bluuebunny/crossref_metadata_2025_split huggingface dataset:
Governance basics for the physician-scientist considering business ventures. Lessons from Theranos
Authors: Witek Theodore J. , Klein David 
Published: October 2023

AbstractThe prospect of an innovative laboratory device capable of an array of testing from a tiny amount of blood caught the intense attention of both the medical and investment community. The device, however, was never properly validated, with several false and misleading claims made by its founder. This venture in the business of science went very badly for the firm Theranos with ensuing criminal convictions. Using public domain reports from trial testimony provided a unique opportunity to distill facts for key learnings for future stakeholders in the business of science. Several lessons related to basic governance unfolded during the trial’s testimony and are the basis for this brief case study. These include (1) a board make-up that had a suboptimal understanding of the technology, (2) advisors that did not sufficiently engage, (3) management/employee trust was tarnished and (4) investors failing to perform optimal diligence prior to funding. These lessons are particularly important for the physician-scientist and health executive who may find themselves at the interface of health and commerce. Points to consider in such ventures are discussed toward fostering the avoidance of these breakdowns.
Increased hippocampal blood flow in people at clinical high risk for psychosis and effects of cannabidiol
Authors: Davies Cathy , Bossong Matthijs G , Martins Daniel , Wilson Robin , Appiah-Kusi Elizabeth , Blest-Hopley Grace , Zelaya Fernando , Allen Paul , Brammer Michael , Perez Jesus , McGuire Philip , Bhattacharyya Sagnik 
Published: October 2023

AbstractBackgroundHippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown.MethodsUsing a double-blind, parallel-group design, 33 CHR patients were randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. CBD) and linear between-group relationships, such that placebo > CBD > controls or controls > CBD > placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses.ResultsPlacebo-treated patients had significantly higher hippocampal rCBF bilaterally (all pFWE<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) such that rCBF was highest in the placebo group, lowest in controls and intermediate in the CBD group. Exploratory wholebrain results replicated previous findings of hyperperfusion in the hippocampus, striatum and midbrain in CHR patients, and provided novel evidence of increased rCBF in inferior-temporal and lateral-occipital regions in patients under CBD compared to placebo.ConclusionsThese findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.
Disproportionation of Iron in Almandine‐Pyrope‐Grossular Garnet From 25 to 65 GPa
Authors: Swadba K. E. , Davis A. H. , Zurkowski C. C. , Chariton S. , Prakapenka V. B. , Campbell A. J. 
Published: October 2023

AbstractThe production of metal via the iron disproportionation reaction in the deep Earth has been a long debated topic with important implications for the geochemistry of the lower mantle. To explore the occurrence of the iron disproportionation reaction from 25 to 65 GPa, a natural almandine‐pyrope‐grossular garnet was studied with in situ X‐ray diffraction (XRD) in the laser‐heated diamond anvil cell and ex situ scanning electron microscopy (SEM) techniques. Upon heating the natural almandine‐pyrope‐grossular garnet up to 3000 K up to 65 GPa, the formation of phase assemblage consisting of bridgmanite, stishovite, and davemaoite was confirmed by XRD, but because of the low abundance of Fe metal and small grain size, XRD was determined not to be effective in detecting the disproportionation reaction. Examination of the samples recovered between 39 and 64 GPa by SEM analysis revealed the presence of nm‐scale disproportionated iron metal grains as an additional product of this reaction that was not detectable in the XRD patterns. Volume compression data of bridgmanite synthesized in the experiments were fit to the Birch‐Murnaghan equation of state and compared to similar compositions. Bridgmanite was found to decompress to the LiNbO3‐type structure, indicating a high FeAlO3 content, in accordance with the occurrence of a disproportionation reaction. The experimental confirmation of disproportionated metallic Fe has significant implications for the distribution of siderophile and volatile elements in the lower mantle.
Enhanced Mixing at the Edges of Mesoscale Eddies Observed From High‐Resolution Seismic Data in the Western Arctic Ocean
Authors: Yang Shun , Song Haibin , Coakley Bernard , Zhang Kun 
Published: October 2023

AbstractIn recent years, the Arctic Ocean has experienced a dramatic decrease in sea ice cover, leading to enhanced turbulent mixing and eddy activity. Due to the scarcity of high‐resolution observations, our understanding of turbulent mixing in the Arctic is incomplete. Using three seismic reflection transects with high spatial resolution (∼O (10) m) and concurrent ADCP‐derived current velocity, this study identified 11 mesoscale eddies on the ice‐free Chukchi Borderlands of the western Arctic Ocean. 82% of them are intra‐halocline anticyclones. The total length of horizontal scales of these 11 eddies occupies ∼40% of the total length of three seismic lines. Diapycnal diffusivities estimated from seismic data were enhanced and can be up to 10−4 m2 s−1 at the edges of these eddies, compared with the average values (∼10−6 m2 s−1) at the Chukchi Borderlands. Seismic‐estimated diffusivities were validated by fine‐scale parameterization using ADCP‐derived velocity data and historical hydrographic data. Enhanced diffusivities at the edges of eddies may be attributed to shear instabilities at the top and bottom edges and to submesoscale motions at the lateral edges of these eddies. We highlight the enhanced mixing at the edges of eddies in the halocline can increase the upward heat flux. This upward heat flux can transfer the heat of the warm Atlantic water below to the surface, which may further promote the melting of surface sea ice.
The Benefits and Challenges of Downscaling a Global Reanalysis With Doubly‐Periodic Large‐Eddy Simulations
Authors: van Stratum B. J. H. , van Heerwaarden C. C. , Vilà‐Guerau de Arellano J. 
Published: October 2023

AbstractGlobal reanalyzes like ERA5 accurately capture atmospheric processes at spatial scales of km or larger. By downscaling ERA5 with large‐eddy simulation (LES), LES can provide details about processes at spatio‐temporal scales down to meters and seconds. Here, we present an open‐source Python package named the “Large‐eddy simulation and Single‐column model—Large‐Scale Dynamics,” or (LS)2D in short, designed to simplify the downscaling of ERA5 with doubly‐periodic LES. A validation with observations, for several sensitivity experiments consisting of month‐long LESs over Cabauw (the Netherlands), demonstrates both its usefulness and limitations. The day‐to‐day variability in the weather is well captured by (LS)2D and LES, but the setup under‐performs in conditions with broken or near overcast clouds. As a novel application of this modeling system, we used (LS)2D to study surface solar irradiance variability, as this quantity directly links land‐surface processes, turbulent transport, and clouds, to radiation. At a horizontal resolution of 25 m, the setup reproduces satisfactorily the solar irradiance variability down to a timescale of seconds. This demonstrates that the coupled LES‐ERA5 setup is a useful tool that can provide details on the physics of turbulence and clouds, but can only improve on its host reanalysis when applied to meteorological suitable conditions.
Neuronal RBM5 modulates cell signaling responses to traumatic and hypoxic-ischemic injury in a sex-dependent manner
Authors: Snyder Kara , Gorse Kiersten , Kochanek Patrick M. , Jackson Travis C. 
Published: October 2023

AbstractIt is not clear if inhibiting the pro-death gene RNA binding motif 5 (RBM5) is neuroprotective in isolated primary neurons or if it regulates cell survival in a sex-dependent manner. Here we established sex-dichotomized primary cortical neuron cultures from transgenic mice harboring a floxed RBM5 gene-trap. Lentivirus-mediated expression of CRE was used to silence RBM5 expression. Male and female neurons were maintained in next-generation Neurobasal-Plus media and subjected to a mechanical stretch-injury (to model traumatic brain injury) or oxygen-glucose deprivation/OGD (to model ischemia). RBM5 KO did not affect 24 h post-injury survival as determined by lactate dehydrogenase (LDH) release, in either paradigm. In contrast, female KO neurons had increased spectrin breakdown products post-insult (in both models). Furthermore, in OGD, RBM5 KO in male neurons exacerbated injury-induced downregulation of pro-survival AKT activation (pAKT473) but conversely led to pAKT473 sparing in female neurons. Moreover, global proteomics identified 19 differentially expressed (DE) proteins in OGD-injured male neurons, and 102 DE proteins in injured female neurons. Two novel RBM5-regulated proteins (PIGQ and EST1C) were identified in injured male KO neurons, and 8 novel proteins identified in injured female KO neurons (S35A5, DHTK1, STX3, IF3M, RN167, K1C14, DYHS, and MED13). In summary, RBM5 inhibition does not modify neuronal survival in primary mouse neurons in 2 clinically relevant models of excitotoxic insult, but RBM5 does regulate intracellular responses to injury in a sex-dependent manner.
Metformin potentiates nephrotoxicity by promoting NETosis in response to renal ferroptosis
Authors: Cai Zhaoxian , Wu Xiaotian , Song Zijun , Sun Shumin , Su Yunxing , Wang Tianyi , Cheng Xihao , Yu Yingying , Yu Chao , Chen En , Chen Wenteng , Yu Yongping , Linkermann Andreas , Min Junxia , Wang Fudi 
Published: October 2023

AbstractGiven the rapidly aging population, aging-related diseases are becoming an excessive burden on the global healthcare system. Metformin has been shown to be beneficial to many age-related disorders, as well as increase lifespan in preclinical animal models. During the aging process, kidney function progressively declines. Currently, whether and how metformin protects the kidney remains unclear. In this study, among longevity drugs, including metformin, nicotinamide, resveratrol, rapamycin, and senolytics, we unexpectedly found that metformin, even at low doses, exacerbated experimentally-induced acute kidney injury (AKI) and increased mortality in mice. By single-cell transcriptomics analysis, we found that death of renal parenchymal cells together with an expansion of neutrophils occurs upon metformin treatment after AKI. We identified programmed cell death by ferroptosis in renal parenchymal cells and blocking ferroptosis, or depleting neutrophils protects against metformin-induced nephrotoxicity. Mechanistically, upon induction of AKI, ferroptosis in renal parenchymal cells initiates the migration of neutrophils to the site of injury via the surface receptor CXCR4–bound to metformin–iron–NGAL complex, which results in NETosis aggravated AKI. Finally, we demonstrated that reducing iron showed protective effects on kidney injury, which supports the notion that iron plays an important role in metformin-triggered AKI. Taken together, these findings delineate a novel mechanism underlying metformin-aggravated nephropathy and highlight the mechanistic relationship between iron, ferroptosis, and NETosis in the resulting AKI.
Streamlined structure determination by cryo-electron tomography and subtomogram averaging using TomoBEAR
Authors: Balyschew Nikita , Yushkevich Artsemi , Mikirtumov Vasilii , Sanchez Ricardo M. , Sprink Thiemo , Kudryashev Mikhail 
Published: October 2023

AbstractStructures of macromolecules in their native state provide unique unambiguous insights into their functions. Cryo-electron tomography combined with subtomogram averaging demonstrated the power to solve such structures in situ at resolutions in the range of 3 Angstrom for some macromolecules. In order to be applicable to the structural determination of the majority of macromolecules observable in cells in limited amounts, processing of tomographic data has to be performed in a high-throughput manner. Here we present TomoBEAR—a modular configurable workflow engine for streamlined processing of cryo-electron tomographic data for subtomogram averaging. TomoBEAR combines commonly used cryo-EM packages with reasonable presets to provide a transparent (“white box”) approach for data management and processing. We demonstrate applications of TomoBEAR to two data sets of purified macromolecular targets, to an ion channel RyR1 in a membrane, and the tomograms of plasma FIB-milled lamellae and demonstrate the ability to produce high-resolution structures. TomoBEAR speeds up data processing, minimizes human interventions, and will help accelerate the adoption of in situ structural biology by cryo-ET. The source code and the documentation are freely available.
uAUG creating variants in the 5’UTR of ENG causing Hereditary Hemorrhagic Telangiectasia
Authors: Soukarieh Omar , Tillet Emmanuelle , Proust Carole , Dupont Charlène , Jaspard-Vinassa Béatrice , Soubrier Florent , Goyenvalle Aurélie , Eyries Mélanie , Trégouët David-Alexandre 
Published: October 2023

AbstractHereditary Hemorrhagic Telangiectasia (HHT) is a rare, autosomal dominant, vascular disorder. About 80% of cases are caused by pathogenic variants in ACVRL1 (also known as ALK1) and ENG, with the remaining cases being unexplained. We identified two variants, c.-79C>T and c.-68G>A, in the 5’UTR of ENG in two unrelated patients. They create upstream AUGs at the origin of upstream overlapping open reading frames (uoORFs) ending at the same stop codon. To assess the pathogenicity of these variants, we performed functional assays based on the expression of wild-type and mutant constructs in human cells and evaluated their effect on ALK1 activity in a BMP-response element assay. This assay is mandatory for molecular diagnosis and has been so far only applied to coding ENG variants. These variants were associated with a decrease of protein levels in HeLa and HUVEC cells and a decreased ability to activate ALK1. We applied the same experiments on three additional uoORF-creating variants (c.-142A>T, c.-127C>T and c.-10C>T) located in the 5’UTR of ENG and previously reported in HHT patients. We found that all the analyzed variants alter protein levels and function. Additional experiments relying on an artificial deletion in our mutated constructs show that identified uAUGs could initiate the translation indicating that the associated effect is translation-dependent. Overall, we have identified two 5’UTR ENG variations in HHT patients and shed new light on the role of upstream ORFs on ENG regulation. Our findings contribute to the amelioration of molecular diagnosis in HHT.
Skin-integrated, biocompatible, and stretchable silicon microneedle electrode for long-term EMG monitoring in motion scenario
Authors: Ji Huawei , Wang Mingyu , Wang Yutong , Wang Zhouheng , Ma Yinji , Liu Lanlan , Zhou Honglei , Xu Ze , Wang Xian , Chen Ying , Feng Xue 
Published: October 2023

AbstractElectromyography (EMG) signal is the electrical potential generated by contracting muscle cells. Long-term and accurate EMG monitoring is desirable for neuromuscular function assessment in clinical and the human–computer interfaces. Herein, we report a skin-integrated, biocompatible, and stretchable silicon microneedle electrode (SSME) inspired by the plant thorns. The silicon microneedles are half encapsulated by the polyimide (PI) to enhance the adaptability to deformation and resistance to fatigue. Thorn-like SSME is realized by the semi-additive method with a stretchability of not less than 36%. The biocompatibility of SSME has been verified using cytotoxicity tests. EMG monitoring in motion and long-term has been conducted to demonstrate the feasibility and performance of the SSME, which is compared with a commercial wet electrode. Hopefully, the strategies reported here can lead to accurate and long-term EMG monitoring, facilitating an effective and reliable human–computer interface.
In situ observation of melt pool evolution in ultrasonic vibration-assisted directed energy deposition
Authors: El-Azab Salma A. , Zhang Cheng , Jiang Sen , Vyatskikh Aleksandra L. , Valdevit Lorenzo , Lavernia Enrique J. , Schoenung Julie M. 
Published: October 2023

AbstractThe presence of defects, such as pores, in materials processed using additive manufacturing represents a challenge during the manufacturing of many engineering components. Recently, ultrasonic vibration-assisted (UV-A) directed energy deposition (DED) has been shown to reduce porosity, promote grain refinement, and enhance mechanical performance in metal components. Whereas it is evident that the formation of such microstructural features is affected by the melt pool behavior, the specific mechanisms by which ultrasonic vibration (UV) influences the melt pool remain elusive. In the present investigation, UV was applied in situ to DED of 316L stainless steel single tracks and bulk parts. For the first time, high-speed video imaging and thermal imaging were implemented in situ to quantitatively correlate the application of UV to melt pool evolution in DED. Extensive imaging data were coupled with in-depth microstructural characterization to develop a statistically robust dataset describing the observed phenomena. Our findings show that UV increases the melt pool peak temperature and dimensions, while improving the wettability of injected particles with the melt pool surface and reducing particle residence time. Near the substrate, we observe that UV results in a 92% decrease in porosity, and a 54% decrease in dendritic arm spacing. The effect of UV on the melt pool is caused by the combined mechanisms of acoustic cavitation, ultrasound absorption, and acoustic streaming. Through in situ imaging we demonstrate quantitatively that these phenomena, acting simultaneously, effectively diminish with increasing build height and size due to acoustic attenuation, consequently decreasing the positive effect of implementing UV-A DED. Thus, this research provides valuable insight into the value of in situ imaging, as well as the effects of UV on DED melt pool dynamics, the stochastic interactions between the melt pool and incoming powder particles, and the limitations of build geometry on the UV-A DED technique.
Physiological and biochemical responses of soft coral Sarcophyton trocheliophorum to doxycycline hydrochloride exposure
Authors: Xu Wenxin , Ahmed Waqas , Mahmood Mohsin , Li Weidong , Mehmood Sajid 
Published: October 2023

AbstractIn light of the rapid expansion of the marine aquaculture industry, there has been widespread and irregular usage of aquatic drugs to combat biological diseases, which significantly impact the neighboring aquatic ecosystems. This study delves into the impact of the antibiotic aquatic drug known as doxycycline hydrochloride (DOX) on offshore soft corals, providing valuable data for the responsible use and management of aquatic drugs. In this investigation, we subjected Sarcophyton trocheliophorum to acute exposure to varying concentrations of DOX (0, 1, 5, and 10 mg L−1). We meticulously assessed critical parameters and observed alterations in protein levels, superoxide dismutase (SOD) activity, catalase (CAT) activity, lipid peroxidation (LPO), malondialdehyde (MDA) levels, Acid phosphatase (ACP) activity, alkaline phosphatase (AKP) activity, glutathione (GSH) concentration, glutathione S-transferase (GST) activity, glutathione Peroxidase (GSH-Px) activity, zooxanthellae density, and chlorophyll content. Our findings reveal that in the presence of DOX-induced environmental stress, there is a significant increase in LPO, MDA, chlorophyll, carotenoid levels, and the activities of ACP, GST, and GSH-Px in soft corals. Simultaneously, there is a noteworthy decrease in zooxanthellae density. Additionally, the protein concentration and SOD activity in soft corals experience substantial reduction when exposed to 5 mg L−1 DOX. Notably, CAT activity varies significantly in environments with 1 and 10 mg L−1 DOX. Moreover, these conditions exhibit a discernible influence on AKP activity, GSH content, and chlorophyll levels. These findings suggest that DOX exposure carries the potential for toxicity in aquaculture settings, affecting protein synthesis in soft corals and influencing oxidative stress, lipid peroxidation, immunity, and detoxification processes within these organisms. There is also a risk of compromising the coral defense system, potentially leading to coral bleaching. Furthermore, this study underscores the significant impact on photosynthesis, growth, and the metabolic dynamics of the coral-zooxanthellae symbiotic system. Consequently, our research offers vital insights into the mortality and bleaching effects of aquatic drugs on marine corals, offering a foundation for the prudent use and management of such substances.
Evaluation of a novel MRI-safe needle guidance toolkit for streamlined arthrography procedures
Authors: Monfaredi Reza , Yarmolenko Pavel , Lee Eung-Joo , Cleary Kevin , Sharma Karun 
Published: October 2023

AbstractCurrently, Magnetic Resonance arthrography procedures require two rooms and two imaging modalities: fluoroscopically guided needle insertion in a fluoroscopy suite, followed by diagnostic MRI in a separate MRI suite. The use of fluoroscopy for needle placement exposes patients to ionizing radiation, which is an important concern, especially in pediatrics. The need for two different rooms and coordinating times for these rooms complicates hospital resource scheduling and logistics. In addition, the added delays could expose younger children to additional risks associated with the use of general anesthesia. To address these issues, we propose a new technique to streamline the arthrography procedure. Our proposed technology aims to eliminate exposure to ionizing radiation and to streamline arthrography procedures that are conducted solely under MRI. This toolkit consists of a 3D slicer-based user interface, a spatially unique silicone grid template, and a hand-held needle guidance device. Together, these tools are intended to simplify and shorten the procedure while maintaining accuracy and precision comparable to the current gold standard procedure. In our cadaver study, we evaluated the feasibility and accuracy of our novel MRI-safe Needle Guidance Toolkit for MRI arthrography procedures, achieving an average targeting accuracy of 3.2 ± 1.0 mm. The results presented in this study showed the feasibility and promise of our novel MRI-safe needle guidance toolkit for arthrography procedures.