bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of novel furo[2,3‐d]pyrimidin‐2‐one–1,3,4‐oxadiazole hybrid derivatives as dual antiviral and anticancer agents that induce apoptosis
Authors: El Mansouri Az‐eddine , Oubella Ali , Dânoun Karim , Ahmad Mehdi , Neyts Johan , Jochmans Dirk , Snoeck Robert , Andrei Graciela , Morjani Hamid , Zahouily Mohamed , Lazrek Hassan B.
Published: June 2021

A new series of furo[2,3‐d]pyrimidine–1,3,4‐oxadiazole hybrid derivatives were synthesized via an environmentally friendly, multistep synthetic tool and a one‐pot Songoashira‐heterocyclization protocol using, for the first time, nanostructured palladium pyrophosphate (Na2PdP2O7) as a heterogeneous catalyst. Compounds 9a–c exhibited broad‐spectrum activity with low micromolar EC50 values toward wild and mutant varicella‐zoster virus (VZV) strains. Compound 9b was up to threefold more potent than the reference drug acyclovir against thymidine kinase‐deficient VZV strains. Importantly, derivative 9b was not cytostatic at the maximum tested concentration (CC50 > 100 µM) and had an acceptable selectivity index value of up to 7.8. Moreover, all synthesized 1,3,4‐oxadiazole hybrids were evaluated for their cytotoxic activity in four human cancer cell lines: fibrosarcoma (HT‐1080), breast (MCF‐7 and MDA‐MB‐231), and lung carcinoma (A549). Data showed that compound 8f exhibits moderate cytotoxicity, with IC50 values ranging from 13.89 to 19.43 µM. Besides, compound 8f induced apoptosis through caspase 3/7 activation, cell death independently of the mitochondrial pathway, and cell cycle arrest in the S phase for HT1080 cells and the G1/M phase for A549 cells. Finally, the molecular docking study confirmed that the anticancer activity of the synthesized compounds is mediated by the activation of caspase 3.
Parent responsiveness mediates the association between hyporeactivity at age 1 year and communication at age 2 years in children at elevated likelihood of ASD
Authors: Grzadzinski Rebecca , Nowell Sallie W. , Crais Elizabeth R. , Baranek Grace T. , Turner‐Brown Lauren , Watson Linda R.
Published: June 2021

Studies suggest that higher parent responsiveness is associated with higher child language abilities. Infants and toddlers later diagnosed with autism spectrum disorder (ASD) often display hyporeactivity to sensory stimuli, which has also been associated with lower child communication abilities and lower parent responsiveness. Yet, whether parent responsiveness mediates the relationship between child hyporeactivity and later communication outcomes remains unexplored. This study is a secondary data analysis which includes children (n = 83; 56 males) identified as at elevated likelihood of later ASD. Children completed an observational measure of sensory reactivity and a standard developmental assessment at 14 (Time 1) and 23 months old (Time 2). At each time point, parents reported on the child's adaptive communication behaviors and sensory behaviors, and Parent Verbal Responsiveness (AvgPVR) was coded from parent–child free‐play videos. Results indicated that the association between child sensory hyporeactivity at Time 1 (observed and parent‐reported) and communication at Time 2 (observed and parent reported) was significantly mediated by AvgPVR. Although child hyporeactivity predicts poorer communication outcomes, increased parent verbal responsiveness may attenuate this negative impact. Parent responsiveness, a focus of many parent‐mediated interventions, may be an important mechanism of treatment response that should be directly tested in future research.

Lay Summary

Toddlers at elevated likelihood of autism spectrum disorder (ASD) are often under‐reactive (hyporeactive) to sensory stimuli. This hyporeactivity slows learning of communication skills and provides parents with fewer opportunities to respond to their children. In this study, children with hyporeactivity at 14 months generally had poorer communication at 23 months; however, the more responsive their parents were, the weaker the relationship between early hyporeactivity and later communication. Thus, increasing parent responsiveness may lead to better communication outcomes for toddlers with the early ASD symptom of hyporeactivity.
Performance of prostate health index and PSA density in a diverse biopsy‐naïve cohort with mpMRI for detecting significant prostate cancer
Authors: Carbunaru Samuel , Stinson James , Babajide Rilwan , Hollowell Courtney M. P. , Yang Ximing , Sekosan Marin , Ferrer Karen , Kajdacsy‐Balla Andre , Abelleira Josephine , Ruden Maria , King‐Lee Patrice , Dalton Daniel P. , Casalino David D. , Kittles Rick A. , Gann Peter H. , Schaeffer Edward M. , Murphy Adam B.
Published: June 2021

Objective

To compare Prostate Health Index (PHI) and prostate‐specific antigen (PSA) density as secondary tests after multiparametric magnetic resonance imaging (mpMRI) in improving the detection accuracy of Gleason grade group (GG) 2‐5 prostate cancer (PCa) and in decreasing unnecessary biopsies in a multiethnic biopsy‐naïve population.

Methods

From February 2017 to February 2020, we recruited consecutive biopsy‐naïve men in participating urology clinics for elevated PSA levels. They all had a PHI score, mpMRI, and prostate biopsy. Experienced genitourinary radiologists read all mpMRI studies based on PIRADS version 2.0. Logistic regression models were used to generate receiver operating characteristic curves. Models were tested for effect modification between Race (Black vs White) and both PHI and PSA density, and Race and PIRADS to determine if race impacted their prediction accuracy. Sensitivity, specificity, and predictive values of PHI and PSA density thresholds were calculated by PIRADS scores. The primary outcome was GG2‐5 PCa, that is, Gleason score ≥3 + 4.

Results

The study included 143 men, of which 65 (45.5%) were self‐reported Black. Median age was 62.0 years and 55 men (38.4%) had GG2‐5 PCa. Overall, 18.1% had PIRADS 1‐2, 32.9% had PIRADS 3, and 49.0% had PIRADS 4‐5. For the binary logistic regressions, the interactions between PIRADS and Race (P = .08), Log (PHI) and Race (P = .17), and Log (PSA density) and Race (P = .42) were not statistically significant. Within PIRADS 3 lesions, a PHI ≥49 prevented unnecessary biopsies in 55% of men and missed no GG2‐5 PCa, yielding a negative predictive value of 100%. There was no reliable PHI or PSA density threshold to avoid PCa biopsies in PIRADS 1‐2 or 4‐5.

Conclusions

PHI and PSA density can be used after mpMRI to improve the detection of GG2‐5 PCa in a biopsy‐naïve cohort. PHI may be superior to PSA density in PIRADS 3 lesions by avoiding 55% of unnecessary biopsies. Using both PHI and PSA density in series may further increase specificity and lead to fewer unnecessary biopsies, but further larger studies are warranted to determine the optimal threshold of each biomarker.
Peptide nucleic acids and their role in gene regulation and editing
Authors: Perera J. Dinithi R. , Carufe Kelly E. W. , Glazer Peter M.
Published: June 2021

The unique properties of peptide nucleic acid (PNA) makes it a desirable candidate to be used in therapeutic and biotechnological interventions. It has been broadly utilized for numerous applications, with a major focus in regulation of gene expression, and more recently in gene editing. While the classic PNA design has mainly been employed to date, chemical modifications of the PNA backbone and nucleobases provide an avenue to advance the technology further. This review aims to discuss the recent developments in PNA based gene manipulation techniques and the use of novel chemical modifications to improve the current state of PNA mediated gene targeting.
Systems‐level approaches for understanding and engineering of the oleaginous cell factory Yarrowia lipolytica
Authors: Poorinmohammad Naghmeh , Kerkhoven Eduard J.
Published: June 2021

Concerns about climate change and the search for renewable energy sources together with the goal of attaining sustainable product manufacturing have boosted the use of microbial platforms to produce fuels and high‐value chemicals. In this regard, Yarrowia lipolytica has been known as a promising yeast with potentials in diverse array of biotechnological applications such as being a host for different oleochemicals, organic acid, and recombinant protein production. Having a rapidly increasing number of molecular and genetic tools available, Y. lipolytica has been well studied amongst oleaginous yeasts and metabolic engineering has been used to explore its potentials. More recently, with the advancement in systems biotechnology and the implementation of mathematical modeling and high throughput omics data‐driven approaches, in‐depth understanding of cellular mechanisms of cell factories have been made possible resulting in enhanced rational strain design. In case of Y. lipolytica, these systems‐level studies and the related cutting‐edge technologies have recently been initiated which is expected to result in enabling the biotechnology sector to rationally engineer Y. lipolytica‐based cell factories with favorable production metrics. In this regard, here, we highlight the current status of systems metabolic engineering research and assess the potential of this yeast for future cell factory design development.
Using EEG to decode semantics during an artificial language learning task
Authors: Foster Chris , Williams Chad C. , Krigolson Olave E. , Fyshe Alona
Published: June 2021

Background

As we learn a new nonnative language (L2), we begin to build a new map of concepts onto orthographic representations. Eventually, L2 can conjure as rich a semantic representation as our native language (L1). However, the neural processes for mapping a new orthographic representation to a familiar meaning are not well understood or characterized.

Methods

Using electroencephalography and an artificial language that maps symbols to English words, we show that it is possible to use machine learning models to detect a newly formed semantic mapping as it is acquired.

Results

Through a trial‐by‐trial analysis, we show that we can detect when a new semantic mapping is formed. Our results show that, like word meaning representations evoked by a L1, the localization of the newly formed neural representations is highly distributed, but the representation may emerge more slowly after the onset of the symbol. Furthermore, our mapping of word meanings to symbols removes the confound of the semantics to the visual characteristics of the stimulus, a confound that has been difficult to disentangle previously.

Conclusion

We have shown that the L1 semantic representation conjured by a newly acquired L2 word can be detected using decoding techniques, and we give the first characterization of the emergence of that mapping. Our work opens up new possibilities for the study of semantic representations during L2 learning.
Corporate commitment to climate change action, carbon risk exposure, and a firm's debt financing policy
Authors: Lemma Tesfaye T. , Lulseged Ayalew , Tavakolifar Mohammad
Published: June 2021

Motivated by the rising consensus that corporate engagement in climate change actions holds the key for society's transition into environmentally resilient economy, the study examines whether a firm's commitment to climate change action and its carbon risk exposure shape the firm's debt financing policy. Based on insights drawn from signaling, corporate reputation, and agency theories, we develop models that link corporate commitment to climate change actions and a firm's carbon risk exposure with its debt financing decisions. Using data drawn from S&P 500 companies, for years 2015 to 2019, we find a robust evidence that firms that engage in higher levels of commitment to climate change actions issue a higher proportion of debt with longer terms to maturity, even after controlling for their carbon risk exposure. However, we do not find a robust evidence corroborating an association between firms' carbon risk exposure and their debt financing policy. These findings are consistent with arguments that high‐commitment firms enjoy positive reputation, better credit rating, and reduced agency and information asymmetry costs, allowing them to gain easier access to long‐term debt markets.
Impact of the model of long‐term follow‐up care on adherence to guideline‐recommended surveillance among survivors of adolescent and young adult cancers
Authors: Kagramanov Dalia , Sutradhar Rinku , Lau Cindy , Yao Zhan , Pole Jason D. , Baxter Nancy N. , Gupta Sumit , Nathan Paul C.
Published: June 2021

Purpose

Adolescent and young adult cancer survivors require lifelong healthcare to address the late effects of therapy. We examined the impact of different provider models of long‐term follow‐up (LTFU) care on adherence to recommended surveillance.

Methods

We conducted a retrospective cohort study using administrative health databases in Ontario, Canada. Five‐year survivors were identified from IMPACT, a database of patients aged 15–20.9 years at diagnosis of six cancers between 1992 and 2010. We defined three models of LTFU care hierarchically: specialized survivor clinics (SCCs), general cancer clinics (GCCs), and family physician (FP). We assessed adherence to the Children's Oncology Group surveillance guidelines for cardiomyopathy and breast cancer. Multistate models assessed adherence transitions and impacts of LTFU attendance.

Results

A total of 1574 survivors were followed for a mean of 9.2 years (range 4.3–13.9 years) from index (5‐year survival). The highest level of LTFU attended in the first 2‐years post‐index was a GCC (47%); only 16.7% attended a SCC. By the end of study, 72% no longer attended any of the models of care and only 2% still attended an SCC. Among 188 survivors requiring breast cancer surveillance, 6.9% were adherent to their first required surveillance testing. Attendance at a SCC in the previous year and higher cumulative FP or GCC visits increased the rate of subsequently becoming adherent. Among 857 survivors requiring cardiomyopathy surveillance, 11% were adherent at study entry. Each subsequent SCC visit led to an 11.3% (95% CI: 1.05–1.18) increase in the rate of becoming adherent.

Conclusion

LTFU attendance and surveillance adherence are sub‐optimal. SCC follow‐up is associated with greater adherence, but few survivors receive such care, and this proportion diminished over time. Interventions are needed to improve LTFU attendance and promote surveillance adherence.
Lifestyle interventions can reduce the risk of Barrett’s esophagus: a systematic review and meta‐analysis of 62 studies involving 250,157 participants
Authors: Zhao Zhanwei , Yin Zifang , Zhang Chaojun
Published: June 2021

Background

Barrett's esophagus (BE) is a well‐established risk factor for esophageal adenocarcinoma. Our objective was to investigate the effectiveness of lifestyle interventions on BE risk.

Methods

We searched PubMed, Embase, and Web of Science up to 30 September 2020. The summary relative risks (RRs) and 95% confidence intervals (CIs) for the highest versus lowest categories of exposure were assessed. Analyses of subgroup, dose–response, sensitivity, and publication bias were conducted.

Results

Sixty‐two studies were included that involved more than 250,157 participants and 22,608 cases. Seven lifestyle factors were investigated: smoking, alcohol, body mass index (BMI), physical activity, sleep time, medication, and diet. We observed statistically significant increased BE risks for smoking (RR = 1.35, 95% CI = 1.16–1.57), alcohol intake (RR = 1.23, 95% CI = 1.13–1.34), body fatness (RR = 1.08, 95% CI = 1.03–1.13), less sleep time (RR = 1.76, 95% CI = 1.24–2.49), and proton pump inhibitors use (RR = 1.64, 95% CI = 1.17–2.29). Reduced risks of BE were found for aspirin (RR = 0.70, 95% CI = 0.58–0.84) and the intake of vitamin C (RR = 0.59, 95% CI = 0.44–0.80), folate (RR = 0.47, 95% CI = 0.31–0.71), and fiber (RR = 0.95, 95% CI = 0.93–0.97). The quality of most included studies was high and the subgroup analysis according to the quality score showed significant results (p < 0.05). There was no publication bias for smoking and alcohol. Although the analysis suggested significant evidence of publication bias for BMI, sensitivity analysis showed that the changes in the recalculated RRs were not significant.

Conclusions

The large meta‐analysis revealed that lifestyle modifications could reduce the risks of BE and, consequently, esophageal adenocarcinoma.
Pediatric oncology clinician communication about sexual health with adolescents and young adults: A report from the children’s oncology group
Authors: Frederick Natasha N. , Bingen Kristin , Bober Sharon L. , Cherven Brooke , Xu Xinxin , Quinn Gwendolyn P. , Ji Lingyun , Freyer David R.
Published: June 2021

Background

Sexual health (SH) is an important concern for adolescents and young adults (AYAs). This study determined current SH communication practices, barriers, and additional resources needed among pediatric oncology clinicians who treat AYAs.

Methods

A cross‐sectional survey was developed by the Children's Oncology Group (COG) AYA Committee and sent to pediatric oncologists (n = 1,987; 85.9%) and advanced practice providers (APPs, n = 326; 14.1%) at 226 COG institutions. Responses were tabulated and compared using tests of proportion and trend.

Results

The sample comprised 602 respondents from 168 institutions and was proportionally representative (468 oncologists [77.7%], 76 APPs [12.6%], 58 unidentified [9.6%]; institutional and provider response rates 74.3% and 26.2%, respectively). Almost half of respondents (41.7%) reported no/small role in SH care. Medical topics were discussed most often, including contraception (67.2%), puberty (43.5%), and sexual activity (37.5%). Topics never/rarely discussed included gender identity (64.5%), sexual orientation (53.7%), and sexual function (50.3%). Frequently cited communication barriers included lack of time, low priority, perceived patient discomfort, and the presence of a parent/guardian. Respondents endorsed the need for further education/resources on sexual function (66.1%), gender identity/sexual orientation (59.5%), and body image (46.6%). Preferred education modalities included dissemination of published guidelines (64.7%), skills training modules (62.9%), and webinars (45.3%). By provider type, responses were similar overall but differed for perception of role, barriers identified, and resources desired.

Conclusions

Many pediatric oncology clinicians play minimal roles in SH care of AYAs and most SH topics are rarely discussed. Provider‐directed education/training interventions have potential for improving SH care of AYA cancer patients.
Distinct glycolytic pathway regulation in liver, tumour and skeletal muscle of mice with cancer cachexia
Authors: Visavadiya Nishant P. , Rossiter Harry B. , Khamoui Andy V.
Published: June 2021

Energetically inefficient inter‐organ substrate shuttles are proposed contributors to cachexia‐related weight loss. Here, we examined glycolytic pathway metabolites, enzyme activity and transport proteins in skeletal muscle, liver and tumours of mice with cachexia‐related weight loss induced by colon‐26 cancer cells. Skeletal muscle of cachexic mice had increased [L‐lactate]/[pyruvate], LDH activity and lactate transporter MCT1. Cachexic livers also showed increased MCT1. This is consistent with the proposal that the rate of muscle‐derived lactate shuttling to liver for use in gluconeogenesis is increased, that is, an increased Cori cycle flux in weight‐losing cachexic mice. A second shuttle between liver and tumour may also contribute to disrupted energy balance and weight loss. We found increased high‐affinity glucose transporter GLUT1 in tumours, suggesting active glucose uptake, tumour MCT1 detection and decreased intratumour [L‐lactate]/[pyruvate], implying increased lactate efflux and/or intratumour lactate oxidation. Last, high [L‐lactate]/[pyruvate] and MCT1 in cachexic muscle provides a potential muscle‐derived lactate supply for the tumour (a ‘reverse Warburg effect’), supporting tumour growth and consequent cachexia. Our findings suggest several substrate shuttles among liver, skeletal muscle and tumour contribute to metabolic disruption and weight loss. Therapies that aim to normalize dysregulated substrate shuttling among energy‐regulating tissues may alleviate unintended weight loss in cancer cachexia.

Significance of the study

Cachexia is a serious complication of cancer characterized by severe weight loss, muscle atrophy and frailty. Cachexia occurs in roughly half of all cancer patients, and in up to 80% of patients with advanced disease. Cachexia independently worsens patient prognosis, lowers treatment efficacy, increases hospitalization cost and length of stay, and accounts for 20‐30% of cancer‐related deaths. There are no effective treatments. Our findings suggest several substrate shuttles among liver, skeletal muscle and tumour contribute to metabolic disruption and weight loss in cancer cachexia. Identifying therapies that normalize dysregulated substrate shuttling among energy‐regulating tissues may protect against cachexia‐related weight loss.
Room‐Temperature Phosphorescence Emitters Exhibiting Red to Near‐Infrared Emission Derived from Intermolecular Charge‐Transfer Triplet States of Naphthalenediimide–Halobenzoate Triad Molecules
Authors: Ono Toshikazu , Kimura Kazuki , Ihara Megumi , Yamanaka Yuri , Sasaki Miori , Mori Hirotoshi , Hisaeda Yoshio
Published: June 2021

Invited for the cover of this issue is Toshikazu Ono, Yoshio Hisaeda and co‐workers at Kyushu University and their collaborators at Ochanomizu University, Chuo University, and Institute for Molecular Science. The image depicts a molecular assembly structure shining like a jewel, glowing in the red‐to‐near infrared region. Read the full text of the article at 10.1002/chem.202100906.
Kidney outcomes using a sustained ≥40% decline in eGFR: A meta‐analysis of SGLT2 inhibitor trials
Authors: Cherney David Z. I. , Dagogo‐Jack Samuel , McGuire Darren K. , Cosentino Francesco , Pratley Richard , Shih Weichung J. , Frederich Robert , Maldonado Mario , Liu Jie , Wang Shuai , Cannon Christopher P. ,   the VERTIS CV Investigators
Published: June 2021

Background

A recent meta‐analysis of sodium–glucose cotransporter 2 (SGLT2) inhibitor outcome trials reported that SGLT2 inhibitors were associated with reduction in the risk of adverse composite kidney outcomes, with moderate heterogeneity across the trials; however, the endpoints were defined differently across the trials.

Hypothesis

The apparent heterogeneity of the meta‐analysis of kidney composite outcomes of SGLT2 inhibitor trials will be substantially reduced by using a consistent assessment of sustained ≥40% decline in eGFR/chronic kidney dialysis/transplantation/renal death across trials.

Methods

We performed a meta‐analysis of kidney composite outcomes from the four SGLT2 cardiovascular outcome trial programs conducted in general type 2 diabetes mellitus populations, which included, as a surrogate of progression to kidney failure, a sustained ≥40% decline in eGFR along with kidney replacement therapy and kidney death. The trials assessed were VERTIS CV (NCT01986881), CANVAS Program (NCT01032629 and NCT01989754), DECLARE‐TIMI 58 (NCT01730534), and EMPA‐REG OUTCOME (NCT01131676).

Results

Data from the trials comprised 42 516 individual participants; overall, 998 composite kidney events occurred. SGLT2 inhibition was associated with a significant reduction in the kidney composite endpoint (HR 0.58 [95% CI 0.51–0.65]) and with a highly consistent effect across the trials (Q statistic p = .64; I2 = 0.0%).

Conclusions

Our meta‐analysis highlights the value of using similarly defined endpoints across trials and supports the finding of consistent protection against kidney disease progression with SGLT2 inhibitors as a class in patients with type 2 diabetes mellitus who either have established atherosclerotic cardiovascular disease or are at high cardiovascular risk with multiple cardiovascular risk factors.
Atrial fibrillation catheter ablation complications in obese and diabetic patients: Insights from the US Nationwide Inpatient Sample 2005–2013
Authors: D'Souza Shawn , Elshazly Mohamed B. , Dargham Soha R. , Donnellan Eoin , Asaad Nidal , Hayat Sajjad , Kanj Mohamed , Baranowski Brian , Wazni Oussama , Saliba Walid , Abi Khalil Charbel
Published: June 2021

Background

Obesity and diabetes are risk factors for atrial fibrillation (AF) incidence and recurrence after catheter ablation. However, their impact on post‐ablation complications in real‐world practice is unknown.

Objectives

We examine annual trends in AF ablations and procedural outcomes in obese and diabetic patients in the US and whether obesity and diabetes are independently associated with adverse outcomes.

Methods

Using the Nationwide Inpatient Sample (2005–2013), we identified obese and diabetic patients admitted for AF ablation. Common complications were identified using ICD‐9‐CM codes. The primary outcome included the composite of any in‐hospital complication or death. Annual trends of the primary outcome, length‐of‐stay (LOS) and total‐inflation adjusted hospital charges were examined. Multivariate analyses studied the association of obesity and diabetes with outcomes.

Results

An estimated 106 462 AF ablations were performed in the US from 2005 to 2013. Annual trends revealed a gradual increase in ablations performed in obese and diabetic patients and in complication rates. The overall rate of the primary outcome in obese was 11.7% versus 8.2% in non‐obese and 10.7% in diabetic versus 8.2% in non‐diabetic patients (p < .001).

Conclusions

Obesity was independently associated with increased complications (adjusted OR, 95% CI:1.39, 1.20–1.62), longer LOS (1.36, 1.23–1.49), and higher charges (1.16, 1.12–1.19). Diabetes was only associated with longer LOS (1.27, 1.16–1.38). Obesity, but not diabetes, in patients undergoing AF ablation is an independent risk factor for immediate post‐ablation complications and higher costs. Future studies should investigate whether weight loss prior to ablation reduces complications and costs.
Synthesis of L‐[5‐11C]Leucine and L‐α‐[5‐11C]Methylleucine via Pd0‐mediated 11C‐Methylation and Microfluidic Hydrogenation: Potentiality of Leucine PET Probes for Tumor Imaging
Authors: Takatani Shuhei , Tahara Tsuyoshi , Tsuji Mieko , Ozaki Daiki , Shibata Nina , Hashizume Yoshinobu , Suzuki Masaaki , Onoe Hirotaka , Watanabe Yasuyoshi , Doi Hisashi
Published: June 2021

The efficient synthesis of L‐[5‐11C]leucine and L‐α‐[5‐11C]methylleucine has been investigated using a continuous two‐step sequence of rapid reactions consisting of Pd0‐mediated 11C‐methylation and microfluidic hydrogenation. The synthesis of L‐[5‐11C]leucine and L‐α‐[5‐11C]methylleucine was accomplished within 40 min with a decay‐corrected radiochemical yield of 15–38 % based on [11C]CH3I, radiochemical purity of 95–99 %, and chemical purity of 95–99 %. The Pd impurities in the injectable solution measured using inductively coupled plasma mass spectrometry met the international criteria for human use. Positron emission tomography scanning after an intravenous injection of L‐[5‐11C]leucine or L‐α‐[5‐11C]methyl leucine in A431 tumor‐bearing mice was performed. As a result, L‐α‐[5‐11C]methylleucine was found to be a potentially useful probe for visualizing the tumor. Tissue distribution analysis showed that the accumulation value of L‐α‐[5‐11C]methylleucine in tumor tissue was high [12±3% injected dose/g tissue (%ID/g)].
User defined weight based budget and deadline constrained workflow scheduling in cloud
Authors: Gupta Swati , Singh Ravi S. , Vasant Umare D. , Saxena Vijit
Published: June 2021

Cloud computing is a technology that is being used by scientists for the execution of huge scale workflows as it has various features such as availability, faster, cheaper, elasticity, and high accessibility. In addition, the users are charged on a pay per use basis which makes it more efficient to be used by various clients. Scheduling workflows in the cloud is a difficult task as it takes into account the dependencies of workflows along with quality of service (QoS) demands. The problem becomes more challenging when there are multiple QoS objectives which are often disagreeing to each other. A lot of research has been done to minimize makespan and execution cost under deadline and budget constraints. This article presents a workflow scheduling algorithm based on Jaya to minimize them both and returns solutions according to the weights a user gives. The algorithm has been compared with Min‐Min, Max‐Min, Round Robin, heterogeneous earliest finish time first, first come first serve, minimum completion time, dynamic heterogeneous earliest finish time first in WorkflowSim. The results are compared based on both cost and time. In the end, a trade‐off between the objectives has been shown. Results show that Jaya performs much better than other algorithms when averaged over several iterations.
Ether‐Functionalized Pyrrolidinium‐Based Room Temperature Ionic Liquids: Physicochemical Properties, Molecular Dynamics, and the Lithium Ion Coordination Environment
Authors: Yoshii Kazuki , Uto Takuya , Onishi Takakazu , Kosuga Daichi , Tachikawa Naoki , Katayama Yasushi
Published: June 2021

The physicochemical properties of room temperature ionic liquids (RTILs) consisting of bis(trifluoromethanesulfonyl)amide (TFSA−) combined with 1‐hexyl‐1‐methylpyrrolidinium (Pyr1,6+), 1‐(butoxymethyl)‐1‐methylpyrrolidinium (Pyr1,1O4+), 1‐(4‐methoxybutyl)‐1‐methyl pyrrolidinium (Pyr1,4O1+), and 1‐((2‐methoxyethoxy)methyl)‐1‐methylpyrrolidinium (Pyr1,1O2O1+) were investigated using both experimental and computational approaches. Pyr1,1O2O1TFSA, which contains two ether oxygen atoms, showed the lowest viscosity, and the relationship between its physicochemical properties and the position and number of the ether oxygen atoms was discussed by a careful comparison with Pyr1,1O4TFSA and Pyr1,4O1TFSA. Ab initio calculations revealed the conformational flexibility of the side chain containing the ether oxygen atoms. In addition, molecular dynamics (MD) calculations suggested that the ion distributions have a significant impact on the transport properties. Furthermore, the coordination environments of the Li ions in the RTILs were evaluated using Raman spectroscopy, which was supported by MD calculations using 1000 ion pairs. The presented results will be valuable for the design of functionalized RTILs for various applications.
Detecting Förster resonance energy transfer in living cells by conventional and spectral flow cytometry
Authors: Henderson Jared , Havranek Ondrej , Ma Man Chun John , Herman Vaclav , Kupcova Kristyna , Chrbolkova Tereza , Pacheco‐Blanco Mariana , Wang Zhiqiang , Comer Justin M. , Zal Tomasz , Davis Richard Eric
Published: June 2021

Assays based on Förster resonance energy transfer (FRET) can be used to study many processes in cell biology. Although this is most often done with microscopy for fluorescence detection, we report two ways to measure FRET in living cells by flow cytometry. Using a conventional flow cytometer and the “3‐cube method” for intensity‐based calculation of FRET efficiency, we measured the enzymatic activity of specific kinases in cells expressing a genetically‐encoded reporter. For both AKT and protein kinase A, the method measured kinase activity in time‐course, dose–response, and kinetic assays. Using the Cytek Aurora spectral flow cytometer, which applies linear unmixing to emission measured in multiple wavelength ranges, FRET from the same reporters was measured with greater single‐cell precision, in real time and in the presence of other fluorophores. Results from gene‐knockout studies suggested that spectral flow cytometry might enable the sorting of cells on the basis of FRET. The methods we present provide convenient and flexible options for using FRET with flow cytometry in studies of cell biology.
A cross‐standardized flow cytometry platform to assess phenotypic stability in precursor B‐cell acute lymphoblastic leukemia (B‐ALL) xenografts
Authors: Rolf Nina , Liu Lorraine Y. T. , Tsang Angela , Lange Philipp F. , Lim Chinten James , Maxwell Christopher A. , Vercauteren Suzanne M. , Reid Gregor S. D.
Published: June 2021

With the continued poor outcome of relapsed acute lymphoblastic leukemia (ALL), new patient‐specific approaches for disease progression monitoring and therapeutic intervention are urgently needed. Patient‐derived xenografts (PDX) of primary ALL in immune‐deficient mice have become a powerful tool for studying leukemia biology and therapy response. In PDX mice, the immunophenotype of the patient's leukemia is commonly believed to be stably propagated. In patients, however, the surface marker expression profile of the leukemic population often displays poorly understood immunophenotypic shifts during chemotherapy and ALL progression. We therefore developed a translational flow cytometry platform to study whether the patient‐specific immunophenotype is faithfully recapitulated in PDX mice. To enable valid assessment of immunophenotypic stability and subpopulation complexity of the patient's leukemia after xenotransplantation, we comprehensively immunophenotyped diagnostic B‐ALL from children and their matched PDX using identical, clinically standardized flow protocols and instrument settings. This cross‐standardized approach ensured longitudinal stability and cross‐platform comparability of marker expression intensity at high phenotyping depth. This analysis revealed readily detectable changes to the patient leukemia‐associated immunophenotype (LAIP) after xenotransplantation. To further investigate the mechanism underlying these complex immunophenotypic shifts, we applied an integrated analytical approach that combined clinical phenotyping depth and high analytical sensitivity with unbiased high‐dimensional algorithm‐based analysis. This high‐resolution analysis revealed that xenotransplantation achieves patient‐specific propagation of phenotypically stable B‐ALL subpopulations and that the immunophenotypic shifts observed at the level of bulk leukemia were consistent with changes in underlying subpopulation abundance. By incorporating the immunophenotypic complexity of leukemic populations, this novel cross‐standardized analytical platform could greatly expand the utility of PDX for investigating ALL progression biology and assessing therapies directed at eliminating relapse‐driving leukemic subpopulations.
Multiple co‐occurrent alien invaders constrain aquatic biodiversity in rivers
Authors: Guareschi Simone , Laini Alex , England Judy , Barrett Jon , Wood Paul J.
Published: June 2021

A greater understanding and effective management of biological invasions is a priority for biodiversity conservation globally. Many freshwater ecosystems are experiencing the colonization and spread of multiple co‐occurrent alien species. Here the implications of both the relative abundance and richness of alien invaders on aquatic macroinvertebrate taxonomic and functional richness, ecosystem quality, and functional redundancy are assessed using long‐term data from rivers in England. Based on the most common aquatic invaders, results indicated that their richness, rather than abundance, was the most important factor negatively affecting aquatic macroinvertebrate biodiversity. However, the response of functional redundancy was negatively affected by invader abundance at the river basin scale. The response of communities varied as the number of invading taxa increased, with the most marked reductions following the colonization of the first few invaders. Results indicate that different facets of multiple biological invasions influence distinct aspects of aquatic biodiversity. Preventing the establishment of new invaders and limiting invader taxa richness within a community should therefore be a conservation priority. These findings will assist river scientists in understanding mechanisms driving changes in biodiversity and facilitate the testing of ecological theories while also ensuring environmental managers and regulators can prioritize conservation / management opportunities.
Fine‐scale movements and behaviors of coyotes (Canis latrans) during their reproductive period
Authors: Chamberlain Michael J. , Cohen Bradley S. , Wightman Patrick H. , Rushton Emily , Hinton Joseph W.
Published: June 2021

In canids, resident breeders hold territories but require different resources than transient individuals (i.e., dispersers), which may result in differential use of space, land cover, and food by residents and transients. In the southeastern United States, coyote (Canis latrans) reproduction occurs during spring and is energetically demanding for residents, but transients do not reproduce and therefore can exhibit feeding behaviors with lower energetic rewards. Hence, how coyotes behave in their environment likely differs between resident and transient coyotes. We captured and monitored 36 coyotes in Georgia during 2018–2019 and used data from 11 resident breeders, 12 predispersing residents (i.e., offspring of resident breeders), and 11 transients to determine space use, movements, and relationships between these behaviors and landcover characteristics. Average home range size for resident breeders and predispersing offspring was 20.7 ± 2.5 km² and 50.7 ± 10.0 km², respectively. Average size of transient ranges was 241.4 ± 114.5 km². Daily distance moved was 6.3 ± 3.0 km for resident males, 5.5 ± 2.7 km for resident females, and 6.9 ± 4.2 km for transients. We estimated first‐passage time values to assess the scale at which coyotes respond to their environment, and used behavioral change‐point analysis to determine that coyotes exhibited three behavioral states. We found notable differences between resident and transient coyotes in regard to how landcover characteristics influenced their behavioral states. Resident coyotes tended to select for areas with denser vegetation while resting and foraging, but for areas with less dense vegetation and canopy cover when walking. Transient coyotes selected areas closer to roads and with lower canopy cover while resting, but for areas farther from roads when foraging and walking. Our findings suggest that behaviors of both resident and transient coyotes are influenced by varying landcover characteristics, which could have implications for prey.
COVID‐19 in a country with a very high prevalence of diabetes: The impact of admission hyperglycaemia on mortality
Authors: Martínez‐Murillo Carlos , Ramos Peñafiel Christian , Basurto Lourdes , Balcázar‐Hernández Lourdes , Pellón Karen , Flores López Eder , Li Gómez Beatriz , Ledesma Mercedes Estefania , Rivera Tapia Rodrigo , Madera Maldonado Elizabeth , Bejarano Rosales Monica , Barranco Lampon Gilberto , Zazueta Juan Francisco
Published: June 2021

Aims

To evaluate the frequency of diabetes and admission hyperglycaemia in Mexican COVID‐19 patients, to describe the clinical and biochemical characteristics of patients with admission hyperglycaemia and to determinate the impact of diabetes and admission hyperglycaemia on COVID‐19 severity and mortality.

Methods

A multicentric study was performed in 480 hospitalized patients with COVID‐19. Clinical and biochemical characteristics were evaluated in patients with admission hyperglycaemia and compared with non‐hyperglycaemic patients. The effect of diabetes and admission hyperglycaemia on severity and risk of death were evaluated.

Results

Age was 50.7 ± 13.6 years; 68.3% were male. Some 48.5% (n = 233) had admission hyperglycaemia; 29% (n = 139) of these patients had pre‐existing diabetes. Patients with admission hyperglycaemia had more requirement of invasive mechanical ventilation (IMV), higher levels of urea, D‐dimer and neutrophil‐lymphocyte ratio (NLR), as well as lower lymphocyte count. An association between admission hyperglycaemia with IMV and D‐dimer with glucose was found. Age ≥50 years (OR 2.09; 95%CI 1.37–3.17), pre‐existing diabetes (OR 2.38; 95%CI 1.59–5.04) and admission hyperglycaemia (OR 8.24; 95%CI 4.74–14.32) were risk factors for mortality.

Conclusions

Admission hyperglycaemia is presented in 48.5% of COVID‐19 patients. Diabetes and admission hyperglycaemia are associated with the severity of disease and mortality. This study shows the devastating conjunction of hyperglycaemia and COVID‐19.

Clinical trial registration: Clinical characteristics of patients with COVID‐19, DI/20/204/04/41 (Hospital General de Mexico) and NR‐13‐2020 (Hospital Regional de Alta Especialidad Ixtapaluca).
Utilization of Rhenium(I) Polypyridine Complexes Featuring a Dinitrophenylsulfonamide Moiety as Biothiol‐Selective Phosphorogenic Bioimaging Reagents and Photocytotoxic Agents
Authors: Xu Guang‐Xi , Lee Lawrence Cho‐Cheung , Kwok Cyrus Wing‐Ching , Leung Peter Kam‐Keung , Zhu Jing‐Hui , Lo Kenneth Kam‐Wing
Published: June 2021

We report herein a series of rhenium(I) polypyridine complexes featuring a 2,4‐dinitrophenylsulfonamide (DNPS) unit as phosphorogenic bioimaging reagents and photocytotoxic agents. The biothiol‐selective rhenium(I) polypyridine complexes [Re(N^N)(CO)3(py‐DNPS)](CF3SO3) (py‐DNPS=3‐((2,4‐dinitrophenylsulfonyl)aminomethyl)pyridine) and their DNPS‐free counterparts [Re(N^N)(CO)3(pyridine)](CF3SO3) were synthesized and characterized. Upon photoexcitation, the DNPS complexes exhibited very weak luminescence as a result of photoinduced electron transfer (PET) from the excited rhenium(I) diimine moiety to the DNPS quenching unit. However, upon treatment with glutathione (GSH), the DNPS moiety was removed, resulting in emission enhancement of the solutions (I/Io=12.6–22.2). After reaction of the DNPS complexes with GSH in living cells, intense intracellular emission and potent photocytotoxicity were both observed. Additionally, the modification of the diimine ligand with a tosylamide unit conferred on the complexes an endoplasmic reticulum (ER)‐targeting ability, which can be exploited for selective bioimaging and photocytotoxic applications.
Preparation of Cobalt Nanoparticles
Authors: Khusnuriyalova Aliya F. , Caporali Maria , Hey‐Hawkins Evamarie , Sinyashin Oleg G. , Yakhvarov Dmitry G.
Published: June 2021

The development of modern chemistry is currently proceeding in several priority areas including investigations focused on the synthesis, stabilisation, and application of transition metal nanoparticles (NPs), which are widely used in physical, chemical, engineering, and biomedical processes. A special place among known transition metal NPs is occupied by cobalt nanoparticles, since they are used for highly important targets, such as creation of new catalysts, magnetic devices, composites, or carriers for drug delivery. The selective preparation of NPs is a difficult task that requires special conditions and has some limitations. In this minireview, we summarise the most successful and most efficient methods for obtaining Co NPs, including chemical and physical aspects of their preparation.
Synthesis, Structures and Magnetic Properties of two Heteroleptic Dy3+ Borohydride Complexes
Authors: Long Jérôme , Selikhov Alexander N. , Rad'kova Natalia Yu. , Cherkasov Anton V. , Guari Yannick , Larionova Joulia , Trifonov Alexander A.
Published: June 2021

We report the synthesis, structures and magnetic properties of two Dy3+ heteroleptic complexes [Dy(BH4)2(THF)5][BPh4] (1) and [Dy(BH4)2(tBu4Carb)(THF)] (2) (tBu4Carb=1,3,6,8‐tetra‐tert‐butyl‐9H‐carbazole). Both complexes show a κ3‐coordination mode of the borohydride anion but distinct geometries. Whereas the cationic complex 1 does not exhibit a slow relaxation of the magnetization, the neutral complex 2 behaves as a field‐induced single‐molecule magnet.
Recent Progress in the Synthesis of Heterocycles through Base Metal‐Catalyzed Acceptorless Dehydrogenative and Borrowing Hydrogen Approach
Authors: Mondal Avijit , Sharma Rahul , Pal Debjyoti , Srimani Dipankar
Published: June 2021

Development in the area of acceptorless dehydrogenation (AD) and borrowing hydrogen (BH) catalysis emerge as one of the potential tools for various C−C and C‐heteroatom bond forming reactions. Alcohols, which are important lignocellulosic biomass products, act as pivotal electrophilic coupling partners in such processes and interestingly only H2 or H2O is eliminated as a byproduct. Initially, the area was developed by the use of noble metal catalysts. Recently, base metals such as Mn, Fe, Co, and Ni proved to be environmentally benign and inexpensive alternatives for the noble metals in the application of AD and BH methods. This transition metal catalyzed AD and BH approaches also allow access toward a plethora of structurally important heterocyclic molecules via environmentally benign and atom economical strategy. Herein, we summarize the current and rising expansion of base metal catalyzed heterocycles synthesis through acceptorless dehydrogenation and borrowing hydrogenation strategy.
Save water and energy: A techno‐economic analysis of a floating solar photovoltaic system to power a water integration project in the Brazilian semiarid
Authors: da Costa Luana Carolina Alves , da Silva Gardenio Diogo Pimentel
Published: June 2021

This paper proposes the use of a floating solar photovoltaic (FSPV) power plant as an alternative renewable energy resource for the San Francisco River Integration Project (SFIP), which aims to deliver water to 12 million people in the Brazilian semiarid. The SFIP requires considerable amounts of energy in a region that has had increasing electricity costs and consumption of water in the past decade. By simulating an FSPV power plant at the System Advisor Model (SAM) using techniques and parameters of real FSPV projects, the results demonstrated the techno‐economic feasibility of this technology linked to the SFIP. The economic outcomes are positive net present value (NPV), $2.8 million, and a payback varying from 10.5 to 11.7 years. The levelized cost of electricity (LCOE) of $32.17/MWh is smaller than the current energy rates paid by the SFIP administrator, and the water costs to final consumers could be reduced by 40%. In addition, the FSPV's capacity factor was 21.1%, and the system could minimize water evaporation from one of the SFIP's reservoirs by 16.7%. The system can also create revenues for the San Francisco and Parnaiba Valleys Development Company (CODEVASF) by trading the excess of electricity with the grid. This paper also analyses the FSPV's environmental impacts and its relevance under the water–energy nexus in the Brazilian Northeast. The FSPV could minimize the SFIP's operational costs, avoid environmental impacts, and improve the efficiency of water and energy management. Such components are crucial when analyzing the water–energy nexus in such a region, marked by strong competition for water access and long periods of drought.
Space degradation of triple junction solar cells at low temperatures: II‐electron irradiation
Authors: Park Seonyong , Cavani Olivier , Lefèvre Jérémie , Baur Carsten , Khorenko Victor , Boizot Bruno
Published: June 2021

We investigated the behavior of electron‐irradiated 3G28 InGaP/GaAs/Ge triple junction solar cells and their component (top, middle and bottom) cells at low temperatures from 100 to 300 K and low illumination intensity. Significant degradation of their performances has been observed. We found that it is induced by an excess current associated with tunneling due to the presence of the radiation‐induced defects introduced in the junctions of each sub‐cell. The amount of tunneling current, hence of the effect of degradation, is significantly higher in the bottom sub‐cell than in the top and middle sub‐cells. This particular cell is formed by diffusion of group V atoms into p‐Ge substrate, which leads to relatively inhomogeneous doping profile and thus tunneling current distribution compared to well controlled top and middle sub‐cells deposited by epitaxy. The degradation associated with tunneling recovers significantly at 300 K in the bottom cell.