bluuebunny/crossref_metadata_2025 huggingface dataset:
Only two in five pregnant women have adequate dietary diversity during antenatal care at Hiwot Fana Specialized University Hospital in Eastern Ethiopia
Authors: Mesfin Sinetibeb , Abebe Dawit , Jiru Hirut Dinku , Sori Seboka Abebe
Published: March 2024

Dietary diversification is a sustainable and appealing strategy for pregnant women to ensure a balanced dietary intake. In Ethiopia, despite the implementation of various nutritional initiatives, inadequate dietary diversity remains a significant factor contributing to adverse birth outcomes. Thus, this study aimed to assess the dietary diversity and associated characteristics among pregnant women attending antenatal care in Eastern Ethiopia. Institution-based cross-sectional study was conducted from April 28 to May 28, 2021. A total of 420 pregnant women were selected using a systematic random sampling technique. We used the adjusted odds ratio (AOR) and a 95% confidence interval to estimate the strength of the association. We used a p-value of 0.05 to declare statistical significance. Only 35.0% (95% CI: 30.5, 39.5) of the 420 pregnant women involved in this study received appropriate dietary diversity. Having an educational level of college and above (AOR 3.01, 95% CI: 1.19–7.5), being an urban dweller (AOR = 3.57, 95% CI: 1.68–7.52), eating three meals and above (AOR = 7.62, 95% CI: 2.88–9.03), and having ≤4 family sizes (AOR = 9.33, 95% CI: 4.06–10.4) were significantly associated with an adequate dietary diversity score among pregnant women. This study found that pregnant women had inadequate overall consumption of a diversified diet. Increasing meal frequency, enhancing women’s education, raising awareness of dietary diversity among rural inhabitants, and offering counselling on family planning utilisation during ANC services are all beneficial in promoting dietary diversity among pregnant women.
Inequalities between time and customer averages for HNB(W)UE arrival processes
Authors: Shioda Shigeo , Nakano Kana
Published: March 2024

We show that for arrival processes, the ‘harmonic new better than used in expectation’ (HNBUE) (or ‘harmonic new worse than used in expectation’, HNWUE) property is a sufficient condition for inequalities between the time and customer averages of the system if the state of the system between arrival epochs is stochastically decreasing and convex and the lack of anticipation assumption is satisfied. HNB(W)UE is a wider class than NB(W)UE, being the largest of all available classes of distributions with positive (negative) aging properties. Thus, this result represents an important step beyond existing result on inequalities between time and customer averages, which states that for arrival processes, the NB(W)UE property is a sufficient condition for inequalities.
ON THE FRAGILITY OF INTERPOLATION
Authors: TARLECKI ANDRZEJ
Published: March 2024

We study a version of the Craig interpolation theorem formulated in the framework of the theory of institutions. This formulation proved crucial in the development of a number of key results concerning foundations of software specification and formal development. We investigate preservation of interpolation properties under institution extensions by new models and sentences. We point out that some interpolation properties remain stable under such extensions, even if quite arbitrary new models and sentences are permitted. We give complete characterisations of such situations for institution extensions by new models, by new sentences, as well as by new models and sentences, respectively.
THREE SURPRISING INSTANCES OF DIVIDING
Authors: CONANT GABRIEL , KRUCKMAN ALEX
Published: March 2024

We give three counterexamples to the folklore claim that in an arbitrary theory, if a complete type p over a set B does not divide over

$C\subseteq B$

, then no extension of p to a complete type over

$\operatorname {acl}(B)$

divides over C. Two of our examples are also the first known theories where all sets are extension bases for nonforking, but forking and dividing differ for complete types (answering a question of Adler). One example is an

$\mathrm {NSOP}_1$

theory with a complete type that forks, but does not divide, over a model (answering a question of d’Elbée). Moreover, dividing independence fails to imply M-independence in this example (which refutes another folklore claim). In addition to these counterexamples, we summarize various related properties of dividing that are still true. We also address consequences for previous literature, including an earlier unpublished result about forking and dividing in free amalgamation theories, and some claims about dividing in the theory of generic

$K_{m,n}$

-free incidence structures.
A Sense of a European Present and its Passing during the Revolutions of 1848
Authors: Morris James
Published: March 2024

This article explores the temporality of revolution in 1848. It argues that what united the various revolutionary movements of that year was a sense of participating in a common European ‘present’, in which old imperial hierarchies collapsed and every cause and people seemed to exist in the same historical moment. The significance of that sense of the present was visible across the continent, but it was of greatest significance in the revolutionary theatres beyond the core imperial centres, and it was those places that would suffer first when that present passed. Too much ‘history’ was taking place at once, and as events in different settings followed their own particular courses, minds turned away from a European project. As European unity faltered, it was the representatives of imperial counter-revolution who demonstrated their ability to think strategically on a continent-wide level. They defeated the various movements, which had promised a better European present, and deferred improvements to the future. By doing so, they returned the peoples of the continent to their own particular – rather than common European – ‘nows’.
An applicator for high-power rock comminution using microwave technology in the megawatt range
Authors: Alekajbaf Yasin , Dancila Dragos
Published: March 2024

The mining industry is heavily dependent on energy-intensive processes, such as rock breakage, which leads to significant operational costs. This paper explores microwave-assisted rock breakage as an innovative method to enhance the efficiency of comminution within the mining industry. It introduces a system that employs a Klystron microwave power source with a maximum output of 7.5 MW, using a

$\mathrm{TM}_{010}$

single-mode cavity at 3 GHz, to channel energy inside a specially designed rock cavity. The paper emphasizes the importance of designing an efficient microwave cavity for this system, focusing on the cavity’s design and simulation. Through both simulated results (using HFSS software) and experimental observations, the study reveals the promising application of microwave technology in the field of mining. The simulated frequency response of the designed cavity (S11) is −22 dB, it demonstrates significant potential for reducing both energy consumption and associated costs. Additionally, the designed cavity is fabricated from aluminum and filled with polyether ether ketone material. The measured frequency response (S11) of the cavity at 3 GHz is −17 dB.
Mental health and help-seeking in Czech sexual minorities: a nationally representative cross-sectional study
Authors: Pitoňák Michal , Potočár Libor , Formánek Tomáš
Published: March 2024

Aims

The mental health of sexual minority (SM) individuals remains overlooked and understudied in Czechia. We aimed to estimate (1) the prevalence rate and (2) the relative risk of common mental disorders and (3) the mental distress severity among the Czech SM people compared with the heterosexual population. In addition, we aimed to investigate help-seeking for mental disorders in SM people.

Methods

We used data from a cross-sectional, nationally representative survey of Czech community-dwelling adults, consisting of 3063 respondents (response rate = 58.62%). We used the Mini-International Neuropsychiatric Interview to assess the presence of mental disorders. In individuals scoring positively, we established help-seeking in the past 12 months. We assessed symptom severity using the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder scale. We computed the prevalence of mental disorders and the treatment gap with 95% confidence intervals. To assess the risk of having a mental disorder, we used binary logistic regression.

Results

We demonstrated that the prevalence of current mental disorders was 18.85% (17.43–20.28), 52.27% (36.91–67.63), 33.33% (19.5–47.17) and 25.93% (13.85–38) in heterosexual, gay or lesbian, bisexual and more sexually diverse individuals, respectively. Suicidal thoughts and behaviours were present in 5.73% (4.88–6.57), 25.00% (11.68–38.32), 22.92% (10.58–35.25) and 11.11% (2.45–19.77) of heterosexual, gay or lesbian, bisexual and more sexually diverse individuals, respectively. After confounder adjustment, gay or lesbian individuals were more likely to have at least one current mental disorder compared with heterosexual counterparts (odds ratio = 3.51; 1.83–6.76). For bisexual and sexually more diverse individuals, the results were consistent with a null effect (1.85; 0.96–3.45 and 0.89; 0.42–1.73). The mean depression symptom severity was 2.96 (2.81–3.11) in heterosexual people and 4.68 (2.95–6.42), 7.12 (5.07–9.18) and 5.17 (3.38–6.95) in gay or lesbian, bisexual and more sexually diverse individuals, respectively. The mean anxiety symptom severity was 1.97 (1.85–2.08) in heterosexual people and 3.5 (1.98–5.02), 4.63 (3.05–6.2) and 3.7 (2.29–5.11) in gay or lesbian, bisexual and more sexually diverse individuals, respectively. We demonstrated broadly consistent levels of treatment gap in heterosexual and SM individuals scoring positively for at least one current mental disorder (82.91%; 79.5–85.96 vs. 81.13%; 68.03–90.56).

Conclusions

We provide evidence that SM people in Czechia have substantially worse mental health outcomes than their heterosexual counterparts. Systemic changes are imperative to provide not only better and more sensitive care to SM individuals but also to address structural stigma contributing to these health disparities.
Heat and Moisture Anomalies During Crop Failure Events in the Southeastern Australian Wheat Belt
Authors: Li Hao , Keune Jessica , Gou Qiqi , Holgate Chiara M. , Miralles Diego
Published: March 2024

Prolonged droughts and heatwaves are common causes of agricultural failure in Australia, yet the origins of these climate anomalies remain understudied. Here, we use a Lagrangian trajectory model driven by atmospheric reanalysis and constrained by satellite data to unravel the sources of precipitation and heat over the Southeastern Australia wheat belt. Furthermore, we assess the impact of local and upwind drought conditions on the moisture and heat imports to the region. Results indicate that the most extreme crop failure events over the wheat belt (i.e., 1994, 2002, and 2006) were associated with persistent high‐pressure systems. The ocean provided on average 72% of the moisture for precipitation and 39% of the heat arriving over the wheat belt, with the moisture sources substantially decreasing during crop failure events. Upwind drought further intensified rainfall deficits and heat stress during these events due to lower moisture and higher heat imports to the region. This was particularly clear during the initial phase of the Millennium Drought in 2002. Then, yield deficits exceeded 50%, and ∼4% of the precipitation originated from drought‐affected regions upwind, compared to the 9% that was expected climatologically from those regions. Simultaneously, the heat import from these regions upwind increased by ∼10 W m−2, from the climatological 23%–25%, during this event. While these results indicate a limited potential for upwind land management to mitigate downwind agricultural loss in the Southeastern Australia wheat belt, other agricultural regions with a higher climatic dependency on remote land may benefit from such strategies.
Subseasonal Variability of Humid Heat During the South Asian Summer Monsoon
Authors: Ivanovich C. C. , Horton R. M. , Sobel A. H. , Singh D.
Published: March 2024

The South Asian summer monsoon strongly modulates regional temperature and humidity. While extreme dry heat peaks in the pre‐monsoon season, recent literature suggests that extreme humid heat can continue to build throughout the monsoon season. Here we explore the influence of monsoon onset and subseasonal precipitation variability on the occurrence of extreme wet bulb temperatures (Tw) across South Asia. We find that extreme Tw events often occur on rainy days during the monsoon season. However, the influence of precipitation on Tw varies with the background climatology of surface specific humidity. In climatologically drier areas, positive Tw anomalies tend to occur when precipitation increases due to either early onset or wet spells during the monsoon. In contrast, in climatologically humid areas, positive Tw anomalies occur during periods of suppressed precipitation, including both delayed onset and dry spells during the monsoon.
Informative Modes of Seismicity in Nearest‐Neighbor Earthquake Proximities
Authors: Hsu Yu‐Fang , Zaliapin Ilya , Ben‐Zion Yehuda
Published: March 2024

We analyze nearest‐neighbor proximities of earthquakes in California based on the joint distribution (T, R) of rescaled time T and rescaled distance R between pairs of earthquakes (Zaliapin & Ben‐Zion, 2013a, https://doi.org/10.1002/jgrb.50179), using seismic catalogs from several regions and several catalogs for the San Jacinto Fault Zone (SJFZ). The study aims to identify informative modes in nearest‐neighbor diagrams beyond the general background and clustered modes, and to assess seismic catalogs derived by different methods. The results show that earthquake clusters with large and small‐to‐medium mainshocks have approximately diagonal and horizontal (T, R) distributions of the clustered mode, respectively, reflecting different triggering distances of mainshocks. Earthquakes in the creeping section of San Andreas Fault have a distinct “repeaters mode” characterized by very large rescaled times T and very small rescaled distances R, due to nearly identical locations of repeating events. Induced seismicity in the Geysers and Coso geothermal fields follow mostly the background mode, but with larger rescaled times T and smaller rescaled distances R compared to tectonic background seismicity. We also document differences in (T, R) distributions of catalogs constructed by different techniques (analyst‐picks, template‐matching and deep‐learning) for the SJFZ, and detect a mode with very large R and small T in the template‐matching and deep‐learning based catalogs. This mode may reflect dynamic triggering by passing waves and/or catalog artifacts.
Reconfigurable transmissive metasurface with a combination of scissor and rotation actuators for independently controlling beam scanning and polarization conversion
Authors: Lor Chhunheng , Phon Ratanak , Lim Sungjoon
Published: March 2024

Polarization conversion and beam scanning metasurfaces are commonly used to reduce polarization mismatch and direct electromagnetic waves in a specific direction to improve the strength of a wireless signal. However, identifying suitable active and mechanically reconfigurable metasurfaces for polarization conversion and beam scanning is a considerable challenge, and the reported metasurfaces have narrow scanning ranges, are expensive, and cannot be independently controlled. In this paper, we propose a reconfigurable transmissive metasurface combined with a scissor and rotation actuator for independently controlling beam scanning and polarization conversion functions. The metasurface is constructed with rotatable unit cells (UCs) that can switch the polarization state between right-handed (RHCP) and left-handed circular polarization (LHCP) by flipping the UCs to reverse their phase variation. Moreover, independent beam scanning is achieved using the scissor actuator to linearly change the distance between the UCs. Numerical and experimental results confirm that the proposed metasurface can perform beam scanning in the range of 28° for both the positive and negative regions of a radiation pattern (RHCP and LHCP beams) at an operational frequency of 10.5 GHz.
DNA methylation of IFI44L as a potential blood biomarker for childhood-onset systemic lupus erythematosus
Authors: Wang Jingwei , Dang Xiqiang , Wu Xiaochuan , Xiang Zhongyuan , Li Yongzhen , Fu Yaqian , Shen Tian
Published: March 2024

Background

IFN-induced protein 44-like (IFI44L) promoter methylation has been demonstrated to serve as an effective blood diagnostic biomarker for adult-onset SLE. However, its utility as a diagnostic marker for childhood-onset SLE (cSLE) remains to be verified.

Methods

Initially, we conducted a differential analysis of gene methylation and mRNA expression patterns in cSLE whole blood samples obtained from the public GEO database to determine IFI44L gene expression and assess the methylation status at its CpG sites. Subsequently, we collected clinical whole blood samples from 49 cSLE patients and 12 healthy children, employing an HRM-qPCR-based IFI44L methylation detection technique to evaluate its diagnostic efficacy in pediatric clinical practice.

Results

A total of 26 hypomethylated, highly expressed genes in cSLE were identified by intersecting differentially expressed genes (DEGs) and differentially methylation genes (DMGs). GO enrichment analysis for these 26 genes indicated a robust association with type I IFN. Among the overlapping genes, IFI44L exhibited the most pronounced differential expression and methylation. In subsequent clinical validation experiments, IFI44L methylation was confirmed as an effective blood-based diagnostic biomarker for cSLE, achieving an AUC of 0.867, a sensitivity of 0.753, and a specificity of 1.000.

Conclusions

IFI44L methylation is a promising blood biomarker for cSLE.

Impact

IFI44L promoter methylation was reported to serve as a highly sensitive and specific diagnostic marker for adult-onset SLE. However, the diagnostic efficacy of IFI44L in childhood-onset SLE (cSLE) still remains to be confirmed. In this study, we utilized bioinformatics analysis and conducted clinical experiments to demonstrate that IFI44L methylation can also serve as a promising blood biomarker for cSLE. The findings of this study can facilitate the diagnosis of cSLE and broaden our understanding of its molecular mechanisms, with a particular focus on those related to type I interferons.
Monitoring Activity and Gait in Children (MAGIC) using digital health technologies
Authors: Di Junrui , Tuttle Pirinka Georgiev , Adamowicz Lukas , Lin Wenyi , Zhang Hao , Psaltos Dimitrios , Selig Jessica , Bai Jiawei , Karahanoglu F. Isik , Sheriff Paul , Seelam Vijitha , Williams Bunmi , Ghafoor Sana , Demanuele Charmaine , Santamaria Mar , Cai Xuemei
Published: March 2024

Background

Digital health technologies (DHTs) can collect gait and physical activity in adults, but limited studies have validated these in children. This study compared gait and physical activity metrics collected using DHTs to those collected by reference comparators during in-clinic sessions, to collect a normative accelerometry dataset, and to evaluate participants’ comfort and their compliance in wearing the DHTs at-home.

Methods

The MAGIC (Monitoring Activity and Gait in Children) study was an analytical validation study which enrolled 40, generally healthy participants aged 3–17 years. Gait and physical activity were collected using DHTs in a clinical setting and continuously at-home.

Results

Overall good to excellent agreement was observed between gait metrics extracted with a gait algorithm from a lumbar-worn DHT compared to ground truth reference systems. Majority of participants either “agreed” or “strongly agreed” that wrist and lumbar DHTs were comfortable to wear at home, respectively, with 86% (wrist-worn DHT) and 68% (lumbar-worn DHT) wear-time compliance. Significant differences across age groups were observed in multiple gait and activity metrics obtained at home.

Conclusions

Our findings suggest that gait and physical activity data can be collected from DHTs in pediatric populations with high reliability and wear compliance, in-clinic and in home environments.

Trial registration

ClinicalTrials.gov: NCT04823650

Impact

Digital health technologies (DHTs) have been used to collect gait and physical activity in adult populations, but limited studies have validated these metrics in children.

The MAGIC study comprehensively validates the performance and feasibility of DHT-measured gait and physical activity in the pediatric population.

Our findings suggest that reliable gait and physical activity data can be collected from DHTs in pediatric populations, with both high accuracy and wear compliance both in-clinic and in home environments.

The identified across-age-group differences in gait and activity measurements highlighted their potential clinical value.
Exploring knowledge and implementation gaps of activity-based therapy in centers lacking specialized spinal cord injury services: understanding therapists’ perspectives
Authors: Cesca Nicole , Lin Chantal , Abu-Jurji Zeina , Wexler Aaron , Mark Jonas , McCullum Shane , Kamran Rija , Chan Brian , Musselman Kristin E.
Published: March 2024

Study design

Qualitative exploratory

Objectives

Rehabilitation following spinal cord injury (SCI) is a life-long process involving healthcare in a variety of settings, including facilities lacking SCI-specific services (i.e., non-SCI-specialized centers). Activity-based therapy (ABT) is a neurorestorative approach involving intensive, task-specific movement practice below the injury level. This study explored the existing knowledge, perceptions, and implementation of ABT among physical and occupational therapists working in non-SCI-specialized centers.

Setting

Canadian hospitals and community clinics

Design/methods

Semi-structured interviews were conducted with Canadian therapists who worked at non-SCI-specialized centers and treated at least one patient with SCI within the last 18 months. The Theoretical Domains Framework was used to develop interview questions that queried therapists’ experiences in delivering SCI rehabilitation, their understanding of ABT and experience with its implementation. Interviews were audio-recorded, transcribed verbatim and analyzed using interpretive description.

Results

Four physical therapists and three occupational therapists, from diverse settings (i.e., acute care, inpatient rehabilitation, long-term care, outpatient rehabilitation, rural outpatient clinic) participated. Three themes were identified: (1) Available knowledge, resources and therapy time in non-SCI-specialized centers challenge ABT implementation, (2) How current therapy practices in non-SCI-specialized centers align with ABT and (3) Desire for ABT knowledge. Although participants were not familiar with the term ABT, it was identified that they were unknowingly incorporating some components of ABT into their practice. Participants expressed a keenness to learn more about ABT.

Conclusion

Current knowledge and implementation of ABT in non-SCI-specialized centers is limited. Tailoring ABT education to therapists at non-SCI-specialized centers may increase ABT implementation.
VDR and deubiquitination control neuronal oxidative stress and microglial inflammation in Parkinson’s disease
Authors: Zheng Zihui , Chen Miao , Feng Shengliang , Zhao Huanhuan , Qu Tiange , Zhao Xudong , Ruan Qinli , Li Lei , Guo Jun
Published: March 2024

Close correlation between vitamin D (VitD) deficiency and Parkinson’s Disease (PD) risk, VitD as an adjuvant treatment promising to improve PD progression. However, VitD excessive intake could induce hypercalcemia and renal damage. Therefore, upregulation of vitD receptor (VDR) is considered a compensatory strategy to overcome VitD insufficiency and alleviate PD symptoms. In this study, we discovered that VDR played antioxidative roles in dopaminergic neurons by decreasing reactive oxygen species (ROS) and maintaining mitochondrial membrane potential. Further, we newly identified VDR downstream events in C. elegans, including glutathione S-transferase (gst) and forkhead box transcription factor class O (daf-16) mediated oxidative stress resistance. VDR upregulation also mitigated microglial activation through inhibition of NLRP3/caspase-1-mediated inflammation and membrane permeabilization. These findings highlight the multifaceted protective effects of VDR in both neurons and microglia against the development of PD. Importantly, we discovered a novel deubiquitinase DUB3, whose N-terminal catalytic domain interacted with the C-terminal ligand-binding domain of VDR to reduce VDR ubiquitination. Identification of DUB3 as an essential player in the deubiquitinating mechanism of VDR provides valuable insights into VDR regulation and its potential as a therapeutic target for PD.
Osteocyte mitochondria regulate angiogenesis of transcortical vessels
Authors: Liao Peng , Chen Long , Zhou Hao , Mei Jiong , Chen Ziming , Wang Bingqi , Feng Jerry Q. , Li Guangyi , Tong Sihan , Zhou Jian , Zhu Siyuan , Qian Yu , Zong Yao , Zou Weiguo , Li Hao , Zhang Wenkan , Yao Meng , Ma Yiyang , Ding Peng , Pang Yidan , Gao Chuan , Mei Jialun , Zhang Senyao , Zhang Changqing , Liu Delin , Zheng Minghao , Gao Junjie
Published: March 2024

Transcortical vessels (TCVs) provide effective communication between bone marrow vascular system and external circulation. Although osteocytes are in close contact with them, it is not clear whether osteocytes regulate the homeostasis of TCVs. Here, we show that osteocytes maintain the normal network of TCVs by transferring mitochondria to the endothelial cells of TCV. Partial ablation of osteocytes causes TCV regression. Inhibition of mitochondrial transfer by conditional knockout of Rhot1 in osteocytes also leads to regression of the TCV network. By contrast, acquisition of osteocyte mitochondria by endothelial cells efficiently restores endothelial dysfunction. Administration of osteocyte mitochondria resultes in acceleration of the angiogenesis and healing of the cortical bone defect. Our results provide new insights into osteocyte-TCV interactions and inspire the potential application of mitochondrial therapy for bone-related diseases.
The AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions
Authors: Lanfranchi Marine , Yandiev Sozerko , Meyer-Dilhet Géraldine , Ellouze Salma , Kerkhofs Martijn , Dos Reis Raphael , Garcia Audrey , Blondet Camille , Amar Alizée , Kneppers Anita , Polvèche Hélène , Plassard Damien , Foretz Marc , Viollet Benoit , Sakamoto Kei , Mounier Rémi , Bourgeois Cyril F. , Raineteau Olivier , Goillot Evelyne , Courchet Julien
Published: March 2024

The cellular mechanisms underlying axonal morphogenesis are essential to the formation of functional neuronal networks. We previously identified the autism-linked kinase NUAK1 as a central regulator of axon branching through the control of mitochondria trafficking. However, (1) the relationship between mitochondrial position, function and axon branching and (2) the downstream effectors whereby NUAK1 regulates axon branching remain unknown. Here, we report that mitochondria recruitment to synaptic boutons supports collateral branches stabilization rather than formation in mouse cortical neurons. NUAK1 deficiency significantly impairs mitochondrial metabolism and axonal ATP concentration, and upregulation of mitochondrial function is sufficient to rescue axonal branching in NUAK1 null neurons in vitro and in vivo. Finally, we found that NUAK1 regulates axon branching through the mitochondria-targeted microprotein BRAWNIN. Our results demonstrate that NUAK1 exerts a dual function during axon branching through its ability to control mitochondrial distribution and metabolic activity.
Universal control of a bosonic mode via drive-activated native cubic interactions
Authors: Eriksson Axel M. , Sépulcre Théo , Kervinen Mikael , Hillmann Timo , Kudra Marina , Dupouy Simon , Lu Yong , Khanahmadi Maryam , Yang Jiaying , Castillo-Moreno Claudia , Delsing Per , Gasparinetti Simone
Published: March 2024

Linear bosonic modes offer a hardware-efficient alternative for quantum information processing but require access to some nonlinearity for universal control. The lack of nonlinearity in photonics has led to encoded measurement-based quantum computing, which relies on linear operations but requires access to resourceful (’nonlinear’) quantum states, such as cubic phase states. In contrast, superconducting microwave circuits offer engineerable nonlinearities but suffer from static Kerr nonlinearity. Here, we demonstrate universal control of a bosonic mode composed of a superconducting nonlinear asymmetric inductive element (SNAIL) resonator, enabled by native nonlinearities in the SNAIL element. We suppress static nonlinearities by operating the SNAIL in the vicinity of its Kerr-free point and dynamically activate nonlinearities up to third order by fast flux pulses. We experimentally realize a universal set of generalized squeezing operations, as well as the cubic phase gate, and exploit them to deterministically prepare a cubic phase state in 60 ns. Our results initiate the experimental field of polynomial quantum computing, in the continuous-variables notion originally introduced by Lloyd and Braunstein.
Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction
Authors: Xie Ruoqian , Li Wanlu , Ge Yuhua , Zhou Yutong , Xiao Guolan , Zhao Qin , Han Yunxi , Li Yangyan , Chen Gang
Published: March 2024

Chemically modified nucleosi(ti)des and functional oligonucleotides (ONs, including therapeutic oligonucleotides, aptamer, nuclease, etc.) have been identified playing an essential role in the areas of medicinal chemistry, chemical biology, biotechnology, and nanotechnology. Introduction of functional groups into the nucleobases of ONs mostly relies on the laborious de novo chemical synthesis. Due to the importance of nucleosides modification and aforementioned limitations of functionalizing ONs, herein, we describe a highly efficient site-selective alkylation at the C8-position of guanines in guanosine (together with its analogues), GMP, GDP, and GTP, as well as late-stage functionalization of dinucleotides and single-strand ONs (including ssDNA and RNA) through photo-mediated Minisci reaction. Addition of catechol to assist the formation of alkyl radicals via in situ generated boronic acid catechol ester derivatives (BACED) markedly enhances the yields especially for the reaction of less stable primary alkyl radicals, and is the key to success for the post-synthetic alkylation of ONs. This method features excellent chemoselectivity, no necessity for pre-protection, wide range of substrate scope, various free radical precursors, and little strand lesion. Downstream applications in disease treatment and diagnosis, or as biochemical probes to study biological processes after linking with suitable fluorescent compounds are expected.
An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway
Authors: Liu Grace Y. , Jouandin Patrick , Bahng Raymond E. , Perrimon Norbert , Sabatini David M.
Published: March 2024

Animals sense and respond to nutrient availability in their environments, a task coordinated in part by the mTOR complex 1 (mTORC1) pathway. mTORC1 regulates growth in response to nutrients and, in mammals, senses specific amino acids through specialized sensors that bind the GATOR1/2 signaling hub. Given that animals can occupy diverse niches, we hypothesized that the pathway might evolve distinct sensors in different metazoan phyla. Whether such customization occurs, and how the mTORC1 pathway might capture new inputs, is unknown. Here, we identify the Drosophila melanogaster protein Unmet expectations (CG11596) as a species-restricted methionine sensor that directly binds the fly GATOR2 complex in a fashion antagonized by S-adenosylmethionine (SAM). We find that in Dipterans GATOR2 rapidly evolved the capacity to bind Unmet and to thereby repurpose a previously independent methyltransferase as a SAM sensor. Thus, the modular architecture of the mTORC1 pathway allows it to co-opt preexisting enzymes to expand its nutrient sensing capabilities, revealing a mechanism for conferring evolvability on an otherwise conserved system.
An optofluidic antenna for enhancing the sensitivity of single-emitter measurements
Authors: Morales-Inostroza Luis , Folz Julian , Kühnemuth Ralf , Felekyan Suren , Wieser Franz-Ferdinand , Seidel Claus A. M. , Götzinger Stephan , Sandoghdar Vahid
Published: March 2024

Many single-molecule investigations are performed in fluidic environments, for example, to avoid unwanted consequences of contact with surfaces. Diffusion of molecules in this arrangement limits the observation time and the number of collected photons, thus, compromising studies of processes with fast or slow dynamics. Here, we introduce a planar optofluidic antenna (OFA), which enhances the fluorescence signal from molecules by about 5 times per passage, leads to about 7-fold more frequent returns to the observation volume, and significantly lengthens the diffusion time within one passage. We use single-molecule multi-parameter fluorescence detection (sm-MFD), fluorescence correlation spectroscopy (FCS) and Förster resonance energy transfer (FRET) measurements to characterize our OFAs. The antenna advantages are showcased by examining both the slow (ms) and fast (50 μs) dynamics of DNA four-way (Holliday) junctions with real-time resolution. The FRET trajectories provide evidence for the absence of an intermediate conformational state and introduce an upper bound for its lifetime. The ease of implementation and compatibility with various microscopy modalities make OFAs broadly applicable to a diverse range of studies.
Oxygen-independent organic photosensitizer with ultralow-power NIR photoexcitation for tumor-specific photodynamic therapy
Authors: Tang Yufu , Li Yuanyuan , Li Bowen , Song Wentao , Qi Guobin , Tian Jianwu , Huang Wei , Fan Quli , Liu Bin
Published: March 2024

Photodynamic therapy (PDT) is a promising cancer treatment but has limitations due to its dependence on oxygen and high-power-density photoexcitation. Here, we report polymer-based organic photosensitizers (PSs) through rational PS skeleton design and precise side-chain engineering to generate •O2− and •OH under oxygen-free conditions using ultralow-power 808 nm photoexcitation for tumor-specific photodynamic ablation. The designed organic PS skeletons can generate electron-hole pairs to sensitize H2O into •O2− and •OH under oxygen-free conditions with 808 nm photoexcitation, achieving NIR-photoexcited and oxygen-independent •O2− and •OH production. Further, compared with commonly used alkyl side chains, glycol oligomer as the PS side chain mitigates electron-hole recombination and offers more H2O molecules around the electron-hole pairs generated from the hydrophobic PS skeletons, which can yield 4-fold stronger •O2− and •OH production, thus allowing an ultralow-power photoexcitation to yield high PDT effect. Finally, the feasibility of developing activatable PSs for tumor-specific photodynamic therapy in female mice is further demonstrated under 808 nm irradiation with an ultralow-power of 15 mW cm−2. The study not only provides further insights into the PDT mechanism but also offers a general design guideline to develop an oxygen-independent organic PS using ultralow-power NIR photoexcitation for tumor-specific PDT.
Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer
Authors: Kasikova Lenka , Rakova Jana , Hensler Michal , Lanickova Tereza , Tomankova Jana , Pasulka Josef , Drozenova Jana , Mojzisova Katerina , Fialova Anna , Vosahlikova Sarka , Laco Jan , Ryska Ales , Dundr Pavel , Kocian Roman , Brtnicky Tomas , Skapa Petr , Capkova Linda , Kovar Marek , Prochazka Jan , Praznovec Ivan , Koblizek Vladimir , Taskova Alice , Tanaka Hisashi , Lischke Robert , Mendez Fernando Casas , Vachtenheim Jiri , Heinzelmann-Schwarz Viola , Jacob Francis , McNeish Iain A. , Halaska Michal J. , Rob Lukas , Cibula David , Orsulic Sandra , Galluzzi Lorenzo , Spisek Radek , Fucikova Jitka
Published: March 2024

Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8+ effector T (TEFF) cells and TIM3+PD1+, hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8+ T cells. Conversely, CD8+ T cells from immunologically hot tumors like non-small cell lung carcinoma (NSCLC) are enriched in ICI-responsive TCF1+ PD1+ T cells. Spatial B-cell profiling identifies patterns of in situ maturation and differentiation associated with mTLSs. Moreover, B-cell depletion promotes signs of a dysfunctional CD8+ T cell compartment among tumor-infiltrating lymphocytes from freshly isolated HGSOC and NSCLC biopsies. Taken together, our data demonstrate that – at odds with NSCLC – HGSOC is associated with a low density of follicular helper T cells and thus develops a limited number of mTLS that might be insufficient to preserve a ICI-sensitive TCF1+PD1+ CD8+ T cell phenotype. These findings point to key quantitative and qualitative differences between mTLSs in ICI-responsive vs ICI-irresponsive neoplasms that may guide the development of alternative immunotherapies for patients with HGSOC.
Integrative metagenomic and metabolomic analyses reveal the potential of gut microbiota to exacerbate acute pancreatitis
Authors: Liu Jianjun , Yan Qiulong , Li Shenghui , Jiao Juying , Hao Yiming , Zhang Guixin , Zhang Qingkai , Luo Fei , Zhang Yue , Lv Qingbo , Zhang Wenzhe , Zhang Aiqin , Song Huiyi , Xin Yi , Ma Yufang , Owusu Lawrence , Ma Xiaochi , Yin Peiyuan , Shang Dong
Published: March 2024

Early dysbiosis in the gut microbiota may contribute to the severity of acute pancreatitis (AP), however, a comprehensive understanding of the gut microbiome, potential pathobionts, and host metabolome in individuals with AP remains elusive. Hence, we employed fecal whole-metagenome shotgun sequencing in 82 AP patients and 115 matched healthy controls, complemented by untargeted serum metabolome and lipidome profiling in a subset of participants. Analyses of the gut microbiome in AP patients revealed reduced diversity, disrupted microbial functions, and altered abundance of 77 species, influenced by both etiology and severity. AP-enriched species, mostly potential pathobionts, correlated positively with host liver function and serum lipid indicators. Conversely, many AP-depleted species were short-chain fatty acid producers. Gut microflora changes were accompanied by shifts in the serum metabolome and lipidome. Specifically, certain gut species, like enriched Bilophila wadsworthia and depleted Bifidobacterium spp., appeared to contribute to elevated triglyceride levels in biliary or hyperlipidemic AP patients. Through culturing and whole-genome sequencing of bacterial isolates, we identified virulence factors and clinically relevant antibiotic resistance in patient-derived strains, suggesting a predisposition to opportunistic infections. Finally, our study demonstrated that gavage of specific pathobionts could exacerbate pancreatitis in a caerulein-treated mouse model. In conclusion, our comprehensive analysis sheds light on the gut microbiome and serum metabolome in AP, elucidating the role of pathobionts in disease progression. These insights offer valuable perspectives for etiologic diagnosis, prevention, and intervention in AP and related conditions.
Leveraging language representation for materials exploration and discovery
Authors: Qu Jiaxing , Xie Yuxuan Richard , Ciesielski Kamil M. , Porter Claire E. , Toberer Eric S. , Ertekin Elif
Published: March 2024

Data-driven approaches to materials exploration and discovery are building momentum due to emerging advances in machine learning. However, parsimonious representations of crystals for navigating the vast materials search space remain limited. To address this limitation, we introduce a materials discovery framework that utilizes natural language embeddings from language models as representations of compositional and structural features. The contextual knowledge encoded in these language representations conveys information about material properties and structures, enabling both similarity analysis to recall relevant candidates based on a query material and multi-task learning to share information across related properties. Applying this framework to thermoelectrics, we demonstrate diversified recommendations of prototype crystal structures and identify under-studied material spaces. Validation through first-principles calculations and experiments confirms the potential of the recommended materials as high-performance thermoelectrics. Language-based frameworks offer versatile and adaptable embedding structures for effective materials exploration and discovery, applicable across diverse material systems.
Genomic analysis of lumpy skin disease virus asian variants and evaluation of its cellular tropism
Authors: Xie Shijie , Cui Lianxin , Liao Zhiyi , Zhu Junda , Ren Shuning , Niu Kang , Li Hua , Jiang Fei , Wu Jiajun , Wang Jie , Wu Jian , Song Baifen , Wu Wenxue , Peng Chen
Published: March 2024

Lumpy skin disease virus (LSDV) is a poxvirus that mainly affects cattle and can lead to symptoms such as severe reduction in milk production as well as infertility and mortality, which has resulted in dramatic economic loss in affected countries in Africa, Europe, and Asia. In this study, we successfully isolated two strains of LSDV from different geographical regions in China. Comparative genomic analyses were performed by incorporating additional LSDV whole genome sequences reported in other areas of Asia. Our analyses revealed that LSDV exhibited an ‘open’ pan-genome. Phylogenetic analysis unveiled distinct branches of LSDV evolution, signifying the prevalence of multiple lineages of LSDV across various regions in Asia. In addition, a reporter LSDV expressing eGFP directed by a synthetic poxvirus promoter was generated and used to evaluate the cell tropism of LSDV in various mammalian and avian cell lines. Our results demonstrated that LSDV replicated efficiently in several mammalian cell lines, including human A549 cells. In conclusion, our results underscore the necessity for strengthening LSD outbreak control measures and continuous epidemiological surveillance.
Immunization-induced antigen archiving enhances local memory CD8+ T cell responses following an unrelated viral infection
Authors: Doan Thu A. , Forward Tadg S. , Schafer Johnathon B. , Lucas Erin D. , Fleming Ira , Uecker-Martin Aspen , Ayala Edgardo , Guthmiller Jenna J. , Hesselberth Jay R. , Morrison Thomas E. , Tamburini Beth A. Jirón
Published: March 2024

Antigens from viruses or immunizations can persist or are archived in lymph node stromal cells such as lymphatic endothelial cells (LEC) and fibroblastic reticular cells (FRC). Here, we find that, during the time frame of antigen archiving, LEC apoptosis caused by a second, but unrelated, innate immune stimulus such as vaccina viral infection or CpG DNA administration resulted in cross-presentation of archived antigens and boosted memory CD8 + T cells specific to the archived antigen. In contrast to ”bystander” activation associated with unrelated infections, the memory CD8 + T cells specific to the archived antigen from the immunization were significantly higher than memory CD8 + T cells of a different antigen specificity. Finally, the boosted memory CD8 + T cells resulted in increased protection against Listeria monocytogenes expressing the antigen from the immunization, but only for the duration that the antigen was archived. These findings outline an important mechanism by which lymph node stromal cell archived antigens, in addition to bystander activation, can augment memory CD8 + T cell responses during repeated inflammatory insults.
An intranasal combination vaccine induces systemic and mucosal immunity against COVID-19 and influenza
Authors: Xing Man , Hu Gaowei , Wang Xiang , Wang Yihan , He Furong , Dai Weiqian , Wang Xinyu , Niu Yixin , Liu Jiaojiao , Liu Hui , Zhang Xiaoyan , Xu Jianqing , Cai Qiliang , Zhou Dongming
Published: March 2024

Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses continue to pose a severe global health burden. Thus, we developed a chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 and influenza virus. When used as a standalone vaccine, intranasal immunization with AdC68-HATRBD induced comprehensive and potent immune responses consisting of immunoglobin (Ig) G, mucosal IgA, neutralizing antibodies, and memory T cells, which protected the mice from BA.5.2 and pandemic H1N1 infections. When used as a heterologous booster, AdC68-HATRBD markedly improved the protective immune response of the licensed SARS-CoV-2 or influenza vaccine. Therefore, whether administered intranasally as a standalone or booster vaccine, this combination vaccine is a valuable strategy to enhance the overall vaccine efficacy by inducing robust systemic and mucosal immune responses, thereby conferring dual lines of immunological defenses for these two viruses.
A comprehensive historical and geolocalized database of mining activities in Canada
Authors: Dallaire-Fortier Clara
Published: March 2024

This paper introduces the MinCan database that presents mine-level estimates for the Canadian mining industry with a persistent annual coverage between 1950 and 2022. These estimates are based on archival maps and a selection of historical sources, which follows a hierarchy of criteria-based credibility and standardization. The information contained in MinCan covers 947 mines and provides information about their location (longitude and latitude in decimal), the company ownership, the principal commodities produced, and the years of operation (opening and closing dates). It is the first open access database to propose an exhaustive, free, and reliable compilation of the principal past and present mines producing in Canada. The geographic coordinates enable matching with other local, regional, and national databases, and allow for a wide range of research objectives to be met.
Harmonized disposable income dataset for Europe at subnational level
Authors: Mikou Mehdi , Vallet Améline , Guivarch Céline
Published: March 2024

In recent decades, detailed country-level estimates of income and wealth have become widely available and inform us about the evolution of inequality between and within countries. But a substantial portion of these available datasets lack sub-national geographical information, precluding the exploration of the spatial distribution and evolution of inequalities within countries. We present here a new dataset of disposable income for Europe at the subnational level. It has been compiled from existing income data (gross income, gross earnings, equivalised income, etc.) published by national statistical institutes at different geographical levels. We used linear regressions and numerical operations to estimate disposable income from other available socio-economic statistics (e.g. household size, tax rates). We developed a harmonization and adjustment procedures to ensure of the consistency of statistical units, income indicators, costs of living and inflation. The dataset covers 42 European countries distributed over more than 120,000 geographical entities on the 1995 to 2021 period (most of the data being available for the 2010–2020 decade). This new dataset opens avenues for investigating the links between income inequality and other socio-economic or ecological processes.