bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic literature review to evaluate extended dosing intervals in the pharmacological management of acromegaly
Authors: Fleseriu M. , Zhang Z. , Hanman K. , Haria K. , Houchard A. , Khawaja S. , Ribeiro-Oliveira A. , Gadelha M.
Published: November 2022

Purpose

This systematic literature review investigated whether extended dosing intervals (EDIs) of pharmacological acromegaly treatments reduce patient burden and costs compared with standard dosing, while maintaining effectiveness.

Methods

MEDLINE/Embase/the Cochrane Library (2001–June 2021) and key congresses (2018–2021) were searched and identified systematic literature review bibliographies reviewed. Included publications reported on efficacy/effectiveness, safety and tolerability, health-related quality of life (HRQoL), and patient-reported and economic outcomes in longitudinal/cross-sectional studies in adults with acromegaly. Interventions included EDIs of pegvisomant, cabergoline, and somatostatin receptor ligands (SRLs): lanreotide autogel/depot (LAN), octreotide long-acting release (OCT), pasireotide long-acting release (PAS), and oral octreotide; no comparator was required.

Results

In total, 35 publications reported on 27 studies: 3 pegvisomant monotherapy, 11 pegvisomant combination therapy with SRLs, 9 LAN, and 4 OCT; no studies reported on cabergoline, PAS, or oral octreotide at EDIs. Maintenance of normal insulin-like growth factor I (IGF-I) was observed in ≥ 70% of patients with LAN (1 study), OCT (1 study), and pegvisomant monotherapy (1 study). Achievement of normal IGF-I was observed in ≥ 70% of patients with LAN (3 studies) and pegvisomant in combination with SRLs (4 studies). Safety profiles were similar across EDI and standard regimens. Patients preferred and were satisfied with EDIs. HRQoL was maintained and cost savings were provided with EDIs versus standard regimens.

Conclusions

Clinical efficacy/effectiveness, safety, and HRQoL outcomes in adults with acromegaly were similar and costs lower with EDIs versus standard regimens. Physicians may consider acromegaly treatment at EDIs, especially for patients with good disease control.
Ag-(In-Bi) Solid–Liquid Interdiffusion Bonding
Authors: Kuziora Stéphane Léonard , Nguyen Hoang-Vu , Aasmundtveit Knut Eilif
Published: November 2022

Solid–liquid interdiffusion is a metallurgical bonding technique, suitable for assembly of temperature sensitive materials. We identify Ag-(In-Bi) as meeting the low-temperature bonding requirements, theoretically as low as 73°C. This work focuses on understanding the bonding process and the interactions between the metal elements. Ag-(In-Bi) was bonded using an eutectic In-Bi foil at both 150°C and 180°C. The resulting bondlines were layered as Ag/Ag9In4/AgIn2/In-Bi compounds/AgIn2/Ag9In4/Ag. At some sections the phase growth of AgIn2 or Ag9In4 bridged the bond. Because of this bridging of γ-Ag9In4, temperature stability of ~480–570°C, is readily possible. The majority of the remaining Bi was located within large pockets near the middle of the bondline, and the minority as precipitates in protruding arms. Mechanisms for these Bi precipitates and intermetallic arm growth are discussed, and the evidence indicates that dissolution and surface planarity play important roles in their formation.
Built-in Flood Risk: the Intertwinement of Flood Risk and Unregulated Urban Expansion in African Cities
Authors: Andreasen Manja H. , Agergaard Jytte , Allotey Albert N. M. , Møller-Jensen Lasse , Oteng-Ababio Martin
Published: November 2022

Urban flood risk is significantly shaped by ground conditions and the built environment, which are constantly modified and transformed by human actions. This paper examines the intertwinement of flood risk and unregulated urban expansion processes in three selected sites in Accra’s expanding periphery. All three sites have been included in Accra’s urban extent since the 1990s, but differ with regard to the timing of development and socio-economic characteristics of residents. The research illuminates how flood risk is produced and “built-in” to the urban fabric through widespread practices associated with unregulated urban expansion processes, especially the persistent encroachment on water retention areas, wetlands and riparian zones and the highly fragmented provision of transport infrastructure in emerging residential areas in the periphery. Such harmful development practices are neither confined to homebuilders from poorer segments of the urban population nor spatially concentrated in low-income areas. The research highlights how the actions and inactions of a wide range of social groups and actors engaged in urban land administration and development contribute to flood risk in various ways, making flooding an increasingly alarming issue of citywide concern. Different stakeholders highlight fragmented urban governance as an underlying root cause for the obstruction of sustainable land and water management. Overall, the study calls for a more robust recognition of spatial planning and transport infrastructure provision in flood risk mitigation and highlights the urgent need for planning and governance practices that challenge the existing fragmentation of urban governance systems.
Tracing the Supply Chain of Medicinal Wild Yam Species (Dioscorea spp.) in Cundinamarca, Colombia
Authors: Pérez Darío , Raz Lauren
Published: November 2022

Tracing the Supply Chain of Medicinal Wild Yam Species (Dioscoreaspp.) in Cundinamarca, Colombia. Wild yams (Dioscorea spp.) are widely distributed non-timber forest products that are traditionally used as medicine in Cundinamarca, Colombia, and represent a source of income for rural families in the region. The market for these native medicinal species has been growing due to their increasing popularity as a remedy for circulatory and blood problems; however, the supply and demand dynamics of this plant in the forest have not yet been documented. Through qualitative research methods, this study identifies the links and distribution of the wild yam supply chain in Cundinamarca and considers the implications for conservation and sustainability of the resource. Tuber collection was documented in forested areas in 14 municipalities in the Department of Cundinamarca. The tubers are destined for wholesale markets in Bogotá and are purchased by retailers from all over Cundinamarca, even those based in the municipalities from which the tubers were extracted. The collection, distribution, and consumption of Dioscorea species in Cundinamarca respond to growing demand and rely on extraction of the species directly from forest remnants within the Department; these could be at risk of overharvesting if management measures are not taken, or if participatory propagation programs that benefit harvesters and sellers are not implemented. This is the first study of the supply chain in an emerging new market for wild yams in Latin America. It highlights the dynamic, evolving nature of the medicinal plant trade from the local to the national scale, and beyond.
Improvement of angiographic and clinical outcomes of percutaneous coronary intervention for chronic total occlusion after implementation of a dedicated team: a single-centre experience
Authors: Polimac L. , van Leunen M. M. C. J. , van Steenbergen G. J. , Zelis J. M. , Eerdekens R. , van ’t Veer M. , Schulz D. N. , Wijnbergen I. F. , Vlaar P. J. , Teeuwen K.
Published: November 2022

Introduction

In a Dutch heart centre, a dedicated chronic total occlusion (CTO) team was implemented in June 2017. The aim of this study was to the evaluate treatment success and clinical outcomes before and after this implementation.

Methods

A total of 662 patients who underwent percutaneous coronary intervention (PCI) for a CTO between January 2013 and June 2020 were included and divided into pre– and post–CTO team groups. The primary endpoint was the angiographic success rate of CTO-PCI. Secondary endpoints included angiographic success stratified by complexity using the J‑CTO score and the following clinical outcomes: in-hospital complications and myocardial infarction, target vessel revascularisation, all-cause mortality, quality of life (QoL) and major adverse cardiac events (MACE) at 30-day and 1‑year follow-up.

Results

Compared with the pre–CTO team group, the success rate in the post–CTO team group was higher after the first attempt (81.4% vs 62.7%; p < 0.001) and final attempt (86.7% vs 73.8%; p = 0.001). This was mainly driven by higher success rates for difficult and very difficult CTO lesions according to the J‑CTO score. The MACE rate at 1 year was lower in the post–CTO team group than in the pre–CTO team group (6.4% vs 16.0%; p < 0.01), while it was comparable at 30-day follow-up (0.1% vs 1.7%; p = 0.74). Angina symptoms were significantly reduced at 30-day and 1‑year follow-up, and QoL scores were higher after 1 year.

Conclusion

This study demonstrated higher success rates of CTO-PCI and improved clinical outcomes and QoL at 1‑year follow-up after implementation of a dedicated CTO team using the hybrid algorithm.
Alluvial fans at Cala Gonone (Sardinia), a fast developing touristic village: origins, hazards and potential risks
Authors: Pascucci V. , Martini I. P. , Andreucci S.
Published: November 2022

The study area of Cala Gonone in NE Sardinia (Italy) consists of a wide terraced re-entrance/valley crowned inland by carbonate hills and, near the coast bounded laterally and partly floored by thin basaltic lava lying over carbonate bedrock. In this re-entrance, several inland alluvial fans (500 m length by 700 m wide) have developed, and a local ~ 30 m high, about 10 m wide (thick), 400 m long scarp body-remnant of semi-consolidated alluvial fan deposits is exposed along the coast. The fans experience depositional events mostly developed during the late Pleistocene. They although nowadays dormant may be reactivated by major rainstorms during strong climate changes. In these last few decades, the touristic village of Cala Gonone has been rapidly expanding over the mid to lower parts of two coalescing alluvial fans (Stadium and Gustui) and along the coastal marine scarp edge (Palmasera alluvial fan system). The village thus may become exposed to natural hazards if extreme climatic conditions may re-occur. Moreover, rock falls and the instability of the costal scarp due to wave erosion may add addition hazards for habitations built near the scarp crest and visitors to the frontal replenished beach. As commonly occurring elsewhere since antiquity, the risk perception of such events is low because of the centennial, millennial of longer recurrence. Such perception does not negate the hazards but a long event recurrence may be accepted as a reasonable risk for the human’s activity. Nevertheless, serious consideration should be given to potential problems and plan and build for amelioration and defense. The evidence of what environmentally did and could still happen in the Cala Gonone and similar other area is in part clearly imprinted on the landscape: geology, geomorphology, and relative details in the stratigraphy and sedimentology of the deposits.
We should redefine scientific expertise: an extended virtue account
Authors: Uygun Tunç Duygu
Published: November 2022

An expert is commonly considered to be somebody who possesses the right kind of knowledge and skills to find out true answers for questions in a domain. However, this common conception that focuses only on an individual’s knowledge and skills is not very useful to understand the epistemically interdependent nature of contemporary scientific expertise, which becomes increasingly more relevant due to the rise of large interdisciplinary research collaborations. The typical scientific expert today relies substantially on complex scientific instruments and numerous other experts in forming expert judgment. Moreover, we have research collaborations where multiple scientists interact in a way that gives rise to distributed cognitive systems, which can act as a single informant. Accordingly, our concept of scientific expertise should not consist only in individual knowledge and skills, but also accommodate epistemic dependence and collective knowledge production. To this aim, this paper proposes a reconstruction of the concept of scientific expertise as informant reliability by building on the virtue-epistemological account of epistemic competences and theories of extended and distributed cognition. Considered in reference to the social epistemic function of expertise, a scientific expert should be conceived as a reliable informant in a scientific domain, which implies that when consulted on matters in that domain they assert competently, honestly, and completely. Competent expert assertion involves the epistemic responsibility to draw on nothing but the highest degree of epistemic competence relevant to the given context. Thus, being a reliable informant may require one to draw on an extended epistemic competence that goes beyond one’s individual competence, or to form supra-individual or group-informants that manifest collectively the kind of complex epistemic competence required for the investigation of certain research questions.
Lying in two dimensions
Authors: Geraldes Diogo , Heinicke Franziska , Rosenkranz Stephanie
Published: November 2022

The expanding literature on lying has exclusively considered lying behavior within a one-dimensional context. While this has been an important first step, many real-world contexts involve the possibility of simultaneously lying in more than one dimension (e.g., reporting one’s income and expenses in a tax declaration). We experimentally investigate individual lying behavior in one- and two-dimensional contexts to understand how the multi-dimensionality of a decision affects lying behavior. Our paper provides the first evidence regarding the pure effect of dimensionality on lying behavior. Using a two-dimensional die-roll task, we show that participants distribute lies unevenly across dimensions, which results in greater over-reporting of the lower-outcome die.
Defining terms commonly used in sarcopenia research: a glossary proposed by the Global Leadership in Sarcopenia (GLIS) Steering Committee
Authors: Cawthon Peggy M. , Visser Marjolein , Arai Hidenori , Ávila-Funes José A. , Barazzoni Rocco , Bhasin Shalender , Binder Ellen , Bruyère Olivier , Cederholm Tommy , Chen Liang-Kung , Cooper Cyrus , Duque Gustavo , Fielding Roger A. , Guralnik Jack , Kiel Douglas P. , Kirk Ben , Landi Francesco , Sayer Avan A. , Von Haehling Stephan , Woo Jean , Cruz-Jentoft Alfonso J.
Published: November 2022

Methods

The aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. The Global Leadership Initiative in Sarcopenia (GLIS) aims to bring together leading investigators in sarcopenia research to develop a single definition that can be utilized worldwide; work on a global definition of sarcopenia is ongoing. The first step of GLIS is to develop the common terminology, or a glossary, that will facilitate agreement on a global definition of sarcopenia as well as interpretation of clinical and research findings.

Results

Several terms that are commonly used in sarcopenia research are defined, including self-reported measures of function and ability; objective physical performance tests; and measures related to muscle function and size.

Conclusion

As new methods and technologies are developed, these definitions may be expanded or refined over time. Our goal is to promote this common language to describe sarcopenia and its components in clinical and research settings in order to increase clinical awareness and research interest in this important condition. We hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition.
G2-LIKE CAROTENOID REGULATOR (SlGCR) is a positive regulator of lutein biosynthesis in tomato
Authors: Ren Siyan , Yuan Yong , Wang Hsihua , Zhang Yang
Published: November 2022

Lutein is an oxygen-containing carotenoid synthesized in plant chloroplasts and chromoplasts. It plays an indispensable role in promoting plant growth and maintaining eye health in humans. The rate-limiting step of lutein biosynthesis is catalyzed by the lycopene ε-cyclase enzyme (LCYE). Although great progress has been made in the identification of transcription factors involved in the lutein biosynthetic pathway, many systematic molecular mechanisms remain to be elucidated. Here, using co-expression analysis, we identified a gene, G2-LIKE CAROTENOID REGULATOR (SlGCR), encoding a GARP G2-like transcription factor, as the potential regulator of SlLCYE in tomato. Silencing of SlGCR reduced the expression of carotenoid biosynthetic genes and the accumulation of carotenoids in tomato leaves. By contrast, overexpression of SlGCR in tomato fruit significantly increased the expression of relevant genes and enhanced the accumulation of carotenoids. SlGCR can directly bind to the SlLCYE promoter and activate its expression. In addition, we also discovered that expression of SlGCR was negatively regulated by the master regulator SlRIN, thereby inhibiting lutein synthesis during tomato fruit ripening. Taken together, we identified SlGCR as a novel regulator involved in tomato lutein biosynthesis, elucidated the regulatory mechanism, and provided a potential tool for tomato lutein metabolic engineering.
Diagnose und Behandlung der funktionellen Dyspepsie in der klinischen Praxis
Authors: Fox Mark
Published: November 2022

Unangenehmes Völlegefühl nach den Mahlzeiten, Schmerzen im Oberbauch, Übelkeit und andere dyspeptische Symptome sind in der Allgemeinbevölkerung weit verbreitet, beeinträchtigen die Lebensqualität und verursachen erhebliche Kosten im Gesundheitswesen. In dieser Übersichtsarbeit wird die Rom-IV-Definition der funktionellen Dyspepsie und verwandter „Störungen der Gehirn-Darm-Interaktion“ (früher als funktionelle gastrointestinale Erkrankungen bezeichnet) beschrieben. Die pathophysiologischen Ursachen der Symptome werden erörtert und ein strukturierter Ansatz für die Behandlung von funktioneller Dyspepsie wird vorgestellt. Insbesondere wird die Stellung der klinischen Untersuchung der gastrischen Funktion thematisiert. Es wird vorgeschlagen, dass die Identifizierung spezifischer Phänotypen auf der Grundlage der klinischen Präsentation und der Ergebnisse physiologischer Messungen eine spezifischere und effektivere Behandlung von Patienten mit dyspeptischen Beschwerden ermöglichen kann.
Influence of course content on preschool teacher candidates’ classroom management strategies, professional beliefs and emotion regulation skills
Authors: Asi Derya , Karabay Sakire
Published: November 2022

It is strongly needed to enhance teacher training programs via extensive course content more specifically to improve classroom management skills of teacher candidates. In the current study, we aimed to evaluate effectiveness of an elective course grounded on various strategies and vital aspects of preventive interventions about classroom management competencies, professional beliefs, and emotion regulation skills of preschool teacher candidates. The research is a quasi-experimental field study with pretest–posttest, intervention-comparison groups design including combination of qualitative and quantitative datasets. The participant group consisted of 76 females and 4 males registered in a 4-year university degree preschool teacher training program. The intervention group received training including key aspects of social and emotional intervention programs widely used in preschool settings while the comparison group received training covering inclusive education principles and relevant practices. Findings showed a significant increase in proactive approaches and positive behavioral support rates in the intervention group, while the frequency of reactive approaches was lower than the comparison group. Contrary to expectations, we could not find any influence of the content on emotion regulation skills and teaching beliefs of the intervention group. Results show clear influence of elective course content on improved skills of preschool teacher candidates about classroom management approaches.
Neural modal ordinary differential equations: Integrating physics-based modeling with neural ordinary differential equations for modeling high-dimensional monitored structures
Authors: Lai Zhilu , Liu Wei , Jian Xudong , Bacsa Kiran , Sun Limin , Chatzi Eleni
Published: November 2022

The dimension of models derived on the basis of data is commonly restricted by the number of observations, or in the context of monitored systems, sensing nodes. This is particularly true for structural systems, which are typically high-dimensional in nature. In the scope of physics-informed machine learning, this article proposes a framework—termed neural modal ordinary differential equations (Neural Modal ODEs)—to integrate physics-based modeling with deep learning for modeling the dynamics of monitored and high-dimensional engineered systems. In this initiating exploration, we restrict ourselves to linear or mildly nonlinear systems. We propose an architecture that couples a dynamic version of variational autoencoders with physics-informed neural ODEs (Pi-Neural ODEs). An encoder, as a part of the autoencoder, learns the mappings from the first few items of observational data to the initial values of the latent variables, which drive the learning of embedded dynamics via Pi-Neural ODEs, imposing a modal model structure on that latent space. The decoder of the proposed model adopts the eigenmodes derived from an eigenanalysis applied to the linearized portion of a physics-based model: a process implicitly carrying the spatial relationship between degrees-of-freedom (DOFs). The framework is validated on a numerical example, and an experimental dataset of a scaled cable-stayed bridge, where the learned hybrid model is shown to out perform a purely physics-based approach to modeling. We further show the functionality of the proposed scheme within the context of virtual sensing, that is, the recovery of generalized response quantities in unmeasured DOFs from spatially sparse data.
Contribution to a modern treatment of Graphidaceae biodiversity in South Africa: genera of tribe Graphideae with hyaline ascospores
Authors: Medeiros Ian D. , Lutzoni François
Published: November 2022

Additions and corrections are provided for the South African species of Graphidaceae tribe Graphideae with hyaline ascospores. Allographa oldayana I. Medeiros sp. nov. is described as new to science based on morphological, chemical and molecular data. The new species is characterized by lirellae with striate labia and a complete thalline margin, a completely carbonized excipulum, large, muriform ascospores, and the presence of hirtifructic acid. Allographa consanguinea (Müll. Arg.) Lücking, A. leptospora (Vain.) Lücking & Kalb, Diorygma aff. minisporum Kalb et al., Graphis crebra Vain., Gr. dupaxana Vain., Gr. furcata Fée, Gr. handelii Zahlbr., Gr. longula Kremp., Gr. pinicola Zahlbr., Gr. proserpens Vain, Gr. subhiascens (Müll. Arg.) Lücking and Platythecium sp. are reported as new records for South Africa. Allographa striatula (Ach.) Lücking & Kalb, Graphis analoga Nyl. and Gr. scripta (L.) Ach. are shown to be misapplied names that should be removed from the South African checklist. The new combination Mangoldia bylii (Vain.) I. Medeiros comb. nov. (bas. Graphis bylii Vain) is made; this represents an earlier name for M. atronitens (A. W. Archer) Lücking et al. Taxonomic notes are provided for Graphis bylii var. lividula Vain. and Gr. denudans Vain., species that are known only from their South African holotypes. Phylogenetic analyses that include new DNA sequence data from the nrLSU, mtSSU and RPB2 loci confirm the generic placements of several species for which molecular data were lacking: Allographa consanguinea, Glyphis atrofusca (Müll. Arg.) Lücking, Graphis crebra and Gr. subhiascens.
Identification key to the lichen species of the parmelioid clade in Kenya
Authors: Farkas Edit , Muhoro Arthur Macharia
Published: November 2022

Of the c. 900 lichen species known from Kenya, 178 belong to the parmelioid clade. Several of these parmelioid taxa require further revisionary studies. An identification key to the species of the parmelioid clade, based on updated nomenclature, is produced to support the practical work in collecting and selecting certain parmelioid lichens for further research. A new combination Parmotrema nyasense (C. W. Dodge) R. S. Egan comb. nov. in Egan et al., Bibliotheca Lichenologica110, 383 (2016) is published here by R. S. Egan.
Projecting Compound Flood Hazard Under Climate Change With Physical Models and Joint Probability Methods
Authors: Gori Avantika , Lin Ning
Published: November 2022

Accurate delineation of compound flood hazard requires joint simulation of rainfall‐runoff and storm surges within high‐resolution flood models, which may be computationally expensive. There is a need for supplementing physical models with efficient, probabilistic methodologies for compound flood hazard assessment that can be applied under a range of climate and environment conditions. Here we propose an extension to the joint probability optimal sampling method (JPM‐OS), which has been widely used for storm surge assessment, and apply it for rainfall‐surge compound hazard assessment under climate change at the catchment‐scale. We utilize thousands of synthetic tropical cyclones (TCs) and physics‐based models to characterize storm surge and rainfall hazards at the coast. Then we implement a Bayesian quadrature optimization approach (JPM‐OS‐BQ) to select a small number (∼100) of storms, which are simulated within a high‐resolution flood model to characterize the compound flood hazard. We show that the limited JPM‐OS‐BQ simulations can capture historical flood return levels within 0.25 m compared to a high‐fidelity Monte Carlo approach. We find that the combined impact of 2100 sea‐level rise (SLR) and TC climatology changes on flood hazard change in the Cape Fear Estuary, NC will increase the 100‐year flood extent by 27% and increase inundation volume by 62%. Moreover, we show that probabilistic incorporation of SLR in the JPM‐OS‐BQ framework leads to different 100‐year flood maps compared to using a single mean SLR projection. Our framework can be applied to catchments across the United States Atlantic and Gulf coasts under a variety of climate and environment scenarios.
A Climatology of Extreme Convective Storms in Tropical and Subtropical East Asia and Their Ingredients for Heavy Rainfall as Seen by TRMM
Authors: Panasawatwong Warittha , Rasmussen Kristen L. , Bell Michael M.
Published: November 2022

Heavy rainfall is a challenge to forecast due to the variety of rainfall intensities and durations across a wide spectrum of high‐impact storm types. In this study, we analyze extreme storms in Tropical and Subtropical East Asia, a moisture‐rich environment with complex terrain and oceanic regions. The Tropical Rainfall Measuring Mission's Precipitation Radar is utilized to characterize the frequency and rainfall intensity of four extreme storm types. Extreme storms producing heavy precipitation are categorized into four types: deep convective cores (DCCs), deepwide convective cores (DWCCs), wide convective cores (WCCs), and broad stratiforms regions (BSRs). DCCs and DWCCs occur more frequently and produce stronger rain intensities over land compared to those over ocean. However, WCCs and BSRs occur more frequently over oceans, especially in association with the Meiyu front season and climatological progression in the northern subregions. Although the Convective Cores show higher rain intensities than the BSRs, they show lower volumetric rain rate due to their comparatively smaller horizontal area. An ingredients‐based framework is applied to find key similarities across the different heavy rainfall‐producing storms near Taiwan using ERA5 reanalysis. The analysis shows that the broader systems (i.e., WCCs and BSRs) are associated with larger in area and longer timescales of vertical moisture flux and low‐level wind shear that support the development of the horizontally large, organized storms. Smaller DCCs do not show strong vertical moisture flux on the spatial scales resolved by the reanalysis, suggesting their more local nature and less meso‐ or synoptic scale support.
Optical synaptic devices with ultra-low power consumption for neuromorphic computing
Authors: Zhu Chenguang , Liu Huawei , Wang Wenqiang , Xiang Li , Jiang Jie , Shuai Qin , Yang Xin , Zhang Tian , Zheng Biyuan , Wang Hui , Li Dong , Pan Anlian
Published: November 2022

Brain-inspired neuromorphic computing, featured by parallel computing, is considered as one of the most energy-efficient and time-saving architectures for massive data computing. However, photonic synapse, one of the key components, is still suffering high power consumption, potentially limiting its applications in artificial neural system. In this study, we present a BP/CdS heterostructure-based artificial photonic synapse with ultra-low power consumption. The device shows remarkable negative light response with maximum responsivity up to 4.1 × 108 A W−1 at VD = 0.5 V and light power intensity of 0.16 μW cm−2 (1.78 × 108 A W−1 on average), which further enables artificial synaptic applications with average power consumption as low as 4.78 fJ for each training process, representing the lowest among the reported results. Finally, a fully-connected optoelectronic neural network (FONN) is simulated with maximum image recognition accuracy up to 94.1%. This study provides new concept towards the designing of energy-efficient artificial photonic synapse and shows great potential in high-performance neuromorphic vision systems.
Comparing saliva and blood for the detection of mosaic genomic abnormalities that cause syndromic intellectual disability
Authors: Francis David I. , Stark Zornitza , Scheffer Ingrid E. , Tan Tiong Yang , Murali Krithika , Gallacher Lyndon , Amor David J. , Goel Himanshu , Downie Lilian , Stutterd Chloe A. , Krzesinski Emma I. , Vasudevan Anand , Oertel Ralph , Petrovic Vida , Boys Amber , Wei Vivian , Burgess Trent , Dun Karen , Oliver Karen L. , Baxter Anne , Hackett Anna , Ayres Samantha , Lunke Sebastian , Kalitsis Paul , Wall Meaghan
Published: November 2022

We aimed to determine whether SNP-microarray genomic testing of saliva had a greater diagnostic yield than blood for pathogenic copy number variants (CNVs). We selected patients who underwent CMA testing of both blood and saliva from 23,289 blood and 21,857 saliva samples. Our cohort comprised 370 individuals who had testing of both, 224 with syndromic intellectual disability (ID) and 146 with isolated ID. Mosaic pathogenic CNVs or aneuploidy were detected in saliva but not in blood in 20/370 (4.4%). All 20 individuals had syndromic ID, accounting for 9.1% of the syndromic ID sub-cohort. Pathogenic CNVs were large in size (median of 46 Mb), and terminal in nature, with median mosaicism of 27.5% (not exceeding 40%). By contrast, non-mosaic pathogenic CNVs were 100% concordant between blood and saliva, considerably smaller in size (median of 0.65 Mb), and predominantly interstitial in location. Given that salivary microarray testing has increased diagnostic utility over blood in individuals with syndromic ID, we recommend it as a first-tier testing in this group.
Highly tunable β-relaxation enables the tailoring of crystallization in phase-change materials
Authors: Cheng Yudong , Yang Qun , Wang Jiangjing , Dimitriadis Theodoros , Schumacher Mathias , Zhang Huiru , Müller Maximilian J. , Amini Narges , Yang Fan , Schoekel Alexander , Pries Julian , Mazzarello Riccardo , Wuttig Matthias , Yu Hai-Bin , Wei Shuai
Published: November 2022

In glasses, secondary (β-) relaxations are the predominant source of atomic dynamics. Recently, they have been discovered in covalently bonded glasses, i.e., amorphous phase-change materials (PCMs). However, it is unclear what the mechanism of β-relaxations is in covalent systems and how they are related to crystallization behaviors of PCMs that are crucial properties for non-volatile memories and neuromorphic applications. Here we show direct evidence that crystallization is strongly linked to β-relaxations. We find that the β-relaxation in Ge15Sb85 possesses a high tunability, which enables a manipulation of crystallization kinetics by an order of magnitude. In-situ synchrotron X-ray scattering, dielectric functions, and ab-initio calculations indicate that the weakened β-relaxation intensity stems from a local reinforcement of Peierls-like distortions, which increases the rigidity of the bonding network and decreases the dynamic heterogeneity. Our findings offer a conceptually new approach to tuning the crystallization of PCMs based on manipulating the β-relaxations.
Deficiency and excess of groundwater iodine and their health associations
Authors: Ma Ruoqi , Yan Mingquan , Han Peng , Wang Ting , Li Bin , Zhou Shungui , Zheng Tong , Hu Yandi , Borthwick Alistair G. L. , Zheng Chunmiao , Ni Jinren
Published: November 2022

More than two billion people worldwide have suffered thyroid disorders from either iodine deficiency or excess. By creating the national map of groundwater iodine throughout China, we reveal the spatial responses of diverse health risks to iodine in continental groundwater. Greater non-carcinogenic risks relevant to lower iodine more likely occur in the areas of higher altitude, while those associated with high groundwater iodine are concentrated in the areas suffered from transgressions enhanced by land over-use and intensive anthropogenic overexploitation. The potential roles of groundwater iodine species are also explored: iodide might be associated with subclinical hypothyroidism particularly in higher iodine regions, whereas iodate impacts on thyroid risks in presence of universal salt iodization exhibit high uncertainties in lower iodine regions. This implies that accurate iodine supply depending on spatial heterogeneity and dietary iodine structure optimization are highly needed to mitigate thyroid risks in iodine-deficient and -excess areas globally.
Reactive metal boride nanoparticles trap lipopolysaccharide and peptidoglycan for bacteria-infected wound healing
Authors: Meng Yun , Chen Lijie , Chen Yang , Shi Jieyun , Zhang Zheng , Wang Yiwen , Wu Fan , Jiang Xingwu , Yang Wei , Zhang Li , Wang Chaochao , Meng Xianfu , Wu Yelin , Bu Wenbo
Published: November 2022

Bacteria and excessive inflammation are two main factors causing non-healing wounds. However, current studies have mainly focused on the inhibition of bacteria survival for wound healing while ignoring the excessive inflammation induced by dead bacteria-released lipopolysaccharide (LPS) or peptidoglycan (PGN). Herein, a boron-trapping strategy has been proposed to prevent both infection and excessive inflammation by synthesizing a class of reactive metal boride nanoparticles (MB NPs). Our results show that the MB NPs are gradually hydrolyzed to generate boron dihydroxy groups and metal cations while generating a local alkaline microenvironment. This microenvironment greatly enhances boron dihydroxy groups to trap LPS or PGN through an esterification reaction, which not only enhances metal cation-induced bacterial death but also inhibits dead bacteria-induced excessive inflammation both in vitro and in vivo, finally accelerating wound healing. Taken together, this boron-trapping strategy provides an approach to the treatment of bacterial infection and the accompanying inflammation.
Engineering receptors in the secretory pathway for orthogonal signalling control
Authors: Mahameed Mohamed , Wang Pengli , Xue Shuai , Fussenegger Martin
Published: November 2022

Synthetic receptors targeted to the secretory pathway often fail to exhibit the expected activity due to post-translational modifications (PTMs) and/or improper folding. Here, we engineered synthetic receptors that reside in the cytoplasm, inside the endoplasmic reticulum (ER), or on the plasma membrane through orientation adjustment of the receptor parts and by elimination of dysfunctional PTMs sites. The cytoplasmic receptors consist of split-TEVp domains that reconstitute an active protease through chemically-induced dimerization (CID) that is triggered by rapamycin, abscisic acid, or gibberellin. Inside the ER, however, some of these receptors were non-functional, but their activity was restored by mutagenesis of cysteine and asparagine, residues that are typically associated with PTMs. Finally, we engineered orthogonal chemically activated cell-surface receptors (OCARs) consisting of the Notch1 transmembrane domain fused to cytoplasmic tTA and extracellular CID domains. Mutagenesis of cysteine residues in CID domains afforded functional OCARs which enabled fine-tuning of orthogonal signalling in mammalian cells.
Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen-receptor positive endocrine-resistant and fulvestrant-resistant breast cancer
Authors: Pancholi Sunil , Simigdala Nikiana , Ribas Ricardo , Schuster Eugene , Leal Mariana Ferreira , Nikitorowicz-Buniak Joanna , Rega Camilla , Bihani Teeru , Patel Hitisha , Johnston Stephen R. , Dowsett Mitch , Martin Lesley-Ann
Published: November 2022

The selective oestrogen receptor (ER) degrader (SERD), fulvestrant, is limited in its use for the treatment of breast cancer (BC) by its poor oral bioavailability. Comparison of the orally bioavailable investigational SERD elacestrant, versus fulvestrant, demonstrates both drugs impact tumour growth of ER+ patient-derived xenograft models harbouring severalESR1mutations but that elacestrant is active after acquired resistance to fulvestrant. In cell line models of endocrine sensitive and resistant breast cancer both drugs impact the ER-cistrome, ER-interactome and transcription of oestrogen-regulated genes similarly, confirming the anti-oestrogenic activity of elacestrant. The addition of elacestrant to CDK4/6 inhibitors enhances the antiproliferative effect compared to monotherapy. Furthermore, elacestrant inhibits the growth of palbociclib-resistant cells. Lastly, resistance to elacestrant involves Type-I and Type-II receptor tyrosine kinases which are amenable to therapeutic targeting. Our data support the wider clinical testing of elacestrant.
Inverse design of truss lattice materials with superior buckling resistance
Authors: Maurizi Marco , Gao Chao , Berto Filippo
Published: November 2022

Manipulating the architecture of materials to achieve optimal combinations of properties (inverse design) has always been the dream of materials scientists and engineers. Lattices represent an efficient way to obtain lightweight yet strong materials, providing a high degree of tailorability. Despite massive research has been done on lattice architectures, the inverse design problem of complex phenomena (such as structural instability) has remained elusive. Via deep neural network and genetic algorithm, we provide a machine-learning-based approach to inverse-design non-uniformly assembled lattices. Combining basic building blocks, our approach allows us to independently control the geometry and topology of periodic and aperiodic structures. As an example, we inverse-design lattice architectures with superior buckling performance, outperforming traditional reinforced grid-like and bio-inspired lattices by ~30–90% and 10–30%, respectively. Our results provide insights into the buckling behavior of beam-based lattices, opening an avenue for possible applications in modern structures and infrastructures.
Brain single cell transcriptomic profiles in episodic memory phenotypes associated with temporal lobe epilepsy
Authors: Busch Robyn M. , Yehia Lamis , Hu Bo , Goldman Melissa , Hermann Bruce P. , Najm Imad M. , McCarroll Steven A. , Eng Charis
Published: November 2022

Memory dysfunction is prevalent in temporal lobe epilepsy (TLE), but little is known about the underlying molecular etiologies. Single-nucleus RNA sequencing technology was used to examine differences in cellular heterogeneity among left (language-dominant) temporal neocortical tissues from patients with TLE with (n = 4) or without (n = 2) impairment in verbal episodic memory. We observed marked cell heterogeneity between memory phenotypes and identified numerous differentially expressed genes across all brain cell types. The most notable differences were observed in glutamatergic (excitatory) and GABAergic (inhibitory) neurons with an overrepresentation of genes associated with long-term potentiation, long-term depression, and MAPK signaling, processes known to be essential for episodic memory formation.
Proteomic overview of hepatocellular carcinoma cell lines and generation of the spectral library
Authors: Wang Mingchao , Weng Shuang , Li Chaoying , Jiang Ying , Qian Xiaohong , Xu Ping , Ying Wantao
Published: November 2022

Cell lines are extensively used tools, therefore a comprehensive proteomic overview of hepatocellular carcinoma (HCC) cell lines and an extensive spectral library for data independent acquisition (DIA) quantification are necessary. Here, we present the proteome of nine commonly used HCC cell lines covering 9,208 protein groups, and the HCC spectral library containing 253,921 precursors, 168,811 peptides and 10,098 protein groups. The proteomic overview reveals the heterogeneity between different cell lines, and the similarity in proliferation and metastasis characteristics and drug targets-expression with tumour tissues. The HCC spectral library generating consumed 108 hours’ runtime for data dependent acquisition (DDA) of 48 runs, 24 hours’ runtime for database searching by MaxQuant version 2.0.3.0, and 1 hour’ runtime for processing by SpectronautTM version 15.2. The HCC spectral library supports quantification of 7,637 protein groups of triples 2-hour DIA analysis of HepG2 and discovering biological alteration. This study provides valuable resources for HCC cell lines and efficient DIA quantification on LC-Orbitrap platform, further help to explore the molecular mechanism and candidate therapeutic targets.
Ocular injuries associated with two-wheeled electric transportation devices and motorcycle accidents
Authors: Lev Ari Omer , Shaked Gad , Michael Tal , Givon Adi , Bodas Moran ,   Israel Trauma Group, Acker A. , Aviran N. , Bahouth H. , Bar A. , Becker A. , Braslavsky A. , Fadeev D. , Goldstein A. L. , Grevtsev I. , Jeroukhimov I. , Kedar A. , Korin A. , Levit B. , Schwarz A. D. , Shomar W. , Soffer D. , Schrier I. , Venturero M. , Weiss M. , Yaslowitz O. , Zoarets I. , Tsumi Erez
Published: November 2022

Electric bicycles and scooters have gained popularity among riders; studies assessing these device-related injuries have not specified ocular trauma. Our study examined the types and risk factors for ocular and periocular injuries associated with electric devices compared to motorcycle accidents. The study was conducted on the National Trauma Registry database from 20 trauma centers, including patients involved in accidents with electric bicycles, scooters, and motorcycles between 2014 to 2019. Injured riders were assigned into two groups: motorcycle group (M) and electric bicycle & scooter group (E). Data such as gender, age, protective gear use, ocular injury type, injury severity score (ISS), and ocular surgery were captured. Logistic regression models were conducted for injury types and the need for surgery. 8181 M-riders and 3817 E-riders were involved in an accident and hospitalized. E-riders suffered from ocular injury more than M-riders. Males were most vulnerable and the ages of 15–29. Orbital floor fracture was the most common injury, followed by ocular contusion, eyelid laceration, and other ocular wounds. Electric bicycle and scooter riders are more likely to suffer from ocular injury than motorcycle riders. Riders without helmets are at greater risk for injuries, specifically orbital floor fractures. ISS of 16 + was associated with injury demanding ocular surgery.
Ultrafast laser surgery probe for sub-surface ablation to enable biomaterial injection in vocal folds
Authors: Andrus Liam , Jeon Hamin , Pawlowski Michal , Debord Benoit , Gerome Frederic , Benabid Fetah , Mau Ted , Tkaczyk Tomasz , Ben-Yakar Adela
Published: November 2022

Creation of sub-epithelial voids within scarred vocal folds via ultrafast laser ablation may help in localization of injectable therapeutic biomaterials towards an improved treatment for vocal fold scarring. Several ultrafast laser surgery probes have been developed for precise ablation of surface tissues; however, these probes lack the tight beam focusing required for sub-surface ablation in highly scattering tissues such as vocal folds. Here, we present a miniaturized ultrafast laser surgery probe designed to perform sub-epithelial ablation in vocal folds. The requirement of high numerical aperture for sub-surface ablation, in addition to the small form factor and side-firing architecture required for clinical use, made for a challenging optical design. An Inhibited Coupling guiding Kagome hollow core photonic crystal fiber delivered micro-Joule level ultrashort pulses from a high repetition rate fiber laser towards a custom-built miniaturized objective, producing a 1/e2 focal beam radius of 1.12 ± 0.10 μm and covering a 46 × 46 μm2 scan area. The probe could deliver up to 3.8 μJ pulses to the tissue surface at 40% transmission efficiency through the entire system, providing significantly higher fluences at the focal plane than were required for sub-epithelial ablation. To assess surgical performance, we performed ablation studies on freshly excised porcine hemi-larynges and found that large area sub-epithelial voids could be created within vocal folds by mechanically translating the probe tip across the tissue surface using external stages. Finally, injection of a model biomaterial into a 1 × 2 mm2 void created 114 ± 30 μm beneath the vocal fold epithelium surface indicated improved localization when compared to direct injection into the tissue without a void, suggesting that our probe may be useful for pre-clinical evaluation of injectable therapeutic biomaterials for vocal fold scarring therapy. With future developments, the surgical system presented here may enable treatment of vocal fold scarring in a clinical setting.