bluuebunny/crossref_metadata_2025 huggingface dataset:
Moisture-driven divergence in mineral-associated soil carbon persistence
Authors: Heckman Katherine A. , Possinger Angela R. , Badgley Brian D. , Bowman Maggie M. , Gallo Adrian C. , Hatten Jeff A. , Nave Lucas E. , SanClements Michael D. , Swanston Christopher W. , Weiglein Tyler L. , Wieder William R. , Strahm Brian D.
Published: February 2023

Mineral stabilization of soil organic matter is an important regulator of the global carbon (C) cycle. However, the vulnerability of mineral-stabilized organic matter (OM) to climate change is currently unknown. We examined soil profiles from 34 sites across the conterminous USA to investigate how the abundance and persistence of mineral-associated organic C varied with climate at the continental scale. Using a novel combination of radiocarbon and molecular composition measurements, we show that the relationship between the abundance and persistence of mineral-associated organic matter (MAOM) appears to be driven by moisture availability. In wetter climates where precipitation exceeds evapotranspiration, excess moisture leads to deeper and more prolonged periods of wetness, creating conditions which favor greater root abundance and also allow for greater diffusion and interaction of inputs with MAOM. In these humid soils, mineral-associated soil organic C concentration and persistence are strongly linked, whereas this relationship is absent in drier climates. In arid soils, root abundance is lower, and interaction of inputs with mineral surfaces is limited by shallower and briefer periods of moisture, resulting in a disconnect between concentration and persistence. Data suggest a tipping point in the cycling of mineral-associated C at a climate threshold where precipitation equals evaporation. As climate patterns shift, our findings emphasize that divergence in the mechanisms of OM persistence associated with historical climate legacies need to be considered in process-based models.
Integrated regulation of dopaminergic and epigenetic effectors of neuroprotection in Parkinson’s disease models
Authors: Nourse J. Brucker , Russell Shannon N. , Moniz Nathan A. , Peter Kylie , Seyfarth Lena M. , Scott Madison , Park Han-A , Caldwell Kim A. , Caldwell Guy A.
Published: February 2023

Whole-exome sequencing of Parkinson’s disease (PD) patient DNA identified single-nucleotide polymorphisms (SNPs) in the tyrosine nonreceptor kinase-2 (TNK2) gene. Although this kinase had a previously demonstrated activity in preventing the endocytosis of the dopamine reuptake transporter (DAT), a causal role for TNK2-associated dysfunction in PD remains unresolved. We postulated the dopaminergic neurodegeneration resulting from patient-associated variants inTNK2were a consequence of aberrant or prolonged TNK2 overactivity, the latter being a failure in TNK2 degradation by an E3 ubiquitin ligase, neuronal precursor cell-expressed developmentally down-regulated-4 (NEDD4). Interestingly, systemic RNA interference protein-3 (SID-3) is the sole TNK2 ortholog in the nematodeCaenorhabditis elegans, where it is an established effector of epigenetic gene silencing mediated through the dsRNA-transporter, SID-1. We hypothesized that TNK2/SID-3 represents a node of integrated dopaminergic and epigenetic signaling essential to neuronal homeostasis. Use of a TNK2 inhibitor (AIM-100) or a NEDD4 activator [N-aryl benzimidazole 2 (NAB2)] in bioassays for either dopamine- or dsRNA-uptake into worm dopaminergic neurons revealed thatsid-3mutants displayed robust neuroprotection from 6-hydroxydopamine (6-OHDA) exposures, as did AIM-100 or NAB2-treated wild-type animals. Furthermore, NEDD4 activation by NAB2 in rat primary neurons correlated to a reduction in TNK2 levels and the attenuation of 6-OHDA neurotoxicity. CRISPR-edited nematodes engineered to endogenously express SID-3 variants analogous toTNK2PD-associated SNPs exhibited enhanced susceptibility to dopaminergic neurodegeneration and circumvented the RNAi resistance characteristic of SID-3 dysfunction. This research exemplifies a molecular etiology for PD whereby dopaminergic and epigenetic signaling are coordinately regulated to confer susceptibility or resilience to neurodegeneration.
Epigenetic function during heroin self-administration controls future relapse-associated behavior in a cell type-specific manner
Authors: Anderson Ethan M. , Tsvetkov Evgeny , Galante Allison , DeVries Derek , McCue Lauren M. , Wood Daniel , Barry Sarah , Berto Stefano , Lavin Antonieta , Taniguchi Makoto , Cowan Christopher W.
Published: February 2023

Opioid use produces enduring associations between drug reinforcement/euphoria and discreet or diffuse cues in the drug-taking environment. These powerful associations can trigger relapse in individuals recovering from opioid use disorder (OUD). Here, we sought to determine whether the epigenetic enzyme, histone deacetylase 5 (HDAC5), regulates relapse-associated behavior in an animal model of OUD. We examined the effects of nucleus accumbens (NAc) HDAC5 on both heroin- and sucrose-seeking behaviors using operant self-administration paradigms. We utilized cre-dependent viral-mediated approaches to investigate the cell-type–specific effects of HDAC5 on heroin-seeking behavior, gene expression, and medium spiny neuron (MSN) cell and synaptic physiology. We found that NAc HDAC5 functions during the acquisition phase of heroin self-administration to limit future relapse-associated behavior. Moreover, overexpressing HDAC5 in the NAc suppressed context-associated and reinstated heroin-seeking behaviors, but it did not alter sucrose seeking. We also found that HDAC5 functions within dopamine D1 receptor-expressing MSNs to suppress cue-induced heroin seeking, and within dopamine D2 receptor-expressing MSNs to suppress drug-primed heroin seeking. Assessing cell-type–specific transcriptomics, we found that HDAC5 reduced expression of multiple ion transport genes in both D1- and D2-MSNs. Consistent with this observation, HDAC5 also produced firing rate depression in both MSN classes. These findings revealed roles for HDAC5 during active heroin use in both D1- and D2-MSNs to limit distinct triggers of drug-seeking behavior. Together, our results suggest that HDAC5 might limit relapse vulnerability through regulation of ion channel gene expression and suppression of MSN firing rates during active heroin use.
PKD autoinhibition in
trans
regulates activation loop autophosphorylation in
cis
Authors: Reinhardt Ronja , Hirzel Kai , Link Gisela , Eisler Stephan A. , Hägele Tanja , Parson Matthew A. H. , Burke John E. , Hausser Angelika , Leonard Thomas A.
Published: February 2023

Phosphorylation is a ubiquitous mechanism by which signals are transduced in cells. Protein kinases, enzymes that catalyze the phosphotransfer reaction are, themselves, often regulated by phosphorylation. Paradoxically, however, a substantial fraction of more than 500 human protein kinases are capable of catalyzing their own activation loop phosphorylation. Commonly, these kinases perform this autophosphorylation reaction in
trans
, whereby transient dimerization leads to the mutual phosphorylation of the activation loop of the opposing protomer. In this study, we demonstrate that protein kinase D (PKD) is regulated by the inverse mechanism of dimerization-mediated
trans
-autoinhibition, followed by activation loop autophosphorylation in
cis
. We show that PKD forms a stable face-to-face homodimer that is incapable of either autophosphorylation or substrate phosphorylation. Dissociation of this
trans
-autoinhibited dimer results in activation loop autophosphorylation, which occurs exclusively in
cis
. Phosphorylation serves to increase PKD activity and prevent
trans
-autoinhibition, thereby switching PKD on. Our findings not only reveal the mechanism of PKD regulation but also have profound implications for the regulation of many other eukaryotic kinases.
Gaucher disease protects against tuberculosis
Authors: Fan Jingwen , Hale Victoria L. , Lelieveld Lindsey T. , Whitworth Laura J. , Busch-Nentwich Elisabeth M. , Troll Mark , Edelstein Paul H. , Cox Timothy M. , Roca Francisco J. , Aerts Johannes M. F. G. , Ramakrishnan Lalita
Published: February 2023

Biallelic mutations in the glucocerebrosidase (
GBA1
) gene cause Gaucher disease, characterized by lysosomal accumulation of glucosylceramide and glucosylsphingosine in macrophages. Gaucher and other lysosomal diseases occur with high frequency in Ashkenazi Jews. It has been proposed that the underlying mutations confer a selective advantage, in particular conferring protection against tuberculosis. Here, using a zebrafish Gaucher disease model, we find that the mutation
GBA1
N370S, predominant among Ashkenazi Jews, increases resistance to tuberculosis through the microbicidal activity of glucosylsphingosine in macrophage lysosomes. Consistent with lysosomal accumulation occurring only in homozygotes, heterozygotes remain susceptible to tuberculosis. Thus, our findings reveal a mechanistic basis for protection against tuberculosis by
GBA1
N370S and provide biological plausibility for its selection if the relatively mild deleterious effects in homozygotes were offset by significant protection against tuberculosis, a rampant killer of the young in Europe through the Middle Ages into the 19th century.
Limb girdle muscular disease caused by
HMGCR
mutation and statin myopathy treatable with mevalonolactone
Authors: Yogev Yuval , Shorer Zamir , Koifman Arie , Wormser Ohad , Drabkin Max , Halperin Daniel , Dolgin Vadim , Proskorovski-Ohayon Regina , Hadar Noam , Davidov Geula , Nudelman Hila , Zarivach Raz , Shelef Ilan , Perez Yonatan , Birk Ohad S.
Published: February 2023

Myopathy is the main adverse effect of the widely prescribed statin drug class. Statins exert their beneficial effect by inhibiting HMG CoA-reductase, the rate-controlling enzyme of the mevalonate pathway. The mechanism of statin myopathy is yet to be resolved, and its treatment is insufficient. Through homozygosity mapping and whole exome sequencing, followed by functional analysis using confocal microscopy and biochemical and biophysical methods, we demonstrate that a distinct form of human limb girdle muscular disease is caused by a pathogenic homozygous loss-of-function missense mutation in HMG CoA reductase (
HMGCR
), encoding HMG CoA-reductase
.
We biochemically synthesized and purified mevalonolactone, never administered to human patients before, and establish the safety of its oral administration in mice. We then show that its oral administration is effective in treating a human patient with no significant adverse effects. Furthermore, we demonstrate that oral mevalonolactone resolved statin-induced myopathy in mice. We conclude that
HMGCR
mutation causes a late-onset severe progressive muscular disease, which shows similar features to statin-induced myopathy. Our findings indicate that mevalonolactone is effective both in the treatment of hereditary
HMGCR
myopathy and in a murine model of statin myopathy. Further large clinical trials are in place to enable the clinical use of mevalonolactone both in the rare orphan disease and in the more common statin myopathy.
Allosteric mechanism of transcription inhibition by NusG-dependent pausing of RNA polymerase
Authors: Vishwakarma Rishi K. , Qayyum M. Zuhaib , Babitzke Paul , Murakami Katsuhiko S.
Published: February 2023

NusG is a transcription elongation factor that stimulates transcription pausing in Gram+ bacteria including
B. subtilis
by sequence-specific interaction with a conserved pause-inducing
−
11
TTNTTT
−6
motif found in the non-template DNA (ntDNA) strand within the transcription bubble. To reveal the structural basis of NusG-dependent pausing, we determined a cryo-EM structure of a paused transcription complex (PTC) containing RNA polymerase (RNAP), NusG, and the TTNTTT motif in the ntDNA strand. The interaction of NusG with the ntDNA strand rearranges the transcription bubble by positioning three consecutive T residues in a cleft between NusG and the β-lobe domain of RNAP. We revealed that the RNAP swivel module rotation (swiveling), which widens (swiveled state) and narrows (non-swiveled state) a cleft between NusG and the β-lobe, is an intrinsic motion of RNAP and is directly linked to trigger loop (TL) folding, an essential conformational change of all cellular RNAPs for the RNA synthesis reaction. We also determined cryo-EM structures of RNAP escaping from the paused transcription state. These structures revealed the NusG-dependent pausing mechanism by which NusG-ntDNA interaction inhibits the transition from swiveled to non-swiveled states, thereby preventing TL folding and RNA synthesis allosterically. This motion is also reduced by the formation of an RNA hairpin within the RNA exit channel. Thus, the pause half-life can be modulated by the strength of the NusG-ntDNA interaction and/or the stability of the RNA hairpin. NusG residues that interact with the TTNTTT motif are widely conserved in bacteria, suggesting that NusG-dependent pausing is widespread.
Multimodality in refusals in English as a lingua franca
Authors: Fang Xianming
Published: February 2023

This study investigates how multimodal cues are used for rapport management in refusals in the context of English as a lingua franca (ELF). Ten Chinese and ten Indonesian speakers were put in pairs and conducted role-plays in relation to requests and refusals. After the role-plays, they had immediate interviews to reflect on their own and their partners’ performance. The results suggest that body positions (standing/sitting), smiling voices and smiling facial expressions, and the long gaze aversion are used by ELF refusers to maintain rapport: controlling power relationships, mitigating the force of refusals, and conveying a non-engagement stance. The results show that mitigation in the ELF context is a multimodal achievement which can be intentionally realized through various multimodal cues.
Impact of synthesis temperature and precursor ratio on the crystal quality of MOCVD WSe2 monolayers
Authors: Grundmann Annika , Beckmann Yannick , Ghiami Amir , Bui Minh , Kardynal Beata , Patterer Lena , Schneider Jochen , Kümmell Tilmar , Bacher Gerd , Heuken Michael , Kalisch Holger , Vescan Andrei
Published: February 2023

Structural defects in transition metal dichalcogenide (TMDC) monolayers (ML) play a significant role in determining their (opto)electronic properties, triggering numerous efforts to control defect densities during material growth or by post-growth treatments. Various types of TMDC have been successfully deposited by MOCVD (metal-organic chemical vapor deposition), which is a wafer-scale deposition technique with excellent uniformity and controllability. However, so far there are no findings on the extent to which the incorporation of defects can be controlled by growth parameters during MOCVD processes of TMDC. In this work, we investigate the effect of growth temperature and precursor ratio during MOCVD of tungsten diselenide (WSe2) on the growth of ML domains and their impact on the density of defects. The aim is to find parameter windows that enable the deposition of WSe2 ML with high crystal quality, i.e. a low density of defects. Our findings confirm that the growth temperature has a large influence on the crystal quality of TMDC, significantly stronger than found for the W to Se precursor ratio. Raising the growth temperatures in the range of 688 °C to 791 °C leads to an increase of the number of defects, dominating photoluminescence (PL) at low temperatures (5.6 K). In contrast, an increase of the molar precursor ratio (DiPSe/WCO) from 1000 up to 100 000 leads to less defect-related PL at low temperatures.
Electroplating-based engineering of plasmonic nanorod metamaterials for biosensing applications
Authors: Sahoo Mihir Kumar , Anand VS Abhay , Kumar Anshuman
Published: February 2023

Sensing lower molecular weight in a diluted solution using a label-free biosensor is challenging and requires a miniaturized plasmonic structure, e.g. a vertical Au nanorod (AuNR) array-based metamaterials. The sensitivity of a sensor mainly depends on transducer properties and hence for instance, the AuNR array geometry requires optimization. Physical vapour deposition methods (e.g. sputtering and e-beam evaporation) require a vacuum environment to deposit Au, which is costly, time-consuming, and thickness-limited. On the other hand, chemical deposition, i.e. electroplating deposit higher thickness in less time and at lower cost, becomes an alternative method for Au deposition. In this work, we present a detailed optimization for the electroplating-based fabrication of these metamaterials. We find that slightly acidic (6.0 < pH < 7.0) gold sulfite solution supports immersion deposition, which should be minimized to avoid uncontrolled Au deposition. Immersion deposition leads to plate-like (for smaller radius AuNR) or capped-like, i.e. mushroom (for higher radius AuNR) structure formation. The electroplating time and DC supply are the tuning parameters that decide the geometry of the vertically aligned AuNR array in area-dependent electroplating deposition. This work will have implications for developing plasmonic metamaterial-based sensors.
Nanodiamond surface as a photoluminescent pH sensor
Authors: Padrez Yaraslau , Golubewa Lena , Bahdanava Anastasiya , Jankunec Marija , Matulaitiene Ieva , Semenov Dmitry , Karpicz Renata , Kulahava Tatsiana , Svirko Yuri , Kuzhir Polina
Published: February 2023

A systematic spectroscopic characterization of highly homogeneous water suspensions of ‘buckydiamonds’ comprising sp3 cubic nanodiamond (ND) core covered with disordered sp2 shell densely decorated with oxygen-containing groups demonstrates the excitation-wavelength-dependent photoluminescence (PL) given by at least four types of specific structures on the ND surface (hydroxyl, C=O containing ketones, carboxylic anhydrides, and carboxyl groups). PL properties of NDs suspensions possess concentration-dependent behavior revealing tendency of NDs to agglomerate. PL of NDs has been found to be strongly sensitive to pH of the environment in wide range of pH values, i.e. 2–11. We disclosed the mechanisms of pH sensitivity of the ‘buckydiamond’ and proved that it can serve as all-optical sensor of tiny pH variations suitable for further exploitation for pH sensing locally in the area where NDs have been delivered for any purpose, e.g. bioimaging or therapeutic needs.
A self-powered sound-driven humidity sensor for wearable intelligent dehydration monitoring system
Authors: Hu Lihong , Zhong Tianyan , Long Zhihe , Liang Shan , Xing Lili , Xue Xinyu
Published: February 2023

Self-powered wearable sensing systems have attracted great attention for their application in continuous health monitoring, which can reveal real-time physiological information on the body. Here, an innovative self-powered sound-driven humidity sensor for wearable intelligent dehydration monitoring system has been proposed. The sensor is primarily comprised of PTFE membrane, ZnO nanoarrays and Ti thin film. The piezoelectric/triboelectric effect of ZnO nanoarrays/PTFE membrane is coupled with the humidity sensing process. Sound wave can drive PTFE membrane to vibrate, and the contact and separation between PTFE and ZnO can generate electrical signals through piezoelectric/triboelectric effect. At the same time, the surface of the nanostructures can absorb the water molecules, which will influence the electrical output of the device. The device can convert sound energy into electrical output without any external electricity power supply, and the outputting voltage decreases with increasing relative humidity, acting as the sensing signal. The sensor has been integrated with data processing unit and wireless transmission module to form a self-powered wearable intelligent dehydration monitoring system, which can actively monitor the humidity of exhaled breath and transmit the information to the mobile phone. The results can open a possible new direction for the development of sound-driven gas sensors and will further expand the scope for self-powered nanosystems.
A novel vessel segmentation algorithm for pathological en-face images based on matched filter
Authors: Hu Derong , Pan Lingjiao , Chen Xinjian , Xiao Shuyan , Wu Quanyu
Published: February 2023

The vascular information in fundus images can provide important basis for detection and prediction of retina-related diseases. However, the presence of lesions such as Coroidal Neovascularization can seriously interfere with normal vascular areas in optical coherence tomography (OCT) fundus images. In this paper, a novel method is proposed for detecting blood vessels in pathological OCT fundus images. First of all, an automatic localization and filling method is used in preprocessing step to reduce pathological interference. Afterwards, in terms of vessel extraction, a pore ablation method based on capillary bundle model is applied. The ablation method processes the image after matched filter feature extraction, which can eliminate the interference caused by diseased blood vessels to a great extent. At the end of the proposed method, morphological operations are used to obtain the main vascular features. Experimental results on the dataset show that the proposed method achieves 0.88 ± 0.03, 0.79 ± 0.05, 0.66 ± 0.04, results in DICE, PRECISION and TPR, respectively. Effective extraction of vascular information from OCT fundus images is of great significance for the diagnosis and treatment of retinal related diseases.
Contribution of multiscale analysis to the understanding of friction evolution of aggregates surfaces
Authors: Edjeou Wiyao , Cerezo Veronique , Zahouani Hassan , Do Minh-Tan
Published: February 2023

In this paper, a multiscale texture analysis method is developped and applied to aggregates surfaces to better explain the variation of road friction during polishing process. This method is based on continuous wavelets decomposition. The study is done on five aggregates types by varying aggregates hardness and mineralogical composition. Polishing tests and friction measurement are performed on each formula using Wehner & Schulze appartus to follow the evolution of friction with polishing. At each polishing stage, 3D mapping are made using Alicona Infinite Focus Sensor to follow the evolution of the surface texture. On these cartographies, multiscale texture parameters are calculated and analysed. Correlations between theses parameters and friction show that scales ranging between 0 and 1000 μm seem to be the most relevant to explain friction evolution.
Mechanical, degradation rate, and antibacterial properties of a collagen-chitosan/PVA composite nanofiber
Authors: Hartatiek  , Fathurochman Fadhil , Wuriantika Maulia Ingganis , Yudyanto  , Masruroh  , Djoko Herry Santjojo Dionysius Joseph , Nurhuda Muhammad
Published: February 2023

This study synthesized collagen-chitosan/PVA nanofiber composites using the electrospinning method. Characterizations included Fourier transform infrared spectroscopy (FTIR) and surface morphology using scanning electron microscopy (SEM). Investigations were carried out on tensile strength, degradation rate, and antibacterial test. It was found that the functional groups C–H, –OH, C–O, C–N, and N–H were suitable for PVA, collagen, and chitosan materials. The SEM showed that increasing the PVA composition caused a change in fiber diameter ranging from 34.64 to 71.63 nm. The tensile strength results show that the smallest nanofiber diameter has the highest ultimate strength value of 5.6 ± 0.4 MPa. In addition, it was found that the rate of degradation was directly proportional to the increase in concentration. Antibacterial activity test was carried out using two types of bacteria, namely gram-positive bacteria S. aureus and gram-negative bacteria E. coli. The results showed that the collagen-chitosan/PVA nanofiber composite had a diameter of antibacterial inhibition for E. coli and S. aureus bacteria, respectively.
Evaluating on-board kVCT- and MVCT-based dose calculation accuracy using a thorax phantom for helical tomotherapy treatments
Authors: Tegtmeier Riley C , Ferris William S , Chen Ruiming , Miller Jessica R , Bayouth John E , Culberson Wesley S
Published: February 2023

Purpose. To evaluate the impact of CT number calibration and imaging parameter selection on dose calculation accuracy relative to the CT planning process in thoracic treatments for on-board helical CT imaging systems used in helical tomotherapy. Methods and Materials. Direct CT number calibrations were performed with appropriate protocols for each imaging system using an electron density phantom. Large volume and SBRT treatment plans were simulated and optimized for planning CT scans of an anthropomorphic thorax phantom and transferred to registered kVCT and MVCT scans of the phantom as appropriate. Relevant DVH metrics and dose-difference maps were used to evaluate and compare dose calculation accuracy relative to the planning CT based on a variation in imaging parameters applied for the on-board systems. Results. For helical kVCT scans of the thorax phantom, median differences in DVH parameters for the large volume treatment plan were less than ±1% with dose to the target volume either over- or underestimated depending on the imaging parameters utilized for CT number calibration and thorax phantom acquisition. For the lung SBRT plan calculated on helical kVCT scans, median dose differences were up to –2.7% with a more noticeable dependence on parameter selection. For MVCT scans, median dose differences for the large volume plan were within +2% with dose to the target overestimated regardless of the imaging protocol. Conclusion. Accurate dose calculations (median errors of <±1%) using a thorax phantom simulating realistic patient geometry and scatter conditions can be achieved with images acquired with a helical kVCT system on a helical tomotherapy unit. This accuracy is considerably improved relative to that achieved with the MV-based approach. In a clinical setting, careful consideration should be made when selecting appropriate kVCT imaging parameters for this process as dose calculation accuracy was observed to vary with both parameter selection and treatment type.
Development of an ultra-low-cost planar biaxial tester for soft tissue characterization
Authors: Gupta Vivek , Gupta Shubham , Chanda Arnab
Published: February 2023

Nowadays, the research in the arena of biomedical engineering or specifically soft tissue characterization is rapidly increasing. Due to the complex properties of soft tissues such as, anisotropy and viscoelasticity, it is difficult to predict the deformation behaviour. Hence, soft tissue characterization is essential to analyze these metrics. Soft tissue characterization, specifically, can be done by implementing a planar biaxial tester. Currently, available biaxial testers are mostly developed with respect to other mechanical components such as metals, and not for the soft tissues. Also, these devices are very costly, which makes it difficult for the low and middle income countries to perform this characterization. To solve this problem, in this work, an extremely low-cost biaxial tester was designed and developed. The design of the biaxial tester was simple and modular to allow device modifications according to the applications. The device has a force capability of less than 0.4 kN and a variable speed of 18 mm min−1 to 300 mm min−1. The biaxial tester was validated using a standard test material with mechanical testing machine and was further tested on several wound geometries including circular, square, diamond shaped, L-Plasty, and elliptical. The developed fully automated device exhibited high accuracy with real-time monitoring. Furthermore, test results on the wounds showed the device’s capability to differentiate amongst the considered wound geometries. This device can be helpful to medical students and doctors in understanding the mechanical behaviour of soft tissues during injury induced damage, disease, wounds healing and also for plethora of applications such as expansion testing of skin grafts.
Organ absorbed doses in the IORT treatment of breast cancer with the INTRABEAM device: a Monte-Carlo study
Authors: Nasir Zulfa , Probst Luis , Schneider Frank , Clausen Sven , Bürgy Daniel , Glatting Gerhard , Nwankwo Obioma
Published: February 2023

Purpose: The current prescription and the assessment of the delivered absorbed dose in intraoperative radiation therapy (IORT) with the INTRABEAM system rely mainly on depth-dose measurements in water. The accuracy of this approach is limited because tissue heterogeneity is ignored. It is also difficult to accurately determine the dose delivered to the patient experimentally as the steep dose gradient is highly sensitive to geometric errors. Our goal is to determine the dose to the target volume and the organs at risk of a clinical breast cancer patient from treatment with the system. Methods: A homogeneous water-equivalent CT dataset was derived from the preoperative CT scan of a patient by setting all materials in the patient volume as water-equivalent. This homogeneous CT data represents the current assumption of a homogenous patient, while the original CT data is considered the ground truth. An in-house Monte Carlo algorithm was used to simulate the delivered dose in both setups for a prescribed treatment dose of 20 Gy to the surface of the 3.5 cm diameter spherical applicator. Results: The doses received by 2% (D2%) of the target volume for the homogeneous and heterogeneous geometries are 16.26 Gy and 9.33 Gy, respectively. The D2% for the heart are 0.035 Gy and 0.119 Gy for the homogeneous and heterogeneous geometries, respectively. This trend is also observed for the other organs at risk. Conclusions: The assumption of a homogeneous patient overestimates the dose to the target volume and underestimates the doses to the organs at risk.
Everyday Economic Justice
Authors: Walker Louise E.
Published: February 2023

This article examines economic justice in nineteenth-century Mexico City through analysis of small-claims conflicts—juicios verbales. After the promulgation of the 1812 Cádiz Constitution, this centuries-old tradition of judicial arbitration was shaped by liberal constitutionalism. A new class of officials, the alcaldes constitucionales, were elected by residents to decide cases. Cádiz liberalism inaugurated a new world. What happened when people faced a classic problem, when they did not pay their debts? Microeconomic history—the quantitative and qualitative study of the economic relationships, decisions, and actions of individuals, households, and small enterprises—exposes the workings of economic justice. From 1813 to 1863, tens of thousands of residents pressed their claims before magistrates. As this article shows, justice grounded in Cádiz liberalism was relatively effective for ordinary people and evinced a gender fairness. These small-claims conflicts might seem a petty world of negligible amounts and narrow-minded disputes, but analyzed together, they challenge conventional interpretations about institutional deficiency and historical underdevelopment. Cádiz liberalism established a judicial institution to protect property rights, especially for creditors, that enjoyed broad legitimacy.
Necrotizing Soft Tissue Infection Post VASER-Assisted Liposuction and Lipofilling: A Case Report
Authors: Ahmed Mohamed Badie , Shraim Bara A , Abuelgasim Mutaz , Hammouda Atalla
Published: February 2023

Liposuction is a very common aesthetic procedure nowadays. The complication rate is very minimal, and it increases relatively when combined with other procedures. Infection is an expected complication in liposuction and its risk is below 1% in isolated procedures. Although the risk is very low, it might lead to fatal consequences. In this manuscript, the authors present a previously healthy female who presented to the authors’ emergency department post-vibration amplification of sound energy at resonance (VASER)-assisted liposuction and lipofilling done in a private center. Her signs and symptoms started after the procedure and she visited the private center multiple times; however, no significant improvement was felt. Upon her presentation to the authors’ facility, immediate resuscitation was initiated, and she was admitted for further investigations and management. Despite all resuscitation efforts and interventions, the patient’s condition kept deteriorating. She was admitted to the surgical intensive care unit and taken to the operating theater twice with no observed significant improvement. The patient developed septic shock, a multiorgan failure state, followed by cardiac arrest. All resuscitation measures were taken, but the patient could not be revived and was declared dead. Early recognition of signs and symptoms of infection could be lifesaving. Aggressive resuscitation and surgical interventions (extensive debridement and antibiotics) might be necessary to produce successful outcomes.

Level of Evidence: 5
DeepPheWAS: an R package for phenotype generation and association analysis for phenome-wide association studies
Authors: Packer Richard J , Williams Alex T , Hennah William , Eisenberg Micaela T , Shrine Nick , Fawcett Katherine A , Pearson Willow , Guyatt Anna L , Edris Ahmed , Hollox Edward J , Marttila Mikko , Rao Balasubramanya S , Bratty John Raymond , Wain Louise V , Dudbridge Frank , Tobin Martin D
Published: February 2023

DeepPheWAS is an R package for phenome-wide association studies that creates clinically curated composite phenotypes and integrates quantitative phenotypes from primary care data, longitudinal trajectories of quantitative measures, disease progression and drug response phenotypes. Tools are provided for efficient analysis of association with any genetic input, under any genetic model, with optional sex-stratified analysis, and for developing novel phenotypes.

Availability and implementation

The DeepPheWAS R package is freely available under GNU general public licence v3.0 from at https://github.com/Richard-Packer/DeepPheWAS.

Supplementary information

Supplementary data are available at Bioinformatics online.
Efficient estimation under data fusion
Authors: Li Sijia , Luedtke Alex
Published: February 2023

We aim to make inferences about a smooth, finite-dimensional parameter by fusing together data from multiple sources. Previous works have studied the estimation of a variety of parameters in similar data fusion settings, including estimation of the average treatment effect and average reward under a policy, with the majority of them merging one historical data source with covariates, actions and rewards, and one data source of the same covariates. In this article, we consider the general case where one or more data sources align with each part of the distribution of the target population, such as the conditional distribution of the reward given actions and covariates. We describe potential gains in efficiency that can arise from fusing these data sources together in a single analysis, which we characterize by a reduction in the semiparametric efficiency bound. We also provide a general means of constructing estimators that achieve these bounds. Numerical simulations demonstrate marked improvements in efficiency from using the proposed estimators rather than their natural alternatives. Finally, we illustrate the magnitude of efficiency gains that can be realized in vaccine immunogenicity studies by fusing data from two HIV vaccine trials.
Molecular phylogenetics shed light on polyploid speciation in gorses (Ulex, Fabaceae: Genisteae) and on the origin of the invasive Ulex europaeus
Authors: Bellot Sidonie , Dias Paula M B , Affagard Marc , Aïnouche Malika-Lily , Misset Marie-Thérèse , Aïnouche Abdelkader
Published: February 2023

Hybridization and polyploidy are key evolutionary forces in plant diversification, and their co-occurrence in the context of allopolyploid speciation is often associated with increased ability to colonize new environments and invasiveness. In the genus Ulex (Fabaceae), the European gorse (Ulex europaeus subsp. europaeus) is the only invasive and the only polyploid that has recently spread in different eco-geographical regions across the world. Understanding what confers such ecological advantages to this species, compared to its diploid and polyploid congeners, first requires clarification of the ecogeographical and evolutionary context of its formation. To achieve this, the geographical distributions of all Ulex spp. were estimated from species occurrence records, and phylogenetic analyses including all Ulex spp. were performed based on four nuclear (ITS and ETS nrDNA) and plastid (rps12 intron and trnK-matK) regions. The resulting trees were dated using a secondary calibration. Patterns of DNA sequence variation and dated phylogenetic trees were then interpreted in light of previous knowledge of chromosome numbers in Ulex to infer past events of polyploid speciation in the genus. We show that: (1) most current Ulex spp. radiated in the Iberian Peninsula during the past 1–2 Myr; (2) the history of Ulex was punctuated by multiple whole-genome duplication events; and (3) U. europaeus subsp. europaeus is the only gorse taxon that was formed by hybridization of two well-differentiated lineages (which separated c. 5 Mya) with wide climatic ranges (currently represented by Ulex minor and Ulex europaeus subsp. latebracteatus), possibly contributing to the invasive nature and wider climatic range of U. europaeus subsp. europaeus. These findings provide a much-needed evolutionary framework in which to explore the adaptive consequences of genome mergers and duplication in Ulex.
Pathological changes in the brain after peripheral burns
Authors: Chen Jigang , Zhang Danfeng , Zhang Junhui , Wang Yanni
Published: February 2023

Brain injuries are common complications in patients with thermal burns and are associated with unpleasant outcomes. In clinical settings, it was once believed that brain injuries were not major pathological processes after burn, at least in part due to the unavailability of specific clinical manifestations. Burn-related brain injuries have been studied for more than a century, but the underlying pathophysiology has not been completely clarified. This article reviews the pathological changes in the brain following peripheral burns at the anatomical, histological, cytological, molecular and cognitive levels. Therapeutic indications based on brain injury as well as future directions for research have been summarized and proposed.
Estimating energetic intake for marine mammal bioenergetic models
Authors: Booth Cormac G , Guilpin Marie , Darias-O’Hara Aimee-Kate , Ransijn Janneke M , Ryder Megan , Rosen Dave , Pirotta Enrico , Smout Sophie , McHuron Elizabeth A , Nabe-Nielsen Jacob , Costa Daniel P
Published: February 2023

Bioenergetics is the study of how animals achieve energetic balance. Energetic balance results from the energetic expenditure of an individual and the energy they extract from their environment. Ingested energy depends on several extrinsic (e.g prey species, nutritional value and composition, prey density and availability) and intrinsic factors (e.g. foraging effort, success at catching prey, digestive processes and associated energy losses, and digestive capacity). While the focus in bioenergetic modelling is often on the energetic costs an animal incurs, the robust estimation of an individual’s energy intake is equally critical for producing meaningful predictions. Here, we review the components and processes that affect energy intake from ingested gross energy to biologically useful net energy (NE). The current state of knowledge of each parameter is reviewed, shedding light on research gaps to advance this field. The review highlighted that the foraging behaviour of many marine mammals is relatively well studied via biologging tags, with estimates of success rate typically assumed for most species. However, actual prey capture success rates are often only assumed, although we note studies that provide approaches for its estimation using current techniques. A comprehensive collation of the nutritional content of marine mammal prey species revealed a robust foundation from which prey quality (comprising prey species, size and energy density) can be assessed, though data remain unavailable for many prey species. Empirical information on various energy losses following ingestion of prey was unbalanced among marine mammal species, with considerably more literature available for pinnipeds. An increased understanding and accurate estimate of each of the components that comprise a species NE intake are an integral part of bioenergetics. Such models provide a key tool to investigate the effects of disturbance on marine mammals at an individual and population level and to support effective conservation and management.
Loperamide-induced cardiogenic syncope: a case report of a life-threatening presentation of an over-the-counter drug
Authors: Hegde Vishwajit , Dalia Tarun , Tayeb Taher , Cotter Elizabeth , Vidic Andrija
Published: February 2023

Background

Loperamide at supratherapeutic doses can cause cardiac toxicity, presenting as cardiogenic shock, prolonged QT, malignant arrhythmias, or in severe cases sudden cardiac death. Surreptitious loperamide use is difficult to diagnose. We present an interesting case of loperamide use presenting with polymorphic ventricular tachycardia, cardiogenic shock.

Case summary

A 25-year-old female presented with multiple syncopal episodes for 12 months with an electrocardiogram showing a Brugada-like pattern for which she underwent implantable cardioverter-defibrillator placement. One day following the procedure, she developed cardiogenic shock and was transferred to our tertiary care centre. Extensive workup was unrevealing. She responded well to supportive management, recovering from shock and was transferred to the floor. Unfortunately, she again developed cardiogenic shock, ultimately leading to cardiac arrest. Given the unclear cause for her cardiovascular symptoms, futher medication history was obtained. It was revealed that she was taking 100–150 tablets of loperamide per day. The decision was made to treat with intralipid emulsion therapy empirically given the strong suspicion for loperamide toxicity. The patient recovered well with supportive care. Loperamide levels returned elevated at 190 ng/mL. Repeated studies showed improvement of the conduction block, resolution of arrhythmias, and recovery of right and left ventricular function.

Discussion

Acute loperamide toxicity can present as biventricular failure, with difficult-to-control arrhythmias. It requires a high index of suspicion. Treatment for loperamide toxicity is mainly supportive, lipid emulsion therapy can be considered in severe or refractory cases.
The pulmonary surgical Apgar score for lung cancer surgery predicts postoperative complications and long-term survival
Authors: Hino Haruaki , Hagihira Satoshi , Maru Natsumi , Utsumi Takahiro , Matsui Hiroshi , Taniguchi Yohei , Saito Tomohito , Murakawa Tomohiro
Published: February 2023

OBJECTIVES

The surgical Apgar score, calculated using 3 intraoperative variables (blood loss, lowest mean arterial pressure and lowest heart rate), is associated with mortality in cancer surgery. The original score has less applicability in lung cancer surgery; therefore, we innovated the modified pulmonary surgical Apgar score with additional intraoperative oxygen saturation representing pulmonary parenchymal damage and cardiopulmonary dynamics.

METHODS

We retrospectively analysed the data of 691 patients who underwent surgery for primary lung cancer between 2015 and 2019 at a single institute. We analysed the utility of the pulmonary surgical Apgar score compared with the original surgical Apgar score.

RESULTS

Postoperative complications were observed in 57 (8.2%) and 7 (1.0%) of the 691 patients who were stratified as grade ≥III and V, respectively, according to the Clavien–Dindo classification. We compared the fitness of the score in predicting postoperative complications; the calculated c-index (0.622) was slightly higher than the original c-index (0.604; P = 0.398). Patients were categorized into 3 groups based on their scores as follows: 0–6 points (n = 59), 7–9 points (n = 420) and 10–12 points (n = 212). Univariable and multivariable analyses demonstrated that a lower score was an independent negative risk factor for postoperative complications (odds ratio 3.53; P = 0.02). Patients with lower scores had a considerably poor 5-year overall survival (64.6%) (P = 0.07).

CONCLUSIONS

The pulmonary surgical Apgar score predicts postoperative complications and long-term survival in patients with lung cancer undergoing surgery and may be utilized for postoperative management.
Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis
Authors: Elhakeem Ahmed , Taylor Amy E , Inskip Hazel M , Huang Jonathan Y , Mansell Toby , Rodrigues Carina , Asta Federica , Blaauwendraad Sophia M , Håberg Siri E , Halliday Jane , Harskamp-van Ginkel Margreet W , He Jian-Rong , Jaddoe Vincent W V , Lewis Sharon , Maher Gillian M , Manios Yannis , McCarthy Fergus P , Reiss Irwin K M , Rusconi Franca , Salika Theodosia , Tafflet Muriel , Qiu Xiu , Åsvold Bjørn O , Burgner David , Chan Jerry K Y , Gagliardi Luigi , Gaillard Romy , Heude Barbara , Magnus Maria C , Moschonis George , Murray Deirdre , Nelson Scott M , Porta Daniela , Saffery Richard , Barros Henrique , Eriksson Johan G , Vrijkotte Tanja G M , Lawlor Deborah A
Published: February 2023

Aims

To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age.

Methods and results

Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (−0.53 mmHg; 95% CI:−1.59 to 0.53), DBP (−0.24 mmHg; −0.83 to 0.35), or HR (0.02 beat/min; −0.91 to 0.94). Total cholesterol (2.59%; 0.10–5.07), HDL cholesterol (4.16%; 2.52–5.81), LDL cholesterol (4.95%; 0.47–9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant.

Conclusion

These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease.