bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma IL‐12/IFN‐γ axis predicts cognitive trajectories in cognitively unimpaired older adults
Authors: Yang Hyun‐Sik , Zhang Can , Carlyle Becky C. , Zhen Sherri Y. , Trombetta Bianca A. , Schultz Aaron P. , Pruzin Jeremy J. , Fitzpatrick Colleen D. , Yau Wai‐Ying W. , Kirn Dylan R. , Rentz Dorene M. , Arnold Steven E. , Johnson Keith A. , Sperling Reisa A. , Chhatwal Jasmeer P. , Tanzi Rudolph E.
Published: June 2021

Introduction

Immune dysregulation is implicated in neurodegeneration and altered cytokine levels are seen in people with dementia. However, whether cytokine levels are predictive of cognitive decline in cognitively unimpaired (CU) elderly, especially in the setting of elevated amyloid beta (Aβ), remains unclear.

Methods

We measured nine cytokines in the baseline plasma of 298 longitudinally followed CU elderly and assessed whether these measures were associated with cognitive decline, alone or synergistically with Aβ. We next examined associations between cytokine levels and neuroimaging biomarkers of Aβ/tau/neurodegeneration.

Results

Higher IL‐12p70 was associated with slower cognitive decline in the setting of higher Aβ (false discovery rate [FDR] = 0.0023), whereas higher IFN‐γ was associated with slower cognitive decline independent of Aβ (FDR = 0.013). Higher IL‐12p70 was associated with less tau and neurodegeneration in participants with higher Aβ.

Discussion

Immune dysregulation is implicated in early‐stage cognitive decline, and greater IL‐12/IFN‐γ axis activation may be protective against cognitive decline and early‐stage AD progression.
Stable isotopes reveal the importance of terrestrially derived resources for the diet of the freshwater pearl mussel (Margaritifera margaritifera)
Authors: Brauns Mario , Berendonk Thomas , Berg Sina , Grunicke Felix , Kneis David , Krenek Sascha , Schiller Thomas , Schneider Jana , Wagner Annekatrin , Weitere Markus
Published: June 2021

The freshwater pearl mussel (FPM) is among the most endangered freshwater species worldwide. The few remaining populations suffer from low recruitment rates and are subject to habitat fragmentation, pollution, siltation, decline or loss of host fish populations, and climate change.

Successful conservation strategies for FPM require a holistic understanding of its ecological requirements, life history, population dynamics, and habitat prerequisites. Although habitat requirements are well described, food requirements at different life stages have received less attention.

Stable isotope analyses of FPM and potential food resources in three German streams were combined with mixing model analysis to quantify organic matter resources assimilated by juvenile (first year after encystment from host fish) and semi‐adult (10 years old, immature) individuals.

There were only slight differences in dietary contributions between the two life stages, and terrestrial particulate organic matter and benthic organic matter contributed substantially to the diet. Tissue type was more important in explaining variation in dietary contributions than individual variation for semi‐adult FPM. The strong reliance on terrestrial resources sheds new light on the functional role of unionid mussels and the connection of streams to their riparian area.

The dependence of FPM on terrestrial resources also emphasizes the need for a stronger focus on the restoration and protection of intact riparian areas, including wetlands with their specific vegetation, when planning conservation and management strategies for threatened FPM populations.
Nitrogen Doped Carbon Coated Bi Microspheres as High‐performance Anode for Half and Full Sodium Ion Batteries
Authors: Ma Hao , Wang Tianyi , Li Jiabao , Yang Jian , Liu Zhigang , Wang Na , Su Dawei , Wang Chengyin
Published: June 2021

As two‐dimensional (2D) materials, bismuth (Bi) has large interlayer spacing along c‐axis (0.395 nm) which provides rich active sites for sodium ions, thus guaranteeing high sodium ion storage activity. However, its poor electrical conductivity, combined with its degraded cycling performance, restricts its practical application. Herein, Bi microsphere coated with nitrogen‐doped carbon (Bi@NC) was synthesized. Owing to the unique Bi crystals and nitrogen‐doped carbon layer, the obtained Bi@NC anode exhibited satisfactory cycling stability and superior rate capability. Moreover, after assembling Bi@NC anode with Na3V2(PO4)3@C cathode to full battery, excellent sodium storage performance was obtained (57 mA h g−1 after 2000 cycles at 1.0 A g−1).
Cucurbituril Based Luminescent Materials in Aqueous Media and Solid State
Authors: Bhaumik Shubhra Kanti , Biswas Rakesh , Banerjee Supratim
Published: June 2021

Cucurbit[n]urils, the pumpkin shaped macrocyclic host molecules possessing a hydrophobic cavity and two identical carbonyl portals, have drawn a lot of attention in recent years due to their high‐affinity yet dynamic molecular recognition properties in water. The reversible and stimuli‐responsive nature of their host‐guest complexes imparts “smart” features leading to materials with intriguing optical, mechanical and morphological properties. In this review, we focus on the design of cucurbituril based luminescent materials in aqueous media as well in solid or film state. The design principles of fluorescent complexes, small assemblies as well as supramolecular polymers along with their stimuli‐responsive properties and applications in diverse areas such as optoelectronic devices, light harvesting, anti‐counterfeiting and information technology, cell imaging, etc are highlighted with selected examples from recent literature. We also discuss examples of room temperature phosphorescent materials derived from purely organic luminogens in the presence of cucurbiturils.
Controllability of multilayer networks
Authors: Jiang Lixin , Tang Longkun , Lü Jinhu
Published: June 2021

Network controllability recently stimulates researchers' growing interests, and large‐scale networked systems in real applications can be well described by multilayer networks. The intrinsic relationship between network controllability and multiple types of connection structures is far from clear and needs further investigations. This paper studies the state controllability of multilayer networks with high‐dimensional nodal systems, where the network topology is described by multiple connection structures with different coupling modes. We focus on the impact of multilayer structures, multiple coupling modes, and external control inputs on the controllability of multilayer networked systems, and investigations show that (1) the controllability of multilayer networked system is far more complicated than that of monolayer networked systems and the multilayser topological structures facilitate the controllability; (2) different from that in the monolayer network system, a two‐layer network system may be controllable even if both underlying network topologies are uncontrollable. However, under certain conditions, uncontrollable network topologies lead to the two‐layer network system being uncontrollable; (3) the mutually complementary coupling modes are beneficial to the controllability of multilayer networks.
Study of the properties of carotenoids and key carotenoid biosynthesis genes from Deinococcus xibeiensis R13
Authors: Chu Xiaoting , Liu Jie , Gu Wanyi , Tian Liqing , Tang Susu , Zhang Zhidong , Jiang Ling , Xu Xian
Published: June 2021

To investigate the properties of carotenoids from the extremophile Deinococcus xibeiensis R13, the factors affecting the stability of carotenoids extracted from D. xibeiensis R13, including temperature, illumination, pH, redox chemicals, metal ions, and food additives, were investigated. The results showed that low temperature, neutral pH, reducing agents, Mn2+, and food additives (xylose and glucose) can effectively improve the stability of Deinococcus carotenoids. The carotenoids of D. xibeiensis R13 exhibited strong antioxidant activity, with the scavenging rate of hydroxyl radicals reaching 71.64%, which was higher than the scavenging efficiency for 1,1‐diphenyl‐2‐picrylhydrazyl free radicals and 2,2'‐azino‐bis (3‐ethyl‐benzothiazoline‐6‐sulfonic acid) free radicals (44.55 and 27.65%, respectively). In addition, the total antioxidant capacity reached 0.60 U/ml, which was 2.61‐fold that of carotenoids from the model strain Deinococcus radiodurans R1. Finally, we predicted the gene clusters encoding carotenoid biosynthesis pathways in the genome of R13 and identified putative homologous genes. The key enzyme genes (crtE, crtB, crtI, crtLm, cruF, crtD, and crtO) in carotenoid synthesis of D. xibeiensis R13 were cloned to construct the multigene coexpression plasmids pET‐EBI and pRSF‐LmFDO. The carotenoid biosynthesis pathway was heterologously introduced into engineered Escherichia coli EBILmFDO, which exhibited a higher yield (7.14 mg/L) than the original strain. These analysis results can help us to better understand the metabolic synthesis of carotenoids in extremophiles.
Does transcriptional heterogeneity facilitate the development of genetic drug resistance?
Authors: Farquhar Kevin S. , Rasouli Koohi Samira , Charlebois Daniel A.
Published: June 2021

Non‐genetic forms of antimicrobial (drug) resistance can result from cell‐to‐cell variability that is not encoded in the genetic material. Data from recent studies also suggest that non‐genetic mechanisms can facilitate the development of genetic drug resistance. We speculate on how the interplay between non‐genetic and genetic mechanisms may affect microbial adaptation and evolution during drug treatment. We argue that cellular heterogeneity arising from fluctuations in gene expression, epigenetic modifications, as well as genetic changes contribute to drug resistance at different timescales, and that the interplay between these mechanisms enhance pathogen resistance. Accordingly, developing a better understanding of the role of non‐genetic mechanisms in drug resistance and how they interact with genetic mechanisms will enhance our ability to combat antimicrobial resistance. Also see the video abstract here: https://youtu.be/aefGpdh-bgU
Practicing logical reasoning through Drosophila segmentation gene mutants
Authors: Bargiela Ariadna , Artero Ruben
Published: June 2021

Laboratory practical sessions are critical to scientific training in biology but usually fail to promote logical and hypothesis‐driven reasoning and rely heavily on the teacher's instructions. This paper describes a 2‐day laboratory practicum in which students prepare and analyze larval cuticle preparations of Drosophila segmentation gene mutant strains. Embryonic segmentation involves three major classes of genes according to their loss‐of‐function phenotypes: the establishment of broad regions by gap genes, the specification of the segments by the pair‐rule genes, and the compartments within segments by the segment polarity genes. Students are asked to sort undefined segmentation mutants into gap, pair‐rule, or segment polarity categories based on their knowledge of the Drosophila segmentation process and the microscopic anatomical traits they are capable of finding in the sample preparations. This technically simple practicum prompts students to pay attention to detailed observation to detect anatomic markers of intrasegmental compartments and thorax versus abdomen cuticle, and promote their logical reasoning in hypothesizing to which segmentation type a given mutant fits best.
Physically processing imperfect produce: The impact of prototypicality
Authors: Barone Ada Maria , Donato Carmela , Romani Simona
Published: June 2021

Forty percent of edible produce is wasted because of consumers' aversion toward esthetical imperfections related to size, shape, and blemish for produce. This phenomenon has huge implications in terms of both environmental sustainability and food security, and calls for the development of interventions that could facilitate the sale of products which would otherwise go to waste. This research provides an explanation for why transforming the physical state of imperfect produce—that is, by physically processing it and turning it into other products (e.g., juices)—is a successful strategy in this sense. More specifically, when imperfect produce is transformed, the new processed product (e.g., juice) belongs to a different conceptual category and thus is perceived as more prototypical and a good example of this new category. We show that higher perceptions of prototypicality in turn lead to more positive preferences. We test this effect in three experimental studies and show that this mechanism is robust across a range of possible transformations of imperfect produce (e.g., natural vs. artificial) and across different dependent variables (i.e., purchase intention, product choice, willingness to pay). Our findings provide evidence for the effectiveness of a solution to be enacted by retailers and actors of the food sector and provide suggestions for public policy initiatives aimed at curbing food waste.
Design, Synthesis and Antibacterial Activity of Novel Pyrimidine‐Containing 4H‐Chromen‐4‐One Derivatives**
Authors: Su Shijun , Chen Mei , Tang Xuemei , Peng Feng , Liu Tingting , Zhou Qing , Zhan Wenliang , He Ming , Xie Chengwei , Xue Wei
Published: June 2021

A series of pyrimidine‐containing 4H‐chromen‐4‐one derivatives were designed and synthesized by combining bioactive substructures. Preliminary biological activity results showed that most of the compounds displayed significant inhibitory activities in vitro against Xanthomonas axonopodis pv. Citri (X. axonopodis), Xanthomonas oryzae pv. oryzae (X. oryzae) and Ralstonia solanacearum (R. solanacearum). In particular, compound 2‐[(3‐{[5,7‐dimethoxy‐4‐oxo‐2‐(3,4,5‐trimethoxyphenyl)‐4H‐1‐benzopyran‐3‐yl]oxy}propyl)sulfanyl]‐4‐(4‐methylphenyl)‐6‐oxo‐1,6‐dihydropyrimidine‐5‐carbonitrile (4c) demonstrated a good inhibitory effect against X. axonopodis and X. oryzae, with the half‐maximal effective concentration (EC50) values of 15.5 and 14.9 μg/mL, respectively, and compound 2‐[(3‐{[5,7‐Dimethoxy‐4‐oxo‐2‐(3,4,5‐trimethoxyphenyl)‐4H‐1‐benzopyran‐3‐yl]oxy}propyl)sulfanyl]‐4‐(3‐fluorophenyl)‐6‐oxo‐1,6‐dihydropyrimidine‐5‐carbonitrile (4h) showed the best antibacterial activity against R. solanacearum with an EC50 value of 14.7 μg/mL. These results were better than commercial reagents bismerthiazol (BT, 51.7, 70.1 and 52.7 μg/mL, respectively) and thiodiazole copper (TC, 77.9, 95.8 and 72.1 μg/mL, respectively). In vivo antibacterial activity results indicated that compound 4c displayed better curative (42.4 %) and protective (49.2 %) activities for rice bacterial leaf blight than BT (35.2, 39.1 %) and TC (30.8, 27.3 %). The mechanism of compound 4c against X. oryzae was analyzed through scanning electron microscopy (SEM). These results indicated that pyrimidine‐containing 4H‐chromen‐4‐one derivatives have important value in the research of new agrochemicals.
Photosensitized Oxidative Dimerization at Tyrosine by a Water‐Soluble 4‐Amino‐1,8‐naphthalimide
Authors: Keyes E. Dalles , Kauser Katalin , Warner Kevin S. , Roberts Andrew G.
Published: June 2021

The oxidation of proteins generates reactive amino acid (AA) residue intermediates, leading to protein modification and cross‐linking. Aerobic studies with peptides and photosensitizers allow for the controlled generation of reactive oxygen species (ROS) and reactive AA residue intermediates, providing mechanistic insights as to how natural protein modifications form. Such studies have inspired the development of abiotic methods for protein modification and crosslinking, including applications of biomedical importance. Dityrosine linkages derived from oxidation at tyrosine (Tyr) residues represent one of the more well‐understood oxidation‐induced modifications. Here we demonstrate an aerobic, visible light‐dependent oxidation reaction of Tyr‐containing substrates promoted by a water‐soluble 4‐amino‐1,8‐naphthalimide‐based photosensitizer. The developed procedure converts Tyr‐containing substrates intoo,o’‐Tyr‐Tyr linked dimers. The regioselectively formedo,o’‐Tyr‐Tyr linkage is consistent with dimeric standards prepared using a known enzymatic method. A crossover study with two peptides provides a statistical mixture of three distincto,o’‐Tyr‐Tyr linked dimers, supporting a mechanism that involves Tyr residue oxidation followed by intermolecular combination.
Novel Homologs of Isopentenyl Phosphate Kinase Reveal Class‐Wide Substrate Flexibility
Authors: Kumar Vikas , Johnson Bryce P. , Dimas Dustin A. , Singh Shanteri
Published: June 2021

The widespread utility of isoprenoids has recently sparked interest in efficient synthesis of isoprene‐diphosphate precursors. Current efforts have focused on evaluating two‐step “isoprenol pathways,” which phosphorylate prenyl alcohols using promiscuous kinases/phosphatases. The convergence on isopentenyl phosphate kinases (IPKs) in these schemes has prompted further speculation about the class's utility in synthesizing non‐natural isoprenoids. However, the substrate promiscuity of IPKs in general has been largely unexplored. Towards this goal, we report the biochemical characterization of five novel IPKs from Archaea and the assessment of their substrate specificity using 58 alkyl‐monophosphates. This study reveals the IPK‐catalyzed synthesis of 38 alkyl‐diphosphate analogs and discloses broad substrate specificity of IPKs. Further, to demonstrate the biocatalytic utility of IPK‐generated alkyl‐diphosphates, we also highlight the synthesis of alkyl‐l‐tryptophan derivatives using coupled IPK‐prenyltransferase reactions. These results reveal IPK‐catalyzed reactions are compatible with downstream isoprenoid enzymes and further support their development as biocatalytic tools for the synthesis of non‐natural isoprenoids.
Mechanistic Considerations on the H2 Production by Methanol Thermal‐assisted Photocatalytic Reforming over Cu/TiO2 Catalyst
Authors: Platero Francisco , López‐Martín Angeles , Caballero Alfonso , Colón Gerardo
Published: June 2021

We have studied the gas phase H2 production by methanol thermo‐photoreforming using Cu‐modified TiO2. Metal co‐catalyst has been deposited by means of photodeposition method. The concentration of methanol in the steam was also considered. It appears that H2 production is notably higher as temperature increases. Moreover, the optimum H2 yield is achieved using methanol concentration of 10 % v/v. CO and CO2 were monitored as side products of the overall reaction. It has been stated that CO evolution is significant at lower temperatures. As temperature increases, CO evolution is hindered and H2 appeared boosted. We have demonstrated that other reactions such water‐gas‐shift or formate dehydration would participate in the overall process. On this basis, optimal operational condition for H2 production is attained for thermo‐photocatalytic reforming of methanol solution 10 % v/v at 200 °C.
Six‐Electron Chemistry of a Binuclear Fe(III) Fused Porphyrin
Authors: Reyes Cruz Edgar A. , Nishiori Daiki , Wadsworth Brian L. , Khusnutdinova Diana , Karcher Timothy , Landrot Gautier , Lassalle‐Kaiser Benedikt , Moore Gary F.
Published: June 2021

In this special collection dedicated to Prof. Jean‐Michel Savéant, we report on the synthesis and characterization of a novel binuclear Fe(III) fused porphyrin. Ultraviolet‐visible spectroscopy confirms the extended electronic structure of this macrocycle. In addition, Fourier transform infrared spectroscopy indicates the Fe centers experience a relatively rigid ligand environment as compared to a structurally related mononuclear complex featuring an 18 π‐aromatic porphyrin ligand. X‐ray photoelectron and X‐ray absorption near edge spectroscopies confirm the iron centers of both assemblies are Fe(III) in the as prepared, resting state. In comparison with the mononuclear porphyrin, electrochemical measurements show there is a doubling of the number of redox events associated with the fused, binuclear complex. In summary, key features of the fused‐iron‐porphyrin include: 1) bimetallic‐iron sites, 2) a π‐extended ligand capable of delocalizing electrons across the multimetallic scaffold, and 3) the ability to store up to six electrons.
Role of SnO2 in the Bifunctional Mechanism of CO Oxidation at Pt‐SnO2 Electrocatalysts
Authors: Huang Haoliang , Hayes Edward T. C. , Gianolio Diego , Cibin Giannantonio , Hage Fredrik S. , Ramasse Quentin M. , Russell Andrea E.
Published: June 2021

Pt‐Sn bimetallic catalysts, especially Pt‐Sn alloys, are considered highly CO‐tolerant and are thus candidates for reformate derived hydrogen oxidation and for direct oxidation of fuel cell molecules. However, it remains unclear if this CO‐tolerance originates from Sn in the Pt‐Sn alloy or whether SnO2, present as a separate phase, also contributes. In this work, a carbon‐supported Pt‐SnO2 was carefully synthesized to avoid the formation of Pt‐Sn alloy phases. The resulting structure was analysed by scanning transmission electron microscopy (STEM) and detailed X‐ray absorption spectroscopy (XAS). CO oxidation voltammograms of the Pt‐SnO2/C and other SnO2‐modified Pt surfaces unambiguously suggest that a bifunctional mechanism is indeed operative at such Pt‐SnO2 catalysts for stable CO oxidation at low overpotentials. The results from these studies suggest that the bifunctional mechanism can be attributed to the co‐catalysis role of SnO2, in which the surface hydroxide of SnO2 (Sn‐OH) reacts with CO adsorbed on Pt surface (Pt‐COads) and regenerates via a SnII/SnIV reversible redox couple (−0.2–0.3 V vs. reversible hydrogen electrode).
Nonmalignant meningioma and vestibular schwannoma incidence trends in the United States, 2004‐2017
Authors: Withrow Diana R. , Devesa Susan S. , Deapen Dennis , Petkov Valentina , Van Dyke Alison L. , Adamo Margaret , Armstrong Terri S. , Gilbert Mark R. , Linet Martha S.
Published: June 2021

Background

Given concerns about risks associated with the growing use of mobile phones over recent decades, the authors analyzed temporal trends in incidence rates of nonmalignant meningioma and vestibular schwannoma in the United States.

Methods

The incidence of nonmalignant meningioma and vestibular schwannoma among adults in the Surveillance, Epidemiology, and End Results 18 registries during 2004 through 2017 was evaluated according to the method of diagnosis: microscopically (MC) or radiographically confirmed (RGC). Annual percent changes (APCs) and 95% CIs were estimated using log‐linear models.

Results

Overall meningioma rates (n = 108,043) increased significantly from 2004 to 2009 (APC, 5.4%; 95% CI, 4.4%‐6.4%) but subsequently rose at a slower pace through 2017 (APC, 1.0%; 95% CI, 0.6%‐1.5%). Rates for MC meningiomas changed little from 2004 to 2017 (APC, −0.3%; 95% CI, −0.7%, 0.1%) but rose rapidly for RGC meningiomas until 2009 (APC, 9.5%; 95% CI, 7.8%‐11.1%) and rose more modestly thereafter (APC, 2.3%; 95% CI, 1.5%‐3.0%). Overall vestibular schwannoma rates (n = 17,475) were stable (APC, 0.4%; 95% CI, −0.2%, 1.0%), but MC vestibular schwannoma rates decreased (APC, −1.9%; 95% CI, −2.7%, −1.1%), whereas RGC vestibular schwannoma rates rose (2006‐2017: APC, 1.7%; 95% CI, 0.5%‐3.0%). For each tumor, the trends by diagnostic method were similar for each sex and each racial/ethnic group, but RGC diagnosis was more likely in older patients and for smaller tumors. Meningioma trends and the proportion of RGC diagnoses varied notably by registry.

Conclusions

Overall trends obscured differences by diagnostic method in this first large, detailed assessment, but the recent stable rates argue against an association with mobile phone use. Variation among registries requires evaluation to improve the registration of these nonmalignant tumors.

Lay Summary

The etiology of most benign meningiomas and vestibular schwannomas is poorly understood, but concerns have been raised about whether mobile phone use contributes to risk of developing these tumors.

Descriptive studies examining temporal trends could provide insight; however, globally, few registries collect these nonmalignant cases.

In the United States, reporting benign meningiomas and vestibular schwannomas became required by law in 2004.

This was the first large, systematic study to quantify and characterize incidence trends for meningioma and vestibular schwannoma according to whether the tumors were diagnosed microscopically or only radiographically.

Differential trends across registries and by diagnostic method suggest that caution should be used when interpreting the patterns.
SearcHPV: A novel approach to identify and assemble human papillomavirus–host genomic integration events in cancer
Authors: Pinatti Lisa M. , Gu Wenjin , Wang Yifan , Elhossiny Ahmed , Bhangale Apurva D. , Brummel Collin V. , Carey Thomas E. , Mills Ryan E. , Brenner J. Chad
Published: June 2021

Background

Human papillomavirus (HPV) is a well‐established driver of malignant transformation at a number of sites, including head and neck, cervical, vulvar, anorectal, and penile squamous cell carcinomas; however, the impact of HPV integration into the host human genome on this process remains largely unresolved. This is due to the technical challenge of identifying HPV integration sites, which includes limitations of existing informatics approaches to discovering viral‐host breakpoints from low‐read‐coverage sequencing data.

Methods

To overcome this limitation, the authors developed SearcHPV, a new HPV detection pipeline based on targeted capture technology, and applied the algorithm to targeted capture data. They performed an integrated analysis of SearcHPV‐defined breakpoints with genome‐wide linked‐read sequencing to identify potential HPV‐related structural variations.

Results

Through an analysis of HPV+ models, the authors showed that SearcHPV detected HPV‐host integration sites with a higher sensitivity and specificity than 2 other commonly used HPV detection callers. SearcHPV uncovered HPV integration sites adjacent to known cancer‐related genes, including TP63, MYC, and TRAF2, and near regions of large structural variation. The authors further validated the junction contig assembly feature of SearcHPV, which helped to accurately identify viral‐host junction breakpoint sequences. They found that viral integration occurred through a variety of DNA repair mechanisms, including nonhomologous end joining, alternative end joining, and microhomology‐mediated repair.

Conclusions

In summary, SearcHPV is a new optimized tool for the accurate detection of HPV‐human integration sites from targeted capture DNA sequencing data.
Only SF3B1 mutation involving K700E independently predicts overall survival in myelodysplastic syndromes
Authors: Kanagal‐Shamanna Rashmi , Montalban‐Bravo Guillermo , Sasaki Koji , Darbaniyan Faezeh , Jabbour Elias , Bueso‐Ramos Carlos , Wei Yue , Chien Kelly , Kadia Tapan , Ravandi Farhad , Borthakur Gautam , Soltysiak Kelly A. , Routbort Mark , Patel Keyur , Pierce Sherry , Medeiros L. Jeffrey , Kantarjian Hagop M. , Garcia‐Manero Guillermo
Published: June 2021

Background

SF3B1 mutations (SF3B1mut) in myelodysplastic syndromes (MDS) frequently involve codon K700E and have a favorable prognosis. The prognostic effect of non‐K700E SF3B1mut is uncertain.

Methods

The authors analyzed the clinicopathological features and outcomes of a single‐institution series of 94 treatment‐naive SF3B1mut MDS patients (18%) and 415 treatment‐naive SF3B1wt MDS patients and explored the differences between K700E and non‐K700E SF3B1mut MDS.

Results

Fifty‐five patients (59%) carried K700E. Recurrent non‐K700E mutations (39 [41%]) included R625, H662, and K666. Compared with SF3B1mut K700E patients, non‐K700E patients had a lower median absolute neutrophil count (1.8 vs 2.4; P = .005) and were frequently “high” according to the Revised International Prognostic Scoring System (19% vs 4%; P = .031). Non‐K700E MDS was associated frequently with RUNX1 (26% vs 7%; P = .012) and exclusively with BCOR, IDH2, and SRSF2 mutations. A splicing analysis showed the differential distribution of alternatively spliced events and gene expression profiles between K700 and non‐K700E MDS patients. The majority (at least 80%) of SF3B1mut K700E, SF3B1mut non‐K700E, and SF3B1wt patients were treated with hypomethylating agents. Over a median follow‐up of 16 months, SF3B1mut had superior overall survival (OS) in comparison with SF3B1wt in all MDS patients (not reached vs 25.2 months; P = .0003), in patients with low‐grade MDS, and in patients with myelodysplastic syndromes with ring sideroblasts (MDS‐RS). Compared with SF3B1wt, SF3B1mut K700E had superior outcomes in all MDS (median OS, 25 months vs not reached; P = .0001), in low‐grade MDS (median OS, 41.3 months vs not reached; P = .0015), and in MDS‐RS (median OS, 22.3 months vs not reached; P = .0001), but no significant difference was seen between non‐K700E and SF3B1wt MDS. By multivariable analysis, the absence of SF3B1mut K700E mutations was independently associated with the prognosis.

Conclusions

This study highlights the importance of the SF3B1 mutation subtype in MDS risk assessment.

Lay Summary

Myelodysplastic syndromes (MDS) with SF3B1 mutations are regarded as having a favorable prognosis by both the World Health Organization and the International Working Group for the Prognosis of Myelodysplastic Syndromes.

However, this article shows that only MDS patients with SF3B1 K700E mutations have a favorable prognosis (and not MDS patients with SF3B1 mutations involving other codons).

This has important implications for refining future MDS subclassification and risk assessment criteria.
Role of molecular signature to differentiate second primary lung cancer from metastasis in a patient with squamous cell carcinoma of oral cavity
Authors: Yilmaz Emrullah , Gan Gregory N. , Schroeder Thomas M. , Cowan Andrew , Joste Nancy
Published: June 2021

Background

Lung is the most common site of distant metastasis for patients with head and neck squamous cell carcinoma (HNSCC). However, differentiating second primary lung cancers from metastasis may be difficult for p16 negative HNSCC.

Case

We describe a case of oral cavity squamous cell carcinoma (SCC) who was found to have lung nodule and hilar lymphadenopathy (LAD) after surgery and radiation therapy. Hilar node was consistent with SCC however, it was difficult to differentiate second primary lung cancer and metastasis from oral cavity SCC.

Next‐generation sequencing was done for the primary oral cavity and the hilar node. Both samples had the same type of TP53 mutation and variants of unknown significance suggesting metastatic HNSCC. He was treated with a chemotherapy regimen for metastatic HNSCC.

Conclusion

Molecular studies can help to differentiate metastasis from second primary lung cancers for p16 negative HNSCC.
Aggregation‐Induced Emission: A Challenge for Computational Chemistry Taking TPA‐BMO as an Example**
Authors: de Thieulloy Laure , Le Bras Laura , Zumer Benoît , Sanz García Juan , Lemarchand Claire , Pineau Nicolas , Adamo Carlo , Perrier Aurélie
Published: June 2021

A multi‐environment computational approach is proposed to study the modulation of the emission behavior of the triphenylamine (Z)‐4‐benzylidene‐2‐methyloxazol‐5(4H)‐one (TPA‐BMO) molecule [Tanget al., J. Phys. Chem. C119, 21875 (2015)]. We aim at (1) proposing a realistic description of the molecule in several environments (solution, aggregate, polymer matrix), (2) modelling its absorption and emission properties, and (3) providing a qualitative understanding of the experimental observations by highlighting the photophysical phenomena leading to the emission modulation. To this purpose, we rely on (TD‐)DFT calculations and classical Molecular Dynamics simulations, but also on the hybrid ONIOM QM/QM’ approach and thein situchemical polymerization methodology. In low‐polar solvents, the investigation of the potential energy surfaces and the modulation of the emission quantum yield can be attributed to possible photophysical energy dissipation caused by low‐frequency vibrational modes. In the aggregate and in the polymer matrix, the emission modulation can be qualitatively interpreted in terms of the possible restriction of the intramolecular vibrations. For these two systems, our study highlights that a careful modelling of the environment is far from trivial but is fundamental to model the optical properties of the fluorophore.
Combining Lanthanides with PyBox Ligands: A Simple Route to Circularly Polarized Light Emitters**
Authors: Arrico Lorenzo , Benetti Costanza , Di Bari Lorenzo
Published: June 2021

We report the facile synthesis of TbIII and EuIII adducts able to elicit circularly polarized luminescence. Both the sensitization of the lanthanide‐ion‐centered luminescence (i. e. the antenna effect) and the chiral environment around the metal ions are brought about by commercially available enantiopure 2,6‐bis(oxazolinyl)pyridine ligands (PyBox). This strategy is promising for the development of a wide range of new and simple circularly polarized luminescence (CPL) active LnIII adducts, thanks to the fine tunability of the chemical structure of the PyBox ligands.
Luminescent solar concentrator utilizing energy transfer paired aggregation‐induced emissive fluorophores
Authors: Mateen Fahad , Hwang Tae Gyu , Boesel Luciano F. , Choi Woo Jin , Kim Jae Pil , Gong Xiao , Park Jong Mok , Hong Sung‐Kyu
Published: June 2021

Recently, semitransparent luminescent solar concentrators (LSCs) have attracted considerable attention because they offer an easy and cost‐effective route to harvest incident light. Various fluorophores including semiconducting quantum dots and organic dyes have been prepared and utilized for LSC fabrication. However, the narrow light absorption range, reabsorption losses, and limited photostability of the fluorophores still hinder the widespread use of LSCs under outdoor and indoor light conditions. Here, we rationally designed an LSC utilizing aggregation‐induced emissive fluorophores (AIEgens) and an energy transfer (ET) strategy. We employ diketopyrrolopyrrole with triphenylamine moiety as a highly stable AIEgen that functions as an emissive ET acceptor in LSC; for a donor, we use tetraphenylethene containing triphenylamine moiety that shows good aggregation‐induced emission features and excellent spectral overlap with the acceptor to yield an efficient ET process. A thin‐film LSC device with an optimized donor:acceptor ratio (1:0.5) was fabricated. Under AM 1.5G solar spectrum, an LSC coupled with three side reflectors and a backside diffuser exhibits 18% optical conversion efficiency and a concentration factor of 1.18. Under indoor white LED illumination, the values were 27% and 1.68%, respectively. After exposed to intense UV radiations for 5 hours, the LSCs preserved 98% fluorescence which suggests their superior long‐term photostability. Our results suggest that the combination of AIEgens and ET holds the potential for enhancing the efficiency of the device and extended stability of the fluorophores, two of the major requirements to allow industrial production and large‐scale use of outdoor/indoor light harvesting LSCs.
Upstream morphological effects of a sequential check dam adjustment process
Authors: Chiu Yu‐Fang , Tfwala Samkele S. , Hsu Yung‐Ching , Chiu Yen‐Yu , Lee Chen‐Yang , Chen Su‐Chin
Published: June 2021

Sediment flushing and the morphological responses to the procedure of check dam removal are still unclear. Following laboratory experiments that revealed three stages (deepening, widening, and volume release) of check dam adjustment, a check dam built in 2007 at Landao Creek in central Taiwan was adjusted in 2015 by removing central bars and cutting 2.5 m from the middle two piers (stage 1 + 2), with the purpose of regulating sediment transfer and keeping the thalweg at the center of the channel, while also preventing hill slope toe erosion. In 2019, four central piers were removed (stage 3) to increase the volume of sediment released. Annual surveys were conducted after the initial adjustment in 2015 through to 2020 using unmanned aerial vehicles (UAVs). The check dam adjustments revealed that the channel had narrowed and stabilized as indicated by regenerating riparian vegetation. Additionally, distinct terraces had formed on the hill slope toes of the creek channel in proximity to the check dam. The meander upstream weakened following the dam adjustments. This study combining laboratory experiments with actual field observation contributed immensely to check dam decommissioning. Additionally, this study illustrated how an adjustable check dam may aid regulation of sediment transport and thereby sediment balance. It can be adjusted accordingly based on the prevailing channel condition.
Study on starch content detection and visualization of potato based on hyperspectral imaging
Authors: Wang Fuxiang , Wang Chunguang , Song Shiyong , Xie Shengshi , Kang Feilong
Published: June 2021

Starch is an important quality index in potato, which contributes greatly to the taste and nutritional quality of potato. At present, the determination of starch depends on chemical analysis, which is time consuming and laborious. Thus, rapid and accurate detection of the starch content of potatoes is important. This study combined hyperspectral imaging with chemometrics to predict potato starch content. Two varieties of Kexin No.1 and Holland No.15 potatoes were used as experimental samples. Hyperspectral data were collected from three sampling sites (the top, umbilicus, and middle regions). Standard normal variate (SNV) was used for spectral preprocessing, and three different methods of competitive adaptive reweighted sampling (CARS), iterative variable subset optimization (IVSO), and the variable iterative space shrinkage approach (VISSA) were used for characteristic wavelength selection. Linear partial least‐squares regression (PLSR) and nonlinear support vector regression (SVR) models were then established. The results indicated that the sampling site has a considerable impact on the accuracy of the prediction model, and the umbilicus region with CARS‐SVR model gave best performance with correlation coefficients in calibration (Rc) of 0.9415, in prediction (Rp) of 0.9346, root mean square errors in calibration (RMSEC) of 15.9 g/kg, in prediction (RMSEP) of 17.4 g/kg, and residual predictive deviation (RPD) of 2.69. The starch content in potatoes was visualized using the best model in combination with pseudo‐color technology. Our research provides a method for the rapid and nondestructive determination of starch content in potatoes, providing a good foundation for potato quality monitoring and grading.
Alzheimer's and Aducanumab: Unjust Profits and False Hopes
Authors: Fleck Leonard M.
Published: June 2021

Accelerated approval of aducanumab for mild Alzheimer's by the U.S. Food and Drug Administration on June 7, 2021, has generated substantial medical, scientific, and ethical controversy. That approval was contrary to the nearly unanimous judgment of the FDA's Advisory Committee that little reliable evidence existed of significant benefit, even though the drug did reduce β‐amyloid. Three major ethical problems were created by this approval: (1) Medicare resources would be unjustly squandered, given the drug's $56,000 annual price and the 3.1 million older potential American patients needing the drug; (2) physicians will feel ethically compelled to provide the drug to desperate, insistent patients, given FDA approval and in spite of side effects of brain bleeds and brain swelling; (3) and false hopes are generated for patients. A needed corrective by the federal government would reduce reimbursement to the bare cost of producing the drug (plus only a modest profit) until a phase IV trial has been successfully completed.
COVID‐19 and progress towards achieving universal health coverage in Africa: A case of Nigeria
Authors: Amos Oladunni Abimbola , Adebisi Yusuff Adebayo , Bamisaiye Adeola , Olayemi Alaka Hassan , Ilesanmi Esther Bosede , Micheal Alumuku Iordepuun , Ekpenyong Aniekan , Lucero‐Prisno Don Eliseo
Published: June 2021

Universal Health Coverage (UHC) 2030 is a global health target, and countries are making efforts to convert plans into tangible results. Nigeria, the most populated country in Africa, has made commitments towards UHC2030 target but is underperforming across many building blocks of health and progress has been slow. The arrival of COVID‐19 poses additional pressure on the already feeble health system causing the government to direct focus towards containing the pandemic. However, existing gaps in health workforce density, weak primary health care infrastructure and inadequate budgetary allocation have resulted in inequitable access to basic healthcare services. This situation weighs most heavily on the poor who are mostly part of the informal economy thereby pushing people further into poverty. On the other hand, COVID‐19 has provided valuable insights into Nigeria's current health system status which hopefully can be helpful in strengthening efforts towards building resilient health system and preparing the country towards future pandemic. The pandemic has highlighted the importance of essential health services and the need to strengthen primary healthcare system. It is, therefore, important that stakeholders in Nigeria and other African countries carry out situation analysis of the current health systems towards achieving UHC2030.
Introducing ground cover management in pesticide emission modeling
Authors: Gentil-Sergent Céline , Basset-Mens Claudine , Renaud-Gentié Christel , Mottes Charles , Melero Carlos , Launay Arthur , Fantke Peter
Published: June 2021

Ground cover management (GCM) is an important agricultural practice used to reduce weed growth, erosion and runoff, and improve soil fertility. In the present study, an approach to account for GCM is proposed in the modeling of pesticide emissions to evaluate the environmental sustainability of agricultural practices. As a starting point, we include a cover crop compartment in the mass balance of calculating initial (within minutes after application) and secondary (including additional processes) pesticide emission fractions. The following parameters were considered: (i) cover crop occupation between the rows of main field crops, (ii) cover crop canopy density, and (iii) cover crop family. Two modalities of cover crop occupation and cover crop canopy density were tested for two crop growth stages, using scenarios without cover crops as control. From that, emission fractions and related ecotoxicity impacts were estimated for pesticides applied to tomato production in Martinique (French West Indies) and to grapevine cultivation in the Loire Valley (France). Our results demonstrate that, on average, the presence of a cover crop reduced the pesticide emission fraction reaching field soil by a factor of 3 compared with bare soil, independently of field crop and its growth stage, and cover crop occupation and density. When considering cover exported from the field, ecotoxicity impacts were reduced by approximately 65% and 90%, compared with bare soil for grapevine and tomato, respectively, regardless of the emission distribution used. Because additional processes may influence emission distributions under GCM, such as runoff, leaching, or preferential flow, further research is required to incorporate these processes consistently in our proposed GCM approach. Considering GCM in pesticide emission modeling highlights the potential of soil cover to reduce pesticide emissions to field soil and related freshwater ecotoxicity. Furthermore, the consideration of GCM as common farming practice allows the modeling of pesticide emissions in intercropping systems. Integr Environ Assess Manag 2022;18:274–288. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

KEY POINTS

Ground cover was introduced in pesticide emission modeling (PestLCI). Cover crop decreases pesticide emission to field soil and related freshwater ecotoxicity. The path towards pesticide emission modeling of intercropping systems is now opened. Innovative cropping systems can be better assessed.
Application of mid‐infrared microscopic imaging for the diagnosis and classification of human lymphomas
Authors: Willenbacher Ella , Brunner Andrea , Zelger Bettina , Unterberger Seraphin H. , Stalder Roland , Huck Christian W. , Willenbacher Wolfgang , Pallua Johannes D.
Published: June 2021

Mid‐infrared (MIR) microscopic imaging of indolent and aggressive lymphomas was performed including formalin‐fixed and paraffin‐embedded samples of six follicular lymphomas and 12 diffuse large B‐cell‐lymphomas as well as reactive lymph nodes to investigate benefits and challenges for lymphoma diagnosis. MIR images were compared to defined pathological characteristics such as indolent versus aggressive versus reactive, germinal centre versus activated cell‐of‐origin (COO) subtypes, or a low versus a high proliferative index and level of PD‐L1 expression. We demonstrated that MIR microscopic imaging can differentiate between reactive lymph nodes, indolent and aggressive lymphoma samples. Also, it has potential to be used in the subtyping of lymphomas, as shown with the differentiation between COO subtypes, the level of proliferation and PD‐L1 expression. MIR microscopic imaging is a promising tool for diagnosis and subtyping of lymphoma and further evaluation is needed to fully explore the advantages and disadvantages of this method for pathological diagnosis.
Characterization of the Developing Lacunocanalicular Network During Fracture Repair
Authors: Casanova Michele , Schindeler Aaron , Peacock Lauren , Lee Lucinda , Schneider Philipp , Little David G. , Müller Ralph
Published: June 2021

Fracture repair is a normal physiological response to bone injury. During the process of bony callus formation, a lacunocanalicular network (LCN) is formed de novo that evolves with callus remodeling. Our aim was the longitudinal assessment of the development and evolution of the LCN during fracture repair. To this end, 45 adult wild‐type C57BL/6 mice underwent closed tibial fracture surgery. Fractured and intact contralateral tibias were harvested after 2, 3, and 6 weeks of bone healing (n = 15/group). High‐resolution micro–computed tomography (μCT) and deconvolution microscopy (DV) approaches were applied to quantify lacunar number density from the calluses and intact bone. On histological sections, Goldner's trichrome staining was used to assess lacunar occupancy, fluorescein isothiocyanate staining to visualize the canalicular network, and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate‐biotin nick end labeling (TUNEL) staining to examine osteocyte apoptosis. Analysis of μCT scans showed progressive decreases in mean lacuna volume over time (−27% 2–3 weeks; −13% 3–6 weeks). Lacunar number density increased considerably between 2 and 3 weeks (+156%). Correlation analysis was performed, showing a positive linear relationship between canalicular number density and trabecular thickness (R2 = 0.56, p < 0.001) and an inverse relationship between mean lacuna volume and trabecular thickness (R2 = 0.57, p < 0.001). Histology showed increases in canalicular number density over time (+22% 2–3 weeks, +51% 3–6 weeks). Lacunar occupancy in new bone of the callus was high (>90%), but the old cortical bone within the fracture site appeared necrotic as it underwent resorption. In conclusion, our data shows a progressive increase in the complexity of the LCN over time during fracture healing and demonstrates that this network is initiated during the early stages of repair. Further studies are needed to address the functional importance of osteocytes in bone healing, particularly in detecting and translating the effects of micromotion in the fracture. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.