bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts of the Mesoscale Ocean‐Atmosphere Coupling on the Peru‐Chile Ocean Dynamics: Impact of the Thermal Feedback
Authors: Oerder Vera , Colas François , Echevin Vincent , Masson Sebastien , Lemarié Florian , Renault Lionel
Published: June 2024

Consequences of the mesoscale Thermal FeedBack (TFB) on the ocean dynamics are studied in the South‐East Pacific (SEP) using a high‐resolution regional ocean–atmosphere coupled model. Three simulations are compared: the first one is a fully coupled simulation. In the second one, the TFB has been removed with an online smoothing of the Sea Surface Temperature (SST) conditions used by the atmosphere. In the third one, to disentangle the impact of the nearshore and the offshore TFB, the smoothing is only applied in the offshore region. In the SEP, the coastal upwelling cold tongue constitutes a permanent mesoscale SST pattern. We show that this SST pattern alters the coastal wind structure, reducing the coastal upwelling‐favorable wind intensity. So, the nearshore TFB reduces the coastal surface current and the vertical velocities. As a result, the Eddy Kinetic Energy (EKE) generation by baroclinic conversion is also weakened. In the offshore region, on the contrary, the oceanic mean state is not affected by the TFB and only the EKE is weakened. Composites above the coherent eddies show that the heat flux response to the mesoscale SST anomalies is responsible for the mesoscale activity weakening over the whole studied area. Although the wind response to the SST anomalies has a very weak mean impact on the EKE generation through wind work, we show that it strongly modifies the mean oceanic vertical velocity anomalies over the coherent eddies.
Human Impacts Dominate Global Loss of Lake Ecosystem Resilience
Authors: Han Yaoyao , Lin Qi , Huang Shixin , Du Chenliang , Shen Ji , Zhang Ke
Published: June 2024

Strengthening aquatic resilience to prevent adverse shifts is critical for preserving global freshwater biodiversity and advancing Sustainable Development Goals. Nonetheless, understanding the long‐term trends and underlying causes of lake ecosystem resilience at a global scale remains elusive. Here, we employ an innovative framework, integrating satellite‐derived water quality indices with early warning signals and machine learning techniques, to investigate the dynamics of resilience in 1,049 lakes worldwide during 2000–2018. Our results indicate that 46.7% of lakes are experiencing a significant decline in resilience, particularly since the early 2010s, closely associated with higher human population density and anthropogenic eutrophication. In contrast, most lakes situated in alpine regions exhibit an increase in resilience, probably benefiting from climate warming and wetting. Together, this study provides a novel way to monitor lake resilience and predict undesired transitions, and reveals a widespread erosion in the ability of lakes to withstand stressors associated with global change.
Impacts of Assimilating All‐Sky FY‐4A AGRI Satellite Infrared Radiances on the Prediction of Super Typhoon In‐Fa During the Period With Abnormal Changes
Authors: Xu Dongmei , Zhang Xuewei , Min Jinzhong , Shen Feifei
Published: June 2024

The capabilities of assimilating the all‐sky Fengyun‐4A Advanced Geostationary Radiation Imager (AGRI) infrared radiances (IR) are completed by including hydrometers in the observation operator, its adjoint, and tangent linear model. This allows the three‐dimensional variational data assimilation model to include cloud‐precipitation information from infrared IR observations. Advanced as the all‐sky data assimilation methodologies are, the assimilation of cloudy scene IR radiances for tropical cyclone (TC) systems has not led to consistently better results, especially for the intensity of TCs. This work explores the effects of all‐sky AGRI radiance assimilation on a Super Typhoon In‐Fa (2106) during its stage experiencing abnormal changes in the intensity and the track. It is shown that the all‐sky assimilation of AGRI two channels 9–10 brings no obviously better TC forecasts than the all‐sky AGRI single‐channel assimilation does. Besides, the O − B (observation minus background) bias was corrected to be even larger with the variational bias correction method for the pixels with relatively lower or higher cloud impact. This indicates that traditional bias correction schemes with linear fitting functions are suboptimal if the relations between the predictor and O − B biases are non‐linear. When the conventional observation and IR radiances are assimilated in two steps, the wind in the inner‐core region is better described to properly capture the changes in the typhoon intensity. Generally, the analyses and forecasts of Typhoon In‐Fa from experiments with the all‐sky IR observations are enhanced compared to those with only the clear‐sky IR observations.
Histone H1x in mouse ventral hippocampus associates with, but does not cause behavioral adaptations to stress
Authors: Kim R. Kijoon , Truby Natalie L. , Silva Gabriella M. , Picone Joseph A. , Miller Cary S. , Baldwin Amber N. , Neve Rachael L. , Cui Xiaohong , Hamilton Peter J.
Published: June 2024

Prior research has identified differential protein expression levels of linker histone H1x within the ventral hippocampus (vHipp) of stress-susceptible versus stress-resilient mice. These mice are behaviorally classified based on their divergent responses to chronic social stress. Here, we sought to determine whether elevated vHipp H1x protein levels directly contribute to these diverging behavioral adaptations to stress. First, we demonstrated that stress-susceptible mice uniquely express elevated vHipp H1x protein levels following chronic stress. Given that linker histones coordinate heterochromatin compaction, we hypothesize that elevated levels of H1x in the vHipp may impede pro-resilience transcriptional adaptations and prevent development of the resilient phenotype following social stress. To test this, 8–10-week-old male C57BL/6 J mice were randomly assigned to groups undergoing 10 days of chronic social defeat stress (CSDS) or single housing, respectively. Following CSDS, mice were classified as susceptible versus resilient based on their social interaction behaviors. We synthesized a viral overexpression (OE) vector for H1x and transduced all stressed and single housed mice with either H1x or control GFP within vHipp. Following viral delivery, we conducted social, anxiety-like, and memory-reliant behavior tests on distinct cohorts of mice. We found no behavioral adaptations following H1x OE compared to GFP controls in susceptible, resilient, or single housed mice. In sum, although we confirm elevated vHipp protein levels of H1x associate with susceptibility to social stress, we observe no significant behavioral consequence of H1x OE. Thus, we conclude elevated levels of H1x are associated with, but are not singularly sufficient to drive development of behavioral adaptations to stress.
Realization of monolayer ZrTe5 topological insulators with wide band gaps
Authors: Xu Yong-Jie , Cao Guohua , Li Qi-Yuan , Xue Cheng-Long , Zhao Wei-Min , Wang Qi-Wei , Dou Li-Guo , Du Xuan , Meng Yu-Xin , Wang Yuan-Kun , Gao Yu-Hang , Jia Zhen-Yu , Li Wei , Ji Lianlian , Li Fang-Sen , Zhang Zhenyu , Cui Ping , Xing Dingyu , Li Shao-Chun
Published: June 2024

Two-dimensional topological insulators hosting the quantum spin Hall effect have application potential in dissipationless electronics. To observe the quantum spin Hall effect at elevated temperatures, a wide band gap is indispensable to efficiently suppress bulk conduction. Yet, most candidate materials exhibit narrow or even negative band gaps. Here, via elegant control of van der Waals epitaxy, we have successfully grown monolayer ZrTe5 on a bilayer graphene/SiC substrate. The epitaxial ZrTe5 monolayer crystalizes in two allotrope isomers with different intralayer alignments of ZrTe3 prisms. Our scanning tunneling microscopy/spectroscopy characterization unveils an intrinsic full band gap as large as 254 meV and one-dimensional edge states localized along the periphery of the ZrTe5 monolayer. First-principles calculations further confirm that the large band gap originates from strong spin−orbit coupling, and the edge states are topologically nontrivial. These findings thus provide a highly desirable material platform for the exploration of the high-temperature quantum spin Hall effect.
Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer’s disease
Authors: Ravikumar Sadhana , Denning Amanda E. , Lim Sydney , Chung Eunice , Sadeghpour Niyousha , Ittyerah Ranjit , Wisse Laura E. M. , Das Sandhitsu R. , Xie Long , Robinson John L. , Schuck Theresa , Lee Edward B. , Detre John A. , Tisdall M. Dylan , Prabhakaran Karthik , Mizsei Gabor , de Onzono Martin Maria Mercedes Iñiguez , Arroyo Jiménez Maria del Mar , Mũnoz Monica , Marcos Rabal Maria del Pilar , Cebada Sánchez Sandra , Delgado González José Carlos , de la Rosa Prieto Carlos , Irwin David J. , Wolk David A. , Insausti Ricardo , Yushkevich Paul A.
Published: June 2024

Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer’s Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield. Additionally, we identify granular MTL regions where measures of neurodegeneration are likely to be linked to NFTs specifically, and thus potentially more sensitive as early AD biomarkers.
Gedatolisib shows superior potency and efficacy versus single-node PI3K/AKT/mTOR inhibitors in breast cancer models
Authors: Rossetti Stefano , Broege Aaron , Sen Adrish , Khan Salmaan , MacNeil Ian , Molden Jhomary , Kopher Ross , Schulz Stephen , Laing Lance
Published: June 2024

Abstract

The PI3K, AKT, and mTOR (PAM) pathway is frequently dysregulated in breast cancer (BC) to accommodate high catabolic and anabolic activities driving tumor growth. Current therapeutic options for patients with hormone receptor (HR) + / HER2- advanced BC (ABC) include PAM inhibitors that selectively inhibit only one PAM pathway node, which can lead to drug resistance as cells rapidly adapt to maintain viability. We hypothesized that gedatolisib, which potently inhibits all Class I PI3K isoforms, as well as mTORC1 and mTORC2, may be more effective in BC cells than single-node PAM inhibitors by limiting adaptive resistances. By using multiple functional assays, a panel of BC cell lines was evaluated for their sensitivity to four different PAM inhibitors: gedatolisib (pan-PI3K/mTOR inhibitor), alpelisib (PI3Kα inhibitor), capivasertib (AKT inhibitor), and everolimus (mTORC1 inhibitor). Gedatolisib exhibited more potent and efficacious anti-proliferative and cytotoxic effects regardless of the PAM pathway mutational status of the cell lines compared to the single-node PAM inhibitors. The higher efficacy of gedatolisib was confirmed in three-dimensional culture and in BC PDX models. Mechanistically, gedatolisib decreased cell survival, DNA replication, cell migration and invasion, protein synthesis, glucose consumption, lactate production, and oxygen consumption more effectively than the other PAM inhibitors tested. These results indicate that inhibition of multiple PAM pathway nodes by a pan-PI3K/mTOR inhibitor like gedatolisib may be more effective at inducing anti-tumor activity than single-node PAM inhibitors. A global Phase 3 study is currently evaluating gedatolisib plus fulvestrant with and without palbociclib in patients with HR+/HER2− ABC.
Effect of artificial gravity on neurocognitive performance during head-down tilt bedrest
Authors: Tölgyesi Borbála , Altbäcker Anna , Barkaszi Irén , Stuckenschneider Tim , Braunsmann Leonard , Takács Endre , Ehmann Bea , Balázs László , Abeln Vera
Published: June 2024

This study evaluated the acute and chronic effects of intermittent and continuous Artificial Gravity (AG) on cognitive performance during 60 days of Head-down tilt bedrest (HDTBR), a well-established ground-based spaceflight analogue method. Participants were randomly assigned to three groups: intermittent AG, continuous AG, and HDTBR control group without AG exposure. Task performance and electrophysiological measures of attention and working memory were investigated during Simple and Complex tasks in the Visual and the Auditory modality. Compared to baseline, faster reaction time and better accuracy was present during HDTBR regarding the Complex tasks, however, the practice effect was diminished in the three HDTBR groups compared to an ambulatory control group. Brain potentials showed a modality-specific decrease, as P3a was decreased only in the Auditory, while P3b decreased in the Visual modality. No evidence for acute or chronic AG-related cognitive impairments during HDTBR was found.
Capturing carbon dioxide from air with charged-sorbents
Authors: Li Huaiguang , Zick Mary E. , Trisukhon Teedhat , Signorile Matteo , Liu Xinyu , Eastmond Helen , Sharma Shivani , Spreng Tristan L. , Taylor Jack , Gittins Jamie W. , Farrow Cavan , Lim S. Alexandra , Crocellà Valentina , Milner Phillip J. , Forse Alexander C.
Published: June 2024

Emissions reduction and greenhouse gas removal from the atmosphere are both necessary to achieve net-zero emissions and limit climate change1. There is thus a need for improved sorbents for the capture of carbon dioxide from the atmosphere, a process known as direct air capture. In particular, low-cost materials that can be regenerated at low temperatures would overcome the limitations of current technologies. In this work, we introduce a new class of designer sorbent materials known as ‘charged-sorbents’. These materials are prepared through a battery-like charging process that accumulates ions in the pores of low-cost activated carbons, with the inserted ions then serving as sites for carbon dioxide adsorption. We use our charging process to accumulate reactive hydroxide ions in the pores of a carbon electrode, and find that the resulting sorbent material can rapidly capture carbon dioxide from ambient air by means of (bi)carbonate formation. Unlike traditional bulk carbonates, charged-sorbent regeneration can be achieved at low temperatures (90–100 °C) and the sorbent’s conductive nature permits direct Joule heating regeneration2,3 using renewable electricity. Given their highly tailorable pore environments and low cost, we anticipate that charged-sorbents will find numerous potential applications in chemical separations, catalysis and beyond.
Global shortfalls in documented actions to conserve biodiversity
Authors: Senior Rebecca A. , Bagwyn Ruby , Leng Danyan , Killion Alexander K. , Jetz Walter , Wilcove David S.
Published: June 2024

Threatened species are by definition species that are in need of assistance. In the absence of suitable conservation interventions, they are likely to disappear soon1. There is limited understanding of how and where conservation interventions are applied globally, or how well they work2,3. Here, using information from the International Union for Conservation of Nature Red List and other global databases, we find that for species at risk from three of the biggest drivers of biodiversity loss—habitat loss, overexploitation for international trade and invasive species4—many appear to lack the appropriate types of conservation interventions. Indeed, although there has been substantial recent expansion of the protected area network, we still find that 91% of threatened species have insufficient representation of their habitats within protected areas. Conservation interventions are not implemented uniformly across different taxa and regions and, even when present, have infrequently led to substantial improvements in the status of species. For 58% of the world’s threatened terrestrial species, we find conservation interventions to be notably insufficient or absent. We cannot determine whether such species are truly neglected, or whether efforts to recover them are not included in major conservation databases. If they are indeed neglected, the outlook for many of the world’s threatened species is grim without more and better targeted action.
Senescent glia link mitochondrial dysfunction and lipid accumulation
Authors: Byrns China N. , Perlegos Alexandra E. , Miller Karl N. , Jin Zhecheng , Carranza Faith R. , Manchandra Palak , Beveridge Connor H. , Randolph Caitlin E. , Chaluvadi V. Sai , Zhang Shirley L. , Srinivasan Ananth R. , Bennett F. C. , Sehgal Amita , Adams Peter D. , Chopra Gaurav , Bonini Nancy M.
Published: June 2024

Senescence is a cellular state linked to ageing and age-onset disease across many mammalian species1,2. Acutely, senescent cells promote wound healing3,4 and prevent tumour formation5; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. Whereas senescent cells are active targets for anti-ageing therapy6–11, why these cells form in vivo, how they affect tissue ageing and the effect of their elimination remain unclear12,13. Here we identify naturally occurring senescent glia in ageing Drosophila brains and decipher their origin and influence. Using Activator protein 1 (AP1) activity to screen for senescence14,15, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly lifespan and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally occurring senescent glia in vivo and indicate that these cells link key ageing phenomena: mitochondrial dysfunction and lipid accumulation.
Single-cell nascent RNA sequencing unveils coordinated global transcription
Authors: Mahat Dig B. , Tippens Nathaniel D. , Martin-Rufino Jorge D. , Waterton Sean K. , Fu Jiayu , Blatt Sarah E. , Sharp Phillip A.
Published: June 2024

Transcription is the primary regulatory step in gene expression. Divergent transcription initiation from promoters and enhancers produces stable RNAs from genes and unstable RNAs from enhancers1,2. Nascent RNA capture and sequencing assays simultaneously measure gene and enhancer activity in cell populations3. However, fundamental questions about the temporal regulation of transcription and enhancer–gene coordination remain unanswered, primarily because of the absence of a single-cell perspective on active transcription. In this study, we present scGRO–seq—a new single-cell nascent RNA sequencing assay that uses click chemistry—and unveil coordinated transcription throughout the genome. We demonstrate the episodic nature of transcription and the co-transcription of functionally related genes. scGRO–seq can estimate burst size and frequency by directly quantifying transcribing RNA polymerases in individual cells and can leverage replication-dependent non-polyadenylated histone gene transcription to elucidate cell cycle dynamics. The single-nucleotide spatial and temporal resolution of scGRO–seq enables the identification of networks of enhancers and genes. Our results suggest that the bursting of transcription at super-enhancers precedes bursting from associated genes. By imparting insights into the dynamic nature of global transcription and the origin and propagation of transcription signals, we demonstrate the ability of scGRO–seq to investigate the mechanisms of transcription regulation and the role of enhancers in gene expression.
Structure and topography of the synaptic V-ATPase–synaptophysin complex
Authors: Wang Chuchu , Jiang Wenhong , Leitz Jeremy , Yang Kailu , Esquivies Luis , Wang Xing , Shen Xiaotao , Held Richard G. , Adams Daniel J. , Basta Tamara , Hampton Lucas , Jian Ruiqi , Jiang Lihua , Stowell Michael H. B. , Baumeister Wolfgang , Guo Qiang , Brunger Axel T.
Published: June 2024

Synaptic vesicles are organelles with a precisely defined protein and lipid composition1,2, yet the molecular mechanisms for the biogenesis of synaptic vesicles are mainly unknown. Here we discovered a well-defined interface between the synaptic vesicle V-ATPase and synaptophysin by in situ cryo-electron tomography and single-particle cryo-electron microscopy of functional synaptic vesicles isolated from mouse brains3. The synaptic vesicle V-ATPase is an ATP-dependent proton pump that establishes the proton gradient across the synaptic vesicle, which in turn drives the uptake of neurotransmitters4,5. Synaptophysin6 and its paralogues synaptoporin7 and synaptogyrin8 belong to a family of abundant synaptic vesicle proteins whose function is still unclear. We performed structural and functional studies of synaptophysin-knockout mice, confirming the identity of synaptophysin as an interaction partner with the V-ATPase. Although there is little change in the conformation of the V-ATPase upon interaction with synaptophysin, the presence of synaptophysin in synaptic vesicles profoundly affects the copy number of V-ATPases. This effect on the topography of synaptic vesicles suggests that synaptophysin assists in their biogenesis. In support of this model, we observed that synaptophysin-knockout mice exhibit severe seizure susceptibility, suggesting an imbalance of neurotransmitter release as a physiological consequence of the absence of synaptophysin.
Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results
Authors: Wang Hui , Chen Yuxin , Lv Jun , Cheng Xiaoting , Cao Qi , Wang Daqi , Zhang Longlong , Zhu Biyun , Shen Min , Xu Chunxin , Xun Mengzhao , Wang Zijing , Tang Honghai , Hu Shaowei , Cui Chong , Jiang Luoying , Yin Yanbo , Guo Luo , Zhou Yi , Han Lei , Gao Ziwen , Zhang Jiajia , Yu Sha , Gao Kaiyu , Wang Jinghan , Chen Bing , Wang Wuqing , Chen Zheng-Yi , Li Huawei , Shu Yilai
Published: June 2024

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was >95 dB (>95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181.
A Transcriptomic Dataset of Embryonic Murine Telencephalon
Authors: Ochi Shohei , Manabe Shyu , Kikkawa Takako , Ebrahimiazar Sara , Kimura Ryuichi , Yoshizaki Kaichi , Osumi Noriko
Published: June 2024

Sex bias is known in the prevalence/pathology of neurodevelopmental disorders. Sex-dependent differences of the certain brain areas are known to emerge perinatally through the exposure to sex hormones, while gene expression patterns in the rodent embryonic brain does not seem to be completely the same between male and female. To investigate potential sex differences in gene expression and cortical organization during the embryonic period in mice, we conducted a comprehensive analysis of gene expression for the telencephalon at embryonic day (E) 11.5 (a peak of neural stem cell expansion) and E14.5 (a peak of neurogenesis) using bulk RNA-seq data. As a result, our data showed the existence of notable sex differences in gene expression patterns not obviously at E11.5, but clearly at E14.5 when neurogenesis has become its peak. These data can be useful for exploring potential contribution of genes exhibiting sex differences to the divergence in brain development. Additionally, our data underscore the significance of studying the embryonic period to gain a deeper understanding of sex differences in brain development.
Error-Reduced Digital Elevation Model of the Qinghai-Tibet Plateau using ICESat-2 and Fusion Model
Authors: Zhang Xingang , Guo Shanchuan , Yuan Bo , Mu Haowei , Xia Zilong , Tang Pengfei , Fang Hong , Wang Zhuo , Du Peijun
Published: June 2024

The Qinghai-Tibet Plateau (QTP) holds significance for investigating Earth’s surface processes. However, due to rugged terrain, forest canopy, and snow accumulation, open-access Digital Elevation Models (DEMs) exhibit considerable noise, resulting in low accuracy and pronounced data inconsistency. Furthermore, the glacier regions within the QTP undergo substantial changes, necessitating updates. This study employs a fusion of open-access DEMs and high-accuracy photons from the Ice, Cloud, and land Elevation Satellite-2 (ICESat-2). Additionally, snow cover and canopy heights are considered, and an ensemble learning fusion model is presented to harness the complementary information in the multi-sensor elevation observations. This innovative approach results in the creation of HQTP30, the most accurate representation of the 2021 QTP terrain. Comparative analysis with high-resolution imagery, UAV-derived DEMs, control points, and ICESat-2 highlights the advantages of HQTP30. Notably, in non-glacier regions, HQTP30 achieved a Mean Absolute Error (MAE) of 0.71 m, while in glacier regions, it reduced the MAE by 4.35 m compared to the state-of-the-art Copernicus DEM (COPDEM), demonstrating its versatile applicability.
Electrical lymph node scanning (ELS) system for real-time intra-operative detection of involved axillary lymph nodes in adjuvant breast cancer patients
Authors: Abbasvandi Fereshteh , Mahdavi Reihane , Bayat Mahdis , Hajighasemi Farzane , Jahanbakhshi Fahimeh , Aghaei Faeze , Sami Nafiseh , Khoundabi Batoul , Ataee Hossein , Yousefpour Narges , Hoseinpour Parisa , Mousavi Kiasary Seyed Mohamad Sadegh , Omrani Hashemi Maryam , Shojaeian Fatemeh , Akbari Atieh , Bagherhosseini Najmeh , Moradi Afshin , Akbari Mohammad Esmaeil , Abdolahad Mohammad
Published: June 2024

Lymph node (LN) status is an essential prognostic factor in breast cancer (BC) patients, with an important role in the surgical and therapeutic plan. Recently, we have been developed a novel system for real-time intra-operative electrical LN scanning in BC patients. The ELS scores were calibrated by pathological evaluation of the LNs. Herein, we evaluated the efficacy of ELS in a prospective study for non-chemo-treated breast cancer patients. This is a prospective study in which ELS scores are blind for pathologists who declare the clearance or involvement of LNs based on permanent pathology as the gold standard. ELS and frozen-section (FS) pathology results were achieved intra-operatively, and samples were sent for the permanent pathology. The score of ELS did not affect the surgeons’ decision, and the treatment approach was carried out based on FS pathology and pre-surgical data, such as imaging and probable biopsies. Patients were recruited from October 2021 through November 2022, and 381 lymph nodes of 97 patients were included in the study. In this study we recruited 38 patients (39.2%) with sentinel lymph node biopsy (SLNB) and 59 patients (60.8%) with ALND. Of the 381 LNs scored by ELS, 329 sentinel LNs underwent routine pathology, while others (n = 52) underwent both FS and permanent pathology. ELS showed a sensitivity of 91.4% for node-positive patients, decreasing to 84.8% when considering all LNs. Using ROC analysis, ELS diagnosis showed a significant AUC of 0.878 in relation to the permanent pathology gold standard. Comparison of ELS diagnosis for different tumor types and LN sizes demonstrated no significant differences, while increasing LN size correlated with enhanced ELS sensitivity. This study confirmed ELS’s efficacy in real-time lymph node detection among non-chemo-treated breast cancer patients. The use of ELS’s pathological scoring for intra-operative LN diagnosis, especially in the absence of FS pathology or for non-sentinel LN involvement, could improve prognosis and reduce complications by minimizing unnecessary dissection.
Physiological responses of Atlantic cod to climate change indicate that coastal ecotypes may be better adapted to tolerate ocean stressors
Authors: Perry Diana , Tamarit Elena , Sundell Erika , Axelsson Michael , Bergman Sanne , Gräns Albin , Gullström Martin , Sturve Joachim , Wennhage Håkan
Published: June 2024

Healthy ecosystems and species have some degree of resilience to changing conditions, however as the frequency and severity of environmental changes increase, resilience may be diminished or lost. In Sweden, one example of a species with reduced resilience is the Atlantic cod (Gadus morhua). This species has been subjected to overfishing, and with additional pressures such as habitat degradation and changing environmental conditions there has been little to no recovery, despite more than a decade of management actions. Given the historical ecological, economical, and cultural significance of cod, it is important to understand how Atlantic cod respond to global climate change to recover and sustainably manage this species in the future. A multi-stressor experiment was conducted to evaluate physiological responses of juvenile cod exposed to warming, ocean acidification, and freshening, changes expected to occur in their nursery habitat. The response to single drivers showed variable effects related to fish biometrics and increased levels of oxidative stress dependent parameters. Importantly, two separate responses were seen within a single treatment for the multi-stressor and freshening groups. These within-treatment differences were correlated to genotype, with the offshore ecotype having a heightened stress response compared to the coastal ecotype, which may be better adapted to tolerate future changes. These results demonstrate that, while Atlantic cod have some tolerance for future changes, ecotypes respond differently, and cumulative effects of multiple stressors may lead to deleterious effects for this important species.
Cognitive profile, neuroimaging and fluid biomarkers in post-acute COVID-19 syndrome
Authors: Guillén Núria , Pérez-Millan Agnès , Falgàs Neus , Lledó-Ibáñez Gema M. , Rami Lorena , Sarto Jordi , Botí Maria A. , Arnaldos-Pérez Cristina , Ruiz-García Raquel , Naranjo Laura , Segura Bàrbara , Balasa Mircea , Sala-Llonch Roser , Lladó Albert , Gray Sarah M. , Johannesen Jason K. , Pantoni Madeline M. , Rutledge Grant A. , Sawant Ruta , Wang Yi , Watson Luke S. , Dalmau Josep , Sanchez-Valle Raquel
Published: June 2024

We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ 8 weeks post-acute phase were included. A comprehensive neuropsychological battery (NPS) and health questionnaires were administered at inclusion and at 1, 3 and 6 months. Blood samples were collected at each visit, MRI scan at baseline and at 6 months, and, optionally, cerebrospinal fluid. Cognitive features were analyzed in relation to clinical, neuroimaging, and biochemical markers at inclusion and follow-up. Forty-nine participants, with a mean time from symptom onset of 10.4 months, showed attention-executive function (69%) and verbal memory (39%) impairment. Apathy (64%), moderate-severe anxiety (57%), and severe fatigue (35%) were prevalent. Visual memory (8%) correlated with total gray matter (GM) and subcortical GM volume. Neuronal damage and inflammation markers were within normal limits. Over time, cognitive test scores, depression, apathy, anxiety scores, MRI indexes, and fluid biomarkers remained stable, although fewer participants (50% vs. 75.5%; p = 0.012) exhibited abnormal cognitive evaluations at follow-up. Altered attention/executive and verbal memory, common in PACS, persisted in most subjects without association with structural abnormalities, elevated cytokines, or neuronal damage markers.
A multi-institutional machine learning algorithm for prognosticating facial nerve injury following microsurgical resection of vestibular schwannoma
Authors: Heman-Ackah Sabrina M. , Blue Rachel , Quimby Alexandra E. , Abdallah Hussein , Sweeney Elizabeth M. , Chauhan Daksh , Hwa Tiffany , Brant Jason , Ruckenstein Michael J. , Bigelow Douglas C. , Jackson Christina , Zenonos Georgios , Gardner Paul , Briggs Selena E. , Cohen Yale , Lee John Y. K.
Published: June 2024

Vestibular schwannomas (VS) are the most common tumor of the skull base with available treatment options that carry a risk of iatrogenic injury to the facial nerve, which can significantly impact patients’ quality of life. As facial nerve outcomes remain challenging to prognosticate, we endeavored to utilize machine learning to decipher predictive factors relevant to facial nerve outcomes following microsurgical resection of VS. A database of patient-, tumor- and surgery-specific features was constructed via retrospective chart review of 242 consecutive patients who underwent microsurgical resection of VS over a 7-year study period. This database was then used to train non-linear supervised machine learning classifiers to predict facial nerve preservation, defined as House-Brackmann (HB) I vs. facial nerve injury, defined as HB II–VI, as determined at 6-month outpatient follow-up. A random forest algorithm demonstrated 90.5% accuracy, 90% sensitivity and 90% specificity in facial nerve injury prognostication. A random variable (rv) was generated by randomly sampling a Gaussian distribution and used as a benchmark to compare the predictiveness of other features. This analysis revealed age, body mass index (BMI), case length and the tumor dimension representing tumor growth towards the brainstem as prognosticators of facial nerve injury. When validated via prospective assessment of facial nerve injury risk, this model demonstrated 84% accuracy. Here, we describe the development of a machine learning algorithm to predict the likelihood of facial nerve injury following microsurgical resection of VS. In addition to serving as a clinically applicable tool, this highlights the potential of machine learning to reveal non-linear relationships between variables which may have clinical value in prognostication of outcomes for high-risk surgical procedures.
Association between uric acid and referable diabetic retinopathy in patients with type 2 diabetes
Authors: Rivera-De-la-Parra David , Hernández-Jiménez Sergio , Almeda-Valdés Paloma , Aguilar-Salinas Carlos A. , Graue-Hernández Enrique O. , Pérez-Peralta Liliana , Jiménez-Corona Aida ,   Group of Study CAIPaDi, Rivera-De-la-Parra David , Hernández-Jiménez Sergio , Arcila-Martínez Denise , Del Valle-Ramírez Humberto , Flores-García Arturo , García-Ulloa Ana Cristina , Granados-Arcos Mariana , Hernández-Jasso Arely , Hernández-Juárez Diana , Infanzón-Talango Héctor , Landa-Anell Victoria , Lechuga-Fonseca Claudia , Melgarejo-Hernández Marco Antonio , Palacios-Vargas Angélica , Pérez-Peralta Liliana , Rojas-Torres Francis , Sainos-Muñoz Sandra , Velázquez-Jurado Héctor , Villegas-Narváez Andrea , Urbina-Arronte Luz Elena , Aguilar-Salinas Carlos A. , Gómez-Pérez Francisco J. , Kershenobich-Stalnikowitz David
Published: June 2024

Plasmatic uric acid (UA) has been inconsistently associated with diabetic retinopathy (DR). Specific sight-threatening stages of DR have not been studied for their association with UA. Cross-sectional, comparative study. Between 2014 and 2018 we recruited 210 Mexican individuals > 18 years-old with type 2 diabetes (T2D). Clinical, ophthalmological and biochemical assessment was performed with standardized funduscopic examination. Certified readers classified DR stages. The association between DR and UA was assessed by multiple logistic regression analysis, calculating odds ratios (OR) and 95% CI, after adjustment for covariates. Two hundred and ten patients were included, 41 (19.5%) had referable DR. Subjects with referable (severe or worse) DR had longer diabetes duration, 22 (15–28) vs 15 (8–20) years (P < 0.01); higher levels of UA, 6.5 (5.8–8.1) vs 5.4 (4.5–6.6) mg/dL (P < 0.01); higher systolic blood pressure, 130 (120–140) vs 120 (110–130) mmHg (P < 0.01); higher diastolic blood pressure, 78.4 ± 9.7 vs 75.4 ± 9.2 mmHg (P = 0.03); and lower glomerular filtration rate , 54.1 (41.5–69.6) vs 87.3 (66.8–108.3) mL/min/1.73m2 (P < 0.01) compared with those without referable DR. With multiple logistic regression, after adjustment, per each unit of change (mg/dL) in UA the probability of having referable DR increased 45% (OR = 1.45, 95% CI 1.12–1.87, P < 0.01). When UA was evaluated as dichotomous variable, those with levels ≥ 7.8 mg/dL had almost two times (OR = 2.81, 95% CI 1.00–7.9., P = 0.049) the probability of having referable DR compared with those with levels < 7.8 mg/dL. UA may contribute to the microvascular damage in retinal vessels and therefore hyperuricemia could be a therapeutic target to prevent DR progression.
Evaluation of antibacterial, cytotoxicity, and apoptosis activity of novel chromene-sulfonamide hybrids synthesized under solvent-free conditions and 3D-QSAR modeling studies
Authors: Ghomashi Shakila , Ghomashi Reihane , Damavandi Mohammad Sadegh , Fakhar Zeynab , Mousavi Seyedeh Yasaman , Salari-Jazi Azhar , Gharaghani Sajjad , Massah Ahmad Reza
Published: June 2024

In this study, eleven novel chromene sulfonamide hybrids were synthesized by a convenient method in accordance with green chemistry. At first, chromene derivatives (1–9a) were prepared through the multi-component reaction between aryl aldehydes, malononitrile, and 3-aminophenol. Then, synthesized chromenes were reacted with appropriate sulfonyl chlorides by grinding method to give the corresponding chromene sulfonamide hybrids (1–11b). Synthesized hybrids were obtained in good to high yield and characterized by IR, 1HNMR, 13CNMR, CHN and melting point techniques. In addition, the broth microdilution assay was used to determine the minimal inhibitory concentration of newly synthesized chromene-sulfonamide hybrids. The MTT test was used to determine the cytotoxicity and apoptotic activity of the newly synthesized compounds against fibroblast L929 cells. The 3D‑QSAR analysis confirmed the experimental assays, demonstrating that our predictive model is useful for developing new antibacterial inhibitors. Consequently, molecular docking studies were performed to validate the findings of the 3D-QSAR analysis, confirming the potential binding interactions of the synthesized chromene-sulfonamide hybrids with the target enzymes. Molecular docking studies were employed to support the 3D-QSAR predictions, providing insights into the binding interactions between the newly synthesized chromene-sulfonamide hybrids and their target bacterial enzymes, thereby reinforcing the potential efficacy of these compounds as antibacterial agents. Also, some of the experimental outcomes supported or conflicted with the pharmacokinetic prediction (especially about compound carcinogenicity). The performance of ADMET predictor results was assessed. The work presented here proposes a computationally driven strategy for designing and discovering a new sulfonamide scaffold for bacterial inhibition.
Staphylococcus aureus carriage and prevalence of skin and soft tissue infections among people who inject drugs: a longitudinal study
Authors: Jörgensen Jimmy , Dahlman Disa , Alanko Blomé Marianne , Janson Håkan , Riesbeck Kristian , Nilsson Anna C.
Published: June 2024

People who inject drugs are frequently colonized with Staphylococcus aureus and have an increased risk for skin and soft tissue infections. This longitudinal study aims to describe S. aureus carriage in this group and the risk for infections during a 1-year follow-up. We included 61 participants from the Malmö Needle Exchange Program. Mapping of S. aureus carriage was conducted by screening cultures every third month and S. aureus growth was semi-quantified. Data regarding infections and living conditions were collected from structured interviews. Statistics included univariate analysis with the Fischer’s exact test, univariate logistic regression and multivariate logistic regression. S. aureus carriage was detected in 46–63% of participants, and 75% reported one or more infections during the study period. Self-reported infections were associated with carriage in perineum (OR 5.08 [95% CI 1.45–17.73]), in skin lesions (OR 1.48 [95% CI 1.21–1.81]), and unstable housing situation (OR 12.83 [95% CI 1.56–105.81]). Thus, people who inject drugs are frequent carriers of S. aureus and report a surprisingly high prevalence of skin and soft tissue infections. Homeless people and those with skin carriage seem to be at highest risk. Effective clinical interventions are needed, aiming at preventing infections in this vulnerable group.
Fundamental solution of the time-space bi-fractional diffusion equation with a kinetic source term for anomalous transport
Authors: Allagui Anis , Paradezhenko Georgii , Pervishko Anastasiia , Yudin Dmitry , Benaoum Hachemi
Published: June 2024

The purpose of this paper is to study the fundamental solution of the time-space bi-fractional diffusion equation incorporating an additional kinetic source term in semi-infinite space. The equation is a generalization of the integer-order model $${\partial _{{t}} {\rho (x,t)}} = {\partial ^2_{{x}} {\rho (x,t)}} - { \rho (x,t)}$$

∂
t

ρ
(
x
,
t
)

=

∂
x
2

ρ
(
x
,
t
)

-

ρ
(
x
,
t
)

(also known as the Debye–Falkenhagen equation) by replacing the first-order time derivative with the Caputo fractional derivative of order $$0<\alpha < 1$$

0
<
α
<
1

, and the second-order space derivative with the Riesz-Feller fractional derivative of order $$0< \beta <2$$

0
<
β
<
2

. Using the Laplace-Fourier transforms method, it is shown that the parametric solutions are expressed in terms of the Fox’s H-function that we evaluate for different values of $$\alpha$$
α
and $$\beta$$
β
.
Minimally destructive hDNA extraction method for retrospective genetics of pinned historical Lepidoptera specimens
Authors: Rayo Enrique , Ulrich Gabriel F. , Zemp Niklaus , Greeff Michael , Schuenemann Verena J. , Widmer Alex , Fischer Martin C.
Published: June 2024

The millions of specimens stored in entomological collections provide a unique opportunity to study historical insect diversity. Current technologies allow to sequence entire genomes of historical specimens and estimate past genetic diversity of present-day endangered species, advancing our understanding of anthropogenic impact on genetic diversity and enabling the implementation of conservation strategies. A limiting challenge is the extraction of historical DNA (hDNA) of adequate quality for sequencing platforms. We tested four hDNA extraction protocols on five body parts of pinned false heath fritillary butterflies, Melitaea diamina, aiming to minimise specimen damage, preserve their scientific value to the collections, and maximise DNA quality and yield for whole-genome re-sequencing. We developed a very effective approach that successfully recovers hDNA appropriate for short-read sequencing from a single leg of pinned specimens using silica-based DNA extraction columns and an extraction buffer that includes SDS, Tris, Proteinase K, EDTA, NaCl, PTB, and DTT. We observed substantial variation in the ratio of nuclear to mitochondrial DNA in extractions from different tissues, indicating that optimal tissue choice depends on project aims and anticipated downstream analyses. We found that sufficient DNA for whole genome re-sequencing can reliably be extracted from a single leg, opening the possibility to monitor changes in genetic diversity maintaining the scientific value of specimens while supporting current and future conservation strategies.
Machine learning predicts upper secondary education dropout as early as the end of primary school
Authors: Psyridou Maria , Prezja Fabi , Torppa Minna , Lerkkanen Marja-Kristiina , Poikkeus Anna-Maija , Vasalampi Kati
Published: June 2024

Education plays a pivotal role in alleviating poverty, driving economic growth, and empowering individuals, thereby significantly influencing societal and personal development. However, the persistent issue of school dropout poses a significant challenge, with its effects extending beyond the individual. While previous research has employed machine learning for dropout classification, these studies often suffer from a short-term focus, relying on data collected only a few years into the study period. This study expanded the modeling horizon by utilizing a 13-year longitudinal dataset, encompassing data from kindergarten to Grade 9. Our methodology incorporated a comprehensive range of parameters, including students’ academic and cognitive skills, motivation, behavior, well-being, and officially recorded dropout data. The machine learning models developed in this study demonstrated notable classification ability, achieving a mean area under the curve (AUC) of 0.61 with data up to Grade 6 and an improved AUC of 0.65 with data up to Grade 9. Further data collection and independent correlational and causal analyses are crucial. In future iterations, such models may have the potential to proactively support educators’ processes and existing protocols for identifying at-risk students, thereby potentially aiding in the reinvention of student retention and success strategies and ultimately contributing to improved educational outcomes.