bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of a selective and biologically active low-molecular weight antagonist of human interleukin-1β
Authors: Hommel Ulrich , Hurth Konstanze , Rondeau Jean-Michel , Vulpetti Anna , Ostermeier Daniela , Boettcher Andreas , Brady Jacob Peter , Hediger Michael , Lehmann Sylvie , Koch Elke , Blechschmidt Anke , Yamamoto Rina , Tundo Dottorello Valentina , Haenni-Holzinger Sandra , Kaiser Christian , Lehr Philipp , Lingel Andreas , Mureddu Luca , Schleberger Christian , Blank Jutta , Ramage Paul , Freuler Felix , Eder Joerg , Bornancin Frédéric
Published: September 2023

Human interleukin-1β (hIL-1β) is a pro-inflammatory cytokine involved in many diseases. While hIL-1β directed antibodies have shown clinical benefit, an orally available low-molecular weight antagonist is still elusive, limiting the applications of hIL-1β-directed therapies. Here we describe the discovery of a low-molecular weight hIL-1β antagonist that blocks the interaction with the IL-1R1 receptor. Starting from a low affinity fragment-based screening hit 1, structure-based optimization resulted in a compound (S)-2 that binds and antagonizes hIL-1β with single-digit micromolar activity in biophysical, biochemical, and cellular assays. X-ray analysis reveals an allosteric mode of action that involves a hitherto unknown binding site in hIL-1β encompassing two loops involved in hIL-1R1/hIL-1β interactions. We show that residues of this binding site are part of a conformationally excited state of the mature cytokine. The compound antagonizes hIL-1β function in cells, including primary human fibroblasts, demonstrating the relevance of this discovery for future development of hIL-1β directed therapeutics.
Unexpected worker mating and colony-founding in a superorganism
Authors: Zhuang Mingsheng , Colgan Thomas J. , Guo Yulong , Zhang Zhengyi , Liu Fugang , Xia Zhongyan , Dai Xueyan , Zhang Zhihao , Li Yuanjian , Wang Liuhao , Xu Jin , Guo Yueqin , Qu Yingping , Yao Jun , Yang Huipeng , Yang Fan , Li Xiaoying , Guo Jun , Brown Mark J. F. , Li Jilian
Published: September 2023

The emergence of caste-differentiated colonies, which have been defined as ‘superorganisms’, in ants, bees, and wasps represents a major transition in evolution. Lifetime mating commitment by queens, pre-imaginal caste determination and lifetime unmatedness of workers are key features of these animal societies. Workers in superorganismal species like honey bees and many ants have consequently lost, or retain only vestigial spermathecal structures. However, bumble bee workers retain complete spermathecae despite 25-40 million years since their origin of superorganismality, which remains an evolutionary mystery. Here, we show (i) that bumble bee workers retain queen-like reproductive traits, being able to mate and produce colonies, underlain by queen-like gene expression, (ii) the social conditions required for worker mating, and (iii) that these abilities may be selected for by early queen-loss in these annual species. These results challenge the idea of lifetime worker unmatedness in superorganisms, and provide an exciting new tool for the conservation of endangered bumble bee species.
Coordination of alternative splicing and alternative polyadenylation revealed by targeted long read sequencing
Authors: Zhang Zhiping , Bae Bongmin , Cuddleston Winston H. , Miura Pedro
Published: September 2023

Nervous system development is associated with extensive regulation of alternative splicing (AS) and alternative polyadenylation (APA). AS and APA have been extensively studied in isolation, but little is known about how these processes are coordinated. Here, the coordination of cassette exon (CE) splicing and APA in Drosophila was investigated using a targeted long-read sequencing approach we call Pull-a-Long-Seq (PL-Seq). This cost-effective method uses cDNA pulldown and Nanopore sequencing combined with an analysis pipeline to quantify inclusion of alternative exons in connection with alternative 3’ ends. Using PL-Seq, we identified genes that exhibit significant differences in CE splicing depending on connectivity to short versus long 3’UTRs. Genomic long 3’UTR deletion was found to alter upstream CE splicing in short 3’UTR isoforms and ELAV loss differentially affected CE splicing depending on connectivity to alternative 3’UTRs. This work highlights the importance of considering connectivity to alternative 3’UTRs when monitoring AS events.
Intrinsically disordered CsoS2 acts as a general molecular thread for α-carboxysome shell assembly
Authors: Ni Tao , Jiang Qiuyao , Ng Pei Cing , Shen Juan , Dou Hao , Zhu Yanan , Radecke Julika , Dykes Gregory F. , Huang Fang , Liu Lu-Ning , Zhang Peijun
Published: September 2023

Carboxysomes are a paradigm of self-assembling proteinaceous organelles found in nature, offering compartmentalisation of enzymes and pathways to enhance carbon fixation. In α-carboxysomes, the disordered linker protein CsoS2 plays an essential role in carboxysome assembly and Rubisco encapsulation. Its mechanism of action, however, is not fully understood. Here we synthetically engineer α-carboxysome shells using minimal shell components and determine cryoEM structures of these to decipher the principle of shell assembly and encapsulation. The structures reveal that the intrinsically disordered CsoS2 C-terminus is well-structured and acts as a universal “molecular thread” stitching through multiple shell protein interfaces. We further uncover in CsoS2 a highly conserved repetitive key interaction motif, [IV]TG, which is critical to the shell assembly and architecture. Our study provides a general mechanism for the CsoS2-governed carboxysome shell assembly and cargo encapsulation and further advances synthetic engineering of carboxysomes for diverse biotechnological applications.
Deciphering complex breakage-fusion-bridge genome rearrangements with Ambigram
Authors: Li Chaohui , Chen Lingxi , Pan Guangze , Zhang Wenqian , Li Shuai Cheng
Published: September 2023

Breakage-fusion-bridge (BFB) is a complex rearrangement that leads to tumor malignancy. Existing models for detecting BFBs rely on the ideal BFB hypothesis, ruling out the possibility of BFBs entangled with other structural variations, that is, complex BFBs. We propose an algorithm Ambigram to identify complex BFB and reconstruct the rearranged structure of the local genome during the cancer subclone evolution process. Ambigram handles data from short, linked, long, and single-cell sequences, and optical mapping technologies. Ambigram successfully deciphers the gold- or silver-standard complex BFBs against the state-of-the-art in multiple cancers. Ambigram dissects the intratumor heterogeneity of complex BFB events with single-cell reads from melanoma and gastric cancer. Furthermore, applying Ambigram to liver and cervical cancer data suggests that the BFB mechanism may mediate oncovirus integrations. BFB also exists in noncancer genomics. Investigating the complete human genome reference with Ambigram suggests that the BFB mechanism may be involved in two genome reorganizations of Homo Sapiens during evolution. Moreover, Ambigram discovers the signals of recurrent foldback inversions and complex BFBs in whole genome data from the 1000 genome project, and congenital heart diseases, respectively.
Organic laser power converter for efficient wireless micro power transfer
Authors: Wang Yafei , Zheng Zhong , Wang Jianqiu , Bi Pengqing , Chen Zhihao , Ren Junzhen , An Cunbin , Zhang Shaoqing , Hou Jianhui
Published: September 2023

Wireless power transfer with collimated power transmission and efficient conversion provides an alternative charging mode for off-grid and portable micro-power electronics. However, charging micro-power electronics with low photon flux can be challenging for current laser power converters. Here we show laser power converters with organic photovoltaic cells with good performance for application in laser wireless power transfer. The laser selection strategy is established and the upper limit of efficiency is proposed. The organic laser power converters exhibit a 36.2% efficiency at a 660 nm laser with a photon flux of 9.5 mW cm−2and achieve wireless micro power transfer with an output of 0.5 W on a 2 meter scale. This work shows the good performance of organic photovoltaic cells in constructing organic laser power converters and provides a potential solution for the wireless power transfer of micro-power electronics.
Phase separation of protein mixtures is driven by the interplay of homotypic and heterotypic interactions
Authors: Farag Mina , Borcherds Wade M. , Bremer Anne , Mittag Tanja , Pappu Rohit V.
Published: September 2023

Prion-like low-complexity domains (PLCDs) are involved in the formation and regulation of distinct biomolecular condensates that form via phase separation coupled to percolation. Intracellular condensates often encompass numerous distinct proteins with PLCDs. Here, we combine simulations and experiments to study mixtures of PLCDs from two RNA-binding proteins, hnRNPA1 and FUS. Using simulations and experiments, we find that 1:1 mixtures of A1-LCD and FUS-LCD undergo phase separation more readily than either of the PLCDs on their own due to complementary electrostatic interactions. Tie line analysis reveals that stoichiometric ratios of different components and their sequence-encoded interactions contribute jointly to the driving forces for condensate formation. Simulations also show that the spatial organization of PLCDs within condensates is governed by relative strengths of homotypic versus heterotypic interactions. We uncover rules for how interaction strengths and sequence lengths modulate conformational preferences of molecules at interfaces of condensates formed by mixtures of proteins.
All-round catalytic and atroposelective strategy via dynamic kinetic resolution for N-/2-/3-arylindoles
Authors: Kim Ahreum , Lee Chanhee , Song Jayoung , Lee Sang Kook , Kwon Yongseok
Published: September 2023

As the complexity of organic molecules utilized by mankind increases, the phenomenon of atropisomerism is more frequently encountered. While a variety of well-established methods enable the control of a stereogenic center, a catalytic method for controlling a stereogenic axis in one substrate is typically unavailable for controlling axial chirality in other substrates with a similar structure. Herein, we report o-amidobiaryl as a flexible platform for chiral phosphoric acid-catalyzed atroposelective dynamic kinetic resolution. To demonstrate our strategy, three distinct types of arylindoles were utilized and reacted intermolecularly with ketomalonate in the presence of chiral phosphoric acid. An investigation of 46 substrates having an aromatic ring in different positions yields the desired products with excellent enantioselectivities. Computational investigation into the origin of enantioselectivity highlights the importance of the NH group. Given the biological significance of indoles, antiproliferative effects have been investigated; our scaffold exhibits good efficacy in this regard.
Peroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size
Authors: Gu Ying , Alam Sara , Oliferenko Snezhana
Published: September 2023

Cellular metabolism relies on just a few redox cofactors. Selective compartmentalization may prevent competition between metabolic reactions requiring the same cofactor. Is such compartmentalization necessary for optimal cell function? Is there an optimal compartment size? Here we probe these fundamental questions using peroxisomal compartmentalization of the last steps of lysine and histidine biosynthesis in the fission yeast Schizosaccharomyces japonicus. We show that compartmentalization of these NAD+ dependent reactions together with a dedicated NADH/NAD+ recycling enzyme supports optimal growth when an increased demand for anabolic reactions taxes cellular redox balance. In turn, compartmentalization constrains the size of individual organelles, with larger peroxisomes accumulating all the required enzymes but unable to support both biosynthetic reactions at the same time. Our reengineering and physiological experiments indicate that compartmentalized biosynthetic reactions are sensitive to the size of the compartment, likely due to scaling-dependent changes within the system, such as enzyme packing density.
Quantitative whole-tissue 3D imaging reveals bacteria in close association with mouse jejunum mucosa
Authors: Poceviciute Roberta , Bogatyrev Said R. , Romano Anna E. , Dilmore Amanda H. , Mondragón-Palomino Octavio , Takko Heli , Pradhan Ojas , Ismagilov Rustem F.
Published: September 2023

Because the small intestine (SI) epithelium lacks a thick protective mucus layer, microbes that colonize the thin SI mucosa may exert a substantial effect on the host. For example, bacterial colonization of the human SI may contribute to environmental enteropathy dysfunction (EED) in malnourished children. Thus far, potential bacterial colonization of the mucosal surface of the SI has only been documented in disease states, suggesting mucosal colonization is rare, likely requiring multiple perturbations. Furthermore, conclusive proof of bacterial colonization of the SI mucosal surface is challenging, and the three-dimensional (3D) spatial structure of mucosal colonies remains unknown. Here, we tested whether we could induce dense bacterial association with jejunum mucosa by subjecting mice to a combination of malnutrition and oral co-gavage with a bacterial cocktail (E. coliandBacteroidesspp.) known to induce EED. To visualize these events, we optimized our previously developed whole-tissue 3D imaging tools with third-generation hybridization chain reaction (HCR v3.0) probes. Only in mice that were malnourished and gavaged with the bacterial cocktail did we detect dense bacterial clusters surrounding intestinal villi suggestive of colonization. Furthermore, in these mice we detected villus loss, which may represent one possible consequence that bacterial colonization of the SI mucosa has on the host. Our results suggest that dense bacterial colonization of jejunum mucosa is possible in the presence of multiple perturbations and that whole-tissue 3D imaging tools can enable the study of these rare events.
Phase field modeling with large driving forces
Authors: Zhang Jin , Chadwick Alexander F. , Chopp David L. , Voorhees Peter W.
Published: September 2023

There is growing interest in applying phase field methods as quantitative tools in materials discovery and development. However, large driving forces, common in many materials systems, lead to unstable phase field profiles, thus requiring fine spatial and temporal resolution. This demands more computational resources, limits the ability to simulate systems with a suitable size, and deteriorates the capability of quantitative prediction. Here, we develop a strategy to map the driving force to a constant perpendicular to the interface. Together with the third-order interpolation function, we find a stable phase field profile that is independent of the magnitude of the driving force. The power of this approach is illustrated using three models. We demonstrate that by using the driving force extension method, it is possible to employ a grid size orders of magnitude larger than traditional methods. This approach is general and should apply to many other phase field models.
Evaluation of free-floating tracheal intubation in weightlessness via ice-pick position with a direct laryngoscopy and classic approach with indirect videolaryngoscopy
Authors: Thierry Séamus , Jaulin François , Starck Clément , Ariès Philippe , Schmitz Jan , Kerkhoff Steffen , Bernard Cécile Isabelle , Komorowski Matthieu , Warnecke Tobias , Hinkelbein Jochen
Published: September 2023

Long duration spaceflights to the Moon or Mars are at risk for emergency medical events. Managing a hypoxemic distress and performing an advanced airway procedure such as oro-tracheal intubation may be complicated under weightlessness due to ergonomic constraints. An emergency free-floating intubation would be dangerous because of high failure rates due to stabilization issues that prohibits its implementation in a space environment. Nevertheless, we hypothesized that two configurations could lead to a high first-pass success score for intubation performed by a free-floating operator. In a non-randomized, controlled, cross-over simulation study during a parabolic flight campaign, we evaluated and compared the intubation performance of free-floating trained operators, using either a conventional direct laryngoscope in an ice-pick position or an indirect laryngoscopy with a video-laryngoscope in a classic position at the head of a high-fidelity simulation manikin, in weightlessness and in normogravity. Neither of the two tested conditions reached the minimal terrestrial ILCOR recommendations (95% first-pass success) and therefore could not be recommended for general implementation under weightlessness conditions. Free-floating video laryngoscopy at the head of the manikin had a significant better success score than conventional direct laryngoscopy in an ice-pick position. Our results, combined with the preexisting literature, emphasis the difficulties of performing oro-tracheal intubation, even for experts using modern airway devices, under postural instability in weightlessness. ClinicalTrials registration number NCT05303948.
Quantitative systems-based prediction of antimicrobial resistance evolution
Authors: Charlebois Daniel A.
Published: September 2023

Predicting evolution is a fundamental problem in biology with practical implications for treating antimicrobial resistance, which is a complex system-level phenomenon. In this perspective article, we explore the limits of predicting antimicrobial resistance evolution, quantitatively define the predictability and repeatability of microevolutionary processes, and speculate on how these quantities vary across temporal, biological, and complexity scales. The opportunities and challenges for predicting antimicrobial resistance in the context of systems biology are also discussed. Based on recent research, we conclude that the evolution of antimicrobial resistance can be predicted using a systems biology approach integrating quantitative models with multiscale data from microbial evolution experiments.
A mosaic influenza virus-like particles vaccine provides broad humoral and cellular immune responses against influenza A viruses
Authors: Liu Xuejie , Zhao Tianyi , Wang Liangliang , Yang Zhuolin , Luo Chuming , Li Minchao , Luo Huanle , Sun Caijun , Yan Huacheng , Shu Yuelong
Published: September 2023

The development of a universal influenza vaccine to elicit broad immune responses is essential in reducing disease burden and pandemic impact. In this study, the mosaic vaccine design strategy and genetic algorithms were utilized to optimize the seasonal influenza A virus (H1N1, H3N2) hemagglutinin (HA) and neuraminidase (NA) antigens, which also contain most potential T-cell epitopes. These mosaic immunogens were then expressed as virus-like particles (VLPs) using the baculovirus expression system. The immunogenicity and protection effectiveness of the mosaic VLPs were compared to the commercial quadrivalent inactivated influenza vaccine (QIV) in the mice model. Strong cross-reactive antibody responses were observed in mice following two doses of vaccination with the mosaic VLPs, with HI titers higher than 40 in 15 of 16 tested strains as opposed to limited cross HI antibody levels with QIV vaccination. After a single vaccination, mice also show a stronger level of cross-reactive antibody responses than the QIV. The QIV vaccinations only elicited NI antibodies to a small number of vaccine strains, and not even strong NI antibodies to its corresponding vaccine components. In contrast, the mosaic VLPs caused robust NI antibodies to all tested seasonal influenza virus vaccine strains. Here, we demonstrated the mosaic vaccines induces stronger cross-reactive antibodies and robust more T-cell responses compared to the QIV. The mosaic VLPs also provided protection against challenges with ancestral influenza A viruses of both H1 and H3 subtypes. These findings indicated that the mosaic VLPs were a promising strategy for developing a broad influenza vaccine in future.
Design principles for cyclin K molecular glue degraders
Authors: Kozicka Zuzanna , Suchyta Dakota J. , Focht Vivian , Kempf Georg , Petzold Georg , Jentzsch Marius , Zou Charles , Di Genua Cristina , Donovan Katherine A. , Coomar Seemon , Cigler Marko , Mayor-Ruiz Cristina , Schmid-Burgk Jonathan L. , Häussinger Daniel , Winter Georg E. , Fischer Eric S. , Słabicki Mikołaj , Gillingham Dennis , Ebert Benjamin L. , Thomä Nicolas H.
Published: September 2023

Molecular glue degraders are an effective therapeutic modality, but their design principles are not well understood. Recently, several unexpectedly diverse compounds were reported to deplete cyclin K by linking CDK12–cyclin K to the DDB1–CUL4–RBX1 E3 ligase. Here, to investigate how chemically dissimilar small molecules trigger cyclin K degradation, we evaluated 91 candidate degraders in structural, biophysical and cellular studies and reveal all compounds acquire glue activity via simultaneous CDK12 binding and engagement of DDB1 interfacial residues, in particular Arg928. While we identify multiple published kinase inhibitors as cryptic degraders, we also show that these glues do not require pronounced inhibitory properties for activity and that the relative degree of CDK12 inhibition versus cyclin K degradation is tuneable. We further demonstrate cyclin K degraders have transcriptional signatures distinct from CDK12 inhibitors, thereby offering unique therapeutic opportunities. The systematic structure–activity relationship analysis presented herein provides a conceptual framework for rational molecular glue design.
Regulation with cell size ensures mitochondrial DNA homeostasis during cell growth
Authors: Seel Anika , Padovani Francesco , Mayer Moritz , Finster Alissa , Bureik Daniela , Thoma Felix , Osman Christof , Klecker Till , Schmoller Kurt M.
Published: September 2023

To maintain stable DNA concentrations, proliferating cells need to coordinate DNA replication with cell growth. For nuclear DNA, eukaryotic cells achieve this by coupling DNA replication to cell-cycle progression, ensuring that DNA is doubled exactly once per cell cycle. By contrast, mitochondrial DNA replication is typically not strictly coupled to the cell cycle, leaving the open question of how cells maintain the correct amount of mitochondrial DNA during cell growth. Here, we show that in budding yeast, mitochondrial DNA copy number increases with cell volume, both in asynchronously cycling populations and during G1 arrest. Our findings suggest that cell-volume-dependent mitochondrial DNA maintenance is achieved through nuclear-encoded limiting factors, including the mitochondrial DNA polymerase Mip1 and the packaging factor Abf2, whose amount increases in proportion to cell volume. By directly linking mitochondrial DNA maintenance to nuclear protein synthesis and thus cell growth, constant mitochondrial DNA concentrations can be robustly maintained without a need for cell-cycle-dependent regulation.
A review of the machine learning datasets in mammography, their adherence to the FAIR principles and the outlook for the future
Authors: Logan Joe , Kennedy Paul J. , Catchpoole Daniel
Published: September 2023

The increasing rates of breast cancer, particularly in emerging economies, have led to interest in scalable deep learning-based solutions that improve the accuracy and cost-effectiveness of mammographic screening. However, such tools require large volumes of high-quality training data, which can be challenging to obtain. This paper combines the experience of an AI startup with an analysis of the FAIR principles of the eight available datasets. It demonstrates that the datasets vary considerably, particularly in their interoperability, as each dataset is skewed towards a particular clinical use-case. Additionally, the mix of digital captures and scanned film compounds the problem of variability, along with differences in licensing terms, ease of access, labelling reliability, and file formats. Improving interoperability through adherence to standards such as the BIRADS criteria for labelling and annotation, and a consistent file format, could markedly improve access and use of larger amounts of standardized data. This, in turn, could be increased further by GAN-based synthetic data generation, paving the way towards better health outcomes for breast cancer.
A chromosome-level genome assembly of the darkbarbel catfish Pelteobagrus vachelli
Authors: Gong Gaorui , Ke Wensi , Liao Qian , Xiong Yang , Hu Jingqi , Mei Jie
Published: September 2023

The darkbarbel catfish (Pelteobagrus vachelli), an economically important aquaculture species in China, is extensively employed in hybrid yellow catfish production due to its superior growth rate. However, information on its genome has been limited, constraining further genetic studies and breeding programs. Leveraging the power of PacBio long-read sequencing and Hi-C technologies, we present a high-quality, chromosome-level genome assembly for the darkbarbel catfish. The resulting assembly spans 692.10 Mb, with an impressive 99.9% distribution over 26 chromosomes. The contig N50 and scaffold N50 are 13.30 Mb and 27.55 Mb, respectively. The genome is predicted to contain 22,109 protein-coding genes, with 96.1% having functional annotations. Repeat elements account for approximately 35.79% of the genomic landscape. The completeness of darkbarbel catfish genome assembly is highlighted by a BUSCO score of 99.07%. This high-quality genome assembly provides a critical resource for future hybrid catfish breeding, comparative genomics, and evolutionary studies in catfish and other related species.
MicroCT data provide evidence correcting the previous misidentification of an Eocene amber beetle (Coleoptera, Cicindelidae) as an extant species
Authors: Schmidt Joachim , Scholz Stephan , Wiesner Jürgen , Will Kipling
Published: September 2023

The fossil record suggests some insect species have a marked longevity. The oldest fossils purported to represent extant insect species are from the Oligocene and Eocene. One of the most cited fossils is the extant tiger beetle Tetracha carolina (Coleoptera: Cicindelidae) that was identified over a century ago by Walther Horn in Eocene Baltic amber. We examined this and compared it to the previously described cincindelid Baltic amber fossil Palaeoiresina cassolai using X-ray microscopy and 3D imaging techniques. We conclude that Horn’s fossil tiger beetle specimen is conspecific with the Eocene P. cassolai and is a member of an extinct stem group lineage of Cicindelidae. Based on a review of all the tiger beetle fossils described from Cretaceous and Paleogene deposits, we found that the assignment of these fossil species to extant lineages is not supported. There are currently no synapomorphies known from fossils that can provide evidence for Cretaceous Manticorni or Megacephalini nor is there evidence for Eocene Iresina. We provide evidence that rejects the idea of a recent beetle species persisting since the Eocene period, which is crucial for using the currently known fossil Cicindelidae species to calibrate divergence dating of beetle phylogenies.
Bidirectional referral system between National Taiwan University Hospital medical center and Zhongxiao Branch community hospital of Taipei City Hospital: focus on patient satisfaction
Authors: Kao Mu-Jung , Wang Jenn Yeu , Hu Hsiao-Yun
Published: September 2023

The policy of bidirectional referral between National Taiwan University Hospital and Taipei City Hospital has been launched due to the over-crowding of the emergency department at National Taiwan University Hospital. This research aims to evaluate patient satisfaction with the bidirectional referral. Sixty-six patients have been referred from the emergency department of National Taiwan University Hospital to Taipei City Hospital, Zhongxiao campus from April 2015 to December 2017. The selection criteria of the subjects for bidirectional referral include the management of patients classified as triage classification 2 or 3. Exclusion criteria are as follows: incomplete patient records and patients who chose hospice care. Sixty-six patients completed the questionnaires. Multivariate regression was used to evaluate the determinants of overall satisfaction scores of the bidirectional referral. The two overall satisfaction scores of patients were high (> 7). Three independent variables, (1) overall satisfaction scores of medical care at Taipei City Hospital, Zhongxiao campus, (2) waiting times for examination, treatment, and test, and (3) a positive question regarding quality improvement of delivered care for patients and family explained 69.3% adjusted variability of the overall satisfaction scores of bidirectional referrals. Therefore, the policy of bidirectional referrals and direct admission into the wards of Taipei City Hospital, Zhongxiao campus, from the emergency department of National Taiwan University Hospital met the criteria for patient satisfaction and public accountability.
Study of image sensors for enhanced face recognition at a distance in the Smart City context
Authors: Llauradó José M. , Pujol Francisco A. , Tomás David , Visvizi Anna , Pujol Mar
Published: September 2023

Smart monitoring and surveillance systems have become one of the fundamental areas in the context of security applications in Smart Cities. In particular, video surveillance for Human Activity Recognition (HAR) applied to the recognition of potential offenders and to the detection and prevention of violent acts is a challenging task that is still undergoing. This paper presents a method based on deep learning for face recognition at a distance for security applications. Due to the absence of available datasets on face recognition at a distance, a methodology to generate a reliable dataset that relates the distance of the individuals from the camera, the focal length of the image sensors and the size in pixels of the target face is introduced. To generate the extended dataset, the Georgia Tech Face and Quality Dataset for Distance Faces databases were chosen. Our method is then tested and applied to a set of commercial image sensors for surveillance cameras using this dataset. The system achieves an average accuracy above 99% for several sensors and allows to calculate the maximum distance for a sensor to get the required accuracy in the recognition, which could be crucial in security applications in smart cities.
The sonication-assisted whisker method enables CRISPR-Cas9 ribonucleoprotein delivery to induce genome editing in rice
Authors: Nakamura Akiyoshi , Yano Tsubasa , Mitsuda Nobutaka , Furubayashi Maiko , Ito Seiichiro , Sugano Shigeo S. , Terakawa Teruhiko
Published: September 2023

CRISPR/Cas9-based genome editing represents an unprecedented potential for plant breeding. Unlike animal cells, plant cells contain a rigid cell wall, genome editing tool delivery into plant cells is thus challenging. In particular, the delivery of the Cas9-gRNA ribonucleoprotein (RNP) into plant cells is desired since the transgene insertion into the genome should be avoided for industrial applications in plants. In this study, we present a novel RNP delivery approach in rice. We applied the sonication-assisted whisker method, conventionally developed for DNA delivery in plants, for RNP delivery in rice. Combined with marker gene delivery, we successfully isolated OsLCYβ genome-edited lines generated by RNPs. The calli and regenerated shoot of the ﻿OsLCYβ mutant showed abnormal carotenoid accumulation. In addition, we also detected, although at a low frequency, genome editing events in rice calli cells by RNP delivery using the sonication-assisted whisker method without any additional. Therefore, the sonication-assisted whisker method could be an attractive way to create RNP-based genome-edited lines in plants.
Limitations and solutions of low cost virtual reality mirror therapy for post-stroke patients
Authors: Quintana David , Rodríguez Antonio , Boada Imma
Published: September 2023

Mirror therapy is applied to reduce phantom pain and as a rehabilitation technique in post-stroke patients. Using Virtual Reality and head-mounted displays this therapy can be performed in virtual scenarios. However, for its efficient use in clinical settings, some hardware limitations need to be solved. A new system to perform mirror therapy in virtual scenarios for post-stroke patients is proposed. The system requires the patient a standalone virtual reality headset with hand-tracking features and for the rehabilitator an external computer or tablet device. The system provides functionalities for the rehabilitator to prepare and follow-up rehabilitation sessions and a virtual scenario for the patient to perform rehabilitation. The system has been tested on a real scenario with the support of three experienced rehabilitators and considering ten post-stroke patients in individual sessions focused on upper limb motor rehabilitation. The development team observed all the sessions and took note of detected errors regarding technological aspects. Solutions to solve detected problems will be proposed and evaluated in terms of feasibility, performance cost, additional system cost, number of solved issues, new limitations, or advantages for the patient. Three types of errors were detected and solved. The first error is related to the position of the hands relative to the head-mounted display. To solve it the exercise area can be limited to avoid objectives that require turning the head too far. The second error is related to the interaction between the hands and the virtual objects. It can be solved making the main hand non-interactive. The last type of error is due to patient limitations and can be mitigated by having a virtual hand play out an example motion to bring the patient’s attention back to the exercise. Other solutions have been evaluated positively and can be used in addition or instead of the selected ones. For mirror therapy based on virtual reality to be efficient in post-stroke rehabilitation the current head-mounted display-based solutions need to be complemented with specific strategies that avoid or mitigate the limitations of the technology and the patient. Solutions that help with the most common issues have been proposed.
Prediction of lung papillary adenocarcinoma-specific survival using ensemble machine learning models
Authors: Xia Kaide , Chen Dinghua , Jin Shuai , Yi Xinglin , Luo Li
Published: September 2023

Accurate prognostic prediction is crucial for treatment decision-making in lung papillary adenocarcinoma (LPADC). The aim of this study was to predict cancer-specific survival in LPADC using ensemble machine learning and classical Cox regression models. Moreover, models were evaluated to provide recommendations based on quantitative data for personalized treatment of LPADC. Data of patients diagnosed with LPADC (2004–2018) were extracted from the Surveillance, Epidemiology, and End Results database. The set of samples was randomly divided into the training and validation sets at a ratio of 7:3. Three ensemble models were selected, namely gradient boosting survival (GBS), random survival forest (RSF), and extra survival trees (EST). In addition, Cox proportional hazards (CoxPH) regression was used to construct the prognostic models. The Harrell’s concordance index (C-index), integrated Brier score (IBS), and area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used to evaluate the performance of the predictive models. A user-friendly web access panel was provided to easily evaluate the model for the prediction of survival and treatment recommendations. A total of 3615 patients were randomly divided into the training and validation cohorts (n = 2530 and 1085, respectively). The extra survival trees, RSF, GBS, and CoxPH models showed good discriminative ability and calibration in both the training and validation cohorts (mean of time-dependent AUC: > 0.84 and > 0.82; C-index: > 0.79 and > 0.77; IBS: < 0.16 and < 0.17, respectively). The RSF and GBS models were more consistent than the CoxPH model in predicting long-term survival. We implemented the developed models as web applications for deployment into clinical practice (accessible through https://shinyshine-820-lpaprediction-model-z3ubbu.streamlit.app/). All four prognostic models showed good discriminative ability and calibration. The RSF and GBS models exhibited the highest effectiveness among all models in predicting the long-term cancer-specific survival of patients with LPADC. This approach may facilitate the development of personalized treatment plans and prediction of prognosis for LPADC.
Development of a prognostic model for anoikis and identifies hub genes in hepatocellular carcinoma
Authors: Zhong Zhiwei , Xie Fuchun , Yin Jiajun , Zhao Hua , Zhou Yuehan , Guo Kun , Li Rongkuan , Wang Qimin , Tang Bo
Published: September 2023

Considering the high fatality of hepatocellular carcinoma (HCC), current prognostic systems are insufficient to accurately forecast HCC patients' outcomes. In our study, nine anoikis‑related genes (PTRH2, ITGAV, ANXA5, BIRC5, BDNF, BSG, DAP3, SKP2, and EGF) were determined to establish a risk scoring model using LASSO regression, which could be validated in ICGC dataset. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curve analysis confirmed the risk score possessed an accurate predictive value for the prognosis of HCC patients. The high-risk group showed a higher infiltration of aDCs, macrophages, T-follicular helper cells, and Th2 cells. Besides, PD-L1 was significantly higher in the high-risk group compared to the low-risk group. Several anoikis‑related genes, such as ANX5, ITGAV, BDNF and SKP2, were associated with drug sensitivity in HCC. Finally, we identified BIRC5 and SKP2 as hub genes among the nine model genes using WGCNA analysis. BIRC5 and SKP2 were over-expressed in HCC tissues, and their over-expression was associated with poor prognosis, no matter in our cohort by immunohistochemical staining or in the TCGA cohort by mRNA-Seq. In our cohort, BIRC5 expression was highly associated with the T stage, pathologic stage, histologic grade and AFP of HCC patients. In general, our anoikis-related risk model can enhance the ability to predict the survival outcomes of HCC patients and provide a feasible therapeutic strategy for immunotherapy and drug resistance in HCC. BIRC5 and SKP2 are hub genes of anoikis‑related genes in HCC.
Composition and evolution of the gut microbiota of growing puppies is impacted by their birth weight
Authors: Garrigues Quentin , Apper Emmanuelle , Rodiles Ana , Rovere Nicoletta , Chastant Sylvie , Mila Hanna
Published: September 2023

Low birth weight puppies present an increased risk of neonatal mortality, morbidity, and some long-term health issues. Yet it has not been investigated if those alterations could be linked to the gut microbiota composition and evolution. 57 puppies were weighed at birth and rectal swabs were performed at 5 time points from birth to 28 days of age. Puppies were grouped into three groups based on their birth weight: low birth weight (LBW), normal birth weight (NBW) and high birth weight (HBW). 16S rRNA gene sequencing was used to highlight differences in the fecal microbiota. During the first three weeks, the relative abundance of facultative anaerobic bacteria such as E. coli, C. perfringens and Tyzzerella was higher in LBW feces, but they catch back with the other groups afterwards. HBW puppies showed higher abundances of Faecalibacterium and Bacteroides during the neonatal period, suggesting an earlier maturation of their microbiota. The results of this study suggest that birth weight impact the initial establishment of the gut microbiota in puppies. Innovative strategies would be desired to deal with altered gut microbiota in low birth weight puppies aiming to improve their survival and long term health.
Study on roof movement law of local filling mining under peak cluster landform
Authors: Su Hengyu , Luo Chang , Jia Yichao , Wang Ziyi
Published: September 2023

The strip structure filling mining technology is suggested in response to the environmental issues such as surface subsidence and landslides brought on by the mining of 11,071 working faces in a mine in Guizhou. The mining technology system is studied through indoor testing, numerical simulation, and engineering monitoring. According to theoretical study, the filling strip can be steadily loaded and its value doesn't exceed 10 m when the width of the filling strip and the width of the filling interval are set to be equal. According to laboratory testing, fly ash can replace some of the cement in the cement mixture as a binder to maintain strength while cutting costs. The degree of crystallization gradually distributed into the network in the filling paste of various ages corresponds to its strength when combined with the findings of scanning electron microscopy; The numerical simulation results show that the maximum subsidence of the immediate roof is reduced from 340 to 3 mm from the filling rate of 0 to 100%, the filling effect is remarkable, and the shape of the settlement curve is changed from 'U' to 'basin', then to 'W'; during the local filling mining, the settlement curve of the immediate roof presents a 'wave' shape, and the stress curve of the immediate roof in the middle of the stope is also changed. The peak tension of the coal wall falls synchronously with filling spacing on both sides of the stope. The overall vertical stress below the mountain is larger, and the vertical stress at the top of the filling body eventually shifts from a "saddle" shape to a "inverted U" shape without zero support stress. In conjunction with the plastic zone, it is discovered that the stable bearing of the "filling strip-direct roof" composite structure increases with decreasing tensile and shear damage range of the hollow roof area and both sides of the top of the "filling 3 m interval 3 m" scheme; engineering measurement also reveals that the higher the position of the survey line is, the smaller the displacement is. However, the overall displacement of the strata directly above is negligible, and the greatest displacement is only 10.9 mm, which is consistent with the numerical simulation. At the same time, the displacement beneath the mountain area is too great.
Classification and regression model to manage the hospitalization for laparoscopic cholecystectomy
Authors: Scala Arianna , Trunfio Teresa Angela , Improta Giovanni
Published: September 2023

Gallstone disease (GD) is one of the most common morbidities in the world. Laparoscopic Cholecystectomy (LC) is currently the gold standard, performed in about 96% of cases. The most affected groups are the elderly, who generally have higher pre- and post-operative morbidity and mortality rates and longer Length of Stay (LOS). For this reason, several indicators have been defined to improve quality and efficiency and contain costs. In this study, data from patients who underwent LC at the “San Giovanni di Dio e Ruggi d’Aragona” University Hospital of Salerno in the years 2010–2020 were processed using a Multiple Linear Regression (MLR) model and Classification algorithms in order to identify the variables that most influence LOS. The results of the 2352 patients analyzed showed that pre-operative LOS and Age were the independent variables that most affected LOS. In particular, MLR model had a R2 value equal to 0.537 and the best classification algorithm, Decision Tree, had an accuracy greater than 83%. In conclusion, both the MLR model and the classification algorithms produced significant results that could provide important support in the management of this healthcare process.
Cortical signatures of visual body representation develop in human infancy
Authors: Yang Jiale , Ganea Natasa , Kanazawa So , Yamaguchi Masami K. , Bhattacharya Joydeep , Bremner Andrew J.
Published: September 2023

Human infants cannot report their experiences, limiting what we can learn about their bodily awareness. However, visual cortical responses to the body, linked to visual awareness and selective attention in adults, can be easily measured in infants and provide a promising marker of bodily awareness in early life. We presented 4- and 8-month-old infants with a flickering (7.5 Hz) video of a hand being stroked and recorded steady-state visual evoked potentials (SSVEPs). In half of the trials, the infants also received tactile stroking synchronously with visual stroking. The 8-month-old, but not the 4-month-old infants, showed a significant enhancement of SSVEP responses when they received tactile stimulation concurrent with the visually observed stroking. Follow-up experiments showed that this enhancement did not occur when the visual hand was presented in an incompatible posture with the infant’s own body or when the visual stimulus was a body-irrelevant video. Our findings provide a novel insight into the development of bodily self-awareness in the first year of life.
Time-resolved plasmon-assisted generation of optical-vortex pulses
Authors: Albar Esra Ilke , Bonafé Franco P. , Kosheleva Valeriia P. , Ohlmann Sebastian T. , Appel Heiko , Rubio Angel
Published: September 2023

The microscopic mechanism of the light-matter interactions that induce orbital angular momentum (OAM) in electromagnetic fields is not thoroughly understood. In this work, we employ Archimedean spiral vortex generators in time-resolved numerical simulations using the Octopus code to observe the behind-the-scenes of OAM generation. We send a perfect circularly-polarized plane-wave light onto plasmonic optical vortex generators and observe the resulting twisted light formation with complete spatio-temporal information. In agreement with previous works, we find that emission from the plasmonic spiral branches shapes the vortex-like structure and governs the OAM generation in the outgoing electromagnetic field. To characterize the generated beam further, we emulate the emission from vortex generators with current emitters preserving the spiral geometry. We subject a point-particle system to the generated field and record the orbital angular momentum transfer between the electromagnetic field and the point particle. Finally, we probe the OAM density locally by studying the induced classical trajectory of point particles, which provides further insight into the spatio-temporal features of the induced OAM.
Role of subduction dynamics on the unevenly distributed volcanism at the Middle American subduction system
Authors: Liu Meng , Gao Haiying
Published: September 2023

A typical subduction of an oceanic plate beneath a continent is expected to be accompanied by arc volcanoes along the convergent margin. However, subduction of the Cocos plate at the Middle American subduction system has resulted in an uneven distribution of magmatism/volcanism along strike. Here we construct a new three-dimensional shear-wave velocity model of the entire Middle American subduction system, using full-wave ambient noise tomography. Our model reveals significant variations of the oceanic plates along strike and down dip, in correspondence with either weakened or broken slabs after subduction. The northern and southern segments of the Cocos plate, including the Mexican flat slab subduction, are well imaged as high-velocity features, where a low-velocity mantle wedge exists and demonstrate a strong correlation with the arc volcanoes. Subduction of the central Cocos plate encounters a thick high-velocity feature beneath North America, which hinders the formation of a typical low-velocity mantle wedge and arc volcanoes. We suggest that the presence of slab tearing at both edges of the Mexican flat slab has been modifying the mantle flows, resulting in the unusual arc volcanism.