bluuebunny/crossref_metadata_2025 huggingface dataset:
New technologies developed for treatment of premature ejaculation
Authors: Shechter Arik , Gruenwald Ilan
Published: March 2024

Premature ejaculation (PE), lifelong and acquired, is the most common male sexual disorder, with serious impacts on the patient and his partner’s quality of life, sexual well-being, and psychosocial health. The most popular treatment options are on-demand topical anesthetics and off-label daily or on-demand selective serotonin reuptake inhibitors (SSRIs), followed by behavioral therapy. While SSRI treatments are reportedly safe, they are associated with limited efficacy and provide only a temporary delay in ejaculation latency time. The majority of PE patients are dissatisfied with SSRIs; thus, adherence to on-demand or daily SSRI treatments is low. In this article, we review studies on currently available technologies that are not pharmacological, surgical, cognitive or behavioral therapies. Recent data from studies of newly developed medical devices used in PE treatment are encouraging as they provide drug-free spontaneity during coitus, without severe adverse effects.
Creation of flexible spin-caloritronic material with giant transverse thermoelectric conversion by nanostructure engineering
Authors: Gautam Ravi , Hirai Takamasa , Alasli Abdulkareem , Nagano Hosei , Ohkubo Tadakatsu , Uchida Ken-ichi , Sepehri-Amin Hossein
Published: March 2024

Functional materials such as magnetic, thermoelectric, and battery materials have been revolutionized through nanostructure engineering. However, spin caloritronics, an advancing field based on spintronics and thermoelectrics with fundamental physics studies, has focused only on uniform materials without complex microstructures. Here, we show how nanostructure engineering enables transforming simple magnetic alloys into spin-caloritronic materials displaying significantly large transverse thermoelectric conversion properties. The anomalous Nernst effect, a promising transverse thermoelectric phenomenon for energy harvesting and heat sensing, has been challenging to utilize due to the scarcity of materials with large anomalous Nernst coefficients. We demonstrate a remarkable ~ 70% improvement in the anomalous Nernst coefficients (reaching ~ 3.7 µVK−1) and a significant ~ 200% enhancement in the power factor (reaching ~ 7.7 µWm−1K−2) in flexible Fe-based amorphous materials by nanostructure engineering without changing their composition. This surpasses all reported amorphous alloys and is comparable to single crystals showing large anomalous Nernst effect. The enhancement is attributed to Cu nano-clustering, facilitating efficient transverse thermoelectric conversion. This discovery advances the materials science of spin caloritronics, opening new avenues for designing high-performance transverse thermoelectric devices for practical applications.
Phosphorylation and O-GlcNAcylation at the same α-synuclein site generate distinct fibril structures
Authors: Hu Jinjian , Xia Wencheng , Zeng Shuyi , Lim Yeh-Jun , Tao Youqi , Sun Yunpeng , Zhao Lang , Wang Haosen , Le Weidong , Li Dan , Zhang Shengnan , Liu Cong , Li Yan-Mei
Published: March 2024

α-Synuclein forms amyloid fibrils that are critical in the progression of Parkinson’s disease and serves as the pathological hallmark of this condition. Different posttranslational modifications have been identified at multiple sites of α-synuclein, influencing its conformation, aggregation and function. Here, we investigate how disease-related phosphorylation and O-GlcNAcylation at the same α-synuclein site (S87) affect fibril structure and neuropathology. Using semi-synthesis, we obtained homogenous α-synuclein monomer with site-specific phosphorylation (pS87) and O-GlcNAcylation (gS87) at S87, respectively. Cryo-EM revealed that pS87 and gS87 α-synuclein form two distinct fibril structures. The GlcNAc situated at S87 establishes interactions with K80 and E61, inducing a unique iron-like fold with the GlcNAc molecule on the iron handle. Phosphorylation at the same site prevents a lengthy C-terminal region including residues 73 to 140 from incorporating into the fibril core due to electrostatic repulsion. Instead, the N-terminal half of the fibril (1–72) takes on an arch-like fibril structure. We further show that both pS87 and gS87 α-synuclein fibrils display reduced neurotoxicity and propagation activity compared with unmodified α-synuclein fibrils. Our findings demonstrate that different posttranslational modifications at the same site can produce distinct fibril structures, which emphasizes link between posttranslational modifications and amyloid fibril formation and pathology.
Developmental timing in plants
Authors: Coen Enrico , Prusinkiewicz Przemyslaw
Published: March 2024

Plants exhibit reproducible timing of developmental events at multiple scales, from switches in cell identity to maturation of the whole plant. Control of developmental timing likely evolved for similar reasons that humans invented clocks: to coordinate events. However, whereas clocks are designed to run independently of conditions, plant developmental timing is strongly dependent on growth and environment. Using simplified models to convey key concepts, we review how growth-dependent and inherent timing mechanisms interact with the environment to control cyclical and progressive developmental transitions in plants.
Raman time-delay in attosecond transient absorption of strong-field created krypton vacancy
Authors: Wang Li , Bai Guangru , Wang Xiaowei , Zhao Jing , Gao Cheng , Wang Jiacan , Xiao Fan , Tao Wenkai , Song Pan , Qiu Qianyu , Liu Jinlei , Zhao Zengxiu
Published: March 2024

Strong field ionization injects a transient vacancy in the atom which is entangled to the outgoing photoelectron. When the electron is finally detached, the ion is populated at different excited states with part of coherence information lost. The preserved coherence of matter after interacting with intense short pulses has important consequences on the subsequent nonequilibrium evolution and energy relaxation. Here we employ attosecond transient absorption spectroscopy to measure the time-delay of resonant transitions of krypton vacancy during their creation. We have observed that the absorptions by the two spin-orbit split states are modulated at different paces when varying the time-delay between the near-infrared pumping pulse and the attosecond probing pulse. It is shown that the coupling of the ions with the remaining field leads to a suppression of ionic coherence. Comparison between theory and experiments uncovers that coherent Raman coupling induces time-delay between the resonant absorptions, which provides insight into laser-ion interactions enriching attosecond chronoscopy.
Modeling Si/SiGe quantum dot variability induced by interface disorder reconstructed from multiperspective microscopy
Authors: Peña Luis Fabián , Koepke Justine C. , Dycus Joseph Houston , Mounce Andrew , Baczewski Andrew D. , Jacobson N. Tobias , Bussmann Ezra
Published: March 2024

SiGe heteroepitaxial growth yields pristine host material for quantum dot qubits, but residual interface disorder can lead to qubit-to-qubit variability that might pose an obstacle to reliable SiGe-based quantum computing. By convolving data from scanning tunneling microscopy and high-angle annular dark field scanning transmission electron microscopy, we reconstruct 3D interfacial atomic structure and employ an atomistic multi-valley effective mass theory to quantify qubit spectral variability. The results indicate (1) appreciable valley splitting (VS) variability of ~50% owing to alloy disorder and (2) roughness-induced double-dot detuning bias energy variability of order 1–10 meV depending on well thickness. For measured intermixing, atomic steps have negligible influence on VS, and uncorrelated roughness causes spatially fluctuating energy biases in double-dot detunings potentially incorrectly attributed to charge disorder. Our approach yields atomic structure spanning orders of magnitude larger areas than post-growth microscopy or tomography alone, enabling more holistic predictions of disorder-induced qubit variability.
Exploiting sulfonated covalent organic frameworks to fabricate long-lasting stability and chlorine-resistant thin-film nanocomposite nanofiltration membrane
Authors: Meng Wenqiao , Xue Qiang , Zhu Jinyuan , Zhang Kaisong
Published: March 2024

Incorporating hydrophilic and charged porous nanofillers to prepare high-performance thin film nanocomposite (TFN) nanofiltration (NF) membranes is an effective method to achieve efficient water treatment. In this study, we synthesize the sulfonated covalent organic framework nanosheets (S-CONs) with higher hydrophilicity and electronegativity by immobilizing sulfonic acid groups (–SO3H) on TpPa-1 nanosheets. The S-CONs are incorporated in the PA layer by interfacial polymerization (IP) reaction. The results indicated that the S-CONs could modulate the hydrophilicity, thickness, and electronegativity of TFN-NF membranes. At the optimal addition of S-CONs (0.006 g), the pure water permeance increases to 8.84 $${\rm{L}}\cdot{\rm{m}}^{-2}\cdot{\rm{h}}^{-1}\cdot{\rm{bar}}^{-1}$$

L
⋅

m

−
2

⋅

h

−
1

⋅

bar

−
1

, which is about 1.75 times than the TFC membrane, with a high Na2SO4 rejection reaching 98.97%. The improvement of the separation performance mainly results from the reduction of PA layer thickness (from ~178.00–198.00 to ~100.00–128.00 nm) and the increase of surface electronegativity (from −20.37 to −44.41 mV at pH = 7.00). More interestingly, the amide bond formed between the S-CONs and TMC improved the chlorine resistance of the membranes. This study reveals the potential of using functionalized 2D CONs as nanofillers to modify TFC membranes for efficient nanofiltration.
High-threshold and low-overhead fault-tolerant quantum memory
Authors: Bravyi Sergey , Cross Andrew W. , Gambetta Jay M. , Maslov Dmitri , Rall Patrick , Yoder Theodore J.
Published: March 2024

The accumulation of physical errors1–3 prevents the execution of large-scale algorithms in current quantum computers. Quantum error correction4 promises a solution by encoding k logical qubits onto a larger number n of physical qubits, such that the physical errors are suppressed enough to allow running a desired computation with tolerable fidelity. Quantum error correction becomes practically realizable once the physical error rate is below a threshold value that depends on the choice of quantum code, syndrome measurement circuit and decoding algorithm5. We present an end-to-end quantum error correction protocol that implements fault-tolerant memory on the basis of a family of low-density parity-check codes6. Our approach achieves an error threshold of 0.7% for the standard circuit-based noise model, on par with the surface code7–10 that for 20 years was the leading code in terms of error threshold. The syndrome measurement cycle for a length-n code in our family requires n ancillary qubits and a depth-8 circuit with CNOT gates, qubit initializations and measurements. The required qubit connectivity is a degree-6 graph composed of two edge-disjoint planar subgraphs. In particular, we show that 12 logical qubits can be preserved for nearly 1 million syndrome cycles using 288 physical qubits in total, assuming the physical error rate of 0.1%, whereas the surface code would require nearly 3,000 physical qubits to achieve said performance. Our findings bring demonstrations of a low-overhead fault-tolerant quantum memory within the reach of near-term quantum processors.
Five million years of Antarctic Circumpolar Current strength variability
Authors: Lamy Frank , Winckler Gisela , Arz Helge W. , Farmer Jesse R. , Gottschalk Julia , Lembke-Jene Lester , Middleton Jennifer L. , van der Does Michèlle , Tiedemann Ralf , Alvarez Zarikian Carlos , Basak Chandranath , Brombacher Anieke , Dumm Levin , Esper Oliver M. , Herbert Lisa C. , Iwasaki Shinya , Kreps Gaston , Lawson Vera J. , Lo Li , Malinverno Elisa , Martinez-Garcia Alfredo , Michel Elisabeth , Moretti Simone , Moy Christopher M. , Ravelo Ana Christina , Riesselman Christina R. , Saavedra-Pellitero Mariem , Sadatzki Henrik , Seo Inah , Singh Raj K. , Smith Rebecca A. , Souza Alexandre L. , Stoner Joseph S. , Toyos Maria , de Oliveira Igor M. Venancio P. , Wan Sui , Wu Shuzhuang , Zhao Xiangyu
Published: March 2024

The Antarctic Circumpolar Current (ACC) represents the world’s largest ocean-current system and affects global ocean circulation, climate and Antarctic ice-sheet stability1–3. Today, ACC dynamics are controlled by atmospheric forcing, oceanic density gradients and eddy activity4. Whereas palaeoceanographic reconstructions exhibit regional heterogeneity in ACC position and strength over Pleistocene glacial–interglacial cycles5–8, the long-term evolution of the ACC is poorly known. Here we document changes in ACC strength from sediment cores in the Pacific Southern Ocean. We find no linear long-term trend in ACC flow since 5.3 million years ago (Ma), in contrast to global cooling9 and increasing global ice volume10. Instead, we observe a reversal on a million-year timescale, from increasing ACC strength during Pliocene global cooling to a subsequent decrease with further Early Pleistocene cooling. This shift in the ACC regime coincided with a Southern Ocean reconfiguration that altered the sensitivity of the ACC to atmospheric and oceanic forcings11–13. We find ACC strength changes to be closely linked to 400,000-year eccentricity cycles, probably originating from modulation of precessional changes in the South Pacific jet stream linked to tropical Pacific temperature variability14. A persistent link between weaker ACC flow, equatorward-shifted opal deposition and reduced atmospheric CO2 during glacial periods first emerged during the Mid-Pleistocene Transition (MPT). The strongest ACC flow occurred during warmer-than-present intervals of the Plio-Pleistocene, providing evidence of potentially increasing ACC flow with future climate warming.
Formation of memory assemblies through the DNA-sensing TLR9 pathway
Authors: Jovasevic Vladimir , Wood Elizabeth M. , Cicvaric Ana , Zhang Hui , Petrovic Zorica , Carboncino Anna , Parker Kendra K. , Bassett Thomas E. , Moltesen Maria , Yamawaki Naoki , Login Hande , Kalucka Joanna , Sananbenesi Farahnaz , Zhang Xusheng , Fischer Andre , Radulovic Jelena
Published: March 2024

As hippocampal neurons respond to diverse types of information1, a subset assembles into microcircuits representing a memory2. Those neurons typically undergo energy-intensive molecular adaptations, occasionally resulting in transient DNA damage3–5. Here we found discrete clusters of excitatory hippocampal CA1 neurons with persistent double-stranded DNA (dsDNA) breaks, nuclear envelope ruptures and perinuclear release of histone and dsDNA fragments hours after learning. Following these early events, some neurons acquired an inflammatory phenotype involving activation of TLR9 signalling and accumulation of centrosomal DNA damage repair complexes6. Neuron-specific knockdown of Tlr9 impaired memory while blunting contextual fear conditioning-induced changes of gene expression in specific clusters of excitatory CA1 neurons. Notably, TLR9 had an essential role in centrosome function, including DNA damage repair, ciliogenesis and build-up of perineuronal nets. We demonstrate a novel cascade of learning-induced molecular events in discrete neuronal clusters undergoing dsDNA damage and TLR9-mediated repair, resulting in their recruitment to memory circuits. With compromised TLR9 function, this fundamental memory mechanism becomes a gateway to genomic instability and cognitive impairments implicated in accelerated senescence, psychiatric disorders and neurodegenerative disorders. Maintaining the integrity of TLR9 inflammatory signalling thus emerges as a promising preventive strategy for neurocognitive deficits.
Revealing uncertainty in the status of biodiversity change
Authors: Johnson T. F. , Beckerman A. P. , Childs D. Z. , Webb T. J. , Evans K. L. , Griffiths C. A. , Capdevila P. , Clements C. F. , Besson M. , Gregory R. D. , Thomas G. H. , Delmas E. , Freckleton R. P.
Published: March 2024

Biodiversity faces unprecedented threats from rapid global change1. Signals of biodiversity change come from time-series abundance datasets for thousands of species over large geographic and temporal scales. Analyses of these biodiversity datasets have pointed to varied trends in abundance, including increases and decreases. However, these analyses have not fully accounted for spatial, temporal and phylogenetic structures in the data. Here, using a new statistical framework, we show across ten high-profile biodiversity datasets2–11 that increases and decreases under existing approaches vanish once spatial, temporal and phylogenetic structures are accounted for. This is a consequence of existing approaches severely underestimating trend uncertainty and sometimes misestimating the trend direction. Under our revised average abundance trends that appropriately recognize uncertainty, we failed to observe a single increasing or decreasing trend at 95% credible intervals in our ten datasets. This emphasizes how little is known about biodiversity change across vast spatial and taxonomic scales. Despite this uncertainty at vast scales, we reveal improved local-scale prediction accuracy by accounting for spatial, temporal and phylogenetic structures. Improved prediction offers hope of estimating biodiversity change at policy-relevant scales, guiding adaptive conservation responses.
CGRP sensory neurons promote tissue healing via neutrophils and macrophages
Authors: Lu Yen-Zhen , Nayer Bhavana , Singh Shailendra Kumar , Alshoubaki Yasmin K. , Yuan Elle , Park Anthony J. , Maruyama Kenta , Akira Shizuo , Martino Mikaël M.
Published: March 2024

The immune system has a critical role in orchestrating tissue healing. As a result, regenerative strategies that control immune components have proved effective1,2. This is particularly relevant when immune dysregulation that results from conditions such as diabetes or advanced age impairs tissue healing following injury2,3. Nociceptive sensory neurons have a crucial role as immunoregulators and exert both protective and harmful effects depending on the context4–12. However, how neuro–immune interactions affect tissue repair and regeneration following acute injury is unclear. Here we show that ablation of the NaV1.8 nociceptor impairs skin wound repair and muscle regeneration after acute tissue injury. Nociceptor endings grow into injured skin and muscle tissues and signal to immune cells through the neuropeptide calcitonin gene-related peptide (CGRP) during the healing process. CGRP acts via receptor activity-modifying protein 1 (RAMP1) on neutrophils, monocytes and macrophages to inhibit recruitment, accelerate death, enhance efferocytosis and polarize macrophages towards a pro-repair phenotype. The effects of CGRP on neutrophils and macrophages are mediated via thrombospondin-1 release and its subsequent autocrine and/or paracrine effects. In mice without nociceptors and diabetic mice with peripheral neuropathies, delivery of an engineered version of CGRP accelerated wound healing and promoted muscle regeneration. Harnessing neuro–immune interactions has potential to treat non-healing tissues in which dysregulated neuro–immune interactions impair tissue healing.
Climate velocities and species tracking in global mountain regions
Authors: Chan Wei-Ping , Lenoir Jonathan , Mai Guan-Shuo , Kuo Hung-Chi , Chen I-Ching , Shen Sheng-Feng
Published: March 2024

Mountain ranges contain high concentrations of endemic species and are indispensable refugia for lowland species that are facing anthropogenic climate change1,2. Forecasting biodiversity redistribution hinges on assessing whether species can track shifting isotherms as the climate warms3,4. However, a global analysis of the velocities of isotherm shifts along elevation gradients is hindered by the scarcity of weather stations in mountainous regions5. Here we address this issue by mapping the lapse rate of temperature (LRT) across mountain regions globally, both by using satellite data (SLRT) and by using the laws of thermodynamics to account for water vapour6 (that is, the moist adiabatic lapse rate (MALRT)). By dividing the rate of surface warming from 1971 to 2020 by either the SLRT or the MALRT, we provide maps of vertical isotherm shift velocities. We identify 17 mountain regions with exceptionally high vertical isotherm shift velocities (greater than 11.67 m per year for the SLRT; greater than 8.25 m per year for the MALRT), predominantly in dry areas but also in wet regions with shallow lapse rates; for example, northern Sumatra, the Brazilian highlands and southern Africa. By linking these velocities to the velocities of species range shifts, we report instances of close tracking in mountains with lower climate velocities. However, many species lag behind, suggesting that range shift dynamics would persist even if we managed to curb climate-change trajectories. Our findings are key for devising global conservation strategies, particularly in the 17 high-velocity mountain regions that we have identified.
Xenografted human microglia display diverse transcriptomic states in response to Alzheimer’s disease-related amyloid-β pathology
Authors: Mancuso Renzo , Fattorelli Nicola , Martinez-Muriana Anna , Davis Emma , Wolfs Leen , Van Den Daele Johanna , Geric Ivana , Premereur Jessie , Polanco Paula , Bijnens Baukje , Preman Pranav , Serneels Lutgarde , Poovathingal Suresh , Balusu Sriram , Verfaillie Catherine , Fiers Mark , De Strooper Bart
Published: March 2024

Microglia are central players in Alzheimer’s disease pathology but analyzing microglial states in human brain samples is challenging due to genetic diversity, postmortem delay and admixture of pathologies. To circumvent these issues, here we generated 138,577 single-cell expression profiles of human stem cell-derived microglia xenotransplanted in the brain of the AppNL-G-F model of amyloid pathology and wild-type controls. Xenografted human microglia adopt a disease-associated profile similar to that seen in mouse microglia, but display a more pronounced human leukocyte antigen or HLA state, likely related to antigen presentation in response to amyloid plaques. The human microglial response also involves a pro-inflammatory cytokine/chemokine cytokine response microglia or CRM response to oligomeric Aβ oligomers. Genetic deletion of TREM2 or APOE as well as APOE polymorphisms and TREM2R47H expression in the transplanted microglia modulate these responses differentially. The expression of other Alzheimer’s disease risk genes is differentially regulated across the distinct cell states elicited in response to amyloid pathology. Thus, we have identified multiple transcriptomic cell states adopted by human microglia in a multipronged response to Alzheimer’s disease-related pathology, which should be taken into account in translational studies.
A dataset of thermal preferences for Mediterranean demersal and benthic macrofauna
Authors: Valente Salvatore , Colloca Francesco
Published: March 2024

Climate change is swiftly reshaping marine ecosystems, affecting different biological levels. Changes in thermal conditions profoundly influence ectotherms’ growth, behaviour, and functions, making knowledge of species’ thermal preferences (TP) crucial for understanding their responses to ongoing warming. However, obtaining this data is challenging due to limited studies, especially for deep-sea demersal and bottom-dwelling species. Here, we present the MedFaunaTP dataset, a collection of survey-based TPs for 939 Mediterranean species of fish, crustaceans, molluscs, echinoderms, cnidarians, and tunicates calculated using species abundance data obtained from the international bottom-trawl survey in the Mediterranean (MEDITS) and bottom temperature data derived from the Copernicus Monitoring Environment Marine Service. MEDITS estimates are based on species biomass indices from 27587 sampling stations, collected from 1994 to 2020, covering the northern Mediterranean Sea and spanning depths from 10 to 800 m. The MedFaunaTP dataset may serves as a valuable resource for understanding and addressing marine ecosystem ecological, conservation, and management challenges in the context of climate change and associated global warming.
miR-889-3p targeting BMPR2 promotes the development of retinoblastoma via JNK/MAPK/ERK signaling
Authors: Gao Yuan , Du Pei
Published: March 2024

MicroRNAs (miRNAs) are vital regulators of tumor pathogenesis, including that of retinoblastoma (Rb). This study investigated the functions and mechanisms of action of miR-889-3p in Rb. BMPR2 and miR-889-3p levels were assessed by quantitative reverse transcription PCR (qRT-PCR) or western blotting. Through several cell function tests, the effects of miR-889-3p and BMPR2 on cell proliferation, migration, and JNK/MAPK/ERK signaling were evaluated. The interaction between miR-889-3p and BMPR2 was investigated using a luciferase reporter assay. In vivo tumor development was investigated using a xenograft test. The association between miR-889-3p and BMPR2 expression was identified using Pearson’s correlation analysis. miR-889-3p was increased in Rb cells, and miR-889-3p knockdown inhibited Rb cell proliferation, migration, and phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and ERK1/2 in vitro, as well as tumor growth in vivo. Further, they were inversely associated in Rb tissues and miR-889-3p may directly attached to the 3′-UTR of BMPR2 mRNA. Finally, the inhibition of BMPR2 inverted the negative effects of the miR-889-3p inhibitor on migration, proliferation, and activation of JNK, p38 MAPK, and ERK1/2 in Rb cells. Our results indicate that miR-889-3p, which targets BMPR2 and promotes Rb growth by controlling the JNK/MAPK/ERK pathway, is an oncogene in Rb. These results suggested that the miR-889-3p/BMPR2 axis may be a new therapeutic target for Rb.
Association of maternal leukocyte, monocyte, and neutrophil counts with hypertensive disorders of pregnancy: the Japan Environment and Children’s Study (JECS)
Authors: Ishiyama Shiori , Mochizuki Kazuki , Shinohara Ryoji , Miyake Kunio , Kushima Megumi , Kojima Reiji , Horiuchi Sayaka , Otawa Sanae , Yui Hideki , Ooka Tadao , Akiyama Yuka , Yokomichi Hiroshi , Yamagata Zentaro ,   The Japan Environment and Children’s Study Group, Kamijima Michihiro , Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Mori Chisato , Ito Shuichi , Yamagata Zentaro , Inadera Hidekuni , Nakayama Takeo , Sobue Tomotaka , Shima Masayuki , Kageyama Seiji , Suganuma Narufumi , Ohga Shoichi , Katoh Takahiko
Published: March 2024

Hypertensive disorders of pregnancy (HDP) increase the risk of preterm births and cesarean delivery. This study aimed to investigate whether maternal blood leukocyte, monocyte, or neutrophil counts in the first trimester are related to the development of HDP. Data were collected from the Japan Environment and Children’s Study, a large birth cohort study (n = 38,194) that recruited pregnant women in 15 Regional Centers across Japan (from January 2011 to March 2014). The odds ratios (ORs) for mild/severe HDP according to the cut-off value of leukocyte/neutrophil/monocyte counts by the receiver operating characteristic curve showed high ORs. Furthermore, pregnant women with the highest quartiles of leukocyte and monocyte counts had higher adjusted ORs (aORs) for mild (leukocyte: aOR = 1.27, 95% confidence interval [CI]: 1.02–1.58; monocyte: aOR = 1.30, 95% CI 1.04–1.63) and severe HDP (leukocyte: aOR = 1.51, 95% CI 1.08–2.13; monocyte: aOR = 1.44, 95% CI 1.03–2.01) compared with those with the lowest quartiles of those counts. In addition, pregnant women with the highest neutrophil counts had higher aOR for mild HDP (aOR = 1.26, 95% CI 1.02–1.56) compared with those with the lowest count. In conclusion, high leukocyte and monocyte counts in the first trimester are associated with the development of HDP. Thus, they may be used to predict subsequent HDP.
Clinical and paraclinical characteristics of optic neuritis in the context of the McDonald criteria 2017
Authors: Jendretzky Konstantin F. , Bajor Anna , Lezius Lisa-Marie , Hümmert Martin W. , Konen Franz Felix , Grosse Gerrit M. , Schwenkenbecher Philipp , Sühs Kurt-Wolfram , Trebst Corinna , Framme Carsten , Wattjes Mike P. , Meuth Sven G. , Gingele Stefan , Skripuletz Thomas
Published: March 2024

Optic neuritis is often an initial symptom in multiple sclerosis (MS) or clinically isolated syndrome (CIS), yet comprehensive studies using the 2017 McDonald criteria for MS are scarce. Patient records from our academic centre (2010–2018) were reviewed. Using the 2017 McDonald criteria, three groups were formed: MS optic neuritis (optic neuritis with confirmed MS), CIS optic neuritis (optic neuritis without confirmed MS) and suspected optic neuritis (sON). We compared clinical and paraclinical findings among the groups to identify predictors for CIS- or MS-optic neuritis. The study included 129 MS, 108 CIS, and 44 sON cases. The combination of visual impairment, dyschromatopsia, and retrobulbar pain was observed in 47% of MS patients, 42% of CIS patients, and 30% of sON patients. Dyschromatopsia was the strongest indicator of MS or CIS diagnosis in the backward regression model. 56% of MS patients had relative afferent pupillary defect, 61% optic nerve anomalies within magnetic resonance imaging, and 81% abnormal visual evoked potentials. Our results emphasize the challenges in diagnosing optic neuritis, as not all patients with objectively diagnosed MS exhibit the triad of typical symptoms. To address potentially missing clinical features, incorporating additional paraclinical findings is proposed.
Modified streptavidin–biotin based lateral flow test strip for rapid detection of SARS-CoV-2 S1 antigen in saliva samples
Authors: Kamel Manal , Atta Shimaa , Maher Sara , Abd Elaziz Hesham , Demerdash Zeinab
Published: March 2024

Compared to other infectious diseases, for which LFT development can take years, SARS-CoV-2 antigen LFTS were developed and deployed within months. LFTS for antigen detection were adopted on an unprecedented scale during the COVID-19 pandemic, but many of them lack the sensitivity especially for samples with low viral load. In our previous work, we developed an enhanced signal strip for detection of SARS CoV-2 SI antigens in saliva. Here we introduce some modification to improve the sensitivity, and specificity, and to lower the cost of the strip, by using biotin streptavidin (BS) system. In the modified BS strip, gold-streptavidin and biotinylated Nanobodies (Nbs) against S1 antigen were externally mixed with the tested samples (saliva or nasopharyngeal swab) before their application on the sample pad of the test strip containing angiotensin converting enzyme (ACE-2), as the capturing probe. The study included 320 individuals, with 180 being positively confirmed by RT-PCR and 140 confirmed negative, as well as, 45 health care workers, who were responsible for screening and handling of surgical cases in General Surgery Department and COVID clinic of TBRI. Our results proved that modified BS strip improved the overall sensitivity and specificity of S1antigen detection in saliva samples (95.21% and 99.29% respectively) compared to our previously developed enhanced LFTS (91.66% and 98.57% respectively). Also, the sensitivity of cases with Ct ≤ 30, Ct $$\le$$
≤
35, and Ct $$\le$$
≤
40 using the modified BS strip showed higher values (98.54%, 95.38%, and 88.89% respectively), compared to the corresponding results of our previously developed enhanced LFTS (95.86%, 92.31%, and 82.22% respectively). There were no cross-reactions with either Middle East respiratory syndrome corona virus MERS-CoV or SARS-CoV antigens. Furthermore, we found that the lower viral detection limit (LVD) of BS strip was obviously lower than our previous LVD limit of the enhanced LFTS (0.2 × 104 copies/ml vs. 0.4 × 104 copies/ml, respectively). Our developed BS strip showed that saliva samples gave better results than nasopharyngeal swabs of the same patients. The fact of using smaller amounts of Nbs, and ACE2, as well as the dispensing off of conjugate pad when applying BS strip modifications, justified the expected reduction in the costs of the strip. The implementation of BS strips on saliva samples of 45 health co-workers, who were tested 4 and 6 days after exposure to infection, showed an increase in the sensitivity, starting from the 4th day and reaching its highest level on the 6th day in both high risk and paramedic groups (90.9%, and 80.0%, respectively). This study provides evidence that employment of the modified BS system could increase the sensitivity of the strips, lower their cost, and render them an effective screening tool for early detection of the virus in saliva of suspected Covid-19 patients.
CVRmap—a complete cerebrovascular reactivity mapping post-processing BIDS toolbox
Authors: Rovai A. , Lolli V. , Trotta N. , Goldman S. , De Tiège X.
Published: March 2024

Cerebrovascular Reactivity (CVR) refers to the ability of cerebral blood vessels to dilate or constrict under the effect of vasoactive substances and can be estimated using functional Magnetic Resonance Imaging (fMRI). Computation of CVR maps is relevant in various brain diseases and requires specialized data processing. We introduce CVRmap, an opensource software that automates the computation of CVR map. The toolbox complies with the Brain Imaging Data Structure (BIDS) standards.
Mindfulness meditation modulates stress-eating and its neural correlates
Authors: Torske Alyssa , Bremer Benno , Hölzel Britta Karen , Maczka Alexander , Koch Kathrin
Published: March 2024

Stress-related overeating can lead to excessive weight gain, increasing the risk of metabolic and cardiovascular disease. Mindfulness meditation has been demonstrated to reduce stress and increase interoceptive awareness and could, therefore, be an effective intervention for stress-related overeating behavior. To investigate the effects of mindfulness meditation on stress-eating behavior, meditation-naïve individuals with a tendency to stress-eat (N = 66) participated in either a 31-day, web-based mindfulness meditation training or a health training condition. Behavioral and resting-state fMRI data were acquired before and after the intervention. Mindfulness meditation training, in comparison to health training, was found to significantly increase mindfulness while simultaneously reducing stress- and emotional-eating tendencies as well as food cravings. These behavioral results were accompanied by functional connectivity changes between the hypothalamus, reward regions, and several areas of the default mode network in addition to changes observed between the insula and somatosensory areas. Additional changes between seed regions (i.e., hypothalamus and insula) and brain areas attributed to emotion regulation, awareness, attention, and sensory integration were observed. Notably, these changes in functional connectivity correlated with behavioral changes, thereby providing insight into the underlying neural mechanisms of the effects of mindfulness on stress-eating.

Clinical trial on the ISRCTN registry: trial ID ISRCTN12901054
Potential diagnostic and drug target markers in glioblastoma
Authors: Ahsan Hina , Asghar Muhammad , Malik Shaukat Iqbal
Published: March 2024

Glioblastoma multiforme (GBM) IDH-wildtype is the most prevalent brain malignancy in adults. However, molecular mechanisms, which leads to GBM have not been completely elucidated. Granulocyte colony-stimulating factor (GCSF), Granulocyte colony-stimulating factor receptor GCSFR, and Signal transducers and activators of transcription 3 (STAT3) have been involved in the occurrence and development of various cancers, but their role in GBM is little known. Herein, we have investigated the gene and protein expression of GCSF, GCSFR, and STAT3 in 21 tissue biopsy samples and also in tumor associated normal tissue (TANT) samples derived from glioblastoma patients, which revealed significantly differential expression of these genes. To validate our findings, we performed a comprehensive integrated analysis of transcriptomic and proteomic profiling of respective genes by retrieving GBM RNA-sequence data from Genome Atlas Databases. GO and KEGG analysis revealed enrichment in disease-related pathways, such as JAK/STAT pathway activation, which were associated with GBM progression. We further performed computational docking analysis of potential drug candidate Nisin against GCSF, and the results were validated in vitro through cytotoxic activity assay using a human glioblastoma cell line SF-767 in a dose-dependent manner. Our comprehensive analysis reveals that GCSF augments glioma progression, and its blockade with anticancer bacteriocin peptide Nisin can potentially inhibit the growth and metastasis of GBM.
Supporting re-engagement with HIV services after treatment interruption in South Africa: a mixed method program evaluation of MSF’s Welcome Service
Authors: Arendse Kirsten D. , Walker Caroline , Pfaff Colin , Lebelo Keitumetse , Cassidy Tali , Isaakidis Petros , von der Heyden Erin , Abdullah Fareed , Ellman Tom , Katz Ingrid T. , Euvrard Jonathan , Keene Claire M.
Published: March 2024

Psychosocial challenges impact patients’ ability to remain on antiretroviral therapy lifelong, magnified by disorganized health-systems and healthcare worker (HCW) attitudes. To address this, Médecins Sans Frontières and the Department of Health developed the Welcome Service intervention, to provide person-centered care at re-engagement after HIV treatment interruption. Implemented in Khayelitsha, South Africa, between August 2020 and February 2021, the intervention aimed to reorganize triage, optimize clinical and counselling services and address HCW attitudes. The study used a mixed-methods design, incorporating in-depth interviews, and analyses of programmatic and routine health data. Interviews demonstrated positive patient care experiences. HCWs understood the potential impact of attitudes on patient engagement, however, some continued to demonstrate judgmental attitude. Clinical objectives were variably met at re-engagement: 98% were re-initiated the same day, 50% had a CD4 done, and 45% received tuberculosis prevention. Nevertheless, 4-month retention was 66%, and 88% had a VL < 1000 c/mL. Despite HCWs’ understanding of person-centered care not translating into supportive behaviors, patients had positive care experiences and the intervention ended with a high rate of VL suppression. More efforts are needed to design interventions building on Welcome Service principles to provide person-centered care and sustain retention after re-engagement.
Source attribution of carbonaceous fraction of particulate matter in the urban atmosphere based on chemical and carbon isotope composition
Authors: Skiba Alicja , Styszko Katarzyna , Tobler Anna , Casotto Roberto , Gorczyca Zbigniew , Furman Przemysław , Samek Lucyna , Wideł Dariusz , Zimnoch Mirosław , Kasper-Giebl Anne , Slowik Jay G. , Daellenbach Kaspar R. , Prevot Andre S. H. , Różański Kazimierz
Published: March 2024

Air quality is of large concern in the city of Krakow, southern Poland. A comprehensive study was launched by us in which two PM fractions (PM1 and PM10) were sampled during 1-year campaign, lasting from April 21, 2018 to March 19, 2019. A suite of modern analytical methods was used to characterize the chemical composition of the collected samples. The contents of 14 sugars, sugar alcohols and anhydrosugars, 16 polycyclic aromatic hydrocarbons, selected metals and non-metals and ions were analyzed, in addition to organic and elemental carbon content. The carbon isotope composition in both analysed PM fractions, combined with an isotope-mass balance method, allowed to distinguish three main components of carbonaceous emissions in the city: (1) emissions related to combustion of hard coal, (2) emissions related to road transport, and (3) biogenic emissions. The heating season emissions from coal combustion had the biggest contribution to the reservoir of carbonaceous aerosols in the PM10 fraction (44%) and, together with the biogenic emission, they were the biggest contributors to the PM1 fraction (41% and 44%, respectively). In the non-heating season, the dominant source of carbon in PM10 and PM1 fraction were the biogenic emissions (48 and 54%, respectively).
Theoretical analysis of the effect of isotropy on the effective diffusion coefficient in the porous and agglomerated phase of the electrodes of a PEMFC
Authors: Pacheco C. , Barbosa Romeli , Navarro-Montejo A. , Ordoñez L. C.
Published: March 2024

In polymer membrane fuel cells (PEMFC), the pore microstructure and the effective diffusion coefficient ($$D_{eff}$$

D

eff

) of the catalytic layer have a significant impact on the overall performance of the fuel cell. In this work, numerical methods to simulate PEMFC catalytic layers were used to study the effect of isotropy ($$I_{xy}$$

I

xy

) on the $$D_{eff}$$

D

eff

. The proposed methodology studies reconstructed systems by Simulated Annealing imaging with different surface fractions of microstructures composed by two diffusive phases: agglomerates and pores. The $$D_{eff}$$

D

eff

is determined numerically by the Finite Volume Method solved for Fick's First Law of Diffusion. The results show that the proposed methodology can effectively quantify the effect of isotropy on the $$D_{eff}$$

D

eff

for both diffusion phases. Two trends were obtained in the magnitude of the $$D_{eff}$$

D

eff

concerning the change in isotropy: (1) an analytical equation is proposed in this article for $$D_{eff} \ge 5\% D_{0}$$

D

eff

≥
5
%

D
0

and (2) numerical solutions are determined for $$D_{eff} < 5\% D_{0} .$$

D

eff

<
5
%

D
0

.

In our analytical equation are both a lineal and a logarithmic sweep. When the surface fraction is $$\emptyset =$$

∅
=

50%, the $$D_{eff}$$

D

eff

decreases more linearly than $$\emptyset = 10\%$$

∅
=
10
%

at the beginning of the isotropy change, which indicates that small changes in isotropy in the particulate material modify it drastically; under these conditions the diffusion coefficient in the pore is predominant. (3) When the surface fraction is less than 50%, the $$D_{eff}$$

D

eff

decreases more exponentially at the beginning and more linearly at the end of the isotropy change, which shows that small isotropy changes in the bar-aligned material drastically alter it. In this trend, diffusion in the agglomerate is less affected by isotropy. The proposed methodology can be used as a design tool to improve the mass transport in porous PEMFC electrodes.
Neuropathological changes in the TASTPM mouse model of Alzheimer’s disease and their relation to hyperexcitability and cortical spreading depolarization
Authors: Gimeno-Ferrer Fátima , Eitner Annett , Noora Noor , Bauer Reinhard , Schmidt-Hieber Christoph , Schaible Hans-Georg , Richter Frank
Published: March 2024

Although Alzheimer’s disease (AD) is characterized by distinct pathological changes, their precise impact on cortical functions are not well understood. Here we used TASTPM mice as an AD model and asked whether the development of neurodegenerative changes has an impact on the extracellular space (ECS) and neuronal excitability, in particular cortical spreading depolarization (CSD) which requires intact neuron and glial functions. We studied wildtype (WT) and TASTPM mice (3, 6, and 12 months old). TASTPM mice showed progressive proliferation of neocortical Amyloid-beta (Aβ) plaques between 3 and 12 months (more deposits in females than in males) and Aβ accumulation in cortical vessels. As plaques proliferated, neuroinflammatory microglial reaction (CD68, CD39 and Galectin-3) and astrogliosis (GFAP) developed progressively. The cortical ECS volume shrank significantly to about half the size of the WT. CSD in both WT and TASTPM mice showed considerable heterogeneity but did not correlate with the histological changes. However, CSDs were easier to elicit in TASTPM than in WT mice at 3 months, and also compared to older TASTPM mice. Moreover, TASTPM mice showed more hyperexcitability manifested as clonic-tonic behavior after sodium thiopental anesthesia. Thus, AD pathology was associated with abnormal hyperexcitability but did not homogenously alter CSD susceptibility.
Lack of association between COVID-19 vaccines and miscarriage onset using a case-crossover design
Authors: Gastesi Orbegozo Irati , Cea-Soriano Lucía , Llorente Ana , Huerta-Álvarez Consuelo
Published: March 2024

Pregnant women might have an increased risk of SARS-COV-2 infection. Although evidence towards the efficacy and safety of COVID-19 is growing still there is room for improvement on the knowledge towards pregnancy adverse events, such as miscarriage. We explored the association of COVID-19 vaccine with the risk of miscarriages using the Real-World. We identified a cohort of vaccinated pregnancies using the BIFAP database which contains systematically recorded data on care patients in Spain (N = 4054). We then restricted it to those women who had a miscarriage using a validated algorithm (N = 607). Among them, we performed a case-crossover design to evaluate the effect of intermittent exposures on the risk of miscarriage. Adjusted Odds Ratio with their confidence intervals were calculated using two analytical approaches: conditional logistic regression and Generalized Linear Mixed-Effects Models. A total of 225 (37.1%) were aged 35–39 years. The most common comorbidities were asthma, migraine, gastritis, and hypothyroidism. A total of 14.7% received only one dose of COVID-19 and 85.3% two doses, respectively. A total of 36.8% of women with one dose and 27.6% with two doses received the vaccine 7 days prior to the miscarriage. Corresponding adjusted estimates for the risk of miscarriage using the conditional logistic regression where as follows: 1.65 (95% CI 0.85–3.23) when using as the sum of 3 control moments among women with one dose, 1.02 (95% CI 0.72–1.46) among women with two doses and 1.03 (95% CI 0.72, 1.46) using the whole study population. Very similar results were obtained when conducting the Generalized Linear Mixed-Effects Models. There was no overall increased risk of miscarriage onset associated with COVID-19 vaccine although contradictory results were found according to the number of doses. Further studies are required with larger sample sizes to assess this association.