bluuebunny/crossref_metadata_2025 huggingface dataset:
Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery
Authors: Zheleva Bistra , Verstappen Amy , Overman David M. , Ahmad Farhan , Ali Sulafa K.M. , Al Halees Zohair Y. , Atallah Joumana Ghandour , Badhwar Isabella E. , Baker-Smith Carissa , Balestrini Maria , Basken Amy , Bassuk Jonah S. , Benson Lee , Capelli Horacio , Carollo Santo , Chowdhury Devyani , Çiçek M. Sertaç , Cohen Mitchell I. , Cooper David S. , Deanfield John E. , Dearani Joseph , del Valle Blanca , Dodds Kathryn M. , Du Junbao , Edwin Frank , Ekure Ekanem , Fatema Nurun Nahar , Gomanju Anu , Hasan Babar , Henry Lewis , Hugo-Hamman Christopher , Iyer Krishna S. , Jatene Marcelo B. , Jenkins Kathy J. , Karamlou Tara , Karl Tom R. , Kirklin James K. , Kreutzer Christián , Kumar Raman Krishna , Lopez Keila N. , Macedo Alexis Palacios , Marino Bradley S. , Marwali Eva M. , Meijboom Folkert J. , Mattos Sandra S. , Najm Hani , Newlin Dan , Novick William M. , Qureshi Sir Shakeel A. , Rahmat Budi , Raylman Robert , Saltik Irfan Levent , Sable Craig , Sandoval Nestor , Saxena Anita , Scanlan Emma , Sholler Gary F. , Smith Jodi , St Louis James D. , Tchervenkov Christo I. , Tiong Koh Ghee , Vida Vladimiro , Vosloo Susan , Weinstein Douglas J. “DJ” , Wilkinson James L. , Zuhlke Liesl , Jacobs Jeffrey P.
Published: August 2023

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
Constraints for the Martian Crustal Structure From Rayleigh Waves Ellipticity of Large Seismic Events
Authors: Carrasco Sebastián , Knapmeyer‐Endrun Brigitte , Margerin Ludovic , Xu Zongbo , Joshi Rakshit , Schimmel Martin , Stutzmann Eleonore , Charalambous Constantinos , Lognonné Philippe , Banerdt W. Bruce
Published: August 2023

For the first time, we measured the ellipticity of direct Rayleigh waves at intermediate periods (15–35 s) on Mars using the recordings of three large seismic Martian events, including S1222a, the largest event recorded by the InSight mission. These measurements, together with P‐to‐s receiver functions and P‐wave reflection times, were utilized for performing a joint inversion of the local crustal structure at the InSight landing site. Our inversion results are compatible with previously reported intra‐crustal discontinuities around 10 and 20 km depths, whereas the preferred models show a strong discontinuity at ∼37 km, which is interpreted as the crust‐mantle interface. Additionally, we support the presence of a shallow low‐velocity layer of 2–3 km thickness. Compared to nearby regions, lower seismic wave velocities are derived for the crust, suggesting a higher porosity or alteration of the whole local crust.
Flexible thermoelectric generator and energy management electronics powered by body heat
Authors: Yang Shuai , Li Yumei , Deng Ling , Tian Song , Yao Ye , Yang Fan , Feng Changlei , Dai Jun , Wang Ping , Gao Mingyuan
Published: August 2023

Uninterrupted, efficient power supplies have posed a significant hurdle to the ubiquitous adoption of wearable devices, despite their potential for revolutionizing human‒machine interactions. This challenge is further compounded by the requirement of these devices to supply dependable energy for data-intensive sensing and transmission. Traditional thermoelectric solutions fail to deliver satisfactory performance under conditions of extremely low voltages. Here, we present a novel solution of a wearable thermoelectric generator integrated with an energy management system, which is capable of powering sensors and Bluetooth by harnessing body heat. Distinct from previous works, our innovation lies in its ability to consistently operate even with a minimal temperature difference (i.e., 4 K) between the human skin and the ambient environment, ensuring reliable data transmission within a time as short as 1.6 s. Furthermore, our system can recharge utilizing body heat under ultralow voltage conditions (30 mV). Our developed system provides a novel pathway for the continuous, reliable monitoring of self-contained wearable devices without depending on batteries.
Social circuits and their dysfunction in autism spectrum disorder
Authors: Sato Masaaki , Nakai Nobuhiro , Fujima Shuhei , Choe Katrina Y. , Takumi Toru
Published: August 2023

Social behaviors, how individuals act cooperatively and competitively with conspecifics, are widely seen across species. Rodents display various social behaviors, and many different behavioral paradigms have been used for investigating their neural circuit bases. Social behavior is highly vulnerable to brain network dysfunction caused by neurological and neuropsychiatric conditions such as autism spectrum disorders (ASDs). Studying mouse models of ASD provides a promising avenue toward elucidating mechanisms of abnormal social behavior and potential therapeutic targets for treatment. In this review, we outline recent progress and key findings on neural circuit mechanisms underlying social behavior, with particular emphasis on rodent studies that monitor and manipulate the activity of specific circuits using modern systems neuroscience approaches. Social behavior is mediated by a distributed brain-wide network among major cortical (e.g., medial prefrontal cortex (mPFC), anterior cingulate cortex, and insular cortex (IC)) and subcortical (e.g., nucleus accumbens, basolateral amygdala (BLA), and ventral tegmental area) structures, influenced by multiple neuromodulatory systems (e.g., oxytocin, dopamine, and serotonin). We particularly draw special attention to IC as a unique cortical area that mediates multisensory integration, encoding of ongoing social interaction, social decision-making, emotion, and empathy. Additionally, a synthesis of studies investigating ASD mouse models demonstrates that dysfunctions in mPFC-BLA circuitry and neuromodulation are prominent. Pharmacological rescues by local or systemic (e.g., oral) administration of various drugs have provided valuable clues for developing new therapeutic agents for ASD. Future efforts and technological advances will push forward the next frontiers in this field, such as the elucidation of brain-wide network activity and inter-brain neural dynamics during real and virtual social interactions, and the establishment of circuit-based therapy for disorders affecting social functions.
ICAM2 initiates trans-blood-CSF barrier migration and stemness properties in leptomeningeal metastasis of triple-negative breast cancer
Authors: Pan Jhih-Kai , Lin Wen-Der , Kuo Yao-Lung , Chen Yu-Chia , Loh Zhu-Jun , Lin Forn-Chia , Cheng Hui-Chuan , Hsiao Michael , Lu Pei-Jung
Published: August 2023

Leptomeningeal metastasis (LM) occurs when tumor cells spread to the leptomeningeal space surrounding the brain and the spinal cord, thereby causing poor clinical outcomes. The triple-negative breast cancer (TNBC) has been associated with symptoms of LM and mechanism remained unclear. Through proteomic analysis, we identified high expression of ICAM2 in leptomeningeal metastatic TNBC cells, which promoted the colonization of the spinal cord and resulted in poor survival in vivo. Two-way demonstration indicated that high levels of ICAM2 promoted blood–cerebrospinal fluid barrier (BCB) adhesion, trans-BCB migration, and stemness abilities and determined the specificity of LM in vivo. Furthermore, pull-down and antibody neutralizing assay revealed that ICAM2 determined the specificity of LM through interactions with ICAM1 in the choroid plexus epithelial cells. Therefore, neutralizing ICAM2 can attenuate the progression of LM and prolong survival in vivo. The results suggested that targeting ICAM2 is a potential therapeutic strategy for LM in TNBC.
Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5
Authors: Diegel Cassandra R. , Kramer Ina , Moes Charles , Foxa Gabrielle E. , McDonald Mitchell J. , Madaj Zachary B. , Guth Sabine , Liu Jun , Harris Jennifer L. , Kneissel Michaela , Williams Bart O.
Published: August 2023

Proper regulation of Wnt signaling is critical for normal bone development and homeostasis. Mutations in several Wnt signaling components, which increase the activity of the pathway in the skeleton, cause high bone mass in human subjects and mouse models. Increased bone mass is often accompanied by severe headaches from increased intracranial pressure, which can lead to fatality and loss of vision or hearing due to the entrapment of cranial nerves. In addition, progressive forehead bossing and mandibular overgrowth occur in almost all subjects. Treatments that would provide symptomatic relief in these subjects are limited. Porcupine-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled receptor. Chemical inhibition of porcupine is a highly selective method of Wnt signaling inhibition. We treated three different mouse models of high bone mass caused by aberrant Wnt signaling, including homozygosity for loss-of-function inSost, which models sclerosteosis, and two strains of mice carrying different point mutations inLrp5(equivalent to human G171V and A214V), at 3 months of age with porcupine inhibitors for 5–6 weeks. Treatment significantly reduced both trabecular and cortical bone mass in all three models. This demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.
FOXM1 maintains fatty acid homoeostasis through the SET7-H3K4me1-FASN axis
Authors: Li Xixi , Su Weijie , Wu Honglin , Xu Jiakun , Tang Hongxing , Chen Xiangkun , Yin Zhanqi , Zhang Changming , Yang Jia , Yang Yibing , Zhang Nu , Yang Lixuan
Published: August 2023

Reprogramming of metabolic genes and subsequent alterations in metabolic phenotypes occur widely in malignant tumours, including glioblastoma (GBM). FOXM1 is a potent transcription factor that plays an oncogenic role by regulating the expression of many genes. As a SET domain containing protein, SET7 is a protein lysine methyltransferase which monomethylates histone proteins and other proteins. The epigenetic modification of histones regulates gene expressions by epigenetically modifying promoters of DNAs and inter vening in tumor development. Activation of FASN increased de novo fatty acid (FA) synthesis, a hallmark of cancer cells. Here, we report that FOXM1 may directly promote the transcription of SET7 and activate SET7-H3K4me1-FASN axis, which results in the maintenance of de novo FA synthesis.
Citrullinated fibrinogen-SAAs complex causes vascular metastagenesis
Authors: Han Yibing , Tomita Takeshi , Kato Masayoshi , Ashihara Norihiro , Higuchi Yumiko , Matoba Hisanori , Wang Weiyi , Hayashi Hikaru , Itoh Yuji , Takahashi Satoshi , Kurita Hiroshi , Nakayama Jun , Okumura Nobuo , Hiratsuka Sachie
Published: August 2023

Primary tumor cells metastasize to a distant preferred organ. However, the most decisive host factors that determine the precise locations of metastases in cancer patients remain unknown. We have demonstrated that post-translational citrullination of fibrinogen creates a metastatic niche in the vulnerable spots. Pulmonary endothelial cells mediate the citrullination of fibrinogen, changing its conformation, surface charge, and binding properties with serum amyloid A proteins (SAAs), to make it a host tissue-derived metastatic pathogen. The human-specific SAAs-citrullinated fibrinogen (CitFbg) complex recruits cancer cells to form a protein-metastatic cell aggregation in humanized SAA cluster mice. Furthermore, a CitFbg peptide works as a competitive inhibitor to block the homing of metastatic cells into the SAAs-CitFbg sites. The potential metastatic sites in the lungs of patients are clearly visualized by our specific antibody for CitFbg. Thus, CitFbg deposition displays metastatic risks for cancer patients, and the citrullinated peptide is a new type of metastasis inhibitor.
Fiber supplementation protects from antibiotic-induced gut microbiome dysbiosis by modulating gut redox potential
Authors: Penumutchu Swathi , Korry Benjamin J. , Hewlett Katharine , Belenky Peter
Published: August 2023

Antibiotic-induced gut dysbiosis (AID) is a frequent and serious side effect of antibiotic use and mitigating this dysbiosis is a critical therapeutic target. We propose that the host diet can modulate the chemical environment of the gut resulting in changes to the structure and function of the microbiome during antibiotic treatment. Gut dysbiosis is typically characterized by increases in aerobic respiratory bacterial metabolism, redox potential, and abundance of Proteobacteria. In this study, we explore dietary fiber supplements as potential modulators of the chemical environment in the gut to reduce this pattern of dysbiosis. Using defined-diets and whole-genome sequencing of female murine microbiomes during diet modulation and antibiotic treatment, we find that fiber prebiotics significantly reduced the impact of antibiotic treatment on microbiome composition and function. We observe reduced abundance of aerobic bacteria as well as metabolic pathways associated with oxidative metabolism. These metatranscriptomic results are corroborated by chemical measurements of eH and pH suggesting that fiber dampens the dysbiotic effects of antibiotics. This work indicates that fiber may act as a potential therapeutic for AID by modulating bacterial metabolism in the gut to prevent an increase in redox potential and protect commensal microbes during antibiotic treatment.
Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
Authors: Hiltbrunner Stefanie , Cords Lena , Kasser Sabrina , Freiberger Sandra N. , Kreutzer Susanne , Toussaint Nora C. , Grob Linda , Opitz Isabelle , Messerli Michael , Zoche Martin , Soltermann Alex , Rechsteiner Markus , van den Broek Maries , Bodenmiller Bernd , Curioni-Fontecedro Alessandra
Published: August 2023

Immune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients showing good initial response to immune checkpoint inhibitors, followed by acquired resistance at later time points. By using imaging mass cytometry and whole exome and RNA sequencing, we detect two patterns of resistance¨: One group of patients is characterized by reduced numbers of tumor-infiltrating CD8+ T cells and reduced expression of PD-L1 after development of resistance, whereas the other group shows high CD8+ T cell infiltration and high expression of PD-L1 in addition to markedly elevated expression of other immune-inhibitory molecules. In two cases, we detect downregulation of type I and II IFN pathways following progression to resistance, which could lead to an impaired anti-tumor immune response. This study thus captures the development of immune checkpoint inhibitor resistance as it progresses and deepens our mechanistic understanding of immunotherapy response in NSCLC.
Divergent access to 5,6,7-perifused cycles
Authors: Han Jingpeng , Yang Yongjian , Gong Yingjian , Tang Xuan , Tian Yi , Li Baosheng
Published: August 2023

Nitrogen-containing heterocycles are the key components in many pharmaceuticals and functional materials. In this study, we report a transition metal-catalyzed high-order reaction sequence for synthesizing a structurally unique N-center 5,6,7-perifused cycle (NCPC). The key characteristics include the formation of a seven-membered ring by the 8π electrocyclization of various alkenes and aromatic heterocycles as π-components, in which metal carbene species are generated that further induce the cleavage of the α-C-H or -C-C bond. Specifically, the latter can react with various nucleophilic reagents containing -O, -S, -N, and -C. The stereo-controlled late-stage modification of some complicated pharmaceuticals indicates the versatility of this protocol.
Synthesis of robust underwater glues from common proteins via unfolding-aggregating strategy
Authors: Liu Yongchun , Li Ke , Tian Juanhua , Gao Aiting , Tian Lihua , Su Hao , Miao Shuting , Tao Fei , Ren Hao , Yang Qingmin , Cao Jing , Yang Peng
Published: August 2023

Underwater adhesive proteins secreted by organisms greatly inspires the development of underwater glue. However, except for specific proteins such as mussel adhesive protein, barnacle cement proteins, curli protein and their related recombinant proteins, it is believed that abundant common proteins cannot be converted into underwater glue. Here, we demonstrate that unfolded common proteins exhibit high affinity to surfaces and strong internal cohesion via amyloid-like aggregation in water. Using bovine serum albumin (BSA) as a model protein, we obtain a stable unfolded protein by cleaving the disulfide bonds and maintaining the unfolded state by means of stabilizing agents such as trifluoroethanol (TFE) and urea. The diffusion of stabilizing agents into water exposes the hydrophobic residues of an unfolded protein and initiates aggregation of the unfolded protein into a solid block. A robust and stable underwater glue can thus be prepared from tens of common proteins. This strategy deciphers a general code in common proteins to construct robust underwater glue from abundant biomass.
Switch of cell migration modes orchestrated by changes of three-dimensional lamellipodium structure and intracellular diffusion
Authors: Jiang Chao , Luo Hong-Yu , Xu Xinpeng , Dou Shuo-Xing , Li Wei , Guan Dongshi , Ye Fangfu , Chen Xiaosong , Guo Ming , Wang Peng-Ye , Li Hui
Published: August 2023

Cell migration plays important roles in many biological processes, but how migrating cells orchestrate intracellular molecules and subcellular structures to regulate their speed and direction is still not clear. Here, by characterizing the intracellular diffusion and the three-dimensional lamellipodium structures of fish keratocyte cells, we observe a strong positive correlation between the intracellular diffusion and cell migration speed and, more importantly, discover a switching of cell migration modes with reversible intracellular diffusion variation and lamellipodium structure deformation. Distinct from the normal fast mode, cells migrating in the newly-found slow mode have a deformed lamellipodium with swollen-up front and thinned-down rear, reduced intracellular diffusion and compartmentalized macromolecule distribution in the lamellipodium. Furthermore, in turning cells, both lamellipodium structure and intracellular diffusion dynamics are also changed, with left-right symmetry breaking. We propose a mechanism involving the front-localized actin polymerization and increased molecular crowding in the lamellipodium to explain how cells spatiotemporally coordinate the intracellular diffusion dynamics and the lamellipodium structure in regulating their migrations.
A qPCR technology for direct quantification of methylation in untreated DNA
Authors: Bendixen Kamilla Kolding , Mindegaard Maria , Epistolio Samantha , Dazio Giulia , Marchi Francesco , Spina Paolo , Arnspang Eva C. , Soerensen Mette , Christensen Ulf Bech , Frattini Milo , Petersen Rasmus Koefoed
Published: August 2023

DNA methylation is important for gene expression and alterations in DNA methylation are involved in the development and progression of cancer and other major diseases. Analysis of DNA methylation patterns has until now been dependent on either a chemical or an enzymatic pre-treatment, which are both time consuming procedures and potentially biased due to incomplete treatment. We present a qPCR technology, EpiDirect®, that allows for direct PCR quantification of DNA methylations using untreated DNA. EpiDirect® is based on the ability of Intercalating Nucleic Acids (INA®) to differentiate between methylated and unmethylated cytosines in a special primer design. With this technology, we develop an assay to analyze the methylation status of a region of the MGMT promoter used in treatment selection and prognosis of glioblastoma patients. We compare the assay to two bisulfite-relying, methyl-specific PCR assays in a study involving 42 brain tumor FFPE samples, revealing high sensitivity, specificity, and the clinical utility of the method.
Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: the METS-microbiome study
Authors: Ecklu-Mensah Gertrude , Choo-Kang Candice , Maseng Maria Gjerstad , Donato Sonya , Bovet Pascal , Viswanathan Bharathi , Bedu-Addo Kweku , Plange-Rhule Jacob , Oti Boateng Prince , Forrester Terrence E. , Williams Marie , Lambert Estelle V. , Rae Dale , Sinyanya Nandipha , Luke Amy , Layden Brian T. , O’Keefe Stephen , Gilbert Jack A. , Dugas Lara R.
Published: August 2023

The relationship between microbiota, short chain fatty acids (SCFAs), and obesity remains enigmatic. We employ amplicon sequencing and targeted metabolomics in a large (n = 1904) African origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US. Microbiota diversity and fecal SCFAs are greatest in Ghanaians, and lowest in Americans, representing each end of the urbanization spectrum. Obesity is significantly associated with a reduction in SCFA concentration, microbial diversity, and SCFA synthesizing bacteria, with country of origin being the strongest explanatory factor. Diabetes, glucose state, hypertension, obesity, and sex can be accurately predicted from the global microbiota, but when analyzed at the level of country, predictive accuracy is only universally maintained for sex. Diabetes, glucose, and hypertension are only predictive in certain low-income countries. Our findings suggest that adiposity-related microbiota differences differ between low-to-middle-income compared to high-income countries. Further investigation is needed to determine the factors driving this association.
RNAPII-dependent ATM signaling at collisions with replication forks
Authors: Einig Elias , Jin Chao , Andrioletti Valentina , Macek Boris , Popov Nikita
Published: August 2023

Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and are thought to underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII nucleates activation of the ATM kinase at TRCs to stimulate DNA repair. We show the ATPase WRNIP1 associates with RNAPII and limits ATM activation during unperturbed cell cycle. WRNIP1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase HUWE1. Mutation of HUWE1 induces TRCs, promotes WRNIP1 dissociation from RNAPII and binding to the replisome, stimulating ATM recruitment and activation at RNAPII. TRCs and translocation of WRNIP1 are rapidly induced in response to hydroxyurea treatment to activate ATM and facilitate subsequent DNA repair. We propose that TRCs can provide a controlled mechanism for stalling of replication forks and ATM activation, instrumental in cellular response to replicative stress.
A synthetic cell-free 36-enzyme reaction system for vitamin B12 production
Authors: Kang Qian , Fang Huan , Xiang Mengjie , Xiao Kaixing , Jiang Pingtao , You Chun , Lee Sang Yup , Zhang Dawei
Published: August 2023

Adenosylcobalamin (AdoCbl), a biologically active form of vitamin B12 (coenzyme B12), is one of the most complex metal-containing natural compounds and an essential vitamin for animals. However, AdoCbl can only be de novo synthesized by prokaryotes, and its industrial manufacturing to date was limited to bacterial fermentation. Here, we report a method for the synthesis of AdoCbl based on a cell-free reaction system performing a cascade of catalytic reactions from 5-aminolevulinic acid (5-ALA), an inexpensive compound. More than 30 biocatalytic reactions are integrated and optimized to achieve the complete cell-free synthesis of AdoCbl, after overcoming feedback inhibition, the complicated detection, instability of intermediate products, as well as imbalance and competition of cofactors. In the end, this cell-free system produces 417.41 μg/L and 5.78 mg/L of AdoCbl using 5-ALA and the purified intermediate product hydrogenobyrate as substrates, respectively. The strategies of coordinating synthetic modules of complex cell-free system describe here will be generally useful for developing cell-free platforms to produce complex natural compounds with long and complicated biosynthetic pathways.
SARS-CoV-2 vaccination elicits broad and potent antibody effector functions to variants of concern in vulnerable populations
Authors: Hederman Andrew P. , Natarajan Harini , Heyndrickx Leo , Ariën Kevin K. , Wiener Joshua A. , Wright Peter F. , Bloch Evan M. , Tobian Aaron A. R. , Redd Andrew D. , Blankson Joel N. , Rottenstreich Amihai , Zarbiv Gila , Wolf Dana , Goetghebuer Tessa , Marchant Arnaud , Ackerman Margaret E.
Published: August 2023

SARS-CoV-2 variants have continuously emerged in the face of effective vaccines. Reduced neutralization against variants raises questions as to whether other antibody functions are similarly compromised, or if they might compensate for lost neutralization activity. Here, the breadth and potency of antibody recognition and effector function is surveyed following either infection or vaccination. Considering pregnant women as a model cohort with higher risk of severe illness and death, we observe similar binding and functional breadth for healthy and immunologically vulnerable populations, but considerably greater functional antibody breadth and potency across variants associated with vaccination. In contrast, greater antibody functional activity targeting the endemic coronavirus OC43 is noted among convalescent individuals, illustrating a dichotomy in recognition between close and distant human coronavirus strains associated with exposure history. This analysis of antibody functions suggests the differential potential for antibody effector functions to contribute to protecting vaccinated and convalescent subjects as novel variants continue to evolve.
Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice
Authors: Isidro-Hernández Marta , Casado-García Ana , Oak Ninad , Alemán-Arteaga Silvia , Ruiz-Corzo Belén , Martínez-Cano Jorge , Mayado Andrea , Sánchez Elena G. , Blanco Oscar , Gaspar Ma Luisa , Orfao Alberto , Alonso-López Diego , De Las Rivas Javier , Riesco Susana , Prieto-Matos Pablo , González-Murillo África , Criado Francisco Javier García , Cenador María Begoña García , Ramírez-Orellana Manuel , de Andrés Belén , Vicente-Dueñas Carolina , Cobaleda César , Nichols Kim E. , Sánchez-García Isidro
Published: August 2023

The initial steps of B-cell acute lymphoblastic leukemia (B-ALL) development usually pass unnoticed in children. Several preclinical studies have shown that exposure to immune stressors triggers the transformation of preleukemic B cells to full-blown B-ALL, but how this takes place is still a longstanding and unsolved challenge. Here we show that dysregulation of innate immunity plays a driving role in the clonal evolution of pre-malignantPax5+/−B-cell precursors toward leukemia. Transcriptional profiling reveals thatMyd88is downregulated in immune-stressed pre-malignant B-cell precursors and in leukemic cells. Genetic reduction ofMyd88expression leads to a significant increase in leukemia incidence inPax5+/−Myd88+/−mice through an inflammation-dependent mechanism. Early induction of Myd88-independent Toll-like receptor 3 signaling results in a significant delay of leukemia development inPax5+/−mice. Altogether, these findings identify a role for innate immunity dysregulation in leukemia, with important implications for understanding and therapeutic targeting of the preleukemic state in children.
Exploring anharmonic lattice dynamics and dielectric relations in niobate perovskites from first-principles self-consistent phonon calculations
Authors: Kim Kwangrae , Hwang Woohyun , Oh Seung-Hyun Victor , Soon Aloysius
Published: August 2023

Group I niobates (KNbO3 and NaNbO3) are promising lead-free alternatives for high-performance energy storage applications. Despite their potential, their complex phase transitions arising from temperature-dependent phonon softening and anharmonic effects on dielectric properties remain poorly explored. In this study, we employ density-functional theory (DFT) and self-consistent phonon (SCP) calculations to investigate finite-temperature phonons in cubic niobate perovskites. To include explicit anharmonic vibrational effects, SCP frequencies are shifted by the bubble self-energy correction within the quasiparticle (QP) approximation, providing precise descriptions of phonon softening in these strongly anharmonic solids. We further calculate the static dielectric constant of KNbO3 and NaNbO3 as a function of temperature using the Lyddane-Sachs-Teller (LST) relation and QP-corrected phonon dispersions. Our theoretical results align with experimental data, offering reliable temperature-dependent phonon dispersions while considering anharmonic self-energies and thermal expansion effects, enhancing our understanding of the complex relations between lattice vibrations and phase transitions in these anharmonic oxides.
Pyrite-based denitrification combined with electrochemical disinfection to remove nitrate and microbial contamination from groundwater
Authors: Ntagia Eleftheria , Lens Piet
Published: August 2023

Nitrate and microbial contamination of groundwater can occur in countries that face intense urbanization and inadequate sanitation. When groundwater is the main drinking water source, as is often the case in such countries, the need to remove these contaminants becomes acute. The combination of two technologies is proposed here, a biological step to denitrify and an electrochemical step to disinfect the groundwater, thereby aiming to reduce the chemical input and the footprint of groundwater treatment. As such, a pyrite-based fluidized bed reactor (P-FBR) was constructed to autotrophically denitrify polluted groundwater. The P-FBR effluent was disinfected in an electrochemical cell with electrogenerated Cl2. Nitrate was removed with 79% efficiency from an initial 178 mg NO3− L−1 at an average denitrification rate of 171 mg NO3− L−1 d−1, with 18 h hydraulic retention time (HRT). The electrochemical unit achieved a 3.8-log reduction in total coliforms with a 41.7 A h m−3 charge density.
Lis1 relieves cytoplasmic dynein-1 autoinhibition by acting as a molecular wedge
Authors: Karasmanis Eva P. , Reimer Janice M. , Kendrick Agnieszka A. , Nguyen Kendrick H. V. , Rodriguez Jennifer A. , Truong Joey B. , Lahiri Indrajit , Reck-Peterson Samara L. , Leschziner Andres E.
Published: August 2023

Cytoplasmic dynein-1 transports intracellular cargo towards microtubule minus ends. Dynein is autoinhibited and undergoes conformational changes to form an active complex that consists of one or two dynein dimers, the dynactin complex, and activating adapter(s). The Lissencephaly 1 gene, LIS1, is genetically linked to the dynein pathway from fungi to mammals and is mutated in people with the neurodevelopmental disease lissencephaly. Lis1 is required for active dynein complexes to form, but how it enables this is unclear. Here, we present a structure of two yeast dynein motor domains with two Lis1 dimers wedged in-between. The contact sites between dynein and Lis1 in this structure, termed ‘Chi,’ are required for Lis1’s regulation of dynein in Saccharomyces cerevisiae in vivo and the formation of active human dynein–dynactin–activating adapter complexes in vitro. We propose that this structure represents an intermediate in dynein’s activation pathway, revealing how Lis1 relieves dynein’s autoinhibited state.
Coating the surface of interconnected Cu2O nanowire arrays with HKUST-1 nanocrystals via electrochemical oxidation
Authors: Caddeo Francesco , Himmelstein Florian , Mahmoudi Behzad , Araújo-Cordero Ana María , Eberhart Denis , Zhang Haojie , Lindenberg Titus , Hähnel Angelika , Hagendorf Christian , Maijenburg A. Wouter
Published: August 2023

Controlling the crystallization of Metal–Organic Frameworks (MOFs) at the nanoscale is currently challenging, and this hinders their utilization for multiple applications including photo(electro)chemistry and sensors. In this work, we show a synthetic protocol that enables the preparation of highly homogeneous Cu2O@MOF nanowires standing on a conductive support with extensive control over the crystallization of the MOF nanoparticles at the surface of the Cu2O nanowires. Cu2O nanowires were first prepared via templated electrodeposition, and then partially converted into the well-known Cu-MOF HKUST-1 by pulsed electrochemical oxidation. We show that the use of PVP as a capping agent during the electrochemical oxidation of Cu2O into HKUST-1 provides control over the growth of the MOF nanocrystals on the surface of the Cu2O nanowires, and that the size of the MOF crystals obtained can be tuned by changing the concentration of PVP dissolved in the electrolyte. In addition, we propose the use of benzoic acid as an alternative to achieve control over the size of the obtained MOF nanocrystals when the use of a capping agent should be avoided.
Global ozone loss following extreme solar proton storms based on the July 2012 coronal mass ejection
Authors: Kalakoski Niilo , Verronen Pekka T. , Szeląg Monika E. , Jackman Charles H.
Published: August 2023

Large solar coronal mass ejections pose a threat in the near-Earth space. As a cause of extreme periods of space weather, they can damage satellite-based communications and create geomagnetically induced currents in power and energy grids. Further, the solar wind energetic particles can reduce the protecting layer of atmospheric ozone and pose a threat to life on Earth. The large coronal mass ejection (CME) of July 2012, although directed away from the Earth, is often highlighted as a prime example of a potentially devastating super storm. Here we show, based on proton fluxes recorded by the instruments aboard the STEREO-A satellite, that the atmospheric response to the July 2012 event would have been comparable to those of the largest solar proton events of the satellite era. Significant impact on total ozone outside polar regions would require a much larger event, similar to those recorded in historical proxy data sets. Such an extreme event would cause long-term ozone reduction all the way to the equator and increase the size, duration, and depth of the Antarctic ozone hole. The impact would be comparable to predicted drastic and sudden ozone reduction from major volcanic eruptions, regional nuclear conflicts, or long-term stratospheric geoengineering.
A brief questionnaire for measuring alarm fatigue in nurses and physicians in intensive care units
Authors: Wunderlich Maximilian Markus , Amende-Wolf Sandro , Krampe Henning , Kruppa Jochen , Spies Claudia , Weiß Björn , Memmert Belinda , Balzer Felix , Poncette Akira-Sebastian
Published: August 2023

When exposed to hundreds of medical device alarms per day, intensive care unit (ICU) staff can develop “alarm fatigue” (i.e., desensitisation to alarms). However, no standardised way of quantifying alarm fatigue exists. We aimed to develop a brief questionnaire for measuring alarm fatigue in nurses and physicians. After developing a list of initial items based on a literature review, we conducted 15 cognitive interviews with the target group (13 nurses and two physicians) to ensure that the items are face valid and comprehensible. We then asked 32 experts on alarm fatigue to judge whether the items are suited for measuring alarm fatigue. The resulting 27 items were sent to nurses and physicians from 15 ICUs of a large German hospital. We used exploratory factor analysis to further reduce the number of items and to identify scales. A total of 585 submissions from 707 participants could be analysed (of which 14% were physicians and 64% were nurses). The simple structure of a two-factor model was achieved within three rounds. The final questionnaire (called Charité Alarm Fatigue Questionnaire; CAFQa) consists of nine items along two scales (i.e., the “alarm stress scale” and the “alarm coping scale”). The CAFQa is a brief questionnaire that allows clinical alarm researchers to quantify the alarm fatigue of nurses and physicians. It should not take more than five minutes to administer.
Natural sensitizer extracted from Mussaenda erythrophylla for dye-sensitized solar cell
Authors: Rajaramanan Tharmakularasa , Heidari Gourji Fatemeh , Elilan Yogenthiran , Yohi Shivatharsiny , Senthilnanthanan Meena , Ravirajan Punniamoorthy , Velauthapillai Dhayalan
Published: August 2023

In this study, a natural dye from the flowers of Mussaenda erythrophylla extracted separately in ethanol and de-ionized water was employed as a photosensitizer in DSSCs. The quantitative phytochemical analyses were performed on both extracts. The existence of flavonoids (anthocyanin) and chlorophyll a pigments in the ethanol extract of the dye was confirmed by the UV–Visible spectroscopy. The stability study performed on the said ethanol extract confirmed that the dye extracted in ethanol was stable in the dark and did not degrade for nearly 50 days. The presence of the dye molecules and uniform adsorption of them on the P25-TiO2 surface were confirmed by fourier transform infrared spectroscopy and atomic force microscopy, respectively. Moreover, the influence of dye concentration and pH on the optical properties of the dye was also studied. The natural dye extracted in ethanol was employed in DSSCs, fabricated by utilizing the said dye sensitized P25-TiO2 photoanodes, $${I}^{-}$$

I

-

/$${I}_{3}^{-}$$

I

3

-

electrolyte, and Pt counter electrode. Photovoltaic performances of the fabricated devices were determined under simulated irradiation with the intensity of 100 mWcm–2 using AM 1.5 filter. The device fabricated with the P25-TiO2 photoanode sensitized by the dye extracted in ethanol at pH = 5 exhibited the best power conversion efficiency (PCE) of 0.41% with the JSC of 0.98 mAcm–2 which could be attributed to the optimum light absorption in the visible region of solar spectrum by the chlorophyll a and anthocyanin molecules in the extracted natural dye.
Veterinary education and experience shape beliefs about dog breeds. Part 2: Trust
Authors: Caddiell Rachel M. P. , White Philip , Lascelles B. Duncan X. , Royal Kenneth , Ange-van Heugten Kimberly , Gruen Margaret E.
Published: August 2023

Dog breed stereotypes are frequently used to inform people’s expectations about canine behavior, despite evidence that breed is largely uninformative in predicting individual dog behavior. Further, these beliefs differ among populations. However, it remains unknown how ratings of warmth toward a breed are associated with ratings of other social behavioral domains, and whether differences exist between populations with varying experience with dogs. The purpose of this study was to evaluate ratings of trust and warmth among survey respondents including veterinary students, veterinary faculty and staff, undergraduates in animal-health related majors and members of the general public. Using an online survey, respondents rated their likelihood to trust a dog in varying scenarios for 10 different dog breeds. Additionally, respondents used a feelings thermometer to rate how warm or cool they felt towards each breed. Findings revealed differences in feelings thermometer and trust ratings across populations. All ratings were lower among the veterinary academic respondents compared to the general public and undergraduates. Veterinary students further along in their training, as well as undergraduates with clinical experience, reflected perceptions similar to those of the veterinary faculty and staff providing support for cultural transmission of beliefs during veterinary education and training.
Cross-species comparative analysis of single presynapses
Authors: Berson Eloïse , Gajera Chandresh R. , Phongpreecha Thanaphong , Perna Amalia , Bukhari Syed A. , Becker Martin , Chang Alan L. , De Francesco Davide , Espinosa Camilo , Ravindra Neal G. , Postupna Nadia , Latimer Caitlin S. , Shively Carol A. , Register Thomas C. , Craft Suzanne , Montine Kathleen S. , Fox Edward J. , Keene C. Dirk , Bendall Sean C. , Aghaeepour Nima , Montine Thomas J.
Published: August 2023

Comparing brain structure across species and regions enables key functional insights. Leveraging publicly available data from a novel mass cytometry-based method, synaptometry by time of flight (SynTOF), we applied an unsupervised machine learning approach to conduct a comparative study of presynapse molecular abundance across three species and three brain regions. We used neural networks and their attractive properties to model complex relationships among high dimensional data to develop a unified, unsupervised framework for comparing the profile of more than 4.5 million single presynapses among normal human, macaque, and mouse samples. An extensive validation showed the feasibility of performing cross-species comparison using SynTOF profiling. Integrative analysis of the abundance of 20 presynaptic proteins revealed near-complete separation between primates and mice involving synaptic pruning, cellular energy, lipid metabolism, and neurotransmission. In addition, our analysis revealed a strong overlap between the presynaptic composition of human and macaque in the cerebral cortex and neostriatum. Our unique approach illuminates species- and region-specific variation in presynapse molecular composition.
Assessing the recovery of Y chromosome microsatellites with population genomic data using Papio and Theropithecus genomes
Authors: Mutti Giacomo , Oteo-Garcia Gonzalo , Caldon Matteo , da Silva Maria Joana Ferreira , Minhós Tânia , Cowlishaw Guy , Gottelli Dada , Huchard Elise , Carter Alecia , Martinez Felipe I. , Raveane Alessandro , Capelli Cristian
Published: August 2023

Y chromosome markers can shed light on male-specific population dynamics but for many species no such markers have been discovered and are available yet, despite the potential for recovering Y-linked loci from available genome sequences. Here, we investigated how effective available bioinformatic tools are in recovering informative Y chromosome microsatellites from whole genome sequence data. In order to do so, we initially explored a large dataset of whole genome sequences comprising individuals at various coverages belonging to different species of baboons (genus: Papio) using Y chromosome references belonging to the same genus and more distantly related species (Macaca mulatta). We then further tested this approach by recovering Y-STRs from available Theropithecus gelada genomes using Papio and Macaca Y chromosome as reference sequences. Identified loci were validated in silico by a) comparing within-species relationships of Y chromosome lineages and b) genotyping male individuals in available pedigrees. Each STR was selected not to extend in its variable region beyond 100 base pairs, so that loci can be developed for PCR-based genotyping of non-invasive DNA samples. In addition to assembling a first set of Papio and Theropithecus Y-specific microsatellite markers, we released TYpeSTeR, an easy-to-use script to identify and genotype Y chromosome STRs using population genomic data which can be modulated according to available male reference genomes and genomic data, making it widely applicable across taxa.
MwdpNet: towards improving the recognition accuracy of tiny targets in high-resolution remote sensing image
Authors: Ma Dongling , Liu Baoze , Huang Qingji , Zhang Qian
Published: August 2023

This study aims to develop a deep learning model to improve the accuracy of identifying tiny targets on high resolution remote sensing (HRS) images. We propose a novel multi-level weighted depth perception network, which we refer to as MwdpNet, to better capture feature information of tiny targets in HRS images. In our method, we introduce a new group residual structure, S-Darknet53, as the backbone network of our proposed MwdpNet, and propose a multi-level feature weighted fusion strategy that fully utilizes shallow feature information to improve detection performance, particularly for tiny targets. To fully describe the high-level semantic information of the image, achieving better classification performance, we design a depth perception module (DPModule). Following this step, the channel attention guidance module (CAGM) is proposed to obtain attention feature maps for each scale, enhancing the recall rate of tiny targets and generating candidate regions more efficiently. Finally, we create four datasets of tiny targets and conduct comparative experiments on them. The results demonstrate that the mean Average Precision (mAP) of our proposed MwdpNet on the four datasets achieve 87.0%, 89.2%, 78.3%, and 76.0%, respectively, outperforming nine mainstream object detection algorithms. Our proposed approach provides an effective means and strategy for detecting tiny targets on HRS images.