bluuebunny/crossref_metadata_2025 huggingface dataset:
The carbonyl-lock mechanism underlying non-aromatic fluorescence in biological matter
Authors: Mirón Gonzalo Díaz , Semelak Jonathan A. , Grisanti Luca , Rodriguez Alex , Conti Irene , Stella Martina , Velusamy Jayaramakrishnan , Seriani Nicola , Došlić Nadja , Rivalta Ivan , Garavelli Marco , Estrin Dario A. , Kaminski Schierle Gabriele S. , González Lebrero Mariano C. , Hassanali Ali , Morzan Uriel N.
Published: November 2023

Challenging the basis of our chemical intuition, recent experimental evidence reveals the presence of a new type of intrinsic fluorescence in biomolecules that exists even in the absence of aromatic or electronically conjugated chemical compounds. The origin of this phenomenon has remained elusive so far. In the present study, we identify a mechanism underlying this new type of fluorescence in different biological aggregates. By employing non-adiabatic ab initio molecular dynamics simulations combined with a data-driven approach, we characterize the typical ultrafast non-radiative relaxation pathways active in non-fluorescent peptides. We show that the key vibrational mode for the non-radiative decay towards the ground state is the carbonyl elongation. Non-aromatic fluorescence appears to emerge from blocking this mode with strong local interactions such as hydrogen bonds. While we cannot rule out the existence of alternative non-aromatic fluorescence mechanisms in other systems, we demonstrate that this carbonyl-lock mechanism for trapping the excited state leads to the fluorescence yield increase observed experimentally, and set the stage for design principles to realize novel non-invasive biocompatible probes with applications in bioimaging, sensing, and biophotonics.
Evidence for charge delocalization crossover in the quantum critical superconductor CeRhIn5
Authors: Wang Honghong , Park Tae Beom , Kim Jihyun , Jang Harim , Bauer Eric D. , Thompson Joe D. , Park Tuson
Published: November 2023

The nature of charge degrees-of-freedom distinguishes scenarios for interpreting the character of a second order magnetic transition at zero temperature, that is, a magnetic quantum critical point (QCP). Heavy-fermion systems are prototypes of this paradigm, and in those, the relevant question is where, relative to a magnetic QCP, does the Kondo effect delocalize their f-electron degrees-of-freedom. Herein, we use pressure-dependent Hall measurements to identify a finite-temperature scale Eloc that signals a crossover from f-localized to f-delocalized character. As a function of pressure, Eloc(P) extrapolates smoothly to zero temperature at the antiferromagnetic QCP of CeRhIn5 where its Fermi surface reconstructs, hallmarks of Kondo-breakdown criticality that generates critical magnetic and charge fluctuations. In 4.4% Sn-doped CeRhIn5, however, Eloc(P) extrapolates into its magnetically ordered phase and is decoupled from the pressure-induced magnetic QCP, which implies a spin-density-wave (SDW) type of criticality that produces only critical fluctuations of the SDW order parameter. Our results demonstrate the importance of experimentally determining Eloc to characterize quantum criticality and the associated consequences for understanding the pairing mechanism of superconductivity that reaches a maximum Tc in both materials at their respective magnetic QCP.
RNA m6A methylation modulates airway inflammation in allergic asthma via PTX3-dependent macrophage homeostasis
Authors: Han Xiao , Liu Lijuan , Huang Saihua , Xiao Wenfeng , Gao Yajing , Zhou Weitao , Zhang Caiyan , Zheng Hongmei , Yang Lan , Xie Xueru , Liang Qiuyan , Tu Zikun , Yu Hongmiao , Fu Jinrong , Wang Libo , Zhang Xiaobo , Qian Liling , Zhou Yufeng
Published: November 2023

N6-methyladenosine (m6A), the most prevalent mRNA modification, has an important function in diverse biological processes. However, the involvement of m6A in allergic asthma and macrophage homeostasis remains largely unknown. Here we show that m6A methyltransferases METTL3 is expressed at a low level in monocyte-derived macrophages from childhood allergic asthma patients. Conditional knockout of Mettl3 in myeloid cells enhances Th2 cell response and aggravates allergic airway inflammation by facilitating M2 macrophage activation. Loss and gain functional studies confirm that METTL3 suppresses M2 macrophage activation partly through PI3K/AKT and JAK/STAT6 signaling. Mechanistically, m6A-sequencing shows that loss of METTL3 impairs the m6A-YTHDF3-dependent degradation of PTX3 mRNA, while higher PTX3 expression positively correlates with asthma severity through promoting M2 macrophage activation. Furthermore, the METTL3/YTHDF3-m6A/PTX3 interactions contribute to autophagy maturation in macrophages by modulating STX17 expression. Collectively, this study highlights the function of m6A in regulating macrophage homeostasis and identifies potential targets in controlling allergic asthma.
IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial
Authors: Ackerman Lindsay , Acloque Gerard , Bacchelli Sandro , Schwartz Howard , Feinstein Brian J. , La Stella Phillip , Alavi Afsaneh , Gollerkeri Ashwin , Davis Jeffrey , Campbell Veronica , McDonald Alice , Agarwal Sagar , Karnik Rahul , Shi Kelvin , Mishkin Aimee , Culbertson Jennifer , Klaus Christine , Enerson Bradley , Massa Virginia , Kuhn Eric , Sharma Kirti , Keaney Erin , Barnes Randy , Chen Dapeng , Zheng Xiaozhang , Rong Haojing , Sabesan Vijay , Ho Chris , Mainolfi Nello , Slavin Anthony , Gollob Jared A.
Published: November 2023

Toll-like receptor–driven and interleukin-1 (IL-1) receptor–driven inflammation mediated by IL-1 receptor–associated kinase 4 (IRAK4) is involved in the pathophysiology of hidradenitis suppurativa (HS) and atopic dermatitis (AD). KT-474 (SAR444656), an IRAK4 degrader, was studied in a randomized, double-blind, placebo-controlled phase 1 trial where the primary objective was safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics and clinical activity in patients with moderate to severe HS and in patients with moderate to severe AD. KT-474 was administered as a single dose and then daily for 14 d in 105 healthy volunteers (HVs), followed by dosing for 28 d in an open-label cohort of 21 patients. Degradation of IRAK4 was observed in HV blood, with mean reductions after a single dose of ≥93% at 600–1,600 mg and after 14 daily doses of ≥95% at 50–200 mg. In patients, similar IRAK4 degradation was achieved in blood, and IRAK4 was normalized in skin lesions where it was overexpressed relative to HVs. Reduction of disease-relevant inflammatory biomarkers was demonstrated in the blood and skin of patients with HS and patients with AD and was associated with improvement in skin lesions and symptoms. There were no drug-related infections. These results, from what, to our knowledge, is the first published clinical trial using a heterobifunctional degrader, provide initial proof of concept for KT-474 in HS and AD to be further confirmed in larger trials. ClinicalTrials.gov identifier: NCT04772885.
Integrated chemical and genetic screens unveil FSP1 mechanisms of ferroptosis regulation
Authors: Nakamura Toshitaka , Mishima Eikan , Yamada Naoya , Mourão André Santos Dias , Trümbach Dietrich , Doll Sebastian , Wanninger Jonas , Lytton Elena , Sennhenn Peter , Nishida Xavier da Silva Thamara , Angeli José Pedro Friedmann , Sattler Michael , Proneth Bettina , Conrad Marcus
Published: November 2023

Ferroptosis, marked by iron-dependent lipid peroxidation, may present an Achilles heel for the treatment of cancers. Ferroptosis suppressor protein-1 (FSP1), as the second ferroptosis mainstay, efficiently prevents lipid peroxidation via NAD(P)H-dependent reduction of quinones. Because its molecular mechanisms have remained obscure, we studied numerous FSP1 mutations present in cancer or identified by untargeted random mutagenesis. This mutational analysis elucidates the FAD/NAD(P)H-binding site and proton-transfer function of FSP1, which emerged to be evolutionarily conserved among different NADH quinone reductases. Using random mutagenesis screens, we uncover the mechanism of action of next-generation FSP1 inhibitors. Our studies identify the binding pocket of the first FSP1 inhibitor, iFSP1, and introduce the first species-independent FSP1 inhibitor, targeting the NAD(P)H-binding pocket. Conclusively, our study provides new insights into the molecular functions of FSP1 and enables the rational design of FSP1 inhibitors targeting cancer cells.
Memorability-based multimedia analytics for robotic interestingness prediction system using trimmed Q-learning algorithm
Authors: Ali Hasnain , Gilani Syed Omer , Waris Asim , Shah Umer Hameed , Khattak Muazzam A. Khan , Khan Muhammad Jawad , Afzal Namra
Published: November 2023

Mobile robots are increasingly employed in today’s environment. Perceiving the environment to perform a task plays a major role in the robots. The service robots are wisely employed in the fully (or) partially known user’s environment. The exploration and exploitation of the unknown environment is a tedious task. This paper introduces a novel Trimmed Q-learning algorithm to predict interesting scenes via efficient memorability-oriented robotic behavioral scene activity training. The training process involves three stages: online learning and short-term and long-term learning modules. It is helpful for autonomous exploration and making wiser decisions about the environment. A simplified three-stage learning framework is introduced to train and predict interesting scenes using memorability. A proficient visual memory schema (VMS) is designed to tune the learning parameters. A role-based profile arrangement is made to explore the unknown environment for a long-term learning process. The online and short-term learning frameworks are designed using a novel Trimmed Q-learning algorithm. The underestimated bias in robotic actions must be minimized by introducing a refined set of practical candidate actions. Finally, the recalling ability of each learning module is estimated to predict the interesting scenes. Experiments conducted on public datasets, SubT, and SUN databases demonstrate the proposed technique’s efficacy. The proposed framework has yielded better memorability scores in short-term and online learning at 72.84% and in long-term learning at 68.63%.
Leveraging a novel NFT-enabled blockchain architecture for the authentication of IoT assets in smart cities
Authors: Khalil Usman , Malik Owais Ahmed , Hong Ong Wee , Uddin Mueen
Published: November 2023

The concept of smart city architecture requires a comprehensive solution that can combine real-time response applications for cyber-physical systems. However, the architecture faces challenges that can obstruct the operations in terms of systems, processes, and data flow as far as the breach risk is concerned. Though the field has been researched with the existence of centralized and distributed architectures to support smart cities. Research gaps regarding security concerns, platform assistance, and resource management continue to persist. This research article presents a novel blockchain-based architecture that proposes expansion in the non-fungible tokens (NFTs) to cater to the expansion of IoT-enabled smart assets. It enables NFTs to employ fog computing for all users and smart devices connected to a fog node in a cyber-physical system. The proposed expansion suggested in Non-Fungible Tokens (NFTs) for IoT assets representation in a cyber-physical system, provides devices and user identification and authentication functionality. The proposed NFT architecture has been designed to provide a smart city solution for cyber-physical systems that ensures robust security features (such as CIA) by introducing new attributes and functions for Owner, User, Fog, and IoT device/s authentication. The validation and rigor of the security services, efficiency, and latency have been achieved by deployments on private and public ledgers. The efficiency, and cost-effectiveness of the suggested functions and components have been evaluated in terms of evaluation cost and time complexity which resulted in promising results, obtained and validated on a testnet. The evaluation cost for the devised mint component was approximately 81%, and devisedapprove()was approximately 23% more efficient than other solutions.
Coalescence and mixing dynamics of droplets in acoustic levitation by selective colour imaging and measurement
Authors: Honda Kota , Fujiwara Kota , Hasegawa Koji , Kaneko Akiko , Abe Yutaka
Published: November 2023

Acoustic levitation is well-suited to ‘lab-on-a-drop’ contactless chemical analysis of droplets. Rapid mixing is of fundamental importance in lab-on-a-drop platforms and many other applications involving droplet manipulation. Small droplets, however, have low Reynolds numbers; thus, mixing via turbulence is not possible. Inducing surface oscillation is effective in this regard, however, the relationship between internal flow and mixing dynamics of droplets remains unclear. In this study, we conducted a set of simultaneous optical measurements to assess both the flow field and the distribution of fluid components within acoustically levitated droplets. To achieve this, we developed a technique to selectively separate fluorescent particles within each fluid, permitting the measurement of the concentration field based on the data from the discrete particle distribution. This approach revealed a relationship between the mixing process and the internal flow caused by surface oscillation. Thus, the internal flow induced by surface oscillation could enhance droplet mixing. Our findings will be conducive to the application and further development of lab-on-a-drop devices.
Inhibitory efficiency of Andrographis paniculata extract on viral multiplication and nitric oxide production
Authors: Siridechakorn Ittipon , Bhattarakosol Parvapan , Sasivimolrattana Thanayod , Anoma Sasiprapa , Wongwad Eakkaluk , Nuengchamnong Nitra , Kowitdamrong Ekasit , Boonyasuppayakorn Siwaporn , Waranuch Neti
Published: November 2023

Andrographis paniculata (Burm. F.) Nees is a medicinal plant previously reported with broad-spectrum antivirals but the mode of inhibition remains elusive. The objective of this study was to identify the most active fraction from A. paniculata ethanol extract (APE, APE-2A, APE-2B and APE-2C) and dry powder extract (APSP) against influenza A (H3N2), representing RNA viruses, and herpes simplex virus-1 (HSV-1), representing DNA viruses. The results showed that the fractions APSP, APE, APE-2B, and APE-2C directly neutralized the HSV-1 and influenza A (H3N2) when incubated at room temperature for 60 min before infecting the cells. The results also showed that the additional APE-2A fraction also directly neutralized the influenza A (H3N2), but not the HSV-1. The APE, APE-2B and APE-2C inhibited the HSV-1 by more than 0.5 log when the fractions were introduced after infection. Similarly, the APSP and APE inhibited the influenza A (H3N2) more than 0.5 log after infection. Only 50 μg/mL APE-2C inhibited the viruses greater than 0.5 log. In addition, A. paniculata extracts were also evaluated for their interfering capacities against nitric oxide (NO) production in LPS-activated RAW 264.7 macrophages. As well, APE-2C potently inhibited NO production at the IC50 of 6.08 μg/mL. HPLC and LC–MS analysis indicated that the most actively antiviral fractions did not contain any andrographolide derivatives, whereas the andrographolide-rich fractions showed moderate activity.
Harmonization of multi-site diffusion tensor imaging data for cervical and thoracic spinal cord at 1.5 T and 3 T using longitudinal ComBat
Authors: Middleton Devon M. , Li Yutong , Chen Andrew , Shinohara Russell , Fisher Joshua , Krisa Laura , Elliot Mark , Faro Scott H. , Woo John H. , Flanders Adam E. , Mohamed Feroze B.
Published: November 2023

MRI scanner hardware, field strengths, and sequence parameters are major variables in diffusion studies of the spinal cord. Reliability between scanners is not well known, particularly for the thoracic cord. DTI data was collected for the entire cervical and thoracic spinal cord in thirty healthy adult subjects with different MR vendors and field strengths. DTI metrics were extracted and averaged for all slices within each vertebral level. Metrics were examined for variability and then harmonized using longitudinal ComBat (longComBat). Four scanners were used: Siemens 3 T Prisma, Siemens 1.5 T Avanto, Philips 3 T Ingenia, Philips 1.5 T Achieva. Average full cord diffusion values/standard deviation for all subjects and scanners were FA: 0.63, σ = 0.10, MD: 1.11, σ = 0.12 × 10−3 mm2/s, AD: 1.98, σ = 0.55 × 10−3 mm2/s, RD: 0.67, σ = 0.31 × 10−3 mm2/s. FA metrics averaged for all subjects by level were relatively consistent across scanners, but large variability was found in diffusivity measures. Coefficients of variation were lowest in the cervical region, and relatively lower for FA than diffusivity measures. Harmonized metrics showed greatly improved agreement between scanners. Variability in DTI of the spinal cord arises from scanner hardware differences, pulse sequence differences, physiological motion, and subject compliance. The use of longComBat resulted in large improvement in agreement of all DTI metrics between scanners. This study shows the importance of harmonization of diffusion data in the spinal cord and potential for longitudinal and multisite clinical research and clinical trials.
A deep-learning automated image recognition method for measuring pore patterns in closely related bolivinids and calibration for quantitative nitrate paleo-reconstructions
Authors: Govindankutty Menon Anjaly , Davis Catherine V. , Nürnberg Dirk , Nomaki Hidetaka , Salonen Iines , Schmiedl Gerhard , Glock Nicolaas
Published: November 2023

Eutrophication is accelerating the recent expansion of oxygen-depleted coastal marine environments. Several bolivinid foraminifera are abundant in these oxygen-depleted settings, and take up nitrate through the pores in their shells for denitrification. This makes their pore density a possible nitrate proxy. This study documents three aspects related to the porosity of bolivinids. 1. A new automated image analysis technique to determine the number of pores in bolivinids is tested. 2. The pore patterns ofBolivina spissafrom five different ocean settings are analysed. The relationship between porosity, pore density and mean pore size significantly differs between the studied locations. Their porosity is mainly controlled by the size of the pores at the Gulf of Guayaquil (Peru), but by the number of pores at other studied locations. This might be related to the presence of a different crypticBolivinaspecies in the Gulf of Guayaquil. 3. The pore densities of closely related bolivinids in core-top samples are calibrated as a bottom-water nitrate proxy.Bolivina spissaandBolivina subadvenashowed the same correlation between pore density and bottom-water nitrate concentrations, while the pore density ofBolivina argenteaandBolivina subadvena accumeatais much higher.
Neural correlates of weight-shift training in older adults: a randomized controlled study
Authors: de Rond Veerle , D’Cruz Nicholas , Hulzinga Femke , McCrum Christopher , Verschueren Sabine , de Xivry Jean-Jacques Orban , Nieuwboer Alice
Published: November 2023

Mediolateral weight-shifting is an important aspect of postural control. As it is currently unknown whether a short training session of mediolateral weight-shifting in a virtual reality (VR) environment can improve weight-shifting, we investigated this question and also probed the impact of practice on brain activity. Forty healthy older adults were randomly allocated to a training (EXP, n = 20, age = 70.80 (65–77), 9 females) or a control group (CTR, n = 20, age = 71.65 (65–82), 10 females). The EXP performed a 25-min weight-shift training in a VR-game, whereas the CTR rested for the same period. Weight-shifting speed in both single- (ST) and dual-task (DT) conditions was determined before, directly after, and 24 h after intervention. Functional Near-Infrared Spectroscopy (fNIRS) assessed the oxygenated hemoglobin (HbO2) levels in five cortical regions of interest. Weight-shifting in both ST and DT conditions improved in EXP but not in CTR, and these gains were retained after 24 h. Effects transferred to wider limits of stability post-training in EXP versus CTR. HbO2 levels in the left supplementary motor area were significantly increased directly after training in EXP during ST (change < SEM), and in the left somatosensory cortex during DT (change > SEM). We interpret these changes in the motor coordination and sensorimotor integration areas of the cortex as possibly learning-related.
Chiral domain dynamics and transient interferences of mirrored superlattices in nonequilibrium electronic crystals
Authors: Ravnik J. , Vaskivskyi Ye. , Vodeb J. , Diego M. , Venturini R. , Gerasimenko Ya. , Kabanov V. , Kranjec A. , Mihailovic D.
Published: November 2023

Mirror symmetry plays a major role in determining the properties of matter and is of particular interest in condensed many-body systems undergoing symmetry breaking transitions under non-equilibrium conditions. Typically, in the aftermath of such transitions, one of the two possible broken symmetry states is emergent. However, synthetic systems and those formed under non-equilibrium conditions may exhibit metastable states comprising of both left (L) and right (R) handed symmetry. Here we explore the formation of chiral charge-density wave (CDW) domains after a laser quench in 1T-TaS2 with scanning tunneling microscopy. Typically, we observed transient domains of both chiralities, separated spatially from each other by domain walls with different structure. In addition, we observe transient density of states modulations consistent with interference of L and R-handed charge density waves within the surface monolayer. Theoretical modeling of the intertwined domain structures using a classical charged lattice gas model reproduces the experimental domain wall structures. The superposition (S) state cannot be understood classically within the correlated electron model but is found to be consistent with interferences of L and R-handed charge-density waves within domains, confined by surrounding domain walls, vividly revealing an interference of Fermi electrons with opposite chirality, which is not a result of inter-layer interference, but due to the interaction between electrons within a single layer, confined by domain wall boundaries.
Experimental and numerical investigation on failure mechanism of expansive soil subgrade slope
Authors: Zhang Hongri , Yang Jiming , Wang Lei , Xu Yongfu , Lan Sulian , Luo Junhui , Chang Zhenchao
Published: November 2023

Shallow landslides of expensive soil slopes occur from time to time, and most engineering geological problems are directly or indirectly caused by soil structure cracks. The existence of tensile cracks can significantly affect the hydro-mechanical properties of soils. In this paper, the mechanism of expansive soil landslide formation is explored, and swelling pressures, and drying and wetting cycles are introduced into the discrete element method (DEM), and the landslide process of expansive soils is studied by the numerical simulation mothed. The relationship between the crack development and the instability of expansive soil slopes was investigated. The results show that under the condition of seasonal dry and wet alternation, the cracks of the expansive soil slope gradually develop, the rainwater infiltrates rapidly, the mechanical properties gradually deteriorate, and under the effect of such adverse cycle, the soil gradually softens and the stability decreases. Under the influence of human activities, vehicle loads and other factors, the slope body slides. These findings are helpful for the design and construction of expansive soil slopes and foundations.
Machine learning vs. traditional regression analysis for fluid overload prediction in the ICU
Authors: Sikora Andrea , Zhang Tianyi , Murphy David J. , Smith Susan E. , Murray Brian , Kamaleswaran Rishikesan , Chen Xianyan , Buckley Mitchell S. , Rowe Sandra , Devlin John W.
Published: November 2023

Fluid overload, while common in the ICU and associated with serious sequelae, is hard to predict and may be influenced by ICU medication use. Machine learning (ML) approaches may offer advantages over traditional regression techniques to predict it. We compared the ability of traditional regression techniques and different ML-based modeling approaches to identify clinically meaningful fluid overload predictors. This was a retrospective, observational cohort study of adult patients admitted to an ICU ≥ 72 h between 10/1/2015 and 10/31/2020 with available fluid balance data. Models to predict fluid overload (a positive fluid balance ≥ 10% of the admission body weight) in the 48–72 h after ICU admission were created. Potential patient and medication fluid overload predictor variables (n = 28) were collected at either baseline or 24 h after ICU admission. The optimal traditional logistic regression model was created using backward selection. Supervised, classification-based ML models were trained and optimized, including a meta-modeling approach. Area under the receiver operating characteristic (AUROC), positive predictive value (PPV), and negative predictive value (NPV) were compared between the traditional and ML fluid prediction models. A total of 49 of the 391 (12.5%) patients developed fluid overload. Among the ML models, the XGBoost model had the highest performance (AUROC 0.78, PPV 0.27, NPV 0.94) for fluid overload prediction. The XGBoost model performed similarly to the final traditional logistic regression model (AUROC 0.70; PPV 0.20, NPV 0.94). Feature importance analysis revealed severity of illness scores and medication-related data were the most important predictors of fluid overload. In the context of our study, ML and traditional models appear to perform similarly to predict fluid overload in the ICU. Baseline severity of illness and ICU medication regimen complexity are important predictors of fluid overload.
Structural differences between non-lucid dreams, lucid dreams and out-of-body experience reports assessed by graph analysis
Authors: Gallo Francisco T. , Spiousas Ignacio , Herrero Nerea L. , Godoy Daniela , Tommasel Antonela , Gasca-Rolin Miguel , Ramele Rodrigo , Gleiser Pablo M. , Forcato Cecilia
Published: November 2023

Dreaming is a complex phenomenon that occurs during sleep, involving various conscious dream experiences. Lucid dreams (LDs) involve heightened awareness within the dream environment, while out-of-body experiences (OBEs) involve the sensation of being outside one’s physical body. OBEs occur during sleep paralysis (SP), where voluntary movements are inhibited during sleep/wake transitions while remaining aware of the surroundings. The relationship between LDs and OBEs is debated, with some viewing them as distinct phenomena and others considering them different manifestations of the same underlying experience. This study aimed to characterize non-lucid dreams, LDs, and OBEs by analyzing dream reports’ structural properties. OBE reports displayed a condensed and interconnected network structure compared to non-lucid dreams and LDs. Additionally, OBE reports exhibited a specialized network structure, with specific nodes playing a more central role. These findings suggest that OBE dreams may have a more coherent and unified narrative, with certain nodes being pivotal in the network structure.
Comparative performance analysis of binary variants of FOX optimization algorithm with half-quadratic ensemble ranking method for thyroid cancer detection
Authors: Sharma Rohit , Mahanti Gautam Kumar , Panda Ganapati , Rath Adyasha , Dash Sujata , Mallik Saurav , Zhao Zhongming
Published: November 2023

Thyroid cancer is a life-threatening condition that arises from the cells of the thyroid gland located in the neck’s frontal region just below the adam’s apple. While it is not as prevalent as other types of cancer, it ranks prominently among the commonly observed cancers affecting the endocrine system. Machine learning has emerged as a valuable medical diagnostics tool specifically for detecting thyroid abnormalities. Feature selection is of vital importance in the field of machine learning as it serves to decrease the data dimensionality and concentrate on the most pertinent features. This process improves model performance, reduces training time, and enhances interpretability. This study examined binary variants of FOX-optimization algorithms for feature selection. The study employed eight transfer functions (S and V shape) to convert the FOX-optimization algorithms into their binary versions. The vision transformer-based pre-trained models (DeiT and Swin Transformer) are used for feature extraction. The extracted features are transformed using locally linear embedding, and binary FOX-optimization algorithms are applied for feature selection in conjunction with the Naïve Bayes classifier. The study utilized two datasets (ultrasound and histopathological) related to thyroid cancer images. The benchmarking is performed using the half-quadratic theory-based ensemble ranking technique. Two TOPSIS-based methods (H-TOPSIS and A-TOPSIS) are employed for initial model ranking, followed by an ensemble technique for final ranking. The problem is treated as multi-objective optimization task with accuracy, F2-score, AUC-ROC and feature space size as optimization goals. The binary FOX-optimization algorithm based on the $$V_1$$

V
1

transfer function achieved superior performance compared to other variants using both datasets as well as feature extraction techniques. The proposed framework comprised a Swin transformer to extract features, a Fox optimization algorithm with a V1 transfer function for feature selection, and a Naïve Bayes classifier and obtained the best performance for both datasets. The best model achieved an accuracy of 94.75%, an AUC-ROC value of 0.9848, an F2-Score of 0.9365, an inference time of 0.0353 seconds, and selected 5 features for the ultrasound dataset. For the histopathological dataset, the diagnosis model achieved an overall accuracy of 89.71%, an AUC-ROC score of 0.9329, an F2-Score of 0.8760, an inference time of 0.05141 seconds, and selected 12 features. The proposed model achieved results comparable to existing research with small features space.
RETRACTED ARTICLE: Sciadopitysin mitigates spermatological and testicular damage instigated by paraquat administration in male albino rats
Authors: Ijaz Muhammad Umar , Qamer Mohammad , Hamza Ali , Ahmed Hussain , Afsar Tayyaba , Abulmeaty Mahmoud , Ayub Arusha , Razak Suhail
Published: November 2023

Paraquat (PQ) is a herbicide that has ability to induce testicular toxicity by producing reactive oxygen species (ROS). Sciadopitysin (SPS) is a promising flavonoid that displays multiple pharmacological properties i.e., anti-inflammatory, anti-oxidant and anti-apoptotic. Therefore, the present study was designed to evaluate the mitigative role of SPS against PQ induced testicular toxicity in male rats. The experiment was performed on male albino rats (n = 48) that were divided into 4 groups. The group-1 was control group. Group-2 was administrated orally with PQ (5 mg/kg). Group-3 was administrated orally with PQ (5 mg/kg) and SPS (2 mg/kg). Group-4 was supplemented with SPS (2 mg/kg) through oral gavage. The experiment was conducted for 56 days. The exposure to PQ significantly lowered the activities of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD) as well as glutathione peroxidase (GPx). Whereas, a substantial increase was observed in dead sperms number, abnormalities in the tail, head as well as midpiece of sperms in PQ intoxicated rats. Moreover, a significant increase in the level of ROS and malondialdehyde (MDA) was noticed in PQ administrated group. Furthermore, steroidogenic enzymes expression was significantly decreased in PQ-intoxicated group, whereas the level of inflammatory markers was increased in PQ administrated rats. Besides, the expression of apoptotic markers was significantly escalated in PQ exposed rats, whereas the expression of anti-apoptotic markers was considerably reduced. A significant reduction in hormonal level was also noticed in the rats that were administrated with PQ. Moreover, the histopathological examination revealed that PQ significantly damaged the testicles. However, the supplementation of SPS with PQ significantly reduced the adverse effects of PQ in the testes of albino rats. Therefore, the current investigation demonstrated that SPS possesses a significant potential to avert PQ-induced testicular dysfunction due to its anti-apoptotic, androgenic, anti-oxidant and anti-inflammatory nature.
The association of copeptin with metabolic risk markers is modified by region of origin
Authors: Franzén Anna , Pikkemaat Miriam , Melander Olle , Bennet Louise , Enhörning Sofia
Published: November 2023

Iraqi born immigrants in Sweden have higher prevalence of metabolic diseases compared to native Swedes. Copeptin, a marker for vasopressin, is associated with increased risk of metabolic disease. In this cross-sectional population study based on the MEDIM cohort we investigated differences in copeptin levels between Iraqi and Swedish born individuals and if the association between copeptin and cardiometabolic risk markers differed by region of origin. We included 1109 Iraqi and 613 Swedish born participants (58% men, mean age 47 years). The Swedish participants had a higher concentration of copeptin compared to the Iraqi born group after age and sex adjustment (p < 0.001). This difference existed only among male individuals with the highest copeptin concentrations, i.e. belonging to copeptin quartile 4 (median (25th; 75th percentile) 20.07 (15.27;33.28) pmol/L for the Swedish born versus 15.57 (13.91;19.00) pmol/L for the Iraqi born, p < 0.001). We found a significant interaction between copeptin (continuous ln-transformed) and being born in Iraq regarding the association with plasma triglycerides (Pinteraction = 0.006). The association between copeptin and BMI was stronger amongst the Iraqi born individuals compared to the Swedish born. Together, this could indicate that copeptin is a more potent marker of metabolic disease among individuals born in Iraq compared to Sweden.
Human leukocyte antigen-DQ risk heterodimeric haplotypes of left ventricular dysfunction in cardiac sarcoidosis: an autoimmune view of its role
Authors: Yamamoto Hironori , Miyashita Yohei , Minamiguchi Hitoshi , Hosomichi Kazuyoshi , Yoshida Shohei , Kioka Hidetaka , Shinomiya Haruki , Nagata Haruno , Onoue Kenji , Kawasaki Masato , Kuramoto Yuki , Nomura Akihiro , Toma Yuichiro , Watanabe Tetsuya , Yamada Takahisa , Ishihara Yasuki , Nagata Miho , Kato Hisakazu , Hakui Hideyuki , Saito Yoshihiko , Asano Yoshihiro , Sakata Yasushi
Published: November 2023

Cardiac sarcoidosis (CS) is the scarring of heart muscles by autoimmunity, leading to heart abnormalities and patients with sarcoidosis with cardiac involvements have poor prognoses. Due to the small number of patients, it is difficult to stratify all patients of CS by human leukocyte antigen (HLA) analysis. We focused on the structure of antigen-recognizing pockets in heterodimeric HLA-class II, in addition to DNA sequences, and extracted high-affinity combinations of antigenic epitopes from candidate autoantigen proteins and HLA. Four HLA heterodimer-haplotypes (DQA1*05:03/05:05/05:06/05:08-DQB1*03:01) were identified in 10 of 68 cases. Nine of the 10 patients had low left ventricular ejection fraction (< 50%). Fourteen amino-acid sequences constituting four HLA anchor pockets encoded by the HLA haplotypes were all common, suggesting DQA1*05:0X-DQB1*03:01 exhibit one group of heterodimeric haplotypes. The heterodimeric haplotypes recognized eight epitopes from different proteins. Assuming that autoimmune mechanisms might be activated by molecular mimicry, we searched for bacterial species having peptide sequences homologous to the eight epitopes. Within the peptide epitopes form the SLC25A4 and DSG2, high-homology sequences were found in Cutibacterium acnes and Mycobacterium tuberculosis, respectively. In this study, we detected the risk heterodimeric haplotypes of ventricular dysfunction in CS by searching for high-affinity HLA-class II and antigenic epitopes from candidate cardiac proteins.
Novel RICTOR amplification harbouring entities: FISH validation of RICTOR amplification in tumour tissue after next-generation sequencing
Authors: Sztankovics Dániel , Krencz Ildikó , Moldvai Dorottya , Dankó Titanilla , Nagy Ákos , Nagy Noémi , Bedics Gábor , Rókusz András , Papp Gergő , Tőkés Anna-Mária , Pápay Judit , Sápi Zoltán , Dezső Katalin , Bödör Csaba , Sebestyén Anna
Published: November 2023

Alterations in mTOR signalling molecules, including RICTOR amplification, have been previously described in many cancers, particularly associated with poor prognosis. In this study, RICTOR copy number variation (CNV) results of diagnostic next-generation sequencing (NGS) were analysed in 420 various human malignant tissues. RICTOR amplification was tested by Droplet Digital PCR (ddPCR) and validated using the “gold standard” fluorescence in situ hybridisation (FISH). Additionally, the consequences of Rictor protein expression were also studied by immunohistochemistry. RICTOR amplification was presumed in 37 cases with CNV ≥ 3 by NGS, among these, 16 cases (16/420; 3.8%) could be validated by FISH, however, ddPCR confirmed only 11 RICTOR-amplified cases with lower sensitivity. Based on these, neither NGS nor ddPCR could replace traditional FISH in proof of RICTOR amplification. However, NGS could be beneficial to highlight potential RICTOR-amplified cases. The obtained results of the 14 different tumour types with FISH-validated RICTOR amplification demonstrate the importance of RICTOR amplification in a broad spectrum of tumours. The newly described RICTOR-amplified entities could initiate further collaborative studies with larger cohorts to analyse the prevalence of RICTOR amplification in rare diseases. Finally, our and further work could help to improve and expand future therapeutic opportunities for mTOR-targeted therapies.
Induced alternative splicing an opportunity to study PCSK9 protein isoforms at physiologically relevant concentrations
Authors: Cale Jessica M. , Ham Kristin A. , Li Dunhui , McIntosh Craig S. , Watts Gerald F. , Wilton Steve D. , Aung-Htut May T.
Published: November 2023

Splice modulating antisense oligomers (AOs) are increasingly used to modulate RNA processing. While most are investigated for their use as therapeutics, AOs can also be used for basic research. This study examined their use to investigate internally and terminally truncated proprotein convertase subtilisin/kexin type 9 (PCSK9) protein isoforms. Previous studies have used plasmid or viral-vector-mediated protein overexpression to study different PCSK9 protein isoforms, creating an artificial environment within the cell. Here we designed and tested AOs to remove specific exons that encode for PCSK9 protein domains and produced protein isoforms at more physiologically relevant levels. We evaluated the isoforms’ expression, secretion, and subsequent impact on the low-density lipoprotein (LDL) receptor and its activity in Huh-7 cells. We found that modifying the Cis-His-rich domain by targeting exons 10 or 11 negatively affected LDL receptor activity and hence did not enhance LDL uptake although the levels of LDL receptor were increased. On the other hand, removing the hinge region encoded by exon 8, or a portion of the prodomain encoded by exon 2, have the potential as therapeutics for hypercholesterolemia. Our findings expand the understanding of PCSK9 isoforms and their impact on the LDL receptor and its activity at physiologically relevant concentrations.
Comparative genomics and genome-wide SNPs of endangered Eld’s deer provide breeder selection for inbreeding avoidance
Authors: Pumpitakkul Vichayanee , Chetruengchai Wanna , Srichomthong Chalurmpon , Phokaew Chureerat , Pootakham Wirulda , Sonthirod Chutima , Nawae Wanapinun , Tongsima Sissades , Wangkumhang Pongsakorn , Wilantho Alisa , Utara Yongchai , Thongpakdee Ampika , Sanannu Saowaphang , Maikaew Umaporn , Khuntawee Suphattharaphonnaphan , Changpetch Wirongrong , Phromwat Phairot , Raschasin Kacharin , Sarnkhaeveerakul Phunyaphat , Supapannachart Pannawat , Buthasane Wannapol , Pukazhenthi Budhan S. , Koepfli Klaus-Peter , Suriyaphol Prapat , Tangphatsornruang Sithichoke , Suriyaphol Gunnaporn , Shotelersuk Vorasuk
Published: November 2023

Eld’s deer, a conserved wildlife species of Thailand, is facing inbreeding depression, particularly in the captive Siamese Eld’s deer (SED) subspecies. In this study, we constructed genomes of a male SED and a male Burmese Eld’s deer (BED), and used genome-wide single nucleotide polymorphisms to evaluate the genetic purity and the inbreeding status of 35 SED and 49 BED with limited pedigree information. The results show that these subspecies diverged approximately 1.26 million years ago. All SED were found to be purebred. A low proportion of admixed SED genetic material was observed in some BED individuals. Six potential breeders from male SED with no genetic relation to any female SED and three purebred male BED with no relation to more than 10 purebred female BED were identified. This study provides valuable insights about Eld’s deer populations and appropriate breeder selection in efforts to repopulate this endangered species while avoiding inbreeding.
Effect of N-phenyl substituent on thermal, optical, electrochemical and luminescence properties of 3-aminophthalimide derivatives
Authors: Kotowicz Sonia , Małecki Jan Grzegorz , Cytarska Joanna , Baranowska-Łączkowska Angelika , Siwy Mariola , Łączkowski Krzysztof Z. , Szalkowski Marcin , Maćkowski Sebastian , Schab-Balcerzak Ewa
Published: November 2023

The seven N-phthalimide derivatives substituted with the amine group at the 3-C position in the phenylene ring were synthesized. The effect of N-substituent chemical structure was investigated. The thermal, electrochemical and optical studies were performed and supported by the density functional theory calculations (DFT). The electrochemical investigations of the synthesized low-molecular phthalimides revealed the one oxidation and reduction process with the HOMO energy level under − 5.81 eV and energy-band gap below 3 eV. The N-phthalimide derivatives were emitted light in a blue spectral region in solutions (in polar and non-polar) with the quantum yield between 2 and 68%, dependent on the substituent at the nitrogen atom, solvent and concentration. The N-phthalimide derivatives were emissive also in a solid state as a thin film and powder. They were tested as a component of the active layer with PVK:PBD matrix and as an independent active layer in the organic light-emitting diodes. The registered electroluminescence spectra exhibited the maximum emission band in the 469–505 nm range, confirming the possibility of using N-phthalimides with PVK:PBD matrix as the blue emitters.
DNA barcode reveals occurrence of threatened species and hidden diversity on Teleost fish trade in the Coastal Amazon
Authors: Santana Paula , Martins Thais , Lutz Ítalo , Miranda Josy , da Silva Raimundo , Mesquita David , Martins Rita , Veneza Ivana , Vallinoto Marcelo , Sampaio Iracilda , Evangelista-Gomes Grazielle
Published: November 2023

This study aimed to identify the teleost fish species sold in Bragança, a major fishing hub on the north coast of Brazil. The COI gene analysis was performed for the identification of fish species. The local market uses common names that are not accurate and do not reflect the diversity of the species. 204 sequences were obtained, with 119 haplotypes. 83 species were identified by comparing with public databases and constructing phylogenetic trees, with Carangidae being the most prevalent family. The study also foundHaemulon atlanticus,Menticirrhus cuiaranensisandHoplias misioneira, a newly described species from the Amazon basin, among the samples. Additionally, 73 commercial names were recorded, including 10 categories, and the illegal trade ofEpinephelus itajarawas detected. The DNA Barcode method proved to be effective for discriminating the species. The study highlights that common and commercial names are vague and underestimate the fish diversity, and that Brazil needs to revise its regulations for commercial and scientific names.
The role of MOTS-c-mediated antioxidant defense in aerobic exercise alleviating diabetic myocardial injury
Authors: Tang Mi , Su Quansheng , Duan Yimei , Fu Yu , Liang Min , Pan Yanrong , Yuan Jinghan , Wang Manda , Pang Xiaoli , Ma Jiacheng , Laher Ismail , Li Shunchang
Published: November 2023

Myocardial remodeling and dysfunction are commonly observed in type 2 diabetes mellitus (T2DM). Aerobic exercise can partly alleviate diabetes-induced myocardial dysfunction through its antioxidant actions. MOTS-c is a potential exercise mimic. This study aimed to investigate the effects of MOTS-c on improving diabetic heart function and its mechanism and to identify whether MOTS-c improved antioxidant defenses due to aerobic exercise. Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection. Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks. Myocardial ultrastructure was assessed using transmission electron microscopy (TEM), myocardial lipid peroxidation levels (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) levels were assessed using colorimetric methods, and molecular analyses including MOTS-c, Kelch-like ECH-associated protein 1 (Keap1), Nuclear factor E2-related factor 2 (Nrf2), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)and phospho-AMPK (p-AMPK) were examined using Western blot. The results showed that MOTS-c, with or without exercise, reduced myocardial ultrastructural damage and improved glucolipid metabolism and cardiac function in T2DM. Furthermore, MOTS-c increased antioxidant markers such as SOD, CAT, and the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK. MOTS-c with exercise treatment reduced myocardial MDA and increased p-AMPK significantly comparing to only exercise or MOTS-c alone. Our findings suggest that MOTS-c may be a helpful supplement for overcoming exercise insufficiency and improving myocardial structure and function in diabetes.
Effects and mechanisms of intrauterine chronic hypoxia on ovarian reserve function of zygotic rats
Authors: Huang Yanyan , Su Shanshan , Luo Weiwen , Zhong Huohu , Wang Xiali , Lyu Guorong
Published: November 2023

Chronic intrauterine hypoxia (ICH) may lead to permanent alterations in the offspring's body structure, function, and metabolism through the "developmental programming" pathway, resulting in lasting changes in physiology and metabolism, as well as the onset of adult-onset diseases. The aim was to investigate intrauterine growth restriction caused by ICH and its effect on ovarian reserve function in female offspring at different developmental stages after birth. Healthy female Sprague–Dawley rats (n = 20) were pregnant by normal mating, and the rats in the ICH group were treated with chronic intrauterine hypoxia twice a day for 04 h00 each time from day 4 to 21 of gestation. After the first hypoxic treatment, four pregnant rats were randomly selected from the ICH and natural control groups for arterial blood gas analysis. In the ICH group, birth weight and body weight on the 5th day after birth were less than in the control group, the total number of follicles and the number of primordial follicles in the offspring of the ICH group were significantly reduced on postnatal days 5, 20, and 40 (p < 0.05). ICH decreases ovarian reserve function in female offspring rats and programmatically regulates the differential expression of ovarian miRNAs in female offspring rats.