undertaken by ions exchange reaction. The result shows that the three types of membranes are promising materials for the local treatment of cancer such as local cancers of the pancreas and trachea.
Fatigue failure of SUP-9 spring steel
Authors: Daudpoto Jawaid , Kumar Dileep , Shaikh Shakeel Ahmed , Hussain Tanweer , Memon Zeeshan Ali
Published: June 2021

The SUP-9 is a widely used steel for the construction of springs due to its resistance to permanent deformation and quick vibration relief. Spring steels are subjected to heat treatment to improve their fatigue life. In this paper, the heat treatment procedure to improve the endurance limit of the SUP-9 is reported. The process of heat treatment was carried out to investigate its effect on Brinell and Rockwell hardness metrics. The endurance limits of steel before and after heat treatment were also measured. The heat treatment procedure reported in this paper resulted in an increased harness and endurance limit due to a change in the microstructure of the specimen. The test results showed that Brinell hardness and endurance limit increased by 50% and 20% respectively after heat treatment.
Application of exact solution of complex morse potential to investigate physical systems with complex and negative masses
Authors: Sarathi Partha , Pathak Nilesh Kumar
Published: June 2021

The interest in the study of physical systems characterized by negative and effective negative masses and their behaviour has been a subject of investigation by several researchers. The focus of the majority of these studies is experimental in nature. Inspired by the same, we have solved the Schrodinger equation for complex Morse potential with negative and complex masses and obtained its exact solution. The normalized eigenfunction and eigenvalues are obtained and the condition for admissibility of the reality of eigenvalue spectrum for the ground state of complex Morse potential has been discussed. This study establishes that it is indeed feasible for such negative masses proposed in the literature for various physical systems to be bound together by complex Morse potential. Further, we propose that atoms with complex and negative masses may bind together under the action of complex Morse-like potentials and form molecular structures.
An intervention to increase physical activity in care home residents: results of a cluster-randomised, controlled feasibility trial (the REACH trial)
Authors: Forster Anne , Airlie Jennifer , Ellwood Alison , Godfrey Mary , Green John , Cundill Bonnie , Dawkins Bryony , McMaster Nicola , Hulme Claire , Cicero Robert , McLellan Vicki , Graham Liz , Gallagher Bev , Ellard David R , Firth Joan , Farrin Amanda ,   the REACH Programme Team
Published: June 2021

Background

Care home (CH) residents are mainly inactive, leading to increased dependency and low mood. Strategies to improve activity are required.

Design and setting

Cluster randomised controlled feasibility trial with embedded process and health economic evaluations. Twelve residential CHs in Yorkshire, United Kingdom, were randomised to the MoveMore intervention plus usual care (UC) (n = 5) or UC only (n = 7).

Participants

Permanent residents aged ≥65 years.

Intervention

MoveMore: a whole home intervention involving all CH staff designed to encourage and support increase in movement of residents.

Objectives and measurements

Feasibility objectives relating to recruitment, intervention delivery, data collection and follow-up and safety concerns informed the feasibility of progression to a definitive trial. Data collection at baseline, 3, 6 and 9 months included: participants’ physical function and mobility, perceived health, mood, quality of life, cognitive impairment questionnaires; accelerometry; safety data; intervention implementation.

Results

300 residents were screened; 153 were registered (62 MoveMore; 91 UC). Average cluster size: MoveMore: 12.4 CHs; UC: 13.0 CHs. There were no CH/resident withdrawals. Forty (26.1%) participants were unavailable for follow-up: 28 died (12 MoveMore; 16 UC); 12 moved from the CH. Staff informant/proxy data collection for participants was >80%; data collection from participants was <75%; at 9 months, 65.6% of residents provided valid accelerometer data; two CHs fully, two partially and one failed to implement the intervention. There were no safety concerns.

Conclusions

Recruiting CHs and residents was feasible. Intervention implementation and data collection methods need refinement before a definitive trial. There were no safety concerns.
Strengthening Health Services Research Using Target Trial Emulation: An Application to Volume-Outcomes Studies
Authors: Madenci Arin L , Wanis Kerollos Nashat , Cooper Zara , Haneuse Sebastien , Subramanian S V , Hofman Albert , Hernán Miguel A
Published: June 2021

The number of operations that surgeons have previously performed is associated with their patients’ outcomes. However, this association may not be causal, because previous studies have often been cross-sectional and their analyses have not considered time-varying confounding or positivity violations. In this paper, using the example of surgeons who perform coronary artery bypass grafting, we describe (hypothetical) target trials for estimation of the causal effect of the surgeons’ operative volumes on patient mortality. We then demonstrate how to emulate these target trials using data from US Medicare claims and provide effect estimates. Our target trial emulations suggest that interventions on physicians’ volume of coronary artery bypass grafting operations have little effect on patient mortality. The target trial framework highlights key assumptions and draws attention to areas of bias in previous observational analyses that deviated from their implicit target trials. The principles of the presented methodology may be adapted to other scenarios of substantive interest in health services research.
Crane and the mark of the mental
Authors: Raimondi Andrea
Published: June 2021

Brentano’s (1874: 88–89) suggestion that intentionality is the mark of the mental is typically spelled out in terms of the thesis that all and only mental states are intentional. An influential objection is that intentionality is not necessary for mentality (McGinn 1982; Dretske 1995; Deonna and Teroni 2012; Bordini 2017). What about the idea that only mental states are intentional? In his 2008 paper published in Analysis, Nes shows that on a popular characterization of intentionality, notably defended by Crane (2014 [1998], 2001), some non-mental states come out as intentional. Crane (2008) replies that the concept of representation solves the problem. In this paper, I argue that no representational account of intentionality meets Nes’s challenge. After distinguishing between two notions of representation, I contend that there are two versions of Crane’s representational account, but neither of them is able to solve the problem posed by Nes.
Towards spatio-temporally resolved developmental cardiac gene regulatory networks in zebrafish
Authors: Hallab Jeannette C , Nim Hieu T , Stolper Julian , Chahal Gulrez , Waylen Lisa , Bolk Francesca , Elliott David A , Porrello Enzo , Ramialison Mirana
Published: June 2021

Heart formation in the zebrafish involves a rapid, complex series of morphogenetic events in three-dimensional space that spans cardiac lineage specification through to chamber formation and maturation. This process is tightly orchestrated by a cardiac gene regulatory network (GRN), which ensures the precise spatio-temporal deployment of genes critical for heart formation. Alterations of the timing or spatial localisation of gene expression can have a significant impact in cardiac ontogeny and may lead to heart malformations. Hence, a better understanding of the cellular and molecular basis of congenital heart disease relies on understanding the behaviour of cardiac GRNs with precise spatiotemporal resolution. Here, we review the recent technical advances that have expanded our capacity to interrogate the cardiac GRN in zebrafish. In particular, we focus on studies utilising high-throughput technologies to systematically dissect gene expression patterns, both temporally and spatially during heart development.
Detecting SARS-CoV-2 and its variant strains with a full genome tiling array
Authors: Jiang Limin , Guo Yan , Yu Hui , Hoff Kendal , Ding Xun , Zhou Wei , Edwards Jeremy
Published: June 2021

Coronavirus disease 2019 pandemic is the most damaging pandemic in recent human history. Rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and variant strains is paramount for recovery from this pandemic. Conventional SARS-CoV-2 tests interrogate only limited regions of the whole SARS-CoV-2 genome, which are subjected to low specificity and miss the opportunity of detecting variant strains. In this work, we developed the first SARS-CoV-2 tiling array that captures the entire SARS-CoV-2 genome at single nucleotide resolution and offers the opportunity to detect point mutations. A thorough bioinformatics protocol of two base calling methods has been developed to accompany this array. To demonstrate the effectiveness of the tiling array, we genotyped all genomic positions of eight SARS-CoV-2 samples. Using high-throughput sequencing as the benchmark, we show that the tiling array had a genome-wide accuracy of at least 99.5%. From the tiling array analysis results, we identified the D614G mutation in the spike protein in four of the eight samples, suggesting the widespread distribution of this variant at the early stage of the outbreak in the United States. Two additional nonsynonymous mutations were identified in one sample in the nucleocapsid protein (P13L and S197L), which may complicate future vaccine development. With around $5 per array, supreme accuracy, and an ultrafast bioinformatics protocol, the SARS-CoV-2 tiling array makes an invaluable toolkit for combating current and future pandemics. Our SARS-CoV-2 tilting array is currently utilized by Molecular Vision, a CLIA-certified lab for SARS-CoV-2 diagnosis.
Simultaneous Determination of Iridoid Glycosides, Phenylpropanoid Glycosides, Organic Acids, Nucleosides and Amino Acids in Scrophulariae Radix Processed by Different Processing Methods by HPLC-QTRAP-MS/MS
Authors: Wang Shengnan , Wang Qin , Yin Xiaoqin , Chen Bohua , Liu Xunhong
Published: June 2021

Scrophulariae Radix is one of the widely used traditional Chinese medicines. In this study, a high-performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry method was established for the simultaneous determination of multiple bioactive constituents including four iridoid glycosides, two phenylpropanoid glycosides, six organic acids, 11 nucleosides and 16 amino acids in Scrophulariae Radix. The validated method was used to analyze nine Scrophulariae Radix samples processed by different processing methods. In addition, Grey relational analysis and DTOPSIS were used to evaluate the samples according to the content of 39 ayalytes. The results showed that the quality of Scrophulariae Radix processed by cutting into slices, sun drying and “sweating” methods were better. All the results proved that the developed method was available and could be used to evaluate the quality of Scrophulariae Radix.
Simultaneous Quantification of Four Compounds in Rat Plasma by HPLC–MS/MS and Its Application to Pharmacokinetic Study after Oral Administration of Pomegranate Flowers
Authors: Yisimayili Zainaipuguli , Tian Qiang , Xie Yang , Hu Pei , Abdulla Rahima , Wu Tao , Sun Zhaolin , Chen Mingcang , Aisa Haji Akber , Huang Chenggang
Published: June 2021

Pomegranate flowers (PFs) were reported to possess various biological activities such as antidiabetic, anti-inflammatory and hepatoprotective activities, and using to treat diabetes. Although chemical constituents and pharmacological activities of PFs have been studied, unfortunately, there was no report on the pharmacokinetic profile of PFs in vivo. In this study, a selective high-performance liquid chromatography triple quadrupole tandem mass spectrometry (HPLC–QQQ–MS/MS) method was developed and validated for simultaneous quantification of four compounds (corilagin, ellagic acid, gallic acid and brevifolincarboxylic acid) in rat plasma after oral administration of PFs. The good linearity concentration ranges for the four analytes were from 2.5 to 3000 ng/mL with coefficient value R2 > 0.99 in calibration curves. The intra- and inter-day accuracy of the four analytes was in the range of 85.33–102.50%, with relative standard deviation (RSD) of <14.81%. The stability results showed that accuracy of the four analytes was in the range of 81.88–104.74%, with RSD of <14.86%. The validation method was successfully applied to pharmacokinetic profiles of the four analytes in rats after oral administration of PFs extract. This pharmacokinetic study can provide better understanding to clarify in vivo mechanisms of PFs and may facilitate its further development as therapeutic agent.
A Clean, Sustainable and Stability-Indicating Method for the Quantification of Ceftriaxone Sodium in Pharmaceutical Product by HPLC
Authors: da Trindade Mariana Teixeira , Kogawa Ana Carolina , Salgado Hérida Regina Nunes
Published: June 2021

Ceftriaxone sodium is a widely used antimicrobial, which is only available as a lyophilized powder. The presence of methods for evaluating the quality of this product is very important and helps to ensure its effectiveness, in addition to contributing to the fight against bacterial resistance. Therefore, a clean and sustainable high-performance liquid chromatography (HPLC) method has been developed for evaluating ceftriaxone stability in pharmaceutical product. A Zorbax SB C18 (150 × 4.6 mm, 5 μm) column was maintained at 25°C; the mobile phase consisted of purified water acidified with 0.2% orthophosphoric acid and ethanol (87: 13, v/v) at a flow rate of 0.9 mL min−1. The detection wavelength was set at 260 nm. The method was linear over a concentration range of 20–120 μg mL−1, precise with relative standard deviations <2%, robust in the event of minor changes to the original method conditions, accurate with recovery between 98% and 102% and specific to degradation products. The retention time for ceftriaxone sodium was ~4.6 minutes. This work shows an ecologically correct option by HPLC method for the evaluation of ceftriaxone sodium in pharmaceutical product, as well as its stability, which addresses the requirements of the current green and sustainable analytical chemistry.
Development and Validation of a LC–MS/MS Method for the Profiling of Impurities Formed during Stress Study of Antifungal Agent—Efinaconazole
Authors: Govindarajan S , Asharani I V
Published: June 2021

Liquid chromatography interfaced with mass spectroscopy (LC–MS) is a sensitive and effective analytical method that combines high-resolution separation as well as specific mass detection of impurities in formulated products and as well as in active pharmaceutical ingredient (API). In this study, LC–MS/MS was used to determine impurities formed during the stability period of Efinaconazole (EFZ, a triazole antifungal agent). The method was validated for its assay parameters such as specificity, linearity, accuracy, precision and also for solution stability. The calibration curve was found to be linear for the concentration range from 0.5 μg/mL to 30 μg/mL. A thorough investigation was performed by exposing Efinaconazole (1 mg/mL) to various stress conditions such as hydrolysis (acid and alkaline), oxidation, photolysis and temperature at various time intervals to achieve 10% degradation. The impurities formed during forced degradation were separated using high-performance liquid chromatography later it was identified using LC–MS/MS technique. The obtained results showed that EFZ is prone to oxidation when exposed to a 3% aqueous medium of hydrogen peroxide solution and quite stable in all the remaining stress conditions for a longer period.
Matrix Solid-Phase Dispersion Coupled with HPLC-UV for Simultaneous Extraction, Purification and Determination of Six Lignans in Schisandra chinensis Fruits
Authors: Song Haiyan , Chang Kejian , Zhang Liang , Zhu Wenbo , Li Yingying , Hu Haobin , Zhang Xiaojuan , Xi Yongfeng , Li Lu
Published: June 2021

An efficient method for simultaneous extraction, purification and determination of six lignans in Schisandra chinensis Baill was developed by employing matrix solid-phase dispersion (MSPD) extraction followed by HPLC-UV determination analysis. Several sorbent and desorption solvent that affected the extraction yield of lignans were investigated; neutral alumina and absolute ethanol were selected as the best dispersing material and desorption agent, respectively. Other extraction conditions for MSPD were optimized as follows: 1:2 of S. chinensis raw material to neutral aluminum oxide mass ratio, 1:30 (g/mL) of sample to absolute ethanol, 2.5 h of desorption time and 50°C of desorption temperature. Under the above conditions, the total extraction yield for six lignans have reached (16.99 ± 0.33) x 103 mg/kg with a higher content of 6.88 ± 0.25% in the extracts. Comparative studies were explored by conducting other six extraction approaches including Soxhlet extraction, heat reflux extraction, smashing tissue extraction, microwave-assisted extraction, ultrasonic-assisted extraction and ultrasonic-microwave synergistic extraction. Results showed MSPD technique not only improved the extraction yield, but also improved the purity of lignans, it can be generalized to more extraction of natural compounds. In addition, the validated HPLC-UV method had been successfully applied to analysis of lignans from 10 real S. chinensis samples.
Simultaneous Monitoring of Azathioprine Metabolites in Erythrocytes of Crohn’s Disease Patients by HPLC-UV
Authors: Ribeiro Aline Correa , Barroso Luciane Henriques Furtado , Mourao-Junior Carlos Alberto , Chebli Julio Maria Fonseca , Nascimento Jorge Willian Leandro
Published: June 2021

The conversion of azathioprine (AZA) to active 6-thioguanine nucleotides (6-TGN) is essential for its clinical efficacy; however, another metabolite formed, 6-methylmercaptopurine (6-MMP), is related to hepatotoxicity. Blood samples were collected from 37 patients under AZA’s treatment, and a new HPLC-UV method was validated and applied for simultaneous quantification of 6-TGN and 6-MMP in erythrocytes of Crohn’s disease (CD) patients. The concentration of 6-TGN and 6-MMP found ranged from 4.5 to 2,456 ρmol/8 × 108 red blood cells (RBCs) for 6-TGN and from 170 to 53,951 ρmol/8 × 108 RBCs for 6-MMP. Reduced levels of 6-MMP in patients into combo therapy with AZA and allopurinol (2,031 ρmol/8 × 108 RBCs) have been observed when compared to patients undergoing monotherapy with AZA (9,098 ρmol/8 × 108 RBCs). Additionally, there was a negative correlation (r = −83.7%, P < 0.05) between lymphocyte count and 6-TGN levels. The method developed is reliable, accurate and reproducible and can be used as an important tool in the monitoring routine of patients with CD under AZA treatment, allowing the individualization of the dose, monitoring adherence to the treatment and the evaluation of the clinical outcome of these patients.
Rapid Development of Cefiderocol Resistance in Carbapenem-resistant Enterobacter cloacae During Therapy Is Associated With Heterogeneous Mutations in the Catecholate Siderophore Receptor cirA
Authors: Klein Sabrina , Boutin Sébastien , Kocer Kaan , Fiedler Mascha O , Störzinger Dominic , Weigand Markus A , Tan Benjamin , Richter Daniel , Rupp Christian , Mieth Markus , Mehrabi Arianeb , Hackert Thilo , Zimmermann Stefan , Heeg Klaus , Nurjadi Dennis
Published: June 2021

We report a case of resistance development toward cefiderocol in a patient with intra-abdominal and bloodstream infections caused by carbapenemase-producing Enterobacter cloacae within 21 days of cefiderocol therapy. Whole genome sequencing revealed heterogeneous mutations in the cirA gene, encoding a catecholate siderophore receptor, conferring phenotypic resistance to cefiderocol.
Epidemiology, Natural History, Diagnosis, and Treatment of Trichomonas vaginalis in Men
Authors: Van Gerwen Olivia T , Camino Andres F , Sharma Jyoti , Kissinger Patricia J , Muzny Christina A
Published: June 2021

Trichomonas vaginalis infections in men are traditionally considered to be benign and consequently have been overlooked. However, men with this common sexually transmitted infection can experience urethritis, prostatitis, reduced fertility, and amplified human immunodeficiency virus risk. In addition, men are often asymptomatic and can unknowingly spread the infection to their female sexual partners. With advances in T. vaginalis diagnostics, more men are being diagnosed, yet the optimal method of treatment in men remains unknown. The purpose of this review is to discuss the epidemiology, natural history, diagnosis, and treatment of T. vaginalis among men.
Reconstructing income inequality in a colonial cash crop economy: five social tables for Uganda, 1925–1965
Authors: de Haas Michiel
Published: June 2021

This study contributes to an expanding literature on historical African inequality, presenting five social tables and income inequality estimates for Uganda between 1925 and 1965. I find that income inequality was mostly stable and overall low compared to other African colonies. Decomposition reveals important underlying fault lines and shifts. Income gaps between the African majority and a tiny Asian and European income elite accounted for a large share of overall inequality. Over time, inequality among Africans increased. Income from self-provisioning was a major equalizer in Uganda’s economy, which was characterized by land abundance and widespread smallholder cultivation of labor-intensive export crops.
Effectiveness of home-based cardiac telerehabilitation as an alternative to Phase 2 cardiac rehabilitation of coronary heart disease: a systematic review and meta-analysis
Authors: Ramachandran Hadassah Joann , Jiang Ying , Tam Wilson Wai San , Yeo Tee Joo , Wang Wenru
Published: June 2021

Aims

The onset of the COVID-19 pandemic saw the suspension of centre-based cardiac rehabilitation (CBCR) and has underscored the need for home-based cardiac telerehabilitation (HBCTR) as a feasible alternative rehabilitation delivery model. Yet, the effectiveness of HBCTR as an alternative to Phase 2 CBCR is unknown. We aimed to conduct a meta-analysis to quantitatively appraise the effectiveness of HBCTR.

Methods and results

PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and PsycINFO were searched from inception to January 2021. We included randomized controlled trials (RCTs) comparing HBCTR to Phase 2 CBCR or usual care in patients with coronary heart disease (CHD). Out of 1588 studies, 14 RCTs involving 2869 CHD patients were included in this review. When compared with usual care, participation in HBCTR showed significant improvement in functional capacity {6-min walking test distance [mean difference (MD) 25.58 m, 95% confidence interval (CI) 14.74–36.42]}; daily step count (MD 1.05 K, 95% CI 0.36–1.75) and exercise habits [odds ratio (OR) 2.28, 95% CI 1.30–4.00)]; depression scores (standardized MD −0.16, 95% CI −0.32 to 0.01) and quality of life [Short-Form mental component summary (MD 2.63, 95% CI 0.06–5.20) and physical component summary (MD 1.99, 95% CI 0.83–3.16)]. Effects on medication adherence were synthesized narratively. HBCTR and CBCR were comparably effective.

Conclusion

In patients with CHD, HBCTR was associated with an increase in functional capacity, physical activity (PA) behaviour, and depression when compared with UC. When HBCTR was compared to CBCR, an equivalent effect on functional capacity, PA behaviour, QoL, medication adherence, smoking behaviour, physiological risk factors, depression, and cardiac-related hospitalization was observed.
The impacts of including information about the number of carcinogens in smoke on standardized cigarette packs in the UK
Authors: Moodie Crawford , Best Catherine , Critchlow Nathan , Hitchman Sara , Stead Martine , McNeill Ann
Published: June 2021

Background

Since May 2017, standardized packaging has been mandatory in the UK, with packs required to display an ‘information message’ explaining that there are more than 70 carcinogens in tobacco smoke.

Methods

Three waves of a longitudinal online survey in the UK with smokers pre-standardized packaging (Wave 1: April–May 2016) and followed up post-standardized packaging (Wave 2: September–November 2017, Wave 3: May–July 2019). Of the 6233 smokers at Wave 1, 4293 responded at Wave 2 and 3175 at Wave 3. We explored knowledge of the number of carcinogens in smoke, and whether knowing that smoke contains more than 70 carcinogens mediated change in the belief that the dangers of smoking are exaggerated (risk perception), stubbing out cigarettes, quit intentions and quitting. As the information message is larger on roll-your-own packs than on cigarette packs, as the packs are larger, we also explored whether there was any difference in knowing that smoke contains more than 70 carcinogens between exclusive cigarette smokers and exclusive roll-your-own smokers.

Results

Knowledge that there are over 70 carcinogens in smoke increased among smokers across waves, with the increase from Waves 1 to 3 greater for exclusive roll-your-own smokers than exclusive cigarette smokers (adjusted odds ratio=1.44; 95% CI 1.03–2.03). Knowledge that there are over 70 carcinogens in smoke mediated higher risk perception but not stubbing cigarettes out, quit intentions or quitting.

Conclusions

The information message improved knowledge of how many carcinogens are in smoke, particularly among exclusive roll-your-own smokers, and this was linked to higher risk perception.
Genome-Inferred Correspondence between Phylogeny and Metabolic Traits in the Wild Drosophila Gut Microbiome
Authors: McMullen John G , Bueno Eduardo , Blow Frances , Douglas Angela E
Published: June 2021

Annotated genome sequences provide valuable insight into the functional capabilities of members of microbial communities. Nevertheless, most studies on the microbiome in animal guts use metagenomic data, hampering the assignment of genes to specific microbial taxa. Here, we make use of the readily culturable bacterial communities in the gut of the fruit fly Drosophila melanogaster to obtain draft genome sequences for 96 isolates from wild flies. These include 81 new de novo assembled genomes, assigned to three orders (Enterobacterales, Lactobacillales, and Rhodospirillales) with 80% of strains identified to species level using average nucleotide identity and phylogenomic reconstruction. Based on annotations by the RAST pipeline, among-isolate variation in metabolic function partitioned strongly by bacterial order, particularly by amino acid metabolism (Rhodospirillales), fermentation, and nucleotide metabolism (Lactobacillales) and arginine, urea, and polyamine metabolism (Enterobacterales). Seven bacterial species, comprising 2–3 species in each order, were well-represented among the isolates and included ≥5 strains, permitting analysis of metabolic functions in the accessory genome (i.e., genes not present in every strain). Overall, the metabolic function in the accessory genome partitioned by bacterial order. Two species, Gluconobacter cerinus (Rhodospirillales) and Lactiplantibacillus plantarum (Lactobacillales) had large accessory genomes, and metabolic functions were dominated by amino acid metabolism (G. cerinus) and carbohydrate metabolism (La. plantarum). The patterns of variation in metabolic capabilities at multiple phylogenetic scales provide the basis for future studies of the ecological and evolutionary processes shaping the diversity of microorganisms associated with natural populations of Drosophila.
De novo genome assemblies of butterflies
Authors: Ellis Emily A , Storer Caroline G , Kawahara Akito Y
Published: June 2021

Background

The availability of thousands of genomes has enabled new advancements in biology. However, many genomes have not been investigated for their quality. Here we examine quality trends in a taxonomically diverse and well-known group, butterflies (Papilionoidea), and provide draft, de novo assemblies for all available butterfly genomes. Owing to massive genome sequencing investment and taxonomic curation, this is an excellent group to explore genome quality.

Findings

We provide de novo assemblies for all 822 available butterfly genomes and interpret their quality in terms of completeness and continuity. We identify the 50 highest quality genomes across butterflies and conclude that the ringlet, Aphantopus hyperantus, has the highest quality genome. Our post-processing of draft genome assemblies identified 118 butterfly genomes that should not be reused owing to contamination or extremely low quality. However, many draft genomes are of high utility, especially because permissibility of low-quality genomes is dependent on the objective of the study. Our assemblies will serve as a key resource for papilionid genomics, especially for researchers without computational resources.

Conclusions

Quality metrics and assemblies are typically presented with annotated genome accessions but rarely with de novo genomes. We recommend that studies presenting genome sequences provide the assembly and some metrics of quality because quality will significantly affect downstream results. Transparency in quality metrics is needed to improve the field of genome science and encourage data reuse.
Placental endocrine insufficiency programs anxiety, deficits in cognition and atypical social behaviour in offspring
Authors: Harrison David J , Creeth Hugo D J , Tyson Hannah R , Boque-Sastre Raquel , Hunter Susan , Dwyer Dominic M , Isles Anthony R , John Rosalind M
Published: June 2021

Abnormally elevated expression of the imprinted PHLDA2 gene has been reported in the placenta of human babies that are growth restricted in utero in several studies. We previously modelled this gene alteration in mice and found that just 2-fold increased expression of Phlda2 resulted in placental endocrine insufficiency. In addition, elevated Phlda2 was found to drive fetal growth restriction (FGR) of transgenic offspring and impaired maternal care by their wildtype mothers. Being born small and being exposed to suboptimal maternal care have both been associated with the increased risk of mental health disorders in human populations. In the current study we probed behavioural consequences of elevated Phlda2 for the offspring. We discovered increased anxiety-like behaviours, deficits in cognition and atypical social behaviours, with the greatest impact on male offspring. Subsequent analysis revealed alterations in the transcriptome of the adult offspring hippocampus, hypothalamus and amygdala, regions consistent with these behavioural observations. The inclusion of a group of fully wildtype controls raised in a normal maternal environment allowed us to attribute behavioural and molecular alterations to the adverse maternal environment induced by placental endocrine insufficiency rather than the specific gene change of elevated Phlda2. Our work demonstrates that a highly common alteration reported in human FGR is associated with negative behavioural outcomes later in life. Importantly, we also establish the experimental paradigm that placental endocrine insufficiency can program atypical behaviour in offspring highlighting the under-appreciated role of placental endocrine insufficiency in driving disorders of later life behaviour.
Targeting immunometabolism to treat COVID-19
Authors: O’Carroll Shane M , O’Neill Luke A J
Published: June 2021

The COVID-19 crisis has emphasised the need for antiviral therapies to combat current and future viral zoonoses. Recent studies have shown that immune cells such as macrophages are the main contributors to the inflammatory response seen in the later inflammatory phase of COVID-19. Immune cells in the context of a viral infection such as SARS-CoV-2 undergo metabolic reprogramming to elicit these pro-inflammatory effector functions. The evidence of metabolic reprogramming in COVID-19 offers opportunities for metabolites with immunomodulatory properties to be investigated as potential therapies to combat this hyper-inflammatory response. Recent research indicates that the metabolite itaconate, previously known to be broadly antibacterial, may have both antiviral and immunomodulatory potential. Furthermore, low itaconate levels have shown to correlate with COVID-19 disease severity, potentially implicating its importance in the disease. The antiviral potential of itaconate has encouraged researchers to synthesise itaconate derivatives for antiviral screening, with some encouraging results. This review summarises the antiviral and immunomodulatory potential of immunometabolic modulators including metformin, peroxisome proliferator-activated receptor agonists and TEPP-46 as well as itaconate, and its derivatives and their potential use as broad spectrum anti-viral agents.
Factors affecting performance response of pigs exposed to different challenge models: a multivariate approach
Authors: Rodrigues Lucas A , Ferreira Felipe N A , Costa Matheus O , Wellington Michael O , Columbus Daniel A
Published: June 2021

Factors associated with the severity with which different challenge models (CMs) compromise growth performance in pigs were investigated using hierarchical clustering on principal components (HCPC) analysis. One hundred seventy-eight studies reporting growth performance variables (average daily gain [ADG], average daily feed intake [ADFI], gain:feed [GF], and final body weight [FBW]) of a Control (Ct) vs. a Challenged (Ch) group of pigs using different CMs (enteric [ENT], environmental [ENV], lipopolysaccharide [LPS], respiratory [RES], or sanitary condition [SAN] challenges) were included. Studies were grouped by similarity in performance in three clusters (C1, C2, and C3) by HCPC. The effects of CM, cluster, and sex (males [M], females [F], mixed [Mi]) were investigated. Linear (LRP) and quadratic (QRP) response plateau models were fitted to assess the interrelationships between the change in ADG (∆ADG) and ADFI (∆ADFI) and the duration of challenge. All variables increased from C1 through C3, except for GF, which decreased (P < 0.05). LPS was more detrimental to ADG than ENV, RES, and SAN models (P < 0.05). Furthermore, LPS also lowered GF more than all the other CMs (P < 0.05). The ∆ADG independent of ∆ADFI was significant in LPS and SAN (P < 0.05), showed a trend toward the significance in ENT and RES (P < 0.10), and was not significant in ENV (P > 0.10), while the ∆ADG dependent on ∆ADFI was significant in ENT, ENV, and LPS only (P < 0.05). The critical value of ∆ADFI influencing the ∆ADG was significant in pigs belonging to C1 (P < 0.05) but not C2 or C3 (P > 0.10). The ∆ADG independent of duration post-Ch (irreparable portion of growth) was significant in C1 and C2 pigs, whereas the ∆ADFI independent of duration post-Ch (irreparable portion of feed intake) was significant in C1 pigs only (P < 0.05). Moreover, the time for recovery of ADG and ADFI after Ch was significant in pigs belonging to C1 and C2 (P < 0.05). Control F showed reduced ADG compared with Ct-M, and Ch-F showed reduced ADFI compared with Ch-M (P < 0.05). Moreover, the irreparable portion of ΔADG was 4.8 higher in F (−187.7; P < 0.05) compared with M (−39.1; P < 0.05). There are significant differences in growth performance response to CM based on cluster and sex. Furthermore, bacterial lipopolysaccharide appears to be an appropriate noninfectious model for immune stimulation and growth impairment in pigs.
Middle cerebral artery occlusion due to cardiac tissue following catheter ablation in Wolff–Parkinson–White syndrome
Authors: Phuyal Subash , Paudel Raju , Agrawal Pooja , Lamsal Ritesh
Published: June 2021

Catheter ablation is a commonly performed procedure in patients with Wolff–Parkinson–White syndrome. A 56-year-old man developed an acute ischemic stroke immediately after undergoing radiofrequency catheter ablation of the left-sided accessory pathway. Neuroimaging revealed complete occlusion of the proximal middle cerebral artery. Mechanical thrombectomy (MT) was performed with successful retrieval of the thrombo-embolus. Histopathological examination of the thrombo-embolus confirmed organic cardiac tissue. The patient was later discharged from the hospital with no neurologic deficit. There is no report of successful MT in patients with large-vessel occlusion because of the embolization of cardiac tissue after catheter ablation. This report highlights the need to remain vigilant for signs of stroke after any cardiac intervention.
Detection of the metabolic response to drought stress using hyperspectral reflectance
Authors: Burnett Angela C , Serbin Shawn P , Davidson Kenneth J , Ely Kim S , Rogers Alistair
Published: June 2021

Drought is the most important limitation on crop yield. Understanding and detecting drought stress in crops is vital for improving water use efficiency through effective breeding and management. Leaf reflectance spectroscopy offers a rapid, non-destructive alternative to traditional techniques for measuring plant traits involved in a drought response. We measured drought stress in six glasshouse-grown agronomic species using physiological, biochemical, and spectral data. In contrast to physiological traits, leaf metabolite concentrations revealed drought stress before it was visible to the naked eye. We used full-spectrum leaf reflectance data to predict metabolite concentrations using partial least-squares regression, with validation R2 values of 0.49–0.87. We show for the first time that spectroscopy may be used for the quantitative estimation of proline and abscisic acid, demonstrating the first use of hyperspectral data to detect a phytohormone. We used linear discriminant analysis and partial least squares discriminant analysis to differentiate between watered plants and those subjected to drought based on measured traits (accuracy: 71%) and raw spectral data (66%). Finally, we validated our glasshouse-developed models in an independent field trial. We demonstrate that spectroscopy can detect drought stress via underlying biochemical changes, before visual differences occur, representing a powerful advance for measuring limitations on yield.