bluuebunny/crossref_metadata_2025 huggingface dataset:
Nowhere to run: oligo (p-phenylene vinylene) kills oral intracellular bacteria photodynamically
Authors: Yuan Lintian , Fu Xuancheng , Yu Wen , Wei Huagen , dong Fan , Zhang Ludan , Wang Guiyan , Dong Huihua , Lv Fengting , Wang Yuguang
Published: July 2023

Bacterial infections pose a severe threat to human health due to the exacerbation of antibiotic resistance and intracellular bacterial infections. Research suggests that oligo(p-phenylene vinylene) (OPV), commonly employed in the manufacture of organic solar batteries, can help address this issue. This study demonstrates the ability of OPV to target and sterilize intracellular Porphyromonas gingivalis and methicillin-resistant Staphylococcus aureus (MRSA) photodynamically. Most notably, OPV specifically targets bacteria without affecting healthy cells under dark conditions. Its chemical composition includes a conjugated backbone and ionic imidazole side chains, which allow OPV to bind to cell membranes. Furthermore, dental blue light curing lamps may excite OPV. Compared with antibiotics and traditional photosensitizers, OPV proves to be a potentially superior solution to eradicate intracellular microbial infections, both in fundamental research and clinical applications.
The default network dominates neural responses to evolving movie stories
Authors: Yang Enning , Milisav Filip , Kopal Jakub , Holmes Avram J. , Mitsis Georgios D. , Misic Bratislav , Finn Emily S. , Bzdok Danilo
Published: July 2023

Neuroscientific studies exploring real-world dynamic perception often overlook the influence of continuous changes in narrative content. In our research, we utilize machine learning tools for natural language processing to examine the relationship between movie narratives and neural responses. By analyzing over 50,000 brain images of participants watching Forrest Gump from the studyforrest dataset, we find distinct brain states that capture unique semantic aspects of the unfolding story. The default network, associated with semantic information integration, is the most engaged during movie watching. Furthermore, we identify two mechanisms that underlie how the default network liaises with the amygdala and hippocampus. Our findings demonstrate effective approaches to understanding neural processes in everyday situations and their relation to conscious awareness.
Engineering broad-spectrum inhibitors of inflammatory chemokines from subclass A3 tick evasins
Authors: Devkota Shankar Raj , Aryal Pramod , Pokhrel Rina , Jiao Wanting , Perry Andrew , Panjikar Santosh , Payne Richard J. , Wilce Matthew C. J. , Bhusal Ram Prasad , Stone Martin J.
Published: July 2023

Chemokines are key regulators of leukocyte trafficking and attractive targets for anti-inflammatory therapy. Evasins are chemokine-binding proteins from tick saliva, whose application as anti-inflammatory therapeutics will require manipulation of their chemokine target selectivity. Here we describe subclass A3 evasins, which are unique to the tick genus Amblyomma and distinguished from “classical” class A1 evasins by an additional disulfide bond near the chemokine recognition interface. The A3 evasin EVA-AAM1001 (EVA-A) bound to CC chemokines and inhibited their receptor activation. Unlike A1 evasins, EVA-A was not highly dependent on N- and C-terminal regions to differentiate chemokine targets. Structures of chemokine-bound EVA-A revealed a deep hydrophobic pocket, unique to A3 evasins, that interacts with the residue immediately following the CC motif of the chemokine. Mutations to this pocket altered the chemokine selectivity of EVA-A. Thus, class A3 evasins provide a suitable platform for engineering proteins with applications in research, diagnosis or anti-inflammatory therapy.
Genetic strategies for sex-biased persistence of gut microbes across human life
Authors: Tarracchini Chiara , Alessandri Giulia , Fontana Federico , Rizzo Sonia Mirjam , Lugli Gabriele Andrea , Bianchi Massimiliano Giovanni , Mancabelli Leonardo , Longhi Giulia , Argentini Chiara , Vergna Laura Maria , Anzalone Rosaria , Viappiani Alice , Turroni Francesca , Taurino Giuseppe , Chiu Martina , Arboleya Silvia , Gueimonde Miguel , Bussolati Ovidio , van Sinderen Douwe , Milani Christian , Ventura Marco
Published: July 2023

Although compositional variation in the gut microbiome during human development has been extensively investigated, strain-resolved dynamic changes remain to be fully uncovered. In the current study, shotgun metagenomic sequencing data of 12,415 fecal microbiomes from healthy individuals are employed for strain-level tracking of gut microbiota members to elucidate its evolving biodiversity across the human life span. This detailed longitudinal meta-analysis reveals host sex-related persistence of strains belonging to common, maternally-inherited species, such as Bifidobacterium bifidum and Bifidobacterium longum subsp. longum. Comparative genome analyses, coupled with experiments including intimate interaction between microbes and human intestinal cells, show that specific bacterial glycosyl hydrolases related to host-glycan metabolism may contribute to more efficient colonization in females compared to males. These findings point to an intriguing ancient sex-specific host-microbe coevolution driving the selective persistence in women of key microbial taxa that may be vertically passed on to the next generation.
Tumor-agnostic ctDNA levels by mFAST-SeqS in first-line HR-positive, HER2 negative metastatic breast cancer patients as a biomarker for survival
Authors: Verschoor Noortje , de Weerd Vanja , Van Mai N. , Kraan Jaco , Smid Marcel , Heijns Joan B. , Drooger Jan C. , Zuetenhorst Johanna M. , van der Padt-Pruijsten Annemieke , Jager Agnes , Sleijfer Stefan , Martens John W. M. , Wilting Saskia M.
Published: July 2023

This prospective cohort study reports aneuploidy score by mFast-SeqS as a strong prognostic marker in MBC patients. mFAST-SeqS is an affordable and easily implementable method for the assessment of total ctDNA levels and, as such, provides an alternative prognostic tool. One mixed cohort (cohort A, n = 45) starting any type of treatment in any line of therapy and one larger cohort (cohort B, n = 129) consisting of patients starting aromatase inhibitors (AI) as first-line therapy were used. mFAST-SeqS was performed using plasma of blood in which CTCs (CellSearch) were enumerated. The resulting aneuploidy score was correlated with categorized CTC count and associated with outcome. The aneuploidy score was significantly correlated with CTC count, but discordance was observed in 31.6% when applying cut-offs of 5. In both cohorts, aneuploidy score was a significant prognostic marker for both PFS and OS. In the Cox regression models, the HR for aneuploidy score for PFS was 2.52 (95% CI: 1.56–4.07), and the HR for OS was 2.37 (95% CI: 1.36–4.14). Results presented here warrant further investigations into the clinical utility of this marker in MBC patients.
Quantum advantages for transportation tasks - projectiles, rockets and quantum backflow
Authors: Trillo David , Le Thinh P. , Navascués Miguel
Published: July 2023

Consider a scenario where a quantum particle is initially prepared in some bounded region of space and left to propagate freely. After some time, we verify if the particle has reached some distant target region. We find that there exist ‘ultrafast’ (‘ultraslow’) quantum states, whose probability of arrival is greater (smaller) than that of any classical particle prepared in the same region with the same momentum distribution. For both projectiles and rockets, we prove that the quantum advantage, quantified by the difference between the quantum and optimal classical arrival probabilities, is limited by the Bracken-Melloy constant cbm, originally introduced to study the phenomenon of quantum backflow. In this regard, we substantiate the 29-year-old conjecture that cbm ≈ 0.038 by proving the bounds 0.0315 ≤ cbm ≤ 0.072. Finally, we show that, in a modified projectile scenario where the initial position distribution of the particle is also fixed, the quantum advantage can reach 0.1262.
A geopositioned and evidence-graded pan-species compendium of Mayaro virus occurrence
Authors: Celone Michael , Potter Alexander M. , Han Barbara A. , Beeman Sean P. , Okech Bernard , Forshey Brett , Dunford James , Rutherford George , Mita-Mendoza Neida K. , Estallo Elizabet Lilia , Khouri Ricardo , de Siqueira Isadora Cristina , Petersen Kyle , Maves Ryan C. , Anyamba Assaf , Pollett Simon
Published: July 2023

Mayaro Virus (MAYV) is an emerging health threat in the Americas that can cause febrile illness as well as debilitating arthralgia or arthritis. To better understand the geographic distribution of MAYV risk, we developed a georeferenced database of MAYV occurrence based on peer-reviewed literature and unpublished reports. Here we present this compendium, which includes both point and polygon locations linked to occurrence data documented from its discovery in 1954 until 2022. We describe all methods used to develop the database including data collection, georeferencing, management and quality-control. We also describe a customized grading system used to assess the quality of each study included in our review. The result is a comprehensive, evidence-graded database of confirmed MAYV occurrence in humans, non-human animals, and arthropods to-date, containing 262 geo-positioned occurrences in total. This database - which can be updated over time - may be useful for local spill-over risk assessment, epidemiological modelling to understand key transmission dynamics and drivers of MAYV spread, as well as identification of major surveillance gaps.
Ecological correlation between short term exposure to particulate matter and hospitalization for mental disorders in Shijiazhuang, China
Authors: Wang Lan , Gao Xian , Wang Ran , Song Mei , Liu Xiaoli , Wang Xueyi , An Cuixia
Published: July 2023

The associations between particulate matter (PM) and overall and specific mental disorders (MDs) are investigated using data from two general hospitals in Shijiazhuang, China, from January 2014 to December 2019. A longitudinal time series study, as one type of ecological study, is conducted using a generalized additive model to examine the relationship between short-term exposure to PM2.5, PM10, and daily hospital admissions for MDs, and further stratification by subtypes, age, and gender. A total of 10,709 cases of hospital admissions for MDs have been identified. The significant short-time effects of PM2.5 on overall MDs at lag01 and PM10 at lag05 are observed, respectively. For specific mental disorders, there are substantial associations of PM pollution with mood disorders and organic mental disorders. PM2.5 has the greatest cumulative effect on daily admissions of mood disorders and organic mental disorders in lag01, and PM 10 has the greatest cumulative effect in lag05. Moreover, the effect modification by sex or age is statistically significant, with males and the elderly (≥ 45 years) having a stronger effect. Short-term exposure to PM2.5 and PM10can be associated with an increased risk of daily hospital admissions for MDs.
Learning models for classifying Raman spectra of genomic DNA from tumor subtypes
Authors: Lancia Giacomo , Durastanti Claudio , Spitoni Cristian , De Benedictis Ilaria , Sciortino Antonio , Cirillo Emilio N. M. , Ledda Mario , Lisi Antonella , Convertino Annalisa , Mussi Valentina
Published: July 2023

An early and accurate detection of different subtypes of tumors is crucial for an effective guidance to personalized therapy and in predicting the ability of tumor to metastasize. Here we exploit the Surface Enhanced Raman Scattering (SERS) platform, based on disordered silver coated silicon nanowires (Ag/SiNWs), to efficiently discriminate genomic DNA of different subtypes of melanoma and colon tumors. The diagnostic information is obtained by performing label free Raman maps of the dried drops of DNA solutions onto the Ag/NWs mat and leveraging the classification ability of learning models to reveal the specific and distinct physico-chemical interaction of tumor DNA molecules with the Ag/NW, here supposed to be partly caused by a different DNA methylation degree.
Mitogenomes revealed the history of bison colonization of Northern Plains after the Last Glacial Maximum
Authors: Ovchinnikov Igor V. , McCann Blake
Published: July 2023

American bison demonstrated differential patterns of extinction, survival, and expansion since the terminal Pleistocene. We determined population dynamics of the Northern Great Plains bison using 40 mitochondrial genomes from radiocarbon dated remains with the age ranging from 12,226 to 167 calibrated years before present. Population dynamics correlated with environmental and anthropogenic factors and was characterized by three primary periods: terminal Pleistocene population growth starting 14,000 years ago, mid Holocene demographic stability between 6700 and 2700 years ago, and late Holocene population decline in the last 2700 years. Most diversification of mtDNA haplotypes occurred in the early Holocene when bison colonized new territories opened by retreating ice sheets. Holocene mtDNA lineages were not found in modern bison and lacked association with archaeological sites and morphological forms.
Molecular dissection and testing of PRSS37 function through LC–MS/MS and the generation of a PRSS37 humanized mouse model
Authors: Sutton Courtney , Nozawa Kaori , Kent Katarzyna , Saltzman Alexander , Leng Mei , Nagarajan Sureshbabu , Malovannaya Anna , Ikawa Masahito , Garcia Thomas X. , Matzuk Martin M.
Published: July 2023

The quest for a non-hormonal male contraceptive pill for men still exists. Serine protease 37 (PRSS37) is a sperm-specific protein that when ablated in mice renders them sterile. In this study we sought to examine the molecular sequelae of PRSS37 loss to better understand its molecular function, and to determine whether human PRSS37 could rescue the sterility phenotype of knockout (KO) mice, allowing for a more appropriate model for drug molecule testing. To this end, we used CRISPR-EZ to create mice lacking the entire coding region of Prss37, used pronuclear injection to create transgenic mice expressing human PRSS37, intercrossed these lines to generate humanized mice, and performed LC–MS/MS of KO and control tissues to identify proteomic perturbances that could attribute a molecular function to PRSS37. We found that our newly generated Prss37 KO mouse line is sterile, our human transgene rescues the sterility phenotype of KO mice, and our proteomics data not only yields novel insight into the proteome as it evolves along the male reproductive tract, but also demonstrates the proteins significantly influenced by PRSS37 loss. In summary, we report vast biological insight including insight into PRSS37 function and the generation of a novel tool for contraceptive evaluation.
Monolayer organic thin films as particle-contamination–resistant coatings
Authors: Jia Ruobin , Hoffman Brittany N. , Kozlov Alexei V. , Demos Stavros G. , Shestopalov Alexander A.
Published: July 2023

Three organic monolayers coatings were developed and tested for their effectiveness to increase cleaning efficiency of attached microscale particles by air flows. The experiments were performed using silica substrates coated with these organic thin films and subsequently exposed to stainless-steel and silica microparticles as a model of contamination. Laser-induced–damage tests confirmed that the coatings do not affect the laser-induced–damage threshold values. The particle exposure results suggest that although the accumulation of particles is not significantly affected under the experimental conditions used in this work, the coated substrates exhibit significantly improved cleaning efficiency with a gas flow. A size-distribution analysis was conducted to study the adsorption and cleaning efficiency of particles of different sizes. It was observed that larger size (> 5-μm) particles can be removed from coated substrates with almost 100% efficiency. It was also determined that the coatings improve the cleaning efficiency of the smaller particles (≤ 5 μm) by 17% to 30% for the stainless steel metal and 19% to 38% for the silica particles.
Time series causal relationships discovery through feature importance and ensemble models
Authors: Castro Manuel , Mendes Júnior Pedro Ribeiro , Soriano-Vargas Aurea , de Oliveira Werneck Rafael , Moreira Gonçalves Maiara , Lusquino Filho Leopoldo , Moura Renato , Zampieri Marcelo , Linares Oscar , Ferreira Vitor , Ferreira Alexandre , Davólio Alessandra , Schiozer Denis , Rocha Anderson
Published: July 2023

Inferring causal relationships from observational data is a key challenge in understanding the interpretability of Machine Learning models. Given the ever-increasing amount of observational data available in many areas, Machine Learning algorithms used for forecasting have become more complex, leading to a less understandable path of how a decision is made by the model. To address this issue, we propose leveraging ensemble models, e.g., Random Forest, to assess which input features the trained model prioritizes when making a forecast and, in this way, establish causal relationships between the variables. The advantage of these algorithms lies in their ability to providefeature importance, which allows us to build the causal network. We present our methodology to estimate causality in time series from oil field production. As it is difficult to extract causal relations from a real field, we also included a synthetic oil production dataset and a weather dataset, which is also synthetic, to provide the ground truth. We aim to performcausal discovery, i.e., establish the existing connections between the variables in each dataset. Through an iterative process of improving the forecasting of a target’s value, we evaluate whether the forecasting improves by adding information from a new potential driver; if so, we state that the driver causally affects the target. On the oil field-related datasets, our causal analysis results agree with the interwell connections already confirmed by tracer information; whenever the tracer data are available, we used it as our ground truth. This consistency between both estimated and confirmed connections provides us the confidence about the effectiveness of our proposed methodology. To our knowledge, this is the first time causal analysis using solely production data is employed to discover interwell connections in an oil field dataset.
Immunogenicity of poxvirus-based vaccines against Nipah virus
Authors: Medina-Magües Emily S. , Lopera-Madrid Jaime , Lo Michael K. , Spiropoulou Christina F. , Montgomery Joel M. , Medina-Magües Lex G. , Salas-Quinchucua Cristhian , Jiménez-Mora Angela P. , Osorio Jorge E.
Published: July 2023

Nipah virus (NiV), an emerging zoonotic pathogen in Southeast Asia, is transmitted from Pteropus species of fruit bats to a wide range of species, including humans, pigs, horses, dogs, and cats. NiV has killed millions of animals and caused highly fatal human outbreaks since no vaccine is commercially available. This study characterized the immunogenicity and safety of poxvirus-based Nipah vaccines that can be used in humans and species responsible for NiV transmission. Mice were vaccinated with modified vaccinia Ankara (MVA) and raccoon pox (RCN) viral vectors expressing the NiV fusion (F) and glycoprotein (G) proteins subcutaneously (SC) and intranasally (IN). Importantly, both vaccines did not induce significant weight loss or clinical signs of disease while generating high circulating neutralizing antibodies and lung-specific IgG and IgA responses. The MVA vaccine saw high phenotypic expression of effector and tissue resident memory CD8ɑ+ T cells in lungs and splenocytes along with the expression of central memory CD8ɑ+ T cells in lungs. The RCN vaccine generated effector memory (SC) and tissue resident (IN) CD8ɑ+ T cells in splenocytes and tissue resident (IN) CD8ɑ+ T cells in lung cells. These findings support MVA-FG and RCN-FG viral vectors as promising vaccine candidates to protect humans, domestic animals, and wildlife from fatal disease outcomes and to reduce the global threat of NiV.
Alterations in cortical morphometry of the contralesional hemisphere in children, adolescents, and young adults with perinatal stroke
Authors: Shinde Karan , Craig Brandon T. , Hassett Jordan , Dlamini Nomazulu , Brooks Brian L. , Kirton Adam , Carlson Helen L.
Published: July 2023

Perinatal stroke causes most hemiparetic cerebral palsy and cognitive dysfunction may co-occur. Compensatory developmental changes in the intact contralesional hemisphere may mediate residual function and represent targets for neuromodulation. We used morphometry to explore cortical thickness, grey matter volume, gyrification, and sulcal depth of the contralesional hemisphere in children, adolescents, and young adults after perinatal stroke and explored associations with motor, attention, and executive function. Participants aged 6–20 years (N = 109, 63% male) with unilateral perinatal stroke underwent T1-weighted imaging. Participants had arterial ischemic stroke (AIS; n = 36), periventricular venous infarction (PVI; n = 37) or were controls (n = 36). Morphometry was performed using the Computational Anatomy Toolbox (CAT12). Group differences and associations with motor and executive function (in a smaller subsample) were assessed. Group comparisons revealed areas of lower cortical thickness in contralesional hemispheres in both AIS and PVI and greater gyrification in AIS compared to controls. Areas of greater grey matter volume and sulcal depth were also seen for AIS. The PVI group showed lower grey matter volume in cingulate cortex and less volume in precuneus relative to controls. No associations were found between morphometry metrics, motor, attention, and executive function. Cortical structure of the intact contralesional hemisphere is altered after perinatal stroke. Alterations in contralesional cortical morphometry shown in perinatal stroke may be associated with different mechanisms of damage or timing of early injury. Further investigations with larger samples are required to more thoroughly explore associations with motor and cognitive function.
Thermophilisation of communities differs between land plant lineages, land use types and elevation
Authors: Kiebacher Thomas , Meier Markus , Kipfer Tabea , Roth Tobias
Published: July 2023

Bryophytes provide key ecosystem services at the global scale such as carbon storage and primary production in resource limited habitats, but compared to vascular plants knowledge on how these organisms face recent climate warming is fragmentary. This is particularly critical because bryophytes differ fundamentally from vascular plants in their ecophysiological and biological characteristics, so that community alterations most likely have different dynamics. In a comparative approach, we analysed thermophilisation of bryophyte and vascular plant communities in 1146 permanent plots distributed along an elevational gradient of nearly 3.000 m in Switzerland (Central Europe) that were visited in 5-years intervals between 2001 and 2021. We estimated thermophilisation from changes in unweighted mean temperature indicator values of species, compared it to expected thermophilisation rates given the shift of isotherms and addressed differences between the two lineages, major land use types (managed grasslands, forests, unmanaged open areas), life strategy types (long- and short-lived species) and in elevation. Thermophilisation of bryophyte communities was on average 2.1 times higher than of vascular plant communities and at high elevations it approximated the expected rate given the shift of isotherms. Thermophilisation of both, bryophyte and vascular plant communities was not driven by a loss of cryophilic species but by an increase in thermophilic and mesophilic species, indicating an in-filling process. Furthermore, our data show that thermophilisation is higher in managed grasslands than in forests. We suggest that the higher responsiveness of bryophytes compared to vascular plants depends on their poikilohydry and dispersal capacity and that lower thermophilisation of forests communities is related to the buffering effect of microclimatic conditions in the interior of forests. Our study emphasises the heterogeneity of climate warming effects on plants because response dynamics differ between taxonomic groups as well as between land use types and along elevational gradients.
Evaluating the global, regional, and national impact of syphilis: results from the global burden of disease study 2019
Authors: Chen Tao , Wan Bo , Wang Mingfang , Lin Su , Wu Yinlian , Huang Jiaofeng
Published: July 2023

Syphilis is a global public health concern. This study aimed to assess the global and regional burden of syphilis from 1990 to 2019. Disease burden was evaluated using disability-adjusted life-years (DALYs) and prevalence. Data were extracted from the 2019 global burden of disease Study, an open database available for download. Age-standardized rates (ASR) and estimated annual percentage changes (EAPC) were calculated to evaluate the syphilis burden over time. In 2019, the total number of prevalent cases of syphilis was 49.71 million worldwide. The ASR of prevalence was stable from 1990 to 2019 with an EAPC of 0.00 (95% CI − 0.10–0.11). The number of DALYs caused by syphilis was 7.36 million in 2019, reflecting a reduction of 16.38% compared with that in 1990 (8.80 million). The ASR of DALYs exhibited a decreasing trend from 1990 to 2019 (EAPC =  − 1.01; 95% CI − 1.19 to − 0.84), with the highest rates observed in the younger age group (< 14 years old). In 2019, the highest ASR of DALYs was found in low sociodemographic index (SDI) regions (239.21/100,000), and the lowest in high SDI regions (3.14/100,000). Generally, the ASR of DALYs decreased as the SDI increased. The top three countries with the highest ASR of DALYs for syphilis were the Solomon Islands, Equatorial Guinea, and Liberia. While the global prevalence of syphilis remained persistently high from 1990 to 2019, there has been a recent decrease in the ASR of DALYs. Increased attention should be dedicated to younger populations and regions characterized by low SDIs.
E pluribus unum interpretable convolutional neural networks
Authors: Dimas George , Cholopoulou Eirini , Iakovidis Dimitris K.
Published: July 2023

The adoption of convolutional neural network (CNN) models in high-stake domains is hindered by their inability to meet society’s demand for transparency in decision-making. So far, a growing number of methodologies have emerged for developing CNN models that are interpretable by design. However, such models are not capable of providing interpretations in accordance with human perception, while maintaining competent performance. In this paper, we tackle these challenges with a novel, general framework for instantiating inherently interpretable CNN models, named E pluribus unum interpretable CNN (EPU-CNN). An EPU-CNN model consists of CNN sub-networks, each of which receives a different representation of an input image expressing a perceptual feature, such as color or texture. The output of an EPU-CNN model consists of the classification prediction and its interpretation, in terms of relative contributions of perceptual features in different regions of the input image. EPU-CNN models have been extensively evaluated on various publicly available datasets, as well as a contributed benchmark dataset. Medical datasets are used to demonstrate the applicability of EPU-CNN for risk-sensitive decisions in medicine. The experimental results indicate that EPU-CNN models can achieve a comparable or better classification performance than other CNN architectures while providing humanly perceivable interpretations.
Robust real-time imaging through flexible multimode fibers
Authors: Abdulaziz Abdullah , Mekhail Simon Peter , Altmann Yoann , Padgett Miles J. , McLaughlin Stephen
Published: July 2023

Conventional endoscopes comprise a bundle of optical fibers, associating one fiber for each pixel in the image. In principle, this can be reduced to a single multimode optical fiber (MMF), the width of a human hair, with one fiber spatial-mode per image pixel. However, images transmitted through a MMF emerge as unrecognizable speckle patterns due to dispersion and coupling between the spatial modes of the fiber. Furthermore, speckle patterns change as the fiber undergoes bending, making the use of MMFs in flexible imaging applications even more complicated. In this paper, we propose a real-time imaging system using flexible MMFs, but which is robust to bending. Our approach does not require access or feedback signal from the distal end of the fiber during imaging. We leverage a variational autoencoder to reconstruct and classify images from the speckles and show that these images can still be recovered when the bend configuration of the fiber is changed to one that was not part of the training set. We utilize a MMF 300 mm long with a 62.5 μm core for imaging $$10~\times ~10$$

10

×

10

 cm objects placed approximately at 20 cm from the fiber and the system can deal with a change in fiber bend of 50$$^\circ$$

∘

and range of movement of 8 cm.
Drug resistance profiling of asymptomatic and low-density Plasmodium falciparum malaria infections on Ngodhe island, Kenya, using custom dual-indexing next-generation sequencing
Authors: Osborne Ashley , Phelan Jody E. , Kaneko Akira , Kagaya Wataru , Chan Chim , Ngara Mtakai , Kongere James , Kita Kiyoshi , Gitaka Jesse , Campino Susana , Clark Taane G.
Published: July 2023

Malaria control initiatives require rapid and reliable methods for the detection and monitoring of molecular markers associated with antimalarial drug resistance in Plasmodium falciparum parasites. Ngodhe island, Kenya, presents a unique malaria profile, with lower P. falciparum incidence rates than the surrounding region, and a high proportion of sub-microscopic and low-density infections. Here, using custom dual-indexing and Illumina next generation sequencing, we generate resistance profiles on seventy asymptomatic and low-density P. falciparum infections from a mass drug administration program implemented on Ngodhe island between 2015 and 2016. Our assay encompasses established molecular markers on the Pfcrt, Pfmdr1, Pfdhps, Pfdhfr, and Pfk13 genes. Resistance markers for sulfadoxine-pyrimethamine were identified at high frequencies, including a quintuple mutant haplotype (Pfdhfr/Pfdhps: N51I, C59R, S108N/A437G, K540E) identified in 62.2% of isolates. The Pfdhps K540E biomarker, used to inform decision making for intermittent preventative treatment in pregnancy, was identified in 79.2% of isolates. Several variants on Pfmdr1, associated with reduced susceptibility to quinolones and lumefantrine, were also identified (Y184F 47.1%; D1246Y 16.0%; N86 98%). Overall, we have presented a low-cost and extendable approach that can provide timely genetic profiles to inform clinical and surveillance activities, especially in settings with abundant low-density infections, seeking malaria elimination.
Phytochemical profiling and cytotoxic potential of Arnebia nobilis root extracts against hepatocellular carcinoma using in-vitro and in-silico approaches
Authors: Kiran Asia , Altaf Awais , Sarwar Muhammad , Malik Arif , Maqbool Tahir , Ali Qurban
Published: July 2023

Hepatocellular carcinoma is the fifth most prevalent cancer worldwide. The emergence of drug resistance and other adverse effects in available anticancer options are challenging to explore natural sources. The current study was designed to decipher theArnebia nobilis(A. nobilis) extracts for detecting phytochemicals, in-vitro evaluation of antioxidative and cytotoxic potentials, and in-silico prediction of potent anticancer compounds. The phytochemical analysis revealed the presence of flavonoids, phenols, tannins, alkaloids, quinones, and cardiac glycosides, in the ethanol (ANE) and n-hexane (ANH) extracts ofA. nobilis.ANH extract exhibited a better antioxidant potential to scavenge DPPH, nitric oxide and superoxide anion radicals than ANE extract, which showed better potential only against H2O2radicals. In 24 h treatment, ANH extract revealed higher cytotoxicity (IC50value: 22.77 µg/mL) than ANH extract (IC50value: 46.74 µg/mL) on cancer (HepG2) cells without intoxicating the normal (BHK) cells using MTT assay. A better apoptotic potential was observed in ANH extract (49.10%) compared to ANE extract (41.35%) on HepG2 cells using the annexin V/PI method. GCMS analysis of ANH extract identified 35 phytocompounds, from which only 14 bioactive compounds were selected for molecular docking based on druggability criteria and toxicity filters. Among the five top scorers, deoxyshikonin exhibited the best binding affinities of − 7.2, − 9.2, − 7.2 and − 9.2 kcal/mol against TNF-α, TGF-βR1, Bcl-2 and iNOS, respectively, followed by ethyl cholate and 2-Methyl-6-(4-methylphenyl)hept-2-en-4-one along with their desirable ADMET properties. The phytochemicals of ANH extract could be used as a promising drug candidate for liver cancer after further validations.
Females occasionally create duets with males but they never sing solo-year-round singing behaviour in an Afrotropical songbird
Authors: Budka Michał , Uyeme John Emenike , Osiejuk Tomasz Stanisław
Published: July 2023

Our knowledge of birdsong mainly comes from studies focused on male songs produced in a short breeding period, even though we know that sedentary species sing year-round, female song is quite widespread and many species sing collectively creating duets and choruses. In this study we focused on daily and seasonal changes in singing activity of an endemic, sedentary, duetting, Afrotropical songbird—the Bangwa forest warbler. We collected soundscape recordings in six recording locations and used singing activity index to examine how vocal activity of males and females varies daily and seasonally and how it correlates with the rainfall. We found that Bangwa forest warblers sing year-round, yet they do it more in wet than in dry season. The rapid increase of singing activity occurs after first rain, at the beginning of the rainy season. Males sing significantly more than females. Females never sing solo, however, in 13% of songs they create duets by joining male solos. The pattern of daily singing activity is sex-specific and seasonally variable, with two peaks (dawn and dusk) observed in males and only one in females (dawn). In Bangwa forest warbler male singing behaviour is similar to that of many songbirds, suggesting that territory defence and female attraction as main functions of singing. Females, which create duets and never sing solo may use songs in mate guarding, signalling commitment, resource defence or intersex territory defence. Duets observed year-round may suggest cooperative resource defence. Results of the study show that examining year-round singing behaviour is crucial to fully understand the evolution and functions of male and female songs.
Accuracy of a smart bottle in measuring fluid intake by American football players during pre-season training
Authors: Baker Lindsay B. , Alfred Shelby , Lee Khalil A. , Bonsignore Justina L. , Osterberg Kristin L. , Shepherd Brandon , De Chavez Peter John D. , Bentkovski Kobi
Published: July 2023

Rehydration is important for athlete performance and recovery. However, it can be challenging to follow appropriate fluid replacement practices due in part to difficulties in tracking fluid intake in real time. The purpose of this study was to determine the accuracy of a smart bottle in measuring fluid intake during exercise. Thirty male American football athletes drank from bottles equipped with a smart cap during outdoor pre-season practices (110 ± 30 min; 29.3 ± 3.0 °C; 75 ± 11% rh). The cap technology included optical sensors, microprocessors, batteries, and wireless connectivity that transmitted fluid volume data to a smartphone application in real-time. Reference measurements of fluid intake from the smart bottle were determined by gravimetry followed by conversion to volume using the density of the fluid consumed. There was no significant mean difference in fluid intake between the smart bottle and reference method (1220 ± 371 ml vs. 1236 ± 389 ml, p = 0.39 paired t test). Bland–Altman 95% limits of agreement between methods was − 212 to 180 ml. The smart bottle provided accurate measurements of fluid intake during exercise in real-world field conditions on a group level and within limits of agreement of − 212 to 180 ml (or approximately ± 15% of overall fluid intake) on an individual level.
Development and validation of a nomogram model for predicting chronic kidney disease after liver transplantation: a multi-center retrospective study
Authors: He Zenglei , Lin Yimou , Dong Siyi , Ke Qinghong , Zheng Shusen , Ling Qi
Published: July 2023

Chronic kidney disease (CKD) is a frequent complication after liver transplantation (LT) and associated with poor prognosis. In this study, we retrospectively analyzed 515 adult patients who underwent LT in our center. They were randomly divided into a training set (n = 360) and an internal test set (n = 155). Another 118 recipients in other centers served as external validation set. Univariate and multivariate COX regression analysis were used to determine risk factors. A nomogram model was developed to predict post-LT CKD. The incidence of post-LT CKD in our center was 16.9% (87/515) during a median follow-up time of 22.73 months. The overall survival of recipients with severe CKD (stage IV and V) were significantly lower than those with non or mild CKD (stage III) (p = 0.0015). A nomogram model was established based on recipient’s age, anhepatic phase, estimated glomerular filtration rate and triglyceride levels at 30 days after LT. The calibration curves for post-LT CKD prediction in the nomogram were consistent with the actual observation in both the internal and external validation set. In conclusion, severe post-LT CKD resulted in a significantly reduced survival in liver recipient. The newly established nomogram model had good predictive ability for post-LT CKD.
Multi-decadal variation of ENSO forecast skill since the late 1800s
Authors: Lou Jiale , Newman Matthew , Hoell Andrew
Published: July 2023

Diagnosing El Niño-Southern Oscillation (ENSO) predictability within operational forecast models is hindered by computational expense and the need for initialization with three-dimensional fields generated by global data assimilation. We instead examine multi-year ENSO predictability since the late 1800s using the model-analog technique, which has neither limitation. We first draw global coupled model states from pre-industrial control simulations, from the Coupled Model Intercomparison Project Phase 6, that are chosen to initially match observed monthly sea surface temperature and height anomalies in the Tropics. Their subsequent 36-month model evolution are the hindcasts, whose 20th century ENSO skill is comparable to twice-yearly hindcasts generated by a state-of-the-art European operational forecasting system. Despite the so-called spring predictability barrier, present throughout the record, there is substantial second-year ENSO skill, especially after 1960. Overall, ENSO exhibited notably high values of both amplitude and skill towards the end of the 19th century, and again in recent decades.
Constrained tropical land temperature-precipitation sensitivity reveals decreasing evapotranspiration and faster vegetation greening in CMIP6 projections
Authors: Zhu Boyuan , Cheng Yongzhou , Hu Xuyue , Chai Yuanfang , Berghuijs Wouter R. , Borthwick Alistair G. L. , Slater Louise
Published: July 2023

Over the tropical land surface, accurate estimates of future changes in temperature, precipitation and evapotranspiration are crucial for ecological sustainability, but remain highly uncertain. Here we develop a series of emergent constraints (ECs) by using historical and future outputs from the Coupled Model Inter-comparison Project Phase 6 (CMIP6) Earth System Models under the four basic Shared Socio-economic Pathway scenarios (SSP126, SSP245, SSP370, and SSP585). Results show that the temperature sensitivity to precipitation during 2015–2100, which varies substantially in the original CMIP6 outputs, becomes systematically negative across SSPs after application of the EC, with absolute values between −1.10 °C mm−1 day and −3.52 °C mm−1 day, and with uncertainties reduced by 9.4% to 41.4%. The trend in tropical land-surface evapotranspiration, which was increasing by 0.292 mm yr−1 in the original CMIP6 model outputs, becomes significantly negative (−0.469 mm yr−1) after applying the constraint. Moreover, we find a significant increase of 58.7% in the leaf area index growth rate.
Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function
Authors: Cho Jeong Min , Koh Jung Hun , Kim Seong Geun , Lee Soojin , Kim Yaerim , Cho Semin , Kim Kwangsoo , Kim Yong Chul , Han Seung Seok , Lee Hajeong , Lee Jung Pyo , Joo Kwon Wook , Lim Chun Soo , Kim Yon Su , Kim Dong Ki , Park Sehoon
Published: July 2023

Interleukins (ILs), key cytokine family of inflammatory response, are closely associated with kidney function. However, the causal effect of various ILs on kidney function needs further investigation. Here we show two-sample summary-level Mendelian randomization (MR) analysis that examined the causality between serum IL levels and kidney function. Genetic variants with strong association with serum IL levels were obtained from a previous genome-wide association study meta-analysis. Summary-level data for estimated glomerular filtration rate (eGFR) were obtained from CKDGen database. As a main MR analysis, multiplicative random-effects inverse-variance weighted method was performed. Pleiotropy-robust MR analysis, including MR-Egger with bootstrapped error and weighted median methods, were also implemented. We tested the causal estimates from nine ILs on eGFR traits. Among the results, higher genetically predicted serum IL-1 receptor antagonist level was significantly associated with higher eGFR values in the meta-analysis of CKDGen and the UK Biobank data. In addition, the result was consistent towards eGFR decline phenotype of the outcome database. Otherwise, nonsignificant association was identified between other genetically predicted ILs and eGFR outcome. These findings support the clinical importance of IL-1 receptor antagonist-associated pathway in relation to kidney function in the general individuals, particularly highlighting the importance of IL-1 receptor antagonist.
Crosstalk between KIF1C and PRKAR1A in left atrial myxoma
Authors: Zhou Mengchen , Yao Yan , Wang Xiangyi , Zha Lingfeng , Chen Yilin , Li Yanze , Wang Mengru , Yu Chenguang , Zhou Yingchao , Li Qianqian , Cao Zhubing , Wu Jianfei , Shi Shumei , Jiang Dan , Long Deyong , Wang Jiangang , Wang Qing , Cheng Xiang , Liao Yuhua , Tu Xin
Published: July 2023

Cardiac myxoma (CM) is the most common benign cardiac tumor, and most CMs are left atrial myxomas (LAMs). Six variations of KIF1C, c.899 A > T, c.772 T > G, c.352 A > T, c.2895 C > T, c.3049 G > A, and c.*442_*443dup in left atrial myxoma tissues are identified by whole-exome sequencing (WES) and Sanger sequencing. RNA-seq and function experiments show the reduction of the expression of KIF1C and PRKAR1A caused by rare variations of KIF1C. KIF1C is observed to be located in the nucleus, bind to the promoter region of PRKAR1A, and regulate its transcription. Reduction of KIF1C decreases PRKAR1A expression and activates the PKA, which causes an increase in ERK1/2 phosphorylation and SRC-mediated STAT3 activation, a reduction of CDH1, TP53, CDKN1A, and BAX, and eventually promotes tumor formation both in vitro and in vivo. The results suggest that inhibition of KIF1C promotes the pathogenesis of LAM through positive feedback formed by the crosstalk between KIF1C and PRKAR1A.
Atlasing white matter and grey matter joint contributions to resting-state networks in the human brain
Authors: Nozais Victor , Forkel Stephanie J. , Petit Laurent , Talozzi Lia , Corbetta Maurizio , Thiebaut de Schotten Michel , Joliot Marc
Published: July 2023

Over the past two decades, the study of resting-state functional magnetic resonance imaging has revealed that functional connectivity within and between networks is linked to cognitive states and pathologies. However, the white matter connections supporting this connectivity remain only partially described. We developed a method to jointly map the white and grey matter contributing to each resting-state network (RSN). Using the Human Connectome Project, we generated an atlas of 30 RSNs. The method also highlighted the overlap between networks, which revealed that most of the brain’s white matter (89%) is shared between multiple RSNs, with 16% shared by at least 7 RSNs. These overlaps, especially the existence of regions shared by numerous networks, suggest that white matter lesions in these areas might strongly impact the communication within networks. We provide an atlas and an open-source software to explore the joint contribution of white and grey matter to RSNs and facilitate the study of the impact of white matter damage to these networks. In a first application of the software with clinical data, we were able to link stroke patients and impacted RSNs, showing that their symptoms aligned well with the estimated functions of the networks.
The combined action of the intracellular regions regulates FGFR2 kinase activity
Authors: Lin Chi-Chuan , Wieteska Lukasz , Poncet-Montange Guillaume , Suen Kin Man , Arold Stefan T. , Ahmed Zamal , Ladbury John E.
Published: July 2023

Receptor tyrosine kinases (RTKs) are typically activated through a precise sequence of intracellular phosphorylation events starting with a tyrosine residue on the activation loop (A-loop) of the kinase domain (KD). From this point the mono-phosphorylated enzyme is active, but subject to stringent regulatory mechanisms which can vary dramatically across the different RTKs. In the absence of extracellular stimulation, fibroblast growth factor receptor 2 (FGFR2) exists in the mono-phosphorylated state in which catalytic activity is regulated to allow rapid response upon ligand binding, whilst restricting ligand-independent activation. Failure of this regulation is responsible for pathologic outcomes including cancer. Here we reveal the molecular mechanistic detail of KD control based on combinatorial interactions of the juxtamembrane (JM) and the C-terminal tail (CT) regions of the receptor. JM stabilizes the asymmetric dimeric KD required for substrate phosphorylation, whilst CT binding opposes dimerization, and down-regulates activity. Direct binding between JM and CT delays the recruitment of downstream effector proteins adding a further control step as the receptor proceeds to full activation. Our findings underscore the diversity in mechanisms of RTK oligomerisation and activation.