bluuebunny/crossref_metadata_2025 huggingface dataset:
Connecting hydrological modelling and forecasting from global to local scales: Perspectives from an international joint virtual workshop
Authors: Dasgupta Antara , Arnal Louise , Emerton Rebecca , Harrigan Shaun , Matthews Gwyneth , Muhammad Ameer , O'Regan Karen , Pérez‐Ciria Teresa , Valdez Emixi , van Osnabrugge Bart , Werner Micha , Buontempo Carlo , Cloke Hannah , Pappenberger Florian , Pechlivanidis Ilias G. , Prudhomme Christel , Ramos Maria‐Helena , Salamon Peter
Published: January 2023

The unprecedented progress in ensemble hydro‐meteorological modelling and forecasting on a range of temporal and spatial scales, raises a variety of new challenges which formed the theme of the Joint Virtual Workshop, ‘Connecting global to local hydrological modelling and forecasting: challenges and scientific advances’. Held from 29 June to 1 July 2021, this workshop was co‐organised by the European Centre for Medium‐Range Weather Forecasts (ECMWF), the Copernicus Emergency Management (CEMS) and Climate Change (C3S) Services, the Hydrological Ensemble Prediction EXperiment (HEPEX), and the Global Flood Partnership (GFP). This article aims to summarise the state‐of‐the‐art presented at the workshop and provide an early career perspective. Recent advances in hydrological modelling and forecasting, reflections on the use of forecasts for decision‐making across scales, and means to minimise new barriers to communication in the virtual format are also discussed. Thematic foci of the workshop included hydrological model development and skill assessment, uncertainty communication, forecasts for early action, co‐production of services and incorporation of local knowledge, Earth observation, and data assimilation. Connecting hydrological services to societal needs and local decision‐making through effective communication, capacity‐building and co‐production was identified as critical. Multidisciplinary collaborations emerged as crucial to effectively bring newly developed tools to practice.
MTBDRplus and MTBDRsl for simultaneous diagnosis of gastrointestinal tuberculosis and detection of first‐line and second‐line drug resistance
Authors: Sharma Kusum , Sharma Megha , Sharma Vishal , Sharma Megha , Parmar Uday Pratap Singh , Samanta Jayanta , Sharma Aman , Kochhar Rakesh , Sinha Saroj K
Published: January 2023

Background and Aim

Emergence of drug resistance, especially to second‐line drugs, hampers tuberculosis elimination efforts. The present study aimed to evaluate MTBDRplus and MTBDRsl assays for detecting first‐line and second‐line drug resistance, respectively, in gastrointestinal tuberculosis (GITB).

Methods

Thirty ileocecal biopsy specimens, processed in the Department of Microbiology between 2012 and 2022, that showed growth of Mycobacterium tuberculosis on culture were included in the study. DNA, extracted from culture, was subjected to MTBDRplus and MTBDRsl (Hain Lifescience GmbH, Nehren, Germany), following manufacturer's instructions. Their performance was compared against phenotypic drug susceptibility testing (pDST) and gene sequencing.

Results

Out of the 30 specimens, 4 (13.33%) were mono‐isoniazid resistant, 4 (13.33%) were multidrug resistant (MDR), 2 (6.67%) were pre‐extensively drug resistant (pre‐XDR), and 2 (6.67%) were mono‐fluoroquinolone resistant. The results were 100% concordant with pDST and gene sequencing.

Conclusions

In the wake of growing drug resistance in all forms of extrapulmonary tuberculosis, including GITB, MTBDRplus and MTBDRsl are reliable tools for screening of resistance to both first‐line and second‐line drugs.
Facet type determination based on combined atomic force microscopy and electron backscatter diffraction
Authors: Brüning Ralf , Hajati Mehrad , Lelièvre Peter G. , Bernhard Tobias , Dieter Sascha , Dietrich Grégoire
Published: January 2023

The distribution of facet types affects the functionality of the surfaces of polycrystalline films. However, we are not aware of a previously published convenient method to determine their distribution. This work describes and demonstrates a process to determine and map the Miller indexes (hkl) of crystal facets exposed at the surfaces of polycrystalline films. To find facet types in non‐trivial cases, one must know the orientation of the crystal and the direction in which the facet is facing. The method presented here combines the crystal orientations obtained with electron backscatter diffraction with the topography of the same sample area measured with atomic force microscopy. A challenging step is to transfer the data from the two instruments into a common coordinate system. The sequence of steps in the data processing is presented, with methods to verify the results. The process is illustrated with the analysis of an etched copper clad laminate (CCL) and an electroless Cu film deposited on the CCL. This example relates to facet selection in electroless and galvanic plating processes in printed circuit board production, where an uncontrolled transition from epitaxial to non‐epitaxial growth can lead to surfaces with unacceptable roughness.
Monetary Stimulus amidst the Infrastructure Investment Spree: Evidence from China's Loan‐Level Data
Authors: CHEN KAIJI , GAO HAOYU , HIGGINS PATRICK , WAGGONER DANIEL F. , ZHA TAO
Published: January 2023

We study how a fiscal expansion via infrastructure investment influences the dynamic impacts of monetary stimulus on credit allocation. We develop a two‐stage approach and apply it to the Chinese economy with a confidential loan‐level data set that covers all sectors. We find that infrastructure investment significantly weakened monetary policy's transmission to credit allocated to private firms, while reinforcing the monetary effects on loans to state‐owned firms. This fiscal‐monetary interaction channel is key to understanding the preferential credit access enjoyed by state‐owned firms during the stimulus period. Consequently, monetary stimulus crowded out private investment and decreased capital allocation efficiency.
Input Price Discrimination, Demand Forms, And Welfare*
Authors: Gaudin Germain , Lestage Romain
Published: January 2023

We analyse the effects of input price discrimination in the canonical model where an upstream monopolist sells to downstream firms with various degrees of efficiency. We first recast a series of existing results within our setting, extending previous findings related to discrimination in final‐goods markets to the case of discrimination in input markets. Then, we examine the impact of input price discrimination on welfare. A key determinant of the effects of input price discrimination corresponds to the sum of demand curvature and pass‐through elasticity. We provide examples relying on derived demands with constant curvature, including demands with constant pass‐through rates.
Kinetic factors of physiology and the dynamic light environment influence the economic landscape of short‐term hydraulic risk
Authors: Buckley Thomas N. , Frehner Ethan H. , Bailey Brian N.
Published: January 2023

Optimality‐based models of stomatal conductance unify biophysical and evolutionary constraints and can improve predictions of land‐atmosphere carbon and water exchange. Recent models incorporate hydraulic constraints by penalizing excessive stomatal opening in relation to hydraulic damage caused by low water potentials. We used simulation models to test whether penalties based solely on vulnerability curves adequately represent the optimality hypothesis, given that they exclude the effects of kinetic factors on stomatal behavior and integrated carbon balance.

To quantify the effects of nonsteady‐state phenomena on the landscape of short‐term hydraulic risk, we simulated diurnal dynamics of leaf physiology for 10 000 patches of leaf in a canopy and used a ray‐tracing model, Helios, to simulate realistic variation in sunfleck dynamics.

Our simulations demonstrated that kinetic parameters of leaf physiology and sunfleck properties influence the economic landscape of short‐term hydraulic risk, as characterized by the effect of stomatal strategy (gauged by the water potential causing a 50% hydraulic penalty) on both aggregated carbon gain and the aggregated carbon cost of short‐term hydraulic risk.

Hydraulic penalties in optimization models should be generalized to allow their parameters to account for kinetic factors, in addition to parameters of hydraulic vulnerability.
The Nobel Roll of Honor
Authors: Sneis Jørgen , Spoerhase Carlos
Published: January 2023

This paper analyzes what may be called Olympic Internationalism as a framework for comparing literatures in the early twentieth century. Specifically, it analyzes the practice of tabulating information about the Nobel Prize—in the Swedish Academy, the international press, and repositories of general knowledge such as encyclopedias—and argues that the international circulation of such “thin knowledge” (Orsini) formed the very basis for that framework of comparison. This, it is further argued, played a crucial role in shaping the international perception of what world literature is and in making the Nobel Prize in Literature what it is: a globally acknowledged “world prize.”
Identification of TaGL1‐B1 gene controlling grain length through regulation of jasmonic acid in common wheat
Authors: Niaz Mohsin , Zhang Lingran , Lv Guoguo , Hu Huiting , Yang Xi , Cheng Yongzhen , Zheng Yueting , Zhang Bingyang , Yan Xiangning , Htun Aye , Zhao Lei , Sun Congwei , Zhang Ning , Ren Yan , Chen Feng
Published: January 2023

Grain length is one of the most important factors in determining wheat yield. Here, a stable QTL for grain length was mapped on chromosome 1B in a F10 recombinant inbred lines (RIL) population, and the gene TaGL1‐B1 encoding carotenoid isomerase was identified in a secondary large population through multiple strategies. The genome‐wide association study (GWAS) in 243 wheat accessions revealed that the marker for TaGL1‐B1 was the most significant among all chromosomes. EMS mutants of TaGL1 possessed significantly reduced grain length, whereas TaGL1‐B1‐overexpressed lines possessed significantly increased grain length. Moreover, TaGL1‐B1 strongly interacted with TaPAP6. TaPAP6‐overexpressed lines had significantly increased grain length. Transcriptome analysis suggested that TaPAP6 was possibly involved in the accumulation of JA (jasmonic acid). Consistently, JA content was significantly increased in the TaGL1‐B1 and TaPAP6 overexpression lines. Additionally, the role of TaGL1‐B1 in regulating carotenoids was verified through QTL mapping, GWAS, EMS mutants and overexpression lines. Notably, overexpression of TaGL1‐B1 significantly increased wheat yield in multiple locations. Taken together, overexpression of TaGL1‐B1 enhanced grain length, probably through interaction with TaPAP6 to cause the accumulation of JA that improved carotenoid content and photosynthesis, thereby resulted in increased wheat yield. This study provided valuable genes controlling grain length to improve yield and a potential insight into the molecular mechanism of modulating JA‐mediated grain size in wheat.
Quantitative analysis of wing interference patterns in Drosophila spp. using hyperspectral images
Authors: Takahashi Kazuo H.
Published: January 2023

Recent studies have reported wing interference patterns (WIPs), which reflect the microstructure of the wing, for small insects belonging to the Diptera and Hymenoptera orders. WIPs have been evaluated using RGB or multispectral images, but in contrast to these approaches, hyperspectral images allow a more detailed analysis of spectral variation, which may not be captured by RGB or multispectral images. Here, I investigated the WIPs of 12 Drosophila species using hyperspectral images. The average spectrum was calculated for each of the six compartments of the wing region and for the entire wing, including all six compartments. This information was used to evaluate sexual and interspecific differences in the WIPs of 12 Drosophila species. In addition, the possibility of species discrimination based on WIPs was explored using the random forest machine learning algorithm. The present study demonstrates significant sex and interspecific differences in WIPs for each of the six compartments of the wing regions as well as for the entire wing region. The results of the random forest machine learning algorithm suggested the possibility of species identification based on WIPs.
Dendrobium nobile Lindl Polysaccharides Attenuate UVB‐induced Photodamage by Regulating Oxidative Stress, Inflammation and MMPs Expression in Mice Model
Authors: Long Yunluan , Wang Wuji , Zhang Yanyan , Zhang Shiqian , Li Zheng , Deng Jiang , Li Jingjie
Published: January 2023

Acute ultraviolet B (UVB) irradiation predominantly leads to various skin disorders caused by photodamage. The major causes of UVB‐induced photodamage include oxidative stress, inflammatory infiltration and collagen degradation. The aim of the study was to elucidate whether DNP had protective effect on the skin of KM mice when exposed to UVB irradiation. The DNP protective properties to skin appearance and histopathological alterations in KM mice were evaluated by hematoxylin–eosin staining, toluidine blue staining, Gomori staining and Masson's trichrome staining and mast cell staining. In this study, DNP pretreatment promoted the activities of antioxidant enzymes, including superoxide dismutase, catalase and glutathione peroxidase, while decreased malondialdehyde level in UVB‐irradiated skin, along with downregulation of proteins expression of matrix metalloproteinases and reduction in the level of the proinflammatory cytokines. Based on these findings, we demonstrated that DNP displayed strong ameliorative effects on UVB‐induced acute photodamage for the first time, indicating that it would be a promoting ingredient candidate that could be used in antiphotodamage.
Autophagy regulation of virus infection in aquatic animals
Authors: Li Chen , Zhang Yunli , Zhao Xianliang , Li Li , Kong Xianghui
Published: January 2023

Autophagy is a conserved intracellular degradation process that is required to maintain host homeostasis and cope with invading pathogens. Over the past few decades, studies on mammals have greatly increased our understanding of the relationship between autophagy and virus infection. Autophagy may convey the invader to lysosomes to degrade or activate the host immune response against virus replication. However, many viruses have developed some strategies that evade the degradative nature of autophagy or hijack this pathway for their gain. It follows that autophagy during viral infection is a double‐edged sword. In contrast to mammals, the review on autophagy modulated by the aquatic animal virus is limited. Here, after a brief description of the main information about autophagy, we highlight current progress on the interplays between autophagy and virus infection in aquatic animals, including the phenomenon of autophagy upon virus infection, the effect of modulating autophagy on virus replication, and the crosstalk between autophagy and immune response during virus infection. This review will help us better understand the pathogenic mechanism of aquatic animal viruses and develop proper antiviral countermeasures aimed at modulating autophagy.
Gathering the Nation in the Village: Intellectuals and the Cultural Politics of Nationality in the Late Soviet Period
Authors: Hutchinson Erin
Published: January 2023

This article analyzes the activities of three Soviet intellectuals–the Ukrainian artist Ivan Honchar, the Russian writer Vladimir Soloukhin, and the Gagauz poet Dmitri Kara Çoban–who launched independent projects to collect and preserve artifacts of pre‐Soviet peasant culture in the 1960s. Reacting against representations of their national culture in state museums that they considered inauthentic and incomplete, these three collectors were part of a broader movement of intellectuals in the post‐Stalin period who sought to return to the village as the original source of “authentic” national culture. State responses to these intellectual initiatives were determined not by clearly articulated policies made in Moscow, but through the “cultural politics of nationality”–the interaction of intellectuals, republican leaders and central authorities. Demonstrating the enduring impact of these three independent collecting projects on Soviet and post‐Soviet thought about the nation, this article argues that changing conceptions of the nation in the post‐Stalin period are best understood as the result of a nationalities process involving intellectuals, republican leaders and central authorities, rather than an explicitly defined nationalities policy.
Future‐Oriented Group Training for suicidal individuals: A randomized controlled trial
Authors: De Jaegere Eva , Stas Pauline , van Heeringen Kees , Dumon Eva , van Landschoot Renate , Portzky Gwendolyn
Published: January 2023

Introduction

Suicide is a serious public health concern worldwide. Current psychological interventions targeting suicidal ideation and behavior are, however, limited and often lack convincing empirical support. Future‐Oriented Group Training (FOGT) targets crucial aspects of the suicidal process, thus possibly offering a promising intervention for suicidal ideation. This study aimed at investigating the short‐term and long‐term effects of FOGT on suicidal thoughts and related variables.

Methods

A randomized controlled trial was conducted, comparing the intervention group (FOGT + treatment as usual (TAU)) to a control group (TAU) at pre and posttreatment and at a 12‐week follow‐up. Suicidal ideation was the primary outcome, while depressive symptoms, hopelessness, defeat, entrapment, worrying, and the ability for future‐oriented thinking were secondary outcomes.

Results

When compared to the control group, the intervention group showed significant decreases in worrying at posttreatment and significant increases in future‐oriented thinking at follow‐up. Pre‐post analyses within the intervention group showed significant small‐to‐medium effects for primary as well as most secondary outcomes. Changes in suicidal ideation, depression, hopelessness, and future‐oriented thinking remained significant at follow‐up.

Conclusion

This study provides promising empirical evidence for the use of FOGT for individuals with suicidal ideation.
The dose–response of pain throughout a Nordic hamstring exercise intervention
Authors: Behan Fearghal P. , Opar David A. , Vermeulen Robin , Timmins Ryan G. , Whiteley Rodney
Published: January 2023

The Nordic hamstring exercise (NHE) reduces hamstring injury incidence. Compliance to large exercise volumes of the NHE is poor, with exercise related soreness often seen as a contributing factor. We investigated the dose–response of NHE exposure with delayed onset muscle soreness (DOMS) and non‐DOMS pain. Forty males were randomized to a 6‐week intervention of four different NHE dosages: Group 1: very low volume; Group 2: low volume; Group 3: initial high to low volume; Group 4: low to high volume. Group 4 experienced more DOMS (p < 0.05) and non‐DOMS pain (p = 0.030) than other groups. High volumes of NHE increase DOMS and non‐DOMS pain while lower volume protocols have lesser DOMS and non‐DOMS pain responses.
Does fatigue influence joint‐specific work and ground force production during the first steps of maximal acceleration?
Authors: Vial Shayne , Wilkie Jodie Cochrane , Turner Mitchell , Scanlan Mark , Blazevich Anthony J.
Published: January 2023

During initial acceleration, the first steps of a maximal‐effort (sprint) run often determine success or failure in the capture and evasion of an opponent, and is therefore a vital factor of success in many modern sports. However, accelerative events are commonly performed after having already run considerable distances, and the associated fatigue should impair muscle force production and thus reduce acceleration. Despite this, the effects of running‐induced fatigue on our ability to accelerate as well as the running technique used to achieve it have received little attention. We recorded 3‐D kinematics and ground reaction forces during the first three steps of the acceleration phase from a standing start before and after performing a high‐speed, multi‐directional, fatiguing run‐walk protocol in well‐trained running athletes who were habituated to accelerative sprinting. We found that the athletes were able to maintain their acceleration despite changing running technique, which was associated with use of a more upright posture, longer ground contact time, increased vertical ground reaction impulse, decreased hip flexion and extension velocities, and a shift in peak joint moments, power, and positive work from the hip to the knee joint; no changes were detected in ankle joint function. Thus, a compensatory increase in knee joint function alleviated the reduction in hip flexor‐extensor capacity. These acute adaptations may indicate that the hip extensors (gluteal and hamstring muscle groups) were more susceptible to fatigue than the ankle and knee musculature, and may thus be a primary target for interventions promoting fatigue resistance.
Polymer brushes for friction control: Contributions of molecular simulations
Authors: Abdelbar Mohamed A. , Ewen James P. , Dini Daniele , Angioletti-Uberti Stefano
Published: January 2023

When polymer chains are grafted to solid surfaces at sufficiently high density, they form brushes that can modify the surface properties. In particular, polymer brushes are increasingly being used to reduce friction in water-lubricated systems close to the very low levels found in natural systems, such as synovial joints. New types of polymer brush are continually being developed to improve with lower friction and adhesion, as well as higher load-bearing capacities. To complement experimental studies, molecular simulations are increasingly being used to help to understand how polymer brushes reduce friction. In this paper, we review how molecular simulations of polymer brush friction have progressed from very simple coarse-grained models toward more detailed models that can capture the effects of brush topology and chemistry as well as electrostatic interactions for polyelectrolyte brushes. We pay particular attention to studies that have attempted to match experimental friction data of polymer brush bilayers to results obtained using molecular simulations. We also critically look at the remaining challenges and key limitations to overcome and propose future modifications that could potentially improve agreement with experimental studies, thus enabling molecular simulations to be used predictively to modify the brush structure for optimal friction reduction.
Reflect In and Speak Out: An Autoethnographic Study on Race and the Embedded Sport Psychology Practitioner
Authors: Gupta Sahen
Published: January 2023

This paper aims to present a critical experience of race for the embedded sport psychology practitioner from a non-WEIRD, migratory, Black, Asian, and minority ethnic doctoral student and trainee sport psychologist in the United Kingdom. In particular, I move from intrapersonal reflection to an interpersonal cultural analysis that (re)considers some assumptions in existing training and applied sport psychology practice. In the consequential ripples to these reflections, I evaluate and argue to modify (a) ideology of the culturally isolated practitioner, (b) self-recognition of unconscious bias and discrimination, and (c) routes to incorporate antidiscriminatory practice training in sport psychology education pathways. Using a rigorous autoethnographic approach on this novel area reveals several implications for applied practice and the development of professional philosophy. Using conversation vignettes, personal lived experience accounts on the impact of race on education and development as a practitioner are discussed in this original work. The goal is to make the invisible visible by exploring vulnerabilities in practice, client engagement, and educational training in an equal and nondiscriminatory manner.
Contributions of Tasks With Different Cognitive Load to High School Students’ In-Class Physical Activity
Authors: Deng Anqi , Chen Ang
Published: January 2023

Purpose: Cognitive load theory focuses on providing appropriate cognitive engagement to facilitate knowledge learning. The purpose of this study was to determine the contributions of cognitive load on high school students’ in-class physical activity. Method: A stratified random sample of high school students (N = 150) who participated in a large curriculum intervention study provided the data. A path analysis and Hayes’ PROCESS analysis were used to test a correlation model and moderation effect from gender and race. Results: The results showed that the reasoning learning tasks directly contributed to their in-class physical activity (path coefficient = .54, p < .01) and the gender and race factors were not significant moderators (p > .05). Conclusion: The findings imply that high cognitive load tasks can facilitate in-class physical activity. The findings suggest the power of the concept-based physical education curriculum in providing productive learning opportunities to all students.
Tracking elusive and shifting identities of the global fishing fleet
Authors: Park Jaeyoon , Van Osdel Jennifer , Turner Joanna , Farthing Courtney M. , Miller Nathan A. , Linder Hannah L. , Ortuño Crespo Guillermo , Carmine Gabrielle , Kroodsma David A.
Published: January 2023

Illegal, unreported, and unregulated (IUU) fishing costs billions of dollars per year and is enabled by vessels obfuscating their identity. Here, we combine identities of ~35,000 vessels with a decade of GPS data to provide a global assessment of fishing compliance, reflagging patterns, and fishing by foreign-owned vessels. About 17% of high seas fishing is by potentially unauthorized or internationally unregulated vessels, with hot spots of this activity in the west Indian and the southwest Atlantic Oceans. In addition, reflagging, a tactic often used to obscure oversight, occurs in just a few ports primarily by fleets with high foreign ownership. Fishing by foreign-owned vessels is concentrated in parts of high seas and certain national waters, often flying flags of convenience. These findings can address the global scope of potential IUU fishing and enable authorities to improve oversight.
On-chip mechanical exceptional points based on an optomechanical zipper cavity
Authors: Wu Ning , Cui Kaiyu , Xu Qiancheng , Feng Xue , Liu Fang , Zhang Wei , Huang Yidong
Published: January 2023

Exceptional points (EPs) represent a distinct type of spectral singularity in non-Hermitian systems, and intriguing physics concepts have been studied with optical EPs recently. As a system beyond photonics, the mechanical oscillators coupling with many physical systems are expected to be further exploited EPs for mechanical sensing, topology energy transfer, nonreciprocal dynamics, etc. In this study, we demonstrated on-chip mechanical EPs with a silicon optomechanical zipper cavity, wherein two near-degenerate mechanical breathing modes are coupled via a single colocalized optical mode. By tailoring the dissipative and coherent couplings between two mechanical oscillators, the spectral splitting with 1/2 order response, a distinctive feature of EP, was observed successfully. Our work provides an integrated platform for investigating the physics related to mechanical EPs on silicon chips and suggests their possible applications for ultrasensitive measurements.
Using digital traces to build prospective and real-time county-level early warning systems to anticipate COVID-19 outbreaks in the United States
Authors: Stolerman Lucas M. , Clemente Leonardo , Poirier Canelle , Parag Kris V. , Majumder Atreyee , Masyn Serge , Resch Bernd , Santillana Mauricio
Published: January 2023

Coronavirus disease 2019 (COVID-19) continues to affect the world, and the design of strategies to curb disease outbreaks requires close monitoring of their trajectories. We present machine learning methods that leverage internet-based digital traces to anticipate sharp increases in COVID-19 activity in U.S. counties. In a complementary direction to the efforts led by the Centers for Disease Control and Prevention (CDC), our models are designed to detect the time when an uptrend in COVID-19 activity will occur. Motivated by the need for finer spatial resolution epidemiological insights, we build upon previous efforts conceived at the state level. Our methods—tested in an out-of-sample manner, as events were unfolding, in 97 counties representative of multiple population sizes across the United States—frequently anticipated increases in COVID-19 activity 1 to 6 weeks before local outbreaks, defined when the effective reproduction number

R
t

becomes larger than 1 for a period of 2 weeks.
Variant-to-gene mapping followed by cross-species genetic screening identifies GPI-anchor biosynthesis as a regulator of sleep
Authors: Palermo Justin , Chesi Alessandra , Zimmerman Amber , Sonti Shilpa , Pahl Matthew C. , Lasconi Chiara , Brown Elizabeth B. , Pippin James A. , Wells Andrew D. , Doldur-Balli Fusun , Mazzotti Diego R. , Pack Allan I. , Gehrman Phillip R. , Grant Struan F.A. , Keene Alex C.
Published: January 2023

Genome-wide association studies (GWAS) in humans have identified loci robustly associated with several heritable diseases or traits, yet little is known about the functional roles of the underlying causal variants in regulating sleep duration or quality. We applied an ATAC-seq/promoter focused Capture C strategy in human iPSC-derived neural progenitors to carry out a “variant-to-gene” mapping campaign that identified 88 candidate sleep effector genes connected to relevant GWAS signals. To functionally validate the role of the implicated effector genes in sleep regulation, we performed a neuron-specific RNA interference screen in the fruit fly,
Drosophila melanogaster
, followed by validation in zebrafish. This approach identified a number of genes that regulate sleep including a critical role for glycosylphosphatidylinositol (GPI)–anchor biosynthesis. These results provide the first physical variant-to-gene mapping of human sleep genes followed by a model organism–based prioritization, revealing a conserved role for GPI-anchor biosynthesis in sleep regulation.
Robust dynamic brain coactivation states estimated in individuals
Authors: Peng Xiaolong , Liu Qi , Hubbard Catherine S. , Wang Danhong , Zhu Wenzhen , Fox Michael D. , Liu Hesheng
Published: January 2023

A confluence of evidence indicates that brain functional connectivity is not static but rather dynamic. Capturing transient network interactions in the individual brain requires a technology that offers sufficient within-subject reliability. Here, we introduce an individualized network-based dynamic analysis technique and demonstrate that it is reliable in detecting subject-specific brain states during both resting state and a cognitively challenging language task. We evaluate the extent to which brain states show hemispheric asymmetries and how various phenotypic factors such as handedness and gender might influence network dynamics, discovering a right-lateralized brain state that occurred more frequently in men than in women and more frequently in right-handed versus left-handed individuals. Longitudinal brain state changes were also shown in 42 patients with subcortical stroke over 6 months. Our approach could quantify subject-specific dynamic brain states and has potential for use in both basic and clinical neuroscience research.
Ant waves—Spontaneous activity waves in fire-ant columns
Authors: Anderson Caleb , Goldsztein Guillermo , Fernandez-Nieves Alberto
Published: January 2023

Active matter, which includes crowds of organisms, is composed of constituents that independently consume and dissipate energy. Some active matter systems have been shown to sustain the propagation of various types of waves, resulting from the interplay between density and alignment. Here, we examine a type of solitary wave in dense two-dimensional columns of
Solenopsis invicta
, fire ants, in which the local activity, density and alignment all play a key role. We demonstrate that these waves are nonlinear and that they are composed of aligned ants that are constrained at the top by the time it takes disordered ants to activate and align and at the bottom by a density minimum enforced by gravity. Our results suggest that intrinsically switchable activity can be a productive framework to understand and trigger a broad range of wave-like behaviors, including stampedes in crowds and herds.
High urban NO

x

triggers a substantial chemical downward flux of ozone
Authors: Karl Thomas , Lamprecht Christian , Graus Martin , Cede Alexander , Tiefengraber Martin , Vila-Guerau de Arellano Jordi , Gurarie David , Lenschow Donald
Published: January 2023

Nitrogen oxides (NO

x

) play a central role in catalyzing tropospheric ozone formation. Nitrogen dioxide (NO
2
) has recently reemerged as a key target for air pollution control measures, and observational evidence points toward a limited understanding of ozone in high-NO

x

environments. A complete understanding of the mechanisms controlling the rapid atmospheric cycling between ozone (O
3
)–nitric oxide (NO)–NO
2
in high-NO

x

regimes at the surface is therefore paramount but remains challenging because of competing dynamical and chemical effects. Here, we present long-term eddy covariance measurements of O
3
, NO, and NO
2
, over an urban area, that allow disentangling important physical and chemical processes. When generalized, our findings suggest that the depositional O
3
flux near the surface in urban environments is negligible compared to the flux caused by chemical conversion of O
3
. This leads to an underestimation of the Leighton ratio and is a key process for modulating urban NO
2
mixing ratios. As a consequence, primary NO
2
emissions have been significantly overestimated.
Epigenetic resetting in the human germ line entails histone modification remodeling
Authors: Gruhn Wolfram H. , Tang Walfred W.C. , Dietmann Sabine , Alves-Lopes João P. , Penfold Christopher A. , Wong Frederick C. K. , Ramakrishna Navin B. , Surani M. Azim
Published: January 2023

Epigenetic resetting in the mammalian germ line entails acute DNA demethylation, which lays the foundation for gametogenesis, totipotency, and embryonic development. We characterize the epigenome of hypomethylated human primordial germ cells (hPGCs) to reveal mechanisms preventing the widespread derepression of genes and transposable elements (TEs). Along with the loss of DNA methylation, we show that hPGCs exhibit a profound reduction of repressive histone modifications resulting in diminished heterochromatic signatures at most genes and TEs and the acquisition of a neutral or paused epigenetic state without transcriptional activation. Efficient maintenance of a heterochromatic state is limited to a subset of genomic loci, such as evolutionarily young TEs and some developmental genes, which require H3K9me3 and H3K27me3, respectively, for efficient transcriptional repression. Accordingly, transcriptional repression in hPGCs presents an exemplary balanced system relying on local maintenance of heterochromatic features and a lack of inductive cues.
Drone-assisted collection of environmental DNA from tree branches for biodiversity monitoring
Authors: Aucone Emanuele , Kirchgeorg Steffen , Valentini Alice , Pellissier Loïc , Deiner Kristy , Mintchev Stefano
Published: January 2023

The protection and restoration of the biosphere is crucial for human resilience and well-being, but the scarcity of data on the status and distribution of biodiversity puts these efforts at risk. DNA released into the environment by organisms, i.e., environmental DNA (eDNA), can be used to monitor biodiversity in a scalable manner if equipped with the appropriate tool. However, the collection of eDNA in terrestrial environments remains a challenge because of the many potential surfaces and sources that need to be surveyed and their limited accessibility. Here, we propose to survey biodiversity by sampling eDNA on the outer branches of tree canopies with an aerial robot. The drone combines a force-sensing cage with a haptic-based control strategy to establish and maintain contact with the upper surface of the branches. Surface eDNA is then collected using an adhesive surface integrated in the cage of the drone. We show that the drone can autonomously land on a variety of branches with stiffnesses between 1 and 10
3
 newton/meter without prior knowledge of their structural stiffness and with robustness to linear and angular misalignments. Validation in the natural environment demonstrates that our method is successful in detecting animal species, including arthropods and vertebrates. Combining robotics with eDNA sampling from a variety of unreachable aboveground substrates can offer a solution for broad-scale monitoring of biodiversity.
CD200
+
cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy
Authors: Wang Xinxin , Zha Haoran , Wu Wei , Yuan Ting , Xie Shuanglong , Jin Zheng , Long Haixia , Yang Fei , Wang Zhongyu , Zhang Anmei , Gao Jianbao , Jiang Ying , Wang Lujing , Hu Chunyan , Wan Yisong Y. , Li Qi-Jing , Symonds Alistair L. J. , Jia Qingzhu , Zhu Bo
Published: January 2023

Anti–PD-1/PD-L1 therapy, either by anti–PD-1 antibody or anti–PD-L1 antibody, has efficacy by reinvigorating tumor-infiltrating CD8
+
T cells in a subset of patients with cancer, but it has unequal effects on heterogeneous CD8
+
T cell populations. Hence, the subset crucial to efficacious PD-1 blockade therapy remains elusive. Here, we found an increase in tumor-infiltrating CD200
+
cytotoxic T lymphocytes (CTLs) upon PD-1/PD-L1 blockade, with higher proportions of CD200
+
T cells positively related to a favorable clinical outcome to anti–PD-1/PD-L1 therapy in three independent cohorts of patients with cancer. Using multiple mouse tumor models, we demonstrated that CD200
+
CTLs are essential for efficacious anti–PD-L1 therapy. Mechanistically, we observed a unique chromatin landscape in CD200
+
CTLs and found that these cells are enriched for tumor antigen–specific CTLs and have antitumor effector functions. Coinoculation of CD200
+
CTLs with tumor cells led to robust tumor regression in two transplanted mouse models. Clinically, we found that infiltration of CD200
+
CTLs into tumors could predict immunotherapy efficacy in six patient cohorts. Together, our findings reveal that CD200
+
CTLs in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy and could serve as a predictor of successful immunotherapy in the clinic.
The c-Abl inhibitor IkT-148009 suppresses neurodegeneration in mouse models of heritable and sporadic Parkinson’s disease
Authors: Karuppagounder Senthilkumar S. , Wang Hu , Kelly Terence , Rush Roger , Nguyen Richard , Bisen Shivani , Yamashita Yoko , Sloan Nicholas , Dang Brianna , Sigmon Alexander , Lee Hyeun Woo , Marino Lee Shirley , Watkins Leslie , Kim Erica , Brahmachari Saurav , Kumar Manoj , Werner Milton H. , Dawson Ted M. , Dawson Valina L.
Published: January 2023

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease of the central nervous system, with an estimated 5,000,000 cases worldwide. PD pathology is characterized by the accumulation of misfolded α-synuclein, which is thought to play a critical role in the pathogenesis of the disease. Animal models of PD suggest that activation of Abelson tyrosine kinase (c-Abl) plays an essential role in the initiation and progression of α-synuclein pathology and initiates processes leading to degeneration of dopaminergic and nondopaminergic neurons. Given the potential role of c-Abl in PD, a c-Abl inhibitor library was developed to identify orally bioavailable c-Abl inhibitors capable of crossing the blood-brain barrier based on predefined characteristics, leading to the discovery of IkT-148009. IkT-148009, a brain-penetrant c-Abl inhibitor with a favorable toxicology profile, was analyzed for therapeutic potential in animal models of slowly progressive, α-synuclein–dependent PD. In mouse models of both inherited and sporadic PD, IkT-148009 suppressed c-Abl activation to baseline and substantially protected dopaminergic neurons from degeneration when administered therapeutically by once daily oral gavage beginning 4 weeks after disease initiation. Recovery of motor function in PD mice occurred within 8 weeks of initiating treatment concomitantly with a reduction in α-synuclein pathology in the mouse brain. These findings suggest that IkT-148009 may have potential as a disease-modifying therapy in PD.
Tryptanthrin Reduces Campylobacter jejuni Colonization in the Chicken Gut by a Bactericidal Mechanism
Authors: Iwata Taketoshi , Watanabe-Yanai Ayako , Tamamura-Andoh Yukino , Arai Nobuo , Akiba Masato , Kusumoto Masahiro
Published: January 2023

Campylobacter
is a widespread pathogen in the food chain of chickens. Once chickens become infected, large numbers of
Campylobacter
cells are excreted in their feces.
Do SARS-CoV-2 Variants Differ in Their Neuropathogenicity?
Authors: Bauer Lisa , van Riel Debby
Published: January 2023

Neurological complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are a huge societal problem. Although the neuropathogenicity of SARS-CoV-2 is not yet fully understood, there is evidence that SARS-CoV-2 can invade and infect cells of the central nervous system.
The Riffomonas YouTube Channel: An Educational Resource To Foster Reproducible Research Practices
Authors: Schloss Patrick D.
Published: January 2023

Methods for analyzing data in a reproducible manner are often viewed as impenetrable to scientists more familiar with laboratory research. The Riffomonas YouTube channel is committed to teaching these scientists and others how to engage in reproducible research using modern data science tools.
Whole Genome-Based Characterization of Multidrug Resistant Enterobacter and Klebsiella aerogenes Isolates from Lebanon
Authors: Merhi Georgi , Amayri Sara , Bitar Ibrahim , Araj George F. , Tokajian Sima
Published: January 2023

Drug resistance is an increasing global public health threat that involves most disease-causing organisms and antimicrobial drugs. Drug-resistant organisms spread in health care settings, and resistance to multiple drugs is common.
Genomic Characterization of Salmonella enterica serovar Weltevreden Associated with Human Diarrhea
Authors: Zhang Jianmin , Peng Zhong , Chen Kaifeng , Zhan Zeqiang , Shen Haiyan , Feng Saixiang , Gou Hongchao , Qu Xiaoyun , Ziemann Mark , Layton Daniel S. , Wang Xiangru , Chen Huanchun , Wu Bin , Xu Xuebin , Liao Ming
Published: January 2023

Salmonella
Weltevreden is a pathogen associated with human diarrheal diseases found across the globe. However, knowledge of the genomics and epidemiology of this pathogen is still limited.
Supplemental Material: Carbon released by sill intrusion into young sediments measured through scientific drilling
Authors: Lizarralde Daniel , al. et
Published: January 2023

List of International Ocean Discovery Program (IODP) Expedition 385 co-author scientists; pore-water sulfate and methane profiles for Sites U1545 and U1546; and details of the site-to-site stratigraphic correlation. 
Supplemental Material: Carbon isotope and biostratigraphic evidence for an expanded Paleocene–Eocene Thermal Maximum sedimentary record in the deep Gulf of Mexico
Authors: Vimpere Lucas , al. et
Published: January 2023

Material and methods used in this study, details of the Rock-Eval, granulometric, carbon isotope, and calcareous nannofossil analyses, and correlation of the carbon isotopic curve with other sections worldwide. 
Interactome of Paraoxonase PON2 Reveals New Pathways for Tumor Growth Regulation
Authors: Karlov V. D. , Pestov N. B. , Shakhparonov M. I. , Korneenko T. V.
Published: January 2023

The interactome of paraoxonase-2 encoded by the PON2 gene was investigated. A cDNA library was screened using a yeast two-hybrid system to search for new proteins interacting with human PON2. Analysis of the identified candidates, along with previously published data on interactors obtained by other methods, indicates the presence of a significant number of indirect interactions between PON2 and EGFR and, consequently, possible regulation of tumor growth with mutant EGFR involving PON2.
How to design and deliver a successful paediatric placement for medical students
Authors: Vallabhaneni Pramodh , Thankachan Divya
Published: January 2023

Paediatric placement is an invaluable opportunity for medical students to gain experience in the specialty. It is often their first tangible experience observing how children are looked after. An ideal placement would offer diverse and immersive clinical experiences while providing insight into a career in paediatrics. This article provides a template for a paediatric placement appealing to current medical students and future generations constructed on the strong foundations of evidence-based practices in medical education.
Nephrocolocutaneous fistula from a staghorn calculus
Authors: Jacinto Cesar Karunungan , Lim Michael Geoffrey Lee , Lopez Marc Paul Jose , Serrano Dennis Pestano
Published: January 2023

Fistula formation between the kidney, colon and the skin is an extremely rare complication arising from renal infections secondary to renal stone formation. During the 1980s, reports of nephrocolic fistulas, with or without involvement of the skin, were commonly caused by genitourinary tuberculosis. Due to improvements in diagnosis and specifically the development of anti-Koch’s therapy, the incidence of nephrocolic or nephrocolocutaneous fistulas has become uncommon especially in developed countries.

We report a case of a patient residing in a developing country, presenting with a 20-year history of a left flank lesion extruding minimal purulent output daily. He was seen at the emergency department due to weakness and was managed as a case of urosepsis. Contrast-enhanced CT scan and fistulogram showed a staghorn calculus in the left kidney with connections to the descending colon and skin. The patient eventually underwent a left hemicolectomy with en bloc excision of the kidney and fistula tract.
Ruptured ectopic molar pregnancy and ruptured uterine fibroid: a challenging rare diagnosis
Authors: Tanudisastro Marietta , Chatterjee Rahul , Anderson Lyndal , Smirnova Sofia
Published: January 2023

Although rare and unusual occurrences, a ruptured ectopic molar pregnancy (MP) and a ruptured uterine fibroid can lead to significant maternal morbidity and mortality. We present a unique case of these complications developing concurrently—resulting in the haemodynamic compromise of an otherwise healthy young female patient. The patient underwent a diagnostic laparoscopy which converted into a laparotomy, salpingectomy and myomectomy. Comprehensive histopathology confirmed the diagnosis of a ruptured ectopic complete MP and ruptured uterine fibroid. The patient recovered quickly within days. Prompt definitive management, conclusive histopathology and adequate follow-up were the hallmarks of this singular case. These key factors lead to the rare diagnosis of ruptured ectopic MP and uterine fibroid, prevention of adverse outcomes and provision of comprehensive patient care.