bluuebunny/crossref_metadata_2025 huggingface dataset:
The marriage of coherent Raman scattering imaging and advanced computational tools
Authors: Peterson Walker , Hiramatsu Kotaro , Goda Keisuke
Published: May 2023

Coherent Raman scattering microscopy can provide high-contrast tissue and single-cell images based on the inherent molecular vibrations of the sample. However, conventional techniques face a three-way trade-off between Raman spectral bandwidth, imaging speed, and image fidelity. Although currently challenging to address via optical design, this trade-off can be overcome via emerging computational tools such as compressive sensing and machine learning.
Enabling direct microcalorimetric measurement of metabolic activity and exothermic reactions onto microfluidic platforms via heat flux sensor integration
Authors: Vehusheia Signe L. K. , Roman Cosmin , Braissant Olivier , Arnoldini Markus , Hierold Christofer
Published: May 2023

All biological processes use or produce heat. Traditional microcalorimeters have been utilized to study the metabolic heat output of living organisms and heat production of exothermic chemical processes. Current advances in microfabrication have made possible the miniaturization of commercial microcalorimeters, resulting in a few studies on the metabolic activity of cells at the microscale in microfluidic chips. Here we present a new, versatile, and robust microcalorimetric differential design based on the integration of heat flux sensors on top of microfluidic channels. We show the design, modeling, calibration, and experimental verification of this system by utilizing Escherichia coli growth and the exothermic base catalyzed hydrolysis of methyl paraben as use cases. The system consists of a Polydimethylsiloxane based flow-through microfluidic chip with two 46 µl chambers and two integrated heat flux sensors. The differential compensation of thermal power measurements allows for the measurement of bacterial growth with a limit of detection of 1707 W/m3, corresponding to 0.021OD (2 ∙ 107 bacteria/mL). We also extracted the thermal power of a single Escherichia coli of between 1.3 and 4.5 pW, comparable to values measured by industrial microcalorimeters. Our system opens the possibility for expanding already existing microfluidic systems, such as drug testing lab-on-chip platforms, with measurements of metabolic changes of cell populations in form of heat output, without modifying the analyte and minimal interference with the microfluidic channel itself.
Facial thermal response to non-painful stressor in premature and term neonates
Authors: Kretschmer Sophie C. A. , Paul Michael , Heussen Nicole , Leonhardt Steffen , Orlikowsky Thorsten , Heimann Konrad
Published: May 2023

Background

This study is a preliminary clinical investigation with the objective to evaluate the facial thermal response of premature and term neonates to a non-painful stressor (hunger) using infrared thermography (IRT). The development of objective and reliable parameters to monitor pain and stress is of relevance for optimal neonatal outcome and achieving a better management of patient comfort.

Methods

We enrolled 12 neonates ranging from 27 to 39 weeks gestation (median: 34) and aged 3–79 days (median: 13). Recordings were performed before and after feeding, with and without hunger. Six regions of interest were chosen for evaluation (nose tip, periorbital and corrugator region, forehead, perioral and chin region).

Results

There was an increase in the facial temperature in infants immediately prior to their next feed relative to infants who were not hungry, with the nasal tip being the facial evaluation site with the greatest temperature change.

Conclusions

The IRT appears to be a feasible and suitable method to detect changes in the neonatal patient. The thermal variations observed seem to reflect an arousal mediated by the parasympathetic nervous system, which has been described in existing infant stress research.

Impact

This is the first study to examine the use of infrared thermography (IRT) in monitoring the facial thermal response to a mild stressor (hunger) in premature and term neonates.

Hunger as a mild, non-pain-associated stressor showed a significant effect on the facial temperature. The thermal signature of the regions of interest chosen showed hunger-related thermal variations.

Results suggest the feasibility and suitability of IRT as an objective diagnostic tool to approach stress and changes in the condition of the neonatal patient.
Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines
Authors: Guo Liyan , Lin Sheng , Chen Zimin , Cao Yu , He Bin , Lu Guangwen
Published: May 2023

The ongoing global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused devastating impacts on the public health and the global economy. Rapid viral antigenic evolution has led to the continual generation of new variants. Of special note is the recently expanding Omicron subvariants that are capable of immune evasion from most of the existing neutralizing antibodies (nAbs). This has posed new challenges for the prevention and treatment of COVID-19. Therefore, exploring broad-spectrum antiviral agents to combat the emerging variants is imperative. In sharp contrast to the massive accumulation of mutations within the SARS-CoV-2 receptor-binding domain (RBD), the S2 fusion subunit has remained highly conserved among variants. Hence, S2-based therapeutics may provide effective cross-protection against new SARS-CoV-2 variants. Here, we summarize the most recently developed broad-spectrum fusion inhibitors (e.g., nAbs, peptides, proteins, and small-molecule compounds) and candidate vaccines targeting the conserved elements in SARS-CoV-2 S2 subunit. The main focus includes all the targetable S2 elements, namely, the fusion peptide, stem helix, and heptad repeats 1 and 2 (HR1-HR2) bundle. Moreover, we provide a detailed summary of the characteristics and action-mechanisms for each class of cross-reactive fusion inhibitors, which should guide and promote future design of S2-based inhibitors and vaccines against new coronaviruses.
TLR7-MyD88-DC-CXCL16 axis results neutrophil activation to elicit inflammatory response in pustular psoriasis
Authors: Lu Jiajing , Zhong Xiaoyuan , Guo Chunyuan , Tang Li , Yu Ning , Peng Chen , Ding Yangfeng , Bao Xunxia , Zhou Jing , Shi Yuling
Published: May 2023

Pustular psoriasis (PP) is a chronic inflammatory disease associated with multiple complications, often with hyperthermia and hypoproteinemia, and its continued progression can be life-threatening. Toll-like receptor 7 (TLR7) induces dendritic cell (DC) production of inflammatory factors that exacerbate the inflammatory response in PP. A membrane-bound chemokine expressed on DCs, CXC motif chemokine ligand 16 (CXCL16) is overexpressed in PP lesions, and neutrophils express its receptor CXC chemokine receptor 6 (CXCR6). There are few studies on the PP immune microenvironment and it is unclear whether TLR7 and CXCL16 can be used as targets in PP therapy. Skin tissue (n = 5) and blood (n = 20) samples were collected from PP and healthy normal controls. The skin tissue transcriptome was analyzed to obtain the differentially expressed genes, and the immune microenvironment was deciphered using pathway enrichment. Tissue sequencing analysis indicated that TLR7, CXCL16, DCs, and neutrophils were involved in the PP process. The enzyme-linked immunosorbent assay, reverse transcription–PCR, and scoring table results demonstrated that TLR7 induced DC secretion of CXCL16, which enabled neutrophil activation of the secretion of the inflammatory factors interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α). The co-culture of neutrophils with DCs treated with TLR7 inhibitor or TLR7 agonist demonstrated that TLR7 regulated neutrophil activation, migration, and apoptosis. We constructed imiquimod-induced psoriasis-like skin lesions in wild-type, Cd11c-Cre Myd88f/f, and Mrp8-Cre Cxcr6f/f mice. The mouse models suggested that TLR7 might influence DC release of CXCL16 and neutrophil proinflammatory effects by interfering with the myeloid differentiation primary response gene 88 (MyD88) signaling pathway. In conclusion, the TLR7–MyD88–DC–CXCL16 axis is an important mechanism that promotes neutrophil migration to PP skin lesions and stimulates the inflammatory response.
Hsa_circ_0060467 promotes breast cancer liver metastasis by complexing with eIF4A3 and sponging miR-1205
Authors: Zeng Yan , Du Wei , Huang Zhongying , Wu Song , Ou Xueqi , Zhang Jinhui , Peng Cheng , Sun Xiaoqing , Tang Hailin
Published: May 2023

Breast cancer (BC) is the most common cancer and the top cause of female mortality worldwide. The prognosis for patients with breast cancer liver metastasis (BCLM) remains poor. Emerging studies suggest that circular RNAs (circRNAs) are associated with the progression of BC. Exploration of circRNAs presents a promising avenue for identifying metastasis-targeting agents and improving the prognosis of patients with BCLM. Microarray and bioinformatic analyses were used to analyze differentially expressed circRNAs between three pairs of BCLM and primary BC. The roles of hsa_circ_0060467 (circMYBL2) and its target gene E2F1 in BC cells were explored by multiple functional experiments. And xenograft mouse models and hepatic metastases of BC hemi-spleen models were used to illustrate the function of circMYBL2 in vivo. The intrinsic molecular mechanism involving circMYBL2 was confirmed by bioinformatics analyses, RIP assays, CHIRP assays, luciferase reporter assays, and rescue experiments. CircMYBL2 was overexpressed in BCLM tissues and BC cells. Functionally, circMYBL2 can facilitate the proliferation and liver metastasis of BC. Mechanistically, circMYBL2 upregulated the transcription factor E2F1 by sponging miR-1205 and complexing with eukaryotic translation initiation factor 4A3 (eIF4A3) and then facilitated the epithelial-mesenchymal transition (EMT) process in BC cells. Our findings showed that circMYBL2 promoted the tumorigenesis and aggressiveness of BC through the circMYBL2/miR-1205/E2F1 and circMYBL2/eIF4A3/E2F1 axes, which may provide a novel targeted therapy for patients with BCLM.
CTLA4 protects against maladaptive cytotoxicity during the differentiation of effector and follicular CD4+ T cells
Authors: Hao Yuwei , Miraghazadeh Bahar , Chand Rochna , Davies Ainsley R. , Cardinez Chelisa , Kwong Kristy , Downes Morgan B. , Sweet Rebecca A. , Cañete Pablo F. , D’Orsogna Lloyd J. , Fulcher David A. , Choo Sharon , Yip Desmond , Peters Geoffrey , Yip Sonia , Witney Matthew J. , Nekrasov Maxim , Feng Zhi-Ping , Tscharke David C. , Vinuesa Carola G. , Cook Matthew C.
Published: May 2023

As chronic antigenic stimulation from infection and autoimmunity is a feature of primary antibody deficiency (PAD), analysis of affected patients could yield insights into T-cell differentiation and explain how environmental exposures modify clinical phenotypes conferred by single-gene defects. CD57 marks dysfunctional T cells that have differentiated after antigenic stimulation. Indeed, while circulating CD57+ CD4+ T cells are normally rare, we found that they are increased in patients with PAD and markedly increased with CTLA4 haploinsufficiency or blockade. We performed single-cell RNA-seq analysis of matched CD57+ CD4+ T cells from blood and tonsil samples. Circulating CD57+ CD4+ T cells (CD4cyt) exhibited a cytotoxic transcriptome similar to that of CD8+ effector cells, could kill B cells, and inhibited B-cell responses. CTLA4 restrained the formation of CD4cyt. While CD57 also marked an abundant subset of follicular helper T cells, which is consistent with their antigen-driven differentiation, this subset had a pre-exhaustion transcriptomic signature marked by TCF7, TOX, and ID3 expression and constitutive expression of CTLA4 and did not become cytotoxic even after CTLA4 inhibition. Thus, CD57+ CD4+ T-cell cytotoxicity and exhaustion phenotypes are compartmentalised between blood and germinal centers. CTLA4 is a key modifier of CD4+ T-cell cytotoxicity, and the pathological CD4cyt phenotype is accentuated by infection.
Is there any association between genetically predicted periodontitis and ischemic stroke?
Authors: Kumar Satish
Published: May 2023

Design

Mendelian randomization study.

Case selection

Using a Mendelian randomization framework, the causal relationship between periodontitis [chronic periodontitis (CP) and aggressive periodontitis (AgP)] and ischemic stroke and its subtypes [cardioembolic (CE) stroke, large artery atherosclerosis (LAA), and small vessel occlusion (SVO)], were studied.

Data analysis

Data from three large databanks, namely, UK Biobank, genome-wide association study of European ancestry, and MEGASTROKE consortium of European ancestry were used to obtain genetic variant information of CP, AgP, and ischemic stroke, respectively. UK Biobank contributed 950 cases of CP and 455,398 controls. Genome-wide association study of European ancestry contributed 851 AgP cases and 6836 controls. MEGASTROKE consortium of European ancestry contributed 34,217 cases of ischemic stroke and its subtypes and 406,111 controls. Statistical tests including inverse variant weighted method and sensitivity analyses were performed to analyse the causal inference and to verify the strength of the results.

Results

A total of 15 single nucleotide polymorphisms (SNPs) for CP was obtained as genetic instruments. No causal inference of CP on ischemic stroke was found. Among the ischemic stroke subtypes, with the exception of CE stroke, no significant causal inference of CP on LAA or SVO was found. A total of 9 single nucleotide polymorphisms (SNPs) for AgP was obtained as genetic instruments. No causal inference of AgP on ischemic stroke and its subtypes were found.

Conclusions

Neither CP nor AgP was found to have a causal inference on ischemic stroke and most of its subtypes. A probable causal effect of CP on CE stroke was noted.
Memory-dictated dynamics of single-atom Pt on CeO2 for CO oxidation
Authors: Zhang Zihao , Tian Jinshu , Lu Yubing , Yang Shize , Jiang Dong , Huang Weixin , Li Yixiao , Hong Jiyun , Hoffman Adam S. , Bare Simon R. , Engelhard Mark H. , Datye Abhaya K. , Wang Yong
Published: May 2023

Single atoms of platinum group metals on CeO2represent a potential approach to lower precious metal requirements for automobile exhaust treatment catalysts. Here we show the dynamic evolution of two types of single-atom Pt (Pt1) on CeO2, i.e., adsorbed Pt1in Pt/CeO2and square planar Pt1in PtATCeO2, fabricated at 500 °C and by atom-trapping method at 800 °C, respectively. Adsorbed Pt1in Pt/CeO2is mobile with the in situ formation of few-atom Pt clusters during CO oxidation, contributing to high reactivity with near-zero reaction order in CO. In contrast, square planar Pt1in PtATCeO2is strongly anchored to the support during CO oxidation leading to relatively low reactivity with a positive reaction order in CO. Reduction of both Pt/CeO2and PtATCeO2in CO transforms Pt1to Pt nanoparticles. However, both catalysts retain the memory of their initial Pt1state after reoxidative treatments, which illustrates the importance of the initial single-atom structure in practical applications.
The PECAn image and statistical analysis pipeline identifies Minute cell competition genes and features
Authors: Baumgartner Michael E. , Langton Paul F. , Logeay Remi , Mastrogiannopoulos Alex , Nilsson-Takeuchi Anna , Kucinski Iwo , Lavalou Jules , Piddini Eugenia
Published: May 2023

Investigating organ biology often requires methodologies to induce genetically distinct clones within a living tissue. However, the 3D nature of clones makes sample image analysis challenging and slow, limiting the amount of information that can be extracted manually. Here we develop PECAn, a pipeline for image processing and statistical data analysis of complex multi-genotype 3D images. PECAn includes data handling, machine-learning-enabled segmentation, multivariant statistical analysis, and graph generation. This enables researchers to perform rigorous analyses rapidly and at scale, without requiring programming skills. We demonstrate the power of this pipeline by applying it to the study of Minute cell competition. We find an unappreciated sexual dimorphism in Minute cell growth in competing wing discs and identify, by statistical regression analysis, tissue parameters that model and correlate with competitive death. Furthermore, using PECAn, we identify several genes with a role in cell competition by conducting an RNAi-based screen.
Origin of dendrite-free lithium deposition in concentrated electrolytes
Authors: Chen Yawei , Li Menghao , Liu Yue , Jie Yulin , Li Wanxia , Huang Fanyang , Li Xinpeng , He Zixu , Ren Xiaodi , Chen Yunhua , Meng Xianhui , Cheng Tao , Gu Meng , Jiao Shuhong , Cao Ruiguo
Published: May 2023

The electrolyte solvation structure and the solid-electrolyte interphase (SEI) formation are critical to dictate the morphology of lithium deposition in organic electrolytes. However, the link between the electrolyte solvation structure and SEI composition and its implications on lithium morphology evolution are poorly understood. Herein, we use a single-salt and single-solvent model electrolyte system to systematically study the correlation between the electrolyte solvation structure, SEI formation process and lithium deposition morphology. The mechanism of lithium deposition is thoroughly investigated using cryo-electron microscopy characterizations and computational simulations. It is observed that, in the high concentration electrolytes, concentrated Li+ and anion-dominated solvation structure initiate the uniform Li nucleation kinetically and favor the decomposition of anions rather than solvents, resulting in inorganic-rich amorphous SEI with high interface energy, which thermodynamically facilitates the formation of granular Li. On the contrary, solvent-dominated solvation structure in the low concentration electrolytes tends to exacerbate the solvolysis process, forming organic-rich mosaic SEI with low interface energy, which leads to aggregated whisker-like nucleation and growth. These results are helpful to tackle the long-standing question on the origin of lithium dendrite formation and guide the rational design of high-performance electrolytes for advanced lithium metal batteries.
High-resolution discrimination of homologous and isomeric proteinogenic amino acids in nanopore sensors with ultrashort single-walled carbon nanotubes
Authors: Peng Weichao , Yan Shuaihu , Zhou Ke , Wu Hai-Chen , Liu Lei , Zhao Yuliang
Published: May 2023

The hollow and tubular structure of single-walled carbon nanotubes (SWCNTs) makes them ideal candidates for making nanopores. However, the heterogeneity of SWCNTs hinders the fabrication of robust and reproducible carbon-based nanopore sensors. Here we develop a modified density gradient ultracentrifugation approach to separate ultrashort (≈5-10 nm) SWCNTs with a narrow conductance range and construct high-resolution nanopore sensors with those tubes inserted in lipid bilayers. By conducting ionic current recordings and fluorescent imaging of Ca2+ flux through different nanopores, we prove that the ion mobilities in SWCNT nanopores are 3-5 times higher than the bulk mobility. Furthermore, we employ SWCNT nanopores to discriminate homologue or isomeric proteinogenic amino acids, which are challenging tasks for other nanopore sensors. These successes, coupled with the building of SWCNT nanopore arrays, may constitute a crucial part of the recently burgeoning protein sequencing technologies.
Reversion of breast epithelial polarity alterations caused by obesity
Authors: Holmes Julia , Gaber Mohamed , Jenks Mónica Z. , Wilson Adam , Loy Tucker , Lepetit Cassandra , Vitolins Mara Z. , Herbert Brittney-Shea , Cook Katherine L. , Vidi Pierre-Alexandre
Published: May 2023

Molecular links between breast cancer risk factors and pro-oncogenic tissue alterations are poorly understood. The goal of this study was to characterize the impact of overweight and obesity on tissue markers of risk, using normal breast biopsies, a mouse model of diet-induced obesity, and cultured breast acini. Proliferation and alteration of epithelial polarity, both necessary for tumor initiation, were quantified by immunostaining. High BMI (>30) and elevated leptin were associated with compromised epithelial polarity whereas overweight was associated with a modest increase in proliferation in human and mice mammary glands. Human serum with unfavorable adipokine levels altered epithelial polarization of cultured acini, recapitulating the effect of leptin. Weight loss in mice led to metabolic improvements and restored epithelial polarity. In acini cultures, alteration of epithelial polarity was prevented by antioxidants and could be reverted by normalizing culture conditions. This study shows that obesity and/or dietary factors modulate tissue markers of risk. It provides a framework to set target values for metabolic improvements and to assess the efficacy of interventional studies aimed at reducing breast cancer risk.
Evaluating the prebiotic effect of oligosaccharides on gut microbiome wellness using in vitro fecal fermentation
Authors: Lee Dong Hyeon , Seong Hyunbin , Chang Daniel , Gupta Vinod K. , Kim Jiseung , Cheon Seongwon , Kim Geonhee , Sung Jaeyun , Han Nam Soo
Published: May 2023

We previously proposed the Gut Microbiome Wellness Index (GMWI), a predictor of disease presence based on a gut microbiome taxonomic profile. As an application of this index for food science research, we applied GMWI as a quantitative tool for measuring the prebiotic effect of oligosaccharides. Mainly, in an in vitro anaerobic batch fermentation system, fructooligosaccharides (FOS), galactooligosaccharides (GOS), xylooligosaccharides (XOS), inulin (IN), and 2’-fucosyllactose (2FL), were mixed separately with fecal samples obtained from healthy adult volunteers. To find out how 24 h prebiotic fermentation influenced the GMWI values in their respective microbial communities, changes in species-level relative abundances were analyzed in the five prebiotics groups, as well as in two control groups (no substrate addition at 0 h and for 24 h). The GMWI of fecal microbiomes treated with any of the five prebiotics (IN (0.48 ± 0.06) > FOS (0.47 ± 0.03) > XOS (0.33 ± 0.02) > GOS (0.26 ± 0.02) > 2FL (0.16 ± 0.06)) were positive, which indicates an increase of relative abundances of microbial species previously found to be associated with a healthy, disease-free state. In contrast, the GMWI of samples without substrate addition for 24 h (–0.60 ± 0.05) reflected a non-healthy, disease-harboring microbiome state. Compared to the original prebiotic index (PI) and α-diversity metrics, GMWI provides a more data-driven, evidence-based indexing system for evaluating the prebiotic effect of food components. This study demonstrates how GMWI can be applied as a novel PI in dietary intervention studies, with wider implications for designing personalized diets based on their impact on gut microbiome wellness.
Thermal Bridges on Building Rooftops
Authors: Mayer Zoe , Kahn James , Götz Markus , Hou Yu , Beiersdörfer Tobias , Blumenröhr Nicolas , Volk Rebekka , Streit Achim , Schultmann Frank
Published: May 2023

Thermal Bridges on Building Rooftops (TBBR) is a multi-channel remote sensing dataset. It was recorded during six separate UAV fly-overs of the city center of Karlsruhe, Germany, and comprises a total of 926 high-resolution images with 6927 manually-provided thermal bridge annotations. Each image provides five channels: three color, one thermographic, and one computationally derived height map channel. The data is pre-split into training and test data subsets suitable for object detection and instance segmentation tasks. All data is organized and structured to comply with FAIR principles, i.e. being findable, accessible, interoperable, and reusable. It is publicly available and can be downloaded from the Zenodo data repository. This work provides a comprehensive data descriptor for the TBBR dataset to facilitate broad community uptake.
In-depth Temporal Transcriptome Profiling of Monkeypox and Host Cells using Nanopore Sequencing
Authors: Kakuk Balázs , Dörmő Ákos , Csabai Zsolt , Kemenesi Gábor , Holoubek Jiří , Růžek Daniel , Prazsák István , Dani Virág Éva , Dénes Béla , Torma Gábor , Jakab Ferenc , Tóth Gábor E. , Földes Fanni V. , Zana Brigitta , Lanszki Zsófia , Harangozó Ákos , Fülöp Ádám , Gulyás Gábor , Mizik Máté , Kiss András Attila , Tombácz Dóra , Boldogkői Zsolt
Published: May 2023

The recent human Monkeypox outbreak underlined the importance of studying basic biology of orthopoxviruses. However, the transcriptome of its causative agent has not been investigated before neither with short-, nor with long-read sequencing approaches. This Oxford Nanopore long-read RNA-Sequencing dataset fills this gap. It will enable the in-depth characterization of the transcriptomic architecture of the monkeypox virus, and may even make possible to annotate novel host transcripts. Moreover, our direct cDNA and native RNA sequencing reads will allow the estimation of gene expression changes of both the virus and the host cells during the infection. Overall, our study will lead to a deeper understanding of the alterations caused by the viral infection on a transcriptome level.
Quantitative Mass Spectrometry Analysis of Cerebrospinal Fluid Protein Biomarkers in Alzheimer’s Disease
Authors: Watson Caroline M. , Dammer Eric B. , Ping Lingyan , Duong Duc M. , Modeste Erica , Carter E. Kathleen , Johnson Erik C. B. , Levey Allan I. , Lah James J. , Roberts Blaine R. , Seyfried Nicholas T.
Published: May 2023

Alzheimer’s disease (AD) is the most common form of dementia, with cerebrospinal fluid (CSF) β-amyloid (Aβ), total Tau, and phosphorylated Tau (pTau) providing the most sensitive and specific biomarkers for diagnosis. However, these diagnostic biomarkers do not reflect the complex changes in AD brain beyond amyloid (A) and Tau (T) pathologies. Here, we report a selected reaction monitoring mass spectrometry (SRM-MS) method with isotopically labeled standards for relative protein quantification in CSF. Biomarker positive (AT+) and negative (AT−) CSF pools were used as quality controls (QCs) to assess assay precision. We detected 62 peptides (51 proteins) with an average coefficient of variation (CV) of ~13% across 30 QCs and 133 controls (cognitively normal, AT−), 127 asymptomatic (cognitively normal, AT+) and 130 symptomatic AD (cognitively impaired, AT+). Proteins that could distinguish AT+ from AT− individuals included SMOC1, GDA, 14-3-3 proteins, and those involved in glycolysis. Proteins that could distinguish cognitive impairment were mainly neuronal proteins (VGF, NPTX2, NPTXR, and SCG2). This demonstrates the utility of SRM-MS to quantify CSF protein biomarkers across stages of AD.
Crowd cluster data in the USA for analysis of human response to COVID-19 events and policies
Authors: Swaminathan B. , Kang J. , Vaidya K. , Srinivasan A. , Kumar P. , Byna S. , Barbarash D.
Published: May 2023

We provide data on daily social contact intensity of clusters of people at different types of Points of Interest (POI) by zip code in Florida and California. This data is obtained by aggregating fine-scaled details of interactions of people at the spatial resolution of 10 m, which is then normalized as a social contact index. We also provide the distribution of cluster sizes and average time spent in a cluster by POI type. This data will help researchers perform fine-scaled, privacy-preserving analysis of human interaction patterns to understand the drivers of the COVID-19 epidemic spread and mitigation. Current mobility datasets either provide coarse-level metrics of social distancing, such as radius of gyration at the county or province level, or traffic at a finer scale, neither of which is a direct measure of contacts between people. We use anonymized, de-identified, and privacy-enhanced location-based services (LBS) data from opted-in cell phone apps, suitably reweighted to correct for geographic heterogeneities, and identify clusters of people at non-sensitive public areas to estimate fine-scaled contacts.
M4Raw: A multi-contrast, multi-repetition, multi-channel MRI k-space dataset for low-field MRI research
Authors: Lyu Mengye , Mei Lifeng , Huang Shoujin , Liu Sixing , Li Yi , Yang Kexin , Liu Yilong , Dong Yu , Dong Linzheng , Wu Ed X.
Published: May 2023

Recently, low-field magnetic resonance imaging (MRI) has gained renewed interest to promote MRI accessibility and affordability worldwide. The presented M4Raw dataset aims to facilitate methodology development and reproducible research in this field. The dataset comprises multi-channel brain k-space data collected from 183 healthy volunteers using a 0.3 Tesla whole-body MRI system, and includes T1-weighted, T2-weighted, and fluid attenuated inversion recovery (FLAIR) images with in-plane resolution of ~1.2 mm and through-plane resolution of 5 mm. Importantly, each contrast contains multiple repetitions, which can be used individually or to form multi-repetition averaged images. After excluding motion-corrupted data, the partitioned training and validation subsets contain 1024 and 240 volumes, respectively. To demonstrate the potential utility of this dataset, we trained deep learning models for image denoising and parallel imaging tasks and compared their performance with traditional reconstruction methods. This M4Raw dataset will be valuable for the development of advanced data-driven methods specifically for low-field MRI. It can also serve as a benchmark dataset for general MRI reconstruction algorithms.
Indexing climatic and environmental exposure of refugee camps with a case study in East Africa
Authors: Owen Michael , Kruczkiewicz Andrew , Van Den Hoek Jamon
Published: May 2023

This study presents a novel approach to systematically measure climatic and environmental exposure in refugee camps using remote sensing and geospatial data. Using a case study of seventeen refugee camps across five countries in East Africa, we develop a climatic and environmental exposure index to quantify each camp’s exposure relative to a population of simulated camp locations within the hosting country. Our results show that seven of seventeen refugee camps are within the upper two quartiles of exposure relative to a simulated population, suggesting that more than six-hundred thousand refugees living in these camps face elevated exposure compared to other potential camp locations. This method stands to improve the process of gathering and analyzing climatic and environmental data on geographically remote humanitarian spaces in a reliable, low-cost, and standardized manner. Automation and refinement of this index could enable real-time updates on climatic and environmental exposure to support decision-making related to disaster risk reduction in refugee camp management.
Platelet function suggests cardioembolic aetiology in cryptogenic stroke
Authors: Dev Priya , Ekhlak Mohammad , Dash Debabrata , Pathak Abhishek
Published: May 2023

Platelet-monocyte (PMA) and platelet-neutrophil aggregations (PNA) play critical roles in the evolution of acute ischemic stroke (AIS). The present study investigates the mechanistic basis of platelet responsiveness in cryptogenic stroke compared with cardioembolic stroke. Platelet from 16 subjects, each from cryptogenic and cardioembolic stroke groups and 18 age-matched healthy controls were subjected to different investigations. Compared to healthy controls, platelet-monocyte and platelet-neutrophil interactions were significantly elevated in cryptogenic (2.7 and 2.1 times) and cardioembolic stroke (3.9 and 2.4 times). P-selectin expression on platelet surface was 1.89 and 2.59 times higher in cryptogenic and cardioembolic strokes, respectively, compared to healthy control. Cell population with [Ca2+i] in either stroke group was significantly outnumbered (by 83% and 72%, respectively, in cryptogenic and cardioembolic stroke) in comparison to healthy controls. Noteworthy, TEG experiment revealed that the cryptogenic stroke exhibited significant decline in Reaction Time (R) and amplitude of 20 mm (K) (by 32% and 33%, respectively) while thrombin burst (α-angle) was augmented by 12%, which reflected substantial boost in thrombus formation in cryptogenic stroke. Although TEG analysis reveals a state of hypercoagulability in patients with cryptogenic stroke. However, platelets from both stroke subtypes switch to a ‘hyperactive’ phenotype.
Treatment of hypertension and obstructive sleep apnea counteracts cognitive decline in common neurocognitive disorders in diagnosis-related patterns
Authors: Kujovic Milenko , Lipka Tim , Zalman Mark , Baumann Leonie , Jänner Michaela , Baumann Bruno
Published: May 2023

The aim of this study was to investigate the effect of arterial hypertension (AH) and of obstructive sleep apnea (OSA) on cognitive course in the neurocognitive disorder (NCD) cohort RIFADE which enrolled patients with NCD due to Alzheimer’s disease (AD), vascular NCD (vNCD), and mixed NCD (AD + vNCD = mNCD). Multiple risk factors (RF), including AH and OSA, that contribute to the development of various kinds of dementia have been identified in previous studies. Studies that observed AH lacked investigation of long-term effects and did not isolate it from other RF. Studies involving OSA as a risk factor did not include participants with all stages of NCD. 126 subjects were screened for AH and OSA. Repeated cognitive measurements were performed with the DemTect as primary outcome and the clock drawing test as secondary outcome measure. 90 patients had AH (71.4%) and 40 patients had OSA (31.7%). RF-status had a significant effect on cognitive outcome in models with RF as single factors (AH p = 0.027, OSA p < 0.001), a 2-factor analysis with AH × OSA (AH as main factor p = 0.027) as well as a model including the 3 factors AH × OSA × diagnosis (p = 0.038). Similarly, a 3-factor model was significant for the clock-drawing test, whereas single factor-models remained insignificant. AH and OSA appear to be risk factors in common NCD and cognitive decline can be mitigated by treatment of these RF.
Bio-inspired artificial synapse for neuromorphic computing based on NiO nanoparticle thin film
Authors: Hadiyal Keval , Ganesan Ramakrishnan , Rastogi A. , Thamankar R.
Published: May 2023

The unprecedented need for data processing in the modern technological era has created opportunities in neuromorphic devices and computation. This is primarily due to the extensive parallel processing done in our human brain. Data processing and logical decision-making at the same physical location are an exciting aspect of neuromorphic computation. For this, establishing reliable resistive switching devices working at room temperature with ease of fabrication is important. Here, a reliable analog resistive switching device based on Au/NiO nanoparticles/Au is discussed. The application of positive and negative voltage pulses of constant amplitude results in enhancement and reduction of synaptic current, which is consistent with potentiation and depression, respectively. The change in the conductance resulting in such a process can be fitted well with double exponential growth and decay, respectively. Consistent potentiation and depression characteristics reveal that non-ideal voltage pulses can result in a linear dependence of potentiation and depression. Long-term potentiation (LTP) and Long-term depression (LTD) characteristics have been established, which are essential for mimicking the biological synaptic applications. The NiO nanoparticle-based devices can also be used for controlled synaptic enhancement by optimizing the electric pulses, displaying typical learning-forgetting-relearning characteristics.
Weakly supervised detection and classification of basal cell carcinoma using graph-transformer on whole slide images
Authors: Yacob Filmon , Siarov Jan , Villiamsson Kajsa , Suvilehto Juulia T. , Sjöblom Lisa , Kjellberg Magnus , Neittaanmäki Noora
Published: May 2023

The high incidence rates of basal cell carcinoma (BCC) cause a significant burden at pathology laboratories. The standard diagnostic process is time-consuming and prone to inter-pathologist variability. Despite the application of deep learning approaches in grading of other cancer types, there is limited literature on the application of vision transformers to BCC on whole slide images (WSIs). A total of 1832 WSIs from 479 BCCs, divided into training and validation (1435 WSIs from 369 BCCs) and testing (397 WSIs from 110 BCCs) sets, were weakly annotated into four aggressivity subtypes. We used a combination of a graph neural network and vision transformer to (1) detect the presence of tumor (two classes), (2) classify the tumor into low and high-risk subtypes (three classes), and (3) classify four aggressivity subtypes (five classes). Using an ensemble model comprised of the models from cross-validation, accuracies of 93.5%, 86.4%, and 72% were achieved on two, three, and five class classifications, respectively. These results show high accuracy in both tumor detection and grading of BCCs. The use of automated WSI analysis could increase workflow efficiency.
A system that delivers an antioxidant to mitochondria for the treatment of drug-induced liver injury
Authors: Hibino Mitsue , Maeki Masatoshi , Tokeshi Manabu , Ishitsuka Yoichi , Harashima Hideyoshi , Yamada Yuma
Published: May 2023

Mitochondria, a major source of reactive oxygen species (ROS), are intimately involved in the response to oxidative stress in the body. The production of excessive ROS affects the balance between oxidative responses and antioxidant defense mechanisms thus perturbing mitochondrial function eventually leading to tissue injury. Therefore, antioxidant therapies that target mitochondria can be used to treat such diseases and improve general health. This study reports on an attempt to establish a system for delivering an antioxidant molecule coenzyme Q10 (CoQ10) to mitochondria and the validation of its therapeutic efficacy in a model of acetaminophen (APAP) liver injury caused by oxidative stress in mitochondria. A CoQ10-MITO-Porter, a mitochondrial targeting lipid nanoparticle (LNP) containing encapsulated CoQ10, was prepared using a microfluidic device. It was essential to include polyethylene glycol (PEG) in the lipid composition of this LNP to ensure stability of the CoQ10, since it is relatively insoluble in water. Based on transmission electron microscope (TEM) observations and small angle X-ray scattering (SAXS) measurements, the CoQ10-MITO-Porter was estimated to be a 50 nm spherical particle without a regular layer structure. The use of the CoQ10-MITO-Porter improved liver function and reduced tissue injury, suggesting that it exerted a therapeutic effect on APAP liver injury.
HCV, HIV AND HBV rapid test diagnosis in non-clinical outreach settings can be as accurate as conventional laboratory tests
Authors: Muñoz-Chimeno Milagros , Valencia Jorge , Rodriguez-Recio Alvaro , Cuevas Guillermo , Garcia-Lugo Alejandra , Manzano Samuel , Rodriguez-Paredes Vanessa , Fernandez Beatriz , Morago Lucía , Casado Concepción , Avellón Ana , Ryan Pablo
Published: May 2023

Point of care rapid diagnostic tests (POC-RDT) for Hepatitis C virus (HCV), Human Immunodeficiency virus (HIV) and Hepatitis B virus (HBV), are ideal for screening in non-clinical outreach settings as they can provide immediate results and facilitate diagnosis, allowing high risk population screening. The aim of this study was to compare POC-RDT with laboratory conventional tests. A total of 301 vulnerable evaluable subjects (drug users, migrants and homeless population) were recruited at a mobile screening unit in outreach settings in Madrid. Fingerprick whole blood capillary samples were tested using the SD BIOLINE HCV POC-RDT, Determine HIV Early Detect and Determine HBsAg 2, and the results were assessed against the LIAISON XL HCV, HIV and Murex-HBsAg-Quant, reference assays, respectively. The feasibility and user satisfaction of the POC-RDT were evaluated through a questionnaire. The resolved sensitivity and resolved specificity and their 95% confidence intervals (95% CI) were as follows, respectively: SD-BIOLINE-HCV: 98.8% (95% CI 93.4, 100.0) and 100.0% (95% CI 98.3, 100.0); Determine HIV Early Detect: 100% (95% CI 85.2, 100.0) and 100% (95% CI 98.7, 100); and Determine HBsAg 2: 66.7% (95% CI 9.4, 99.2) and 100.0% (95% CI 98.7, 100.0). As expected, the number of subjects with a confirmed positive result for HBsAg was very low (n = 4). Therefore, the analytical sensitivity has been evaluated in addition: The Determine HBsAg 2 test demonstrated 100% sensitivity for standard concentrations ≥ 0.125 IU/mL. The subject questionnaire yielded positive feedback for most subjects. The POC-RDT fingerprick blood collection method was well received, and the tests demonstrated a comparable clinical performance with conventional tests in outreach settings and vulnerable high-risk populations.
A mechanical theory of competition between plant root growth and soil pressure reveals a potential mechanism of root penetration
Authors: Tomobe Haruka , Tsugawa Satoru , Yoshida Yuki , Arita Tetsuya , Tsai Allen Yi-Lun , Kubo Minoru , Demura Taku , Sawa Shinichiro
Published: May 2023

Root penetration into the soil is essential for plants to access water and nutrients, as well as to mechanically support aboveground structures. This requires a combination of healthy plant growth, adequate soil mechanical properties, and compatible plant–soil interactions. Despite the current knowledge of the static rheology driving the interactions at the root–soil interface, few theoretical approaches have attempted to describe root penetration with dynamic rheology. In this work, we experimentally showed that radish roots in contact with soil of specific density during a specific growth stage fail to penetrate the soil. To explore the mechanism of root penetration into the soil, we constructed a theoretical model to explore the relevant conditions amenable to root entry into the soil. The theory indicates that dimensionless parameters such as root growth anisotropy, static root–soil competition, and dynamic root–soil competition are important for root penetration. The consequent theoretical expectations were supported by finite element analysis, and a potential mechanism of root penetration into the soil is discussed.
Robust morphogenesis by chaotic dynamics
Authors: Reinitz J. , Vakulenko S. , Sudakow I. , Grigoriev D.
Published: May 2023

This research illustrates that complex dynamics of gene products enable the creation of any prescribed cellular differentiation patterns. These complex dynamics can take the form of chaotic, stochastic, or noisy chaotic dynamics. Based on this outcome and previous research, it is established that a generic open chemical reactor can generate an exceptionally large number of different cellular patterns. The mechanism of pattern generation is robust under perturbations and it is based on a combination of Turing’s machines, Turing instability and L. Wolpert’s gradients. These results can help us to explain the formidable adaptive capacities of biochemical systems.
Damage characteristics of weak rocks with different dip angles during creep
Authors: Miao Haibin , Zhao Na , Meng Lixin , Zhang Yibin , Wang Laigui
Published: May 2023

To investigate the influence of the weak layer dip angle on the creep rupture of the composite rock mass, this paper conducts a graded loading creep experiment on the composite rock mass with different dip angles using the acoustic emission method to examine the fracture evolution process. With increasing load grade, the cumulative total ring count of the rock mass shows a “U”-shaped trend, and the acoustic emission spatial positioning results show that acoustic emission events in the rock mass fracture process are primarily concentrated in the vicinity of the weak layer, while events in other areas are few and dispersed. For rock masses with weak layer dip angles of 0° and 15°, cracks occur in both soft and hard rocks, where shear cracks are dominant in soft rocks, tensile cracks are dominant in hard rocks, and finally, the rock mass mainly exhibits tensile splitting failure. For rock masses with weak layer dip angles of 30° and 45°, most of the cracks exist in the interior of the soft rock, which is dominated by shear cracks. With increasing graded loads, the shear cracks continue to develop along the direction of the weak layer, the upper rock mass keeps slipping and dislocating, and the final failure mode is mainly shear-slip failure. The damage evolution varies with the inclination angle of the weak layer, which can be divided into three stages: initial damage accumulation, damage acceleration, and damage destruction. This demonstrates the ability to predict, prevent, and control the occurrence of creep disasters in rock masses with weak layers.
Study on crystal growth of Ge/Si quantum dots at different Ge deposition by using magnetron sputtering technique
Authors: Shu Qijiang , Huang Pengru , Yang Fuhua , Yang Linjing , Chen Lei
Published: May 2023

We investigated the growth and evolution of Si-based Ge quantum dots (Ge/Si QDs) under low Ge deposition (1.2–4.4 nm thick) using magnetron sputtering. The morphology and structure of QDs were analyzed with the help of an atomic force microscope (AFM), scanning electron microscope, transmission electron microscope, Raman, surface energy theory and dynamics theory, the photoelectric properties of QDs were characterized by photoluminescence (PL) spectra. The results showed that the growth mechanism of QDs conformed to Stranski–Krastanow mode, but the typical thickness of the wetting layer was nearly three times higher than those derived from conventional technologies such as molecular beam epitaxy, chemical vapor deposition, solid phase epitaxy and so on. Meanwhile, the shape evolution of QDs was very different from existing reports. The specific internal causes of these novel phenomena were analyzed and confirmed and reported in this paper. In addition, the AFM, Raman, and PL tests all indicated that the QDs grown when 3.4 nm Ge was deposited have the most excellent morphology, structure, and optoelectronic performance. Our work lays a foundation for further exploration of the controllable growth of QDs at high deposition rates, which is a new way to realize the industrialization of QDs used for future devices.
Oxidation-induced nanolite crystallization triggered the 2021 eruption of Fukutoku-Oka-no-Ba, Japan
Authors: Yoshida Kenta , Miyake Akira , Okumura Shota H. , Ishibashi Hidemi , Okumura Satoshi , Okamoto Atsushi , Niwa Yasuhiro , Kimura Masao , Sato Tomoki , Tamura Yoshihiko , Ono Shigeaki
Published: May 2023

Nanometer-sized crystals (nanolites) play an important role in controlling eruptions by affecting the viscosity of magmas and inducing bubble nucleation. We present detailed microscopic and nanoscopic petrographic analyses of nanolite-bearing and nanolite-free pumice from the 2021 eruption of Fukutoku-Oka-no-Ba, Japan. The nanolite mineral assemblage includes biotite, which is absent from the phenocryst mineral assemblage, and magnetite and clinopyroxene, which are observed as phenocrysts. The boundary between the nanolite-bearing brown glass and nanolite-free colorless glass is either sharp or gradational, and the sharp boundaries also appear sharp under the transmitted electron microscope. X-ray absorption fine structure (XAFS) analysis of the volcanic glass revealed that the nanolite-free colorless glass records an oxygen fugacity of QFM + 0.98 (log units), whereas the nanolite-bearing brown glass records a higher apparent oxygen fugacity (~ QFM + 2). Thermodynamic modelling using MELTS indicates that higher oxygen fugacities increase the liquidus temperature and thus induced the crystallization of magnetite nanolites. The hydrous nanolite mineral assemblage and glass oxygen fugacity estimates suggest that an oxidizing fluid supplied by a hot mafic magma induced nanolite crystallization in the magma reservoir, before the magma fragmentation. The oxidation-induced nanolite crystallization then enhanced heterogeneous bubble nucleation, resulting in convection in the magma reservoir and triggering the eruption.