bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability and accuracy of artificial intelligence ChatGPT in providing information on ophthalmic diseases and management to patients
Authors: Cappellani Francesco , Card Kevin R. , Shields Carol L. , Pulido Jose S. , Haller Julia A.
Published: January 2024

Purpose

To assess the accuracy of ophthalmic information provided by an artificial intelligence chatbot (ChatGPT).

Methods

Five diseases from 8 subspecialties of Ophthalmology were assessed by ChatGPT version 3.5. Three questions were asked to ChatGPT for each disease: what is x?; how is x diagnosed?; how is x treated? (x = name of the disease). Responses were graded by comparing them to the American Academy of Ophthalmology (AAO) guidelines for patients, with scores ranging from −3 (unvalidated and potentially harmful to a patient’s health or well-being if they pursue such a suggestion) to 2 (correct and complete).

Main outcomes

Accuracy of responses from ChatGPT in response to prompts related to ophthalmic health information in the form of scores on a scale from −3 to 2.

Results

Of the 120 questions, 93 (77.5%) scored ≥ 1. 27. (22.5%) scored ≤ −1; among these, 9 (7.5%) obtained a score of −3. The overall median score amongst all subspecialties was 2 for the question “What is x”, 1.5 for “How is x diagnosed”, and 1 for “How is x treated”, though this did not achieve significance by Kruskal-Wallis testing.

Conclusions

Despite the positive scores, ChatGPT on its own still provides incomplete, incorrect, and potentially harmful information about common ophthalmic conditions, defined as the recommendation of invasive procedures or other interventions with potential for adverse sequelae which are not supported by the AAO for the disease in question. ChatGPT may be a valuable adjunct to patient education, but currently, it is not sufficient without concomitant human medical supervision.
Origin of the multi-phasic quenching dynamics in the BLUF domains across the species
Authors: Zhou Yalin , Tang Siwei , Chen Zijing , Zhou Zhongneng , Huang Jiulong , Kang Xiu-Wen , Zou Shuhua , Wang Bingyao , Zhang Tianyi , Ding Bei , Zhong Dongping
Published: January 2024

Blue light using flavin (BLUF) photoreceptors respond to light via one of nature’s smallest photo-switching domains. Upon photo-activation, the flavin cofactor in the BLUF domain exhibits multi-phasic dynamics, quenched by a proton-coupled electron transfer reaction involving the conserved Tyr and Gln. The dynamic behavior varies drastically across different species, the origin of which remains controversial. Here, we incorporate site-specific fluorinated Trp into three BLUF proteins, i.e., AppA, OaPAC and SyPixD, and characterize the percentages for the Wout, WinNHin and WinNHout conformations using 19F nuclear magnetic resonance spectroscopy. Using femtosecond spectroscopy, we identify that one key WinNHin conformation can introduce a branching one-step proton transfer in AppA and a two-step proton transfer in OaPAC and SyPixD. Correlating the flavin quenching dynamics with the active-site structural heterogeneity, we conclude that the quenching rate is determined by the percentage of WinNHin, which encodes a Tyr-Gln configuration that is not conducive to proton transfer.
Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma
Authors: Lu Jia-Cheng , Wu Lei-Lei , Sun Yi-Ning , Huang Xiao-Yong , Gao Chao , Guo Xiao-Jun , Zeng Hai-Ying , Qu Xu-Dong , Chen Yi , Wu Dong , Pei Yan-Zi , Meng Xian-Long , Zheng Yi-Min , Liang Chen , Zhang Peng-Fei , Cai Jia-Bin , Ding Zhen-Bin , Yang Guo-Huan , Ren Ning , Huang Cheng , Wang Xiao-Ying , Gao Qiang , Sun Qi-Man , Shi Ying-Hong , Qiu Shuang-Jian , Ke Ai-Wu , Shi Guo-Ming , Zhou Jian , Sun Yi-Di , Fan Jia
Published: January 2024

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+–CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.
Shifting patterns of dengue three years after Zika virus emergence in Brazil
Authors: Pinotti Francesco , Giovanetti Marta , de Lima Maricelia Maia , de Cerqueira Erenilde Marques , Alcantara Luiz C. J. , Gupta Sunetra , Recker Mario , Lourenço José
Published: January 2024

In 2015, the Zika virus (ZIKV) emerged in Brazil, leading to widespread outbreaks in Latin America. Following this, many countries in these regions reported a significant drop in the circulation of dengue virus (DENV), which resurged in 2018-2019. We examine age-specific incidence data to investigate changes in DENV epidemiology before and after the emergence of ZIKV. We observe that incidence of DENV was concentrated in younger individuals during resurgence compared to 2013-2015. This trend was more pronounced in Brazilian states that had experienced larger ZIKV outbreaks. Using a mathematical model, we show that ZIKV-induced cross-protection alone, often invoked to explain DENV decline across Latin America, cannot explain the observed age-shift without also assuming some form of disease enhancement. Our results suggest that a sudden accumulation of population-level immunity to ZIKV could suppress DENV and reduce the mean age of DENV incidence via both protective and disease-enhancing interactions.
Using big sequencing data to identify chronic SARS-Coronavirus-2 infections
Authors: Harari Sheri , Miller Danielle , Fleishon Shay , Burstein David , Stern Adi
Published: January 2024

The evolution of SARS-Coronavirus-2 (SARS-CoV-2) has been characterized by the periodic emergence of highly divergent variants. One leading hypothesis suggests these variants may have emerged during chronic infections of immunocompromised individuals, but limited data from these cases hinders comprehensive analyses. Here, we harnessed millions of SARS-CoV-2 genomes to identify potential chronic infections and used language models (LM) to infer chronic-associated mutations. First, we mined the SARS-CoV-2 phylogeny and identified chronic-like clades with identical metadata (location, age, and sex) spanning over 21 days, suggesting a prolonged infection. We inferred 271 chronic-like clades, which exhibited characteristics similar to confirmed chronic infections. Chronic-associated mutations were often high-fitness immune-evasive mutations located in the spike receptor-binding domain (RBD), yet a minority were unique to chronic infections and absent in global settings. The probability of observing high-fitness RBD mutations was 10-20 times higher in chronic infections than in global transmission chains. The majority of RBD mutations in BA.1/BA.2 chronic-like clades bore predictive value, i.e., went on to display global success. Finally, we used our LM to infer hundreds of additional chronic-like clades in the absence of metadata. Our approach allows mining extensive sequencing data and providing insights into future evolutionary patterns of SARS-CoV-2.
Discovery of a peripheral 5HT2A antagonist as a clinical candidate for metabolic dysfunction-associated steatohepatitis
Authors: Pagire Haushabhau S. , Pagire Suvarna H. , Jeong Byung-kwan , Choi Won-Il , Oh Chang Joo , Lim Chae Won , Kim Minhee , Yoon Jihyeon , Kim Seong Soon , Bae Myung Ae , Jeon Jae-Han , Song Sungmin , Lee Hee Jong , Lee Eun Young , Goughnour Peter C. , Kim Dooseop , Lee In-Kyu , Loomba Rohit , Kim Hail , Ahn Jin Hee
Published: January 2024

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is currently the leading cause of chronic liver disease worldwide. Metabolic Dysfunction-Associated Steatohepatitis (MASH), an advanced form of MASLD, can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Based on recent findings by our team that liver 5HT2A knockout male mice suppressed steatosis and reduced fibrosis-related gene expression, we developed a peripheral 5HT2A antagonist, compound 11c for MASH. It shows good in vitro activity, stability, and in vivo pharmacokinetics (PK) in rats and dogs. Compound 11c also shows good in vivo efficacy in a diet-induced obesity (DIO) male mice model and in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) male mice model, effectively improving histologic features of MASH and fibrosis. According to the tissue distribution study using [14C]-labeled 11c, the compound was determined to be a peripheral 5HT2A antagonist. Collectively, first-in-class compound 11c shows promise as a therapeutic agent for the treatment of MASLD and MASH.
Cryo- EM structure of the mycobacterial 70S ribosome in complex with ribosome hibernation promotion factor RafH
Authors: Kumar Niraj , Sharma Shivani , Kaushal Prem S.
Published: January 2024

Ribosome hibernation is a key survival strategy bacteria adopt under environmental stress, where a protein, hibernation promotion factor (HPF), transitorily inactivates the ribosome. Mycobacterium tuberculosis encounters hypoxia (low oxygen) as a major stress in the host macrophages, and upregulates the expression of RafH protein, which is crucial for its survival. The RafH, a dual domain HPF, an orthologue of bacterial long HPF (HPFlong), hibernates ribosome in 70S monosome form, whereas in other bacteria, the HPFlong induces 70S ribosome dimerization and hibernates its ribosome in 100S disome form. Here, we report the cryo- EM structure of M. smegmatis, a close homolog of M. tuberculosis, 70S ribosome in complex with the RafH factor at an overall 2.8 Å resolution. The N- terminus domain (NTD) of RafH binds to the decoding center, similarly to HPFlong NTD. In contrast, the C- terminus domain (CTD) of RafH, which is larger than the HPFlong CTD, binds to a distinct site at the platform binding center of the ribosomal small subunit. The two domain-connecting linker regions, which remain mostly disordered in earlier reported HPFlong structures, interact mainly with the anti-Shine Dalgarno sequence of the 16S rRNA.
Microwave quantum diode
Authors: Upadhyay Rishabh , Golubev Dmitry S. , Chang Yu-Cheng , Thomas George , Guthrie Andrew , Peltonen Joonas T. , Pekola Jukka P.
Published: January 2024

The fragile nature of quantum circuits is a major bottleneck to scalable quantum applications. Operating at cryogenic temperatures, quantum circuits are highly vulnerable to amplifier backaction and external noise. Non-reciprocal microwave devices such as circulators and isolators are used for this purpose. These devices have a considerable footprint in cryostats, limiting the scalability of quantum circuits. As a proof-of-concept, here we report a compact microwave diode architecture, which exploits the non-linearity of a superconducting flux qubit. At the qubit degeneracy point we experimentally demonstrate a significant difference between the power levels transmitted in opposite directions. The observations align with the proposed theoretical model. At − 99 dBm input power, and near the qubit-resonator avoided crossing region, we report the transmission rectification ratio exceeding 90% for a 50 MHz wide frequency range from 6.81 GHz to 6.86 GHz, and over 60% for the 250 MHz range from 6.67 GHz to 6.91 GHz. The presented architecture is compact, and easily scalable towards multiple readout channels, potentially opening up diverse opportunities in quantum information, microwave read-out and optomechanics.
Hydrogen-bonded organic frameworks in solution enables continuous and high-crystalline membranes
Authors: Yin Qi , Pang Kuan , Feng Ya-Nan , Han Lili , Morsali Ali , Li Xi-Ya , Liu Tian-Fu
Published: January 2024

Hydrogen-Bonded organic frameworks (HOFs) are a type of emerging porous materials. At present, little research has been conducted on their solution state. This work demonstrates that HOFs fragment into small particles while maintaining their original assemblies upon dispersing in solvents, as confirmed by Cryo-electron microscopy coupled with 3D electron diffraction technology. 1D and 2D-Nuclear Magnetic Resonance (NMR) and zeta potential analyses indicate the HOF-based colloid solution and the isolated molecular solution have significant differences in intermolecular interactions and aggregation behavior. Such unique solution processibility allows for fabricating diverse continuous HOF membranes with high crystallinity and porosity through solution-casting approach on various substrates. Among them, HOF-BTB@AAO membranes show high C3H6 permeance (1.979 × 10−7 mol·s−1·m−2·Pa−1) and excellent separation performance toward C3H6 and C3H8 (SF = 14). This continuous membrane presents a green, low-cost, and efficient separation technology with potential applications in petroleum cracking and purification.
Programmable integrated photonics for topological Hamiltonians
Authors: On Mehmet Berkay , Ashtiani Farshid , Sanchez-Jacome David , Perez-Lopez Daniel , Yoo S. J. Ben , Blanco-Redondo Andrea
Published: January 2024

A variety of topological Hamiltonians have been demonstrated in photonic platforms, leading to fundamental discoveries and enhanced robustness in applications such as lasing, sensing, and quantum technologies. To date, each topological photonic platform implements a specific type of Hamiltonian with inexistent or limited reconfigurability. Here, we propose and demonstrate different topological models by using the same reprogrammable integrated photonics platform, consisting of a hexagonal mesh of silicon Mach-Zehnder interferometers with phase shifters. We specifically demonstrate a one-dimensional Su-Schrieffer-Heeger Hamiltonian supporting a localized topological edge mode and a higher-order topological insulator based on a two-dimensional breathing Kagome Hamiltonian with three corner states. These results highlight a nearly universal platform for topological models that may fast-track research progress toward applications of topological photonics and other coupled systems.
ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover
Authors: Yuan Zhen , Cai Kun , Li Jiajia , Chen Ruifeng , Zhang Fuhai , Tan Xuan , Jiu Yaming , Chang Haishuang , Hu Bing , Zhang Weiyi , Ding Binbin
Published: January 2024

Lipid droplets (LDs) are dynamic lipid storage organelles that can be degraded by autophagy machinery to release neutral lipids, a process called lipophagy. However, specific receptors and regulation mechanisms for lipophagy remain largely unknown. Here, we identify that ATG14, the core unit of the PI3KC3-C1 complex, also targets LD and acts as an autophagic receptor that facilitates LD degradation. A negative regulator, Syntaxin18 (STX18) binds ATG14, disrupting the ATG14-ATG8 family members interactions and subverting the PI3KC3-C1 complex formation. Knockdown of STX18 activates lipophagy dependent on ATG14 not only as the core unit of PI3KC3-C1 complex but also as the autophagic receptor, resulting in the degradation of LD-associated anti-viral protein Viperin. Furthermore, coronavirus M protein binds STX18 and subverts the STX18-ATG14 interaction to induce lipophagy and degrade Viperin, facilitating virus production. Altogether, our data provide a previously undescribed mechanism for additional roles of ATG14 in lipid metabolism and virus production.
Interaction-selective molecular sieving adsorbent for direct separation of ethylene from senary C2-C4 olefin/paraffin mixture
Authors: Peng Yong , Xiong Hanting , Zhang Peixin , Zhao Zhiwei , Liu Xing , Tang Shihui , Liu Yuan , Zhu Zhenliang , Zhou Weizhen , Deng Zhenning , Liu Junhui , Zhong Yao , Wu Zeliang , Chen Jingwen , Zhou Zhenyu , Chen Shixia , Deng Shuguang , Wang Jun
Published: January 2024

Olefin/paraffin separations are among the most energy-intensive processes in the petrochemical industry, with ethylene being the most widely consumed chemical feedstock. Adsorptive separation utilizing molecular sieving adsorbents can optimize energy efficiency, whereas the size-exclusive mechanism alone cannot achieve multiple olefin/paraffin sieving in a single adsorbent. Herein, an unprecedented sieving adsorbent, BFFOUR-Cu-dpds (BFFOUR = BF4-, dpds = 4,4’-bipyridinedisulfide), is reported for simultaneous sieving of C2-C4 olefins from their corresponding paraffins. The interlayer spaces can be selectively opened through stronger guest-host interactions induced by unsaturated C = C bonds in olefins, as opposed to saturated paraffins. In equimolar six-component breakthrough experiments (C2H4/C2H6/C3H6/C3H8/n-C4H8/n-C4H10), BFFOUR-Cu-dpds can simultaneously divide olefins from paraffins in the first column, while high-purity ethylene ( > 99.99%) can be directly obtained through the subsequent column using granular porous carbons. Moreover, gas-loaded single-crystal analysis, in-situ infrared spectroscopy measurements, and computational simulations demonstrate the accommodation patterns, interaction bonds, and energy pathways for olefin/paraffin separations.
Endogenous Coriobacteriaceae enriched by a high-fat diet promotes colorectal tumorigenesis through the CPT1A-ERK axis
Authors: Tang Qiulin , Huang Huixi , Xu Huanji , Xia Hongwei , Zhang Chenliang , Ye Di , Bi Feng
Published: January 2024

A high-fat diet (HFD) may be linked to an increased colorectal cancer (CRC) risk. Stem cell proliferation and adipokine release under inflammatory and obese conditions are the main factors regulating CRC progression. Furthermore, alterations in intestinal flora have been linked to tumorigenesis and tumour progression. However, whether a HFD can promote CRC occurrence by altering intestinal flora remains unclear. The objective of this study was to identify bacterial strains enriched by a HFD and investigate the association and mechanism by which a HFD and bacterial enrichment promote CRC occurrence and development. In this study, the intestinal microbiota of mice was assessed using 16S rRNA and metagenomic sequencing. Serum metabolites of HFD-fed mice were assessed using tandem liquid chromatography-mass spectrometry. CRC cell lines and organoids were co-cultured with Coriobacteriaceae to evaluate the effect of these bacteria on the CPT1A-ERK signalling pathway. We found that Coriobacteriaceae were enriched in the colons of HFD-fed mice. An endogenous Coriobacteriaceae strain, designated as Cori.ST1911, was successfully isolated and cultured from the stools of HFD-fed mice, and the tumorigenic potential of Cori.ST1911 in CRC was validated in several CRC mouse models. Furthermore, Cori.ST1911 increased acylcarnitine levels by activating CPT1A, demonstrating the involvement of the CPT1A-ERK axis. We also found that the endogenous Lactobacillus strain La.mu730 can interfere with Cori.ST1911 colonisation and restore gut barrier function. In conclusion, we identified a novel endogenous intestinal Coriobacteriaceae, Cori.ST1911, which might lead to a new gut microbiota intervention strategy for the prevention and treatment of CRC.
Predicting response to neoadjuvant chemotherapy with liquid biopsies and multiparametric MRI in patients with breast cancer
Authors: Janssen L. M. , Janse M. H. A. , Penning de Vries B. B. L. , van der Velden B. H. M. , Wolters-van der Ben E. J. M. , van den Bosch S. M. , Sartori A. , Jovelet C. , Agterof M. J. , Ten Bokkel Huinink D. , Bouman-Wammes E. W. , van Diest P. J. , van der Wall E. , Elias S. G. , Gilhuijs K. G. A.
Published: January 2024

Accurate prediction of response to neoadjuvant chemotherapy (NAC) can help tailor treatment to individual patients’ needs. Little is known about the combination of liquid biopsies and computer extracted features from multiparametric magnetic resonance imaging (MRI) for the prediction of NAC response in breast cancer. Here, we report on a prospective study with the aim to explore the predictive potential of this combination in adjunct to standard clinical and pathological information before, during and after NAC. The study was performed in four Dutch hospitals. Patients without metastases treated with NAC underwent 3 T multiparametric MRI scans before, during and after NAC. Liquid biopsies were obtained before every chemotherapy cycle and before surgery. Prediction models were developed using penalized linear regression to forecast residual cancer burden after NAC and evaluated for pathologic complete response (pCR) using leave-one-out-cross-validation (LOOCV). Sixty-one patients were included. Twenty-three patients (38%) achieved pCR. Most prediction models yielded the highest estimated LOOCV area under the curve (AUC) at the post-treatment timepoint. A clinical-only model including tumor grade, nodal status and receptor subtype yielded an estimated LOOCV AUC for pCR of 0.76, which increased to 0.82 by incorporating post-treatment radiological MRI assessment (i.e., the “clinical-radiological” model). The estimated LOOCV AUC was 0.84 after incorporation of computer-extracted MRI features, and 0.85 when liquid biopsy information was added instead of the radiological MRI assessment. Adding liquid biopsy information to the clinical-radiological resulted in an estimated LOOCV AUC of 0.86. In conclusion, inclusion of liquid biopsy-derived markers in clinical-radiological prediction models may have potential to improve prediction of pCR after NAC in breast cancer.
A polygenic score associated with fracture risk in breast cancer patients treated with aromatase inhibitors
Authors: Hook Christine , Chatterjee Udit , Sheng Haiyang , Zhu Qianqian , Robinson Timothy , Roh Janise M. , Laurent Cecile A. , Lee Catherine , Delmerico Jennifer , Lo Joan C. , Ambrosone Christine B. , Kushi Lawrence H. , Kwan Marilyn L. , Yao Song
Published: January 2024

Identifying women at high risk of osteoporotic fracture from aromatase inhibitor (AI) therapy for breast cancer is largely based on known risk factors for healthy postmenopausal women, which might not accurately reflect the risk in breast cancer patients post-AI therapy. To determine whether a polygenic score associated with fracture in healthy women is also significant in women treated with AIs for breast cancer, we used data from a prospective observational cohort of 2152 women diagnosed with hormonal receptor positive breast cancer treated with AIs as the initial endocrine therapy and examined a polygenic score of heel quantitative ultrasound speed of sound (gSOS) in relation to incident osteoporotic fracture after AI therapy during a median 6.1 years of follow up after AI initiation. In multivariable models, patients with the second and third highest tertiles (T) versus the lowest tertile of gSOS had significantly lower risk of fracture (T2: adjusted HR = 0.61, 95% CI: 0.46-0.80; T3: adjusted HR = 0.53, 95% CI: 0.40-0.70). The lower risk of fracture in patients with the highest tertile of gSOS remained significant after further adjustment for BMD at the hip (T3: adjusted HR = 0.62, 95% CI: 0.42-0.91). In conclusion, our analysis showed gSOS as a novel genetic predictor for fracture risk independent of BMD among breast cancer patients treated with AIs. Future studies are warranted to evaluate the performance of incorporating gSOS in prediction models for the risk of AI-related fracture in breast cancer patients.
Machine learned force-fields for an Ab-initio quality description of metal-organic frameworks
Authors: Wieser Sandro , Zojer Egbert
Published: January 2024

Metal-organic frameworks (MOFs) are an incredibly diverse group of highly porous hybrid materials, which are interesting for a wide range of possible applications. For a meaningful theoretical description of many of their properties accurate and computationally highly efficient methods are in high demand. These would avoid compromises regarding either the quality of modelling results or the level of complexity of the calculated properties. With the advent of machine learning approaches, it is now possible to generate such approaches with relatively little human effort. Here, we build on existing types of machine-learned force fields belonging to the moment-tensor and kernel-based potential families to develop a recipe for their efficient parametrization. This yields exceptionally accurate and computationally highly efficient force fields. The parametrization relies on reference configurations generated during molecular dynamics based, active learning runs. The performance of the potentials is benchmarked for a representative selection of commonly studied MOFs revealing a close to DFT accuracy in predicting forces and structural parameters for a set of validation structures. The same applies to elastic constants and phonon band structures. Additionally, for MOF-5 the thermal conductivity is obtained with full quantitative agreement to single-crystal experiments. All this is possible while maintaining a very high degree of computational efficiency. The exceptional accuracy of the parameterized force field potentials combined with their computational efficiency has the potential of lifting the computational modelling of MOFs to the next level.
Whole genome sequencing enables new genetic diagnosis for inherited retinal diseases by identifying pathogenic variants
Authors: Liu Xubing , Hu Fangyuan , Zhang Daowei , Li Zhe , He Jianquan , Zhang Shenghai , Wang Zhenguo , Zhao Yingke , Wu Jiawen , Liu Chen , Li Chenchen , Li Xin , Wu Jihong
Published: January 2024

Inherited retinal diseases (IRDs) are a group of common primary retinal degenerative disorders. Conventional genetic testing strategies, such as panel-based sequencing and whole exome sequencing (WES), can only elucidate the genetic etiology in approximately 60% of IRD patients. Studies have suggested that unsolved IRD cases could be attributed to previously undetected structural variants (SVs) and intronic variants in IRD-related genes. The aim of our study was to obtain a definitive genetic diagnosis by employing whole genome sequencing (WGS) in IRD cases where the causative genes were inconclusive following an initial screening by panel sequencing. A total of 271 unresolved IRD patients and their available family members (n = 646) were screened using WGS to identify pathogenic SVs and intronic variants in 792 known ocular disease genes. Overall, 13% (34/271) of IRD patients received a confirmed genetic diagnosis, among which 7% were exclusively attributed to SVs, 4% to a combination of single nucleotide variants (SNVs) and SVs while another 2% were linked to intronic variants. 22 SVs, 3 deep-intronic variants, and 2 non-canonical splice-site variants across 14 IRD genes were identified in the entire cohort. Notably, all of these detected SVs and intronic variants were novel pathogenic variants. Among those, 74% (20/27) of variants were found in genes causally linked to Retinitis Pigmentosa (RP), with the gene EYS being the most frequently affected by SVs. The identification of SVs and intronic variants through WGS enhances the genetic diagnostic yield of IRDs and broadens the mutational spectrum of known IRD-associated genes.
Early-stage idiopathic Parkinson’s disease is associated with reduced circular RNA expression
Authors: Whittle Benjamin J. , Izuogu Osagie G. , Lowes Hannah , Deen Dasha , Pyle Angela , Coxhead Jon , Lawson Rachael A. , Yarnall Alison J. , Jackson Michael S. , Santibanez-Koref Mauro , Hudson Gavin
Published: January 2024

Neurodegeneration in Parkinson’s disease (PD) precedes diagnosis by years. Early neurodegeneration may be reflected in RNA levels and measurable as a biomarker. Here, we present the largest quantification of whole blood linear and circular RNAs (circRNA) in early-stage idiopathic PD, using RNA sequencing data from two cohorts (PPMI = 259 PD, 161 Controls; ICICLE-PD = 48 PD, 48 Controls). We identified a replicable increase inTMEM252andLMNB1gene expression in PD. We identified novel differences in the expression of circRNAs fromESYT2,BMS1P1andCCDC9, and replicated trends of previously reported circRNAs. Overall, using circRNA as a diagnostic biomarker in PD did not show any clear improvement over linear RNA, minimising its potential clinical utility. More interestingly, we observed a general reduction in circRNA expression in both PD cohorts, accompanied by an increase inRNASELexpression. This imbalance implicates the activation of an innate antiviral immune response and suggests a previously unknown aspect of circRNA regulation in PD.
High-field immiscibility of electrons belonging to adjacent twinned bismuth crystals
Authors: Ye Yuhao , Yamada Akiyoshi , Kinoshita Yuto , Wang Jinhua , Nie Pan , Xu Liangcai , Zuo Huakun , Tokunaga Masashi , Harrison Neil , McDonald Ross D. , Suslov Alexey V. , Ardavan Arzhang , Nam Moon-Sun , LeBoeuf David , Proust Cyril , Fauqué Benoît , Fuseya Yuki , Zhu Zengwei , Behnia Kamran
Published: January 2024

Bulk bismuth has a complex Landau spectrum. The small effective masses and the large g-factors are anisotropic. The chemical potential drifts at high magnetic fields. Moreover, twin boundaries further complexify the interpretation of the data by producing extra anomalies in the extreme quantum limit. Here, we present a study of angle dependence of magnetoresistance up to 65 T in bismuth complemented with Nernst, ultrasound, and magneto-optic data. All observed anomalies can be explained in a single-particle picture of a sample consisting of two twinned crystals tilted by 108° and with two adjacent crystals keeping their own chemical potentials despite a shift between chemical potentials as large as 68 meV at 65 T. This implies an energy barrier between adjacent twinned crystals reminiscent of a metal- semiconductor Schottky barrier or a p-n junction. We argue that this barrier is built by accumulating charge carriers of opposite signs across a twin boundary.
MSCs mediate long-term efficacy in a Crohn’s disease model by sustained anti-inflammatory macrophage programming via efferocytosis
Authors: Dave Maneesh , Dev Atul , Somoza Rodrigo A. , Zhao Nan , Viswanath Satish , Mina Pooja Rani , Chirra Prathyush , Obmann Verena Carola , Mahabeleshwar Ganapati H. , Menghini Paola , Durbin-Johnson Blythe , Nolta Jan , Soto Christopher , Osme Abdullah , Khuat Lam T. , Murphy William J. , Caplan Arnold I. , Cominelli Fabio
Published: January 2024

Mesenchymal stem cells (MSCs) are novel therapeutics for the treatment of Crohn’s disease. However, their mechanism of action is unclear, especially in disease-relevant chronic models of inflammation. Thus, we used SAMP-1/YitFc (SAMP), a chronic and spontaneous murine model of small intestinal inflammation, to study the therapeutic effects and mechanism of action of human bone marrow-derived MSCs (hMSC). hMSC dose-dependently inhibited naïve T lymphocyte proliferation via prostaglandin E2 (PGE2) secretion and reprogrammed macrophages to an anti-inflammatory phenotype. We found that the hMSCs promoted mucosal healing and immunologic response early after administration in SAMP when live hMSCs are present (until day 9) and resulted in a complete response characterized by mucosal, histological, immunologic, and radiological healing by day 28 when no live hMSCs are present. hMSCs mediate their effect via modulation of T cells and macrophages in the mesentery and mesenteric lymph nodes (mLN). Sc-RNAseq confirmed the anti-inflammatory phenotype of macrophages and identified macrophage efferocytosis of apoptotic hMSCs as a mechanism that explains their long-term efficacy. Taken together, our findings show that hMSCs result in healing and tissue regeneration in a chronic model of small intestinal inflammation and despite being short-lived, exert long-term effects via sustained anti-inflammatory programming of macrophages via efferocytosis.
An analysis of emerging food safety and fraud risks of novel insect proteins within complex supply chains
Authors: Traynor A. , Burns D. Thorburn , Wu D. , Karoonuthaisiri N. , Petchkongkaew A. , Elliott C. T.
Published: January 2024

Food consumption play a crucial role in human life, yet conventional food production and consumption patterns can be detrimental to the environment. Thus, research and development has been directed towards alternative proteins, with edible insects being promising sources. Edible insects have been recognised for their sustainable benefits providing protein, with less emission of greenhouse gas, land and water usage compared to sources, such as beef, chicken, and dairy products. Among the over 2000 known edible insect species, only four, namely yellow mealworm (Tenebrio molitor), migratory locust/grasshopper (Locusta migratoria), grain mould beetle, also known as lesser mealworm which is a larval form of Alphitobius diaperinus (from the family of Tenebrionidae of darkling beetles) and house cricket (Acheta domesticus), are currently authorised in specific products through specific producers in the EU. The expansion of such foods into Western diets face challenges such as consumer barriers, gaps in microbiological and chemical safety hazard data during production and processing, and the potential for fraudulent supply chain activity. The main aim of this study was to map the supply chain, through interviews with personnel along the supply chain, coupled with searches for relevant publications and governmental documents. Thus, the main potential points of food safety and fraud along the edible insect supply chain were identified. Feed substrate was identified as the main area of concern regarding microbiological and chemical food safety and novel processing techniques were forecast to be of most concern for future fraudulent activity. Despite the on-going authorisation of insect species in many countries there are substantial food safety and authenticity information gaps in this industry that need to be addressed before edible insects can be viewed as a safe and sustainable protein sources by Western consumers.
Development of performance and learning rate evaluation models in robot-assisted surgery using electroencephalography and eye-tracking
Authors: Shafiei Somayeh B. , Shadpour Saeed , Sasangohar Farzan , Mohler James L. , Attwood Kristopher , Jing Zhe
Published: January 2024

The existing performance evaluation methods in robot-assisted surgery (RAS) are mainly subjective, costly, and affected by shortcomings such as the inconsistency of results and dependency on the raters’ opinions. The aim of this study was to develop models for an objective evaluation of performance and rate of learning RAS skills while practicing surgical simulator tasks. The electroencephalogram (EEG) and eye-tracking data were recorded from 26 subjects while performing Tubes, Suture Sponge, and Dots and Needles tasks. Performance scores were generated by the simulator program. The functional brain networks were extracted using EEG data and coherence analysis. Then these networks, along with community detection analysis, facilitated the extraction of average search information and average temporal flexibility features at 21 Brodmann areas (BA) and four band frequencies. Twelve eye-tracking features were extracted and used to develop linear random intercept models for performance evaluation and multivariate linear regression models for the evaluation of the learning rate. Results showed that subject-wise standardization of features improved the R2 of the models. Average pupil diameter and rate of saccade were associated with performance in the Tubes task (multivariate analysis; p-value = 0.01 and p-value = 0.04, respectively). Entropy of pupil diameter was associated with performance in Dots and Needles task (multivariate analysis; p-value = 0.01). Average temporal flexibility and search information in several BAs and band frequencies were associated with performance and rate of learning. The models may be used to objectify performance and learning rate evaluation in RAS once validated with a broader sample size and tasks.
Bio-inspired design of next-generation ultrapermeable membrane systems
Authors: Luo Jiu , Li Mingheng , Heng Yi
Published: January 2024

Ultrapermeable membranes (UPMs) have the potential of improving water production efficiency. However, operating at high water fluxes will intensify concentration polarization and membrane fouling. Inspired by the V-formation of birds in nature we propose a transformative membrane module that enables a doubled mass transfer coefficient with a moderately increased friction loss coefficient. Moreover, we present a practical technological pathway for the UPM systems to achieve 338% improvement of average water flux and 18% energy savings relative to state-of-the-art seawater desalination plants. The work makes it practical to operate at a high average water flux of 84 L m−2 h−1 with a controlled concentration polarization for the UPM systems. It breaks through the module development bottlenecks for the next-generation UPM systems and has enormous potential application for alleviating water scarcity crisis in the coming decades.
Open Fundus Photograph Dataset with Pathologic Myopia Recognition and Anatomical Structure Annotation
Authors: Fang Huihui , Li Fei , Wu Junde , Fu Huazhu , Sun Xu , Orlando José Ignacio , Bogunović Hrvoje , Zhang Xiulan , Xu Yanwu
Published: January 2024

Pathologic myopia (PM) is a common blinding retinal degeneration suffered by highly myopic population. Early screening of this condition can reduce the damage caused by the associated fundus lesions and therefore prevent vision loss. Automated diagnostic tools based on artificial intelligence methods can benefit this process by aiding clinicians to identify disease signs or to screen mass populations using color fundus photographs as inputs. This paper provides insights about PALM, our open fundus imaging dataset for pathological myopia recognition and anatomical structure annotation. Our databases comprises 1200 images with associated labels for the pathologic myopia category and manual annotations of the optic disc, the position of the fovea and delineations of lesions such as patchy retinal atrophy (including peripapillary atrophy) and retinal detachment. In addition, this paper elaborates on other details such as the labeling process used to construct the database, the quality and characteristics of the samples and provides other relevant usage notes.
Utility and impact of magnetic resonance elastography in the clinical course and management of chronic liver disease
Authors: Feuille Colin , Kari Swathi , Patel Roshan , Oberoi Rohan , Liu Jonathan , Ohliger Michael , Khalili Mandana , Tana Michele
Published: January 2024

We aimed to characterize scenarios where magnetic resonance elastography (MRE) of the liver was ordered and its impact on clinical course and management. 96 consecutive MRE examinations and subsequent encounters over 14 months were reviewed. Indication for MRE of the liver and subsequent management were abstracted from the medical record. In all cases, non-invasive assessment of liver fibrosis was the primary indication and at least one additional rationale was noted. There was a significant decrease in recommendations to undergo liver biopsy after MRE. Additionally, a greater percentage of those recommended to undergo biopsy completed the procedure after discussion of the results. Given the significant cost and rare but serious risks of liver biopsy, MRE of the liver provides an attractive, safer alternative that may have a comparable impact on management, or select cases where biopsy is essential to guide management. We demonstrate the versatility of MRE in real-world hepatology practice, including its utility as a non-invasive surrogate for liver biopsy.
Residential mobility restrictions and adverse mental health outcomes during the COVID-19 pandemic in the UK
Authors: Chan Ho Fai , Cheng Zhiming , Mendolia Silvia , Paloyo Alfredo R. , Tani Massimiliano , Proulx Damon , Savage David A. , Torgler Benno
Published: January 2024

During the COVID-19 pandemic, several governments tried to contain the spread of SARS-CoV-2, the virus that causes COVID-19, with lockdowns that prohibited leaving one’s residence unless carrying out a few essential services. We investigate the relationship between limitations to mobility and mental health in the UK during the first year and a half of the pandemic using a unique combination of high-frequency mobility data from Google and monthly longitudinal data collected through the Understanding Society survey. We find a strong and statistically robust correlation between mobility data and mental health survey data and show that increased residential stationarity is associated with the deterioration of mental wellbeing even when regional COVID-19 prevalence and lockdown stringency are controlled for. The relationship is heterogeneous, as higher levels of distress are seen in young, healthy people living alone; and in women, especially if they have young children.
Development of a human-analogue, 3-symptom domain Dog ADHD and Functionality Rating Scale (DAFRS)
Authors: Csibra Barbara , Bunford Nóra , Gácsi Márta
Published: January 2024

The family dog, in its natural environment, exhibits neuropsychological deficits redolent of human psychiatric disorders, including behaviours that are similar to human attention-deficit/hyperactivity disorder (ADHD) symptoms. Based on standard questionnaire methods in humans, we aimed to develop and validate a detailed, psychometrically improved tool to assess owner views on relevant dog behaviours. We modified available questionnaires by adding items that allow for separate analysis of impulsivity, and items on functional impairment. We collected data from 1168 owners for different validation steps of the new questionnaire and, similarly to assessment of humans where teachers also evaluate as an expert control, we collected data from dog trainers. Exploratory and confirmatory factor analysis revealed 3 factors: inattention (IA), hyperactivity (H) and impulsivity (I), corresponding to all three human symptom dimensions in dogs. Test–retest analyses showed excellent agreement between measurements for all factors. Similarly to findings with humans, trainer-owner rating comparisons showed fair (IA) to moderate (H, I) agreement. As in humans, greater ADHD scores were associated with greater functional impairment scores. We suggest that in dogs, similarly to humans, parallel examination of (extreme) ADHD and functional impairment scores could help distinguish diagnosable individuals, after further validation of the questionnaire using a relevant behaviour test.
Effect of acid proticity on the thermodynamic parameters of charge transfer resistance in corrosion and passivation of nickel based glass alloy
Authors: Emran Khadijah M. , Ouerfelli Noureddine
Published: January 2024

The effect of temperature on electrochemical properties of Ni82.3Cr7Fe3Si4.5B3.2 glassy alloy in different acid proticity has been investigated utilizing AC and DC methods. Firstly, the handling of experimental data on the temperature dependence of charge transfer resistance, as well as corrosion current density permits us to determine the values of classical Arrhenius parameters as well as the thermodynamic ones considered approximately independent of temperature. This leads us to deduce a global interpretation on the phenomenon of corrosion and polarization. Secondly, the deviation to the linearity of the Arrhenius behavior and the real dependence on temperature of the thermodynamic parameters, permit us to clearly quantify the effect of the acid proticity and define, for the first time, the concept of current Arrhenius parameters and the current thermodynamic ones, as well as the modeling of the enthalpy–enthalpy compensation. Moreover, the effect of temperature can be investigated using the Vogel–Fulcher–Tammann model to reveal that the corresponding Vogel temperature has an interesting physical meaning.
ECC-based three-factor authentication and key agreement scheme for wireless sensor networks
Authors: Huang Wenfeng
Published: January 2024

In wireless sensor networks (WSNs), protocols with authentication and key agreement functions can enhance the security of the interaction between users and sensor nodes, guaranteeing the security of user access and sensor node information. Existing schemes have various security vulnerabilities and are susceptible to security attacks (e.g., masquerading user, password guessing, internal privilege, and MITT attacks), so they cannot meet the anonymity requirements or achieve forward security. To effectively improve the security performance of WSNs, an elliptic curve cryptography (ECC)-based three-factor authentication and key agreement scheme for WSNs is proposed. The scheme is based on the ECC protocol and combines biometrics, smart card and password authentication technology; uses a challenge/response mechanism to complete the authentication between users, gateways, and sensors; and negotiates a secure session key. The Burrows, Abadi and Needham logic for formal security analysis proves the correctness and security of the scheme, and the informal analysis of multiple known attacks proves that the scheme can resist various attacks and has high security characteristics. The feasibility of the scheme has been analysed and verified with the ProVerif tool. The efficiency analysis results show that the scheme is suitable for resource-constrained WSNs.
A novel gear RUL prediction method by diffusion model generation health index and attention guided multi-hierarchy LSTM
Authors: Chen Xinping
Published: January 2024

Gears, as indispensable components of machinery, demand accurate prediction of their Remaining Useful Life (RUL). To enhance the utilization of ordered information within time series data and elevate RUL prediction precision, this study introduces the attention-guided multi-hierarchy LSTM (AGMLSTM). This innovative approach leverages attention mechanisms to capture the intricate interplay between high and low hierarchical features of the input data, marking the first application of such a technique in gear RUL prediction. Additionally, a refined health indicator (HI) is introduced, constructed through a diffusion model, to precisely reflect the gears' health condition. The proposed RUL prediction method unfolds as follows: firstly, HIs are computed from gear vibration data. Subsequently, leveraging the known HIs, AGMLSTM predicts future HIs, and the RUL of the gear is determined upon surpassing the failure threshold. Quantitative analysis of experimental results conclusively demonstrates the superiority of the proposed RUL prediction method over existing approaches for gear RUL estimation.