bluuebunny/crossref_metadata_2025 huggingface dataset:
The Idea of Epilepsy
Authors: Shorvon Simon D.
Published: January 2023

Epilepsy has a fascinating history. To the medical historian Oswei Temkin it was 'the paradigm of the suffering of both body and soul in disease'. It is justifiably considered a window on brain function. And yet its story is more than simply a medical narrative, but one influenced also by scientific, societal and personal themes. Written for a medical and non-medical readership, this book describes the major developments in epilepsy between 1860–2020, a turbulent era in which science dominated as an explanatory model, medical theories and practices steered an erratic course, and societal attitudes and approaches to epilepsy fluctuated dramatically. In the middle of this maelstrom was the person with epilepsy at the mercy of social attitudes and legislation, and at times harmed as well as helped by medicine and science. So entangled is the history that intriguingly, as an entity, epilepsy may now be thought not even to exist.
The Songs of Johanna Kinkel
Authors: Bunzel Anja
Published: January 2023

Drawing on a wealth of unpublished sources surrounding Kinkel, this book explores the extent to which Kinkel's Lieder reflect and transcend compositional-aesthetic, cultural, and socio-political facets typically associated with the first half of the nineteenth century.
Allegri's Miserere in the Sistine Chapel
Authors: O'Reilly Graham
Published: January 2023

The Miserere by Italian composer Gregorio Allegri (1582-1652) is one of the most popular, oft performed and recorded choral pieces of late Renaissance/early Baroque music. Yet the piece known today bears little resemblanceto Allegri's original or to the piece as it was performed before 1870.
Anomalous 13C enrichment in Mesozoic vertebrate enamel reflects environmental conditions in a “vanished world” and not a unique dietary physiology
Authors: Cullen Thomas M. , Longstaffe Fred J. , Wortmann Ulrich G. , Huang Li , Evans David C.
Published: January 2023

Biogeochemical analyses of organisms’ tissues provide direct proxies for diets, behaviors, and environmental interactions that have proven invaluable for studies of extant and extinct species. Applying these to Cretaceous ecosystems has at times produced anomalous results, however, as dinosaurs preserve unusually positive stable carbon isotope compositions relative to extant C3-feeding vertebrates. This has been hypothesized to be a unique property of dinosaur dietary physiology, with potential significance for our interpretations of their paleobiology. We test that hypothesis through multi-taxic stable carbon isotope analyses of a spatiotemporally constrained locality in the Late Cretaceous of Canada, and compare the results to a modern near-analogue environment in Louisiana. The stable carbon isotope anomaly is present in all sampled fossil vertebrates, dinosaur or not. This suggests another more widespread factor is responsible. Examinations of diagenetic effects suggest that, where present, they are insufficient to explain the isotope anomaly. The isotope anomaly is therefore not primarily the result of a unique dietary physiology of dinosaurs, but rather a mix of factors impacting all taxa, such as environmental and/or source-diet differences. Our study underscores the importance of multi-taxic samples from spatiotemporally constrained localities in testing hypotheses of extinct organisms and ecosystems, and in the use of modern data to “ground truth” when evaluating analogue versus non-analogue conditions in greenhouse paleoecosystems.
Introduction to the special issue Experimental and Corpus-based Approaches to Ellipsis
Authors: BÎLBÎIE GABRIELA , NYKIEL JOANNA
Published: January 2023

Ellipsis has been, and continues to be, of both theoretical and empirical interest. It affects the syntax of phrases or clauses by stranding their various constituents but keeps the semantics of the stranded constituents identical to that of their non-elliptical counterparts. The theoretical value of ellipsis lies, therefore, in the relationship between meaning and form that it encodes, such that a complete propositional meaning is paired with what appears to be a syntactically incomplete form. This property of ellipsis has inspired researchers to probe, in particular, the syntax of ellipsis and the role the surrounding context plays in helping resolve ellipsis, as stranded constituents depend on the surrounding context for their interpretation. Among the constructions that have attracted considerable attention over the years are clausal ellipsis (e.g. sluicing (Example 1), sprouting (Example 2), stripping (Example 3), and fragments (Example 4)), pseudogapping (Example 5), gapping (Example 6), and Right Node Raising (RNR) (Example 7), all of which are discussed in the contributions to this special issue.
The cultural meaning of ‘female genital mutilation’ in rural Malaysia: The female body and sexuality through the medical gaze
Authors: Iguchi Yufu , Rashid Abdul
Published: January 2023

This article explores increasing medical control over sexuality and the female body in rural Malaysia by examining the formation of the global discourse of ‘female genital mutilation’ (FGM) through local discourses on sunat (circumcision). Regarding FGM as a Foucauldian discourse, the article analyses interviews with traditional practitioners and villagers’ statements. The expansion of modern medical systems, along with the medical gaze, has brought notions of sexuality in rural areas of Malaysia as revealed from local discourses on sunat that mention it as a means of controlling female sexuality. By examining the cultural gaps between global discourse and categories of FGM and the local practice of sunat, the article concludes that the incorporation of local practices in the global is ongoing rather than complete.
Reintervention and mortality risk after total anomalous pulmonary venous connection repair
Authors: Beers Kevin M. , Jacobsen Christian P. , Miller Stewart R. , Lehenbauer David G. , Maldonado Elaine , Husain S. Adil , Calhoon John H.
Published: January 2023

Background:

Management of total anomalous pulmonary venous connections has been extensively studied to further improve outcomes. Our institution previously reported factors associated with mortality, recurrent obstruction, and reintervention. The study purpose was to revisit the cohort of patients and evaluate factors associated with reintervention, and mortality in early and late follow-up.

Methods:

A retrospective review at our institution identified 81 patients undergoing total anomalous pulmonary venous connection repair from January 2002 to January 2018. Demographic and operative variables were evaluated. Anastomotic reintervention (interventional or surgical) and/or mortality were primary endpoints.

Results:

Eighty-one patients met the study criteria. Follow-up ranged from 0 to 6,291 days (17.2 years), a mean of 1263 days (3.5 years). Surgical mortality was 16.1% and reintervention rates were 19.8%. In re-interventions performed, 80% occurred within 1.2 years, while 94% of mortalities were within 4.1 months. Increasing cardiopulmonary bypass times (p = 0.0001) and the presence of obstruction at the time of surgery (p = 0.025) were predictors of mortality, while intracardiac total anomalous pulmonary venous connection type (p = 0.033) was protective. Risk of reintervention was higher with increasing cardiopulmonary bypass times (p = 0.015), single ventricle anatomy (p = 0.02), and a post-repair gradient >2 mmHg on transesophageal echocardiogram (p = 0.009).

Conclusions:

Evaluation of a larger cohort with longer follow-up demonstrated the relationship of anatomic complexity and symptoms at presentation to increased mortality risk after total anomalous pulmonary venous connection repair. The presence of a single ventricle or a post-operative confluence gradient >2 mmHg were risk factors for reintervention. These findings support those found in our initial study.
Domestic Investment Laws, International Economic Law, and Economic Development
Authors: Olaoye Kehinde Folake , Sornarajah Muthucumaraswamy
Published: January 2023

‘Development’ is a legal concept which has been central to the practice of international economic law (IEL). This Article examines how ‘development’ continues to be at the heart of struggles between domestic investment laws (DILs) and international economic law. By examining over 3000 international investment agreements (IIAs) and DILs signed in the last seven decades, this Article identifies the ways in which the concept of development has evolved in tandem with the growth of international economic law by dividing the history of international investment law into six main phases. It traces the emergence of ‘development’ in DIL to the decolonization era arguing that post 1990, the proliferation of international investment treaties and growth of investment treaty arbitration have been used as tools of liberalization on the weak premise that this would lead to economic development. In this context, this Article examines closely the interpretation of ‘investment’ by ICSID tribunals, promotion of international arbitration for economic development, attempts to internationalize economic development contracts, continued relevance of the New International Economic Order, and shift to sustainable development in IEL discourse.
International Organizations, Technical Assistance, and Domestic Investment Laws
Authors: Berge Tarald Gulseth , Fauchald Ole Kristian
Published: January 2023

Can supranational actors influence domestic policy? In this article, we study how international organizations have sought to shape the contents of domestic laws aimed at protecting foreign investment. Traditionally, the influence of international organizations on public policy has been assumed to run through loan conditionalities. We build on a recent strand of literature indicating that international organizations can also influence public policy through technical assistance. Empirically, we present a cross-sectional mapping of the protection that states offer foreign investors in domestic investment laws, and a mapping of the advisory activities of the three main organizations offering technical assistance on foreign investment laws: the United Nations Conference on Trade and Development, the Organization for Economic Co-operation and Development, and the World Bank. We find that there are significant variations in protection offered under domestic investment laws, and variation in international organizations’ technical assistance over time and across organizations. To explore technical assistance as a causal mechanism for influence on public policy more closely in this field, we conduct a case study of the development of domestic investment legislation in Bosnia and Herzegovina.
Co‐ and Post‐Seismic Mechanisms of the 2020 Mw 6.3 Yutian Earthquake and Local Stress Evolution
Authors: Liu Zhenjiang , Yu Chen , Li Zhenhong , Zhang Xuesong , Zhang Miaomiao , Feng Wanpeng , Han Bingquan , Peng Jianbing
Published: January 2023

The Mw 6.3 Yutian earthquake, occurred in northwestern Tibet on 25 June 2020, is one of the major events sequentially occurring in the region following the 2008 Mw 7.2, 2012 Mw 6.2, and 2014 Mw 6.9 earthquakes, and is of great significance for studying the tectonic activity and assessing future seismic hazards in the region. In this study, we used Sentinel‐1 Synthetic Aperture Radar images to retrieve co‐ and post‐seismic deformation and to investigate the coseismic rupture behavior of the fault and the mechanisms of postseismic deformation. Based on the slip models of recent four nearby major earthquakes, we explored the local stress evolution, triggering mechanism of the 2020 event and future regional seismic hazards. Postseismic modeling reveals that afterslip on fault patches surrounding the ruptured co‐seismic patches is the main mechanism responsible for the near‐field deformation, with the poroelastic rebound relaxation only accounts for maximumly 25% of the ground displacement and limited impact on the overall deformation pattern. The Coulomb failure stress changes (ΔCFS) suggest that the 2020 Yutian earthquake was inhibited by the 2008 Mw 7.2 earthquake but facilitated by the 2012 Mw 6.2 and 2014 Mw 6.9 earthquakes, resulting in an overall ΔCFS with a large lateral gradient on the 2020 fault. Stress concentrations on nearby major faults indicate increasing chances of seismic hazards in the eastern section of the Altyn Tagh fault at 82.8°E, the western section of the Guozha Co fault at 81.5°E and the entire section of the Ashikule fault.
The Effects of Trash, Residential Biofuel, and Open Biomass Burning Emissions on Local and Transported PM2.5 and Its Attributed Mortality in Africa
Authors: Gordon Janica N. D. , Bilsback Kelsey R. , Fiddler Marc N. , Pokhrel Rudra P. , Fischer Emily V. , Pierce Jeffrey R. , Bililign Solomon
Published: January 2023

Long‐term exposure to ambient fine particulate matter (PM2.5) is the second leading risk factor of premature death in Sub‐Saharan Africa. We use GEOS‐Chem to quantify the effects of (a) trash burning, (b) residential solid‐fuel burning, and (c) open biomass burning (BB) (i.e., landscape fires) on ambient PM2.5 and PM2.5‐attributable mortality in Africa. Using a series of sensitivity simulations, we excluded each of the three combustion sources in each of five African regions. We estimate that in 2017 emissions from these three combustion sources within Africa increased global ambient PM2.5 by 2%, leading to 203,000 (95% confidence interval: 133,000–259,000) premature mortalities yr−1 globally and 167,000 premature mortalities yr−1 in Africa. BB contributes more ambient PM2.5‐related premature mortalities per year (63%) than residential solid‐fuel burning (29%) and trash burning (8%). Open BB in Central Africa leads to the largest number of PM2.5‐attributed mortalities inside the region, while trash burning in North Africa and residential solid‐fuel burning in West Africa contribute the most regional mortalities for each source. Overall, Africa has a unique ambient air pollution profile because natural sources, such as windblown dust and BB, contribute strongly to ambient PM2.5 levels and PM2.5‐related mortality. Air pollution policies may need to focus on taking preventative measures to avoid exposure to ambient PM2.5 from these less‐controllable sources.
The Emergence of Four Types of Slow Slip Cycles on Dilatant, Fluid Saturated Faults
Authors: Chen Jianye
Published: January 2023

A variety of mechanisms have been proposed to explain how a fault might deform relatively slowly, rather than manifesting as earthquakes. Several rely on the frictional properties of the fault interface. In this study I analyze the slip stability of a fluid‐infiltrated fault in the framework of a microphysically‐based friction model, which has shear zone porosity as its state variable. Linear stability analysis of the model, incorporating the evolution of fluid pressure, gives the critical stiffness () and frequency () as a function of normalized dilatancy () and diffusivity () factors. The theoretical results are similar to those derived from the previous friction laws, except that a positive always exists, even for a highly‐dilatant, impermeable fault where the value is proportional to the diffusivity. This implies that dilatant faults in impermeable media are potentially seismogenic, while the previous models predict negative , implying a stable fault regardless of loading stiffness (k). Adopting a spring‐slider fault analogue, the analytical results are verified numerically under a wide span of spring stiffness, dilatancy, and diffusivity factors. The numerical results further reveal that four different modes of periodic slow slips can emerge in the model, without invoking inertia, which is distinct from previous friction models. Translating into the scenario of an elastically‐deformable medium, the critical wavelength on a dilatant fault can be as long as tens of kilometers. Gaining insights from all these features, I posit that the microphysical model is inherently favorable for generating slow slips.
Foreshocks of the 2010 Mw 6.7 Yushu, China Earthquake Occurred Near an Extensional Step‐Over
Authors: Chuang Lindsay Y. , Peng Zhigang , Lei Xinglin , Wang Baoshan , Liu Jiayue , Zhai Qiushi , Tu Hongwei
Published: January 2023

We conduct a detailed study of the foreshock sequence preceding the 2010 Mw 6.7 Yushu, Qinghai earthquake in the Tibetan plateau by examining continuous waveforms recorded at a seismic station near the mainshock rupture zone. By using a deep learning phase picker—EQTransformer and a matched‐filter technique, we identify 120 foreshocks with magnitude ranging from −0.7 to 1.6, starting with a Mw 4.6 foreshock approximately 2 hr before the Mw 6.7 Yushu mainshock. Our analyses show that the foreshock sequence follows a typical Omori's law decay with a p‐value of 0.73 and the Gutenberg‐Richer frequency‐magnitude b‐value of 0.66. We do not find any evidence of accelerating events leading up to the Yushu mainshock. Hence, they could be considered as aftershocks of the Mw 4.6 earthquake. We further invert for the focal mechanisms and rupture directions for both the largest foreshock and the mainshock. The Mw 4.6 foreshock likely occurred on a NE‐SW trending fault conjugating to the NW‐SE trending fault of the mainshock. Coulomb stress analysis suggests the Mw 4.6 foreshock induces negative stress on the mainshock source area. These observations do not support either the pre‐slip or the cascade triggering model for foreshock generation. The occurrence of the foreshock, mainshock and large aftershocks appear to be modulated by the Earth's tidal forces, likely reflecting the role of high pore‐fluid pressures. Our observations, together with other recent studies, suggest that extensional step‐overs and conjugate faults along major strike‐slip faults play an important role in generating short‐term foreshock sequences.
Investigation Into the Potential Value of Stratospheric Balloon Winds Assimilated in NOAA's Finite‐Volume Cubed‐Sphere Global Forecast System (FV3GFS)
Authors: Lukens Katherine E. , Ide Kayo , Garrett Kevin
Published: January 2023

Near‐space balloon networks have the potential to improve numerical weather prediction (NWP) through data assimilation (DA) by providing in situ observations in an otherwise data‐sparse stratosphere. This study investigates the prospective value of stratospheric balloon winds to NOAA NWP by examining Loon data quality and conducting a 2‐month observing system experiment (OSE) using NOAA's Finite‐Volume Cubed‐Sphere Global Forecast System. During the study period (December 2018–January 2019), Loon winds show good correspondence to collocated rawinsonde (RAOBS) winds, while a considerable difference in tropical stratospheric winds is observed between NOAA and ECMWF operational analyses. The OSE, one run with Loon winds assimilated and another without, suggests that additional stratospheric wind observations can improve NWP. Loon wind assimilation acts to decelerate the strong tropical easterly stratospheric jet west of where Loon winds are observed while accelerating less intense subtropical easterly motions. Differences in observation‐minus‐background statistics between the two runs reveal that the backgrounds for Loon winds and RAOBS winds and temperatures improve when Loon winds are assimilated. This positively impacts short‐term forecasts of the lower stratospheric circulation during the study period. Additionally, Loon wind assimilation improves the tropical stratospheric response to the 2019 New Year sudden stratospheric warming (SSW) event by significantly reducing the short‐term forecast error following the SSW. The findings emphasize the value of stratospheric winds toward improving global NWP, and imply the importance of including near‐space observing systems in the Earth‐observing architecture.
SF3B4 promotes Twist1 expression and clear cell renal cell carcinoma progression by facilitating the export of KLF 16 mRNA from the nucleus to the cytoplasm
Authors: Yang Zhan , Wang Ya-Xuan , Wen Jin-Kun , Gao Hai-Tao , Han Zhen-Wei , Qi Jin-Chun , Gu Jun-Fei , Zhao Chen-Ming , Zhang Hong , Shi Bei , Wang Dan-Dan , Wang Xiao-Lu , Qu Chang-Bao
Published: January 2023

Splicing factor 3B subunit 4 (SF3B4) plays important functional roles not only in pre-mRNA splicing, but also in the regulation of transcription, translation, and cell signaling, and its dysregulation contributes to various diseases including Nager syndrome and tumorigenesis. However, the role of SF3B4 and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) remain obscure. In the present study, we found that the expression of SF3B4 was significantly elevated in ccRCC tissues and negatively correlated with the overall survival of ccRCC patients. Upregulation of SF3B4 promotes migration and invasion of ccRCC cells in vitro and in vivo. The promoting effect of SF3B4 on cell migration and invasion is mediated by Twist1, a key transcription factor to mediate EMT. Interestingly, SF3B4, a component of the pre-mRNA spliceosome, is able to promote KLF16 expression by facilitating the transport of KLF16 mRNA into the cytoplasm. Mechanistically, SF3B4 promotes the export of KLF16 mRNA from the nucleus to the cytoplasm and thus enhances KLF16 expression, and in turn elevated KLF16 directly binds to the Twist1 promoter to activate its transcription, leading to EMT and ccRCC progression. Our findings provide evidence that the SF3B4-KLF16-Twist1 axis plays important functional roles in the development and progression of ccRCC, and manipulating this pathway may be a novel therapeutic target for the treatment of ccRCC.
Therapeutic adenine base editing of human hematopoietic stem cells
Authors: Liao Jiaoyang , Chen Shuanghong , Hsiao Shenlin , Jiang Yanhong , Yang Yang , Zhang Yuanjin , Wang Xin , Lai Yongrong , Bauer Daniel E. , Wu Yuxuan
Published: January 2023

In β-thalassemia, either γ-globin induction to form fetal hemoglobin (α2γ2) or β-globin repair to restore adult hemoglobin (α2β2) could be therapeutic. ABE8e, a recently evolved adenine base editor variant, can achieve efficient adenine conversion, yet its application in patient-derived hematopoietic stem cells needs further exploration. Here, we purified ABE8e for ribonucleoprotein electroporation of β-thalassemia patient CD34+ hematopoietic stem and progenitor cells to introduce nucleotide substitutions that upregulate γ-globin expression in the BCL11A enhancer or in the HBG promoter. We observed highly efficient on-target adenine base edits at these two regulatory regions, resulting in robust γ-globin induction. Moreover, we developed ABE8e-SpRY, a near-PAMless ABE variant, and successfully applied ABE8e-SpRY RNP to directly correct HbE and IVS II-654 mutations in patient-derived CD34+ HSPCs. Finally, durable therapeutic editing was produced in self-renewing repopulating human HSCs as assayed in primary and secondary recipients. Together, these results support the potential of ABE-mediated base editing in HSCs to treat inherited monogenic blood disorders.
CD4+ helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment
Authors: Lei Xin , Khatri Indu , de Wit Tom , de Rink Iris , Nieuwland Marja , Kerkhoven Ron , van Eenennaam Hans , Sun Chong , Garg Abhishek D. , Borst Jannie , Xiao Yanling
Published: January 2023

Despite their low abundance in the tumor microenvironment (TME), classical type 1 dendritic cells (cDC1) play a pivotal role in anti-cancer immunity, and their abundance positively correlates with patient survival. However, their interaction with CD4+ T-cells to potentially enable the cytotoxic T lymphocyte (CTL) response has not been elucidated. Here we show that contact with activated CD4+ T-cells enables human ex vivo cDC1, but no other DC types, to induce a CTL response to cell-associated tumor antigens. Single cell transcriptomics reveals that CD4+ T-cell help uniquely optimizes cDC1 in many functions that support antigen cross-presentation and T-cell priming, while these changes don’t apply to other DC types. We robustly identify “helped” cDC1 in the TME of a multitude of human cancer types by the overlap in their transcriptomic signature with that of recently defined, tumor-infiltrating DC states that prove to be positively prognostic. As predicted from the functional effects of CD4+ T-cell help, the transcriptomic signature of “helped” cDC1 correlates with tumor infiltration by CTLs and Thelper(h)−1 cells, overall survival and response to PD-1-targeting immunotherapy. These findings reveal a critical role for CD4+ T-cell help in enabling cDC1 function in the TME and may establish the helped cDC1 transcriptomic signature as diagnostic marker in cancer.
Global patterns of climate change impacts on desert bird communities
Authors: Ma Liang , Conradie Shannon R. , Crawford Christopher L. , Gardner Alexandra S. , Kearney Michael R. , Maclean Ilya M. D. , McKechnie Andrew E. , Mi Chun-Rong , Senior Rebecca A. , Wilcove David S.
Published: January 2023

The world’s warm deserts are predicted to experience disproportionately large temperature increases due to climate change, yet the impacts on global desert biodiversity remain poorly understood. Because species in warm deserts live close to their physiological limits, additional warming may induce local extinctions. Here, we combine climate change projections with biophysical models and species distributions to predict physiological impacts of climate change on desert birds globally. Our results show heterogeneous impacts between and within warm deserts. Moreover, spatial patterns of physiological impacts do not simply mirror air temperature changes. Climate change refugia, defined as warm desert areas with high avian diversity and low predicted physiological impacts, are predicted to persist in varying extents in different desert realms. Only a small proportion (<20%) of refugia fall within existing protected areas. Our analysis highlights the need to increase protection of refugial areas within the world’s warm deserts to protect species from climate change.
Topographic representation of current and future threats in the mouse nociceptive amygdala
Authors: Bowen Anna J. , Huang Y. Waterlily , Chen Jane Y. , Pauli Jordan L. , Campos Carlos A. , Palmiter Richard D.
Published: January 2023

Adaptive behaviors arise from an integration of current sensory context and internal representations of past experiences. The central amygdala (CeA) is positioned as a key integrator of cognitive and affective signals, yet it remains unknown whether individual populations simultaneously carry current- and future-state representations. We find that a primary nociceptive population within the CeA of mice, defined by CGRP-receptor (Calcrl) expression, receives topographic sensory information, with spatially defined representations of internal and external stimuli. While Calcrl+ neurons in both the rostral and caudal CeA respond to noxious stimuli, rostral neurons promote locomotor responses to externally sourced threats, while caudal CeA Calcrl+ neurons are activated by internal threats and promote passive coping behaviors and associative valence coding. During associative fear learning, rostral CeA Calcrl+ neurons stably encode noxious stimulus occurrence, while caudal CeA Calcrl+ neurons acquire predictive responses. This arrangement supports valence-aligned representations of current and future threats for the generation of adaptive behaviors.
Understanding the emergence of the boson peak in molecular glasses
Authors: González-Jiménez Mario , Barnard Trent , Russell Ben A. , Tukachev Nikita V. , Javornik Uroš , Hayes Laure-Anne , Farrell Andrew J. , Guinane Sarah , Senn Hans M. , Smith Andrew J. , Wilding Martin , Mali Gregor , Nakano Motohiro , Miyazaki Yuji , McMillan Paul , Sosso Gabriele C. , Wynne Klaas
Published: January 2023

A common feature of glasses is the “boson peak”, observed as an excess in the heat capacity over the crystal or as an additional peak in the terahertz vibrational spectrum. The microscopic origins of this peak are not well understood; the emergence of locally ordered structures has been put forward as a possible candidate. Here, we show that depolarised Raman scattering in liquids consisting of highly symmetric molecules can be used to isolate the boson peak, allowing its detailed observation from the liquid into the glass. The boson peak in the vibrational spectrum matches the excess heat capacity. As the boson peak intensifies on cooling, wide-angle x-ray scattering shows the simultaneous appearance of a pre-peak due to molecular clusters consisting ofcirca20 molecules. Atomistic molecular dynamics simulations indicate that these are caused by over-coordinated molecules. These findings represent an essential step toward our understanding of the physics of vitrification.
Assessing and advancing the safety of CRISPR-Cas tools: from DNA to RNA editing
Authors: Tao Jianli , Bauer Daniel E. , Chiarle Roberto
Published: January 2023

CRISPR-Cas gene editing has revolutionized experimental molecular biology over the past decade and holds great promise for the treatment of human genetic diseases. Here we review the development of CRISPR-Cas9/Cas12/Cas13 nucleases, DNA base editors, prime editors, and RNA base editors, focusing on the assessment and improvement of their editing precision and safety, pushing the limit of editing specificity and efficiency. We summarize the capabilities and limitations of each CRISPR tool from DNA editing to RNA editing, and highlight the opportunities for future improvements and applications in basic research, as well as the therapeutic and clinical considerations for their use in patients.
Risk factors and injury patterns of e-scooter associated injuries in Germany
Authors: Kleinertz Holger , Volk Annabelle , Dalos Dimitris , Rutkowski Rico , Frosch Karl-Heinz , Thiesen Darius M.
Published: January 2023

Since the introduction of widely available e-scooter rentals in Hamburg, Germany in June of 2019, our emergency department has seen a sharp increase in the amount of e-scooter related injuries. Despite a rising number of studies certain aspects of e-scooter mobility remain unclear. This study examines the various aspects of e-scooter associated injuries with one of the largest cohorts to date. Electronic patient records of emergency department admissions were screened for e-scooter associated injuries between June 2019 and December 2021. Patient demographic data, mechanism of injury, alcohol consumption, helmet usage, sustained injuries and utilized medical resources were recorded. Overall, 268 patients (57% male) with a median age of 30.3 years (IQR 23.3; 40.0) were included. 252 (94%) were e-scooter riders themselves, while 16 (6%) were involved in crashes associated with an e-scooter. Patients in non-rider e-scooter crashes were either cyclists who collided with e-scooter riders or older pedestrians (median age 61.2 years) who tripped over parked e-scooters. While e-scooter riders involved in a crash sustained an impact to the head or face in 58% of cases, those under the influence of alcohol fell on their head or face in 84% of cases. This resulted in a large amount of maxillofacial soft tissue lacerations and fractures. Extremity fractures and dislocations were more often recorded for the upper extremities. This study comprises one of the largest cohorts of e-scooter associated injuries to date. Older pedestrians are at risk to stumble over parked e-scooters. E-scooter crashes with riders who consumed alcohol were associated with more severe injuries, especially to the head and face. Restricted e-scooter parking, enforcement of drunk driving laws for e-scooters, and helmet usage should be recommended.
Exploring the latent structure of behavior using the Human Connectome Project’s data
Authors: Schöttner Mikkel , Bolton Thomas A. W. , Patel Jagruti , Nahálka Anjali Tarun , Vieira Sandra , Hagmann Patric
Published: January 2023

How behavior arises from brain physiology has been one central topic of investigation in neuroscience. Considering the recent interest in predicting behavior from brain imaging using open datasets, there is the need for a principled approach to the categorization of behavioral variables. However, this is not trivial, as the definitions of psychological constructs and their relationships—their ontology—are not always clear. Here, we propose to use exploratory factor analysis (EFA) as a data-driven approach to find robust and interpretable domains of behavior in the Human Connectome Project (HCP) dataset. Additionally, we explore the clustering of behavioral variables using consensus clustering. We find that four and five factors offer the best description of the data, a result corroborated by the consensus clustering. In the four-factor solution, factors for Mental Health, Cognition, Processing Speed, and Substance Use arise. With five factors, Mental Health splits into Well-Being and Internalizing. Clustering results show a similar pattern, with clusters for Cognition, Processing Speed, Positive Affect, Negative Affect, and Substance Use. The factor structure is replicated in an independent dataset using confirmatory factor analysis (CFA). We discuss how the content of the factors fits with previous conceptualizations of general behavioral domains.
Neolithic hydroclimatic change and water resources exploitation in the Fertile Crescent
Authors: Regattieri Eleonora , Forti Luca , Drysdale Russell N. , Mannella Giorgio , Hellstrom John C. , Conati Barbaro Cecilia , Bonacossi Daniele Morandi , Zerboni Andrea
Published: January 2023

In the first millennia of the Holocene, human communities in the Fertile Crescent experienced drastic cultural and technological transformations that modified social and human-environments interactions, ultimately leading to the rise of complex societies. The potential influence of climate on this “Neolithic Revolution” has long been debated. Here we present a speleothem record from the Kurdistan Region of Iraq, covering from Early Neolithic to Early Chalcolithic periods (~ 11 to 7.3 ka, 9000–5300 BCE). The record reveals the influence of the Siberian High on regional precipitation, and shows large hydroclimatic variability at the multicentennial scale. In particular, it highlights wetter conditions between 9.7 and 9.0 ka, followed by an abrupt reduction of precipitation between 9.0 and 8.5 ka, and a wetter interval between 8.5 and 8.0 ka. A comparison with regional and local archaeological data demonstrates an influence of recorded hydroclimatic changes on settlement patterns (size, distribution, permanent vs. seasonal occupation) and on the exploitation of water resources by Neolithic to Chalcolithic populations. Our record does not show prominent hydroclimatic changes at 9.3 and 8.2 ka, thus not supporting direct influence of such rapid and widespread events on the process of Neolithization and its cultural dispersal.
Theta tACS impairs episodic memory more than tDCS
Authors: Murray Nicholas W. G. , Graham Petra L. , Sowman Paul F. , Savage Greg
Published: January 2023

Episodic memory deficits are a common consequence of aging and are associated with a number of neurodegenerative disorders (e.g., Alzheimer’s disease). Given the importance of episodic memory, a great deal of research has investigated how we can improve memory performance. Transcranial electrical stimulation (TES) represents a promising tool for memory enhancement but the optimal stimulation parameters that reliably boost memory are yet to be determined. In our double-blind, randomised, sham-controlled study, 42 healthy adults (36 females; 23.3 ± 7.7 years of age) received anodal transcranial direct current stimulation (tDCS), theta transcranial alternating current stimulation (tACS) and sham stimulation during a list-learning task, over three separate sessions. Stimulation was applied over the left temporal lobe, as encoding and recall of information is typically associated with mesial temporal lobe structures (e.g., the hippocampus and entorhinal cortex). We measured word recall within each stimulation session, as well as the average number of intrusion and repetition errors. In terms of word recall, participants recalled fewer words during tDCS and tACS, compared to sham stimulation, and significantly fewer words recalled during tACS compared with tDCS. Significantly more memory errors were also made during tACS compared with sham stimulation. Overall, our findings suggest that TES has a deleterious effect on memory processes when applied to the left temporal lobe.
Biostimulants alleviate water deficit stress and enhance essential oil productivity: a case study with savory
Authors: Rezaei-Chiyaneh Esmaeil , Mahdavikia Hassan , Alipour Hadi , Dolatabadian Aria , Battaglia Martin Leonardo , Maitra Sagar , Harrison Matthew Tom
Published: January 2023

Water deficit stress exposure frequently constrains plant and agri-food production globally. Biostimulants (BSs) can be considered a new tool in mitigating water deficit stress. This study aimed to understand how BSs influence water deficit stress perceived by savory plants (Satureja hortensisL.), an important herb used for nutritional and herbal purposes in the Middle East. Three BS treatments, including bio-fertilizers, humic acid and foliar application of amino acid (AA), were implemented. Each treatment was applied to savory plants using three irrigation regimes (low, moderate and severe water deficit stress FC100, FC75 and FC50, respectively). Foliar application of AA increased dry matter yield, essential oil (EO) content and EO yield by 22%, 31% and 57%, respectively. The greatest EO yields resulted from the moderate (FC75) and severe water deficit stress (FC50) treatments treated with AA. Primary EO constituents included carvacrol (39–43%), gamma-terpinene (27–37%), alpha-terpinene (4–7%) andp-cymene (2–5%). Foliar application of AA enhanced carvacrol, gamma-terpinene, alpha-terpinene andp-cymene content by 6%, 19%, 46% and 18%, respectively. Physiological characteristics were increased with increasing water shortage and application of AA. Moreover, the maximum activities of superoxide dismutase (3.17 unit mg−1 min−1), peroxidase (2.60 unit mg−1 min−1) and catalase (3.08 unit mg−1 min−1) were obtained from plants subjected to severe water deficit stress (FC50) and treated with AA. We conclude that foliar application of AA under water deficit stress conditions would improve EO quantity and quality in savory.
Exchange bias coupling and bipolar resistive switching at room temperature on GaSb/Mn multilayers for resistive memories applications
Authors: Calderón Jorge A. , Quiroz Heiddy P. , Terán Cristian L. , Manso-Silván M. , Dussan A. , Muñoz Noval Álvaro
Published: January 2023

This work present structural, morphological, magnetic, and electrical properties of GaSb/Mn multilayer deposited via DC magnetron sputtering at room temperature and at 423 K. The samples are characterized by forming layers of 3, 6 and 12 periods of the GaSb/Mn structure. Through XRD patterns, it was possible to stablish the formation of GaSb, Mn3Ga, and Mn2Sb2 phases. FTIR measurements present an optical interference associated with periodicity and the homogenous thickness of the layers. HR-SEM shows the multilayer architecture with columnar microstructure in the formation of layers with grain nucleation on the surface. A ferromagnetic-like behavior was observed in the multilayers at room temperature related to the domains and interlayers interaction. Additionally, the hysteresis curves present shifts attributed to the effect of exchange bias coupling. I-V curves show RESET-SET states of the multilayer system with bipolar resistive behavior, which can be modified by external magnetic fields. The resistive switching evidenced corresponds to the conductive mechanism based on the capacitive conductance and the formation of conductive filaments in multilayer structure.
Valorization of rice straw, sugarcane bagasse and sweet sorghum bagasse for the production of bioethanol and phenylacetylcarbinol
Authors: Nunta Rojarej , Techapun Charin , Sommanee Sumeth , Mahakuntha Chatchadaporn , Porninta Kritsadaporn , Punyodom Winita , Phimolsiripol Yuthana , Rachtanapun Pornchai , Wang Wen , Zhuang Xinshu , Qi Wei , Jantanasakulwong Kittisak , Reungsang Alissara , Kumar Anbarasu , Leksawasdi Noppol
Published: January 2023

Open burning of agricultural residues causes numerous complications including particulate matter pollution in the air, soil degradation, global warming and many more. Since they possess bio-conversion potential, agro-industrial residues including sugarcane bagasse (SCB), rice straw (RS), corncob (CC) and sweet sorghum bagasse (SSB) were chosen for the study. Yeast strains, Candida tropicalis, C. shehatae, Saccharomyces cerevisiae, and Kluyveromyces marxianus var. marxianus were compared for their production potential of bioethanol and phenylacetylcarbinol (PAC), an intermediate in the manufacture of crucial pharmaceuticals, namely, ephedrine, and pseudoephedrine. Among the substrates and yeasts evaluated, RS cultivated with C. tropicalis produced significantly (p ≤ 0.05) higher ethanol concentration at 15.3 g L−1 after 24 h cultivation. The product per substrate yield (Yeth/s) was 0.38 g g-1 with the volumetric productivity (Qp) of 0.64 g L−1 h−1 and fermentation efficiency of 73.6% based on a theoretical yield of 0.51 g ethanol/g glucose. C. tropicalis grown in RS medium produced 0.303 U mL−1 pyruvate decarboxylase (PDC), a key enzyme that catalyzes the production of PAC, with a specific activity of 0.400 U mg−1 protein after 24 h cultivation. This present study also compared the whole cells biomass of C. tropicalis with its partially purified PDC preparation for PAC biotransformation. The whole cells C. tropicalis PDC at 1.29 U mL−1 produced an overall concentration of 62.3 mM PAC, which was 68.4% higher when compared to partially purified enzyme preparation. The results suggest that the valorization of lignocellulosic residues into bioethanol and PAC will not only aid in mitigating the environmental challenge posed by their surroundings but also has the potential to improve the bioeconomy.
Diagnostic and prognostic potential of the microbiome in ovarian cancer treatment response
Authors: Asangba Abigail E. , Chen Jun , Goergen Krista M. , Larson Melissa C. , Oberg Ann L. , Casarin Jvan , Multinu Francesco , Kaufmann Scott H. , Mariani Andrea , Chia Nicholas , Walther-Antonio Marina R. S.
Published: January 2023

Ovarian cancer (OC) is the second most common gynecological malignancy and the fifth leading cause of death due to cancer in women in the United States mainly due to the late-stage diagnosis of this cancer. It is, therefore, critical to identify potential indicators to aid in early detection and diagnosis of this disease. We investigated the microbiome associated with OC and its potential role in detection, progression as well as prognosis of the disease. We identified a distinct OC microbiome with general enrichment of several microbial taxa, including Dialister, Corynebacterium, Prevotella, and Peptoniphilus in the OC cohort in all body sites excluding stool and omentum which were not sampled from the benign cohort. These taxa were, however, depleted in the advanced-stage and high-grade OC patients compared to early-stage and low-grade OC patients suggestive of decrease accumulation in advanced disease and could serve as potential indicators for early detection of OC. Similarly, we also observed the accumulation of these mainly pathogenic taxa in OC patients with adverse treatment outcomes compared to those without events and could also serve as potential indicators for predicting patients’ responses to treatment. These findings provide important insights into the potential use of the microbiome as indicators in (1) early detection of and screening for OC and (2) predicting patients’ response to treatment. Given the limited number of patients enrolled in the study, these results would need to be further investigated and confirmed in a larger study.
Investigating metropolitan change through mathematical morphology and a dynamic factor analysis of structural and functional land-use indicators
Authors: Sadat Nickayin Samaneh , Egidi Gianluca , Cudlin Pavel , Salvati Luca
Published: January 2023

We presented an operational rationale grounded on complex system thinking to quantify structural and functional landscape transformations along three stages representative of post-war metropolitan development in Rome, Italy (urbanisation with population/settlement densification, 1949–1974; suburbanisation with medium-density settlement expansion, 1974–1999; counter-urbanisation with settlement sprawl, 1999–2016). A mathematical morphology approach assessing the geometric form of land patches and a multi-way factor analysis (MFA) of landscape metrics were used to investigate the joint evolution of urban form and land-use functions over time. The empirical results of the MFA delineated the multivariate relationship between nine land-use classes (with distinctive socioeconomic functions) and seven morphological types (reflecting different landscape structures) according to four observation times (1949, 1974, 1999, 2016). Taken as an intrinsic attribute of complex landscape systems experiencing intense transformations, an estimation of the ‘rapidity-of-change’ in the form-functions relationship at a given development stage was derived from MFA outcomes separately for urbanisation, suburbanisation, and counter-urbanisation. A simplified form-functions relationship, reflecting the spatial polarisation in compact settlements and rural (low-density) landscapes, was observed with compact urbanisation. By stimulating urban sprawl into fringe farmland, suburbanisation resulted in patchy and heterogeneous rural landscapes. Counter-urbanization was associated with the fragmentation of built-up settlements leading to a chaotic mosaic of land structures that mixes urban and rural traits. Rapidity-of-change in form-function relationships was greater during suburbanisation than urbanisation and counter-urbanisation. It reflects the intrinsic pressure of economic growth in contemporary cities.
The identification of metabolites from gut microbiota in NAFLD via network pharmacology
Authors: Oh Ki-Kwang , Gupta Haripriya , Min Byeong Hyun , Ganesan Raja , Sharma Satya Priya , Won Sung Min , Jeong Jin Ju , Lee Su Been , Cha Min Gi , Kwon Goo Hyun , Jeong Min Kyo , Hyun Ji Ye , Eom Jung A , Park Hee Jin , Yoon Sang Jun , Choi Mi Ran , Kim Dong Joon , Suk Ki Tae
Published: January 2023

The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. We obtained a total of 208 metabolites from the gutMgene database and retrieved 1256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD and therefore to understanding its processes and possible therapeutic approaches. The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights on which to base further research.