bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic regulation of Neuregulin 1 promotes breast cancer progression associated to hyperglycemia
Authors: Lee Changhu , Kim Min , Park Chanho , Jo Woobeen , Seo Jeong Kon , Kim Sahee , Oh Jiyoung , Kim Chu-Sook , Ryu Han Suk , Lee Kyung-Hun , Park Jiyoung
Published: January 2023

Hyperglycemia is a risk factor for breast cancer-related morbidity and mortality. Hyperglycemia inducesNeuregulin 1(Nrg1) overexpression in breast cancer, which subsequently promotes tumor progression. However, molecular mechanisms underlying hyperglycemia-inducedNrg1overexpression remain poorly understood. Here, we show that hyperglycemia causes active histone modifications at theNrg1enhancer, forming enhanceosome complexes where recombination signal binding protein for immunoglobulin kappa J region (RBPJ), E1A binding protein p300 (P300), and SET domain containing 1 A (SETD1A) are recruited to upregulate Nrg1 expression. Deletions in RBPJ-binding sites causes hyperglycemia-controlledNrg1levels to be downregulated, resulting in decreased tumor growth in vitro and in vivo. Mice with modest-temporary hyperglycemia, induced by low-dose short-exposure streptozotocin, display accelerated tumor growth and lapatinib resistance, whereas combining lapatinib with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S42 phenylglycine t-butyl ester (DAPT) ameliorates tumor growth under these modest hyperglycemic conditions by inhibiting NOTCH and EGFR superfamilies. NOTCH activity is correlated withNRG1levels, and highNRG1levels predicts poor outcomes, particularly in HER2-positive breast cancer patients. Our findings highlight the hyperglycemia-linked epigenetic modulation ofNRG1as a potential therapeutic strategy for treating breast cancer patients with diabetes.
A chromosome-level genome assembly of Plantago ovata
Authors: Herliana Lina , Schwerdt Julian G. , Neumann Tycho R. , Severn-Ellis Anita , Phan Jana L. , Cowley James M. , Shirley Neil J. , Tucker Matthew R. , Bianco-Miotto Tina , Batley Jacqueline , Watson-Haigh Nathan S. , Burton Rachel A.
Published: January 2023

Plantago ovatais cultivated for production of its seed husk (psyllium). When wet, the husk transforms into a mucilage with properties suitable for pharmaceutical industries, utilised in supplements for controlling blood cholesterol levels, and food industries for making gluten-free products. There has been limited success in improving husk quantity and quality through breeding approaches, partly due to the lack of a reference genome. Here we constructed the first chromosome-scale reference assembly ofP. ovatausing a combination of 5.98 million PacBio and 636.5 million Hi-C reads. We also used corrected PacBio reads to estimate genome size and transcripts to generate gene models. The final assembly covers ~ 500 Mb with 99.3% gene set completeness. A total of 97% of the sequences are anchored to four chromosomes with an N50 of ~ 128.87 Mb. TheP. ovatagenome contains 61.90% repeats, where 40.04% are long terminal repeats. We identified 41,820 protein-coding genes, 411 non-coding RNAs, 108 ribosomal RNAs, and 1295 transfer RNAs. This genome will provide a resource for plant breeding programs to, for example, reduce agronomic constraints such as seed shattering, increase psyllium yield and quality, and overcome crop disease susceptibility.
SPITFIR(e): a supermaneuverable algorithm for fast denoising and deconvolution of 3D fluorescence microscopy images and videos
Authors: Prigent Sylvain , Nguyen Hoai-Nam , Leconte Ludovic , Valades-Cruz Cesar Augusto , Hajj Bassam , Salamero Jean , Kervrann Charles
Published: January 2023

Modern fluorescent microscopy imaging is still limited by the optical aberrations and the photon budget available in the specimen. A direct consequence is the necessity to develop flexible and “off-road” algorithms in order to recover structural details and improve spatial resolution, which is critical when restraining the illumination to low levels in order to limit photo-damages. Here, we report SPITFIR(e) a flexible method designed to accurately and quickly restore 2D–3D fluorescence microscopy images and videos (4D images). We designed a generic sparse-promoting regularizer to subtract undesirable out-of-focus background and we developed a primal-dual algorithm for fast optimization. SPITFIR(e) is a ”swiss-knife” method for practitioners as it adapts to any microscopy techniques, to various sources of signal degradation (noise, blur), to variable image contents, as well as to low signal-to-noise ratios. Our method outperforms existing state-of-the-art algorithms, and is more flexible than supervised deep-learning methods requiring ground truth datasets. The performance, the flexibility, and the ability to push the spatiotemporal resolution limit of sub-diffracted fluorescence microscopy techniques are demonstrated on experimental datasets acquired with various microscopy techniques from 3D spinning-disk confocal up to lattice light sheet microscopy.
Automated monitoring of honey bees with barcodes and artificial intelligence reveals two distinct social networks from a single affiliative behavior
Authors: Gernat Tim , Jagla Tobias , Jones Beryl M. , Middendorf Martin , Robinson Gene E.
Published: January 2023

Barcode-based tracking of individuals is revolutionizing animal behavior studies, but further progress hinges on whether in addition to determining an individual’s location, specific behaviors can be identified and monitored. We achieve this goal using information from the barcodes to identify tightly bounded image regions that potentially show the behavior of interest. These image regions are then analyzed with convolutional neural networks to verify that the behavior occurred. When applied to a challenging test case, detecting social liquid transfer (trophallaxis) in the honey bee hive, this approach yielded a 67% higher sensitivity and an 11% lower error rate than the best detector for honey bee trophallaxis so far. We were furthermore able to automatically detect whether a bee donates or receives liquid, which previously required manual observations. By applying our trophallaxis detector to recordings from three honey bee colonies and performing simulations, we discovered that liquid exchanges among bees generate two distinct social networks with different transmission capabilities. Finally, we demonstrate that our approach generalizes to detecting other specific behaviors. We envision that its broad application will enable automatic, high-resolution behavioral studies that address a broad range of previously intractable questions in evolutionary biology, ethology, neuroscience, and molecular biology.
Effect and mechanism of apelin on lipopolysaccharide induced acute pulmonary vascular endothelial barrier dysfunction
Authors: Huang Tianpeng , Chen Danyang , Ye Wei , Chen Wenwen , Zhang Min , Hao Jiale , Xu Licong , Bai Xiaoqing , Mao Sunzhong
Published: January 2023

Vascular endothelial barrier dysfunction is the most prominent manifestation and important cause of mortality in infectious acute lung injury (ALI). Exogenous apelin is effective in ameliorating lipopolysaccharide (LPS)-induced inflammatory response in ALI lungs, reducing exudation of lung tissue and decreasing mortality. This study set out to investigate the association between apelin and Friend leukemia integration-1 (Fli-1) in the prevention and treatment of ALI, and to elucidate the molecular mechanism by which apelin protects the permeability of the vascular endothelial barrier. At the vivo functional level, lung wet/dry weight ratio was used to detect whole lung permeability, evans blue assay and dual fluorescent protein tracking assay were used to detect lung vascular endothelial permeability, HE staining to observe the inflammatory status of lung tissue, and immunofluorescence staining for VE-cadherin expression levels in blood vessels. The changes in inflammatory factors in bronchoalveolar lavage fluid (BALF) were detected by ELASA. Western blot was used to detect the expression level of proteins. qRT-PCR was performed to detect changes in mRNA expression of Fli-1 and adherent junction-related proteins. The correlation analysis of Fli-1 with vascular endothelial permeability and SRC showed that Fli-1 participated in the process of ALI. After preventive and therapeutic treatment of ALI mice with exogenous apelin, Fli-1, APJ, VE-cadherin, phosphorylated-VE-cadherin (p-VE-cadherin) and β-catenin were up-regulated, while SRC, phosphorylated-SRC (p-SRC), VEGF and VEGF-R were down-regulated, which indicated that the stability of vascular endothelial barrier was enhanced. With the use of Fli-1 inhibitor irinotecan, the protective effect of apelin was weakened in various functional indexes, genes and proteins. The lung was maintained at the level of the injury. Our research shows that Fli-1 is involved in the LPS-induced ALI process. The molecular mechanism for apelin in preventing endothelial barrier dysfunction in ALI is through up-regulating Fli-1, thus regulating adherens junction-related proteins, and finally recovering the endothelial barrier function.
Women with familial hypercholesterolemia phenotype are undertreated and poorly controlled compared to men
Authors: Zamora Alberto , Ramos Rafel , Comas-Cufi Marc , García-Gil María , Martí-Lluch Ruth , Plana Nuria , Alves-Cabratosa Lia , Ponjoan Anna , Rodríguez-Borjabad Celia , Ibarretxe Daiana , Roman-Degano Irene , Marrugat Jaume , Elosua Roberto , Martín-Urda Anabel , Masana Lluis
Published: January 2023

Familial hypercholesterolemia (FH) is an autosomal dominant disease that has a prevalence of approximately 1/250 inhabitants and is the most frequent cause of early coronary heart disease (CHD). We included 1.343.973 women and 1.210.671 men with at least one LDL-c measurement from the Catalan primary care database. We identified 14.699 subjects with Familial hypercholesterolemia-Phenotype (FH-P) based on LDL-c cut-off points by age (7.033 and 919 women, and 5.088 and 1659 men in primary and secondary prevention, respectively). Lipid lower therapy (LLT), medication possession ratio (MPR) as an indicator of adherence, and number of patients that reached their goal on lipid levels were compared by sex. In primary and secondary prevention, 69% and 54% of women (P = 0.001) and 64% and 51% of men (P = 0.001) were on low-to-moderate-potency LLT. Adherence to LLT was reduced in women older than 55 years, especially in secondary prevention (P = 0.03), where the percentage of women and men with LDL-c > 1.81 mmol/L were 99.9% and 98.9%, respectively (P = 0.001). Women with FH-P are less often treated with high-intensity LLT, less adherent to LLT, and have a lower probability of meeting their LDL-c goals than men, especially in secondary prevention.
TOR1B: a predictor of bone metastasis in breast cancer patients
Authors: Nguyen Minh Nam , Akter Salima , Akhter Hajara , Ansary Shahina , Han Sunhee , Shin Yoonhwa , Ha Joohun , Kang Insug , Kim Sung Soo , Choi Tae Gyu
Published: January 2023

Recent therapeutic advances in breast cancer (BC) have improved survival outcomes; however, the prognosis for patients with bone metastasis (BM) remains poor. Hence, novel clinical biomarkers are needed to accurately predict BC BM as well as to promote personalized medicine. Here, we discovered a novel biomarker, TOR1B, for BM in BC patients via analysis of BC gene expression data and clinical information downloaded from open public databases. In cancer cells, we found high expression levels of TOR1B in the nucleus and endoplasmic reticulum. Regarding gene expression, the level of TOR1B was significantly upregulated in BC patients with BM (p < 0.05), and the result was externally validated. In addition, gene expression clearly demonstrated two distinct types of prognoses in ER- and PR-positive patients. In multivariate regression, the gene could be an independent predictor of BM in BC patients, i.e., a low expression level of TOR1B was associated with delayed metastasis to bone in BC patients (HR, 0.28; 95% CI 0.094–0.84). Conclusively, TOR1B might be a useful biomarker for predicting BM; specifically, patients with ER- and PR-positive subtypes would benefit from the clinical use of this promising prognostic biomarker.
Product progression: a machine learning approach to forecasting industrial upgrading
Authors: Albora Giambattista , Pietronero Luciano , Tacchella Andrea , Zaccaria Andrea
Published: January 2023

Economic complexity methods, and in particular relatedness measures, lack a systematic evaluation and comparison framework. We argue that out-of-sample forecast exercises should play this role, and we compare various machine learning models to set the prediction benchmark. We find that the key object to forecast is the activation of new products, and that tree-based algorithms clearly outperform both the quite strong auto-correlation benchmark and the other supervised algorithms. Interestingly, we find that the best results are obtained in a cross-validation setting, when data about the predicted country was excluded from the training set. Our approach has direct policy implications, providing a quantitative and scientifically tested measure of the feasibility of introducing a new product in a given country.
CMOS-compatible ising machines built using bistable latches coupled through ferroelectric transistor arrays
Authors: Mallick Antik , Zhao Zijian , Bashar Mohammad Khairul , Alam Shamiul , Islam Md Mazharul , Xiao Yi , Xu Yixin , Aziz Ahmedullah , Narayanan Vijaykrishnan , Ni Kai , Shukla Nikhil
Published: January 2023

Realizing compact and scalable Ising machines that are compatible with CMOS-process technology is crucial to the effectiveness and practicality of using such hardware platforms for accelerating computationally intractable problems. Besides the need for realizing compact Ising spins, the implementation of the coupling network, which describes the spin interaction, is also a potential bottleneck in the scalability of such platforms. Therefore, in this work, we propose an Ising machine platform that exploits the novel behavior of compact bi-stable CMOS-latches (cross-coupled inverters) as classical Ising spins interacting through highly scalable and CMOS-process compatible ferroelectric-HfO2-based Ferroelectric FETs (FeFETs) which act as coupling elements. We experimentally demonstrate the prototype building blocks of this system, and evaluate the scaling behavior of the system using simulations. Our work not only provides a pathway to realizing CMOS-compatible designs but also to overcoming their scaling challenges.
Screening and validating of endogenous reference genes in Chlorella sp. TLD 6B under abiotic stress
Authors: Zhou Yongshun , Meng Fanze , Han Kai , Zhang Kaiyue , Gao Jianfeng , Chen Fulong
Published: January 2023

Chlorella sp. TLD 6B, a microalgae growing in the Taklamakan Desert, Xinjiang of China, is a good model material for studying the physiological and environmental adaptation mechanisms of plants in their arid habitats, as its adaptation to the harsh desert environment has led to its strong resistance. However, when using real-time quantitative polymerase chain reaction (RT-qPCR) to analyze the gene expression of this algae under abiotic stress, it is essential to find the suitable endogenous reference genes so to obtain reliable results. This study assessed the expression stability of 9 endogenous reference genes of Chlorella sp. TLD 6B under four abiotic stresses (drought, salt, cold and heat). These genes were selected based on the analysis results calculated by the three algorithmic procedures of geNorm, NormFinder, and BestKeeper, which were ranked by refinder. Our research showed that 18S and GTP under drought stress, 18S and IDH under salt stress, CYP and 18S under cold stress, GTP and IDH under heat stress were the most stable endogenous reference genes. Moreover, UBC and 18S were the most suitable endogenous reference gene combinations for all samples. In contrast, GAPDH and α-TUB were the two least stable endogenous reference genes in all experimental samples. Additionally, the selected genes have been verified to be durable and reliable by detecting POD and PXG3 genes using above endogenous reference genes. The identification of reliable endogenous reference genes guarantees more accurate RT-qPCR quantification for Chlorella sp. TLD 6B, facilitating functional genomics studies of deserts Chlorella as well as the mining of resistance genes.
The effects of distractors on brightness perception based on a spiking network
Authors: Liu Weisi , Liu Xinsheng
Published: January 2023

Visual perception can be modified by the surrounding context. Particularly, experimental observations have demonstrated that visual perception and primary visual cortical responses could be modified by properties of surrounding distractors. However, the underlying mechanism remains unclear. To simulate primary visual cortical activities in this paper, we design a k-winner-take-all (k-WTA) spiking network whose responses are generated through probabilistic inference. In simulations, images with the same target and various surrounding distractors perform as stimuli. Distractors are designed with multiple varying properties, including the luminance, the sizes and the distances to the target. Simulations for each varying property are performed with other properties fixed. Each property could modify second-layer neural responses and interactions in the network. To the same target in the designed images, the modified network responses could simulate distinguishing brightness perception consistent with experimental observations. Our model provides a possible explanation of how the surrounding distractors modify primary visual cortical responses to induce various brightness perception of the given target.
On the inverse problem in optical coherence tomography
Authors: Macdonald Callum M. , Arridge Simon R. , Munro Peter R. T.
Published: January 2023

We examine the inverse problem of retrieving sample refractive index information in the context of optical coherence tomography. Using two separate approaches, we discuss the limitations of the inverse problem which lead to it being ill-posed, primarily as a consequence of the limited viewing angles available in the reflection geometry. This is first considered from the theoretical point of view of diffraction tomography under a weak scattering approximation. We then investigate the full non-linear inverse problem using a variational approach. This presents another illustration of the non-uniqueness of the solution, and shows that even the non-linear (strongly scattering) scenario suffers a similar fate as the linear problem, with the observable spatial Fourier components of the sample occupying a limited support. Through examples we demonstrate how the solutions to the inverse problem compare when using the variational and diffraction-tomography approaches.
Combined evaluation of audiology examination and self-reported symptoms in patients with hyperacusis
Authors: Huang Yu , Xiang Tao , Jiang Fan , Ren Jing , Xu Tao , Lai Dan
Published: January 2023

To investigate the application of combined audiological examination and a self-reported symptoms survey in the evaluation of hyperacusis. Patients who visited the outpatient department of Otolaryngology Head and Neck Surgery and Otological medicine, Affiliated Hospital of Southwest Medical University, from January 2019 to March 2021 were divided into a hyperacusis group and a normal control group. We measured the loudness discomfort level (LDL) and hearing threshold (HT) of the subjects and investigated their self-reported symptoms. We compared the demographic characteristics, loudness discomfort level, and hearing threshold of the two groups and analyzed the self-reported symptoms and audiological characteristics of hyperacusis. We considered 87 subjects, comprising 40 patients with hyperacusis and 47 healthy individuals. Among the hyperacusis patients, bilateral disease was predominant. Among them, 33 were females, 23 had hearing loss, and 20 had tinnitus. Patients are mainly in the 21–60 age group. Patients with hyperacusis had low discomfort thresholds at all frequencies except 500 Hz (P ≤ 0.05, mean LDL decreased by 6.14–1.37 dB HL for all frequencies). The incidences of feeling upset, pain, and anxiety or fear were 95%, 65%, and 82.5%, respectively, in patients with hyperacusis. The severity of symptoms varies between patients with hyperacusis and healthy individuals. A combination of LDL measurements and self-reported symptom surveys allows for an accurate and comprehensive assessment of hyperacusis.

Trial registration: This study was retrospectively registered (TRN: ChiCTR2100047391) on June 13, 2021.
Multidecadal fluctuations in green turtle hatchling production related to climate variability
Authors: del Monte-Luna Pablo , Nakamura Miguel , Guzmán-Hernández Vicente , Cuevas Eduardo , López-Castro Melania C. , Arreguín-Sánchez Francisco
Published: January 2023

The state of Campeche, Mexico, harbors one of the largest green turtle (Chelonia mydas) rookeries of the Wider Caribbean Region. Since the 1970s, harvesting of this population was common practice, but it has since ceased, and the population is rebounding as a consequence. In this rookery, during the past 37 years (1984–2020), the positive relationship between the annual number of nesting females and the number of hatchlings they produce has revealed a long-term population signal that we postulate could be related to environmental factors. To investigate this relationship more deeply, we adopt a stock-recruitment (SR) approach, which is commonly used in fisheries. Regression analysis methods for the SR relationship, including a dynamic version of the model that incorporates the effect of sea surface temperature, show that the number of recruits produced and the number of hatchlings per unit nester were significantly and inversely correlated with a 26-year cycle of the Atlantic Multidecadal Oscillation (AMO) with a three year lag. A possible explanation for this finding is that environmental conditions during warming periods of the 26-year AMO cycle may negatively affect hatchling production by altering the nest moisture content during the incubation period, and increasing embryonic mortality, while the annual female abundance at nesting beaches may decrease due to trophic effects. The time series of abundance corresponding to other population units of green turtles as well as other species of sea turtles in the Gulf of Mexico present a similar behavior to that evaluated here, suggesting a basin-wide environmental effect.
Psychometric properties of the 12-item Stroke-Specific Quality of Life Scale among stroke survivors in Hong Kong
Authors: Fong Ted C. T. , Lo Temmy L. T. , Ho Rainbow T. H.
Published: January 2023

The present study examined the psychometric properties of the 12-item Stroke-Specific Quality of Life Scale (SSQOL-12) in 184 stroke survivors in Hong Kong. The participants completed a self-report questionnaire including the SSQOL-12, SF-12 health survey, and validating variables at baseline and 148 stroke survivors completed SSQOL-12 two months later. Confirmatory factor analysis investigated the construct validity, reliability, and measurement invariance of SSQOL-12 across two months. Concurrent, convergent, and divergent validity was examined with respect to SF-12, hope, self-esteem, functional disability, anxiety, and depression. The original 2-factor model did not reveal a superior fit over the 1-factor model and a modified 1-factor model provided an acceptable fit to the data in both waves. The SSQOL-12 factor displayed substantial factor loadings (λ = 0.40–0.87), good internal consistency (Ω = 0.88), temporal stability (r = 0.70), and scalar measurement invariance across time. Stroke-specific quality of life was significantly associated with higher levels of SF-12, hope, and self-esteem and lower levels of functional disability, anxiety, and depression. Most correlations remained significant after controlling for demographic covariates and SF-12. The present findings offered empirical support for the validity and reliability of the unidimensional structure for SSQOL-12 as a measure of stroke-specific quality of life among stroke survivors.
Time-dependent microbial shifts during crayfish decomposition in freshwater and sediment under different environmental conditions
Authors: Mähler Bastian , Janssen Kathrin , Lönartz Mara Iris , Lagos Markus , Geisler Thorsten , Rust Jes , Bierbaum Gabriele
Published: January 2023

Fossilization processes and especially the role of bacterial activity during the preservation of organic material has not yet been well understood. Here, we report the results of controlled taphonomic experiments with crayfish in freshwater and sediment. 16S rRNA amplicon analyzes showed that the development of the bacterial community composition over time was correlated with different stages of decay and preservation. Three dominating genera, Aeromonas, Clostridium and Acetobacteroides were identified as the main drivers in the decomposition of crayfish in freshwater. Using micro-computed tomography (µ-CT), scanning electron microscopy (SEM) and confocal Raman spectroscopy (CRS), calcite clusters were detected after 3–4 days inside crayfish carcasses during their decomposition in freshwater at 24 °C. The precipitation of calcite clusters during the decomposition process was increased in the presence of the bacterial genus Proteocatella. Consequently, Proteocatella might be one of the bacterial genera responsible for fossilization.
Anthropogenic impact on soils of protected areas—example of PAHs
Authors: Kicińska Alicja , Dmytrowski Piotr
Published: January 2023

The following study presents the concentrations of 10 individual polycyclic aromatic hydrocarbons (PAHs10) and the total concentration of PAHs (ΣPAHs) determined in soils of protected areas in Southern Poland (EU). The protected areas discussed here include 5 landscape parks and 5 nature reserves located in the Małopolska region. Surface soil samples were collected at 39 locations characterised by different natural conditions and different human pressure level. The samples were used to determine the contents of anthracene, benzo[a]pyrene, benz[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[g,h,i]perylene, chrysene, dibenz[a,h]anthracene, indeno[1,2,3-cd]pyrene and naphthalene. These concentrations of individual PAHs ranged from < 0.005 to 6.34 mg/kg. When considering the legal regulations currently in force, this meant that permissible values were exceeded in 23% of the samples analysed, while increased concentrations were found in another 26% of the samples. The limit values were exceeded most in the case of benzo[b]fluoranthene and benzo[a]pyrene. This occurred with samples collected in the vicinity of transportation routes, mainly local roads. In the case of naphthalene and anthracene, the limit values were not exceeded. Increased or excessive PAHs concentrations do not occur in the vicinity of major industrial plants located near the boundaries of individual landscape parks, which indicates how these pollutants spread. The paper also points to the need to develop new legal solutions to improve the method for assessing PAHs concentrations and their impact on valuable natural areas.
Molecular identification of Cryptosporidium, Giardia, and Blastocystis from stray and household cats and cat owners in Tehran, Iran
Authors: Karimi Poorya , Shafaghi-Sisi Soheila , Meamar Ahmad Reza , Razmjou Elham
Published: January 2023

Cryptosporidiosis, giardiasis, and blastocystosis are among the most important parasitic diseases common between humans and cats. In addition, there are concerns about the possible transmission of zoonotic parasites from infected cats to humans. Hence, we investigated the molecular epidemiology of Cryptosporidium spp., Giardia duodenalis, and Blastocystis sp. in stray and household cats and cat owners. Our study was performed on 132, 33, and 33 fecal samples of stray and household cats, as well as cat owners in Tehran, Iran. Cryptosporidium spp. was identified using a nested PCR targeting the small subunit ribosomal RNA gene (SSU rRNA) and sequencing the internal amplified fragments. Furthermore, to perform multilocus genotyping of G. duodenalis, the ß-giardin (bg), glutamate dehydrogenase (gdh), and triosephosphate isomerase (tpi) genes were amplified to assess the DNA of G. duodenalis in the fecal samples of cats and cat owners. In addition, Blastocystis was detected by targeting the SSU rRNA gene, and the subtypes of Blastocystis were determined via the sequencing of amplicons. Cryptosporidium felis and Cryptosporidium canis were detected in seven stray cats (5.3%) and one household cat (3%). The bg gene of G. duodenalis was amplified and successfully sequenced in two (1.5%) stray cats and revealed assemblages F and B of G. duodenalis. Sequencing and phylogenic analysis of SSU rRNA gene nucleotide sequences of Blastocystis detected ST5 and ST10 in stray cats (1.5%), ST1 in household cats (9.1%), and ST1, ST2, ST3, and ST7 in owners (30.3%). The low prevalence of Cryptosporidium, Giardia and Blastocystis in cats and the presence of species/assemblages/subtypes with limited zoonotic potential indicate that cats had a minor role in their owners' infection in the investigated population. However, the presence of zoonotic protozoa in cats suggests the necessity of special attention to high-risk individuals during close contact with cats. Therefore, it is recommended that veterinarians, physicians, and urban managers plan to prevent, control, or treat these parasites to help the urban community live healthily alongside cats.
Multidisciplinary diagnosis and treatment training simulation by paired teachers using case-based teaching of oral histopathology that promotes clinical thinking
Authors: Wang Shan , Qiu Yanfen
Published: January 2023

The multidisciplinary diagnosis and treatment (MDT) model has significant advantages in the diagnosing and treatment of intricate cases. In addition, it can eliminate subspecialty barriers and provide a more accurate and individualized diagnosis and treatment plan. It has been assumed that the future development of diagnosis and treatment will retain this course, and the MDT is an essential type of clinical thinking, especially for medical students. This study attempted to guide stomatology undergraduates’ thinking via an MDT simulation in oral histopathology practicums through typical case-based education and paired-teachers’ explanations. The aim was to cultivate clinical thinking among students based on individual cases and to improve class participation and students’ clinical thinking ability. Forty-six undergraduates in a 5-year stomatology program who enrolled in 2018 participated in a simulation MDT model. Ten typical clinical cases were selected, and they were previously collected and analyzed by clinicians in accordance with the simulation MDT model and handed out to teachers and students before the class. Two to three cases were interpreted by teacher pairs that included a pathologist (oral pathology teacher) and a radiologist (oral imaging teacher). The rest of the cases were used for simulation MDT student groups in class. The oral pathology teacher and oral imaging teacher illustrated the corresponding data from typical cases in advance. The simulation MDT group members acting as a surgeon, pathologist, or radiologist demonstrated their own cases assigned randomly before the class. A curriculum satisfaction survey illustrated that the simulation MDT group agreed that simulation MDT was novel for them, and they had a strong sense of participation. The mimic MDT training with typical cases guided by paired teachers was useful for establishing student clinical thinking.
Low-volume label-free SARS-CoV-2 detection with the microcavity-based optical fiber sensor
Authors: Janik Monika , Gabler Tomasz , Koba Marcin , Panasiuk Mirosława , Dashkevich Yanina , Łęga Tomasz , Dąbrowska Agnieszka , Naskalska Antonina , Żołędowska Sabina , Nidzworski Dawid , Pyrć Krzysztof , Gromadzka Beata , Śmietana Mateusz
Published: January 2023

Accurate and fast detection of viruses is crucial for controlling outbreaks of many diseases; therefore, to date, numerous sensing systems for their detection have been studied. On top of the performance of these sensing systems, the availability of biorecognition elements specific to especially the new etiological agents is an additional fundamental challenge. Therefore, besides high sensitivity and selectivity, such advantages as the size of the sensor and possibly low volume of analyzed samples are also important, especially at the stage of evaluating the receptor-target interactions in the case of new etiological agents when typically, only tiny amounts of the receptor are available for testing. This work introduces a real-time, highly miniaturized sensing solution based on microcavity in-line Mach–Zehnder interferometer (μIMZI) induced in optical fiber for SARS-CoV-2 virus-like particles detection. The assay is designed to detect conserved regions of the SARS-CoV-2 viral particles in a sample with a volume as small as hundreds of picoliters, reaching the detection limit at the single ng per mL level.
Health risk assessment and metal contamination in fish, water and soil sediments in the East Kolkata Wetlands, India, Ramsar site
Authors: Kumar Neeraj , Chandan Nitish Kumar , Bhushan Shashi , Singh Dilip Kumar , Kumar Satish
Published: January 2023

East Kolkata Wetlands (EKW) is an important site for fish culture in sewage-fed areas, which are major receivers of pollutants and wastages from Kolkata. EKW is internationally important as the Ramsar site was declared on Aug 2002 with an area of 125 km2. EKW is a natural water body where wastewater-fed natural aquaculture has been practiced for more than 70 years. It is ecologically vulnerable due to the discharge of toxic waste through sewage canals from cities. Assessing the EKW to understand the inflow and load of the toxic metal (s) in fish, water, and sediments samples is essential. The field (samples collection from 13 sites) and lab (determination of toxic level of metals) based research were carried out to assess metal toxicity and health risk assessment in EKW. The levels of eighteen metals (18), namely Chromium, Vanadium, Cobalt, Manganese, Copper, Nickel, Zinc, Silver, Molybdenum, Arsenic, Selenium, Tin, Gallium, Germanium, Strontium, Cadmium, Mercury, and Lead, were determined using Inductively coupled plasma mass spectrometry (ICP-MS) in five fish tissues viz. muscle, liver, kidney, gill and brain, along with the water samples and soil sediments in 13 sampling sites. The bioaccumulation and concentration of metals in fish tissues, soil sediments, and water samples were well within the safe level concerning the recommendation of different national and international agencies except for a few metals in a few sampling sites like Cd, As, and Pb. The geoaccumulation index (Igeo) was also determined in the soil sediments, indicating moderate arsenic, selenium, and mercury contamination in a few sites. The contamination index in water was also determined in 13 sampling sites. The estimated daily intake (EDI), reference dose (RfD), target hazard quotient (THQ), slope factor and cancer risk of Cr, Mn, Co, Ni, Cu, Zn, As, Se, Cd, Pb and Hg from fish muscle were determined. Based on the results of the present investigation, it is concluded that fish consumption in the East Kolkata Wetland (EKW) is safe. The effects of bioaccumulation of metals in muscle tissue were well within the safe level for consumption as recommended by WHO/FAO.
LINE-1 ORF1p as a candidate biomarker in high grade serous ovarian carcinoma
Authors: Sato Sho , Gillette Michael , de Santiago Pamela R. , Kuhn Eric , Burgess Michael , Doucette Kristen , Feng Yi , Mendez-Dorantes Carlos , Ippoliti Paul J. , Hobday Sara , Mitchell Marilyn A. , Doberstein Kai , Gysler Stefan M. , Hirsch Michelle S. , Schwartz Lauren , Birrer Michael J. , Skates Steven J. , Burns Kathleen H. , Carr Steven A. , Drapkin Ronny
Published: January 2023

Long interspersed element 1 (LINE-1) open reading frame 1 protein (ORF1p) expression is a common feature of many cancer types, including high-grade serous ovarian carcinoma (HGSOC). Here, we report that ORF1p is not only expressed but also released by ovarian cancer and primary tumor cells. Immuno-multiple reaction monitoring-mass spectrometry assays showed that released ORF1p is confidently detectable in conditioned media, ascites, and patients’ plasma, implicating ORF1p as a potential biomarker. Interestingly, ORF1p expression is detectable in fallopian tube (FT) epithelial precursors of HGSOC but not in benign FT, suggesting that ORF1p expression in an early event in HGSOC development. Finally, treatment of FT cells with DNA methyltransferase inhibitors led to robust expression and release of ORF1p, validating the regulatory role of DNA methylation in LINE-1 repression in non-tumorigenic tissue.
Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats
Authors: Silva Beatriz , Gonçalves Lídia M. , São Braz Berta , Delgado Esmeralda
Published: January 2023

Topical instillation of drugs targeting the posterior ocular segment is an expanding area of research. Chitosan and hyaluronic acid have remarkable mucoadhesive properties and potentially enhance pre-corneal retention time after topical instillation. Bearing this in mind, we explored the possibility of delivering epoetin beta (EPOβ) to the posterior segment of the eye in a chitosan-hyaluronic acid (CS/HA-EPOβ) nanoparticulate system using the topical route of administration. Complete ophthalmological examinations, electroretinography and microhematocrit evaluations were performed in Wistar Hannover (WH) rats, before and after topical administration of nanoparticles. The right eye received CS/HA-EPOβ and the left eye received only empty nanocarriers (control). Animals were split into 6 groups and at designated timepoints, all animals from each group (n = 3) were euthanized and both eyes enucleated. Retinal morphology and EPOβ ocular distribution were assessed, respectively, through hematoxylin and eosin (HE) and immunofluorescence staining. After topical administration, no adverse ocular signs were noted and no significant changes either in microhematocrits nor in electroretinographies were detected. During the study, intraocular pressure (IOP) was always kept within physiological range bilaterally. No histological changes were detected in any of the ocular globes. Immunofluorescence enabled the identification of EPOβ in the retina 12 h after the administration, its presence still being detectable at day 21. In conclusion, CS/HA nanoparticles could efficiently deliver EPOβ to the retina of WH rats after topical instillation, being considered biologically safe. Topical administration of this nanoformulation could be a valuable tool for retinal neuroprotection, decreasing risks associated with more invasive routes of administration, being cost effective and also increasing long-term patients’ compliance.
Investigation of predictors for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome
Authors: Song Li , Zhao Yingjie , Wang Gang , Zou Wenlu , Sai Lintao
Published: January 2023

Patients with severe fever with thrombocytopenia syndrome (SFTS) had been confirmed to have immune dysfunction and were prone to invasive pulmonary aspergillosis (IPA), which was directly related to the increased mortality. The aim of this study was to investigate the predictors for IPA in SFTS patients, and the results were expected to be helpful for early identification of IPA and initiation of anti-fungal therapy. The study was performed to review laboratory confirmed SFTS patients in two tertiary hospitals in Shandong province (Qilu Hospital of Shandong University and Shandong Public Health Clinical Center) from April 2021 to August 2022. The enrolled patients were further divided into IPA group and non-IPA group. Demographic characteristics, clinical manifestations and laboratory parameters between IPA group and non-IPA group patients were analyzed and compared to identify the independent predictors for IPA by univariate analysis and multivariable logistic regression analysis. Sensitivity and specificity of independent predictors were evaluated by receiver operating characteristic (ROC) curve analysis. In total, 67 SFTS patients were enrolled with an average age of 64.7 (± 8.4) years old. The incidence of IPA was 32.8% (22/67). Mortality of patients in IPA group was 27.3% (6/22), which was significantly higher than that in non-IPA group. Results of univariate analysis showed that uncontrolled diabetes, central nervous system symptoms, platelet < 40 × 109/L, CD4+ T cell < 300/μL and CD8+ T cell < 400/μL were risk factors for development of IPA. These factors were further analyzed by multivariable logistic regression analysis and the results indicated that uncontrolled diabetes, platelet < 40 × 109/L, CD4+ T cell < 300/μL and CD8+ T cell < 400/μL could be recognized as independent predictors for IPA in SFTS patients. In conclusion, IPA is a serious complication for SFTS patients and increases mortality. It is necessary to early identify predictors of IPA for improving survival of SFTS patients.
Germline rare deleterious variant load alters cancer risk, age of onset and tumor characteristics
Authors: Esai Selvan Myvizhi , Onel Kenan , Gnjatic Sacha , Klein Robert J. , Gümüş Zeynep H.
Published: January 2023

Recent studies show that rare, deleterious variants (RDVs) in certain genes are critical determinants of heritable cancer risk. To more comprehensively understand RDVs, we performed the largest-to-date germline variant calling analysis in a case-control setting for a multi-cancer association study from whole-exome sequencing data of 20,789 participants, split into discovery and validation cohorts. We confirm and extend known associations between cancer risk and germline RDVs in specific gene-sets, including DNA repair (OR = 1.50; p-value = 8.30e-07; 95% CI: 1.28–1.77), cancer predisposition (OR = 1.51; p-value = 4.58e-08; 95% CI: 1.30–1.75), and somatic cancer drivers (OR = 1.46; p-value = 4.04e-06; 95% CI: 1.24–1.72). Furthermore, personal RDV load in these gene-sets associated with increased risk, younger age of onset, increased M1 macrophages in tumor and, increased tumor mutational burden in specific cancers. Our findings can be used towards identifying high-risk individuals, who can then benefit from increased surveillance, earlier screening, and treatments that exploit their tumor characteristics, improving prognosis.
Self-recycling and partially conservative replication of mycobacterial methylmannose polysaccharides
Authors: Maranha Ana , Costa Mafalda , Ripoll-Rozada Jorge , Manso José A. , Miranda Vanessa , Mendes Vera M. , Manadas Bruno , Macedo-Ribeiro Sandra , Ventura M. Rita , Pereira Pedro José Barbosa , Empadinhas Nuno
Published: January 2023

The steep increase in nontuberculous mycobacteria (NTM) infections makes understanding their unique physiology an urgent health priority. NTM synthesize two polysaccharides proposed to modulate fatty acid metabolism: the ubiquitous 6-O-methylglucose lipopolysaccharide, and the 3-O-methylmannose polysaccharide (MMP) so far detected in rapidly growing mycobacteria. The recent identification of a unique MMP methyltransferase implicated the adjacent genes in MMP biosynthesis. We report a wide distribution of this gene cluster in NTM, including slowly growing mycobacteria such as Mycobacterium avium, which we reveal to produce MMP. Using a combination of MMP purification and chemoenzymatic syntheses of intermediates, we identified the biosynthetic mechanism of MMP, relying on two enzymes that we characterized biochemically and structurally: a previously undescribed α–endomannosidase that hydrolyses MMP into defined-sized mannoligosaccharides that prime the elongation of new daughter MMP chains by a rare α-(1→4)-mannosyltransferase. Therefore, MMP biogenesis occurs through a partially conservative replication mechanism, whose disruption affected mycobacterial growth rate at low temperature.
Suspicions of two bridgehead invasions of Xylella fastidiosa subsp. multiplex in France
Authors: Dupas Enora , Durand Karine , Rieux Adrien , Briand Martial , Pruvost Olivier , Cunty Amandine , Denancé Nicolas , Donnadieu Cécile , Legendre Bruno , Lopez-Roques Céline , Cesbron Sophie , Ravigné Virginie , Jacques Marie-Agnès
Published: January 2023

Of American origin, a wide diversity of Xylella fastidiosa strains belonging to different subspecies have been reported in Europe since 2013 and its discovery in Italian olive groves. Strains from the subspecies multiplex (ST6 and ST7) were first identified in France in 2015 in urban and natural areas. To trace back the most probable scenario of introduction in France, the molecular evolution rate of this subspecies was estimated at 3.2165 × 10-7 substitutions per site per year, based on heterochronous genome sequences collected worldwide. This rate allowed the dating of the divergence between French and American strains in 1987 for ST6 and in 1971 for ST7. The development of a new VNTR-13 scheme allowed tracing the spread of the bacterium in France, hypothesizing an American origin. Our results suggest that both sequence types were initially introduced and spread in Provence-Alpes-Côte d’Azur (PACA); then they were introduced in Corsica in two waves from the PACA bridgehead populations.
Fetal temporal sulcus depth asymmetry has prognostic value for language development
Authors: Bartha-Doering Lisa , Kollndorfer Kathrin , Schwartz Ernst , Fischmeister Florian Ph.S. , Langs Georg , Weber Michael , Lackner-Schmelz Sonja , Kienast Patric , Stümpflen Marlene , Taymourtash Athena , Mandl Sophie , Alexopoulos Johanna , Prayer Daniela , Seidl Rainer , Kasprian Gregor
Published: January 2023

In most humans, the superior temporal sulcus (STS) shows a rightward depth asymmetry. This asymmetry can not only be observed in adults, but is already recognizable in the fetal brain. As the STS lies adjacent to brain areas important for language, STS depth asymmetry may represent an anatomical marker for language abilities. This study investigated the prognostic value of STS depth asymmetry in healthy fetuses for later language abilities, language localization, and language-related white matter tracts. Less right lateralization of the fetal STS depth was significantly associated with better verbal abilities, with fetal STS depth asymmetry explaining more than 40% of variance in verbal skills 6–13 years later. Furthermore, less right fetal STS depth asymmetry correlated with increased left language localization during childhood. We hypothesize that earlier and/or more localized fetal development of the left temporal cortex is accompanied by an earlier development of the left STS and is favorable for early language learning. If the findings of this pilot study hold true in larger samples of healthy children and in different clinical populations, fetal STS asymmetry has the potential to become a diagnostic biomarker of the maturity and integrity of neural correlates of language.
The impact of secondary channels on the wetting properties of interconnected hydrophobic nanopores
Authors: Paulo Gonçalo , Gubbiotti Alberto , Grosu Yaroslav , Meloni Simone , Giacomello Alberto
Published: January 2023

Pores in nanoporous materials can be interconnected in different ways; preliminary evidence exists that connecting channels can affect the overall hydrophobicity of the material thus providing an additional parameter in designing applications that require controlled wetting properties. In this work, we show that the length of secondary channels is a key parameter to tune the overall hydrophobicity of the material: short secondary channels make the main pore effectively more hydrophilic than a simple cylindrical pore, while long secondary channels enhance its hydrophobicity, producing the macroscopic effect of superhydrophobic textures. This rich behavior is rooted in the spontaneous filling of the secondary channels, which is unexpected based on classical capillarity. This length-dependent filling is explained by the formation of hydrogen bonds bridging the main pores which becomes less frequent with longer channels. These findings could be useful for designing nanoporous materials with tailored wetting properties.