bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution and international spread of extensively drug resistant Shigella sonnei
Authors: Mason Lewis C. E. , Greig David R. , Cowley Lauren A. , Partridge Sally R. , Martinez Elena , Blackwell Grace A. , Chong Charlotte E. , De Silva P. Malaka , Bengtsson Rebecca J. , Draper Jenny L. , Ginn Andrew N. , Sandaradura Indy , Sim Eby M. , Iredell Jonathan R. , Sintchenko Vitali , Ingle Danielle J. , Howden Benjamin P. , Lefèvre Sophie , Njamkepo Elisabeth , Weill François-Xavier , Ceyssens Pieter-Jan , Jenkins Claire , Baker Kate S.
Published: April 2023

Shigella sonnei causes shigellosis, a severe gastrointestinal illness that is sexually transmissible among men who have sex with men (MSM). Multidrug resistance in S. sonnei is common including against World Health Organisation recommended treatment options, azithromycin, and ciprofloxacin. Recently, an MSM-associated outbreak of extended-spectrum β-lactamase producing, extensively drug resistant S. sonnei was reported in the United Kingdom. Here, we aimed to identify the genetic basis, evolutionary history, and international dissemination of the outbreak strain. Our genomic epidemiological analyses of 3,304 isolates from the United Kingdom, Australia, Belgium, France, and the United States of America revealed an internationally connected outbreak with a most recent common ancestor in 2018 carrying a low-fitness cost resistance plasmid, previously observed in travel associated sublineages of S. flexneri. Our results highlight the persistent threat of horizontally transmitted antimicrobial resistance and the value of continuing to work towards early and open international sharing of genomic surveillance data.
Topological antichiral surface states in a magnetic Weyl photonic crystal
Authors: Xi Xiang , Yan Bei , Yang Linyun , Meng Yan , Zhu Zhen-Xiao , Chen Jing-Ming , Wang Ziyao , Zhou Peiheng , Shum Perry Ping , Yang Yihao , Chen Hongsheng , Mandal Subhaskar , Liu Gui-Geng , Zhang Baile , Gao Zhen
Published: April 2023

Chiral edge states that propagate oppositely at two parallel strip edges are a hallmark feature of Chern insulators which were first proposed in the celebrated two-dimensional (2D) Haldane model. Subsequently, counterintuitive antichiral edge states that propagate in the same direction at two parallel strip edges were discovered in a 2D modified Haldane model. Recently, chiral surface states, the 2D extension of one-dimensional (1D) chiral edge states, have also been observed in a photonic analogue of a 3D Haldane model. However, despite many recent advances in antichiral edge states and chiral surface states, antichiral surface states, the 2D extension of 1D antichiral edge states, have never been realized in any physical system. Here, we report the experimental observation of antichiral surface states by constructing a 3D modified Haldane model in a magnetic Weyl photonic crystal with two pairs of frequency-shifted Weyl points (WPs). The 3D magnetic Weyl photonic crystal consists of gyromagnetic cylinders with opposite magnetization in different triangular sublattices of a 3D honeycomb lattice. Using microwave field-mapping measurements, unique properties of antichiral surface states have been observed directly, including the antichiral robust propagation, tilted surface dispersion, a single open Fermi arc connecting two projected WPs and a single Fermi loop winding around the surface Brillouin zone (BZ). These results extend the scope of antichiral topological states and enrich the family of magnetic Weyl semimetals.
The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot
Authors: Loiseau Chloé , Windels Etthel M. , Gygli Sebastian M. , Jugheli Levan , Maghradze Nino , Brites Daniela , Ross Amanda , Goig Galo , Reinhard Miriam , Borrell Sonia , Trauner Andrej , Dötsch Anna , Aspindzelashvili Rusudan , Denes Rebecca , Reither Klaus , Beisel Christian , Tukvadze Nestani , Avaliani Zaza , Stadler Tanja , Gagneux Sebastien
Published: April 2023

Multidrug-resistant tuberculosis (MDR-TB) is among the most frequent causes of death due to antimicrobial resistance. Although only 3% of global TB cases are MDR, geographical hotspots with up to 40% of MDR-TB have been observed in countries of the former Soviet Union. While the quality of TB control and patient-related factors are known contributors to such hotspots, the role of the pathogen remains unclear. Here we show that in the country of Georgia, a known hotspot of MDR-TB, MDR Mycobacterium tuberculosis strains of lineage 4 (L4) transmit less than their drug-susceptible counterparts, whereas most MDR strains of L2 suffer no such defect. Our findings further indicate that the high transmission fitness of these L2 strains results from epistatic interactions between the rifampicin resistance-conferring mutation RpoB S450L, compensatory mutations in the RNA polymerase, and other pre-existing genetic features of L2/Beijing clones that circulate in Georgia. We conclude that the transmission fitness of MDR M. tuberculosis strains is heterogeneous, but can be as high as drug-susceptible forms, and that such highly drug-resistant and transmissible strains contribute to the emergence and maintenance of hotspots of MDR-TB. As these strains successfully overcome the metabolic burden of drug resistance, and given the ongoing rollout of new treatment regimens against MDR-TB, proper surveillance should be implemented to prevent these strains from acquiring resistance to the additional drugs.
Order-disorder phase transition driven by interlayer sliding in lead iodides
Authors: Cha Seyeong , Lee Giyeok , Lee Sol , Ryu Sae Hee , Sohn Yeongsup , An Gijeong , Kang Changmo , Kim Minsu , Kim Kwanpyo , Soon Aloysius , Kim Keun Su
Published: April 2023

A variety of phase transitions have been found in two-dimensional layered materials, but some of their atomic-scale mechanisms are hard to clearly understand. Here, we report the discovery of a phase transition whose mechanism is identified as interlayer sliding in lead iodides, a layered material widely used to synthesize lead halide perovskites. The low-temperature crystal structure of lead iodides is found not 2H polytype as known before, but non-centrosymmetric 4H polytype. This undergoes the order-disorder phase transition characterized by the abrupt spectral broadening of valence bands, taken by angle-resolved photoemission, at the critical temperature of 120 K. It is accompanied by drastic changes in simultaneously taken photocurrent and photoluminescence. The transmission electron microscopy is used to reveal that lead iodide layers stacked in the form of 4H polytype at low temperatures irregularly slide over each other above 120 K, which can be explained by the low energy barrier of only 10.6 meV/atom estimated by first principles calculations. Our findings suggest that interlayer sliding is a key mechanism of the phase transitions in layered materials, which can significantly affect optoelectronic and optical characteristics.
Conformational cycle of human polyamine transporter ATP13A2
Authors: Mu Jianqiang , Xue Chenyang , Fu Lei , Yu Zongjun , Nie Minhan , Wu Mengqi , Chen Xinmeng , Liu Kun , Bu Ruiqian , Huang Ying , Yang Baisheng , Han Jianming , Jiang Qianru , Chan Kevin C. , Zhou Ruhong , Li Huilin , Huang Ancheng , Wang Yong , Liu Zhongmin
Published: April 2023

Dysregulation of polyamine homeostasis strongly associates with human diseases. ATP13A2, which is mutated in juvenile-onset Parkinson’s disease and autosomal recessive spastic paraplegia 78, is a transporter with a critical role in balancing the polyamine concentration between the lysosome and the cytosol. Here, to better understand human ATP13A2-mediated polyamine transport, we use single-particle cryo-electron microscopy to solve high-resolution structures of human ATP13A2 in six intermediate states, including the putative E2 structure for the P5 subfamily of the P-type ATPases. These structures comprise a nearly complete conformational cycle spanning the polyamine transport process and capture multiple substrate binding sites distributed along the transmembrane regions, suggesting a potential polyamine transport pathway. Integration of high-resolution structures, biochemical assays, and molecular dynamics simulations allows us to obtain a better understanding of the structural basis of how hATP13A2 transports polyamines, providing a mechanistic framework for ATP13A2-related diseases.
Segmentation strategy of de novo designed four-helical bundles expands protein oligomerization modalities for cell regulation
Authors: Merljak Estera , Malovrh Benjamin , Jerala Roman
Published: April 2023

Protein–protein interactions govern most biological processes. New protein assemblies can be introduced through the fusion of selected proteins with di/oligomerization domains, which interact specifically with their partners but not with other cellular proteins. While four-helical bundle proteins (4HB) have typically been assembled from two segments, each comprising two helices, here we show that they can be efficiently segmented in various ways, expanding the number of combinations generated from a single 4HB. We implement a segmentation strategy of 4HB to design two-, three-, or four-chain combinations for the recruitment of multiple protein components. Different segmentations provide new insight into the role of individual helices for 4HB assembly. We evaluate 4HB segmentations for potential use in mammalian cells for the reconstitution of a protein reporter, transcriptional activation, and inducible 4HB assembly. Furthermore, the implementation of trimerization is demonstrated as a modular chimeric antigen receptor for the recognition of multiple cancer antigens.
RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes
Authors: Subramanian Megha , McIninch James , Zlatev Ivan , Schlegel Mark K. , Kaittanis Charalambos , Nguyen Tuyen , Agarwal Saket , Racie Timothy , Alvarado Martha Arbaiza , Wassarman Kelly , Collins Thomas S. , Chickering Tyler , Brown Christopher R. , Schmidt Karyn , Castoreno Adam B. , Shulga-Morskaya Svetlana , Stamenova Elena , Buckowing Kira , Berman Daniel , Barry Joseph D. , Bisbe Anna , Maier Martin A. , Fitzgerald Kevin , Jadhav Vasant
Published: April 2023

Adeno-associated virus (AAV)-based gene therapy could be facilitated by the development of molecular switches to control the magnitude and timing of expression of therapeutic transgenes. RNA interference (RNAi)-based approaches hold unique potential as a clinically proven modality to pharmacologically regulate AAV gene dosage in a sequence-specific manner. We present a generalizable RNAi-based rheostat wherein hepatocyte-directed AAV transgene expression is silenced using the clinically validated modality of chemically modified small interfering RNA (siRNA) conjugates or vectorized co-expression of short hairpin RNA (shRNA). For transgene induction, we employ REVERSIR technology, a synthetic high-affinity oligonucleotide complementary to the siRNA or shRNA guide strand to reverse RNAi activity and rapidly recover transgene expression. For potential clinical development, we report potent and specific siRNA sequences that may allow selective regulation of transgenes while minimizing unintended off-target effects. Our results establish a conceptual framework for RNAi-based regulatory switches with potential for infrequent dosing in clinical settings to dynamically modulate expression of virally-delivered gene therapies.
Light-independent regulation of algal photoprotection by CO2 availability
Authors: Ruiz-Sola M. Águila , Flori Serena , Yuan Yizhong , Villain Gaelle , Sanz-Luque Emanuel , Redekop Petra , Tokutsu Ryutaro , Küken Anika , Tsichla Angeliki , Kepesidis Georgios , Allorent Guillaume , Arend Marius , Iacono Fabrizio , Finazzi Giovanni , Hippler Michael , Nikoloski Zoran , Minagawa Jun , Grossman Arthur R. , Petroutsos Dimitris
Published: April 2023

Photosynthetic algae have evolved mechanisms to cope with suboptimal light and CO2 conditions. When light energy exceeds CO2 fixation capacity, Chlamydomonas reinhardtii activates photoprotection, mediated by LHCSR1/3 and PSBS, and the CO2 Concentrating Mechanism (CCM). How light and CO2 signals converge to regulate these processes remains unclear. Here, we show that excess light activates photoprotection- and CCM-related genes by altering intracellular CO2 concentrations and that depletion of CO2 drives these responses, even in total darkness. High CO2 levels, derived from respiration or impaired photosynthetic fixation, repress LHCSR3/CCM genes while stabilizing the LHCSR1 protein. Finally, we show that the CCM regulator CIA5 also regulates photoprotection, controlling LHCSR3 and PSBS transcript accumulation while inhibiting LHCSR1 protein accumulation. This work has allowed us to dissect the effect of CO2 and light on CCM and photoprotection, demonstrating that light often indirectly affects these processes by impacting intracellular CO2 levels.
Coupled mixed-potential and thermal-hydraulics model for long-term corrosion of copper canisters in deep geological repository
Authors: Chae Nakkyu , Park Samuel , Seo Seungjin , Foster Richard I. , Ju Heejae , Choi Sungyeol
Published: April 2023

Canister performance is a major issue for constructing reliable deep geological repositories for storing spent nuclear fuels, and corrosion resistance is main the factor determining canister durability. We developed a 2-D multiphysics model, which can predict both the corrosion rate and potential, for simulating copper canister corrosion in deep geological repositories. We found that canisters corroded through the long-cell action in a deep geological repository, the corrosion was quite limited, and the overall canister durability was around 1.7 million years. Our results demonstrated that copper exhibits sufficient corrosion resistance and that long-cell action-based corrosion cannot severely damage copper canisters.
Care by general practitioners for patients with asthma or COPD during the COVID-19 pandemic
Authors: Rijpkema Corinne , Ramerman Lotte , Homburg Maarten , Meijer Eline , Muris Jean , olde Hartman Tim , Berger Marjolein , Peters Lilian , Verheij Robert
Published: April 2023

The impact of the COVID-19 pandemic on general practitioners’ (GP) care for patients with asthma and/or COPD is largely unknown. To describe the impact of the pandemic on asthma or COPD-related GP care, we analysed routinely recorded electronic health records data from Dutch general practices and out-of-hours (OOH) services. During the COVID-19 pandemic (2020), the contact rates for asthma and/or COPD were significantly lower in GP practices and OOH services compared with the pre-pandemic period (2019) (respectively, 15% lower and 28% lower). The proportion of telephone contacts increased significantly with 13%-point in GP practices and 12%-point at OOH services, while the proportion of face-to-face contacts decreased. Furthermore, the proportion of high urgent contacts with OOH services decreased by 8.5%-point. To conclude, the overall contact rates in GP practices and OOH services decreased, while more contacts were remote. Lower contact rates have, after a short follow-up, not resulted in more patients with exacerbations in OOH care. However, this might still be expected after a longer follow-up.
Orbital degree of freedom induced multiple sets of second-order topological states in two-dimensional breathing Kagome crystals
Authors: Zhou Hui , Liu Hang , Ji Hongyan , Li Xuanyi , Meng Sheng , Sun Jia-Tao
Published: April 2023

The lattice geometry induced second-order topological corner states in breathing Kagome lattice have attracted enormous research interests, while the realistic breathing Kagome materials identified as second-order topological insulators are still lacking. Here, we report by first-principles calculations the second-order topological states emerging in two-dimensional d-orbital breathing Kagome crystals, i.e., monolayer niobium/tantalum chalcogenide halides M3QX7 (M = Nb, Ta; Q = S, Se, Te; X = Cl, Br, I). We find that the orbital degree of freedom of d orbitals can give rise to multiple sets of corner states. Combining fraction corner anomaly, orbital components and real space distribution of the corner states, we can also identify the topology of these corner states. Our work not only extends the lattice geometry induced second-order topological states to realistic materials, but also builds a clear and complete picture on their multiple sets of second-order topological states.
Cholec80-CVS: An open dataset with an evaluation of Strasberg’s critical view of safety for AI
Authors: Ríos Manuel Sebastián , Molina-Rodriguez María Alejandra , Londoño Daniella , Guillén Camilo Andrés , Sierra Sebastián , Zapata Felipe , Giraldo Luis Felipe
Published: April 2023

Strasberg’s criteria to detect a critical view of safety is a widely known strategy to reduce bile duct injuries during laparoscopic cholecystectomy. In spite of its popularity and efficiency, recent studies have shown that human miss-identification errors have led to important bile duct injuries occurrence rates. Developing tools based on artificial intelligence that facilitate the identification of a critical view of safety in cholecystectomy surgeries can potentially minimize the risk of such injuries. With this goal in mind, we present Cholec80-CVS, the first open dataset with video annotations of Strasberg’s Critical View of Safety (CVS) criteria. Our dataset contains CVS criteria annotations provided by skilled surgeons for all videos in the well-known Cholec80 open video dataset. We consider that Cholec80-CVS is the first step towards the creation of intelligent systems that can assist humans during laparoscopic cholecystectomy.
Genome-wide chromatin accessibility and gene expression profiling during flatfish metamorphosis
Authors: Guerrero-Peña Laura , Suarez-Bregua Paula , Gil-Gálvez Alejandro , Naranjo Silvia , Méndez-Martínez Luis , Tur Ricardo , García-Fernández Pablo , Tena Juan J , Rotllant Josep
Published: April 2023

Metamorphosis is a widely studied post-embryonic process in which many tissues undergo dramatic modifications to adapt to the new adult lifestyle. Flatfishes represent a good example of metamorphosis in teleost fishes. During metamorphosis of flatfish, organ regression and neoformation occur, with one of the most notable changes being the migration of one of the eyes to the other side of the body. In order to create a useful and reliable tool to advance the molecular study of metamorphosis in flatfish, we generated a chromatin accessible atlas as well as gene expression profile during four developmental stages ranging from a phylotypic to a post-metamorphic stage. We identified 29,019 differentially accessible chromatin regions and 3,253 differentially expressed genes. We found stage-specific regulatory regions and gene expression profiles, supporting the quality of the results. Our work provides strongly reproducible data for further studies to elucidate the regulatory elements that ensure successful metamorphosis in flatfish species.
Prognostic value of pre-therapeutic FDG-PET radiomic analysis in gastro-esophageal junction cancer
Authors: Amrane Karim , Thuillier Philippe , Bourhis David , Le Meur Coline , Quere Chloe , Leclere Jean-Christophe , Ferec Marc , Jestin-Le Tallec Veronique , Doucet Laurent , Alemany Pierre , Salaun Pierre-Yves , Metges Jean-Philippe , Schick Ulrike , Abgral Ronan
Published: April 2023

The main aim of this study was to evaluate the prognostic value of radiomic approach in pre-therapeutic18F-fluorodeoxyglucose positron-emission tomography (FDG-PET/CT) in a large cohort of patients with gastro-esophageal junction cancer (GEJC). This was a retrospective monocenter study including 97 consecutive patients with GEJC who underwent a pre-therapeutic FDG-PET and were followed up for 3 years. Standard first-order radiomic PET indices including SUVmax, SUVmean, SUVpeak, MTV and TLG and 32 textural features (TFs) were calculated using LIFEx software on PET imaging. Prognostic significance of these parameters was assessed in univariate and multivariate analysis. Relapse-free survival (RFS) and overall survival (OS) were respectively chosen as primary and secondary endpoints. An internal validation cohort was used by randomly drawing one-third of included patients. The main characteristics of this cohort were: median age of 65 years [41–88], sex ratio H/F = 83/14, 81.5% of patients with a histopathology of adenocarcinoma and 43.3% with a stage IV disease. The median follow-up was 28.5 months [4.2–108.5]. Seventy-seven (79.4%) patients had locoregional or distant progression or recurrence and 71 (73.2%) died. In univariate analysis, SUVmean, Histogram-Entropy and 2 TFs (GLCM-Homogeneity and GLCM-Energy) were significantly correlated with RFS and OS, as well as 2 others TFs (GLRLM-LRE and GLRLM-GLNU) with OS only. In multivariate analysis, Histogram-Entropy remained an independent prognostic factor of both RFS and OS whereas SUVmeanwas an independent prognostic factor of OS only. These results were partially confirmed in our internal validation cohort of 33 patients. Our results suggest that radiomic approach reveals independent prognostic factors for survival in patients with GEJC.
Novel Google Maps and Google Earth application for chemical industry disaster risk assessment during complex emergencies in Eastern Ukraine
Authors: Gan Rick Kye , Bruni Emanuele , Castro Delgado Rafael , Alsua Carlos , Arcos González Pedro
Published: April 2023

The war in Ukraine has led to complex emergencies, humanitarian crises, and other severe consequences, such as chemical industry disasters. The chemical industry is one of the principal sectors of Ukraine’s economy. In 2019, Ukraine had a total volume of hazardous chemical accumulation of more than a 5.1billion tons. Therefore, an attack on chemical industrial facilities will lead to catastrophic consequences such as chemical disasters. This paper aims to study the disaster risk of chemical industrial facilities and its effects on public health and the environment during complex emergencies in Eastern Ukraine. Observational cross-sectional risk assessment method was utilized to assess hazard, vulnerability, and exposure of the chemical industry in Eastern Ukraine in Donetsk Oblast and Luhansk Oblast. Data on chemical factories in Eastern Ukraine was collected on Google Maps and Google Earth on May 2022. Lastly, the semi-quantitative risk assessment method was utilized to describe the risk from the perspective of consequences for life and health, the environment, property, and speed of development. Our disaster risk assessment found more than 1 million people (1,187,240 people) in Donetsk Oblast and more than 350 thousand people (353,716 people) in Luhansk Oblast are exposed to potential hazards from the chemical facilities clusters. The aggregation risk of bombardment of chemical facilities cluster in Eastern Ukraine is also high due to ongoing war. Therefore, the chemical industry disaster risks for Eastern Ukraine during complex emergencies in Donetsk Oblast and Luhansk Oblast are high in terms of likelihood and consequences to life and health, environment, property, and speed of development.
Response of varied rice genotypes on cell membrane stability, defense system, physio-morphological traits and yield under transplanting and aerobic cultivation
Authors: Zayed Bassiouni A. , Ghazy Hasnaa A. , Negm Mahrous E. , Bassiouni Sherif M. , Hadifa Adel A. , El-Sharnobi Dalia E. , Abdelhamed Mohamed M. , Abo-Marzoka Elsayed A. , Okasha Amira M. , Elsayed Salah , Farooque Aitazaz A. , Yaseen Zaher Mundher
Published: April 2023

Aerobic rice cultivation progresses water productivity, and it can save almost 50% of irrigation water compared to lowland rice with the appropriate development of genotypes and management practices. Two field trials were conducted during 2020, and 2021 seasons to determine the validation of different rice varieties under aerobic cultivation based on their plant defense system, physio-morphological traits, stress indices, grain yield, and water productivity. The experiments were designed in a split-plot design with four replications. Two planting methods, transplanting and aerobic cultivation, were denoted as the main plots, and ten rice genotypes were distributed in the subplots. The results revealed that the planting method varied significantly in all measured parameters. The transplanting method with well watering had the highest value of all measured parameters except leaf rolling, membrane stability index, antioxidant, proline, and the number of unfilled grains. EHR1, Giza179 and GZ9399 as well as A22 genotypes a chief more antioxidant defense system that operated under aerobic conditions. Giza179, EHR1, GZ9399, and Giza178 showed high cell membrane stability and subsequently high validation under such conditions, and also showed efficiency in decreasing water consumption and improving water use efficiency. In conclusion, this study proves that Giza179, EHR1, GZ9399, Giza178, and A22 are valid genotypes for aerobic conditions.
Electrophysiological, emotional and behavioural responses of female targets of sexual objectification
Authors: Monachesi Bianca , Deruti Alice , Grecucci Alessandro , Vaes Jeroen
Published: April 2023

Sexual objectification and the interiorized objectifying gaze (self-objectification) are dangerous phenomena for women’s psychological wellness. However, their specific effects on women’s socio-affective reactions are still poorly understood, and their neural activity has never been explored before. In the present study, we investigated women’s emotional and electrophysiological responses during simulated computer-based objectifying social interactions, and we examined consequent punishing behaviours towards the perpetrator using the ultimatum game. Behavioural results (N = 36) showed that during objectifying encounters women generally felt angrier/disgusted and tended to punish the perpetrator in later interactions. However, the more the women self-objectified, the more they felt ashamed (p = 0.011) and tended to punish the perpetrators less (p = 0.008). At a neural level (N = 32), objectifying interactions modulated female participants’ neural signal elicited during the processing of the perpetrator, increasing early (N170) and later (EPN, LPP) ERP components. In addition, only the amplitude of the LPP positively correlated with shame (p = 0.006) and the level of self-objectification (p = 0.018). This finding provides first evidence for the specific time-course of sexual objectification, self-objectification and its associated shame response, and proves that emotional and social consequences of sexual objectification in women may depend on their tendency to self-objectify.
First continuous marine sponge cell line established
Authors: Hesp Kylie , van der Heijden Jans M. E. , Munroe Stephanie , Sipkema Detmer , Martens Dirk E. , Wijffels Rene H. , Pomponi Shirley A.
Published: April 2023

The potential of sponge-derived chemicals for pharmaceutical applications remains largely unexploited due to limited available biomass. Although many have attempted to culture marine sponge cells in vitro to create a scalable production platform for such biopharmaceuticals, these efforts have been mostly unsuccessful. We recently showed that Geodia barretti sponge cells could divide rapidly in M1 medium. In this study we established the first continuous marine sponge cell line, originating from G. barretti. G. barretti cells cultured in OpM1 medium, a modification of M1, grew more rapidly and to a higher density than in M1. Cells in OpM1 reached 1.74 population doublings after 30 min, more than twofold higher than the already rapid growth rate of 0.74 population doublings in 30 min in M1. The maximum number of population doublings increased from 5 doublings in M1 to at least 98 doublings in OpM1. Subcultured cells could be cryopreserved and used to inoculate new cultures. With these results, we have overcome a major obstacle that has blocked the path to producing biopharmaceuticals with sponge cells at industrial scale for decades.
Ablation of TRPC3 disrupts Ca2+ signaling in salivary ductal cells and promotes sialolithiasis
Authors: Choi Bok-Eum , Shin Samuel , Evans Sade , Singh Brij B. , Bandyopadhyay Bidhan C.
Published: April 2023

Clinical studies and structural analyses of salivary stones strongly suggest a linkage between higher saliva calcium (Ca2+) and salivary stone formation, sialolithiasis; however, the process and the mechanism leading to Ca2+ overload during sialolithiasis is not well understood. Here, we show that TRPC3 null (−/−) mice presented with a reduction in Ca2+ entry and current in ductal cells with higher saliva [Ca2+] suggesting diminished transepithelial Ca2+ flux across the salivary ductal cells, leaving more Ca2+ in ductal fluid. Significantly, we found that TRPC3 was expressed in mice and human salivary ductal cells, while intraductal stones were detected in both mice (TRPC3−/−) and patient (sialolithiasis) salivary glands. To identify the mechanism, we found that TRPC3 was crucial in preventing the expression of calcification genes (BMP2/6, Runx2) in ductal cells which may be due to higher extracellular Ca2+ in SMG tissues. Similarly, inflammatory (IL6, NLRP3), fibrotic (FN1, TGFβ1) and apoptotic (Bax1/Bcl2) markers were also elevated, suggesting that the loss of TRPC3 induces genetic changes that leads to salivary gland cell death and induction of inflammatory response. Overall, ablation of TRPC3−/− leads to higher saliva [Ca2+], along with elevated detrimental gene expressions, altogether contributing to salivary gland stone formation.
A moderated mediation analysis of the association between smoking and suicide attempts among adolescents in 28 countries
Authors: Peprah Prince , Asare Bernard Yeboah-Asiamah , Okwei Reforce , Agyemang-Duah Williams , Osafo Joseph , Kretchy Irene A. , Gyasi Razak M.
Published: April 2023

Globally, evidence has shown that many adolescents are victims of substance use, mainly cigarette smoking, and it has been associated with suicidal ideation. However, the mechanisms underlying this association are poorly understood. This study examines whether truancy mediates and gender moderates the association of cigarette smoking with suicide attempts among adolescents in 28 countries. Data from the Global School-Based Student Health Survey were used. Hierarchical multiple logistic regression analyses were used to estimate the effect-modification of gender on cigarette smoking and suicide attempt. The mediating effect of truancy on the association between cigarette smoking and suicidal attempt was assessed using the generalized decomposition method. Cigarette smoking was associated with suicide attempts after adjusting for several confounding variables (aOR = 1.21; 95% CI = 1.09–1.33). The bootstrap results from the generalized decomposition analysis indicated that truancy partially mediated the association of cigarette smoking with a suicide attempt, contributing 21% of the total effect among in-school adolescents. Hierarchical regression analyses suggested that gender moderated the effect of cigarette smoking on suicidal attempts: female adolescents who smoked had 36% higher odds of suicidal attempts compared to male adolescents. The findings suggest possible pathways for designing and implementing interventions to address adolescents' cigarette smoking and truancy to prevent suicidal attempts.
Electron–phonon interaction toward engineering carrier mobility of periodic edge structured graphene nanoribbons
Authors: Hsu Teng-Chin , Wu Bi-Xian , Lin Rong-Teng , Chien Chia-Jen , Yeh Chien-Yu , Chang Tzu-Hsuan
Published: April 2023

Graphene nanoribbons have many extraordinary electrical properties and are the candidates for semiconductor industry. In this research, we propose a design of Coved GNRs with periodic structure ranged from 4 to 8 nm or more, of which the size is within practical feature sizes by advanced lithography tools. The carrier transport properties of Coved GNRs with the periodic coved shape are designed to break the localized electronic state and reducing electron–phonon scattering. In this way, the mobility of Coved GNRs can be enhanced by orders compared with the zigzag GNRs in same width. Moreover, in contrast to occasional zero bandgap transition of armchair and zigzag GNRs without precision control in atomic level, the Coved GNRs with periodic edge structures can exclude the zero bandgap conditions, which makes practical the mass production process. The designed Coved-GNRs is fabricated over the Germanium (110) substrate where the graphene can be prepared in the single-crystalline and single-oriented formants and the edge of GNRs is later repaired under "balanced condition growth" and we demonstrate that the propose coved structures are compatible to current fabrication facility.
Live 4D-OCT denoising with self-supervised deep learning
Authors: Nienhaus Jonas , Matten Philipp , Britten Anja , Scherer Julius , Höck Eva , Freytag Alexander , Drexler Wolfgang , Leitgeb Rainer A. , Schlegl Thomas , Schmoll Tilman
Published: April 2023

By providing three-dimensional visualization of tissues and instruments at high resolution, live volumetric optical coherence tomography (4D-OCT) has the potential to revolutionize ophthalmic surgery. However, the necessary imaging speed is accompanied by increased noise levels. A high data rate and the requirement for minimal latency impose major limitations for real-time noise reduction. In this work, we propose a low complexity neural network for denoising, directly incorporated into the image reconstruction pipeline of a microscope-integrated 4D-OCT prototype with an A-scan rate of 1.2 MHz. For this purpose, we trained a blind-spot network on unpaired OCT images using a self-supervised learning approach. With an optimized U-Net, only a few milliseconds of additional latency were introduced. Simultaneously, these architectural adaptations improved the numerical denoising performance compared to the basic setup, outperforming non-local filtering algorithms. Layers and edges of anatomical structures in B-scans were better preserved than with Gaussian filtering despite comparable processing time. By comparing scenes with and without denoising employed, we show that neural networks can be used to improve visual appearance of volumetric renderings in real time. Enhancing the rendering quality is an important step for the clinical acceptance and translation of 4D-OCT as an intra-surgical guidance tool.
Unveiling the paths of COVID-19 in a large city based on public transportation data
Authors: Araújo Jorge L. B. , Oliveira Erneson A. , Lima Neto Antonio S. , Andrade José S. , Furtado Vasco
Published: April 2023

Human mobility plays a key role in the dissemination of infectious diseases around the world. However, the complexity introduced by commuting patterns in the daily life of cities makes such a role unclear, especially at the intracity scale. Here, we propose a multiplex network fed with 9 months of mobility data with more than 107 million public bus validations in order to understand the relation between urban mobility and the spreading of COVID-19 within a large city, namely, Fortaleza in the northeast of Brazil. Our results suggest that the shortest bus rides in Fortaleza, measured in the number of daily rides among all neighborhoods, decreased$$\approx 25$$≈25% more than the longest ones after an epidemic wave. Such a result is the opposite of what has been observed at the intercity scale. We also find that mobility changes among the neighborhoods are synchronous and geographically homogeneous. Furthermore, we find that the most central neighborhoods in mobility are the first targets for infectious disease outbreaks, which is quantified here in terms of the positive linear relation between the disease arrival time and the average of the closeness centrality ranking. These central neighborhoods are also the top neighborhoods in the number of reported cases at the end of an epidemic wave as indicated by the exponential decay behavior of the disease arrival time in relation to the number of accumulated reported cases with decay constant$$\lambda \approx 33$$λ≈33days. We believe that these results can help in the development of new strategies to impose restriction measures in the cities guiding decision-makers with smart actions in public health policies, as well as supporting future research on urban mobility and epidemiology.
Pyrazole-sulfonamide scaffold featuring dual-tail strategy as apoptosis inducers in colon cancer
Authors: El-Hazek Reham M. M. , Zaher Nashwa H. , Emam Hagar E. S. , El-Gazzar Marwa G. , Khalil Amira
Published: April 2023

Dual-tail strategy has been successfully utilized in the development of novel carbonic anhydrase IX (CA IX) inhibitors. Herein we adopted this approach in the design and synthesis of a series of novel pyridine sulfonamide-pyrazole hybrid scaffold mimicking dual-tail inhibitors of CA IX. A library of 15 compounds was synthesized and assessed for their potential cytotoxic effects against colorectal cancer cells. Compounds 3, and 11 induced potential cytotoxic effects against the three cancer cell lines (HCT-116, HT-29, and SW-620) with IC50s’ of 45.88, 28.27, and 16.57 uM, 25.01, 8.99, and 3.27 µM, respectively. Both compounds induced cellular apoptosis on HCT-116 and SW-620 cells, while compound 3 induced necrosis as well. In addition, both compounds induced cell cycle arrest on G0/G1, and S phases. Also, compound 11 showed potential autophagy induction on both colon cancer cell lines (HCT-116, and HT-29), and a little bit on metastatic type. Both compounds were less cytotoxic than the reference drug on normal epithelial cell. The migration rates of HCT-116 and the metastatic one SW-620 were reduced by both compounds. Finally, molecular docking of compounds 3 and 11 into the active site of CA IX confirmed in vitro inhibitory activity for both compounds.
Measurement and simulation of irrigation performance in continuous and surge furrow irrigation using WinSRFR and SIRMOD models
Authors: Radmanesh Mojgan , Ahmadi Seyed Hamid , Sepaskhah Ali Reza
Published: April 2023

The SIRMOD and WinSRFR models were used to model and assess the irrigation performance under continuous and surge irrigation strategies with two furrow lengths of 70 m and 90 m and stream sizes of 0.4 l/s and 0.6 l/s for each length. According to the normalized root mean squared error (NRMSE) and the relative error (RE), WinSRFR had, on average, excellent accuracy in the continuous and surge irrigation for simulating advance-recession times (NRMSE: 6.15 and 4.24% for advance time, and 2.20 and 5.20% for recession time), infiltrated water depth (NRMSE: 3.37 and 6.38%), and runoff volume (RE: 6.93 and 2.57%), respectively. SIRMOD had also, on average, excellent simulation in the continuous and surge irrigation for advance-recession times (NRMSE: 3.34 and 2.45% for advance time, and 2.28 and 6.41% for recession time), infiltrated water depth (NRMSE: 2.98 and 5.27%), and runoff volume (RE: 5.31 and 17.49%), respectively. The average of irrigation application efficiency (AE), distribution uniformity (DU), deep percolation (DP), and tail-water ratio (TWR) were 61.50, 90.25, 11.75, and 26.75% in continuous irrigation, and 72.03, 94.09, 8.39, and 19.57% in surge irrigation, respectively, which shows that surge irrigation increased AE (irrigation management performance) and DU (irrigation method performance) and reduced DP and TWR compared to continuous irrigation. Moreover, longer furrow lengths increased AE and DP under both irrigation methods, while it decreased TWR and DU. However, increasing the stream size decreased AE and DP and increased TWR under both continuous and surge irrigations. The higher stream size improved DU in continuous irrigation but reduced DU in surge irrigation. The results confirmed that both SIRMOD and WinSRFR are reliable analytical tools to evaluate furrow irrigation strategies for improving irrigation management. In conclusion, this study showed that surface irrigation models could be employed in practice by irrigation engineers and practitioners to design and define the optimized furrow length and stream size in arid and semi-arid areas where efficient and high performance irrigation strategies are required to save water and reduce water loss.
Calibrating contact parameters of typical rotary tillage components cutting soil based on different simulation methods
Authors: Zhang Xiongye , Zhang Lixin , Hu Xue , Wang Huan , Shi Xuebin
Published: April 2023

This report analyzes the problem of complex soil movement patterns under the action of coupled forces, such as tension and shear, in agricultural processes and aims to improve the accuracy of contact parameters used in discrete element simulation studies of rototiller-soil interactions. This study focuses on the soil of Shihezi cotton field in the 8th division of Xinjiang and investigates the rotating tiller roller as a soil-touching component of tillage machinery. A combination of simulations and physical testing is used. We perform angle of repose tests and use edge detection, fitting, and other image processing methods to automatically, quickly, and accurately detect the soil accumulation and angle calibration of the contact parameters with soil particles. Additionally, soil slip tests are conducted to calibrate the contact parameters between the soil and the rotary blades. Optimization is achieved based on orthogonal simulations and the Box-Behnken response surface method using physically measured values as the target. A regression model of the stacking angle and rolling friction angle is established to determine the optimal combination of simulation contact parameters: between soil and soil, the recovery coefficient is 0.402, static friction coefficient is 0.621, and rolling friction coefficient is 0.078; between soil contact parts and soil, the recovery coefficient is 0.508, static friction coefficient is 0.401, and rolling friction coefficient is 0.2. Furthermore, the calibration parameters are selected as contact parameters for the discrete element simulation. By combining the above two simulation methods to analyze and compare the simulation process of cutting soil from rototiller roller parts to rototiller single blade parts, we obtained the changes in energy, cutting resistance, and soil particle movement at different depths of the soil cutting process. Finally, the average cutting resistance was used as an index for validation in the field tests. The measured value is 0.96 kN and the error of the discrete element simulation is 13%. This demonstrates the validity of the calibrated contact parameters and the accuracy of the simulation, which can provide a theoretical reference and technical support for the study of the interaction mechanisms between of tillage equipment parts and soil, as well as the design and optimization of these interactions in the future.
Social aspects of collision avoidance: a detailed analysis of two-person groups and individual pedestrians
Authors: Gregorj Adrien , Yücel Zeynep , Zanlungo Francesco , Feliciani Claudio , Kanda Takayuki
Published: April 2023

Pedestrian groups are commonly found in crowds but research on their social aspects is comparatively lacking. To fill that void in literature, we study the dynamics of collision avoidance between pedestrian groups (in particular dyads) and individual pedestrians in an ecological environment, focusing in particular on (i) how such avoidance depends on the group’s social relation (e.g. colleagues, couples, friends or families) and (ii) its intensity of social interaction (indicated by conversation, gaze exchange, gestures etc). By analyzing relative collision avoidance in the “center of mass” frame, we were able to quantify how much groups and individuals avoid each other with respect to the aforementioned properties of the group. A mathematical representation using a potential energy function is proposed to model avoidance and it is shown to provide a fair approximation to the empirical observations. We also studied the probability that the individuals disrupt the group by “passing through it” (termed as intrusion). We analyzed the dependence of the parameters of the avoidance model and of the probability of intrusion on groups’ social relation and intensity of interaction. We confirmed that the stronger social bonding or interaction intensity is, the more prominent collision avoidance turns out. We also confirmed that the probability of intrusion is a decreasing function of interaction intensity and strength of social bonding. Our results suggest that such variability should be accounted for in models and crowd management in general. Namely, public spaces with strongly bonded groups (e.g. a family-oriented amusement park) may require a different approach compared to public spaces with loosely bonded groups (e.g. a business-oriented trade fair).
The correlation between high-density lipoprotein cholesterol and bone mineral density in adolescents: a cross-sectional study
Authors: Wang Gao-Xiang , Li Jun-Tong , Liu De-Liang , Chu Shu-Fang , Li Hui-Lin , Zhao Heng-Xia , Fang Ze-Bin , Xie Wei
Published: April 2023

Recent studies have shown a correlation between high-density lipoprotein cholesterol (HDL-C) and bone mineral density (BMD) in adults, but their relationship is unclear in adolescents. This study aimed to explore whether a correlation existed between them among adolescents aged 12–19. Data analyzed in our study was fetched from the National Health and Nutrition Examination Survey (NHANES) database 2011–2018. The relationship between HDL-C level and total BMD value was analyzed by multivariate logistic regression models, fitted smoothing curves, and generalized additive models. 3770 participants participated in this analysis. After adjusting for all relevant covariates involved in this study, we found a negative correlation between HDL-C levels and total bone density in male adolescents.Furthermore, the stratified analysis showed that all covariables-adjusted models retained the negative correlation excepting female, black, or Mexican American subgroups. An inverted U-shaped curve represented the correlation of HDL-C and total BMD among adolescents aged 16 to 19, and the turning point was 1.06 mmol/L. After adjusting for all relevant covariates involved in this study, the study found a negative correlation between HDL-C levels and total BMD in male adolescents aged 12 to 19, particularly among those of races other than Black and Mexican. There was a saturation effect between HDL-C level and total BMD in 16–19-year-old adolescents. The turning point was 1.06 mmol/L. Therefore, HDL-C might be a biomarker to detect bone health and further perform a more detailed examination.
Explainable artificial intelligence-based prediction of poor neurological outcome from head computed tomography in the immediate post-resuscitation phase
Authors: Kawai Yasuyuki , Kogeichi Yohei , Yamamoto Koji , Miyazaki Keita , Asai Hideki , Fukushima Hidetada
Published: April 2023

Predicting poor neurological outcomes after resuscitation is important for planning treatment strategies. We constructed an explainable artificial intelligence-based prognostic model using head computed tomography (CT) scans taken immediately within 3 h of resuscitation from cardiac arrest and compared its predictive accuracy with that of previous methods using gray-to-white matter ratio (GWR). We included 321 consecutive patients admitted to our institution after resuscitation for out-of-hospital cardiopulmonary arrest with circulation resumption over 6 years. A machine learning model using head CT images with transfer learning was used to predict the neurological outcomes at 1 month. These predictions were compared with the predictions of GWR for multiple regions of interest in head CT using receiver operating characteristic (ROC)-area under curve (AUC) and precision recall (PR)-AUC. The regions of focus were visualized using a heatmap. Both methods had similar ROC-AUCs, but the machine learning model had a higher PR-AUC (0.73 vs. 0.58). The machine learning-focused area of interest for classification was the boundary between gray and white matter, which overlapped with the area of focus when diagnosing hypoxic– ischemic brain injury. The machine learning model for predicting poor outcomes had superior accuracy to conventional methods and could help optimize treatment.