bluuebunny/crossref_metadata_2025 huggingface dataset:
Tunable Metasurfaces: The Path to Fully Active Nanophotonics
Authors: Badloe Trevon , Lee Jihae , Seong Junhwa , Rho Junsuk
Published: May 2021

In the field of nanophotonics, metasurfaces have come to the forefront in real‐world applications, owing to their accessible exotic optical properties that can be readily designed and fabricated using currently available techniques. The subwavelength dimensions and lightweight characteristics of metasurfaces are attractive qualities for the miniaturization of optical devices and are already exploited in devices that can rival, and sometimes even outperform, conventional bulky optics. Over the past decade, ample research has been undertaken to produce high‐performance metasurfaces with exciting optical properties that cannot be found in nature or achieved with conventional optics. To open the path to widely used devices in our everyday lives, the next obvious step for metasurfaces is the development of tunability. Herein, the techniques and development of applications of tunable metasurfaces are presented through the incorporation of active materials and controllable external stimuli, and the uncovered tunable characteristics are critically analyzed. The review rounds up by proposing the future directions and prospects for actively tunable metasurfaces and their potential practical applications.
Wideband Spectral Enhancement through On‐Chip Bragg‐Soliton Dynamics
Authors: Sahin Ezgi , Blanco-Redondo Andrea , Sohn Byoung-Uk , Cao Yanmei , Chen George F. R. , Ng Doris K. T. , Eggleton Benjamin J. , Tan Dawn T. H.
Published: May 2021

Supercontinuum generation (SCG) through soliton fission provides high‐brightness, spectrally‐rich light needed for hyperspectral imaging, broadband spectroscopy, and fluorescence microscopy. The prospect of miniaturization has led to many demonstrations of this phenomenon in integrated platforms. However, due to the moderate dispersion and nonlinearity generally available in channel waveguides, femtosecond pulses have typically been required to date, as the use of picosecond pulses would require unpractically long devices to achieve soliton fission. Here, spectral bandwidth enhancement of the supercontinuum process through Bragg grating induced soliton‐effect compression and soliton fission is demonstrated. This approach uses picosecond pulses on a complementary metal oxide semiconductor (CMOS)‐compatible, millimeter‐scale platform, consisting of a monolithically integrated cladding‐modulated Bragg grating with a channel waveguide. The strong dispersion near the stopband of the grating enables compression and fission of picosecond higher‐order solitons, which enhances the spectral broadening in the channel waveguide. A 4.3 spectral bandwidth enhancement is reported, with respect to a reference waveguide of the same length. The output spectra are further studied both through simulations and experiments and determined to possess high spectral coherence. These results highlight a simple route to significantly augment the bandwidth of nonlinear processes such as SCG while maintaining low power and compact footprint.
Identification of Key Contributive Compounds in a Herbal Medicine: A Novel Mathematic—Biological Evaluation Approach
Authors: Zhang Cheng , Wang Ning , Xu Yu , Tan Hor‐Yue , Feng Yibin
Published: May 2021

A pattern or syndrome in response to a multicomponent system is the actual target of herbal medicine treatment. However, it is a substantial challenge to fill the gap between a contributive compound profile in herbal medicine (especially a formula) and its biological features. This study aims to establish a feasible component‐mining strategy, which provides a strong prediction of key compounds in support of experimental and clinical observations. Given interdisciplinary scope of life science and mathematical statistics, the relationship between chemical profile and bioactivities is measured by a model termed mathematical prediction bioactivity, in which gray relational analysis, multiple linear/non‐linear regression analysis (including t‐distributed stochastic neighbor embedding), and radial basis function analysis are involved. R language programming‐dependent analysis is adopted with add‐on packages, including UniDOE, Factoextra, FactoMineR, Factanal, Rtsne, and Nnet. By using this assessment method in a biological experiment, it is identified that 6‐shogaol extracted from Ginger‐Coptis formula (a herbal formula) is beneficial for diabetic retinopathy (DR) treatment. The study provides both a novel compound 6‐shogalol for DR treatment and a new strategy for mining key contributors in a multicomponent system.
Long‐Term Imaging of Wound Angiogenesis with Large Scale Optoacoustic Microscopy
Authors: Rebling Johannes , Ben‐Yehuda Greenwald Maya , Wietecha Mateusz , Werner Sabine , Razansky Daniel
Published: May 2021

Wound healing is a well‐coordinated process, necessitating efficient formation of new blood vessels. Vascularization defects are therefore a major risk factor for chronic, non‐healing wounds. The dynamics of mammalian tissue revascularization, vessel maturation, and remodeling remain poorly understood due to lack of suitable in vivo imaging tools. A label‐free large‐scale optoacoustic microscopy (LSOM) approach is developed for rapid, non‐invasive, volumetric imaging of tissue regeneration over large areas spanning up to 50 mm with a depth penetration of 1.5 mm. Vascular networks in dorsal mouse skin and full‐thickness excisional wounds are imaged with capillary resolution during the course of healing, revealing previously undocumented views of the angiogenesis process in an unperturbed wound environment. Development of an automatic analysis framework enables the identification of key features of wound angiogenesis, including vessel length, diameter, tortuosity, and angular alignment. The approach offers a versatile tool for preclinical research in tissue engineering and regenerative medicine, empowering label‐free, longitudinal, high‐throughput, and quantitative studies of the microcirculation in processes associated with normal and impaired vascular remodeling, and analysis of vascular responses to pharmacological interventions in vivo.
Tribo‐Induced Color Tuner toward Smart Lighting and Self‐Powered Wireless Sensing
Authors: Wang Jiaqi , Wang Haoyu , Yin Kedong , Zi Yunlong
Published: May 2021

The color‐tuning capability of solid‐state lighting (SSL) systems are highly demanded for smart lighting according to the environmental conditions, as well as wireless sensing of the environmental information. In the meanwhile, state‐of‐the‐art triboelectric nanogenerator (TENG)‐based sensing systems rely on bulky and expensive devices, which require cable connections and additional power consumptions. This work aims at solving these challenges, through developing a tribo‐induced color tuner that can be integrated into the vastly distributed commercial SSL system. This tribo‐induced color tuner includes a concentric color conversion plate consisting of (Sr,Ca)AlSiN3:Eu phosphor and TiO2, a tribo‐induced liquid lens, and a rotary freestanding sliding TENG. The color oscillation between purple and pink is achieved upon the tribo‐charging by the TENG, which reveals the input mechanical motion signals. The signal can be conveniently sent by everywhere‐existed lamps and processed by everyone‐owned smartphone cameras or closed‐circuit televisions. Through this approach, the function of wireless sensing is achieved without the need of preamplification, with no additional power supply required, as demonstrated for wireless sensing of the rotation speed. The smart lighting for underwater photographing is also demonstrated by the color‐tunable SSL system with the best imaging quality achieved.
Tunable NaBH4 Nanostructures Revealing Structure‐Dependent Hydrogen Release
Authors: Salman Muhammad Saad , Rawal Aditya , Aguey-Zinsou Kondo-Francois
Published: May 2021

Borohydrides are promising candidates for hydrogen storage and generation assuming these can be tuned to reversibly deliver hydrogen under practical conditions. Nanostructuring of borohydrides has the potential to enable such control but this has remained elusive due to the lack of approaches to effectively prepare and stabilize borohydride nanostructures. Herein, a simple and straightforward method to assemble NaBH4, as a model borohydride, into sphere, cube, and bar‐like shapes using tetrabutylammonium bromide (TBAB), octadecylamine (ODA), and tridecanoic acid (TDA), respectively, is demonstrated. More importantly, the shape of the NaBH4 nanostructures could be tuned from one morphology to another by simply adjusting the ratio of surfactants and this is found to lead to distinct hydrogen properties. In particular, remarkable shifts in the melting points and hydrogen desorption temperatures are observed depending on the NaBH4 morphologies, i.e., spheres, cubes, or bars. For example, for the NaBH4 spheres, hydrogen release starts at ≈50 °C compared to the >500 °C of bulk NaBH4 without any transition metal dopant or catalyst. Observation of such structure‐dependent relationships finally enables new avenues to deliberately tune borohydrides toward nanostructures with specific hydrogen properties otherwise difficult to control.
Explaining output price heterogeneity in Dutch horticulture
Authors: Los Evert , Gardebroek Cornelis , Huirne Ruud
Published: May 2021

Recent empirical literature pays increasing attention to farmer‐retail power relations in agricultural supply chains, yet seems to neglect potential differences between prices that primary producers receive for their products. Via both a Markov chain analysis and a hybrid panel data model, we empirically test whether primary producers receive prices in a consistent way and what explains any price differences. Using a unique data set containing individual farm‐specific output prices in various horticultural markets, we show substantial price dispersion across farms and reveal relations between farm characteristics and observed output prices. The Markov analysis shows that the same farms are constantly found in the higher and lower quartiles of the price distribution, implying prices are not distributed randomly. The results of the hybrid panel data model show that characteristics as farm size and production orientation are strongly associated with differences in the obtained output prices as well as the price/cost ratio between farms. [EconLit Citations: D22, D40, L11, Q13].
Patterns of population genomic diversity in the invasive Japanese knotweed species complex
Authors: VanWallendael Acer , Alvarez Mariano , Franks Steven J.
Published: May 2021

PREMISE

Invasive species are expected to undergo a reduction in genetic diversity due to founder effects, which should limit their ability to adapt to new habitats. Still, many invasive species achieve widespread distributions and dense populations. This paradox of invasions could potentially be overcome through multiple introductions or hybridization, both of which increase genetic diversity. We conducted a population genomics study of Japanese knotweed (Reynoutria japonica), which is a polyploid, clonally reproducing invasive species that has been notoriously successful worldwide despite supposedly low genetic diversity.

METHODS

We used genotyping by sequencing to collect 12,912 SNP markers from 88 samples collected at 38 locations across North America for the species complex. We used alignment‐free k‐mer hashing analysis in addition to traditional population genetic analyses to account for the challenges of genotyping polyploids.

RESULTS

Genotypes conformed to three genetic clusters, likely representing Japanese knotweed, giant knotweed, and hybrid bohemian knotweed. We found that, contrary to previous findings, the Japanese knotweed cluster had substantial genetic diversity, though it had no apparent genetic structure across the landscape. In contrast, giant knotweed and hybrids showed distinct population groups. We did not find evidence of isolation by distance in the species complex, likely reflecting the stochastic introduction history of this species complex.

CONCLUSIONS

The results indicate that clonal invasive species can show substantial genetic diversity and can be successful at colonizing a variety of habitats without showing evidence of local adaptation or genetic structure.
Natural history of alpha‐thalassemia X‐linked intellectual disability syndrome: A case report of a 45‐year‐old man
Authors: Arvio Maria , Lähdetie Jaana
Published: May 2021

We have followed the clinical course of a 45‐year‐old man with a severe form of alpha‐thalassemia X‐linked intellectual disability syndrome for 40 years. The most challenging health issue is the combination of rumination, drooling, and vomiting. The patient achieved present adaptive and motor skills in his teenage years. He is able to move on the floor in a sitting position. He seems happy and has not shown any behavioral or psychiatric symptoms. New signs not described in the literature before are accelerated growth after puberty and atypical sleeping position with upper body resting on legs.
Incidence and characteristics of medical emergencies related to dental treatment: a retrospective single‐center study
Authors: Obata Kyoichi , Naito Hiromichi , Yakushiji Hiromasa , Obara Takafumi , Ono Kisho , Nojima Tsuyoshi , Tsukahara Kohei , Yamada Taihei , Sasaki Akira , Nakao Atsunori
Published: May 2021

Aim

Although uncommon, medical emergencies arise in general dental practice. Inadequate data on their severity and frequency makes targeting medical education for general dental practitioners difficult. This also makes planning for unexpected events challenging for practitioners and makes collaborating with emergency physicians burdensome. We aimed to clarify the incidence and characteristics of a dental outpatient department’s medical emergencies.

Methods

This single‐center, retrospective, observational study was undertaken with patients who visited the dental outpatient department of Okayama University Hospital during the 8‐year period. The primary outcome of the study was to identify the incidence and characteristics of medical emergencies in the dental outpatient department. Then we examined the timing of medical emergencies, administered medications, and final disposition (home/admission).

Results

During the period, 1,146,929 patients were enrolled. Forty‐two patients (0.0037%) were consulted as medical emergencies. More than 60% of the incidents were vasovagal syncope, and dehydration and hypoglycemia were the second most prevalent at 9.5%. The most common types of dental treatments were tooth extraction (45.2%), followed by general dental treatment (28.6%), and other dental surgery such as implant placement (14.3%). Types of medical emergencies occurred equally before, during, and after dental treatment. Antihypertensive agents, sedatives, or glucose were used. For patients with emergencies, 90.5% recovered during the day and returned home, and 9.5% were hospitalized.

Conclusion

The incidence of medical emergencies was low in our dental outpatient department. Knowledge of basic management principles, regular education for emergency care, and practicing first aid skills are mandatory for safe patient management.
π‐Stacked Donor–Acceptor Dendrimers for Highly Efficient White Electroluminescence
Authors: Wang Xingdong , Hu Jun , Lv Jianhong , Yang Qingqing , Tian Hongkun , Shao Shiyang , Wang Lixiang , Jing Xiabin , Wang Fosong
Published: May 2021

π‐Stacked dendrimers consisting of cofacially aligned donors and acceptors are developed by introducing three dendritic teracridan donors with orthogonal configuration and three triazine acceptors in periphery of hexaphenylbenzene skeleton. The dendritic structure and orthogonal configuration of teracridan not only make their outer acridan segments approaching to acceptor in close distance, but also fix donor and acceptor in face‐to‐face alignment, leading to through‐space charge transfer emission with thermally activated delayed fluorescence (TADF) effect. By regulating charge transfer strength via substituent effect of acceptor, emission color of the dendrimers can be tuned from blue to yellow/red region. Solution‐processed two‐color white organic light‐emitting diodes (OLEDs) based on blue and yellow π‐stacked donor–acceptor dendrimers exhibit the maximum external quantum efficiency of 20.6 % and maximum power efficiency of 58.9 lm W−1, representing the state‐of‐the‐art efficiency for all‐TADF white OLEDs by solution process.
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

Herein, 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

The 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

Malaria 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

During 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

Somatic 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

The 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

Tuning 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

When 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

Background

The paradigm of medical treatment for metastatic urothelial carcinoma is dramatically changing through the introduction of pembrolizumab.

Aim

We investigated the treatment effectiveness, the safety profile, and the prognostic factors of pembrolizumab in Japanese real‐world clinical practice.

Methods and results

The 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.

Conclusion

We 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

Background

In 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.

Aim

We assessed the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with non‐small cell lung cancer (NSCLC) aged ≥80 years.

Methods

We 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.

Results

A 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.

Conclusion

This 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

ZnO 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

The 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

Introduction

This study aimed to investigate cognitive aging trajectories, the associated sociodemographic characteristics, and the association of these trajectories with dementia.

Methods

Generally 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.

Results

Four 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%).

Discussion

Inter‐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

Introduction

Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre‐dementia stages.

Methods

We 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.

Results

There 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.

Discussion

We 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

Introduction

We investigated the frequency, neuropathology, and phenotypic characteristics of spastic paraplegia (SP) that precedes dementia in presenilin 1 (PSEN1) related familial Alzheimer's disease (AD).

Methods

We 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.

Results

We 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.

Discussion

We 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.
Prenatal antidepressant exposure and sex differences in neonatal corpus callosum microstructure
Authors: Campbell Kayleigh S. J. , Williams Lynne J. , Bjornson Bruce H. , Weik Ella , Brain Ursula , Grunau Ruth E. , Miller Steven P. , Oberlander Tim F.
Published: May 2021

Prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants may influence white matter (WM) development, as previous studies report widespread microstructural alterations and reduced interhemispheric connectivity in SSRI‐exposed infants. In rodents, perinatal SSRIs had sex‐specific disruptions in corpus callosum (CC) axon architecture and connectivity; yet it is unknown whether SSRI‐related brain outcomes in humans are sex specific. In this study, the neonate CC was selected as a region‐of‐interest to investigate whether prenatal SSRI exposure has sex‐specific effects on early WM microstructure. On postnatal day 7, diffusion tensor imaging was used to assess WM microstructure in SSRI‐exposed (n = 24; 12 male) and nonexposed (n = 48; 28 male) term‐born neonates. Fractional anisotropy was extracted from CC voxels and a multivariate discriminant analysis was used to identify latent patterns differing between neonates grouped by SSRI‐exposure and sex. Analysis revealed localized variations in CC fractional anisotropy that significantly discriminated neonate groups and correctly predicted group membership with an 82% accuracy. Such effects were identified across three dimensions, representing sex differences in SSRI‐exposed neonates (genu, splenium), SSRI‐related effects independent of sex (genu‐to‐rostral body), and sex differences in nonexposed neonates (isthmus‐splenium, posterior midbody). Our findings suggest that CC microstructure may have a sex‐specific, localized, developmental sensitivity to prenatal SSRI exposure.
Environmental drivers of Cheirogaleidae population density: Remarkable resilience of Madagascar’s smallest lemurs to habitat degradation
Authors: Hending Daniel
Published: May 2021

Aim

Global animal populations are in decline due to destruction and degradation of their natural habitat. Understanding the factors that determine the distribution and density of threatened animal populations is therefore now a crucial component of their study and conservation. The Cheirogaleidae are a diverse family of small‐bodied, nocturnal lemurs that are widespread throughout the forests of Madagascar. However, many cheirogaleid lemurs are now highly threatened with extinction and the environmental factors that determine their distribution and population density are still little known. Here, I investigated the environmental drivers of Cheirogaleidae population density at genus level.

Location

Various forest sites across Madagascar.

Methods

I investigated how six environmental variables affect Cheirogaleidae population density at the genus level via random‐effect meta‐analyses. I then used a generalized linear mixed‐effects model to identify the primary predictors of Cheirogaleidae population density. Finally, I investigated how the population density of this family of lemurs varies between protected and unprotected areas of Madagascar via a GLM analysis.

Results

My results indicate that the relationships between the tested environmental factors and population density are genus‐specific among the Cheirogaleidae. Rather remarkably, the density of Microcebus appears to have a profoundly positive relationship with anthropogenic disturbance and a negative relationship with forest cover, a finding that is also reflected by larger population densities within unprotected areas in comparison with localities within Madagascar's protected area network.

Main Conclusions

The results of this study are highly encouraging for the conservation of the Cheirogaleidae and highlight the remarkable resilience of these lemurs to habitat degradation and anthropogenic activity. However, this study also outlines the dearth of knowledge that we have for many species, and why these data are urgently needed to understand the biogeography and ecology of threatened animal populations and implement successful conservation.
Intact landscape promotes gene flow and low genetic structuring in the threatened Eastern Massasauga Rattlesnake
Authors: Kudla Nathan , McCluskey Eric M. , Lulla Vijay , Grundel Ralph , Moore Jennifer A.
Published: May 2021

Genetic structuring of wild populations is dependent on environmental, ecological, and life‐history factors. The specific role environmental context plays in genetic structuring is important to conservation practitioners working with rare species across areas with varying degrees of fragmentation. We investigated fine‐scale genetic patterns of the federally threatened Eastern Massasauga Rattlesnake (Sistrurus catenatus) on a relatively undisturbed island in northern Michigan, USA. This species often persists in habitat islands throughout much of its distribution due to extensive habitat loss and distance‐limited dispersal. We found that the entire island population exhibited weak genetic structuring with spatially segregated variation in effective migration and genetic diversity. The low level of genetic structuring contrasts with previous studies in the southern part of the species’ range at comparable fine scales (~7 km), in which much higher levels of structuring were documented. The island population's genetic structuring more closely resembles that of populations from Ontario, Canada, that occupy similarly intact habitats. Intrapopulation variation in effective migration and genetic diversity likely corresponds to the presence of large inland lakes acting as barriers and more human activity in the southern portion of the island. The observed genetic structuring in this intact landscape suggests that the Eastern Massasauga is capable of sufficient interpatch movements to reduce overall genetic structuring and colonize new habitats. Landscape mosaics with multiple habitat patches and localized barriers (e.g., large water bodies or roads) will promote gene flow and natural colonization for this declining species.
Exaggerated evolution of male armaments via male–male competition
Authors: Areja‐Gavina Maica Krizna D. , Torres Monica C. , Gamilla Gimelle B. , Sakaguchi Tomohiko , Ito Hiromu , Rabajante Jomar F. , Tubay Jerrold M. , Yoshimura Jin , Morita Satoru
Published: May 2021

Males usually compete to gain access to prospective mates. Through this male–male competition, superior males have a higher chance of passing on their traits to the next generation of male offspring. One category of male traits is armaments, which are weapons used during competition, for example, the chelae of fiddler crabs and the antlers of deer. One consequence of intrasexual selection is the exaggerated evolution of armaments, which can be limited by trade‐offs, such as trade‐offs with male body size. Here, we formulate a game‐theoretic sexual selection model to explore the exaggerated evolution of armaments through male–male competition. The model is used to determine how competition affects the evolution of an armament that is subject to trade‐offs. Our simulation can be used to support the exaggerated evolution hypothesis, that is, male–male competition escalates the rate of evolution of armaments.