bluuebunny/crossref_metadata_2025 huggingface dataset:
Priority setting for health technology adoption at the national level: Lessons learned over 25 years’ experience
Authors: Luxenburg Osnat , Morginstin Tal , Myers Vicki , Saban Mor , Shemer Joshua , Wilf-Miron Rachel
Published: November 2023

Background

Limited health budgets and continual advancement of health technologies require mechanisms for prioritization. Israel, with a publicly funded health service basket, has implemented and optimized such a health technology assessment process since 1999.

We describe the process of evaluating technologies according to the Israeli model, analyze its outputs and benefits over two decades of implementation, and compare its key features with international experience.

Methods

Retrospective data were collected between 1998 and 2023, including work processes, committee composition, number of applications submitted and approved by a clinical domain, and yearly cost of the basket. Features were evaluated within the evidence-informed deliberative process (EDP) framework.

Results

This national model involves relevant stake holders in a participatory and transparent process, in a timely manner, and is accepted by the public, health professionals, and policy makers, facilitating early adoption of the newest medical technologies. Between 11 and 19 percent of applications are approved for reimbursement annually, mostly pharmaceuticals. On average 26 percent of approved technologies are added to the list without additional budget. Major domains of approved technologies were oncology, cardiology, and neurology.

Conclusions

Israel created a unique model for the expansion of the health service basket. Despite an increasing number of applications and rising costs, the mechanism enables a consensus to be reached on which technologies to fund, while remaining within budget constraints and facilitating immediate implementation. The process, which prioritizes transparency and stake holder involvement, allows just a resource allocation while maximizing the adoption of novel technologies, contributing to an outstanding national level of health despite relatively low health spending.
Leveraging the developmental neuroscience of caregiving to promote resilience among youth exposed to adversity
Authors: Gee Dylan G. , Cohodes Emily M.
Published: November 2023

Early adversity is a major risk factor for the emergence of psychopathology across development. Identifying mechanisms that support resilience, or favorable mental health outcomes despite exposure to adversity, is critical for informing clinical intervention and guiding policy to promote youth mental health. Here we propose that caregivers play a central role in fostering resilience among children exposed to adversity via caregiving influences on children’s corticolimbic circuitry and emotional functioning. We first delineate the numerous ways that caregivers support youth emotional learning and regulation and describe how early attachment lays the foundation for optimal caregiver support of youth emotional functioning in a developmental stage-specific manner. Second, we outline neural mechanisms by which caregivers foster resilience—namely, by modulating offspring corticolimbic circuitry to support emotion regulation and buffer stress reactivity. Next, we highlight the importance of developmental timing and sensitive periods in understanding caregiving-related mechanisms of resilience. Finally, we discuss clinical implications of this line of research and how findings can be translated to guide policy that promotes the well-being of youth and families.
Contract lenses: Reasoning about bidirectional programs via calculation
Authors: ZHANG HANLIANG , TANG WENHAO , XIE RUIFENG , WANG MENG , HU ZHENJIANG
Published: November 2023

Bidirectional transformations (BXs) are a mechanism for maintaining consistency between multiple representations of related data. The lens framework, which usually constructs BXs from lens combinators, has become the mainstream approach to BX programming because of its modularity and correctness by construction. However, the involved bidirectional behaviors of lenses make the equational reasoning and optimization of them much harder than unidirectional programs. We propose a novel approach to deriving efficient lenses from clear specifications via program calculation, a correct-by-construction approach to reasoning about functional programs by algebraic laws. To support bidirectional program calculation, we propose contract lenses, which extend conventional lenses with a pair of predicates to enable safe and modular composition of partial lenses. We define several contract-lens combinators capturing common computation patterns including

$\textit{fold}, \textit{filter},\textit{map}$

, and

$\textit{scan}$

, and develop several bidirectional calculation laws to reason about and optimize contract lenses. We demonstrate the effectiveness of our new calculation framework based on contract lenses with nontrivial examples.
The Dawn of the Jazz Age in the Caribbean: Dance, Consumer Culture, and the Imperial Shape of Modern Entertainment
Authors: OSPINA ROMERO SERGIO
Published: November 2023

After 1917 the word ‘jazz’ disseminated rapidly throughout the world attaining, along the way, a multiplicity of meanings, sometimes related to musical practices from the United States, but often associated with a diverse array of things, objects, ideas, and situations in the worlds of music entertainment, dance, leisure, and fashion. In the Caribbean, this process entailed not only the constitution of jazz as a symbol of social modernity but also revealed a long history of exchanges between the United States and the Caribbean – not to mention the Afrodiasporic origins of jazz. By examining jazz as a by-product and an expression of Caribbean modernity, this article disentangles some of the cultural meanings of the word ‘jazz’ in the Caribbean between 1917 and 1920, considering, ultimately, how imagining jazz as Caribbean was inevitably intertwined with imagining it as modern.
Exploring the Validity of the Work Preferences Questionnaire
Authors: Stamate Alina N. , Denis Pascale L.
Published: November 2023

Abstract: This study aimed was to develop and validate a new instrument called the Work Preferences Questionnaire (WPQ) to measure individuals’ preferences for work characteristics that are relevant to today’s work environment. A multi-step approach and two samples were used to develop and validate the WPQ across various industries. In the first study, a group of experts developed a bank of items that were then administered to 984 workers. Exploratory factor analysis revealed a nine-factor structure with good internal consistency. In the second study, an independent sample of 687 workers was used to confirm the factorial structure and highlight the distinctness of the work preference dimensions. The study found small mean differences in interindividual preference scores based on age and confirmed data equivalence between gender and education level. The WPQ addresses limitations of existing measures by focusing on a narrow set of work preferences that are highly relevant in the current work environment and includes modern aspects such as teleworking and work-life balance. The WPQ promises to be an effective tool for research and human resources practices, enabling individuals and organizations to better understand work preferences and make informed decisions about work design and personnel selection.
Committed Global Warming Risks Triggering Multiple Climate Tipping Points
Authors: Abrams Jesse F. , Huntingford Chris , Williamson Mark S. , Armstrong McKay David I. , Boulton Chris A. , Buxton Joshua E. , Sakschewski Boris , Loriani Sina , Zimm Caroline , Winkelmann Ricarda , Lenton Timothy M.
Published: November 2023

Many scenarios for limiting global warming to 1.5°C assume planetary‐scale carbon dioxide removal sufficient to exceed anthropogenic emissions, resulting in radiative forcing falling and temperatures stabilizing. However, such removal technology may prove unfeasible for technical, environmental, political, or economic reasons, resulting in continuing greenhouse gas emissions from hard‐to‐mitigate sectors. This may lead to constant concentration scenarios, where net anthropogenic emissions remain non‐zero but small, and are roughly balanced by natural carbon sinks. Such a situation would keep atmospheric radiative forcing roughly constant. Fixed radiative forcing creates an equilibrium “committed” warming, captured in the concept of “equilibrium climate sensitivity.” This scenario is rarely analyzed as a potential extension to transient climate scenarios. Here, we aim to understand the planetary response to such fixed concentration commitments, with an emphasis on assessing the resulting likelihood of exceeding temperature thresholds that trigger climate tipping points. We explore transients followed by respective equilibrium committed warming initiated under low to high emission scenarios. We find that the likelihood of crossing the 1.5°C threshold and the 2.0°C threshold is 83% and 55%, respectively, if today's radiative forcing is maintained until achieving equilibrium global warming. Under the scenario that best matches current national commitments (RCP4.5), we estimate that in the transient stage, two tipping points will be crossed. If radiative forcing is then held fixed after the year 2100, a further six tipping point thresholds are crossed. Achieving a trajectory similar to RCP2.6 requires reaching net‐zero emissions rapidly, which would greatly reduce the likelihood of tipping events.
Examining Infrasound Propagation at High Spatial Resolution Using a Nodal Seismic Array
Authors: Toney Liam , Fee David , Schmandt Brandon , Bishop Jordan W.
Published: November 2023

Infrasound—acoustic waves in the atmosphere below 20 Hz—is a useful monitoring tool. Topography and atmospheric structure strongly control infrasound propagation, and at common source–receiver distances neither of these effects can be ignored when quantitative source constraints are sought. Detailed spatial measurements of the infrasound wavefield would inform propagation models and improve source estimates. However, the “large‐N” deployment strategy now well‐known in seismology has not yet been realized for infrasound studies. Here, we use the 900‐node seismic array from the 2014 Imaging Magma Under St. Helens (iMUSH) experiment as a proxy for a large‐N infrasound network, by leveraging acoustic–seismic coupled arrivals. The active‐source component of iMUSH consisted of 23 shallowly buried explosions around Mount Saint Helens volcano; these explosions produced epicentral infrasound recorded on the nodes. We find that the bulk presence of ground‐coupled infrasound on the nodes is controlled by wind noise and source–receiver distance, with observed arrivals for eight explosions. Explosions with the most extensive coupling produce complex spatial waveform patterns across the array. These patterns are related to both topographic and atmospheric propagation effects, as well as spatially variable site (coupling) effects. We compare our observations to simple topographic diffraction and high‐resolution wind advection models, and full‐wave numerical simulations. We find strong spatial correlations between (a) coupled arrival strength and modeled topographic obstruction and (b) coupled arrival time and along‐path winds. Our seismoacoustic analyses and results are applicable to other existing and future nodal seismic data sets and can expand the utility of such deployments.
Correspondence of Drought Occurrences at Multi‐Temporal Scales Between North China and Upper Hanjiang River
Authors: Zhang Xiaodan , Ren Guoyu , Mikami Takehiko , Matsumoto Jun , Yang Guowei
Published: November 2023

Using the drought and flood grades, the historical co‐drought probabilities of the water source area (i.e., the Upper Hanjiang River or UH) and the receiving area (i.e., North China or NC) of the Middle Route of the South‐to‐North Water Diversion project from 1470 to 2017 were analyzed. It was found that there is relatively high possibility for co‐droughts to occur in the UH and NC at interannual to multi‐decadal time scales. When extreme drought occurred in NC, there was a 52% probability that the UH was on the drier side and even a 40% probability of severe drought. During the three typical severe drought events that occurred mainly in NC (i.e., 1637–1643, 1877–1878, and 1997–2002), severe droughts also appeared in the UH, with 1877–1878 even more severe than in NC. Among the seven driest years of the study period in NC (i.e., 1640, 1641, 1832, 1920, 1965, 1968, and 1997), only 1832 was wet in the UH, and 1920 even experienced the same severe region‐wide drought as NC did. Furthermore, when severe consecutive droughts occurred in NC, there was at least a 66% probability that the UH was also experiencing a drought. In addition, there were obvious cycles of drought and flood variability of around 3–6 years, 10 years, 30 years, and 55–80 years in both the UH and NC. These findings are of importance to in‐depth understanding of the regional drought variability and its mechanism at varied temporal scales and the effective management of the world‐class hydro project.
Wave Velocities and Poisson Ratio in a Loose Sandy Martian Regolith Simulant Under Low Stresses: 1. Laboratory Investigation
Authors: Betancourt J. P. Castillo , Delage P. , Caicedo B. , Lognonné P. , Banerdt B.
Published: November 2023

Wave velocity measurements were performed on Fontainebleau sand samples used as a Martian regolith simulant to investigate the elastic properties of the surface material at the InSight landing site on Mars (Elysium Planitia). Loose samples (density 1.4 Mg/m3, density index 6%) were prepared by using the pluviation method to mimic the low regolith density at the InSight landing site. A novel device derived from triaxial testing was designed to measure wave velocities at low stresses along a horizontal cylindrical specimen. Four tests were made, in which the confining stress was applied by applying a vacuum between 1 and 80 kPa. Wave velocities were measured by using bender elements under stresses as low as 1.75 kPa, a very low value compared to the standard stress ranges generally considered in terrestrial geotechnics (>10 kPa). The changes in compression and shear wave velocities obey a standard power law, with two slightly different exponents for Vp and Vs, indicating a not perfectly elastic behavior. Data showed greater variability below 5 kPa, indicating some limitations of the bender element technique in this range. A slight decrease in Poisson ratio was detected below 5 kPa, which certainly deserves more investigation. This investigation is useful to better analyze the data of the InSight mission, both in terms of wave propagation at the surface and to interpret some in situ elastic tests carried out with the scoop. These data are interpreted in the light of a granular contact mechanics theory in a companion paper.
Iterative Gradient Correction (IGC) Method for True Height Analysis of Ionograms
Authors: Ankita M. , Tulasi Ram S.
Published: November 2023

Inversion of precise true height electron density profile from the measured virtual heights by the Ionosonde is a quite challenging and ill‐posed problem. In this paper, we present a new method to compute the true height profiles from ionograms that relies on computing the propagation path of radio waves with time. This method does not use predefined polynomial functions to fit the vertical electron density distribution; hence, it is free from fitting errors. Instead, this method implements iterative corrections in the electron density gradient between the successive points and progressively reconstructs the true height profile. This Iterative Gradient Correction (IGC) method assures minimizing the error to below a tolerance limit at all sampled points on the ionogram. The true height profiles derived from this method exhibit better accuracy than those derived from the widely used POLynomial ANalysis, particularly, at cusp and F2‐peak regions. Further, the IGC method gives the best results at higher sampling resolutions of ionograms and is less sensitive to scaling errors.
Assessment of the Value of Remotely Sensed Surface Water Extent Data for the Calibration of a Lumped Hydrological Model
Authors: Meyer Oliveira Aline , van Meerveld H. J. (Ilja) , Vis Marc , Seibert Jan
Published: November 2023

For many catchments, there is insufficient field data to calibrate the hydrological models that are needed to answer water resources management questions. One way to overcome this lack of data is to use remotely sensed data. In this study, we assess whether Landsat‐based surface water extent observations can inform the calibration of a lumped bucket‐type model for Brazilian catchments. We first performed synthetic experiments with daily, monthly, and limited monthly data (April–October), assuming a perfect monotonic relation between streamflow and stream width. The median relative performance was 0.35 for daily data and 0.17 for monthly data, where values above 0 imply an improvement in model performance compared to the lower benchmark. This indicates that the limited temporal resolution of remotely sensed data is not an impediment for model calibration. In a second step, we used real remotely sensed water extent data for calibration. For only 76 of the 671 sites the remotely sensed water extent was large and variable enough to be used for model calibration. For 30% of these sites, calibration with the actual remotely sensed water extent data led to a model fit that was better than the lower benchmark (i.e., relative performance >0). Model performance increased with river width and variation therein. This indicates that the coarse spatial resolution of the freely‐available, long time series of water extent used in this study hampered model calibration. We, therefore, expect that newer higher‐resolution imagery will be helpful for model calibration for more sites, especially when time series length increases.
Preneoplastic liver colonization by 11p15.5 altered mosaic cells in young children with hepatoblastoma
Authors: Pilet Jill , Hirsch Theo Z. , Gupta Barkha , Roehrig Amélie , Morcrette Guillaume , Pire Aurore , Letouzé Eric , Fresneau Brice , Taque Sophie , Brugières Laurence , Branchereau Sophie , Chardot Christophe , Aerts Isabelle , Sarnacki Sabine , Fabre Monique , Guettier Catherine , Rebouissou Sandra , Zucman-Rossi Jessica
Published: November 2023

Pediatric liver tumors are very rare tumors with the most common diagnosis being hepatoblastoma. While hepatoblastomas are predominantly sporadic, around 15% of cases develop as part of predisposition syndromes such as Beckwith-Wiedemann (11p15.5 locus altered). Here, we identify mosaic genetic alterations of 11p15.5 locus in the liver of hepatoblastoma patients without a clinical diagnosis of Beckwith-Wiedemann syndrome. We do not retrieve these alterations in children with other types of pediatric liver tumors. We show that mosaic 11p15.5 alterations in liver FFPE sections of hepatoblastoma patients display IGF2 overexpression and H19 downregulation together with an alteration of the liver zonation. Moreover, mosaic livers’ microenvironment is enriched in extracellular matrix and angiogenesis. Spatial transcriptomics and single-nucleus RNAseq analyses identify a 60-gene signature in 11p15.5 altered hepatocytes. These data provide insights for 11p15.5 mosaicism detection and its functional consequences during the early steps of carcinogenesis.
Elevator-like movements of prestin mediate outer hair cell electromotility
Authors: Kuwabara Makoto F. , Haddad Bassam G. , Lenz-Schwab Dominik , Hartmann Julia , Longo Piersilvio , Huckschlag Britt-Marie , Fuß Anneke , Questino Annalisa , Berger Thomas K. , Machtens Jan-Philipp , Oliver Dominik
Published: November 2023

The outstanding acuity of the mammalian ear relies on cochlear amplification, an active mechanism based on the electromotility (eM) of outer hair cells. eM is a piezoelectric mechanism generated by little-understood, voltage-induced conformational changes of the anion transporter homolog prestin (SLC26A5). We used a combination of molecular dynamics (MD) simulations and biophysical approaches to identify the structural dynamics of prestin that mediate eM. MD simulations showed that prestin samples a vast conformational landscape with expanded (ES) and compact (CS) states beyond previously reported prestin structures. Transition from CS to ES is dominated by the translational-rotational movement of prestin’s transport domain, akin to elevator-type substrate translocation by related solute carriers. Reversible transition between CS and ES states was supported experimentally by cysteine accessibility scanning, cysteine cross-linking between transport and scaffold domains, and voltage-clamp fluorometry (VCF). Our data demonstrate that prestin’s piezoelectric dynamics recapitulate essential steps of a structurally conserved ion transport cycle.
High-resolution neural recordings improve the accuracy of speech decoding
Authors: Duraivel Suseendrakumar , Rahimpour Shervin , Chiang Chia-Han , Trumpis Michael , Wang Charles , Barth Katrina , Harward Stephen C. , Lad Shivanand P. , Friedman Allan H. , Southwell Derek G. , Sinha Saurabh R. , Viventi Jonathan , Cogan Gregory B.
Published: November 2023

Patients suffering from debilitating neurodegenerative diseases often lose the ability to communicate, detrimentally affecting their quality of life. One solution to restore communication is to decode signals directly from the brain to enable neural speech prostheses. However, decoding has been limited by coarse neural recordings which inadequately capture the rich spatio-temporal structure of human brain signals. To resolve this limitation, we performed high-resolution, micro-electrocorticographic (µECoG) neural recordings during intra-operative speech production. We obtained neural signals with 57× higher spatial resolution and 48% higher signal-to-noise ratio compared to macro-ECoG and SEEG. This increased signal quality improved decoding by 35% compared to standard intracranial signals. Accurate decoding was dependent on the high-spatial resolution of the neural interface. Non-linear decoding models designed to utilize enhanced spatio-temporal neural information produced better results than linear techniques. We show that high-density µECoG can enable high-quality speech decoding for future neural speech prostheses.
Foxp3 orchestrates reorganization of chromatin architecture to establish regulatory T cell identity
Authors: Liu Zhi , Lee Dong-Sung , Liang Yuqiong , Zheng Ye , Dixon Jesse R.
Published: November 2023

Chromatin conformation reorganization is emerging as an important layer of regulation for gene expression and lineage specification. Yet, how lineage-specific transcription factors contribute to the establishment of cell type-specific 3D chromatin architecture in the immune cells remains unclear, especially for the late stages of T cell subset differentiation and maturation. Regulatory T cells (Treg) are mainly generated in the thymus as a subpopulation of T cells specializing in suppressing excessive immune responses. Here, by comprehensively mapping 3D chromatin organization during Treg cell differentiation, we show that Treg-specific chromatin structures were progressively established during its lineage specification, and highly associated with Treg signature gene expression. Additionally, the binding sites of Foxp3, a Treg lineage specifying transcription factor, were highly enriched at Treg-specific chromatin loop anchors. Further comparison of the chromatin interactions between wide-type Tregs versus Treg cells from Foxp3 knock-in/knockout or newly-generated Foxp3 domain-swap mutant mouse revealed that Foxp3 was essential for the establishment of Treg-specific 3D chromatin architecture, although it was not dependent on the formation of the Foxp3 domain-swapped dimer. These results highlighted an underappreciated role of Foxp3 in modulating Treg-specific 3D chromatin structure formation.
An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission
Authors: Li Weizhong , Wang Tao , Rajendrakumar Arunraj M. , Acharya Gyanada , Miao Zizhen , Varghese Berin P. , Yu Hailiang , Dhakal Bibek , LeRoith Tanya , Karunakaran Athira , Tuo Wenbin , Zhu Xiaoping
Published: November 2023

SARS-CoV-2 is primarily transmitted through droplets and airborne aerosols, and in order to prevent infection and reduce viral spread vaccines should elicit protective immunity in the airways. The neonatal Fc receptor (FcRn) transfers IgG across epithelial barriers and can enhance mucosal delivery of antigens. Here we explore FcRn-mediated respiratory delivery of SARS-CoV-2 spike (S). A monomeric IgG Fc was fused to a stabilized spike; the resulting S-Fc bound to S-specific antibodies and FcRn. Intranasal immunization of mice with S-Fc and CpG significantly induced antibody responses compared to the vaccination with S alone or PBS. Furthermore, we intranasally immunized mice or hamsters with S-Fc. A significant reduction of virus replication in nasal turbinate, lung, and brain was observed following nasal challenges with SARS-CoV-2 and its variants. Intranasal immunization also significantly reduced viral airborne transmission in hamsters. Nasal IgA, neutralizing antibodies, lung-resident memory T cells, and bone-marrow S-specific plasma cells mediated protection. Hence, FcRn delivers an S-Fc antigen effectively into the airway and induces protection against SARS-CoV-2 infection and transmission.
Printed sustainable elastomeric conductor for soft electronics
Authors: Lv Jian , Thangavel Gurunathan , Xin Yangyang , Gao Dace , Poh Wei Church , Chen Shaohua , Lee Pooi See
Published: November 2023

The widespread adoption of renewable and sustainable elastomers in stretchable electronics has been impeded by challenges in their fabrication and lacklustre performance. Here, we realize a printed sustainable stretchable conductor with superior electrical performance by synthesizing sustainable and recyclable vegetable oil polyurethane (VegPU) elastomeric binder and developing a solution sintering method for their composites with Ag flakes. The binder impedes the propagation of cracks through its porous network, while the solution sintering reaction reduces the resistance increment upon stretching, resulting in high stretchability (350%), superior conductivity (12833 S cm−1), and low hysteresis (0.333) after 100% cyclic stretching. The sustainable conductor was used to print durable and stretchable impedance sensors for non-obstructive detection of fruit maturity in food sensing technology. The combination of sustainable materials and strategies for realizing high-performance stretchable conductors provides a roadmap for the development of sustainable stretchable electronics.
Evolution of a ZW sex chromosome system in willows
Authors: Hu Nan , Sanderson Brian J. , Guo Minghao , Feng Guanqiao , Gambhir Diksha , Hale Haley , Wang Deyan , Hyden Brennan , Liu Jianquan , Smart Lawrence B. , DiFazio Stephen P. , Ma Tao , Olson Matthew S.
Published: November 2023

Transitions in the heterogamety of sex chromosomes (e.g., XY to ZW or vice versa) fundamentally alter the genetic basis of sex determination, however the details of these changes have been studied in only a few cases. In an XY to ZW transition, the X is likely to give rise to the W because they both carry feminizing genes and the X is expected to harbour less genetic load than the Y. Here, using a new reference genome for Salix exigua, we trace the X, Y, Z, and W sex determination regions during the homologous transition from an XY system to a ZW system in willow (Salix). We show that both the W and the Z arose from the Y chromosome. We find that the new Z chromosome shares multiple homologous putative masculinizing factors with the ancestral Y, whereas the new W lost these masculinizing factors and gained feminizing factors. The origination of both the W and Z from the Y was permitted by an unexpectedly low genetic load on the Y and this indicates that the origins of sex chromosomes during homologous transitions may be more flexible than previously considered.
Adjustment of light-responsive NADP dynamics in chloroplasts by stromal pH
Authors: Fukuda Yusuke , Ishiyama Chinami , Kawai-Yamada Maki , Hashida Shin-nosuke
Published: November 2023

Cyclic electron transfer (CET) predominates when NADP+ is at basal levels, early in photosynthetic induction; however, the mechanism underlying the subsequent supply of NADP+ to fully drive steady-state linear electron transfer remains unclear. Here, we investigated whether CET is involved in de novo NADP+ supply in Arabidopsis thaliana and measured chloroplastic NADP dynamics to evaluate responsiveness to variable light, photochemical inhibitors, darkness, and CET activity. The sum of oxidized and reduced forms shows that levels of NADP and NAD increase and decrease, respectively, in response to light; levels of NADP and NAD decrease and increase in the dark, respectively. Moreover, consistent with the pH change in the stroma, the pH preference of chloroplast NAD+ phosphorylation and NADP+ dephosphorylation is alkaline and weakly acidic, respectively. Furthermore, CET is correlated with upregulation of light-responsive NADP level increases and downregulation of dark-responsive NADP level reductions. These findings are consistent with CET helping to regulate NADP pool size via stromal pH regulation under fluctuating light conditions.
Selection of isomerization pathways of multistep photoswitches by chalcogen bonding
Authors: Jia Shuaipeng , Ye Hebo , He Peng , Lin Xin , You Lei
Published: November 2023

Multistep photoswitches are able to engage in different photoisomerization pathways and are challenging to control. Here we demonstrate a multistep sequence of E/Z isomerization and photocyclization/cycloreversion of photoswitches via manipulating the strength and mechanism of noncovalent chalcogen bonding interactions. The incorporation of chalcogens and the formyl group on open ethene bridged dithienylethenes offers a versatile skeleton for single photochromic molecules. While bidirectional E/Z photoswitching is dominated by neutral tellurium arising from enhanced resonance-assisted chalcogen bonding, the creation of cationic telluronium enables the realization of photocyclization/cycloreversion. The reversible nucleophilic substitution reactions further allow interconversion between neutral tellurium and cationic telluronium and selection of photoisomerization mechanisms on purpose. By leveraging unique photoswitching patterns and dynamic covalent reactivity, light and pH stimuli-responsive multistate rewritable materials were constructed, triggered by an activating reagent for additional control. The results should provide ample opportunities to molecular recognition, intelligent switches, information encryption, and smart materials.
The genomics and evolution of inter-sexual mimicry and female-limited polymorphisms in damselflies
Authors: Willink Beatriz , Tunström Kalle , Nilén Sofie , Chikhi Rayan , Lemane Téo , Takahashi Michihiko , Takahashi Yuma , Svensson Erik I. , Wheat Christopher West
Published: November 2023

Sex-limited morphs can provide profound insights into the evolution and genomic architecture of complex phenotypes. Inter-sexual mimicry is one particular type of sex-limited polymorphism in which a novel morph resembles the opposite sex. While inter-sexual mimics are known in both sexes and a diverse range of animals, their evolutionary origin is poorly understood. Here, we investigated the genomic basis of female-limited morphs and male mimicry in the common bluetail damselfly. Differential gene expression between morphs has been documented in damselflies, but no causal locus has been previously identified. We found that male mimicry originated in an ancestrally sexually dimorphic lineage in association with multiple structural changes, probably driven by transposable element activity. These changes resulted in ~900 kb of novel genomic content that is partly shared by male mimics in a close relative, indicating that male mimicry is a trans-species polymorphism. More recently, a third morph originated following the translocation of part of the male-mimicry sequence into a genomic position ~3.5 mb apart. We provide evidence of balancing selection maintaining male mimicry, in line with previous field population studies. Our results underscore how structural variants affecting a handful of potentially regulatory genes and morph-specific genes can give rise to novel and complex phenotypic polymorphisms.
Synthesis of novel pyrazolone candidates with studying some biological activities and in-silico studies
Authors: Abdellattif Magda H. , Hamed Eman O. , Elhoseni Nourhan Kh. R. , Assy Mohamed G. , Emwas Abdul-Hamid M. , Jaremko Mariusz , Celik Ismail , Titi Abderrahim , Kumar Yadav Krishna , Elgendy Marwa S. , Shehab Wesam S.
Published: November 2023

Pyranopyrazole derivatives have a vital role in the class of organic compounds because of their broad spectrum of biological and pharmacological importance. Our current goal is the [3 + 3] cycloaddition of benzoyl isothiocyanate and pyrazolone 1 to undergo oxidation cyclization, producing pyrazoloxadiazine 3. The diol 5 was obtained as a condensation of two equivalents of 1 with thiophene-2-carboxaldehyde in acetic acid above the sodium acetate mixture. When the condensation was carried out in piperidine under fusion, unsaturated ketone 4 was obtained. The pyrazolo pyran derivative 11 resulted from the [3 + 3] cycloaddition of 1 and cinnamic acid, while the Pyrone derivative was prepared by acylation of 12 with two equivalents of acetic anhydride. Phthalic anhydride undergoes arylation using zinc chloride as a catalyst. The cyclic keto acid 23 was synthesized by the action of succinic anhydride on 12 in the acetic medium, while the latter reacted with cinnamic acid, leading to pyrazole derivative 24. All of these reactions were through the Michael reaction mechanism. All the tested compounds showed good antimicrobial activity against pathogenic microorganisms; newly synthesized compounds were also screened for their antioxidant activity. Rational studies were carried out by the ABTs method to allow a broader choice of activities. In addition, similar off-compounds were conducted. Molecular docking studies with the CB-Dock server and MD simulations were created with the default settings of the Solution Builder on the CHARMM-GUI server at 150 nm. A good correlation was obtained between the experimental results and the theoretical bioavailability predictions using POM theory.
Integration of risk variants from GWAS with SARS-CoV-2 RNA interactome prioritizes FUBP1 and RAB2A as risk genes for COVID-19
Authors: Shi Weiwen , Chen Mengke , Pan Tingting , Chen Mengjie , Cheng Yongjun , Hao Yimei , Chen Sheng , Tang Yuanjia
Published: November 2023

The role of host genetic factors in COVID-19 outcomes remains unclear despite various genome-wide association studies (GWAS). We annotate all significant variants and those variants in high LD (R2 > 0.8) from the COVID-19 host genetics initiative (HGI) and identify risk genes by recognizing genes intolerant nonsynonymous mutations in coding regions and genes associated with cis-expression quantitative trait loci (cis-eQTL) in non-coding regions. These genes are enriched in the immune response pathway and viral life cycle. It has been found that host RNA binding proteins (RBPs) participate in different phases of the SARS-CoV-2 life cycle. We collect 503 RBPs that interact with SARS-CoV-2 RNA concluded from in vitro studies. Combining risk genes from the HGI with RBPs, we identify two COVID-19 risk loci that regulate the expression levels of FUBP1 and RAB2A in the lung. Due to the risk allele, COVID-19 patients show downregulation of FUBP1 and upregulation of RAB2A. Using single-cell RNA sequencing data, we show that FUBP1 and RAB2A are expressed in SARS-CoV-2-infected upper respiratory tract epithelial cells. We further identify NC_000001.11:g.77984833C>A and NC_000008.11:g.60559280T>C as functional variants by surveying allele-specific transcription factor sites and cis-regulatory elements and performing motif analysis. To sum up, our research, which associates human genetics with expression levels of RBPs, identifies FUBP1 and RAB2A as two risk genes for COVID-19 and reveals the anti-viral role of FUBP1 and the pro-viral role of RAB2A in the infection of SARS-CoV-2.
Differential effects of interleukin-17A and 17F on cell interactions between immune cells and stromal cells from synovium or skin
Authors: Tout Issam , Noack Mélissa , Miossec Pierre
Published: November 2023

We compared the contribution of IL-17A and IL-17F in co-culture systems mimicking cell interactions as found in inflamed synovium and skin. Synoviocytes or skin fibroblasts were co-cultured with activated PBMC, with IL-17A, IL-17 A/F, IL-17F, IL-23, anti-IL-17A, anti-IL-17A/F or anti-IL-17F antibodies. IL-17A, IL-17F, IL-6 and IL-10 production was measured at 48 h. mRNA expression of receptor subunits for IL-23, IL-12 and IL-17 was assessed at 24 h. Both cell activation and interactions were needed for a high IL-17A secretion while IL-17F was stimulated by PHA activation alone and further increased in co-cultures. IL-17F levels were higher than IL-17A in both co-cultures (p < 0.05). IL-17F addition decreased IL-17A secretion (p < 0.05) but IL-17A addition had no effect on IL-17F secretion. Interestingly, IL-17A and IL-17F upregulated IL-17RA and IL-17RC mRNA expression in PBMC/skin fibroblast co-cultures (p < 0.05) while only IL-17F exerted this effect in synoviocytes (p < 0.05). Monocyte exclusion in both co-cultures increased IL-17A and IL-17F (twofold, p < 0.05) while decreasing IL-10 and IL-6 secretion (twofold, p < 0.05). IL-17A and F had differential effects on their receptor expression with a higher sensitivity for skin fibroblasts highlighting the differential contribution of IL-17A and F in joint vs. skin diseases.
Surgical delay increases the survival of expanded random-pattern flap in pediatric patients
Authors: Ha Jeong Hyun , Lee Se Yeon , Choi Tae Hyun , Park Seong Oh
Published: November 2023

Despite the aid of tissue expansion, the ideal design of random pattern flap is not always available in patients with extensive skin lesions. We investigated the effectiveness of surgical delay on expanded flaps in pediatric patients. Retrospective cohort study was performed on patients who underwent tissue expansion surgery for extensive skin lesions at Seoul National University Children’s Hospital. The surgical delay technique was employed for patients with unfavorable flap conditions related to location or transposition angles. The dimensions of skin lesions and flaps were measured based on medical photographs. Fifty patients underwent a total of 66 tissue expansion procedures (49 conventional procedures among 41 patients, 17 surgical delay procedures among 15 patients) from January 2016 to September 2019. Although flaps in the surgical delay group were more narrow-based (p < 0.001), the partial flap loss rate and excised area-to-inflation amount ratio was comparable between the two groups (p = 0.093 and p = 0.194, respectively). Viable flaps, excluding postoperative necrosis, in the surgical delay group were significantly more narrow-based in terms of the length-to-base width ratio and the area-to-base width ratio compared to conventional group (p < 0.01, p < 0.01). Surgical delay can result in outcomes comparable to well-designed random flaps, even in disadvantageous conditions. Patients with large skin lesions but limited areas for expansion may benefit from surgical delay.
First observation of fluid-like eddy-dominant bursty bulk flow turbulence in the Earth’s tail plasma sheet
Authors: Zhang L. Q. , Wang Chi. , Baumjohann W. , Wang R. S. , Wang J. Y. , Burch James L. , Khotyaintsev Yu. V.
Published: November 2023

Turbulence is a ubiquitous phenomenon in neutral and conductive fluids. According to classical theory, turbulence is a rotating flow containing vortices of different scales. Eddies play a fundamental role in the nonlinear cascade of kinetic energy at different scales in turbulent flow. In conductive fluids, the Alfvénic/kinetic Alfvénic wave (AW/KAW) is the new “cell” of magnetohydrodynamic (MHD) turbulence (frozen-in condition). Wave energy, which has equal kinetic and magnetic energy, is redistributed among multiple-scale Fourier modes and transferred from the large MHD scale to the small kinetic scale through the collision of counter-propagating Alfvénic wave packages propagating along the magnetic field line. Fluid-like eddy-dominant plasma flow turbulence has never been found in space since the launch of the first satellite in 1957. In this paper, we report the first observation of eddy-dominant turbulence within magnetic reconnection-generated fast flow in the Earth’s tail plasma sheet by the Magnetospheric Multiscale Spacecraft (MMS). In eddy-dominant turbulent reconnection jet, ions dominate the flow field while electrons dominate current and magnetic fluctuations. Our findings shed new light on the nonlinear kinetic and magnetic energy cascade in MHD turbulence.
A scalable approach to optimize traffic signal control with federated reinforcement learning
Authors: Bao Jingjing , Wu Celimuge , Lin Yangfei , Zhong Lei , Chen Xianfu , Yin Rui
Published: November 2023

Intelligent Transportation has seen significant advancements with Deep Learning and the Internet of Things, making Traffic Signal Control (TSC) research crucial for reducing congestion, travel time, emissions, and energy consumption. Reinforcement Learning (RL) has emerged as the primary method for TSC, but centralized learning poses communication and computing challenges, while distributed learning struggles to adapt across intersections. This paper presents a novel approach using Federated Learning (FL)-based RL for TSC. FL integrates knowledge from local agents into a global model, overcoming intersection variations with a unified agent state structure. To endow the model with the capacity to globally represent the TSC task while preserving the distinctive feature information inherent to each intersection, a segment of the RL neural network is aggregated to the cloud, and the remaining layers undergo fine-tuning upon convergence of the model training process. Extensive experiments demonstrate reduced queuing and waiting times globally, and the successful scalability of the proposed model is validated on a real-world traffic network in Monaco, showing its potential for new intersections.
Human amniotic membrane inhibits migration and invasion of muscle-invasive bladder cancer urothelial cells by downregulating the FAK/PI3K/Akt/mTOR signalling pathway
Authors: Janev Aleksandar , Ramuta Taja Železnik , Jerman Urška Dragin , Obradović Hristina , Kamenšek Urška , Čemažar Maja , Kreft Mateja Erdani
Published: November 2023

Bladder cancer is the 10th most commonly diagnosed cancer with the highest lifetime treatment costs. The human amniotic membrane (hAM) is the innermost foetal membrane that possesses a wide range of biological properties, including anti-inflammatory, antimicrobial and anticancer properties. Despite the growing number of studies, the mechanisms associated with the anticancer effects of human amniotic membrane (hAM) are poorly understood. Here, we reported that hAM preparations (homogenate and extract) inhibited the expression of the epithelial–mesenchymal transition markers N-cadherin and MMP-2 in bladder cancer urothelial cells in a dose-dependent manner, while increasing the secretion of TIMP-2. Moreover, hAM homogenate exerted its antimigratory effect by downregulating the expression of FAK and proteins involved in actin cytoskeleton reorganisation, such as cortactin and small RhoGTPases. In muscle-invasive cancer urothelial cells, hAM homogenate downregulated the PI3K/Akt/mTOR signalling pathway, the key cascade involved in promoting bladder cancer. By using normal, non-invasive papilloma and muscle-invasive cancer urothelial models, new perspectives on the anticancer effects of hAM have emerged. The results identify new sites for therapeutic intervention and are prompt encouragement for ongoing anticancer drug development studies.
Hexagonal-shaped graphene quantum plasmonic nano-antenna sensor
Authors: Kavitha S. , Saxena Ravi Shankar , Singh Ashish , Kumari Kamakshi , Aneesh Mohammed
Published: November 2023

In this manuscript, a hexagonal-shaped graphene quantum plasmonic nanopatch antenna sensor is designed and investigated on silicon dioxide, zinc oxide and silicon substrates for quantum plasmonic biosensing applications. The optical properties of graphene are demonstrated using Kubo modeling to analyze the plasmon resonance characteristics of the nanopatch antenna. Nano-circuit modeling of the hexagonal-shaped graphene nano-antenna is proposed and validated using CST simulations. The parametric analysis of the hexagonal-shaped nanopatch antenna is performed using design parameters such as R (radius of the hexagon), Tp (thickness of the hexagon) and µc (chemical potential of graphene) to obtain optimum characteristics suitable for quantum plasmonic sensing applications. The study demonstrates that the proposed hexagonal-shaped nano-antenna exhibits gain of 4.9 dBi, 2.46 dBi, 14.99 dBi, 8.25 dBi, 5.15 dBi, 10.87 dBi and 2.4 dBi at 29.87 THz, 30 THz, 35 THz, 113.5 THz, 132.5 THz, 85 THz and 24 THz, respectively. The field enhancement factors observed at these frequencies are 794, 779, 584, 255, 234, 654 and 217, respectively.
Kif21a deficiency leads to impaired glomerular filtration barrier function
Authors: Riedmann Hanna , Kayser Séverine , Helmstädter Martin , Epting Daniel , Bergmann Carsten
Published: November 2023

The renal glomerulus represents the major filtration body of the vertebrate nephron and is responsible for urine production and a number of other functions such as metabolic waste elimination and the regulation of water, electrolyte and acid–base balance. Podocytes are highly specialized epithelial cells that form a crucial part of the glomerular filtration barrier (GFB) by establishing a slit diaphragm for semipermeable plasma ultrafiltration. Defects of the GFB lead to proteinuria and impaired kidney function often resulting in end-stage renal failure. Although significant knowledge has been acquired in recent years, many aspects in podocyte biology are still incompletely understood. By using zebrafish as a vertebrate in vivo model, we report a novel role of the Kinesin-like motor protein Kif21a in glomerular filtration. Our studies demonstrate specific Kif21a localization to the podocytes. Its deficiency resulted in altered podocyte morphology leading to podocyte foot process effacement and altered slit diaphragm formation. Finally, we proved considerable functional consequences of Kif21a deficiency by demonstrating a leaky GFB resulting in severe proteinuria. Conclusively, our data identified a novel role of Kif21a for proper GFB function and adds another piece to the understanding of podocyte architecture and regulation.