bluuebunny/crossref_metadata_2025 huggingface dataset:
Anterior cingulate cortex provides the neural substrates for feedback-driven iteration of decision and value representation
Authors: Chen Wenqi , Liang Jiejunyi , Wu Qiyun , Han Yunyun
Published: July 2024

Adjusting decision-making under uncertain and dynamic situations is the hallmark of intelligence. It requires a system capable of converting feedback information to renew the internal value. The anterior cingulate cortex (ACC) involves in error and reward events that prompt switching or maintenance of current decision strategies. However, it is unclear whether and how the changes of stimulus-action mapping during behavioral adaptation are encoded, nor how such computation drives decision adaptation. Here, we tracked ACC activity in male mice performing go/no-go auditory discrimination tasks with manipulated stimulus-reward contingencies. Individual ACC neurons integrate the outcome information to the value representation in the next-run trials. Dynamic recruitment of them determines the learning rate of error-guided value iteration and decision adaptation, forming a non-linear feedback-driven updating system to secure the appropriate decision switch. Optogenetically suppressing ACC significantly slowed down feedback-driven decision switching without interfering with the execution of the established strategy.
A deterministic, c-di-GMP-dependent program ensures the generation of phenotypically similar, symmetric daughter cells during cytokinesis
Authors: Pérez-Burgos María , Herfurth Marco , Kaczmarczyk Andreas , Harms Andrea , Huber Katrin , Jenal Urs , Glatter Timo , Søgaard-Andersen Lotte
Published: July 2024

Phenotypic heterogeneity in bacteria can result from stochastic processes or deterministic programs. The deterministic programs often involve the versatile second messenger c-di-GMP, and give rise to daughter cells with different c-di-GMP levels by deploying c-di-GMP metabolizing enzymes asymmetrically during cell division. By contrast, less is known about how phenotypic heterogeneity is kept to a minimum. Here, we identify a deterministic c-di-GMP-dependent program that is hardwired into the cell cycle of Myxococcus xanthus to minimize phenotypic heterogeneity and guarantee the formation of phenotypically similar daughter cells during division. Cells lacking the diguanylate cyclase DmxA have an aberrant motility behaviour. DmxA is recruited to the cell division site and its activity is switched on during cytokinesis, resulting in a transient increase in the c-di-GMP concentration. During cytokinesis, this c-di-GMP burst ensures the symmetric incorporation and allocation of structural motility proteins and motility regulators at the new cell poles of the two daughters, thereby generating phenotypically similar daughters with correct motility behaviours. Thus, our findings suggest a general c-di-GMP-dependent mechanism for minimizing phenotypic heterogeneity, and demonstrate that bacteria can ensure the formation of dissimilar or similar daughter cells by deploying c-di-GMP metabolizing enzymes to distinct subcellular locations.
Score-based denoising for atomic structure identification
Authors: Hsu Tim , Sadigh Babak , Bertin Nicolas , Park Cheol Woo , Chapman James , Bulatov Vasily , Zhou Fei
Published: July 2024

We propose an effective method for removing thermal vibrations that complicate the task of analyzing complex dynamics in atomistic simulation of condensed matter. Our method iteratively subtracts thermal noises or perturbations in atomic positions using a denoising score function trained on synthetically noised but otherwise perfect crystal lattices. The resulting denoised structures clearly reveal underlying crystal order while retaining disorder associated with crystal defects. Purely geometric, agnostic to interatomic potentials, and trained without inputs from explicit simulations, our denoiser can be applied to simulation data generated from vastly different interatomic interactions. The denoiser is shown to improve existing classification methods, such as common neighbor analysis and polyhedral template matching, reaching perfect classification accuracy on a recent benchmark dataset of thermally perturbed structures up to the melting point. Demonstrated here in a wide variety of atomistic simulation contexts, the denoiser is general, robust, and readily extendable to delineate order from disorder in structurally and chemically complex materials.
Clonal inactivation of TERT impairs stem cell competition
Authors: Hasegawa Kazuteru , Zhao Yang , Garbuzov Alina , Corces M. Ryan , Neuhöfer Patrick , Gillespie Victoria M. , Cheung Peggie , Belk Julia A. , Huang Yung-Hsin , Wei Yuning , Chen Lu , Chang Howard Y. , Artandi Steven E.
Published: July 2024

Telomerase is intimately associated with stem cells and cancer, because it catalytically elongates telomeres—nucleoprotein caps that protect chromosome ends1. Overexpression of telomerase reverse transcriptase (TERT) enhances the proliferation of cells in a telomere-independent manner2–8, but so far, loss-of-function studies have provided no evidence that TERT has a direct role in stem cell function. In many tissues, homeostasis is shaped by stem cell competition, a process in which stem cells compete on the basis of inherent fitness. Here we show that conditional deletion of Tert in the spermatogonial stem cell (SSC)-containing population in mice markedly impairs competitive clone formation. Using lineage tracing from the Tert locus, we find that TERT-expressing SSCs yield long-lived clones, but that clonal inactivation of TERT promotes stem cell differentiation and a genome-wide reduction in open chromatin. This role for TERT in competitive clone formation occurs independently of both its reverse transcriptase activity and the canonical telomerase complex. Inactivation of TERT causes reduced activity of the MYC oncogene, and transgenic expression of MYC in the TERT-deleted pool of SSCs efficiently rescues clone formation. Together, these data reveal a catalytic-activity-independent requirement for TERT in enhancing stem cell competition, uncover a genetic connection between TERT and MYC and suggest that a selective advantage for stem cells with high levels of TERT contributes to telomere elongation in the male germline during homeostasis and ageing.
Inhibition of IL-11 signalling extends mammalian healthspan and lifespan
Authors: Widjaja Anissa A. , Lim Wei-Wen , Viswanathan Sivakumar , Chothani Sonia , Corden Ben , Dasan Cibi Mary , Goh Joyce Wei Ting , Lim Radiance , Singh Brijesh K. , Tan Jessie , Pua Chee Jian , Lim Sze Yun , Adami Eleonora , Schafer Sebastian , George Benjamin L. , Sweeney Mark , Xie Chen , Tripathi Madhulika , Sims Natalie A. , Hübner Norbert , Petretto Enrico , Withers Dominic J. , Ho Lena , Gil Jesus , Carling David , Cook Stuart A.
Published: July 2024

For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark1–7. Here we examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK–AMPK–mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies. Deletion of Il11 or Il11ra1 protects against metabolic decline, multi-morbidity and frailty in old age. Administration of anti-IL-11 to 75-week-old mice for 25 weeks improves metabolism and muscle function, and reduces ageing biomarkers and frailty across sexes. In lifespan studies, genetic deletion of Il11 extended the lives of mice of both sexes, by 24.9% on average. Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%. Together, these results demonstrate a role for the pro-inflammatory factor IL-11 in mammalian healthspan and lifespan. We suggest that anti-IL-11 therapy, which is currently in early-stage clinical trials for fibrotic lung disease, may provide a translational opportunity to determine the effects of IL-11 inhibition on ageing pathologies in older people.
Integrated analyses highlight interactions between the three-dimensional genome and DNA, RNA and epigenomic alterations in metastatic prostate cancer
Authors: Zhao Shuang G. , Bootsma Matthew , Zhou Stanley , Shrestha Raunak , Moreno-Rodriguez Thaidy , Lundberg Arian , Pan Chu , Arlidge Christopher , Hawley James R. , Foye Adam , Weinstein Alana S. , Sjöström Martin , Zhang Meng , Li Haolong , Chesner Lisa N. , Rydzewski Nicholas R. , Helzer Kyle T. , Shi Yue ,   West Coast Dream Team Consortium, Bailey Adina M. , Zhang Li , Beer Tomasz M. , Thomas George , Chi Kim N. , Gleave Martin , Zoubeidi Amina , Reiter Robert E. , Rettig Matthew B. , Witte Owen , Bose Rohit , Huang Franklin W. , Fong Larry , Lara Primo N. , Evans Christopher P. , Huang Jiaoti , Lynch Molly , Dehm Scott M. , Lang Joshua M. , Alumkal Joshi J. , He Hansen H. , Wyatt Alexander W. , Aggarwal Rahul , Zwart Wilbert , Small Eric J. , Quigley David A. , Lupien Mathieu , Feng Felix Y.
Published: July 2024

The impact of variations in the three-dimensional structure of the genome has been recognized, but solid cancer tissue studies are limited. Here, we performed integrated deep Hi-C sequencing with matched whole-genome sequencing, whole-genome bisulfite sequencing, 5-hydroxymethylcytosine (5hmC) sequencing and RNA sequencing across a cohort of 80 biopsy samples from patients with metastatic castration-resistant prostate cancer. Dramatic differences were present in gene expression, 5-methylcytosine/5hmC methylation and in structural variation versus mutation rate between A and B (open and closed) chromatin compartments. A subset of tumors exhibited depleted regional chromatin contacts at the AR locus, linked to extrachromosomal circular DNA (ecDNA) and worse response to AR signaling inhibitors. We also identified topological subtypes associated with stark differences in methylation structure, gene expression and prognosis. Our data suggested that DNA interactions may predispose to structural variant formation, exemplified by the recurrent TMPRSS2–ERG fusion. This comprehensive integrated sequencing effort represents a unique clinical tumor resource.
Streamflow in the United States: Characteristics, trends, regime shifts, and extremes
Authors: Wang Yiming , Zhang Xuesong , Zhao Kaiguang , Singh Debjani
Published: July 2024

Long-term streamflow observations contain essential information for understanding hydrological changes and managing water resources. A continental-scale dataset or analysis of temporal streamflow change is still lacking across hydrologic gauges in the Conterminous United States (CONUS). Here, we compiled 70 years of streamflow records from 1951 to 2021 at ~ 8000 hydrologic stations across the CONUS and characterized temporal trends, regime shifts, and extreme events using a Bayesian time series analysis algorithm. We found that the occurrences of sudden streamflow changes (e.g., regime shifts and extreme events) have been increasing with time across the CONUS. In addition, we derived 181 streamflow indicators that are valuable for hydrological and biological applications, such as the duration and frequency of high or low streamflow events. The Mississippi River Basin, especially the middle and lower parts, was a hot spot of high-frequency high-flow events. Overall, we anticipate the dataset generated here offers valuable information for understanding and quantifying changes in water resources across the CONUS.
Optimizing decision-making with aggregation operators for generalized intuitionistic fuzzy sets and their applications in the tech industry
Authors: Wasim Muhammad , Yousaf Awais , Alolaiyan Hanan , Akbar Muhammad Azeem , Alburaikan Alhanouf , El-Wahed Khalifa Hamiden Abd
Published: July 2024

Intuitionistic fuzzy sets (IFSs) represent a significant advancement in classical fuzzy set (FS) theory. This study advances IFS theory to generalized intuitionistic fuzzy sets (GIFSBs) and introduces novel operators GIFWAA, GIFWGA, GIFOWAA, and GIFOWGA, tailored for GIFSBs. The primary aim is to enhance decision-making capabilities by introducing aggregation operators within the GIFSB framework that align with preferences for optimal outcomes. The article introduces new operators for GIFSBs characterized by attributes like idempotency, boundedness, monotonicity and commutativity, resulting in aggregated values aligned with GIFNs. A comprehensive analysis of the relationships among these operations is conducted, offering a thorough understanding of their applicability. These operators are practically demonstrated in a multiple-criteria decision-making process for evaluating startup success in the Tech Industry.
Delivery of CDNF by AAV-mediated gene transfer protects dopamine neurons and regulates ER stress and inflammation in an acute MPTP mouse model of Parkinson’s disease
Authors: Nam Jinhan , Richie Christopher T. , Harvey Brandon K. , Voutilainen Merja H.
Published: July 2024

Cerebral dopamine neurotrophic factor (CDNF) and its close structural relative, mesencephalic astrocyte-derived neurotrophic factor (MANF), are proteins with neurotrophic properties. CDNF protects and restores the function of dopamine (DA) neurons in rodent and non-human primate (NHP) toxin models of Parkinson’s disease (PD) and therefore shows promise as a drug candidate for disease-modifying treatment of PD. Moreover, CDNF was found to be safe and to have some therapeutic effects on PD patients in phase 1/2 clinical trials. However, the mechanism underlying the neurotrophic activity of CDNF is unknown. In this study, we delivered human CDNF (hCDNF) to the brain using an adeno-associated viral (AAV) vector and demonstrated the neurotrophic effect of AAV-hCDNF in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. AAV-hCDNF resulted in the expression of hCDNF in the striatum (STR) and substantia nigra (SN), and no toxic effects on the nigrostriatal pathway were observed. Intrastriatal injection of AAV-hCDNF reduced motor impairment and partially alleviated gait dysfunction in the acute MPTP mouse model. In addition, gene therapy with AAV-hCDNF had significant neuroprotective effects on the nigrostriatal pathway and decreased the levels of interleukin 1beta (IL-1β) and complement 3 (C3) in glial cells in the acute MPTP mouse model. Moreover, AAV-hCDNF reduced C/EBP homologous protein (CHOP) and glucose regulatory protein 78 (GRP78) expression in astroglia. These results suggest that the neuroprotective effects of CDNF may be mediated at least in part through the regulation of neuroinflammation and the UPR pathway in a mouse MPTP model of PD in vivo.
Impact of the digital economy on carbon dioxide emissions in resource-based cities
Authors: Kuang Yiming , Fan Yaojun , Bin Jie , Fan Min
Published: July 2024

With the rapid development of the digital economy, its environmental impact, particularly on carbon dioxide emissions in resource-based cities, has emerged as a vital research topic. Resource-based cities, often central to traditional industries, are confronted with the dual challenges of environmental pollution and economic transformation. This study employs empirical analysis to examine the influence of the digital economy on carbon dioxide emissions in these cities. The findings reveal that the digital economy significantly reduces carbon dioxide emissions, with this impact being more pronounced in the early stages of digital economic development and gradually diminishing thereafter. In the mechanism analysis, we found that the digital economy can reduce carbon dioxide emissions in resource-based cities by raising public concern about the environment. Moreover, the study highlights significant variations in carbon reduction effects among different types of resource-based cities, noting that stronger environmental regulations further enhance these effects. These insights not only provide a new theoretical perspective but also offer practical guidance for policymakers in promoting sustainable development within the digital economy.
Kiwifruit-Agaricus blazei intercropping effectively improved yield productivity, nutrient uptake, and rhizospheric bacterial community
Authors: Shen Chuan , Li Xia , Qin Jianfeng
Published: July 2024

Intercropping systems have garnered attention as a sustainable agricultural approach for efficient land use, increased ecological diversity in farmland, and enhanced crop yields. This study examined the effect of intercropping on the kiwifruit rhizosphere to gain a deeper understanding of the relationships between cover plants and kiwifruit in this sustainable agricultural system. Soil physicochemical properties and bacterial communities were analyzed using the Kiwifruit-Agaricus blazei intercropping System. Moreover, a combined analysis of 16S rRNA gene sequencing and metabolomic sequencing was used to identify differential microbes and metabolites in the rhizosphere. Intercropping led to an increase in soil physicochemical and enzyme activity, as well as re-shaping the bacterial community and increasing microbial diversity. Proteobacteria, Bacteroidota, Myxococcota, and Patescibacteria were the most abundant and diverse phyla in the intercropping system. Expression analysis further revealed that the bacterial genera BIrii41, Acidibacter, and Altererythrobacter were significantly upregulated in the intercropping system. Moreover, 358 differential metabolites (DMs) were identified between the monocropping and intercropping cultivation patterns, with fatty acyls, carboxylic acids and derivatives, and organooxygen compounds being significantly upregulated in the intercropping system. The KEGG metabolic pathways further revealed considerable enrichment of DMs in ABC transporters, histidine metabolism, and pyrimidine metabolism. This study identified a significant correlation between 95 bacterial genera and 79 soil metabolites, and an interactive network was constructed to explore the relationships between these differential microbes and metabolites in the rhizosphere. This study demonstrated that Kiwifruit-Agaricus blazei intercropping can be an effective, labor-saving, economic, and sustainable practice for reshaping bacterial communities and promoting the accumulation and metabolism of beneficial microorganisms in the rhizosphere.
Catalytic reduction of toxic dyes over nickel oxide nanoparticles supported on CMK-3 catalyst
Authors: Younus Mohammed M. , Sayed M. A. , El Saied Mohamed , El Naga Ahmed O. Abo
Published: July 2024

In the current paper, a NiO nanoparticles-loaded mesoporous carbon (CMK-3) catalyst, denoted as NiO/CMK-3, has been successfully synthesized using a facile strategy. The as-prepared material has been characterized through XRD, Raman spectroscopy, low-temperature N2 physisorption measurements, FTIR, FE-SEM, TEM, and XPS. The as-fabricated NiO/CMK-3 catalyst manifested a superior activity in the NaBH4-assisted reduction of methylene blue (MB) dye to its colorless leuco form. Remarkably, over 99% of 25 mg L−1 MB was reduced by 7.5 mM/L NaBH4 using 0.1 g L−1 NiO/CMK-3 within 3 min at room temperature. Furthermore, the kinetics study confirmed the appropriateness of the pseudo-first-order kinetic model for elucidating the kinetics of MB reduction by the catalyst. Importantly, the NiO/CMK-3 catalyst maintained almost constant catalytic activity even after 5 times of reuse in MB reduction, demonstrating its superior stability and reusable ability. So, NiO/CMK-5 appears as a promising heterogeneous catalyst for the effective remediation of dye-containing wastewater.
Boosting piezoelectric properties of PVDF nanofibers via embedded graphene oxide nanosheets
Authors: Salama Mahmoud , Hamed Aya , Noman Sara , Magdy Germein , Shehata Nader , Kandas Ishac
Published: July 2024

Tremendous research efforts have been directed toward developing polymer-based piezoelectric nanogenerators (PENG) in a promising step to investigate self-charging powered systems (SCPSs) and consequently, support the need for flexible, intelligent, and ultra-compact wearable electronic devices. In our work, electrospun polyvinylidene fluoride (PVDF) nanofiber mats were investigated while graphene oxide (GO) was added with different concentrations (from 0 to 3 wt.%). Sonication treatment was introduced for 5 min to GO nanosheets before combined PVDF solution. A comprehensive study was conducted to examine the GO incremental effect. Microstructural and mechanical properties were examined using a scanning electron microscope (SEM) and a texture analyzer. Moreover, piezoelectric properties were assessed via various tests including impulse response, frequency effect, d33 coefficient, charging and discharging analysis, and sawyer tower circuit. Experimental results indicate that incorporation of GO nanosheets enhances piezoelectric properties for all concentrations, which was linked to the increase in β phase inside the nanofibers, which has a significant potential of enhancing nanogenerator performance. PVDF-GO 1.5 wt.% shows a notably higher enhancing effect where the electroactive β-phase and γ-phase are recorded to be boosted to ~ 68.13%, as well as piezoelectric coefficient (d33 ~ 55.57 pC/N). Furthermore, increasing impact force encouraged the output voltage. Also noted that the delivered open circuit voltage is ~ 3671 V/g and the power density is ~ 150 µw/cm2. It was observed that GO of concentration 1.5 wt.% recorded a conversion efficiency of ~ 74.73%. All results are in line, showing better performance for PVDF-GO 1.5 wt.% for almost all concentrations.
The implementation of conscious sedation by dental professionals in Egypt: an analytical cross-sectional study
Authors: Elfezary Mohamed Taha , Moteea Mohamed Elsayed , Abu Samadah Mohammed Said , Waly Ahmed S
Published: July 2024

Conscious sedation is widely considered one of the techniques most commonly used to manage anxiety in both children and adults during dental procedures. The application of procedural sedation exhibits considerable variation globally. The purpose of the study was to determine the prevalence of conscious sedation in the current situation in the dental healthcare sector in Egypt and to identify the factors influencing it. An online cross-sectional analytical survey, consisting of nine multiple choice questions, was distributed through the contact lists of national dentists and social media platforms. 163 respondents completed the survey. Regarding the use of conscious sedation, only 25 (15.3%),95% confidence interval (10–21) utilized it. The percentage of participants who used conscious sedation was higher among dentists practicing pediatric dental specialists (n = 19, 76%). Academic qualification correlates significantly with the practice of conscious sedation (P = 0.002), but this was not reflected in multiple logistic regression. Indeed, while conscious sedation is part of the dental study curriculum in Egypt, its application rate is relatively low compared to other countries. This discrepancy could be attributed to a variety of factors, including resource availability, lack of training, reflecting the need to develop strategies to improve the implementation of conscious sedation in Egyptian dental practices.
Finite element models with automatic computed tomography bone segmentation for failure load computation
Authors: Saillard Emile , Gardegaront Marc , Levillain Aurélie , Bermond François , Mitton David , Pialat Jean-Baptiste , Confavreux Cyrille , Grenier Thomas , Follet Hélène
Published: July 2024

Bone segmentation is an important step to perform biomechanical failure load simulations on in-vivo CT data of patients with bone metastasis, as it is a mandatory operation to obtain meshes needed for numerical simulations. Segmentation can be a tedious and time consuming task when done manually, and expert segmentations are subject to intra- and inter-operator variability. Deep learning methods are increasingly employed to automatically carry out image segmentation tasks. These networks usually need to be trained on a large image dataset along with the manual segmentations to maximize generalization to new images, but it is not always possible to have access to a multitude of CT-scans with the associated ground truth. It then becomes necessary to use training techniques to make the best use of the limited available data. In this paper, we propose a dedicated pipeline of preprocessing, deep learning based segmentation method and post-processing for in-vivo human femurs and vertebrae segmentation from CT-scans volumes. We experimented with three U-Net architectures and showed that out-of-the-box models enable automatic and high-quality volume segmentation if carefully trained. We compared the failure load simulation results obtained on femurs and vertebrae using either automatic or manual segmentations and studied the sensitivity of the simulations on small variations of the automatic segmentation. The failure loads obtained using automatic segmentations were comparable to those obtained using manual expert segmentations for all the femurs and vertebrae tested, demonstrating the effectiveness of the automated segmentation approach for failure load simulations.
Prospective environmental burdens and benefits of fast-swing direct air carbon capture and storage
Authors: Ottenbros Anne B. , van Zelm Rosalie , Simons Jasper , van der Hulst Mitchell K. , de Kleijne Kiane , de Neve Hans , Huijbregts Mark A. J.
Published: July 2024

Direct air capture (DAC) in combination with storage of CO2 can lower atmospheric CO2 concentrations. This study investigates the environmental impact of a new fast-swing solid sorbent DAC system, including CO2 transport and storage, over its life cycle, using prospective life cycle assessment. This DAC technology is currently on technology readiness level 5 and is expected to operate on an industrial scale by 2030. The technology was upscaled to the industrial scale and future changes in the background over the lifetime of the system were included, such as electricity grid mix decarbonization. Environmental trade-offs for the new DAC system were assessed by comparing environmental benefits from CO2 sequestration with environmental burdens from production, operation and decommissioning. We considered three electricity generation configurations: grid-connected, wind-connected, and a hybrid configuration. We found net environmental benefits for all configurations and background scenarios for ecosystem damage and climate change. Net human health benefits were observed when the electricity grid decarbonizes quickly and without the use of a battery. The environmental benefits increase with decreasing electricity footprint and are comparable with other DAC technologies. This illustrates that the new DAC system can help to meet the climate goals.
Variable-stiffness prosthesis improves biomechanics of walking across speeds compared to a passive device
Authors: Rogers-Bradley Emily , Yeon Seong Ho , Landis Christian , Lee Duncan R. C. , Herr Hugh M.
Published: July 2024

Ankle push-off power plays an important role in healthy walking, contributing to center-of-mass acceleration, swing leg dynamics, and accounting for 45% of total leg power. The majority of existing passive energy storage and return prostheses for people with below-knee (transtibial) amputation are stiffer than the biological ankle, particularly at slower walking speeds. Additionally, passive devices provide insufficient levels of energy return and push-off power, negatively impacting biomechanics of gait. Here, we present a clinical study evaluating the kinematics and kinetics of walking with a microprocessor-controlled, variable-stiffness ankle-foot prosthesis (945 g) compared to a standard low-mass passive prosthesis (Ottobock Taleo, 463 g) with 7 study participants having unilateral transtibial amputation. By modulating prosthesis stiffness under computer control across walking speeds, we demonstrate that there exists a stiffness that increases prosthetic-side energy return, peak power, and center-of-mass push-off work, and decreases contralateral limb peak ground reaction force compared to the standard passive prosthesis across all evaluated walking speeds. We demonstrate a significant increase in center-of-mass push-off work of 26.1%, 26.2%, 29.6% and 29.9% at 0.75 m/s, 1.0 m/s, 1.25 m/s, and 1.5 m/s, respectively, and a significant decrease in contralateral limb ground reaction force of 3.1%, 3.9%, and 3.2% at 1.0 m/s, 1.25 m/s, and 1.5 m/s, respectively. This study demonstrates the potential for a quasi-passive microprocessor-controlled variable-stiffness prosthesis to increase push-off power and energy return during gait at a range of walking speeds compared to a passive device of a fixed stiffness.
Distribution of control during bimanual movement and stabilization
Authors: Takagi Atsushi , Kashino Makio
Published: July 2024

In two-handed actions like baseball batting, the brain can allocate the control to each arm in an infinite number of ways. According to hemispheric specialization theory, the dominant hemisphere is adept at ballistic control, while the non-dominant hemisphere is specialized at postural stabilization, so the brain should divide the control between the arms according to their respective specialization. Here, we tested this prediction by examining how the brain shares the control between the dominant and non-dominant arms during bimanual reaching and postural stabilization. Participants reached with both hands, which were tied together by a stiff virtual spring, to a target surrounded by an unstable repulsive force field. If the brain exploits each hemisphere’s specialization, then the dominant arm should be responsible for acceleration early in the movement, and the non-dominant arm will be the prime actor at the end when holding steady against the force field. The power grasp force, which signifies the postural stability of each arm, peaked at movement termination but was equally large in both arms. Furthermore, the brain predominantly used the arm that could use the stronger flexor muscles to mainly accelerate the movement. These results point to the brain flexibly allocating the control to each arm according to the task goal without adhering to a strict specialization scheme.
Risk factors associated with the severity of overactive bladder among Syrian patients with type 2 diabetes
Authors: Khadour Fater A. , Khadour Younes A. , Alhatem Weaam , Al Barroush Deema
Published: July 2024

The prevalence of overactive bladder (OAB) is known to be higher in patients with type 2 diabetes (T2DM). However, few studies have examined specific risk factors contributing to its progression among diabetes mellitus (DM) patients, so this study aimed to investigate the risk factors specific to diabetes mellitus that influence overactive bladder in the Syrian population. This cross-sectional study was conducted at four endocrinology centers in four Syrian provinces: Damascus, Aleppo, Homs, Hama, and Latakia. The study was comprised of patients who had been diagnosed with both T2DM and OAB and had visited these centers from February 2020 to January 2023. The Arabic version of the Overactive Bladder Symptom Score (OABSS) scale was used to categorize the participants based on the severity score into two groups: the mild OAB group and the moderate-severe OAB group. A logistic analysis was conducted to assess the risk factors associated with the OAB among patients with diabetes. Among the 153 patients diagnosed with both DM and OAB, significant distinctions were found between the two groups concerning the severity of overactive bladder, age, duration of diabetes, symptomatic diabetic peripheral neuropathy (DPN), and ankle reflex (P < 0.05). Furthermore, a multivariate analysis revealed that age (OR 1.48, 95% CI 0.89–2.19), duration of diabetes (OR 1.94, 95% CI 0.53–2.23), and symptomatic DPN (OR 2.74, 95% CI 1.39–4.13) independently acted as risk factors for the advancement of OAB. The severity of OAB in Syrian patients with diabetes is closely associated with the severity of DM. Factors such as age, duration of diabetes, and symptomatic DPN are independent predictors of the severity of OAB. Patients who experience symptomatic DPN are at an increased risk of developing OAB.
Observation of a moderate major Baltic Sea inflow in December 2023
Authors: Purkiani Kaveh , Jochumsen Kerstin , Fischer Jens-Georg
Published: July 2024

Just before Christmas 2023, the low-pressure system storm “Zoltan” struck Germany, resulting in widespread damage and two consecutive large storm surges on the North Sea coast in the night from Thursday 21 December 2023 to Friday 22 December 2023. Storm Zoltan brought heavy rainfall, accompanied by thunderstorms and winds ranging between 90 and 115 $$\mathrm {km\,h^{-1}}$$

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, with gusts reaching up to 140 $$\mathrm {km\,h^{-1}}$$

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along the coast which caused severe damage, particularly in northern Germany. Characteristics of the inflowing water at the Fehmarn Belt buoy (FEB), Darss Sill station (DAR) and the Arkona Basin buoy (ARK), including salinity, temperature, dissolved oxygen and ocean currents properties, were analysed to understand the impact of storm Zoltan in the western Baltic Sea. In addition to the damage along its path, following the onset of strong westerly winds associated with storm Zoltan, a large volume of water, containing saline (17–22 psu), cold (5–6 °C), and oxygen-rich 7–8 ($$\,\mathrm { ml\,l^{-1}}$$

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) water from the Kattegat and the North Sea reached into the western Baltic Sea. The sea level at Landsort Norra increased by +57 cm over a period of 14 days, from 15 December to 29 December 2023. This resulted in a total volume change of 198 $$\mathrm {km^3}$$

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in the entire Baltic Sea, with 169 $$\mathrm {km^3}$$

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and 29 $$\mathrm {km^3}$$

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provided via the Belt Sea and the Sound Sea, respectively. Observations at the DAR indicated a significant inflow between 19 December 2023 and 1 January 2024 with salinity above 13 psu, temperature below 5.5 °C and dissolved oxygen of about 7.5–8 $$\mathrm { ml\,l^{-1}}$$

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l

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. While the maximum salinity of the bottom layer at the DAR was about 17 psu, the ARK exhibited significantly higher salinities, reaching up to 22 psu at the bottom layer. During the main inflow period, 75 $$\mathrm {km^3}$$

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of highly saline water entered the western Baltic Sea. This corresponds to an average salt transport of 1.75 Gt into the western Baltic Sea (1.39 Gt from the Belt Sea and 0.36 Gt from the Sound Sea), representing more than 20% of the total annual salt import into the Baltic Sea), which places the event in the moderate range of major Baltic inflows. This event brought an amount of about 0.8 $$\mathrm {10^6}$$

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t oxygen into the Baltic Sea. This was the strongest inflow into the Baltic Sea since 2016.
Controlling glycolysis to generate characteristic volatile organic compounds of lung cancer cells
Authors: Chu Yajing , Ge Dianlong , Zhou Jijuan , Liu Yue , Zheng Xiangxue , Liu Wenting , Ke Li , Lu Yan , Chu Yannan
Published: July 2024

Characteristic volatile organic compounds (VOCs) are anticipated to be used for the identification of lung cancer cells. However, to date, consistent biomarkers of VOCs in lung cancer cells have not been obtained through direct comparison between cancer and healthy groups. In this study, we regulated the glycolysis, a common metabolic process in cancer cells, and employed solid phase microextraction gas chromatography mass spectrometry (SPME–GC–MS) combined with untargeted analysis to identify the characteristic VOCs shared by cancer cells. The VOCs released by three types of lung cancer cells (A549, PC-9, NCI-H460) and one normal lung epithelial cell (BEAS-2B) were detected using SPME–GC–MS, both in their resting state and after treatment with glycolysis inhibitors (2-Deoxy-d-glucose, 2-DG/3-Bromopyruvic acid, 3-BrPA). Untargeted analysis methods were employed to compare the VOC profiles between each type of cancer cell and normal cells before and after glycolysis regulation. Our findings revealed that compared to normal cells, the three types of lung cancer cells exhibited three common differential VOCs in their resting state: ethyl propionate, acetoin, and 3-decen-5-one. Furthermore, under glycolysis control, a single common differential VOC—acetoin was identified. Notably, acetoin levels increased by 2.60–3.29-fold in all three lung cancer cell lines upon the application of glycolysis inhibitors while remaining relatively stable in normal cells. To further elucidate the formation mechanism of acetoin, we investigated its production by blocking glutaminolysis. This interdisciplinary approach combining metabolic biochemistry with MS analysis through interventional synthetic VOCs holds great potential for revolutionizing the identification of lung cancer cells and paving the way for novel cytological examination techniques.
Brain activity changes after high/low frequency stimulation in a nonhuman primate model of central post-stroke pain
Authors: Nagasaka Kazuaki , Higo Noriyuki
Published: July 2024

Central post-stroke pain (CPSP) is a chronic pain resulting from a lesion in somatosensory pathways. Neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) that target the primary motor cortex (M1), have shown promise for the treatment of CPSP. High-frequency (Hf) rTMS exhibits analgesic effects compared to low-frequency (Lf) rTMS; however, its analgesic mechanism is unknown. We aimed to elucidate the mechanism of rTMS-induced analgesia by evaluating alterations of tactile functional magnetic resonance imaging (fMRI) due to Hf- and Lf-rTMS in a CPSP monkey model. Consistent with the patient findings, the monkeys showed an increase in pain threshold after Hf-rTMS, which indicated an analgesic effect. However, no change after Lf-rTMS was observed. Compared to Lf-rTMS, Hf-rTMS produced enhanced tactile-evoked fMRI signals not only in M1 but also in somatosensory processing regions, such as the primary somatosensory and midcingulate cortices. However, the secondary somatosensory cortex (S2) was less active after Hf-rTMS than after Lf-rTMS, suggesting that activation of this region was involved in CPSP. Previous studies showed pharmacological inhibition of S2 reduces CPSP-related behaviors, and the present results emphasize the involvement of an S2 inhibitory system in rTMS-induced analgesia. Verification using the monkey model is important to elucidate the inhibition system.
Effectiveness of extracorporeal shock wave therapy on functional ability in grade IV knee osteoarthritis – a randomized controlled trial
Authors: CP Arshed , Jayaraman Kavitha , Babkair Reem Abdullah , Nuhmani Shibili , Nawed Alvina , Khan Masood , Alghadir Ahmad H.
Published: July 2024

Extracorporeal shockwave therapy (ESWT) is a non-invasive physical therapy intervention that has emerged in the recent past to address the upswing of osteoarthritis (OA). However, insufficient evidence is present to prove the efficacy of ESWT on grade IV knee osteoarthritis (KOA). The present study aimed to examine the effects of ESWT on functional ability in patients suffering from grade IV KOA. Thirty volunteers aged 45–60 years with grade IV primary KOA diagnosed by an orthopaedic surgeon based on the Kellgren-Lawrence score participated in the study. The participants were equally and randomly divided into two groups (i.e. experimental and control), with 15 participants in each group. The participants in the control group performed conventional physiotherapy (CPT) that included ultrasound therapy, isometric quadriceps, SLR and isometric hip adductor strengthening exercises. The participants in the experimental group received ESWT in addition to CPT. Lower extremity functional scale (LEFS) score was measured before and after the four weeks of intervention. In both groups, a statistically significant (p = 0.001) improvement in LEFS was observed. In the experimental groups, it improved by 81.92% and in the control groups by 48.15%. A statistically significant (p < 0.001) difference was observed in LEFS post-intervention values between both groups. As demonstrated by our trial results, the addition of ESWT to the CPT program will yield beneficial results in ameliorating the functional disability in patients with primary KOA (grade IV). Further studies are needed to confirm and apply these findings to a larger cohort.
Development of a first-in-class antibody and a specific assay for α-1,6-fucosylated prostate-specific antigen
Authors: Halldórsson Steinar , Hillringhaus Lars , Hojer Caroline , Muranyi Andrea , Schraeml Michael , Lange Magdalena Swiatek-de , Tabarés Gloria
Published: July 2024

Prostate-specific antigen (PSA) levels are widely used to screen for prostate cancer, yet the test has poor sensitivity, specificity and predictive value, which leads to overdiagnosis and overtreatment. Alterations in the glycosylation status of PSA, including fucosylation, may offer scope for an improved biomarker. We sought to generate a monoclonal antibody (mAb) targeting α-1,6-fucosylated PSA (fuc-PSA) and to develop a tissue-based immunological assay for fuc-PSA detection. Immunogens representing fuc-PSA were used for immunisation and resultant mAbs were extensively characterised. The mAbs reacted specifically with fuc-PSA-specific glycopeptide, but not with aglycosylated PSA or glycan without the PSA peptide. Reactivity was confirmed using high-throughput surface plasmon resonance spectroscopy. X-ray crystallography investigations showed that the mAbs bound to an α-helical form of the peptide, whereas the native PSA epitope is linear. Protein unfolding was required for detection of fuc-PSA in patient samples. Peptide inhibition of fuc-PSA mAbs was observed with positive screening reagents, and target epitope specificity was observed in formalin-fixed, paraffin-embedded tissue samples. This research introduces a well-characterised, first-in-class antibody targeting fuc-PSA and presents the first crystal structure of an antibody demonstrating glycosylation-specific binding to a peptide.
Insights into two-phase flow dynamics in closed-loop pulsating heat pipes utilizing Fe3O4/water: experimental visualization study
Authors: Goshayeshi Hamid Reza , Mousavi Seyed Borhan , Heris Saeed Zeinali , Chaer Issa
Published: July 2024

This article discusses a focused study on visualizing the flow patterns in a two-phase pulsating heat pipe (PHP) using Fe3O4/water as the working fluid at 3 V/V% concentration. The research also aims to meticulously examine phase change phenomena in the heating section, particularly focusing on bubble formation and expansion processes. A high-speed video camera was utilized to capture dynamic insights into the behavior of the Fe3O4/water mixture. Based on the findings, a straightforward model was developed to explain bubble generation and growth in the mixture, serving as a useful reference for future PHP designs and optimizations. Visual observations also noted the stable nature of the Fe3O4/water nanofluid over a 4-day period, confirming its consistency throughout the experiments. Moreover, the impact of heat load variation on the evaporator section was assessed using controlled heat inputs ranging from 10 to 80 W. Observations on the arrangement of slugs and plugs at a 50% filling ratio revealed interesting self-adjusting flow patterns in response to increasing heat inputs, providing valuable insights into PHP operational dynamics. Notably, the oscillatory flow behavior of Fe3O4/water, the chosen working fluid, exhibited greater activity in comparison to water. This distinctive flow behavior contributed to achieving heightened thermal performance efficiency for the Fe3O4/water system, attributed to its faster attainment of the annular flow condition.
High-throughput screening for cell binding and repulsion peptides on multifunctionalized surfaces
Authors: Sonnentag Steffen J. , Jenne Felix , Orian-Rousseau Véronique , Nesterov-Mueller Alexander
Published: July 2024

The adhesion of cells to the extracellular matrix engages cell surface receptors such as integrins, proteoglycans and other types of cell adhesion molecules such as CD44. To closely examine the determinants of cell adhesion, herein we describe the generation of high-density peptide arrays and test the growth of cells on these multifunctionalized surfaces. The peptide library used consists of over 11,000 different sequences, either random or derived from existing proteins. By applying this screen to SW620 mCherry colorectal cancer cells, we select for peptides with both maximum cell adhesion and maximum cell repulsion. All of these extreme properties are based on unique combinations of amino acids. Here, we identify peptides with maximum cell repulsion on secreted frizzled- and Dickkopf-related proteins. Peptides with strong cell repulsion are found at the poles of the TNF-alpha homotrimer. The formation of cellular patterns on alternating highly repulsive and adhesive peptides are examined. Our screen allows the identification of peptides suitable for biomedical and tissue engineering applications.
Silicon photonics for high-speed communications and photonic signal processing
Authors: Zhou Xuetong , Yi Dan , Chan David W. U , Tsang Hon Ki
Published: July 2024

Leveraging on the mature processing infrastructure of silicon microelectronics, silicon photonic integrated circuits may be readily scaled to large volume production for low-cost high-volume applications such as optical transceivers for data centers. Driven by the rapid growth of generative artificial intelligence and the resultant rapid increase in data traffic in data centers, new integrated optical transceivers will be needed to support multichannel high-capacity communications beyond 1.6Tb/s. In this paper, we review some of the recent advances in high performance optical waveguide grating couplers (WGC) as a key enabling technology for future high capacity communications. We describe the novel use of shifted-polysilicon overlay gratings on top of the silicon grating that enabled foundry manufactured chips to have fiber-chip coupling losses of under 1 dB. The use of mirror symmetry and resonant cavity enhancement in the design of gratings can increase the 1-dB optical bandwidths of grating couplers to over 100 nm. Multimode waveguide grating couplers (MWGC) may be designed for the selective launch of different modes channels in multimode fibers for mode-division-multiplexing (MDM) communications. The use of different modes or polarizations in optical fibers for high capacity communications requires the unscrambling of data lanes which are mixed together during the optical fiber transmission. We describe how silicon photonic circuits can be used to perform unitary matrix operations and unscramble the different data lanes in multichannel optical communication systems. We also describe recent advances on high-speed silicon modulators for enabling data rates of individual data lanes in an integrated optical transceiver beyond 300 Gb/s.
Advances in resonator-based Kerr frequency combs with high conversion efficiencies
Authors: Zhang Xucheng , Wang Chunxue , Cheng Zhibo , Hu Congyu , Ji Xingchen , Su Yikai
Published: July 2024

Recent developments in resonator-based Kerr frequency combs promise excellent applications in a wide range of fields such as biosensing, spectroscopy, optical communications, light detection and ranging (LiDAR), frequency synthesis, astronomical detection, and quantum optics. A key figure of merit (FOM) for Kerr frequency combs is the pump-to-comb conversion efficiency, which is critical for applications requiring sufficient comb power and low power consumption. In this review, we first discuss the limited conversion efficiency of dissipative Kerr soliton in an anomalous dispersion microresonator based on its underlying physical characteristics. And then, we summarize the recent advances in Kerr frequency combs with high conversion efficiencies in both anomalous and normal dispersion regimes. We classify them according to various soliton states, excitation methods as well as novel material platforms. The final section of the paper presents an overview of current progress and glances at potential directions for future research.