bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconsidering repurposing: long-term metformin treatment impairs cognition in Alzheimer’s model mice
Authors: Cho So Yeon , Kim Eun Woo , Park Soo Jin , Phillips Benjamin U. , Jeong Jihyeon , Kim Hyunjeong , Heath Christopher J. , Kim Daehwan , Jang Yurim , López-Cruz Laura , Saksida Lisa M. , Bussey Timothy J. , Lee Do Yup , Kim Eosu
Published: January 2024

Metformin, a primary anti-diabetic medication, has been anticipated to provide benefits for Alzheimer’s disease (AD), also known as “type 3 diabetes”. Nevertheless, some studies have demonstrated that metformin may trigger AD pathology and even elevate AD risk in humans. Despite this, limited research has elucidated the behavioral outcomes of metformin treatment, which would hold significant translational value. Thus, we aimed to perform thorough behavioral research on the prolonged administration of metformin to mice: We administered metformin (300 mg/kg/day) to transgenic 3xTg-AD and non-transgenic (NT) C57BL/6 mice over 1 and 2 years, respectively, and evaluated their behaviors across multiple domains via touchscreen operant chambers, including motivation, attention, memory, visual discrimination, and cognitive flexibility. We found metformin enhanced attention, inhibitory control, and associative learning in younger NT mice (≤16 months). However, chronic treatment led to impairments in memory retention and discrimination learning at older age. Furthermore, metformin caused learning and memory impairment and increased levels of AMPKα1-subunit, β-amyloid oligomers, plaques, phosphorylated tau, and GSK3β expression in AD mice. No changes in potential confounding factors on cognition, including levels of motivation, locomotion, appetite, body weight, blood glucose, and serum vitamin B12, were observed in metformin-treated AD mice. We also identified an enhanced amyloidogenic pathway in db/db mice, as well as in Neuro2a-APP695 cells and a decrease in synaptic markers, such as PSD-95 and synaptophysin in primary neurons, upon metformin treatment. Our findings collectively suggest that the repurposing of metformin should be carefully reconsidered when this drug is used for individuals with AD.
The constitutive activation of STAT3 gene and its mutations are at the crossroad between LGL leukemia and autoimmune disorders
Authors: Semenzato Gianpietro , Calabretto Giulia , Teramo Antonella , Gasparini Vanessa Rebecca , Rampazzo Elisa , Barilà Gregorio , Zambello Renato
Published: January 2024

Type T Large Granular Lymphocyte Leukemia (T-LGLL) is a chronic disorder characterized by the abnormal proliferation of clonal cytotoxic T cells. The intriguing association of T-LGLL with autoimmune and inflammatory diseases, the most prominent example being rheumatoid arthritis, raises questions about the underlying pathophysiologic relationships between these disorders which share several biological and clinical features, most notably neutropenia, which is considered as a clinical hallmark. Recent progress in molecular genetics has contributed to a better understanding of pathogenetic mechanisms, thus moving our knowledge in the field of LGL leukemias forward. Focusing on the constitutive activation of STAT3 pathway and the well-established role of STAT3 mutations in T-LGLL, we herein discuss whether the T cell clones occurring in comorbid conditions are the cause or the consequence of the immune-inflammatory associated events. Overall, this review sheds light on the intricate relationships between inflammation and cancer, emphasizing the importance of the STAT3 gene and its activation in the pathophysiology of these conditions. Gaining a deeper understanding of these underlying mechanisms seeks to pave the way for the development of novel targeted therapies for patients affected by inflammation-related cancers.
miR-277 targets the proapoptotic gene-hid to ameliorate Aβ42-mediated neurodegeneration in Alzheimer’s model
Authors: Deshpande Prajakta , Chen Chao-Yi , Chimata Anuradha Venkatakrishnan , Li Jian-Chiuan , Sarkar Ankita , Yeates Catherine , Chen Chun-Hong , Kango-Singh Madhuri , Singh Amit
Published: January 2024

Alzheimer’s disease (AD), an age-related progressive neurodegenerative disorder, exhibits reduced cognitive function with no cure to date. One of the reasons for AD is the accumulation of Amyloid-beta 42 (Aβ42) plaque(s) that trigger aberrant gene expression and signaling, which results in neuronal cell death by an unknown mechanism(s). Misexpression of human Aβ42 in the developing retina of Drosophila exhibits AD-like neuropathology. Small non-coding RNAs, microRNAs (miRNAs), post-transcriptionally regulate the expression of their target genes and thereby regulate different signaling pathways. In a forward genetic screen, we identified miR-277 (human ortholog is hsa-miR-3660) as a genetic modifier of Aβ42-mediated neurodegeneration. Loss-of-function of miR-277 enhances the Aβ42-mediated neurodegeneration. Whereas gain-of-function of miR-277 in the GMR > Aβ42 background downregulates cell death to maintain the number of neurons and thereby restores the retinal axonal targeting defects indicating the functional rescue. In addition, gain-of-function of miR-277 rescues the eclosion- and climbing assays defects observed in GMR > Aβ42 background. Thus, gain-of-function of miR-277 rescues both structurally as well as functionally the Aβ42-mediated neurodegeneration. Furthermore, we identified head involution defective (hid), an evolutionarily conserved proapoptotic gene, as one of the targets of miR-277 and validated these results using luciferase- and qPCR -assays. In the GMR > Aβ42 background, the gain-of-function of miR-277 results in the reduction of hid transcript levels to one-third of its levels as compared to GMR > Aβ42 background alone. Here, we provide a novel molecular mechanism where miR-277 targets and downregulates proapoptotic gene, hid, transcript levels to rescue Aβ42-mediated neurodegeneration by blocking cell death. These studies shed light on molecular mechanism(s) that mediate cell death response following Aβ42 accumulation seen in neurodegenerative disorders in humans and provide new therapeutic targets for neurodegeneration.
Targeting PAK4 reverses cisplatin resistance in NSCLC by modulating ER stress
Authors: Liu Shixin , Yang Pingshan , Wang Lu , Zou Xiaofang , Zhang Dongdong , Chen Wenyou , Hu Chuang , Xiao Duqing , Ren Hongzheng , Zhang Hao , Cai Songwang
Published: January 2024

Chemoresistance poses a significant impediment to effective treatments for non-small-cell lung cancer (NSCLC). P21-activated kinase 4 (PAK4) has been implicated in NSCLC progression by invasion and migration. However, the involvement of PAK4 in cisplatin resistance is not clear. Here, we presented a comprehensive investigation into the involvement of PAK4 in cisplatin resistance within NSCLC. Our study revealed enhanced PAK4 expression in both cisplatin-resistant NSCLC tumors and cell lines. Notably, PAK4 silencing led to a remarkable enhancement in the chemosensitivity of cisplatin-resistant NSCLC cells. Cisplatin evoked endoplasmic reticulum stress in NSCLC. Furthermore, inhibition of PAK4 demonstrated the potential to sensitize resistant tumor cells through modulating endoplasmic reticulum stress. Mechanistically, we unveiled that the suppression of the MEK1-GRP78 signaling pathway results in the sensitization of NSCLC cells to cisplatin after PAK4 knockdown. Our findings establish PAK4 as a promising therapeutic target for addressing chemoresistance in NSCLC, potentially opening new avenues for enhancing treatment efficacy and patient outcomes.
Clinical application of tumour-in-normal contamination assessment from whole genome sequencing
Authors: Mitchell Jonathan , Milite Salvatore , Bartram Jack , Walker Susan , Volkova Nadezda , Yavorska Olena , Zarowiecki Magdalena , Chalker Jane , Thomas Rebecca , Vago Luca , Sosinsky Alona , Caravagna Giulio
Published: January 2024

The unexpected contamination of normal samples with tumour cells reduces variant detection sensitivity, compromising downstream analyses in canonical tumour-normal analyses. Leveraging whole-genome sequencing data available at Genomics England, we develop a tool for normal sample contamination assessment, which we validate in silico and against minimal residual disease testing. From a systematic review of $$771$$
771
patients with haematological malignancies and sarcomas, we find contamination across a range of cancer clinical indications and DNA sources, with highest prevalence in saliva samples from acute myeloid leukaemia patients, and sorted CD3+ T-cells from myeloproliferative neoplasms. Further exploration reveals 108 hotspot mutations in genes associated with haematological cancers at risk of being subtracted by standard variant calling pipelines. Our work highlights the importance of contamination assessment for accurate somatic variants detection in research and clinical settings, especially with large-scale sequencing projects being utilised to deliver accurate data from which to make clinical decisions for patient care.
Altered DNA methylation within DNMT3A, AHRR, LTA/TNF loci mediates the effect of smoking on inflammatory bowel disease
Authors: Zhang Han , Kalla Rahul , Chen Jie , Zhao Jianhui , Zhou Xuan , Adams Alex , Noble Alexandra , Ventham Nicholas T. , Wellens Judith , Ho Gwo-Tzer , Dunlop Malcolm G. , Nowak Jan Krzysztof , Ding Yuan , Liu Zhanju , Satsangi Jack , Theodoratou Evropi , Li Xue
Published: January 2024

This work aims to investigate how smoking exerts effect on the development of inflammatory bowel disease (IBD). A prospective cohort study and a Mendelian randomization study are first conducted to evaluate the association between smoking behaviors, smoking-related DNA methylation and the risks of Crohn’s disease (CD) and ulcerative colitis (UC). We then perform both genome-wide methylation analysis and co-localization analysis to validate the observed associations. Compared to never smoking, current and previous smoking habits are associated with increased CD (P = 7.09 × 10−10) and UC (P < 2 × 10−16) risk, respectively. DNA methylation alteration at cg17742416 [DNMT3A] is linked to both CD (P = 7.30 × 10−8) and UC (P = 1.04 × 10−4) risk, while cg03599224 [LTA/TNF] is associated with CD risk (P = 1.91 × 10−6), and cg14647125 [AHRR] and cg23916896 [AHRR] are linked to UC risk (P = 0.001 and 0.002, respectively). Our study identifies biological mechanisms and pathways involved in the effects of smoking on the pathogenesis of IBD.
Benchmark for welding gun fault prediction with multivariate time series data
Authors: Wang Xiaoye , Zhang Changsheng , Wang Tao
Published: January 2024

In the automotive industry, machinery failures of the resistance spot welding (RSW) guns would interrupt the manufacturing lines and cause unplanned downtime, potentially resulting in a significant loss of production and reliability. Predicting the machinery failures of the RSW gun can provide more scientific strategies for predictive maintenance and decision-making. However, fault prediction of RSW guns has become increasingly challenging due to their complex behavior and data variability. In this paper, we created a benchmark dataset and proposed welding gun fault prediction benchmarks to aid in the development of machine learning approaches toward welding gun fault prediction. The dataset was collected at the Body-Shop (BS) of BMW Brilliance Automotive Ltd. from different components of hundreds of RSW guns to capture the patterns and trends before welding errors with historical data. Then we provide state-of-the-art machine learning (ML) benchmarks on time series forecasting methods in a welding gun fault prediction use case. This study will provide insights for time series forecasting while enabling ML researchers to contribute towards the fault prediction of the RSW guns.
A novel on design and implementation of hybrid MPPT controllers for solar PV systems under various partial shading conditions
Authors: Hussaian Basha Chakarajamula , Palati Madhu , Dhanamjayulu C. , Muyeen S. M. , Venkatareddy Prashanth
Published: January 2024

At present, fossil fuel-based power generation systems are reducing drastically because of their less availability in nature. In addition, it produces hazardous gasses and high environmental pollution. So, in this work, the solar natural source is selected for generating the electricity. Due to the nonlinear behavior of PV, achieving maximum voltage from the Photovoltaic (PV) system is a more tough job. In this work, various hybrid optimization controllers are studied for tracing the working power point of the PV under different Partial Shading Conditions. The studied hybrid optimization MPPT methods are equated in terms of oscillations across MPP, output power extraction, settling time of the MPP, dependency on the PV modeling, operating duty value of the converter, error finding accuracy of MPPT, algorithm complexity, tracking speed, periodic tuning required, and the number of sensing parameters utilized. Based on the simulative comparison results, it has been observed that the modified Grey Wolf Optimization based ANFIS hybrid MPPT method provides good results when equated with the other power point tracking techniques. Here, the conventional converter helps increase the PV source voltage from one level to another level. The proposed system is investigated by using the MATLAB/Simulink tool.
Identification of human skin microbiome odorants that manipulate mosquito landing behavior
Authors: Coutinho-Abreu Iliano V. , Jamshidi Omid , Raban Robyn , Atabakhsh Katayoon , Merriman Joseph A. , Akbari Omar S.
Published: January 2024

The resident human skin microbiome is responsible for the production of most of the human scents that are attractive to mosquitoes. Hence, engineering the human skin microbiome to synthesize less of mosquito attractants or produce repellents could potentially reduce bites and prevent the transmission of deadly mosquito-borne pathogens. In order to further characterize the human skin volatilome, we quantified the major volatiles of 39 strains of skin commensals (Staphylococci and Corynebacterium). Importantly, to validate the behavioral activity of these volatiles, we first assessed landing behavior triggered by human skin volatiles. We demonstrated that landing behavior is gated by the presence of carbon dioxide and L-(+)-lactic acid. This is similar to the combinatorial coding triggering mosquito short range attraction. Repellency behavior to selected skin volatiles and terpenes was tested in the presence of carbon dioxide and L-(+)-lactic acid. In a 2-choice landing behavior context, the skin volatiles 2- and 3-methyl butyric acids reduced mosquito landing by 62.0–81.6% and 87.1–99.6%, respectively. Similarly, the terpene geraniol was capable of reducing mosquito landing behavior by 74.9%. We also tested the potential repellency effects of terpenes in mosquitoes at short-range using a 4-port olfactometer. In these assays, geraniol reduced mosquito attraction (69–78%) to a mixture of key human kairomones carbon dioxide, L-(+)-lactic acid, and ammonia. These findings demonstrate that carbon dioxide and L-(+)-lactic acid change the valence of other skin volatiles towards mosquito landing behavior. Moreover, this study offers candidate odorants to be targeted in a novel strategy to reduce attractants or produce repellents by the human skin microbiota that may curtail mosquito bites, and subsequent mosquito-borne disease.
Broadband stripline Lenz lens achieves 11 × NMR signal enhancement
Authors: Liang Jianyi , Davoodi Hossein , Wadhwa Sagar , Badilita Vlad , Korvink Jan G.
Published: January 2024

A Lenz lens is an electrically passive conductive element that, when placed in a time-varying magnetic field, acts as a magnetic flux concentrator or a magnetic lens. In the realm of nuclear magnetic resonance (NMR), Lenz lenses have been exploited as electrically passive metallic radiofrequency interposers placed between a sample and a tuned or untuned NMR detector in order to focus the $${B}_1$$

B
1

-field of the detector onto a smaller sample space. Here we explore a novel embodiment of the Lenz lens, which acts as a non-resonant stripline interposer, i.e., the $${B}_1$$

B
1

-field acts along the longitudinal volume of a sample container, such as a capillary or other microfluidic channel that is coincident with the axis of the stripline. The almost vanishing self-resonance of the stripline Lenz lens, at frequencies relevant for NMR, leads to a desirable $${B}_1$$

B
1

-field amplitude that is nearly perfectly uniform across the sample and hence lacking a characteristic sinusoidal modal shape. The action of Lenz’ law ensures that no stray $${B}_1$$

B
1

-field is found outside of the stripline’s active volume. Because the stripline Lenz lens does not rely on its own geometry to achieve resonance, its frequency response is thus widely broadband for field enhancements up to a factor of 11, with only the external driving resonator properties governing the overall resonant behaviour. We explore the use of the stripline Lenz lens with a sub-nanolitre sample volume, readily detecting 4 isotopes with resonances ranging from 125.76 to 500 MHz. The concept holds potential for the NMR study of thin films, small biological samples, as well as the in situ study of battery materials.
Learning in hybrid classes: the role of off-task activities
Authors: Ochs Carli , Gahrmann Caroline , Sonderegger Andreas
Published: January 2024

Hybrid teaching (synchronous online and on-site teaching) offers many advantages (e.g., increased flexibility). However, previous research has suggested that students who join classes online suffer higher levels of distractibility, which might translate into students engaging in more off-task activities. This, in turn, can impair students’ learning performance. The following quasi-experimental field study investigated this specific link between teaching mode, engagement in off-task activities, and learning performance. We collected survey data from N = 690 students in six hybrid classes (N = 254 online, N = 436 on-site). Participants reported the amount of time they spent engaging in digital and non-digital off-task activities and responded to a quiz on the course material. Results revealed that online students spent more time engaging in off-task activities than on-site students. Further, results were consistent with our hypothesis that joining the class online is associated with lower learning performance via time spent on digital off-task activities.
Simulated digestions of free oligosaccharides and mucin-type O-glycans reveal a potential role for Clostridium perfringens
Authors: McDonald Andrew G. , Lisacek Frédérique
Published: January 2024

The development of a stable human gut microbiota occurs within the first year of life. Many open questions remain about how microfloral species are influenced by the composition of milk, in particular its content of human milk oligosaccharides (HMOs). The objective is to investigate the effect of the human HMO glycome on bacterial symbiosis and competition, based on the glycoside hydrolase (GH) enzyme activities known to be present in microbial species. We extracted from UniProt a list of all bacterial species catalysing glycoside hydrolase activities (EC 3.2.1.-), cross-referencing with the BRENDA database, and obtained a set of taxonomic lineages and CAZy family data. A set of 13 documented enzyme activities was selected and modelled within an enzyme simulator according to a method described previously in the context of biosynthesis. A diverse population of experimentally observed HMOs was fed to the simulator, and the enzymes matching specific bacterial species were recorded, based on their appearance of individual enzymes in the UniProt dataset. Pairs of bacterial species were identified that possessed complementary enzyme profiles enabling the digestion of the HMO glycome, from which potential symbioses could be inferred. Conversely, bacterial species having similar GH enzyme profiles were considered likely to be in competition for the same set of dietary HMOs within the gut of the newborn. We generated a set of putative biodegradative networks from the simulator output, which provides a visualisation of the ability of organisms to digest HMO and mucin-type O-glycans. B. bifidum, B. longum and C. perfringens species were predicted to have the most diverse GH activity and therefore to excel in their ability to digest these substrates. The expected cooperative role of Bifidobacteriales contrasts with the surprising capacities of the pathogen. These findings indicate that potential pathogens may associate in human gut based on their shared glycoside hydrolase digestive apparatus, and which, in the event of colonisation, might result in dysbiosis. The methods described can readily be adapted to other enzyme categories and species as well as being easily fine-tuneable if new degrading enzymes are identified and require inclusion in the model.
Brain control of bimanual movement enabled by recurrent neural networks
Authors: Deo Darrel R. , Willett Francis R. , Avansino Donald T. , Hochberg Leigh R. , Henderson Jaimie M. , Shenoy Krishna V.
Published: January 2024

Brain-computer interfaces have so far focused largely on enabling the control of a single effector, for example a single computer cursor or robotic arm. Restoring multi-effector motion could unlock greater functionality for people with paralysis (e.g., bimanual movement). However, it may prove challenging to decode the simultaneous motion of multiple effectors, as we recently found that a compositional neural code links movements across all limbs and that neural tuning changes nonlinearly during dual-effector motion. Here, we demonstrate the feasibility of high-quality bimanual control of two cursors via neural network (NN) decoders. Through simulations, we show that NNs leverage a neural ‘laterality’ dimension to distinguish between left and right-hand movements as neural tuning to both hands become increasingly correlated. In training recurrent neural networks (RNNs) for two-cursor control, we developed a method that alters the temporal structure of the training data by dilating/compressing it in time and re-ordering it, which we show helps RNNs successfully generalize to the online setting. With this method, we demonstrate that a person with paralysis can control two computer cursors simultaneously. Our results suggest that neural network decoders may be advantageous for multi-effector decoding, provided they are designed to transfer to the online setting.
Integrated image and sensor-based food intake detection in free-living
Authors: Ghosh Tonmoy , Han Yue , Raju Viprav , Hossain Delwar , McCrory Megan A. , Higgins Janine , Boushey Carol , Delp Edward J. , Sazonov Edward
Published: January 2024

The first step in any dietary monitoring system is the automatic detection of eating episodes. To detect eating episodes, either sensor data or images can be used, and either method can result in false-positive detection. This study aims to reduce the number of false positives in the detection of eating episodes by a wearable sensor, Automatic Ingestion Monitor v2 (AIM-2). Thirty participants wore the AIM-2 for two days each (pseudo-free-living and free-living). The eating episodes were detected by three methods: (1) recognition of solid foods and beverages in images captured by AIM-2; (2) recognition of chewing from the AIM-2 accelerometer sensor; and (3) hierarchical classification to combine confidence scores from image and accelerometer classifiers. The integration of image- and sensor-based methods achieved 94.59% sensitivity, 70.47% precision, and 80.77% F1-score in the free-living environment, which is significantly better than either of the original methods (8% higher sensitivity). The proposed method successfully reduces the number of false positives in the detection of eating episodes.
Regnase-2 inhibits glioblastoma cell proliferation
Authors: Sowinska Weronika , Wawro Mateusz , Kochan Jakub , Solecka Aleksandra , Polak Jarosław , Kwinta Borys , Kasza Aneta
Published: January 2024

Regnase-2 (Reg-2/MCPIP2/ZC3H12B) is uniquely expressed at a high level in the healthy brain and down-regulated in samples from patients with glioma, reaching the lowest level in high-grade glioblastoma multiforme (GBM). This RNase is involved in the regulation of neuroinflammation through the degradation of IL-6 and IL-1 mRNAs, key pro-inflammatory cytokines for GBM pathology. Reg-2 is a strong inhibitor of the proliferation of human glioblastoma cell lines and blocks their potential to form colonies. Here, we describe that overexpression of Reg-2 stalls glioblastoma cells in the G1 phase of the cell cycle and reduces the level of transcripts implicated in cell cycle progression. These newly identified targets include CCND1, CCNE1, CCNE2, CCNA2, CCNB1, and CCNB2, encoding the cyclins as well as AURKA and PLK1, encoding two important mitosis regulators. By RNA immunoprecipitation we confirmed the direct interaction of Reg-2 with the investigated transcripts. We also tested mRNA regions involved in their interaction with Reg-2 on the example of CCNE2. Reg-2 interacts with the 3’UTR of CCNE2 in a dose-dependent manner. In conclusion, our results indicate that Reg-2 controls key elements in GBM biology by restricting neuroinflammation and inhibiting cancer cell proliferation.
Biodiesel production potential of Eichhornia crassipes (Mart.) Solms: comparison of collection sites and different alcohol transesterifications
Authors: Leite Aricely Aparecida Silva , Weber Luciana Vincenzi , Correa João Paulo Aquino , de Castro Thiago Luis Aguayo , da Silva Carmem Cícera Maria , da Costa e Silva Rosangela Maria Ferreira , Cardoso Claudia Andrea Lima , Konradt-Moraes Leila Cristina
Published: January 2024

Renewable resources have stood out as raw materials in producing biofuels. This study aimed to evaluate the parameters of alcohol transesterification (ethanol and methanol) and localization of collection of aquatic macrophyte Eichhornia crassipes (Mart.) Solms in the production of biodiesel by in situ transesterification. E. crassipes was collected in Dourados and Corumbá (Brazil) municipalities. The fatty acid ester composition of the biodiesel was characterized and quantified by gas chromatography. The biodiesel properties were estimated using the BiodieselAnalyzer© program prediction. The ethyl transesterification resulted in higher yields, but the localization of collection was the most relevant parameter in biodiesel production according to the Permutation Multivariate Analysis of Variance. The simulation and comparison of the physical–chemical properties of E. crassipes biodiesel and BD 100 (commercial biodiesel) were promising for commercial application.
Modelling the impact of sublingual immunotherapy versus subcutaneous immunotherapy on patient travel time and CO2 emissions in Sweden
Authors: Cardell Lars-Olaf , Sterner Thomas , Ahmed Waqas , Slættanes Andreas Kallsoy , Svärd Mikael , Pollock Richard F.
Published: January 2024

In Sweden, allergy immunotherapy (AIT) is available as either subcutaneous immunotherapy (SCIT) injections or sublingual immunotherapy (SLIT) tablets and is used to treat moderate-severe allergic rhinitis (AR). This study sought to determine treatment-related CO2 emissions and travel times in Swedish patients receiving either SCIT or SLIT-tablets. A list of specialized Swedish AR clinics that administer AIT was determined, and respective co-ordinates retrieved. Swedish municipality population data were obtained from a national database. The mean distance from each Swedish municipality to the nearest AR clinic was calculated, adjusted using a detour index, and weighted by estimated patient population size. Transport modality data were obtained from a Swedish urban transport study and CO2 emissions were obtained from Government sources. The mean number of annual SLIT-tablets and SCIT doses required were calculated based on product labels and clinical expert input. The annual number of healthcare professional interactions were layered into the model to estimate changes in mean patient travel time, distance, and travel-related CO2 emissions associated with using SCIT versus SLIT-tablets. Mean annual travel-related CO2 emissions were 410 tonnes (to two significant figures [s.f.]; standard deviation [SD] 90) with SLIT-tablets, versus 1700 tonnes (SD 380) for SCIT, resulting in mean annual savings of approximately 1300 tonnes (SD 290) of CO2 if all AIT patients were to receive SLIT-tablets instead of SCIT, over 380 times greater than 2021 average Swedish CO2 emissions per capita. Approximate mean annual travel times for patients taking SLIT-tablets were 66,500 h (three s.f.; SD 14,400), and 278,000 h (SD 60,200) for SCIT, resulting in mean annual savings of 211,000 h (SD 45,800) if all AIT patients were to receive SLIT-tablets instead of SCIT. Compared with SCIT injections, SLIT-tablets led to substantial reductions in treatment-related CO2 emissions and travel times for Swedish patients.
AI-based shape optimization of galloping micro-power generators: exploring the benefits of curved surfaces
Authors: Alhussein Hussam , Dalaq Ahmed S. , Daqaq Mohammed
Published: January 2024

The advent of flow micro-power generation has resparked the interest in researching the galloping instability with the objective of determining the shape of the bluff body that is most prone to galloping. Such shape, which is sought to maximize the efficacy of galloping micro-power generators (GMPGs), must possess a very low cut-in flow speed while achieving large-amplitude steady-state oscillations beyond it. Additionally, since GMPGs can operate in environments with fluctuating flow conditions, the optimal shape must also have a very short rise time to its steady-state amplitude. In this work, we utilize computational fluid dynamics in conjunction with machine learning to optimize the shape of the bluff body of GMPGs for both steady-state and transient performance. We investigate a continuum shape description which encapsulates most of the cases studied earlier in the literature. The continuum has a straight frontal and dorsal faces with varying lengths, and side faces described by surfaces of different curvatures. The optimization study reveals that a curved-trapezoidal bluff body with the highest side surface curvature and frontal-to-dorsal ratio is the perfect shape for steady flow conditions. On the other hand, a square profile with the highest side surface curvature is the ideal choice for highly-fluctuating flow conditions because of its shortest rise time. The theoretical findings are replicated experimentally using wind tunnel tests.
Assessing the reliability of paleomagnetic datasets using the R package PmagDiR
Authors: Dallanave Edoardo
Published: January 2024

Paleomagnetism is the most important source of information for determining the position of tectonic plates in the geological past. Over the last few decades significant advancements have been made in improving the reliability of paleomagnetic data, ranging from analytical methods to statistical assessments. Here I present the first version of PmagDiR, an R-based open-source package which displays, assesses the reliability, and, when possible, corrects given paleomagnetic directions distributions. The main functions of the package are to: plot paleomagnetic directions, their averages and confidence boundaries; apply different direction cut-offs to identify and filter outliers; perform a test for antipodality; compare the distribution shape with the one predicted by a widely accepted paleosecular variation model; correct flawed distributions for paleomagnetic inclination flattening; and correct for strain-derived paleomagnetic directions deviations when the strain fabric is known. Furthermore, directions can be converted in virtual geomagnetic poles and plotted on a spherical projection for comparison with reference apparent polar wander paths. All main functions of the PmagDiR package return results as comma separated value text files as well as vector graphic files (pdf), optimized for publication purpose with minimal manipulation.
ATF4 expression in thermogenic adipocytes is required for cold-induced thermogenesis in mice via FGF21-independent mechanisms
Authors: Bjorkman Sarah H. , Marti Alex , Jena Jayashree , García-Peña Luis Miguel , Weatherford Eric T. , Kato Kevin , Koneru Jivan , Chen Jason , Sood Ayushi , Potthoff Matthew J. , Adams Christopher M. , Abel E. Dale , Pereira Renata O.
Published: January 2024

In brown adipose tissue (BAT), short-term cold exposure induces the activating transcription factor 4 (ATF4), and its downstream target fibroblast growth factor 21 (FGF21). Induction of ATF4 in BAT in response to mitochondrial stress is required for thermoregulation, partially by increasing FGF21 expression. In the present study, we tested the hypothesis that Atf4 and Fgf21 induction in BAT are both required for BAT thermogenesis under physiological stress by generating mice selectively lacking either Atf4 (ATF4 BKO) or Fgf21 (FGF21 BKO) in UCP1-expressing adipocytes. After 3 days of cold exposure, core body temperature was significantly reduced in ad-libitum-fed ATF4 BKO mice, which correlated with Fgf21 downregulation in brown and beige adipocytes, and impaired browning of white adipose tissue. Conversely, despite having reduced browning, FGF21 BKO mice had preserved core body temperature after cold exposure. Mechanistically, ATF4, but not FGF21, regulates amino acid import and metabolism in response to cold, likely contributing to BAT thermogenic capacity under ad libitum-fed conditions. Importantly, under fasting conditions, both ATF4 and FGF21 were required for thermogenesis in cold-exposed mice. Thus, ATF4 regulates BAT thermogenesis under fed conditions likely in a FGF21-independent manner, in part via increased amino acid uptake and metabolism.
Cell cycle specific, differentially tagged ribosomal proteins to measure phase specific transcriptomes from asynchronously cycling cells
Authors: Cochran Jesse D. , Leathers Tess A. , Maldosevic Emir , Siejda Klara W. , Vitello Julian , Lee Haesol , Bradley Leigh A. , Young Alex , Jomaa Ahmad , Wolf Matthew J.
Published: January 2024

Asynchronously cycling cells pose a challenge to the accurate characterization of phase-specific gene expression. Current strategies, including RNAseq, survey the steady state gene expression across the cell cycle and are inherently limited by their inability to resolve dynamic gene regulatory networks. Single cell RNAseq (scRNAseq) can identify different cell cycle transcriptomes if enough cycling cells are present, however some cells are not amenable to scRNAseq. Therefore, we merged two powerful strategies, the CDT1 and GMNN degrons used in Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) cell cycle sensors and the ribosomal protein epitope tagging used in RiboTrap/Tag technologies to isolate cell cycle phase-specific mRNA for sequencing. The resulting cell cycle dependent, tagged ribosomal proteins (ccTaggedRP) were differentially expressed during the cell cycle, had similar subcellular locations as endogenous ribosomal proteins, incorporated into ribosomes and polysomes, and facilitated the recovery of cell cycle phase-specific RNA for sequencing. ccTaggedRP has broad applications to investigate phase-specific gene expression in complex cell populations.
Ecological determinants of Cope’s rule and its inverse
Authors: Roy Shovonlal , Brännström Åke , Dieckmann Ulf
Published: January 2024

Cope’s rule posits that evolution gradually increases the body size in lineages. Over the last decades, two schools of thought have fueled a debate on the applicability of Cope’s rule by reporting empirical evidence, respectively, for and against Cope’s rule. The apparent contradictions thus documented highlight the need for a comprehensive process-based synthesis through which both positions of this debate can be understood and reconciled. Here, we use a process-based community-evolution model to investigate the eco-evolutionary emergence of Cope’s rule. We report three characteristic macroevolutionary patterns, of which only two are consistent with Cope’s rule. First, we find that Cope’s rule applies when species interactions solely depend on relative differences in body size and the risk of lineage extinction is low. Second, in environments with higher risk of lineage extinction, the recurrent evolutionary elimination of top predators induces cyclic evolution toward larger body sizes, according to a macroevolutionary pattern we call the recurrent Cope’s rule. Third, when interactions between species are determined not only by their body sizes but also by their ecological niches, the recurrent Cope’s rule may get inverted, leading to cyclic evolution toward smaller body sizes. This recurrent inverse Cope’s rule is characterized by highly dynamic community evolution, involving the diversification of species with large body sizes and the extinction of species with small body sizes. To our knowledge, these results provide the first theoretical foundation for reconciling the contrasting empirical evidence reported on body-size evolution.
Recent progress on Bi4O5Br2-based photocatalysts for environmental remediation and energy conversion
Authors: Qian Xingyue , Ma Yu , Xia Xin , Xia Jiawei , Ye Jingrui , He Guangyu , Chen Haiqun
Published: January 2024

This review comprehensively outlines the modification and application of Bi4O5Br2-based photocatalysts from recent developments in structural regulation.
Efficacy of antioxidant supplementation in improving endocrine, hormonal, inflammatory, and metabolic statuses of PCOS: a meta-analysis and systematic review
Authors: He Junhui , Deng Renhe , Wei Yanhong , Zhang Shun , Su Mingxuan , Tang Masong , Wang Jinyuan , Nong Weihua , Lei Xiaocan
Published: January 2024

The advantageous effect of antioxidants on PCOS.
Selenium-silk microgels as antifungal and antibacterial agents
Authors: Wiita Elizabeth G. , Toprakcioglu Zenon , Jayaram Akhila K. , Knowles Tuomas P. J.
Published: January 2024

Silk-based microgels that contain selenium nanoparticles embedded within the protein scaffold, that display potent antibacterial and antifungal properties, while importantly remain highly biocompatible with mammalian cells.
Pressure-driven multiple optoelectronic evolution in CsMoO3(IO3) with dual functional [MoO6] and [IO3] groups
Authors: Jiang Dequan , Li Chen , Wen Ting , Liu Ke , Ma Yingying , Chen En , Pei Tianyao , Wang Yonggang
Published: January 2024

Pressure-induced optoelectronic changes were observed in CsMoO3(IO3) by evolutions of dual functional groups, including piezochromism, second harmonic generation transformation, and the enhancement of the photocurrent switching ratio.
Update on novel synthetic approaches towards the construction of carbazole nuclei: a review
Authors: Munawar Saba , Zahoor Ameer Fawad , Mansha Asim , Bokhari Tanveer Hussain , Irfan Ahmad
Published: January 2024

The carbazole ring construction has been achieved via annulation, C–H activation, carboamination, hydroarylation and cycloaddition reactions. The synthesized scaffolds exhibit various biological activities and participate in drug development.
A photothermal MoS2 decorated biomass carbon-based aerogel with a directionally aligned porous structure for mitigating heavy metal stress under seawater acidification
Authors: Yu Fang , Cheng Xiangyu , Xu Juntian , Zhang Qinfang
Published: January 2024

Marine animals and human are threatened by seawater acidification and metal contamination.
Study of the molecular interaction of a phosphonium-based ionic liquid within myo-inositol and non-steroidal anti-inflammatory drugs
Authors: Banjare Manoj Kumar , Banjare Bhupendra Singh
Published: January 2024

A study of the micellar behavior of ([P666(14)][THPP]) with myo-inositol and aspirin/ibuprofen, using surface tension, conductivity, colorimetry, viscometry, DLS and FTIR, methods.
Lithocholic acid derivatives as potent modulators of the nuclear receptor RORγt
Authors: Abdel-Rahman Somaya A. , Brogi Simone , Gabr Moustafa T.
Published: January 2024

RORγt is a nuclear receptor found in various tissues that plays a crucial role in the differentiation and proliferation of Th17 cells, as well as in their generation of the pro-inflammatory cytokine IL-17A.
Preparation of PEG/P(U-AM-ChCl) composite hydrogels using ternary DES light polymerization and their properties
Authors: Li Bin , Liu Haiying , Zhou Mengjing , Wu Aolin , Hao Wenrui , Jiang YaJun , Hu Zhigang
Published: January 2024

Deep eutectic solvents (DES) were prepared using urea (U) and acrylamide (AM) as hydrogen bond donors and choline chloride (ChCl) as hydrogen bond acceptor. Polyethylene glycol (PEG) was selected as a filler and uniformly dispersed in DES to prepare PEG/P(U-AM-ChCl) composite hydrogels.
Efficient C–N coupling for urea electrosynthesis on defective Co3O4 with dual-functional sites
Authors: Li Pengsong , Zhu Qinggong , Liu Jiyuan , Wu Tianbin , Song Xinning , Meng Qinglei , Kang Xinchen , Sun Xiaofu , Han Buxing
Published: January 2024

Defective Co3O4 catalysts featuring dual-functional sites were synthesized using a facile thermal annealing strategy to enhance the adsorption of reactants/intermediates and facilitate effective C–N coupling for urea production from CO2 and nitrite.
A 19‐GHz low‐phase‐noise frequency synthesizer for a K‐band FMCW radar sensor of detecting micro unmanned aerial vehicles
Authors: Lee Jayol , Park Kyung Hwan , Koo Bon Tae
Published: January 2024

A 19‐GHz low‐phase‐noise PLL‐frequency synthesizer is presented in this letter that is intended to be used in a K‐band FMCW radar which requires strict phase noise for detecting a small unmanned aerial vehicle. The 17.9 to 19.5‐GHz PLL includes a Darlington cross‐coupled capacitive‐degeneration VCO which presents higher maximum attainable oscillation frequency (ƒtrans) and larger negative transconductance (gm), thus resulting in low phase noise. Manufactured using the SiGe BiCMOS process, the K‐band synthesizer demonstrates −114 dBc/Hz at 1 MHz offset and −138 dBc/Hz at 10 MHz offset from 19.456 GHz locking carrier frequency.
Vibration feature extraction and fault detection method for transmission towers
Authors: Zhao Long , Liu Zhicheng , Yuan Peng , Wen Guanru , Huang Xinbo
Published: January 2024

This paper presents a novel bolt looseness detection method for power transmission towers based on vibration signal analysis. The proposed method utilizes pulse excitation to extract the vibration signal of the tower, which is then adaptively decomposed using the Variational Mode Decomposition of Spider Wasp optimizer (SWVMD). This overcomes limitations of traditional Variational Mode Decomposition methods by leveraging bio‐inspired optimization to improve signal decomposition. Simulated signals processed with different optimization methods verify the superiority of the SWO approach. Field tests on a 110‐kV transmission tower further demonstrate the effectiveness of the proposed SWVMD technique for analyzing on‐site vibration data. A new improved intrinsic multiscale sample entropy feature is also introduced for bolt state characterization. A Spider Wasp Support Vector Machine classifier is developed to realize accurate bolt loosening monitoring using the extracted features. Dynamic response tests under varying bolt conditions show that the method can identify early loosening and reduce tower damage risks compared to conventional techniques. This novel vibration‐based detection framework presents an innovative application of nature‐inspired computing for power infrastructure health monitoring.
Effect of Invasive Pelvic Floor Management in Vaginismus among Reproductive Aged Females-A Case Study
Authors: Rasotra Reema , K Shanthakumar
Published: January 2024

Vaginismus is defined as condition which leads to involuntary vaginal muscle spasm leading to painful sexual Intercourse. It is also classified as sexual pain disorder. It is one of the most common conditions prevalent among females who experience pain during vaginal intercourse leading to sexual pain disorder. The main objective of the study was to rule out the effectiveness of intra-vaginal management on patient with Vaginismus. Vaginismus is a sexual pain disorder in which female have difficulties in vaginal penetration during sexual Intercourse due to number of reasons such as fear, involuntary muscle contraction, sexual abuse and pelvic pain etc. As per studies, it had been showed that vaginismus is also one of the main reasons behind Infertility among many females. Most of the females in North India are not aware regarding the pelvic floor examination or to consult the pelvic floor practitioner for their problems related to Infertility. In many cases, as per studies we had founded that most of the females are being focused to go for number of testing procedures but they are not being guided to undergo pelvic floor examination.
Virosome: A vector in vaccine delivery
Authors: Karpe Shubham , Gupta Khushi , Vyas Ganesh , Rana Princy , Khan Fahad , Kumar Rajesh
Published: January 2024

These days vaccines are considered the best economical and effective technique for preventing and handling bacterial infections, like human papillomavirus (HPV) or meningitis, allergies, autoimmune Relevant Disorders, Microbial Infections, and many more viral diseases. Annually millions of lives are saved from death-causing infections and other relevant disorders with the help of proper immunization with the help of vaccines. But still, many diseases are not yet preventable by vaccines and there is a chance of the improvement of current vaccines with help of many approaches. One of these is a compound known as a virosome, which is produced when pure haemagglutinin and neuraminidase projections of the influenza virus surface are removed from viral envelope and deposited on the exterior of unilamellar liposomes.Studies have shown that in order to attain the desired therapeutic effect, a physical attachment between the target antigen and the virosomal carrier is necessary. A virosome can bind to and “infect” host cells and deliver the antigen directly into the processing pathway which is an Alternatively, the virosome may be phagocytosed by an APC. So Our review gives a novel idea of the vector technology for vaccine delivery, its properties, method of preparation, and importance as well as some applications of different virosomal vaccine discoveries.
Exploring the Potential of Curry Leaves for their Therapeutic Action
Authors: Kumar Rahul , Gupta Shifali , Kaur Paranjeet , Kumar Sahu Sanjeev
Published: January 2024

Curry leaves (Murryakoenigii), which are valued for their aromatic flavour, have been mainstay of Indian cuisine for ages. These leaves are becoming more well known for their potential to affect metabolic pathways in additional to their gastronomic value. The molecular mechanistic potential of curry leaves in relation to metabolic control is examined in this abstract. Curry leaves contain a variety of bioactive substance, such as antioxidant, anti-inflammatory agent, and substance that modulate insulin sensitivity, which have potential to have an effect on crucial metabolic processes. Their contribution to the management of oxidative stress, inflammation, blood sugar, cholesterol, weight, gut health, liver function, thermogenesis, and appetite regulation is discussed in this work. Although encouraging, more study is necessary to complete clarify the mechanism of action and to determine the efficacy of curry leaves in metabolic disorder.