bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Highly Strained All‐Phenylene Conjoined Bismacrocycle
Authors: Zhang Xinyu , Shi Hong , Zhuang Guilin , Wang Shengda , Wang Jinyi , Yang Shangfeng , Shao Xiang , Du Pingwu 
Published: May 2021

AbstractHerein, we report the precise synthesis of a 3D highly strained all‐phenylene bismacrocycle, termed conjoined (1,4)[10]cycloparaphenylenophane (SCPP[10]). This structure consists of a twisted benzene ring which is bridged twice by phenylene units anchored in two para‐positions. The conjoined structure of SCPP[10] was confirmed in real space at the atomic scale by scanning tunneling microscopy. Theoretical calculations indicate that this bismacrocycle has a very high strain energy of 110.59 kcal mol−1 and the largest interphenylene torsion angle of 46.07° caused by multiple repulsive interactions. Furthermore, a 1:2 host–guest complex of SCPP[10] and [6,6]‐phenyl‐C61‐butyric acid methyl ester was investigated, which represents the first peanut‐shaped 1:2 host–guest complex based on bismacrocycles.
Upgrading poly(styrene‐co‐divinylbenzene) beads: Incorporation of organomodified metal‐free semiconductor graphitic carbon nitride through suspension photopolymerization to generate photoactive resins
Authors: Esen Cansu , Antonietti Markus , Kumru Baris 
Published: May 2021

AbstractThe inclusion of the metal free semiconductor graphitic carbon nitride (g‐CN) into polymer systems brings a variety of new options, for instance as a heterogeneous photoredox polymer initiator. In this context, we present here the decoration of the inner surface of poly(styrene‐co‐divinylbenzene) beads with organomodified g‐CN via one pot suspension photopolymerization. The resulting beads are varied by changing reaction parameters, such as, crosslinking ratio, presence of porogens, and mechanical agitation. The photocatalytic activity of so‐formed beads was tested by aqueous rhodamine B dye photodegradation experiments. Additionally, dye adsorption/desorption properties were examined in aqueous as well as in organic solvents. Photoinduced surface modification with vinylsulfonic acid and 4‐vinyl pyridine is introduced. Overall, metal‐free semiconductor g‐CN donates photoactivity to polymer networks that can be employed for dye photodegradation and acid–base catalyst transformation through facile photoinduced surface modifications.
Eliminating again, for the last time: A case study of donor support for malaria in Solomon Islands
Authors: Burkot Camilla , Gilbert Katherine 
Published: May 2021

AbstractMalaria elimination has been a recurring policy goal in Solomon Islands and has historically succeeded in attracting substantial donor support. Drawing on literature review and key informant interviews, we examine the influence of foreign aid on malaria control and elimination efforts in Solomon Islands between 2002 and 2016, as a unique case study of an Asia‐Pacific country with high malaria burden and high donor funding. While aid appears to have contributed to reduced malaria prevalence, the ways in which aid was delivered in the short term had health systems impacts with implications for the elimination agenda. Key areas that will be critical to the future pursuit of malaria elimination in Solomon Islands include: integration of the vertical malaria program, while strengthening provincial‐level service delivery; maximising incentives of performance‐based financing modalities; and policy alignment between donors and domestic actors. We conclude by discussing principles exemplified in the case study of broader relevance to malaria‐endemic countries.
Omics analysis reveals mechanism underlying metabolic oscillation during continuous very‐high‐gravity ethanol fermentation by Saccharomyces cerevisiae
Authors: Zhang Xue , Wang Liang , Li Qian , den Haan Riaan , Li Fan , Liu Chen‐Guang , Bai Feng‐Wu 
Published: May 2021

AbstractDuring continuous very‐high‐gravity (VHG) ethanol fermentation with Saccharomyces cerevisiae, the process exhibits sustained oscillation in residual glucose, ethanol, and biomass, raising a question: how do yeast cells respond to this phenomenon? In this study, the oscillatory behavior of yeast cells was characterized through transcriptome and metabolome analysis for one complete oscillatory period. By analyzing the accumulation of 26 intracellular metabolites and the expression of 90 genes related to central carbon metabolism and stress response, we confirmed that the process oscillation was attributed to intracellular metabolic oscillation with phase difference, and the expression of HXK1, HXT1,2,4, and PFK1 was significantly different from other genes in the Embden–Meyerhof–Parnas pathway, indicating that glucose transport and phosphorylation could be key nodes for regulating the intracellular metabolism under oscillatory conditions. Moreover, the expression of stress response genes was triggered and affected predominately by ethanol inhibition in yeast cells. This progress not only contributes to the understanding of mechanisms underlying the process oscillation observed for continuous VHG ethanol fermentation, but also provides insights for understanding unsteady state that might develop in other continuous fermentation processes operated under VHG conditions to increase product titers for robust production.
Comprehensive mutational analysis of background mucosa in patients with Lugol‐voiding lesions
Authors: Akizue Naoki , Okimoto Kenichiro , Arai Makoto , Hirotsu Yosuke , Amemiya Kenji , Oura Hirotaka , Kaneko Tatsuya , Tokunaga Mamoru , Ishikawa Kentaro , Ohta Yuki , Taida Takashi , Saito Keiko , Maruoka Daisuke , Matsumura Tomoaki , Nakagawa Tomoo , Nishimura Motoi , Chiba Tetsuhiro , Matsushita Kazuyuki , Mochizuki Hitoshi , Yokosuka Osamu , Omata Masao , Kato Naoya 
Published: May 2021

AbstractSomatic mutations including the background mucosa in patients with Lugol‐voiding lesions (LVLs) are still not well known. The aim of this study was to evaluate the somatic mutations of the background mucosa in patients with LVLs (Squamous cell carcinoma (SCC), intraepithelial neoplasia (IN), and hyperplasia). Twenty‐five patients with LVLs (9 with SCC, 6 with IN, and 10 with hyperplasia) were included. A targeted sequence was performed for LVLs and background mucosa using an esophageal cancer panel. Each mutation was checked whether it was oncogenic or not concerning OncoKB. In LVLs, TP53 was the most dominant mutation (80%). Furthermore, 72% of TP53 mutations was putative drivers. In background mucosa, NOTCH1 was the most dominant mutation (88%) and TP53 was the second most dominant mutation (48%). Furthermore, 73% of TP53 mutations and 8% of NOTCH1 mutations were putative drivers. Putative driver mutations of TP53 had significantly higher allele frequency (AF) in SCC than in IN and hyperplasia. Conversely, putative driver mutations of NOTCH1 did not have a significant accumulation of AF in the progression of carcinogenesis. Furthermore, in SCC, AF of TP53 mutations was significantly higher in LVLs than in background mucosa, but not in IN and hyperplasia. Regarding NOTCH1, a significant difference was not observed between LVLs and background mucosa in each group. The background mucosa in patients with LVLs already had putative driver mutations such as TP53 and NOTCH1. Of these two genes, TP53 mutation could be the main target gene of carcinogenesis in esophageal SCC.Clinical Trials registry: UMIN000034247.
miR‐25‐5p regulates endothelial progenitor cell differentiation in response to shear stress through targeting ABCA1
Authors: Li Zhe , Li Jia‐Nan , Li Qiang , Liu Chun , Zhou Lin‐Hua , Zhang Qi , Xu Yi 
Published: May 2021

AbstractThe importance of flow shear stress (SS) on the differentiation of endothelial progenitor cells (EPCs) has been demonstrated in various studies. Cholesterol retention and microRNA regulation have been also proposed as relevant factors involved in this process, though evidence regarding their regulatory roles in the differentiation of EPCs is currently lacking. In the present study on high shear stress (HSS)‐induced differentiation of EPCs, we investigated the importance of ATP‐binding cassette transporter 1 (ABCA1), an important regulator in cholesterol efflux, and miR‐25‐5p, a potential regulator of endothelial reconstruction. We first revealed an inverse correlation between miR‐25‐5p and ABCA1 expression levels in EPCs under HSS treatment; their direct interaction was subsequently validated by a dual‐luciferase reporter assay. Further studies using flow cytometry and quantitative polymerase chain reaction demonstrated that both miR‐25‐5p overexpression and ABCA1 inhibition led to elevated levels of specific markers of endothelial cells, with concomitant downregulation of smooth muscle cell markers. Finally, knockdown of ABCA1 in EPCs significantly promoted tube formation, which confirmed our conjecture. Our current results suggest that miR‐25‐5p might regulate the differentiation of EPCs partially through targeting ABCA1, and such a mechanism might account for HSS‐induced differentiation of EPCs.
Steric Effects on the Thermal Processes of Hemithioindigo Based Molecular Motor Rotation
Authors: Huber Ludwig A. , Thumser Stefan , Grill Kerstin , Voßiek David , Bach Nicolai N. , Mayer Peter , Dube Henry 
Published: May 2021

AbstractTuning the thermal behavior of light driven molecular motors is fundamentally important for their future rational design. In many molecular motors thermal ratcheting steps are comprised of helicity inversions, energetically stabilizing the initial photoproducts. In this work we investigated a series of five hemithioindigo (HTI) based molecular motors to reveal the influence of steric hindrance in close proximity to the rotation axle on this process. Applying a high yielding synthetic procedure, we synthesized constitutional isomeric derivatives to distinguish between substitution effects at the aromatic and aliphatic position on the rotor fragment. The kinetics of thermal helix inversions were elucidated using low temperature 1H NMR spectroscopy and an in situ irradiation technique. In combination with a detailed theoretical description, a comparative analysis of substituent effects on the thermal helix inversions of the rotation cycle is now possible. Such deeper understanding of the rotational cycle of HTI molecular motors is essential for speed regulation and future applications of visible light triggered nanomachines.
Molecular Recognition of Disaccharides in Water: Preorganized Macrocyclic or Adaptive Acyclic?
Authors: Francesconi Oscar , Milanesi Francesco , Nativi Cristina , Roelens Stefano 
Published: May 2021

AbstractWhen facing the dilemma of following a preorganized or adaptive design approach in conceiving the architecture of new biomimetic receptors for carbohydrates, shape‐persistent macrocyclic structures were most often chosen to achieve effective recognition of neutral saccharides in water. In contrast, acyclic architectures have seldom been explored, even though potentially simpler and more easily accessible. In this work, comparison of the binding properties of two structurally related diaminocarbazolic receptors, featuring a macrocyclic and an acyclic tweezer‐shaped architecture, highlighted the advantages provided by the acyclic receptor in terms of selectivity in the recognition of 1,4‐disaccharides of biological interest. Selective recognition of GlcNAc2, the core fragment of N‐glycans exposed on the surface of enveloped viruses, stands as an emblematic example. NMR spectroscopic data and molecular modeling calculations were used to ascertain the differences in binding mode and to shed light on the origin of recognition efficacy and selectivity.
Effectiveness and safety profile of pembrolizumab for metastatic urothelial cancer: A retrospective single‐center analysis in Japan
Authors: Fujiwara Motohiro , Yuasa Takeshi , Urasaki Tetsuya , Komai Yoshinobu , Fujiwara Ryo , Numao Noboru , Yamamoto Shinya , Yonese Junji 
Published: May 2021

AbstractBackgroundThe paradigm of medical treatment for metastatic urothelial carcinoma is dramatically changing through the introduction of pembrolizumab.AimWe investigated the treatment effectiveness, the safety profile, and the prognostic factors of pembrolizumab in Japanese real‐world clinical practice.Methods and resultsThe medical records of 74 consecutive Japanese patients with metastatic urothelial cancer (UC), who started pembrolizumab as a second‐ or later‐line treatment at our institution between January 2018 and March 2020, were reviewed and statistically analyzed. The median follow‐up period after initiation of pembrolizumab was 8.5 (interquartile range: 3.5–15.7) months. The objective response rate was 30.2%, the median progression‐free survival period was 4.9 months, and the median overall survival (OS) period was 13.3 months. Evaluation revealed that 39 (52.9%) patients experienced adverse events (AEs), among whom eight patients (10.9%) had severe AEs (grade 3 or more), including grade 5 hemophagocytic syndrome. Multivariate analysis indicated that the presence of liver metastasis, worse performance status (≥2), elevated serum lactate dehydrogenase, and increased C‐reactive protein were predictive of shorter OS.ConclusionWe studied the effectiveness and safety profile of pembrolizumab therapy in Japanese UC patients. We believe that the data presented here will be useful for clinical physicians.
Efficacy and safety of immune checkpoint inhibitors in patients with non‐small cell lung cancer aged 80 years or older
Authors: Saito Zentaro , Fujita Kohei , Okamura Misato , Ito Takanori , Yamamoto Yuki , Kanai Osamu , Hashimoto Masayuki , Nakatani Koichi , Sawai Satoru , Mio Tadashi 
Published: May 2021

AbstractBackgroundIn Japan, over 25% of the population is elderly. As the risk of lung cancer increases with age, the number of elderly patients with lung cancer also increases. Given the challenges of an aging society, it is critical that elderly patients receive safe therapies.AimWe assessed the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with non‐small cell lung cancer (NSCLC) aged ≥80 years.MethodsWe retrospectively reviewed NSCLC patients aged ≥80 years old who received ICIs in the National Hospital Organization Kyoto Medical Center. We collected data on patient characteristics, prior treatments, number of cycles, response, and immune‐related adverse events (irAEs) during ICI monotherapy.ResultsA total of 45 patients were reviewed. The patients' median age was 85 years. Twenty‐one, 17, and 7 patients received nivolumab, pembrolizumab, and atezolizumab, respectively. The disease control rate (partial response [PR] + stable disease [SD]) was 60.0%, and the progression‐free survival was 3.4 months. In patients with nivolumab, seven patients (33.3%) achieved SD, and three patients (14.2%) achieved PR. In patients treated with pembrolizumab, seven patients (41.2%) achieved SD, and six patients (35.3%) achieved PR. In patients with atezolizumab, three patients (42.9%) achieved SD, and one patient (14.2%) achieved PR. Sixteen (36%) patients presented with a poor performance status. Three patients treated with pembrolizumab experienced grade 3 pneumonia, while one patient treated with nivolumab experienced grade 5 pneumonia.ConclusionThis study suggested that ICIs are an acceptable treatment option for NSCLC patients aged ≥80 years. Oncologists should pay attention to severe irAEs.
Electroreduction of Aryldiazonium Ion at the Polar and Non‐Polar Faces of ZnO: Characterisation of the Grafted Films and Their Influence on Near‐Surface Band Bending
Authors: McNeill Alexandra R. , Martinez‐Gazoni Rodrigo , Reeves Roger J. , Allen Martin W. , Downard Alison J. 
Published: May 2021

AbstractZnO is a strong candidate for transparent electronic devices due to its wide band gap and earth‐abundance, yet its practical use is limited by its surface metallicity arising from a surface electron accumulation layer (SEAL). The SEAL forms by hydroxylation of the surface under normal atmospheric conditions, and is present at all crystal faces of ZnO, although with differing hydroxyl structures. Multilayer aryl films grafted from aryldiazonium salts have previously been shown to decrease the downward bending at O‐polar ZnO thin films, with Zn−O−C bonds anchoring the aryl films to the substrate. Herein we show that the Zn‐polar (0001), O‐polar (000
), and non‐polar m‐plane (10
0) faces of ZnO single crystals, can also be successfully electrografted with nitrophenyl (NP) films. In all cases, X‐ray photoelectron spectroscopy (XPS) measurements reveal that the downward surface band bending decreases after modification. XPS provides strong evidence for Zn−O−C bonding at each face. Electrochemical reduction of NP films on O‐polar ZnO single crystals converts the film to a mainly aminophenyl layer, although with negligible further change in band bending. This contrasts with the large upward shifts in band bending caused by X‐ray induced reduction.
Matrix Isolation‐Vibrational Circular Dichroism Spectroscopic Study of Conformations and Non‐Covalent Interactions of Tetrahydro‐2‐Furoic Acid
Authors: Yang Yanqing , Cheramy Joseph , Xu Yunjie 
Published: May 2021

AbstractThe conformational landscape and aggregation behaviour of tetrahydro‐2‐furoic acid (THFA) were investigated by using matrix isolation‐vibrational circular dichroism (MI‐VCD). The well‐resolved experimental MI‐IR and MI‐VCD features in an argon matrix at 10 K allow one to identify two dominant monomeric conformations astrans‐THFA where the hydroxyl and carbonyl groups of COOH are at opposite sides, as well as onecis‐conformer. At 24 K and 30 K deposition temperatures, the experimental IR and VCD spectral features reveal further growth of the binary THFA aggregates. Systematic conformational searches identified three vastly different binary binding topologies, resulting in a few hundred stable (THFA)2conformers. Interestingly, the main binary structures observed correspond to an unusual type of structure which is made of twotrans‐THFA subunits, in contrast to the usual double H‐bonded ring binary structures, identified in a previous solution study. The present work showcases the power of MI‐VCD spectroscopy in revealing unusual structures formed in a cold rare gas matrix.
Trajectories of cognitive function in community‐dwelling older adults: A longitudinal study of population heterogeneity
Authors: Wu Zimu , Woods Robyn L. , Wolfe Rory , Storey Elsdon , Chong Trevor T. J. , Shah Raj C. , Orchard Suzanne G. , McNeil John J. , Murray Anne M. , Ryan Joanne ,   the ASPREE Investigator Group
Published: May 2021

AbstractIntroductionThis study aimed to investigate cognitive aging trajectories, the associated sociodemographic characteristics, and the association of these trajectories with dementia.MethodsGenerally healthy older adults (n = 19,114) were followed for up to 7 years, with regular cognitive assessments. Group‐based trajectory modeling identified distinct cognitive trajectories.ResultsFour to seven trajectories were identified per cognitive domain. Stable trajectories were observed across domains. Improvement in verbal fluency and minor psychomotor slowing were common. Substantial decline in global cognition and episodic memory were observed in a small proportion of individuals. Older, less educated participants and men were more common in lower‐functioning trajectories (p < .001). The highest proportions of dementia cases were in trajectories with major decline in global cognition (56.9%) and memory (33.2%).DiscussionInter‐individual variability in cognitive trajectories was observed across all domains. Some individuals appear resilient to cognitive decline even with advancing age. Further research into factors promoting cognitive resilience is needed.
Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer's disease
Authors: Aschenbrenner Andrew J. , Baksh R. Asaad , Benejam Bessy , Beresford‐Webb Jessica A. , Coppus Antonia , Fortea Juan , Handen Benjamin L. , Hartley Sigan , Head Elizabeth , Jaeger Judith , Levin Johannes , Loosli Sandra V. , Rebillat Anne‐Sophie , Sacco Silvia , Schmitt Frederick A. , Thurlow Kate E. , Zaman Shahid , Hassenstab Jason , Strydom Andre 
Published: May 2021

AbstractIntroductionDown syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre‐dementia stages.MethodsWe used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time. We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria.ResultsThere were common cognitive domains across site composites, which were sensitive to early decline. The final composite consisted of memory, language/executive functioning, selective attention, orientation, and praxis tests.DiscussionWe have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS.
Spastic paraplegia preceding PSEN1‐related familial Alzheimer's disease
Authors: Chelban Viorica , Breza Marianthi , Szaruga Maria , Vandrovcova Jana , Murphy David , Lee Chia‐Ju , Alikhwan Sondos , Bourinaris Thomas , Vavougios George , Ilyas Muhammad , Halim Sobia Ahsan , Al‐Harrasi Ahmed , Kartanou Chrisoula , Ronald Coras , Blumcke Ingmar , Alexoudi Athanasia , Gatzonis Stylianos , Stefanis Leonidas , Karadima Georgia , Wood Nicholas W. , Chávez‐Gutiérrez Lucía , Hardy John , Houlden Henry , Koutsis Georgios 
Published: May 2021

AbstractIntroductionWe investigated the frequency, neuropathology, and phenotypic characteristics of spastic paraplegia (SP) that precedes dementia in presenilin 1 (PSEN1) related familial Alzheimer's disease (AD).MethodsWe performed whole exome sequencing (WES) in 60 probands with hereditary spastic paraplegia (HSP) phenotype that was negative for variants in known HSP‐related genes. Where PSEN1 mutation was identified, brain biopsy was performed. We investigated the link between HSP and AD with PSEN1 in silico pathway analysis and measured in vivo the stability of PSEN1 mutant γ‐secretase.ResultsWe identified a PSEN1 variant (p.Thr291Pro) in an individual presenting with pure SP at 30 years of age. Three years later, SP was associated with severe, fast cognitive decline and amyloid deposition with diffuse cortical plaques on brain biopsy. Biochemical analysis of p.Thr291Pro PSEN1 revealed that although the mutation does not alter active γ‐secretase reconstitution, it destabilizes γ‐secretase‐amyloid precursor protein (APP)/amyloid beta (Aβn) interactions during proteolysis, enhancing the production of longer Aβ peptides. We then extended our analysis to all 226 PSEN1 pathogenic variants reported and show that 7.5% were associated with pure SP onset followed by cognitive decline later in the disease. We found that PSEN1 cases manifesting initially as SP have a later age of onset, are associated with mutations located beyond codon 200, and showed larger diffuse, cored plaques, amyloid‐ring arteries, and severe CAA.DiscussionWe show that pure SP can precede dementia onset in PSEN1‐related familial AD. We recommend PSEN1 genetic testing in patients presenting with SP with no variants in known HSP‐related genes, particularly when associated with a family history of cognitive decline.