bluuebunny/crossref_metadata_2025 huggingface dataset:
Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk
Authors: Brandhorst Sebastian , Levine Morgan E. , Wei Min , Shelehchi Mahshid , Morgan Todd E. , Nayak Krishna S. , Dorff Tanya , Hong Kurt , Crimmins Eileen M. , Cohen Pinchas , Longo Valter D.
Published: February 2024

In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging) and increased lymphoid to myeloid ratio: an indicator of immune system age. Based on a validated measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss. Nearly identical findings resulted from  a second clinical study (NCT04150159). Together these results provide initial support for beneficial effects of the FMD on multiple cardiometabolic risk factors and biomarkers of biological age.
Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge
Authors: Hsieh Ching-Lin , Leist Sarah R. , Miller Emily Happy , Zhou Ling , Powers John M. , Tse Alexandra L. , Wang Albert , West Ande , Zweigart Mark R. , Schisler Jonathan C. , Jangra Rohit K. , Chandran Kartik , Baric Ralph S. , McLellan Jason S.
Published: February 2024

Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the need to reformulate COVID-19 vaccines. Here, we rationally engineer the sequence-conserved S2 subunit of the SARS-CoV-2 spike protein and characterize the resulting S2-only antigens. Structural studies demonstrate that the introduction of interprotomer disulfide bonds can lock S2 in prefusion trimers, although the apex samples a continuum of conformations between open and closed states. Immunization with prefusion-stabilized S2 constructs elicits broadly neutralizing responses against several sarbecoviruses and protects female BALB/c mice from mouse-adapted SARS-CoV-2 lethal challenge and partially protects female BALB/c mice from mouse-adapted SARS-CoV lethal challenge. These engineering and immunogenicity results should inform the development of next-generation pan-coronavirus therapeutics and vaccines.
Traffic light optimization with low penetration rate vehicle trajectory data
Authors: Wang Xingmin , Jerome Zachary , Wang Zihao , Zhang Chenhao , Shen Shengyin , Kumar Vivek Vijaya , Bai Fan , Krajewski Paul , Deneau Danielle , Jawad Ahmad , Jones Rachel , Piotrowicz Gary , Liu Henry X.
Published: February 2024

Traffic light optimization is known to be a cost-effective method for reducing congestion and energy consumption in urban areas without changing physical road infrastructure. However, due to the high installation and maintenance costs of vehicle detectors, most intersections are controlled by fixed-time traffic signals that are not regularly optimized. To alleviate traffic congestion at intersections, we present a large-scale traffic signal re-timing system that uses a small percentage of vehicle trajectories as the only input without reliance on any detectors. We develop the probabilistic time-space diagram, which establishes the connection between a stochastic point-queue model and vehicle trajectories under the proposed Newellian coordinates. This model enables us to reconstruct the recurrent spatial-temporal traffic state by aggregating sufficient historical data. Optimization algorithms are then developed to update traffic signal parameters for intersections with optimality gaps. A real-world citywide test of the system was conducted in Birmingham, Michigan, and demonstrated that it decreased the delay and number of stops at signalized intersections by up to 20% and 30%, respectively. This system provides a scalable, sustainable, and efficient solution to traffic light optimization and can potentially be applied to every fixed-time signalized intersection in the world.
Identification of HDV-like theta ribozymes involved in tRNA-based recoding of gut bacteriophages
Authors: Kienbeck Kasimir , Malfertheiner Lukas , Zelger-Paulus Susann , Johannsen Silke , von Mering Christian , Sigel Roland K. O.
Published: February 2024

Trillions of microorganisms, collectively known as the microbiome, inhabit our bodies with the gut microbiome being of particular interest in biomedical research. Bacteriophages, the dominant virome constituents, can utilize suppressor tRNAs to switch to alternative genetic codes (e.g., the UAG stop-codon is reassigned to glutamine) while infecting hosts with the standard bacterial code. However, what triggers this switch and how the bacteriophage manipulates its host is poorly understood. Here, we report the discovery of a subgroup of minimal hepatitis delta virus (HDV)-like ribozymes – theta ribozymes – potentially involved in the code switch leading to the expression of recoded lysis and structural phage genes. We demonstrate their HDV-like self-scission behavior in vitro and find them in an unreported context often located with their cleavage site adjacent to tRNAs, indicating a role in viral tRNA maturation and/or regulation. Every fifth associated tRNA is a suppressor tRNA, further strengthening our hypothesis. The vast abundance of tRNA-associated theta ribozymes – we provide 1753 unique examples – highlights the importance of small ribozymes as an alternative to large enzymes that usually process tRNA 3’-ends. Our discovery expands the short list of biological functions of small HDV-like ribozymes and introduces a previously unknown player likely involved in the code switch of certain recoded gut bacteriophages.
Unsupervised classification of brain-wide axons reveals the presubiculum neuronal projection blueprint
Authors: Wheeler Diek W. , Banduri Shaina , Sankararaman Sruthi , Vinay Samhita , Ascoli Giorgio A.
Published: February 2024

We present a quantitative strategy to identify all projection neuron types from a given region with statistically different patterns of anatomical targeting. We first validate the technique with mouse primary motor cortex layer 6 data, yielding two clusters consistent with cortico-thalamic and intra-telencephalic neurons. We next analyze the presubiculum, a less-explored region, identifying five classes of projecting neurons with unique patterns of divergence, convergence, and specificity. We report several findings: individual classes target multiple subregions along defined functions; all hypothalamic regions are exclusively targeted by the same class also invading midbrain and agranular retrosplenial cortex; Cornu Ammonis receives input from a single class of presubicular axons also projecting to granular retrosplenial cortex; path distances from the presubiculum to the same targets differ significantly between classes, as do the path distances to distinct targets within most classes; the identified classes have highly non-uniform abundances; and presubicular somata are topographically segregated among classes. This study thus demonstrates that statistically distinct projections shed light on the functional organization of their circuit.
Imputation of plasma lipid species to facilitate integration of lipidomic datasets
Authors: Dakic Aleksandar , Wu Jingqin , Wang Tingting , Huynh Kevin , Mellett Natalie , Duong Thy , Beyene Habtamu B. , Magliano Dianna J. , Shaw Jonathan E. , Carrington Melinda J. , Inouye Michael , Yang Jean Y. , Figtree Gemma A. , Curran Joanne E. , Blangero John , Simes John ,   LIPID Study Investigators, Giles Corey , Meikle Peter J.
Published: February 2024

Recent advancements in plasma lipidomic profiling methodology have significantly increased specificity and accuracy of lipid measurements. This evolution, driven by improved chromatographic and mass spectrometric resolution of newer platforms, has made it challenging to align datasets created at different times, or on different platforms. Here we present a framework for harmonising such plasma lipidomic datasets with different levels of granularity in their lipid measurements. Our method utilises elastic-net prediction models, constructed from high-resolution lipidomics reference datasets, to predict unmeasured lipid species in lower-resolution studies. The approach involves (1) constructing composite lipid measures in the reference dataset that map to less resolved lipids in the target dataset, (2) addressing discrepancies between aligned lipid species, (3) generating prediction models, (4) assessing their transferability into the targe dataset, and (5) evaluating their prediction accuracy. To demonstrate our approach, we used the AusDiab population-based cohort (747 lipid species) as the reference to impute unmeasured lipid species into the LIPID study (342 lipid species). Furthermore, we compared measured and imputed lipids in terms of parameter estimation and predictive performance, and validated imputations in an independent study. Our method for harmonising plasma lipidomic datasets will facilitate model validation and data integration efforts.
Crystal net catalog of model flat band materials
Authors: Neves Paul M. , Wakefield Joshua P. , Fang Shiang , Nguyen Haimi , Ye Linda , Checkelsky Joseph G.
Published: February 2024

Flat band systems are currently under intense investigation in quantum materials, optical lattices, and metamaterials. These efforts are motivated by potential realization of strongly correlated phenomena enabled by frustration-induced flat band dispersions; identification of candidate platforms plays an important role in these efforts. Here, we develop a high-throughput materials search for bulk crystalline flat bands by automated construction of uniform-hopping near-neighbor tight-binding models. We show that this approach captures many of the essential features relevant to identifying flat band lattice motifs in candidate materials in a computationally inexpensive manner, and is of use to identify systems for further detailed investigation as well as theoretical and metamaterials studies of model systems. We apply this algorithm to 139,367 materials in the Materials Project database and identify 63,076 materials that host at least one flat band elemental sublattice. We further categorize these candidate systems into at least 31,635 unique flat band crystal nets and identify candidates of interest from both lattice and band structure perspectives. This work expands the number of known flat band lattices that exist in physically realizable crystal structures and classifies the majority of these systems by the underlying lattice, providing additional insights for familiar (e.g., kagome, pyrochlore, Lieb, and dice) as well as previously unknown motifs.
A new recumbirostran ‘microsaur’ from the lower Permian Bromacker locality, Thuringia, Germany, and its fossorial adaptations
Authors: MacDougall Mark J. , Jannel Andréas , Henrici Amy C. , Berman David S. , Sumida Stuart S. , Martens Thomas , Fröbisch Nadia B. , Fröbisch Jörg
Published: February 2024

Several recumbirostran ‘microsaurs’ are known from early Permian sites across Germany, including the Tambach Formation in Thuringia, central Germany. The only ‘microsaur’ thus far described from the Tambach Formation was the ostodolepid recumbirostran Tambaroter carrolli. However, there is also the documented presence of an undescribed recumbirostran ‘microsaur’ at the well-known Bromacker locality. The Bromacker locality is highly recognized and best known for its very diverse and extremely well-preserved terrestrial tetrapod assemblage combined with the co-occurrence of an exceptional vertebrate ichnofossil record. Here we describe a second new recumbirostran taxon from the Tambach Formation, which is also the first from the Bromacker locality itself. Phylogenetic analysis indicates that the new taxon, Bromerpeton subcolossus gen. et sp. nov., is a brachystelechid recumbirostran, a group also known elsewhere in Germany. The following features differentiate Bromerpeton from the other members of the clade: the presence of 13 maxillary teeth, narrow postorbitals that do not substantially contribute to the postorbital region of the skull, the frontal does not contribute to the orbital margin, and the presence of five manual digits. This new recumbirostran ‘microsaur’ further adds to the unique ecosystem that is preserved at the Bromacker locality, granting us a better understanding of what was living underfoot the larger more well-known animals at the locality. Likewise, it expands our understanding of the evolution of recumbirostran ‘microsaurs’, especially with regards to digit and limb reduction within the clade.
A modified shuffled frog leaping algorithm with inertia weight
Authors: Zhao Zhuanzhe , Wang Mengxian , Liu Yongming , Chen Yu , He Kang , Liu Zhibo
Published: February 2024

The shuffled frog leaping algorithm (SFLA) is a promising metaheuristic bionics algorithm, which has been designed by the shuffled complex evolution and the particle swarm optimization (PSO) framework. However, it is easily trapped into local optimum and has the low optimization accuracy when it is used to optimize complex engineering problems. To overcome the shortcomings, a novel modified shuffled frog leaping algorithm (MSFLA) with inertia weight is proposed in this paper. To extend the scope of the direction and length of the updated worst frog (vector) of the original SFLA, the inertia weight α was introduced and its meaning and range of the new parameters are fully explained. Then the convergence of the MSFLA is deeply analyzed and proved theoretically by a new dynamic equation formed by Z-transform. Finally, we have compared the solution of the 7 benchmark functions with the original SFLA, other improved SFLAs, genetic algorithm, PSO, artificial bee colony algorithm, and the grasshopper optimization algorithm with invasive weed optimization. The testing results showed that the modified algorithms can effectively improve the solution accuracy and convergence property, and exhibited an excellent ability of global optimization in high-dimensional space and complex function problems.
Pediatric diabetes prediction using deep learning
Authors: El-Bashbishy Abeer El-Sayyid , El-Bakry Hazem M.
Published: February 2024

This study proposed a novel technique for early diabetes prediction with high accuracy. Recently, Deep Learning (DL) has been proven to be expeditious in the diagnosis of diabetes. The supported model is constructed by implementing ten hidden layers and a multitude of epochs using the Deep Neural Network (DNN)-based multi-layer perceptron (MLP) algorithm. We proceeded to meticulously fine-tune the hyperparameters within the fully automated DL architecture to optimize data preprocessing, prediction, and classification using a novel dataset of Mansoura University Children's Hospital Diabetes (MUCHD), which allowed for a comprehensive evaluation of the system’s performance. The system was validated and tested using a sample of 548 patients, each with 18 significant features. Various validation metrics were employed to ensure the reliability of the results using cross-validation approaches with various statistical measures of accuracy, F-score, precision, sensitivity, specificity, and Dice similarity coefficient. The high performance of the proposed system can help clinicians accurately diagnose diabetes, with a remarkable accuracy rate of 99.8%. According to our analysis, implementing this method results in a noteworthy increase of 0.39% in the overall system performance compared to the current state-of-the-art methods. Therefore, we recommend using this method to predict diabetes.
Analysis of related factors for RA flares after SARS-CoV-2 infection: a retrospective study from patient survey
Authors: Li Rong , Zhao Jun-Kang , Li Qian , Zhao Li , Su Ya-Zhen , Zhang Jun-yan , Zhang Li-Yun
Published: February 2024

SARS-CoV-2 and its variants are widely prevalent worldwide. With frequent secondary and breakthrough infections, immune dysfunction in RA patients, and long-term use of immune preparations, SARS-CoV-2 infection poses a significant challenge to patients and rheumatologists. Whether SARS-CoV-2 infection causes RA flares and what factors aggravate RA flares are poorly studied. A questionnaire survey was conducted on RA patients infected with SARS-CoV-2 after December 7, 2022, in China through a multicenter and inter-network platform regarding general personal condition, primary disease, comorbidity, SARS-CoV-2 vaccination, viral infection, and impact on the primary disease. A total of 306 RA patients were included in this study, and the patient data were analyzed, in which the general condition of RA patients, medication use before SARS-CoV-2 infection and post-infection typing and manifestations, and medication adjustment did not affect the Flare of RA patients after SARS-CoV-2 infection. The control of disease before SARS-CoV-2 infection (OR = 2.10), RA involving pulmonary lesions (OR = 2.28), and the recovery time of COVID-19 (OR = 2.50) were risk factors for RA flare. RA involving pulmonary lesions, control status of disease before infection, and recovery time of COVID-19 disease are risk factors for RA flare after SARS-CoV-2 infection.
Efficacy of 3D-printed eye model to enhance retinoscopy skills
Authors: Kim Dong Hyun , Yang Hee Kyung , Baek Changhoon , Seo Jongmo , Hwang Jeong-Min
Published: February 2024

We conducted a prospective study to evaluate the efficacy of simulation-based education using a three-dimensional (3D)-printed schematic eye model in improving the retinoscopy refraction skills of medical students. A schematic eye model was printed using a fused deposition modeling-based 3D printer. Twenty medical students randomized into 3D (n = 10) and control (n = 10) groups received a 1-h lecture on the principles and methods of manifest refraction and were shown how to use the retinoscope and sciascope bars. The 3D group additionally attended a tutorial on the schematic eye. Both groups performed refractive examinations on four eyes of volunteer patients, and the results were recorded as a baseline. Instructor feedback and refraction practice was provided with the 3D group or with control group. To account for subject fatigue, patients spent no more than 8 min on the examination. After a 1-h break to allow for fatigue and familiarity, refraction tests were repeated on four randomly selected eyes of patients. Students’ refraction readings were compared with the autorefractor values using a spherical equivalent value and blur strength. All participants measured the time required to complete the refraction test and reported their subjective confidence in the results of each refraction test. Refractive errors before and after training did not differ between the control and 3D groups, with a significant improvement in errors observed in both groups (p = 0.005 and 0.008, respectively). The time to complete refraction before and after training did not differ between the two groups, both of which showed a significant reduction in time (p = 0.005 and 0.028, respectively). Pre- and post-training confidence scores for the accuracy of each refraction on a 10-point Likert scale were not significantly different. However, when comparing score changes between pre- and post-training, only the control group showed a significant increase in confidence (p = 0.005). Tests for the non-inferiority of refractive errors after training indicated that the 3D group was non-inferior to the control group. In conclusion, training in retinoscopy refraction skills using a 3D-printed eye model resulted in significant improvement in accuracy and speed compared to practice with real patients. Except for better confidence in the control group, schematic eye model training was not inferior to practice with real patients.
Ancient reindeer mitogenomes reveal island-hopping colonisation of the Arctic archipelagos
Authors: Hold Katharina , Lord Edana , Brealey Jaelle C. , Le Moullec Mathilde , Bieker Vanessa C. , Ellegaard Martin R. , Rasmussen Jacob A. , Kellner Fabian L. , Guschanski Katerina , Yannic Glenn , Røed Knut H. , Hansen Brage B. , Dalén Love , Martin Michael D. , Dussex Nicolas
Published: February 2024

Climate warming at the end of the last glacial period had profound effects on the distribution of cold-adapted species. As their range shifted towards northern latitudes, they were able to colonise previously glaciated areas, including remote Arctic islands. However, there is still uncertainty about the routes and timing of colonisation. At the end of the last ice age, reindeer/caribou (Rangifer tarandus) expanded to the Holarctic region and colonised the archipelagos of Svalbard and Franz Josef Land. Earlier studies have proposed two possible colonisation routes, either from the Eurasian mainland or from Canada via Greenland. Here, we used 174 ancient, historical and modern mitogenomes to reconstruct the phylogeny of reindeer across its whole range and to infer the colonisation route of the Arctic islands. Our data shows a close affinity among Svalbard, Franz Josef Land and Novaya Zemlya reindeer. We also found tentative evidence for positive selection in the mitochondrial gene ND4, which is possibly associated with increased heat production. Our results thus support a colonisation of the Eurasian Arctic archipelagos from the Eurasian mainland and provide some insights into the evolutionary history and adaptation of the species to its High Arctic habitat.
The correlation between the frequent intake of dietary migraine triggers and increased clinical features of migraine (analytical cross-sectional study from Egypt)
Authors: Fayed Abdel-Ghaffar I. , Emam Hossam , Abdel-Fattah Alyaa N. , Shamloul Reham M. , Elkholy Thanaa A. , Yassen Ensaf M. , Hamdy Eman , Mohamed Mohie-eldin T. , Seddeek Mahrous I. , Abed Elsayed
Published: February 2024

Despite the high prevalence of primary headaches, the role of food in modifying clinical characteristics among migraine patients is often overlooked. The aim is to detect the correlation between adopting unhealthy dietary habits and migraine severity and identify foods that have a greater chance of triggering specific subtypes of migraine. The present study was a cross-sectional analytical study that was conducted at Kasralainy Hospital, Cairo University, headache clinic at Alexandria University Hospital, and Al-Azhar University Hospitals from January to June 2020. We included 124 patients fulfilling the ICHD-3 criteria for migraine. A full clinical profile for migraine headaches was reported using a headache sheet applied to the Al-Azhar University headache unit. A nutritionist obtained data collected about dietary habits using many reliable scales and questionnaires such as food frequently sheets questionnaire. Logistic regression and Pearson correlation coefficients have been used to identify foods that are more likely to be associated with increased clinical features of migraine. Our participants reported that the fried meat, fried chicken, processed meats, fava beans, falafel, aged cheese “Pottery salted cheese” and “Rummy cheese”, salted-full fatty cheese “Damietta cheese”, citrus fruits, tea, coffee, soft drinks, nuts, pickles, chocolate, canned foods, sauces, ice cream, smoked herring, in addition to the stored food in the refrigerator for many days were significantly associated with the diagnosis of chronic migraine CM compared to episodic migraine (EM). Margarine, pickles, and smoked herring were significantly associated with the diagnosis of migraine with aura (MA) compared to migraine without aura (MO). Adopting unhealthy eating habits was a more prevalent dietary consumption pattern among people with chronic migraines compared to those with episodic migraine.
Retinal dysfunction in Huntington’s disease mouse models concurs with local gliosis and microglia activation
Authors: Cano-Cano Fátima , Martín-Loro Francisco , Gallardo-Orihuela Andrea , González-Montelongo María del Carmen , Ortuño-Miquel Samanta , Hervás-Corpión Irati , de la Villa Pedro , Ramón-Marco Lucía , Navarro-Calvo Jorge , Gómez-Jaramillo Laura , Arroba Ana I. , Valor Luis M.
Published: February 2024

Huntington’s disease (HD) is caused by an aberrant expansion of CAG repeats in the HTT gene that mainly affects basal ganglia. Although striatal dysfunction has been widely studied in HD mouse models, other brain areas can also be relevant to the pathology. In this sense, we have special interest on the retina as this is the most exposed part of the central nervous system that enable health monitoring of patients using noninvasive techniques. To establish the retina as an appropriate tissue for HD studies, we need to correlate the retinal alterations with those in the inner brain, i.e., striatum. We confirmed the malfunction of the transgenic R6/1 retinas, which underwent a rearrangement of their transcriptome as extensive as in the striatum. Although tissue-enriched genes were downregulated in both areas, a neuroinflammation signature was only clearly induced in the R6/1 retina in which the observed glial activation was reminiscent of the situation in HD patient’s brains. The retinal neuroinflammation was confirmed in the slow progressive knock-in zQ175 strain. Overall, these results demonstrated the suitability of the mouse retina as a research model for HD and its associated glial activation.
Cacao pod transcriptome profiling of seven genotypes identifies features associated with post-penetration resistance to Phytophthora palmivora
Authors: Baruah Indrani K. , Shao Jonathan , Ali Shahin S. , Schmidt Martha E. , Meinhardt Lyndel W. , Bailey Bryan A. , Cohen Stephen P.
Published: February 2024

The oomycetePhytophthora palmivorainfects the fruit of cacao trees (Theobroma cacao) causing black pod rot and reducing yields. Cacao genotypes vary in their resistance levels toP. palmivora, yet our understanding of how cacao fruit respond to the pathogen at the molecular level during disease establishment is limited. To address this issue, disease development and RNA-Seq studies were conducted on pods of seven cacao genotypes (ICS1, WFT, Gu133, Spa9, CCN51, Sca6 and Pound7) to better understand their reactions to the post-penetration stage ofP. palmivorainfection. The pod tissue-P. palmivorapathogen assay resulted in the genotypes being classified as susceptible (ICS1, WFT, Gu133 and Spa9) or resistant (CCN51, Sca6 and Pound7). The number of differentially expressed genes (DEGs) ranged from 1625 to 6957 depending on genotype. A custom gene correlation approach identified 34 correlation groups. De novo motif analysis was conducted on upstream promoter sequences of differentially expressed genes, identifying 76 novel motifs, 31 of which were over-represented in the upstream sequences of correlation groups and associated with gene ontology terms related to oxidative stress response, defense against fungal pathogens, general metabolism and cell function. Genes in one correlation group (Group 6) were strongly induced in all genotypes and enriched in genes annotated with defense-responsive terms. Expression pattern profiling revealed that genes in Group 6 were induced to higher levels in the resistant genotypes. An additional analysis allowed the identification of 17 candidatecis-regulatory modules likely to be involved in cacao defense againstP. palmivora. This study is a comprehensive exploration of the cacao pod transcriptional response toP. palmivoraspread after infection. We identified cacao genes, promoter motifs, and promoter motif combinations associated with post-penetration resistance toP. palmivorain cacao pods and provide this information as a resource to support future and ongoing efforts to breedP. palmivora-resistant cacao.
High-order asymptotic methods provide accurate, analytic solutions to intractable potential problems
Authors: Wray Alexander W. , Moore Madeleine R.
Published: February 2024

The classical problem of determining the density and capacity of arrays of potential sources is studied. This corresponds to a wide variety of physical problems such as electrostatic capacitance, stress in elastostatics and the evaporation of fluid droplets. An asymptotic solution is derived that is shown to give excellent accuracy for arbitrary arrays of sources with non-circular footprints, including polygonal footprints. The solution is extensively validated against both experimental and numerical results. We illustrate the power of the solution by showcasing a variety of newly accessible classical problems that may be solved in a rapid, accurate manner.
Immunogenicity and protective efficacy of a co-formulated two-in-one inactivated whole virus particle COVID-19/influenza vaccine
Authors: Handabile Chimuka , Ohno Marumi , Sekiya Toshiki , Nomura Naoki , Kawakita Tomomi , Kawahara Mamiko , Endo Masafumi , Nishimura Tomohiro , Okumura Minako , Toba Shinsuke , Sasaki Michihito , Orba Yasuko , Chua Brendon Y. , Rowntree Louise C. , Nguyen Thi H. O. , Shingai Masashi , Sato Akihiko , Sawa Hirofumi , Ogasawara Kazumasa , Kedzierska Katherine , Kida Hiroshi
Published: February 2024

Due to the synchronous circulation of seasonal influenza viruses and severe acute respiratory coronavirus 2 (SARS-CoV-2) which causes coronavirus disease 2019 (COVID-19), there is need for routine vaccination for both COVID-19 and influenza to reduce disease severity. Here, we prepared individual WPVs composed of formalin-inactivated SARS-CoV-2 WK 521 (Ancestral strain; Co WPV) or influenza virus [A/California/07/2009 (X-179A) (H1N1) pdm; Flu WPV] to produce a two-in-one Co/Flu WPV. Serum analysis from vaccinated mice revealed that a single dose of Co/Flu WPV induced antigen-specific neutralizing antibodies against both viruses, similar to those induced by either type of WPV alone. Following infection with either virus, mice vaccinated with Co/Flu WPV showed no weight loss, reduced pneumonia and viral titers in the lung, and lower gene expression of proinflammatory cytokines, as observed with individual WPV-vaccinated. Furthermore, a pentavalent vaccine (Co/qFlu WPV) comprising of Co WPV and quadrivalent influenza vaccine (qFlu WPV) was immunogenic and protected animals from severe COVID-19. These results suggest that a single dose of the two-in-one WPV provides efficient protection against SARS-CoV-2 and influenza virus infections with no evidence of vaccine interference in mice. We propose that concomitant vaccination with the two-in-one WPV can be useful for controlling both diseases.
Long-term complications and outcomes of augmentation cystoplasty in children with neurogenic bladder
Authors: Chang Jei-Wen , Kuo Fang-Cheng , Lin Tzu-Ching , Chin Tai-Wai , Yang Ling-Yu , Chen Hsin-Hung , Fan Yu-Hua , Yang Hui-Hsin , Liu Chin-Su , Tsai Hsin-Lin
Published: February 2024

Augmentation cystoplasty (AC) is an effective surgical procedure for patients with neurogenic bladder whenever conservative treatments have failed. The present study aimed to determine the risks of metabolic complications, malignancy, long-term outcomes and histopathologic changes of native bladder and the augmented intestine after AC in children with neurogenic bladder. Pediatric patients < 18 years who underwent AC between 2000 and 2020 were enrolled. Early postoperative complications, long-term outcomes and histopathologic changes in mucosal biopsies of native bladder and the augmented intestine after AC were reviewed. Twenty-two patients with a mean age of 7.6 ± 4.4 years were included. The ileum was used in 19 patients and the sigmoid colon in 3 patients. The length of hospital stay was 14.8 ± 6.8 days. Post-operatively, the urinary continence rate improved from 22.7 to 81.8% (p < 0.001). Hydronephrosis resolved in 17 of 19 patients. Vesicoureteral reflux resolved in 16 (64.0%) of the refluxing ureter units and was downgraded in 7 (28.0%). Grades of hydronephrosis and reflux significantly improved following AC (p < 0.001). The estimated glomerular filtration rate also significantly increased (p = 0.012). Formation of urinary tract stones was the most frequent late complication (in 8 patients, 36.4%). Life-threatening spontaneous bladder perforation occurred in 1 patient. After a mean follow-up of 13.4 ± 5.9 years, there were no cases of mortality, new-onset symptomatic metabolic acidosis, or changes in serum electrolytes. Of the 17 patients who were followed for > 10 years, no cases of malignancy or metaplastic changes were identified in the native bladder or augmented bowel epithelium. AC is a safe and effective procedure with low surgical and metabolic complication rates. In addition, AC provides a satisfactory continence rate and long-term protection of renal function, increases functional capacity, and regresses reflux and hydronephrosis. Individualized surveillance is recommended for the early identification of urolithiasis and metabolic disturbances.
Fabricating a 3D floating porous PDMS − Ag/AgBr decorated g-C3N4 nanocomposite sponge as a re-usable visible light photocatalyst
Authors: Taha Mohamed , Khalid A. , Elmahgary Maryam G. , Medany Shymaa S. , Attia Yasser A.
Published: February 2024

In this study, polymeric graphitic carbon nitride (g-C3N4) semiconductors was synthesized via a thermal condensation method. Subsequently, Ag/AgBr nanoparticles with varying ratios were decorated onto the g-C3N4 surface using the water/oil emulsion method. The resulting nanocomposites were characterized using XRD for phase identification and structural analysis, HR-TEM and SEM&EDAX for morphological structure, particle size, and elemental composition analysis, and XPS for investigating the chemical state and electronic structure. The impact of Ag/AgBr content on the optical properties of g-C3N4 were also studied such as (optical bandgap (Eg), refractive index (n), extinction coefficient (k), optical conductivity (σopt) and dielectric function (ε*)), Electrochemical impedance spectroscopy (EIS), PL spectroscopy and Chrono-amperometric investigations were conducted to assess the charge transfer capabilities and long-term durability of the prepared nanocomposites. The results revealed a reduction in Ag/AgBr particle size with an increase in g-C3N4 content, accompanied by a decrease in the optical bandgap from 2.444 eV to 2.393 eV. Furthermore, the nanocomposites exhibited enhanced degradation efficiencies of RhB dye, with the highest tested content of Ag/AgBr achieving 100% degradation after 120 min of irradiation. However, the challenge of catalyst separation after the degradation process remained. To address this issue, we developed a novel approach by impregnating Ag/AgBr@g-C3N4 photocatalyst onto a floating porous sponge using a simple sugar-template technique, offering potential as a reusable photocatalyst material. Furthermore, the 3D PDMS − Ag/AgBr@g-C3N4 photocatalyst was evaluated and found to maintain nearly the same photocatalytic efficiency for up to 5 consecutive cycles.
Si-based agent alleviated small bowel ischemia–reperfusion injury through antioxidant effects
Authors: Shimada Masato , Koyama Yoshihisa , Kobayashi Yuki , Matsumoto Yasunari , Kobayashi Hikaru , Shimada Shoichi
Published: February 2024

The progression of small bowel ischemia–reperfusion (IR) injury causes cells in the intestinal tract to undergo necrosis, necessitating surgical resection, which may result in loss of intestinal function. Therefore, developing therapeutic agents that can prevent IR injury at early stages and suppress its progression is imperative. As IR injury may be closely related to oxidative stress, antioxidants can be effective therapeutic agents. Our silicon (Si)-based agent, an antioxidant, generated a large amount of hydrogen in the intestinal tract for a prolonged period after oral administration. As it has been effective for ulcerative colitis, renal failure, and IR injury during skin flap transplantation, it could be effective for small intestinal IR injury. Herein, we investigated the efficacy of an Si-based agent in a mouse model of small intestinal IR injury. The Si-based agent suppressed the apoptosis of small intestinal epithelial cells by reducing the oxidative stress induced by IR injury. In addition, the thickness of the mucosal layer in the small intestine of the Si-based agent-administered group was significantly higher than that in the untreated group, revealing that Si-based agent is effective against small intestinal IR injuries. In the future, Si-based agents may improve the success rate of small intestine transplantation.
Cultivable fungal diversity in two karstic caves in Italy: under-investigated habitats as source of putative novel taxa
Authors: Poli A. , Zanellati A. , Piano E. , Biagioli F. , Coleine C. , Nicolosi G. , Selbmann L. , Isaia M. , Prigione V. , Varese G. C.
Published: February 2024

Microbial diversity of caves is largely understudied and its possible applications are still unknown. Autochthonous fungi, in particular, may have the potential to biomineralize metals and may be used as promising agents for bioremediation of polluted sites; thus, unearthing the fungal diversity in hypogean ecosystems is nowadays of utmost importance. To start addressing this knowledge gap, the cultivable mycobiota of two neighbouring caves—one natural and one exploited for touristic purposes—were characterised and compared by studying fungi isolated from sediments collected at increasing distances from the entrance. Overall, 250 fungal isolates ascribable to 69 taxa (mainly Ascomycota) were found, a high percentage of which was reported in caves for the first time. The sediments of the touristic cave displayed a richer and more diversified community in comparison with the natural one, possibly due to visitors carrying propagules or organic material. Considering that these environments are still poorly explored, chances to detect new fungal lineages are not negligible.
Machine learning enhanced evaluation of semiconductor quantum dots
Authors: Corcione Emilio , Jakob Fabian , Wagner Lukas , Joos Raphael , Bisquerra Andre , Schmidt Marcel , Wieck Andreas D. , Ludwig Arne , Jetter Michael , Portalupi Simone L. , Michler Peter , Tarín Cristina
Published: February 2024

A key challenge in quantum photonics today is the efficient and on-demand generation of high-quality single photons and entangled photon pairs. In this regard, one of the most promising types of emitters are semiconductor quantum dots, fluorescent nanostructures also described as artificial atoms. The main technological challenge in upscaling to an industrial level is the typically random spatial and spectral distribution in their growth. Furthermore, depending on the intended application, different requirements are imposed on a quantum dot, which are reflected in its spectral properties. Given that an in-depth suitability analysis is lengthy and costly, it is common practice to pre-select promising candidate quantum dots using their emission spectrum. Currently, this is done by hand. Therefore, to automate and expedite this process, in this paper, we propose a data-driven machine-learning-based method of evaluating the applicability of a semiconductor quantum dot as single photon source. For this, first, a minimally redundant, but maximally relevant feature representation for quantum dot emission spectra is derived by combining conventional spectral analysis with an autoencoding convolutional neural network. The obtained feature vector is subsequently used as input to a neural network regression model, which is specifically designed to not only return a rating score, gauging the technical suitability of a quantum dot, but also a measure of confidence for its evaluation. For training and testing, a large dataset of self-assembled InAs/GaAs semiconductor quantum dot emission spectra is used, partially labelled by a team of experts in the field. Overall, highly convincing results are achieved, as quantum dots are reliably evaluated correctly. Note, that the presented methodology can account for different spectral requirements and is applicable regardless of the underlying photonic structure, fabrication method and material composition. We therefore consider it the first step towards a fully integrated evaluation framework for quantum dots, proving the use of machine learning beneficial in the advancement of future quantum technologies.
Tropical decadal variability in nutrient supply and phytoplankton community in the Central Equatorial Pacific during the late Holocene
Authors: Guilderson T. P. , Glynn D. S. , McCarthy M. D.
Published: February 2024

We have reconstructed baseline δ15N and δ13C of export production at Kingman Reef in the Central Equatorial Pacific (CEP) at sub-decadal resolution, nearly continuously over the last 2000 years. The changes in δ15N reflects the strength of the North Equatorial Counter Current (NECC) relative to the South Equatorial Current (SEC), and to a lesser extent, the North Equatorial Current (NEC). Seasonal to multi-decadal variation in the strength of these currents, through the redistribution of heat, have global climate impacts and influence marine and terrestrial ecosystems. We use modern El Niño-La Nina dynamics and the Tropical Pacific Decadal Variability (TPDV) pattern, which is defined in the CEP, as a framework for analyzing the isotopic data. The CEP δ15N and δ13C records exhibit multi-decadal (50–60 year) variability consistent with TPDV. A large multi-centennial feature in the CEP δ15N data, within age-model uncertainties, is consistent with one of the prolonged dry-pluvial sequences in the American west at the end of the Medieval Climate Anomaly, where low TPDV is correlated with drier conditions. This unique record shows that the strength of the NECC, as reflected in baseline δ15N and δ13C, has at quasi-predictable intervals throughout the late Holocene, toggled the phytoplankton community between prokaryotes and picoplankton versus eukaryotes.
Machine learning-based investigation of regulated cell death for predicting prognosis and immunotherapy response in glioma patients
Authors: Zhang Wei , Dang Ruiyue , Liu Hongyi , Dai Luohuan , Liu Hongwei , Adegboro Abraham Ayodeji , Zhang Yihao , Li Wang , Peng Kang , Hong Jidong , Li Xuejun
Published: February 2024

Glioblastoma is a highly aggressive and malignant type of brain cancer that originates from glial cells in the brain, with a median survival time of 15 months and a 5-year survival rate of less than 5%. Regulated cell death (RCD) is the autonomous and orderly cell death under genetic control, controlled by precise signaling pathways and molecularly defined effector mechanisms, modulated by pharmacological or genetic interventions, and plays a key role in maintaining homeostasis of the internal environment. The comprehensive and systemic landscape of the RCD in glioma is not fully investigated and explored. After collecting 18 RCD-related signatures from the opening literature, we comprehensively explored the RCD landscape, integrating the multi-omics data, including large-scale bulk data, single-cell level data, glioma cell lines, and proteome level data. We also provided a machine learning framework for screening the potentially therapeutic candidates. Here, based on bulk and single-cell sequencing samples, we explored RCD-related phenotypes, investigated the profile of the RCD, and developed an RCD gene pair scoring system, named RCD.GP signature, showing a reliable and robust performance in predicting the prognosis of glioblastoma. Using the machine learning framework consisting of Lasso, RSF, XgBoost, Enet, CoxBoost and Boruta, we identified seven RCD genes as potential therapeutic targets in glioma and verified that the SLC43A3 highly expressed in glioma grades and glioma cell lines through qRT-PCR. Our study provided comprehensive insights into the RCD roles in glioma, developed a robust RCD gene pair signature for predicting the prognosis of glioma patients, constructed a machine learning framework for screening the core candidates and identified the SLC43A3 as an oncogenic role and a prediction biomarker in glioblastoma.
Microcirculatory changes in the skin after postmastectomy radiotherapy in women with breast cancer
Authors: Elawa Sherif , Mirdell Robin , Stefanis Aristotelis , Tesselaar Erik , Farnebo Simon
Published: February 2024

Postmastectomy radiotherapy (PMRT) increases the risk for complications after breast reconstruction. The pathophysiological mechanism underlying this increased risk is not completely understood. The aim of this study was to examine if there is a relationship between PMRT and microvascular perfusion in the skin directly after, and at 2 and 6 months after PMRT and to assess if there is impaired responsiveness to a topically applied vasodilator (Methyl nicotinate—MN) after PMRT. Skin microvascular responses after PMRT were measured on two sites in the irradiated chest wall of 22 women before, immediately after, and at 2 and 6 months after unilateral PMRT with the contralateral breast as a control. A significant increase in basal skin perfusion was observed in the irradiated chest wall immediately after RT (p < 0.0001). At 2 and 6 months after RT, there was no longer a difference in basal skin perfusion compared to the contralateral breast and compared to baseline. Similarly, the blood flow response in the skin after application of MN was stronger immediately after RT compared to before RT (p < 0.0001), but there was no difference at later time points. These results indicate that the increased risk for complications after surgical procedures are not directly related to changes in skin perfusion and microvascular responsiveness observed after postmastectomy RT.
Anticipatory postural control in adaptation of goal-directed lower extremity movements
Authors: Moriyama Mai , Kouzaki Motoki , Hagio Shota
Published: February 2024

Skilled football players can adapt their kicking movements depending on external environments. Predictive postural control movements, known as anticipatory postural adjustments (APAs), are needed preceding kicking movements to precisely control them while maintaining a standing posture only with the support leg. We aimed to clarify APAs of the support leg in the process of adaptation of goal-directed movements with the lower limb. Participants replicated ball-kicking movements such that they reached a cursor, representing a kicking-foot position towards a forward target while standing with the support leg. APAs were observed as the centre of pressure of the support leg shifted approximately 300 ms in advance of the onset of movement of the kicking foot. When the cursor trajectory of the kicking foot was visually rotated during the task, the kicking-foot movement was gradually modified to reach the target, indicating adaptation to the novel visuomotor environment. Interestingly, APAs in the mediolateral direction were also altered following the change in kicking-foot movements. Additionally, the APAs modified more slowly than the kicking-foot movements. These results suggest that flexible changes in predictive postural control might support the adaptation of goal-directed movements of the lower limb.