bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wide-field imaging with smartphone based fundus camera: grading of severity of diabetic retinopathy and locating peripheral lesions in diabetic retinopathy
Authors: Rajalakshmi Ramachandran , Mohammed Rajah , Vengatesan Kalaivani , PramodKumar Thyparambil Aravindakshan , Venkatesan Ulagamathesan , Usha Manoharan , Arulmalar Subramanian , Prathiba Vijayaraghavan , Mohan Viswanathan 
Published: January 2024

Abstract
Aim
To assess the performance of smartphone based wide-field retinal imaging (WFI) versus ultra-wide-field imaging (UWFI) for assessment of sight-threatening diabetic retinopathy (STDR) as well as locating predominantly peripheral lesions (PPL) of DR.

Methods
Individuals with type 2 diabetes with varying grades of DR underwent nonmydriatic UWFI with Daytona Plus camera followed by mydriatic WFI with smartphone-based Vistaro camera at a tertiary care diabetes centre in South India in 2021–22. Grading of DR as well as identification of PPL (DR lesions beyond the posterior pole) in the retinal images of both cameras was performed by senior retina specialists. STDR was defined by the presence of severe non-proliferative DR, proliferative DR or diabetic macular oedema (DME). The sensitivity and specificity of smartphone based WFI for detection of PPL and STDR was assessed. Agreement between the graders for both cameras was compared.

Results
Retinal imaging was carried out in 318 eyes of 160 individuals (mean age 54.7 ± 9 years; mean duration of diabetes 16.6 ± 7.9 years). The sensitivity and specificity for detection of STDR by Vistaro camera was 92.7% (95% CI 80.1–98.5) and 96.6% (95% CI 91.5–99.1) respectively and 95.1% (95% CI 83.5–99.4) and 95.7% (95% CI 90.3–98.6) by Daytona Plus respectively. PPL were detected in 89 (27.9%) eyes by WFI by Vistaro camera and in 160 (50.3%) eyes by UWFI. However, this did not translate to any significant difference in the grading of STDR between the two imaging systems. In both devices, PPL were most common in supero-temporal quadrant (34%). The prevalence of PPL increased with increasing severity of DR with both cameras (p < 0.001). The kappa comparison between the 2 graders for varying grades of severity of DR was 0.802 (p < 0.001) for Vistaro and 0.753 (p < 0.001) for Daytona Plus camera.

Conclusion
Mydriatic smartphone-based widefield imaging has high sensitivity and specificity for detecting STDR and can be used to screen for peripheral retinal lesions beyond the posterior pole in individuals with diabetes.
GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region
Authors: Ishikawa Yuki , Tanaka Nao , Asano Yoshihide , Kodera Masanari , Shirai Yuichiro , Akahoshi Mitsuteru , Hasegawa Minoru , Matsushita Takashi , Saito Kazuyoshi , Motegi Sei-ichiro , Yoshifuji Hajime , Yoshizaki Ayumi , Kohmoto Tomohiro , Takagi Kae , Oka Akira , Kanda Miho , Tanaka Yoshihito , Ito Yumi , Nakano Kazuhisa , Kasamatsu Hiroshi , Utsunomiya Akira , Sekiguchi Akiko , Niiro Hiroaki , Jinnin Masatoshi , Makino Katsunari , Makino Takamitsu , Ihn Hironobu , Yamamoto Motohisa , Suzuki Chisako , Takahashi Hiroki , Nishida Emi , Morita Akimichi , Yamamoto Toshiyuki , Fujimoto Manabu , Kondo Yuya , Goto Daisuke , Sumida Takayuki , Ayuzawa Naho , Yanagida Hidetoshi , Horita Tetsuya , Atsumi Tatsuya , Endo Hirahito , Shima Yoshihito , Kumanogoh Atsushi , Hirata Jun , Otomo Nao , Suetsugu Hiroyuki , Koike Yoshinao , Tomizuka Kohei , Yoshino Soichiro , Liu Xiaoxi , Ito Shuji , Hikino Keiko , Suzuki Akari , Momozawa Yukihide , Ikegawa Shiro , Tanaka Yoshiya , Ishikawa Osamu , Takehara Kazuhiko , Torii Takeshi , Sato Shinichi , Okada Yukinori , Mimori Tsuneyo , Matsuda Fumihiko , Matsuda Koichi , Amariuta Tiffany , Imoto Issei , Matsuo Keitaro , Kuwana Masataka , Kawaguchi Yasushi , Ohmura Koichiro , Terao Chikashi 
Published: January 2024

AbstractHere we report the largest Asian genome-wide association study (GWAS) for systemic sclerosis performed to date, based on data from Japanese subjects and comprising of 1428 cases and 112,599 controls. The lead SNP is in the FCGR/FCRL region, which shows a penetrating association in the Asian population, while a complete linkage disequilibrium SNP, rs10917688, is found in a cis-regulatory element for IRF8. IRF8 is also a significant locus in European GWAS for systemic sclerosis, but rs10917688 only shows an association in the presence of the risk allele of IRF8 in the Japanese population. Further analysis shows that rs10917688 is marked with H3K4me1 in primary B cells. A meta-analysis with a European GWAS detects 30 additional significant loci. Polygenic risk scores constructed with the effect sizes of the meta-analysis suggest the potential portability of genetic associations beyond populations. Prioritizing the top 5% of SNPs of IRF8 binding sites in B cells improves the fitting of the polygenic risk scores, underscoring the roles of B cells and IRF8 in the development of systemic sclerosis. The results also suggest that systemic sclerosis shares a common genetic architecture across populations.
Bacterial protoplast-derived nanovesicles carrying CRISPR-Cas9 tools re-educate tumor-associated macrophages for enhanced cancer immunotherapy
Authors: Zhao Mingming , Cheng Xiaohui , Shao Pingwen , Dong Yao , Wu Yongjie , Xiao Lin , Cui Zhiying , Sun Xuedi , Gao Chuancheng , Chen Jiangning , Huang Zhen , Zhang Junfeng 
Published: January 2024

AbstractThe CRISPR-Cas9 system offers substantial potential for cancer therapy by enabling precise manipulation of key genes involved in tumorigenesis and immune response. Despite its promise, the system faces critical challenges, including the preservation of cell viability post-editing and ensuring safe in vivo delivery. To address these issues, this study develops an in vivo CRISPR-Cas9 system targeting tumor-associated macrophages (TAMs). We employ bacterial protoplast-derived nanovesicles (NVs) modified with pH-responsive PEG-conjugated phospholipid derivatives and galactosamine-conjugated phospholipid derivatives tailored for TAM targeting. Utilizing plasmid-transformed E. coli protoplasts as production platforms, we successfully load NVs with two key components: a Cas9-sgRNA ribonucleoprotein targeting Pik3cg, a pivotal molecular switch of macrophage polarization, and bacterial CpG-rich DNA fragments, acting as potent TLR9 ligands. This NV-based, self-assembly approach shows promise for scalable clinical production. Our strategy remodels the tumor microenvironment by stabilizing an M1-like phenotype in TAMs, thus inhibiting tumor growth in female mice. This in vivo CRISPR-Cas9 technology opens avenues for cancer immunotherapy, overcoming challenges related to cell viability and safe, precise in vivo delivery.
Flexible power generators by Ag2Se thin films with record-high thermoelectric performance
Authors: Yang Dong , Shi Xiao-Lei , Li Meng , Nisar Mohammad , Mansoor Adil , Chen Shuo , Chen Yuexing , Li Fu , Ma Hongli , Liang Guang Xing , Zhang Xianghua , Liu Weidi , Fan Ping , Zheng Zhuanghao , Chen Zhi-Gang 
Published: January 2024

AbstractExploring new near-room-temperature thermoelectric materials is significant for replacing current high-cost Bi2Te3. This study highlights the potential of Ag2Se for wearable thermoelectric electronics, addressing the trade-off between performance and flexibility. A record-high ZT of 1.27 at 363 K is achieved in Ag2Se-based thin films with 3.2 at.% Te doping on Se sites, realized by a new concept of doping-induced orientation engineering. We reveal that Te-doping enhances film uniformity and (00l)-orientation and in turn carrier mobility by reducing the (00l) formation energy, confirmed by solid computational and experimental evidence. The doping simultaneously widens the bandgap, resulting in improved Seebeck coefficients and high power factors, and introduces TeSe point defects to effectively reduce the lattice thermal conductivity. A protective organic-polymer-based composite layer enhances film flexibility, and a rationally designed flexible thermoelectric device achieves an output power density of 1.5 mW cm−2 for wearable power generation under a 20 K temperature difference.
Slow light topological photonics with counter-propagating waves and its active control on a chip
Authors: Kumar Abhishek , Tan Yi Ji , Navaratna Nikhil , Gupta Manoj , Pitchappa Prakash , Singh Ranjan 
Published: January 2024

AbstractTopological slow light exhibits potential to achieve stopped light by virtue of its widely known robust and non-reciprocal behaviours. Conventional approach for achieving topological slow light often involves flat-band engineering without disentangling the underlying physical mechanism. Here, we unveil the presence of counter-propagating waves within valley kink states as the distinctive hallmark of the slow light topological photonic waveguides. These counter-propagating waves, supported by topological vortices along glide-symmetric interface, provide significant flexibility for controlling the slowness of light. We tune the group velocity of light by changing the spatial separation between vortices adjacent to the glide-symmetric interface. We also dynamically control the group delay by introducing a non-Hermitian defect using photoexcitation to adjust the relative strength of the counter-propagating waves. This study introduces active slow light topological photonic device on a silicon chip, opening new horizons for topological photon transport through defects, topological light-matter interactions, nonlinear topological photonics, and topological quantum photonics.
Homo sapiens reached the higher latitudes of Europe by 45,000 years ago
Authors: Mylopotamitaki Dorothea , Weiss Marcel , Fewlass Helen , Zavala Elena Irene , Rougier Hélène , Sümer Arev Pelin , Hajdinjak Mateja , Smith Geoff M. , Ruebens Karen , Sinet-Mathiot Virginie , Pederzani Sarah , Essel Elena , Harking Florian S. , Xia Huan , Hansen Jakob , Kirchner André , Lauer Tobias , Stahlschmidt Mareike , Hein Michael , Talamo Sahra , Wacker Lukas , Meller Harald , Dietl Holger , Orschiedt Jörg , Olsen Jesper V. , Zeberg Hugo , Prüfer Kay , Krause Johannes , Meyer Matthias , Welker Frido , McPherron Shannon P. , Schüler Tim , Hublin Jean-Jacques 
Published: January 2024

AbstractThe Middle to Upper Palaeolithic transition in Europe is associated with the regional disappearance of Neanderthals and the spread of Homo sapiens. Late Neanderthals persisted in western Europe several millennia after the occurrence of H. sapiens in eastern Europe1. Local hybridization between the two groups occurred2, but not on all occasions3. Archaeological evidence also indicates the presence of several technocomplexes during this transition, complicating our understanding and the association of behavioural adaptations with specific hominin groups4. One such technocomplex for which the makers are unknown is the Lincombian–Ranisian–Jerzmanowician (LRJ), which has been described in northwestern and central Europe5–8. Here we present the morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains directly associated with an LRJ assemblage at the site Ilsenhöhle in Ranis (Germany). These human remains are among the earliest directly dated Upper Palaeolithic H. sapiens remains in Eurasia. We show that early H. sapiens associated with the LRJ were present in central and northwestern Europe long before the extinction of late Neanderthals in southwestern Europe. Our results strengthen the notion of a patchwork of distinct human populations and technocomplexes present in Europe during this transitional period.
Single-neuronal elements of speech production in humans
Authors: Khanna Arjun R. , Muñoz William , Kim Young Joon , Kfir Yoav , Paulk Angelique C. , Jamali Mohsen , Cai Jing , Mustroph Martina L. , Caprara Irene , Hardstone Richard , Mejdell Mackenna , Meszéna Domokos , Zuckerman Abigail , Schweitzer Jeffrey , Cash Sydney , Williams Ziv M. 
Published: January 2024

AbstractHumans are capable of generating extraordinarily diverse articulatory movement combinations to produce meaningful speech. This ability to orchestrate specific phonetic sequences, and their syllabification and inflection over subsecond timescales allows us to produce thousands of word sounds and is a core component of language1,2. The fundamental cellular units and constructs by which we plan and produce words during speech, however, remain largely unknown. Here, using acute ultrahigh-density Neuropixels recordings capable of sampling across the cortical column in humans, we discover neurons in the language-dominant prefrontal cortex that encoded detailed information about the phonetic arrangement and composition of planned words during the production of natural speech. These neurons represented the specific order and structure of articulatory events before utterance and reflected the segmentation of phonetic sequences into distinct syllables. They also accurately predicted the phonetic, syllabic and morphological components of upcoming words and showed a temporally ordered dynamic. Collectively, we show how these mixtures of cells are broadly organized along the cortical column and how their activity patterns transition from articulation planning to production. We also demonstrate how these cells reliably track the detailed composition of consonant and vowel sounds during perception and how they distinguish processes specifically related to speaking from those related to listening. Together, these findings reveal a remarkably structured organization and encoding cascade of phonetic representations by prefrontal neurons in humans and demonstrate a cellular process that can support the production of speech.
Ultracold field-linked tetratomic molecules
Authors: Chen Xing-Yan , Biswas Shrestha , Eppelt Sebastian , Schindewolf Andreas , Deng Fulin , Shi Tao , Yi Su , Hilker Timon A. , Bloch Immanuel , Luo Xin-Yu 
Published: January 2024

AbstractUltracold polyatomic molecules offer opportunities1 in cold chemistry2,3, precision measurements4 and quantum information processing5,6, because of their rich internal structure. However, their increased complexity compared with diatomic molecules presents a challenge in using conventional cooling techniques. Here we demonstrate an approach to create weakly bound ultracold polyatomic molecules by electroassociation7 (F.D. et al., manuscript in preparation) in a degenerate Fermi gas of microwave-dressed polar molecules through a field-linked resonance8–11. Starting from ground-state NaK molecules, we create around 1.1 × 103 weakly bound tetratomic (NaK)2 molecules, with a phase space density of 0.040(3) at a temperature of 134(3) nK, more than 3,000 times colder than previously realized tetratomic molecules12. We observe a maximum tetramer lifetime of 8(2) ms in free space without a notable change in the presence of an optical dipole trap, indicating that these tetramers are collisionally stable. Moreover, we directly image the dissociated tetramers through microwave-field modulation to probe the anisotropy of their wavefunction in momentum space. Our result demonstrates a universal tool for assembling weakly bound ultracold polyatomic molecules from smaller polar molecules, which is a crucial step towards Bose–Einstein condensation of polyatomic molecules and towards a new crossover from a dipolar Bardeen–Cooper–Schrieffer superfluid13–15 to a Bose–Einstein condensation of tetramers. Moreover, the long-lived field-linked state provides an ideal starting point for deterministic optical transfer to deeply bound tetramer states16–18.
First experimental demonstration of real-time neutron capture discrimination in helium and carbon ion therapy
Authors: Kielly Marissa , Caracciolo Anita , Chacon Andrew , Vohradsky James , Di Vita Davide , Hamato Akram , Tashima Hideaki , Franklin Daniel R. , Yamaya Taiga , Rosenfeld Anatoly , Carminati Marco , Fiorini Carlo , Guatelli Susanna , Safavi-Naeini Mitra 
Published: January 2024

AbstractThis work provides the first experimental proof of an increased neutron capture photon signal following the introduction of boron to a PMMA phantom during helium and carbon ion therapies in Neutron Capture Enhanced Particle Therapy (NCEPT). NCEPT leverages $$^{10}$$

10

B neutron capture, leading to the emission of detectable 478 keV photons. Experiments were performed at the Heavy Ion Medical Accelerator in Chiba, Japan, with two Poly(methyl methacrylate) (PMMA) targets, one bearing a boron insert. The BeNEdiCTE gamma-ray detector measured an increase in the 478 keV signal of 45 ± 7% and 26 ± 2% for carbon and helium ion irradiation, respectively. Our Geant4 Monte Carlo simulation model, developed to investigate photon origins, found less than 30% of detected photons originated from the insert, while boron in the detector’s circuit boards contributed over 65%. Further, the model investigated detector sensitivity, establishing its capability to record a 10% increase in 478 keV photon detection at a target $$^{10}$$

10

B concentration of 500 ppm using spectral windowing alone, and 25% when combined with temporal windowing. The linear response extended to concentrations up to 20,000 ppm. The increase in the signal in all evaluated cases confirm the potential of the proposed detector design for neutron capture quantification in NCEPT.
A language-independent hearing screening self-test at school-entry
Authors: Van den Borre Elien , Tufatulin Gaziz , Zupan Lea , Božanić Urbančič Nina , Lavie Limor , Holube Inga , Swarnalatha Nagaraj Vinay , Gurses Emre , Denys Sam , van Wieringen Astrid , Wouters Jan 
Published: January 2024

AbstractThe usage of a tablet-based language-independent self-test involving the recognition of ecological sounds in background noise, the Sound Ear Check, was investigated. The results of 692 children, aged between 5 and 9 years and 4 months, recruited in seven different countries, were used to analyze the validity and the cultural independence of test. Three different test procedures, namely a monaural adaptive procedure, a procedure presenting the sounds dichotically in diotic noise, and a procedure presenting all the sounds with a fixed signal-to-noise ratio and a stopping rule were studied. Results showed high sensitivity and specificity of all three procedures to detect conductive, sensorineural and mixed hearing loss > 30 dB HL. Additionally, the data collected from different countries were consistent, and there were no clinically relevant differences observed between countries. Therefore, the Sound Ear Check can offer an international hearing screening test for young children at school entry, solving the current lack of hearing screening services on a global scale.
DEEPOMICS FFPE, a deep neural network model, identifies DNA sequencing artifacts from formalin fixed paraffin embedded tissue with high accuracy
Authors: Heo Dong-hyuk , Kim Inyoung , Seo Heejae , Kim Seong-Gwang , Kim Minji , Park Jiin , Park Hongsil , Kang Seungmo , Kim Juhee , Paik Soonmyung , Hong Seong-Eui 
Published: January 2024

AbstractFormalin-fixed, paraffin-embedded (FFPE) tissue specimens are routinely used in pathological diagnosis, but their large number of artifactual mutations complicate the evaluation of companion diagnostics and analysis of next-generation sequencing data. Identification of variants with low allele frequencies is challenging because existing FFPE filtering tools label all low-frequency variants as artifacts. To address this problem, we aimed to develop DEEPOMICS FFPE, an AI model that can classify a true variant from an artifact. Paired whole exome sequencing data from fresh frozen and FFPE samples from 24 tumors were obtained from public sources and used as training and validation sets at a ratio of 7:3. A deep neural network model with three hidden layers was trained with input features using outputs of the MuTect2 caller. Contributing features were identified using the SHapley Additive exPlanations algorithm and optimized based on training results. The performance of the final model (DEEPOMICS FFPE) was compared with those of existing models (MuTect filter, FFPolish, and SOBDetector) by using well-defined test datasets. We found 41 discriminating properties for FFPE artifacts. Optimization of property quantification improved the model performance. DEEPOMICS FFPE removed 99.6% of artifacts while maintaining 87.1% of true variants, with an F1-score of 88.3 in the entire dataset not used for training, which is significantly higher than those of existing tools. Its performance was maintained even for low-allele-fraction variants with a specificity of 0.995, suggesting that it can be used to identify subclonal variants. Different from existing methods, DEEPOMICS FFPE identified most of the sequencing artifacts in the FFPE samples while retaining more of true variants, including those of low allele frequencies. The newly developed tool DEEPOMICS FFPE may be useful in designing capture panels for personalized circulating tumor DNA assay and identifying candidate neoepitopes for personalized vaccine design. DEEPOMICS FFPE is freely available on the web (http://deepomics.co.kr/ffpe) for research.
Increasing risks of extreme salt intrusion events across European estuaries in a warming climate
Authors: Lee Jiyong , Biemond Bouke , de Swart Huib , Dijkstra Henk A. 
Published: January 2024

AbstractOver the last decade, many estuaries worldwide have faced increased salt intrusion as a result of human activities and a changing climate. Despite its socio-economic importance, our current projections on the statistics of future salt intrusion are limited to case studies in certain regions. Here, we show that, compared to present-day conditions, river discharge in the summer months is projected to be reduced by 10–60% in 17 out of 22 investigated major European river basins at the end of the 21st century under the high CO2 emission scenario (Shared Socioeconomic Pathways, SSP 3-7.0). We find that the reduced future river discharge in the summer months, in turn, increases salt intrusion lengths by 10–30% in 9 representative European estuaries at low and mid latitudes. Our analysis further indicates that the European estuaries are projected to experience more than five times more frequent extreme salt intrusion events.
Interaction network of human early embryonic transcription factors
Authors: Gawriyski Lisa , Tan Zenglai , Liu Xiaonan , Chowdhury Iftekhar , Malaymar Pinar Dicle , Zhang Qin , Weltner Jere , Jouhilahti Eeva-Mari , Wei Gong-Hong , Kere Juha , Varjosalo Markku 
Published: January 2024

AbstractEmbryonic genome activation (EGA) occurs during preimplantation development and is characterized by the initiation of de novo transcription from the embryonic genome. Despite its importance, the regulation of EGA and the transcription factors involved in this process are poorly understood. Paired-like homeobox (PRDL) family proteins are implicated as potential transcriptional regulators of EGA, yet the PRDL-mediated gene regulatory networks remain uncharacterized. To investigate the function of PRDL proteins, we are identifying the molecular interactions and the functions of a subset family of the Eutherian Totipotent Cell Homeobox (ETCHbox) proteins, seven PRDL family proteins and six other transcription factors (TFs), all suggested to participate in transcriptional regulation during preimplantation. Using mass spectrometry-based interactomics methods, AP-MS and proximity-dependent biotin labeling, and chromatin immunoprecipitation sequencing we derive the comprehensive regulatory networks of these preimplantation TFs. By these interactomics tools we identify more than a thousand high-confidence interactions for the 21 studied bait proteins with more than 300 interacting proteins. We also establish that TPRX2, currently assigned as pseudogene, is a transcriptional activator.