bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyber Intelligence and Influence: In Defense of “Cyber Manipulation Operations” to Parry Atrocities
Authors: Neilsen Rhiannon
Published: August 2023

Intelligence operations overwhelmingly focus on obtaining secrets (espionage) and the unauthorized disclosure of secrets by a public official in one political community to another (treason). It is generally understood that the principal responsibility of spies is to successfully procure secrets about the enemy. Yet, in this essay, I ask: Are spies and traitors ethically justified in using cyber operations not merely to acquire secrets (cyber espionage) but also to covertly manipulate or falsify information (cyber manipulation) to prevent atrocities? I suggest that using cyber manipulation operations to parry atrocities is pro tanto morally permissible and, on occasion, required.
Multilateralism and the Global Co-Responsibility of Care in Times of a Pandemic: The Legal Duty to Cooperate
Authors: de Campos-Rudinsky Thana C.
Published: August 2023

This article challenges the orthodox view of international law, according to which states have no legal duty to cooperate. It argues for this legal duty in the context of COVID-19, based on the ethical principles of solidarity, stewardship, and subsidiarity. More specifically, the article argues that states have a legal duty to cooperate during a pandemic (as solidarity requires); and while this duty entails an extraterritorial responsibility to care for and assist other nations (as stewardship requires), the legal duty to cooperate still allows states to attend first to the basic needs of those under their own jurisdiction—namely, fellow nationals and residents (as subsidiarity requires). The article provides a definition and philosophical justifications for this legal duty that are lacking in the literature by examining its application to a current COVID-19 controversy: namely, states’ responsibility to assist other countries in greater need by, inter alia, exporting at a discount or donating scarce COVID-19 treatments (including vaccines). In providing a principled tripartite account of pandemic governance, this conceptual and normative article offers a new lens for debating the potential international treaty for pandemic prevention, preparedness, and response that has now been drafted and is under negotiation at the World Health Assembly, by responding to the recent backlash against multilateralism by substantiating global co-responsibilities in times of pandemics and beyond.
Assessment for learning of paediatric cardiology trainees in 41 centres from 19 European countries
Authors: McMahon Colin J. , Milanesi Ornella , Pitkänen-Argillander Olli , Albert-Brotons Dimpna C. , Michel-Behnke Ina , Voges Inga , Sendzikaite Skaiste , Heying Ruth
Published: August 2023

Background:

Limited data exist on how trainees in paediatric cardiology are assessed among countries affiliated with the Association of European Paediatric and Congenital Cardiology.

Methods:

A structured and approved questionnaire was circulated to educationalists/trainers in 95 Association for European Paediatric and Congenital Cardiology training centres.

Results:

Trainers from 46 centres responded with complete data in 41 centres. Instructional design included bedside teaching (41/41), didactic teaching (38/41), problem-based learning (28/41), cardiac catheterisation calculations (34/41), journal club (31/41), fellows presenting in the multidisciplinary meeting (41/41), fellows reporting on echocardiograms (34/41), clinical simulation (17/41), echocardiography simulation (10/41), and catheterisation simulation (3/41). Assessment included case-based discussion (n = 27), mini-clinical evaluation exercise (mini-CEX) (n = 12), directly observed procedures (n = 12), oral examination (n = 16), long cases (n = 11), written essay questions (n = 6), multiple choice questions (n = 5), and objective structured clinical examination (n = 2). Entrustable professional activities were utilised in 10 (24%) centres. Feedback was summative only in 17/41 (41%) centres, formative only in 12/41 (29%) centres and a combination of formative and summative feedback in 10/41 (24%) centres. Written feedback was provided in 10/41 (24%) centres. Verbal feedback was most common in 37/41 (90 %) centres.

Conclusion:

There is a marked variation in instructional design and assessment across European paediatric cardiac centres. A wide mix of assessment tools are used. Feedback is provided by the majority of centres, mostly verbal summative feedback. Adopting a programmatic assessment focusing on competency/capability using multiple assessment tools with regular formative multisource feedback may promote assessment for learning of paediatric cardiology trainees.
Smooth scouringrush (Equisetum laevigatum) control with glyphosate is affected by surfactant choice and application time
Authors: Savic Marija , Thorne Mark E. , Lyon Drew J.
Published: August 2023

Smooth scouringrush is a creeping perennial with a high silica content in stems that may impede herbicide uptake. Smooth scouringrush has become a troublesome weed in no-till cropping systems across eastern Washington. In previous field studies, glyphosate provided inconsistent control of smooth scouringrush. The objective of this study was to determine if the addition of an organosilicone surfactant to glyphosate would improve the efficacy and consistency of control through stomatal flooding. To test this hypothesis, glyphosate was applied at three field sites at 3.78 kg ae ha–1 alone, with an organosilicone surfactant (OS1 or OS2), an organosilicone plus nonionic surfactant blend, or an alcohol-based surfactant applied during the day or at night. Stem counts were recorded 1 yr after herbicide applications. Five of the six effective treatments observed across the three study sites included organosilicone surfactant or an organosilicone plus nonionic surfactant blend. At two sites, when there was a difference in efficacy between application times; daytime applications were more effective than nighttime applications. These results support the hypothesis of stomatal flooding as a likely mechanism for enhanced efficacy of glyphosate with the addition of an organosilicone surfactant. However, at one site, the treatments containing organosilicone surfactant were more efficacious when applied at night than during the day. At this site, high daytime temperatures and low relative humidity may have resulted in rapid evaporation of spray droplets. The addition of an organosilicone surfactant to glyphosate is recommended for smooth scouringrush control, and daytime treatments are preferred but should be applied when temperatures and humidity are not conducive to rapid droplet drying. Further research is necessary to confirm that stomatal flooding is responsible for improved glyphosate efficacy.
Unprecedented July Rainfall in North China in 2021: Combined Effect of Atlantic Warming and Arctic Sea‐Ice Loss
Authors: Liu Xuefeng , Zhu Zhiwei , Lu Rui , Miao Zishu , Li Wei , Hsu Pangchi
Published: August 2023

Record‐breaking July‐mean precipitation hit North China in 2021, resulting in huge economic losses and human casualties. The prevailing easterlies over the southern flank of a remarkable anomalous anticyclone centered over the Kuril Islands transported sufficient water vapor into North China, resulting in persistent downpours on the windward side of the North China Plain. The anomalous anticyclone was a portion of the Eurasian Rossby wave trains. The record‐high Atlantic sea surface temperature anomalies induced the Rossby wave trains, which ended with an anomalous anticyclone over the Kuril Islands; meanwhile, the record‐low sea‐ice concentration over the Laptev–East Siberian Seas reinforced the anomalous anticyclone. Therefore, the combined effect of Atlantic and Arctic thermal forcings caused the record‐breaking July‐mean rainfall in North China in 2021. Using these two boundary layer forcings as independent predictors to run a multiple regression model produced encouraging hindcasting skills.
Using 228Th/228Ra Disequilibrium to Constrain Particulate Organic Carbon Export From the Upper Twilight Zone of the Northern South China Sea
Authors: Deng Fangfang , Lin Feng
Published: August 2023

We utilized the 228Th/228Ra and 234Th/238U disequilibrium methods to estimate the export of particulate organic carbon (POC) from the upper twilight zone in the northern South China Sea during four cruises from August 2009 to May 2011, covering an entire seasonal cycle of spring, summer, autumn, and winter. A significant finding of this study is that 228Th/228Ra disequilibrium method is highly sensitive for tracing POC export in the twilight zone, as demonstrated by the comparison of the “Minimum Detection Limit” (MDL) of various methods. We thus further conclude that 228Th/228Ra disequilibrium is suitable for the research of the twilight zone by comparing the POC export fluxes derived from 228Th/228Ra and 228Ra‐NO3− disequilibrium. The mesopelagic transfer efficiency (Teff), defined as the ratio of POC flux at 500–100 m, varied from 8% to 130%. The Teff derived from >53 μm 234Th (228Th) was higher than that based on 1–53 μm. Large particles were observed to sink rapidly and exit the twilight zone. The Teff was lower at the sampling station influenced by the Kuroshio waters in winter and spring, where the exported organic matter was relatively labile and prone to remineralization in the twilight zone. Conversely, the Teff was relatively higher at other stations, indicating that the exported organic matter was refractory and underwent comparatively less degradation in the twilight zone.
Wind‐Associated Melt Trends and Contrasts Between the Greenland and Antarctic Ice Sheets
Authors: Laffin Matthew K. , Zender Charles S. , van Wessem Melchior , Noël Brice , Wang Wenshan
Published: August 2023

Föhn and katabatic winds (downslope winds) can increase ice sheet surface melt, run‐off, and ice‐shelf vulnerability to hydrofracture and are poorly constrained on the Greenland and Antarctic ice sheets (GIS and AIS). We use regional climate model simulations of the GIS and AIS to quantify and intercompare trends in downslope winds and associated melt since 1960. Results reveal surface melt associated with downslope wind is significant on both the GIS and AIS representing 27.5 ± 4.5% and 19.7 ± 3.8% of total surface melt respectively. Wind‐associated melt has decreased 31.8 ± 5.3% on the AIS while total melt decreased 15.4 ± 2.4% due to decreased föhn‐induced melt on the Antarctic Peninsula and increasing stratospheric ozone. Wind‐associated melt has increased 10.3 ± 2.5% on the GIS, combining with a more positive North Atlantic Oscillation and warmer surface to increase total melt 34 ± 5.8%.
Inferring the Basal Friction Law From Long Term Changes of Glacier Length, Thickness and Velocity on an Alpine Glacier
Authors: Gilbert A. , Gimbert F. , Gagliardini O. , Vincent C.
Published: August 2023

Basal sliding of glaciers and ice sheets remains a source of uncertainty in simulating the long‐term evolution of ice masses. In particular, the response of ice flow to changes in driving stress depends strongly on the value of the exponent m in nonlinear friction laws (e.g., Weertman's law), which is poorly constrained by observations. Here we constrain the friction law at a natural scale on Argentière Glacier (French Alps, hard‐bed), taking advantage of well‐resolved observations of glacier mass balance, geometry and basal sliding over time spans that include large changes in driving stress. By combining three different independent methods based on (a) surface velocity inversion, (b) transient length change modeling, and (c) direct local sliding measurements, we consistently find a value of m = 3.1 ± 0.3. We suggest that Weertman's law is suitable for modeling the long‐term evolution of hard‐bedded glaciers and ice sheets.
Polymeric and biological membranes for organ-on-a-chip devices
Authors: Corral-Nájera Kendra , Chauhan Gaurav , Serna-Saldívar Sergio O. , Martínez-Chapa Sergio O. , Aeinehvand Mohammad Mahdi
Published: August 2023

Membranes are fundamental elements within organ-on-a-chip (OOC) platforms, as they provide adherent cells with support, allow nutrients (and other relevant molecules) to permeate/exchange through membrane pores, and enable the delivery of mechanical or chemical stimuli. Through OOC platforms, physiological processes can be studied in vitro, whereas OOC membranes broaden knowledge of how mechanical and chemical cues affect cells and organs. OOCs with membranes are in vitro microfluidic models that are used to replace animal testing for various applications, such as drug discovery and disease modeling. In this review, the relevance of OOCs with membranes is discussed as well as their scaffold and actuation roles, properties (physical and material), and fabrication methods in different organ models. The purpose was to aid readers with membrane selection for the development of OOCs with specific applications in the fields of mechanistic, pathological, and drug testing studies. Mechanical stimulation from liquid flow and cyclic strain, as well as their effects on the cell’s increased physiological relevance (IPR), are described in the first section. The review also contains methods to fabricate synthetic and ECM (extracellular matrix) protein membranes, their characteristics (e.g., thickness and porosity, which can be adjusted depending on the application, as shown in the graphical abstract), and the biological materials used for their coatings. The discussion section joins and describes the roles of membranes for different research purposes and their advantages and challenges.
Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression
Authors: Zhang Shao-Qi , Deng Qiao , Zhu Qi , Hu Zhuang-Li , Long Li-Hong , Wu Peng-Fei , He Jin-Gang , Chen Hong-Sheng , Yue Zhenyu , Lu Jia-Hong , Wang Fang , Chen Jian-Guo
Published: August 2023

Dysfunctional autophagy and impairment of adult hippocampal neurogenesis (AHN) each contribute to the pathogenesis of major depressive disorder (MDD). However, whether dysfunctional autophagy is linked to aberrant AHN underlying MDD remains unclear. Here we demonstrate that the expression of nuclear receptor binding factor 2 (NRBF2), a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, is attenuated in the dentate gyrus (DG) under chronic stress. NRBF2 deficiency inhibits the activity of the VPS34 complex and impairs autophagic flux in adult neural stem cells (aNSCs). Moreover, loss of NRBF2 disrupts the neurogenesis-related protein network and causes exhaustion of aNSC pool, leading to the depression-like phenotype. Strikingly, overexpressing NRBF2 in aNSCs of the DG is sufficient to rescue impaired AHN and depression-like phenotype of mice. Our findings reveal a significant role of NRBF2-dependent autophagy in preventing chronic stress-induced AHN impairment and suggest the therapeutic potential of targeting NRBF2 in MDD treatment.
Electrostatic interactions guide substrate recognition of the prokaryotic ubiquitin-like protein ligase PafA
Authors: Block Matthias F. , Delley Cyrille L. , Keller Lena M. L. , Stuehlinger Timo T. , Weber-Ban Eilika
Published: August 2023

Pupylation, a post-translational modification found in Mycobacterium tuberculosis and other Actinobacteria, involves the covalent attachment of prokaryotic ubiquitin-like protein (Pup) to lysines on target proteins by the ligase PafA (proteasome accessory factor A). Pupylated proteins, like ubiquitinated proteins in eukaryotes, are recruited for proteasomal degradation. Proteomic studies suggest that hundreds of potential pupylation targets are modified by the sole existing ligase PafA. This raises intriguing questions regarding the selectivity of this enzyme towards a diverse range of substrates. Here, we show that the availability of surface lysines alone is not sufficient for interaction between PafA and target proteins. By identifying the interacting residues at the pupylation site, we demonstrate that PafA recognizes authentic substrates via a structural recognition motif centered around exposed lysines. Through a combination of computational analysis, examination of available structures and pupylated proteomes, and biochemical experiments, we elucidate the mechanism by which PafA achieves recognition of a wide array of substrates while retaining selective protein turnover.
Skeletal metalation of lactams through a carbonyl-to-nickel-exchange logic
Authors: Zhong Hongyu , Egger Dominic T. , Gasser Valentina C. M. , Finkelstein Patrick , Keim Loris , Seidel Merlin Z. , Trapp Nils , Morandi Bill
Published: August 2023

Classical metalation reactions such as the metal-halogen exchange have had a transformative impact on organic synthesis owing to their broad applicability in building carbon-carbon bonds from carbon-halogen bonds. Extending the metal-halogen exchange logic to a metal-carbon exchange would enable the direct modification of carbon frameworks with new implications in retrosynthetic analysis. However, such a transformation requires the selective cleavage of highly inert chemical bonds and formation of stable intermediates amenable to further synthetic elaborations, hence its development has remained considerably challenging. Here we introduce a skeletal metalation strategy that allows lactams, a prevalent motif in bioactive molecules, to be readily converted into well-defined, synthetically useful organonickel reagents. The reaction features a selective activation of unstrained amide C–N bonds mediated by an easily prepared Ni(0) reagent, followed by CO deinsertion and dissociation under mild room temperature conditions in a formal carbonyl-to-nickel-exchange process. The underlying principles of this unique reactivity are rationalized by organometallic and computational studies. The skeletal metalation is further applied to a direct CO excision reaction and a carbon isotope exchange reaction of lactams, underscoring the broad potential of metal-carbon exchange logic in organic synthesis.
Operando monitoring of thermal runaway in commercial lithium-ion cells via advanced lab-on-fiber technologies
Authors: Mei Wenxin , Liu Zhi , Wang Chengdong , Wu Chuang , Liu Yubin , Liu Pengjie , Xia Xudong , Xue Xiaobin , Han Xile , Sun Jinhua , Xiao Gaozhi , Tam Hwa-yaw , Albert Jacques , Wang Qingsong , Guo Tuan
Published: August 2023

Operando monitoring of complex physical and chemical activities inside rechargeable lithium-ion batteries during thermal runaway is critical to understanding thermal runaway mechanisms and giving early warning of safety-related failure. However, most existing sensors cannot survive during such extremely hazardous thermal runaway processes (temperature up to 500 °C accompanied by fire and explosion). To address this, we develop a compact and multifunctional optical fiber sensor (12 mm in length and 125 µm in diameter) capable of insertion into commercial 18650 cells to continuously monitor internal temperature and pressure effects during cell thermal runaway. We observe a stable and reproducible correlation between the cell thermal runaway and the optical response. The sensor’s signal shows two internal pressure peaks corresponding to safety venting and initiation of thermal runaway. Further analysis reveals that a scalable solution for predicting imminent thermal runaway is the detection of the abrupt turning range of the differential curves of cell temperature and pressure, which corresponds to an internal transformation between the cell reversible and irreversible reactions. By raising an alert even before safety venting, this new operando measurement tool can provide crucial capabilities in cell safety assessment and warning of thermal runaway.
Readiness for Parkinson’s disease genetic testing and counseling in patients and their relatives in urban settings in the Dominican Republic
Authors: Hackl Margaret , Cook Lola , Wetherill Leah , Walsh Laurence E. , Delk Paula , De León Rebeca , Carbonell Janfreisy , Vicioso Rossy Cruz , Hodges Priscila Delgado
Published: August 2023

Genetic testing for Parkinson’s disease (PD) is increasing globally, and genetic counseling is an important service that provides information and promotes understanding about PD genetics and genetic testing. PD research studies have initiated outreach to underrepresented regions in North America, including regions in Latin America, such as the Dominican Republic (DR); some studies may include return of genetic test results. Thus, understanding what individuals know about PD, genetic testing for PD, and their interest in speaking with a genetic counselor, is crucial when assessing readiness. In this cross-sectional study, a survey was distributed to people with Parkinson’s disease (PwP) and their unaffected biological relatives in the DR. Questions assessed genetics knowledge, attitude toward genetic testing, and interest in genetic testing and counseling. Of 45 participants, 69% scored the maximum on the attitude scale, indicating an overall positive attitude toward genetic testing; 95% indicated interest in genetic testing for PD, and 98% were at least somewhat interested in meeting with a genetic counselor. The mean PD genetics knowledge score was similar to previously published data. Through free text responses, participants expressed a desire to know more about PD treatment and management, prevention, cause, and their personal risk for PD. These results provide further evidence of readiness for genetic testing in this country but also underscore some gaps in knowledge that should be addressed with targeted educational efforts, as part of building genetic testing and counseling capacities.
Identifying the mediating role of socioeconomic status on the relationship between schizophrenia and major depressive disorder: a Mendelian randomisation analysis
Authors: Xu Qiang , Cai Mengjing , Ji Yuan , Ma Juanwei , Liu Jiawei , Zhao Qiyu , Chen Yayuan , Zhao Yao , Zhang Yijing , Wang He , Guo Lining , Xue Kaizhong , Wang Zirui , Liu Mengge , Wang Chunyang , Zhu Dan , Liu Feng
Published: August 2023

Depressive disorder prevalence in patients with schizophrenia has been reported to be 40%. People with low socioeconomic status (SES) are more likely to suffer from schizophrenia and major depressive disorder (MDD). However, the causal relationship between schizophrenia and depression and the potential mediating role of SES remains unclear. Two-sample Mendelian randomization (MR) analyses were conducted to explore the bidirectional causal relationship between schizophrenia and MDD with the largest sample size of European ancestry from public genome-wide association studies (sample size ranged from 130,644 to 480,359). Inverse variance weighted (IVW) method was used as the primary analysis, and several canonical MR methods were used as validation analyses. The mediating role of SES (educational years, household income, employment status, and Townsend deprivation index) was estimated by the two-step MR method. MR analyses showed that genetically predicted schizophrenia was associated with an increased risk of MDD (IVW odds ratio [OR] = 1.137 [95% CI 1.095, 1.181]). Reversely, MDD was also associated with an increased risk of schizophrenia (IVW OR = 1.323 [95% CI 1.118, 1.565]). The mediation analysis via the two-step MR method revealed that the causal effect of schizophrenia on MDD was partly mediated by the Townsend deprivation index with a proportion of 10.27%, but no significant mediation effect was found of SES on the causal effect of MDD on schizophrenia. These results suggest a robust bidirectional causal effect between schizophrenia and MDD. Patients with schizophrenia could benefit from the early and effective intervention of the Townsend deprivation index.
re3data – Indexing the Global Research Data Repository Landscape Since 2012
Authors: Pampel Heinz , Weisweiler Nina Leonie , Strecker Dorothea , Witt Michael , Vierkant Paul , Elger Kirsten , Bertelmann Roland , Buys Matthew , Ferguson Lea Maria , Kindling Maxi , Kotarski Rachael , Petras Vivien
Published: August 2023

For more than ten years, re3data, a global registry of research data repositories (RDRs), has been helping scientists, funding agencies, libraries, and data centers with finding, identifying, and referencing RDRs. As the world’s largest directory of RDRs, re3data currently describes over 3,000 RDRs on the basis of a comprehensive metadata schema. The service allows searching for RDRs of any type and from all disciplines, and users can filter results based on a wide range of characteristics. The re3data RDR descriptions are available as Open Data accessible through an API and are utilized by numerous Open Science services. re3data is engaged in various initiatives and projects concerning data management and is mentioned in the policies of many scientific institutions, funding organizations, and publishers. This article reflects on the ten-year experience of running re3data and discusses ten key issues related to the management of an Open Science service that caters to RDRs worldwide.
Chromosomal level genome assembly of medicinal plant Sophora flavescens
Authors: Qu Zhipeng , Wang Wei , Adelson David L.
Published: August 2023

Sophora flavescens is a medicinal plant in the genus Sophora of the Fabaceae family. The root of S. flavescens is known in China as Kushen and has a long history of wide use in multiple formulations of Traditional Chinese Medicine (TCM). In this study, we used third-generation Nanopore long-read sequencing technology combined with Hi-C scaffolding technology to de novo assemble the S. flavescens genome. We obtained a chromosomal level high-quality S. flavescens draft genome. The draft genome size is approximately 2.08 Gb, with more than 80% annotated as Transposable Elements (TEs), which have recently and rapidly proliferated. This genome size is ~5x larger than its closest sequenced relative Lupinus albus L. . We annotated 60,485 genes and examined their expression profiles in leaf, stem and root tissues, and also characterised the genes and pathways involved in the biosynthesis of major bioactive compounds, including alkaloids, flavonoids and isoflavonoids. The assembled genome highlights the very different evolutionary trajectories that have occurred in recently diverged Fabaceae, leading to smaller duplicated genomes.
Newborn weight nomograms in selected low and middle-income countries
Authors: Ginsburg Amy Sarah , Jehan Fyezah , Ariff Shabina , Nisar Muhammad Imran , Schaefer Eric , Flaherman Valerie , Shrestha Akina , Dongol Srijana , Laleau Victoria , de Sa Augusto Braima , Co Raimundo , Nankabirwa Victoria
Published: August 2023

Growth impairment is common in low- and middle-income countries (LMIC) and may begin during early infancy, increasing morbidity and mortality. To ensure healthy infant growth, healthcare providers in high-income countries (HIC) track newborn weight change using tools developed and validated in HIC. To understand the utility of these tools for LMIC, we conducted a secondary analysis to compare weight trajectories in the first 5 days of life among newborns born in our LMIC cohort to an existing HIC newborn weight tool designed to track early weight change. Between April 2019 and March 2020, a convenience sample of 741 singleton healthy breastfeeding newborns who weighed ≥ 2000 g at birth were enrolled at selected health facilities in Guinea-Bissau, Nepal, Pakistan, and Uganda. Using a standardized protocol, newborn weights were obtained within 6 h of birth and at 1, 2, 3, 4, and 5 days, and nomograms depicting newborn weight change were generated. The trajectories of early newborn weight change in our cohort were largely similar to published norms derived from HIC infants, with the exceptions that initial newborn weight loss in Guinea-Bissau was more pronounced than HIC norms and newborn weight gain following weight nadir was more pronounced in Guinea-Bissau, Pakistan, and Uganda than HIC norms. These data demonstrate that HIC newborn weight change tools may have utility in LMIC settings.
Emphysema subtyping on thoracic computed tomography scans using deep neural networks
Authors: Xie Weiyi , Jacobs Colin , Charbonnier Jean-Paul , Slebos Dirk Jan , van Ginneken Bram
Published: August 2023

Accurate identification of emphysema subtypes and severity is crucial for effective management of COPD and the study of disease heterogeneity. Manual analysis of emphysema subtypes and severity is laborious and subjective. To address this challenge, we present a deep learning-based approach for automating the Fleischner Society’s visual score system for emphysema subtyping and severity analysis. We trained and evaluated our algorithm using 9650 subjects from the COPDGene study. Our algorithm achieved the predictive accuracy at 52%, outperforming a previously published method’s accuracy of 45%. In addition, the agreement between the predicted scores of our method and the visual scores was good, where the previous method obtained only moderate agreement. Our approach employs a regression training strategy to generate categorical labels while simultaneously producing high-resolution localized activation maps for visualizing the network predictions. By leveraging these dense activation maps, our method possesses the capability to compute the percentage of emphysema involvement per lung in addition to categorical severity scores. Furthermore, the proposed method extends its predictive capabilities beyond centrilobular emphysema to include paraseptal emphysema subtypes.
Clarifying the composition of the ATP consumption factors required for maintaining ion homeostasis in mouse rod photoreceptors
Authors: Muangkram Yuttamol , Himeno Yukiko , Amano Akira
Published: August 2023

To date, no effective treatment has been established for photoreceptor loss due to energy imbalances, but numerous therapeutic approaches have reported some success in slowing photoreceptor degeneration by downregulating energy demand. However, the detailed mechanisms remain unclear. This study aimed to clarify the composition of ATP consumption factors in photoreceptors in darkness and in light. We introduced mathematical formulas for ionic current activities combined with a phototransduction model to form a new mathematical model for estimating the energy expenditure of each ionic current. The proposed model included various ionic currents identified in mouse rods using a gene expression database incorporating an available electrophysiological recording of each specific gene. ATP was mainly consumed by Na+/K+-ATPase and plasma membrane Ca2+-ATPase pumps to remove excess Na+ and Ca2+. The rod consumed 7 $$\times$$
×
107 molecules of ATP s−1, where 65% was used to remove ions from the cyclic nucleotide-gated channel and 20% from the hyperpolarization-activated current in darkness. Increased light intensity raised the energy requirements of the complex phototransduction cascade mechanisms. Nevertheless, the overall energy consumption was less than that in darkness due to the significant reduction in ATPase activities, where the hyperpolarization-activated current proportion increased to 83%. A better understanding of energy demand/supply may provide an effective tool for investigating retinal pathophysiological changes and analyzing novel therapeutic treatments related to the energy consumption of photoreceptors.
Partially defatted rather than native poppy seeds beneficially alter lipid metabolism in rats fed a high-fat diet
Authors: Koza Jarosław , Jurgoński Adam
Published: August 2023

Partially defatted poppy seeds, a by-product of poppy oil cold pressing, could be an interesting dietary supplement for obesity management. The aim of this study was to compare the effects of dietary supplementation with a small amount of native or partially defatted poppy seeds on gastrointestinal function and lipid metabolism in rats fed a high-fat diet. The defatted poppy seeds had, among others, lower fat content and higher fibre and protein content than native poppy seeds. The rats fed with a high-fat diet were characterised by severe metabolic disorders, especially in the liver, and poppy seeds were unable to prevent them. However, depending on the seed form, dietary supplementation with poppy seeds differentially affected the microbial and endogenous lipid metabolism in rats. In the distal intestine, both dietary seed forms stimulated microbial acetate production, and the supplementation with partially defatted poppy seeds additionally inhibited isobutyrate and isovalerate formation, which indicates a reduction in putrefaction. Both dietary seed forms increased cholesterol accumulation in the liver. Only dietary supplementation with partially defatted poppy seeds attenuated visceral fat and hepatic triglyceride accumulations and lowered blood triglyceride concentrations, and at the transcriptional level, the inhibition of SREBP-1c, which upregulates genes responsible for de novo lipogenesis, was additionally observed in this organ. In conclusion, a low and regular consumption of partially defatted poppy seeds may be beneficial in managing obesity-related disorders.
Carbonic anhydrase IV in lizard chemical signals
Authors: Mangiacotti Marco , Fumagalli Marco , Casali Claudio , Biggiogera Marco , Forneris Federico , Sacchi Roberto
Published: August 2023

The evolution of chemical signals is subject to environmental constraints. A multicomponent signal may combine semiochemical molecules with supporting compounds able to enhance communication efficacy. Carbonic anhydrases (CAs) are ubiquitous enzymes catalysing the reversible hydration of carbon dioxide, a reaction involved in a variety of physiological processes as it controls the chemical environment of the different tissues or cellular compartments, thus contributing to the overall system homeostasis. CA-IV isoform has been recently identified by mass spectrometry in the femoral gland secretions (FG) of the marine iguana, where it has been hypothesized to contribute to the chemical stability of the signal, by regulating blend pH. Lizards, indeed, use FG to communicate by delivering the waxy secretion on bare substrate, where it is exposed to environmental stressors. Therefore, we expect that some molecules in the mixture may play supporting functions, enhancing the stability of the chemical environment, or even conferring homeostatic properties to the blend. CA-IV may well represent an important candidate to this hypothesized supporting/homeostatic function, and, therefore, we can expect it to be common in FG secretions of other lizard species. To evaluate this prediction and definitely validate CA identity, we analysed FG secretions of eight species of wall lizards (genus Podarcis), combining mass spectrometry, immunoblotting, immunocytochemistry, and transmission electron microscopy. We demonstrate CA-IV to actually occur in the FG of seven out of the eight considered species, providing an immunochemistry validation of mass-spectrometry identifications, and localizing the enzyme within the secretion mass. The predicted structure of the identified CA is compatible with the known enzymatic activity of CA-IV, supporting the hypothesis that CA play a signal homeostasis function and opening to new perspective about the role of proteins in vertebrate chemical communication.
Role of puboperinealis and rectourethralis muscles as a urethral support system to maintain urinary continence after robot-assisted radical prostatectomy
Authors: Kataoka Masao , Meguro Satoru , Tanji Ryo , Onagi Akifumi , Matsuoka Kanako , Honda-Takinami Ruriko , Hoshi Seiji , Hata Junya , Sato Yuichi , Akaihata Hidenori , Ogawa Soichiro , Uemura Motohide , Kojima Yoshiyuki
Published: August 2023

The present study investigated the role of a urethral support system to maintain urinary continence after robot-assisted radical prostatectomy (RARP), with a focus on pelvic floor muscles, such as the puboperinealis muscle (PPM) and rectourethralis muscle (RUM). Finally, 323 patients who underwent RARP were analyzed in this study. All patients performed a one-hour pad test 1, 3, 6, 9, and 12 months after RARP to assess urinary incontinence and MRI before and 9 months after RARP to evaluate the pelvic anatomical structure. The preoperative cross-sectional area of PPM (2.21 ± 0.69 cm2) was significantly reduced by 19% after RARP (1.79 ± 0.60 cm2; p < 0.01). Positive correlations were observed between the amount of urinary leakage according to the 1-h pad test 1, 3, 6, 9, and 12 months after RARP and the change in the cross-sectional area of PPM by RARP (p < 0.01, < 0.001, < 0.001, < 0.001, and < 0.001, respectively). A positive correlation was also noted between the amount of urinary leakage 6 and 12 months after RARP and the preoperative RUM diameter (p < 0.05). The amount of urinary leakage 1, 3, 6, 9, and 12 months after RARP negatively correlated with the change in the antero-posterior diameter of the membranous urethra (MU diameter) from the static to dynamic phases during the Valsalva maneuver by cine MRI. Furthermore, the change in the MU diameter negatively correlated with the change in the cross-sectional area of PPM (p < 0.05). PPM and RUM play significant roles as a supportive mechanism to maintain urinary continence by functioning as a urethral support.
Mechanism of salidroside in the treatment of endometrial cancer based on network pharmacology and molecular docking
Authors: Yang Panpan , Chai Yihong , Wei Min , Ge Yan , Xu Feixue
Published: August 2023

Salidroside is a natural product of phenols, which has a wide scape of pharmacological effects, but its pharmacological effects and molecular mechanism on endometrial cancer are not clear. To systematically explore the pharmacological effects and molecular mechanisms of salidroside on endometrial cancer through the method of network pharmacology. The possible target genes of salidroside were obtained through different pharmacological databases and analysis platforms, and then the relevant target genes of endometrial cancer were obtained through the GeneCards website, and the target genes were uniformly converted into standardized gene names with Uniprot. The collected data were then processed to obtain common target genes and further analyzed through the String website to construct a protein–protein interaction (PPI) network, followed by gene ontology (GO) functional annotation and Kyoto Gene and Genome Encyclopedia (KEGG) pathway analysis. We further interpreted the molecular mechanism of salidroside for the treatment of endometrial cancer by constructing a “drug component–target gene–disease” network. Finally, we performed molecular docking to validate the binding conformation between salidroside and the candidate target genes. There were 175 target genes of salidroside after normalization, among which 113 target genes interacted with endometrial cancer. GO analysis indicated that the anti-endometrial cancer effect of salidroside may be strongly related to biological processes such as apoptosis and response to drug. KEGG analysis indicated that its mechanism may be related to pathway in cancer and PI3K-AKT signaling pathway. Molecular docking showed that salidroside had high affinity with five key genes. Based on the novel network pharmacology and molecular docking validation research methods, we have revealed for the first time the potential mechanism of salidroside in the therapy of endometrial cancer.
Single-cell sequencing of a novel model of neonatal bile duct ligation in mice identifies macrophage heterogeneity in obstructive cholestasis
Authors: Antala Swati , Gromer Kyle D. , Gadhvi Gaurav , Kriegermeier Alyssa , Wang Jiao-Jing , Abdala-Valencia Hiam , Wechsler Joshua B. , Perlman Harris , Winter Deborah R. , Zhang Zheng J. , Green Richard M. , Taylor Sarah A.
Published: August 2023

Macrophages (MΦ) play a role in neonatal etiologies of obstructive cholestasis, however, the role for precise MΦ subsets remains poorly defined. We developed a neonatal murine model of bile duct ligation (BDL) to characterize etiology-specific differences in neonatal cholestatic MΦ polarization. Neonatal BDL surgery was performed on female BALB/c mice at 10 days of life (DOL) with sham laparotomy as controls. Comparison was made to the Rhesus Rotavirus (RRV)-induced murine model of biliary atresia (BA). Evaluation of changes at day 7 after surgery (BDL and sham groups) and murine BA (DOL14) included laboratory data, histology (H&E, anti-CD45 and anti-CK19 staining), flow cytometry of MΦ subsets by MHCII and Ly6c expression, and single cell RNA-sequencing (scRNA-seq) analysis. Neonatal BDL achieved a 90% survival rate; mice had elevated bile acids, bilirubin, and alanine aminotransferase (ALT) versus controls (p < 0.05 for all). Histology demonstrated hepatocellular injury, CD45+ portal infiltrate, and CK19+ bile duct proliferation in neonatal BDL. Comparison to murine BA showed increased ALT in neonatal BDL despite no difference in histology Ishak score. Neonatal BDL had significantly lower MHCII-Ly6c+ MΦ versus murine BA, however, scRNA-seq identified greater etiology-specific MΦ heterogeneity with increased endocytosis in neonatal BDL MΦ versus cellular killing in murine BA MΦ. We generated an innovative murine model of neonatal obstructive cholestasis with low mortality. This model enabled comparison to murine BA to define etiology-specific cholestatic MΦ function. Further comparisons to human data may enable development of immune modulatory therapies to improve patient outcomes.
The effect of mycophenolate mofetil on podocytes in nephrotoxic serum nephritis
Authors: Hackl A. , Nüsken E. , Voggel J. , Abo Zed S. E. D. , Binz-Lotter J. , Unnersjö-Jess D. , Müller C. , Fink G. , Bohl K. , Wiesner E. , Diefenhardt P. , Dafinger C. , Chen H. , Wohlfarth M. , Müller R.-U. , Hackl M. J. , Schermer B. , Nüsken K.-D. , Weber L. T.
Published: August 2023

Mycophenolate mofetil (MMF) is applied in proteinuric kidney diseases, but the exact mechanism of its effect on podocytes is still unknown. Our previous in vitro experiments suggested that MMF can ameliorate podocyte damage via restoration of the Ca2+-actin cytoskeleton axis. The goal of this study was to characterize podocyte biology during MMF treatment in nephrotoxic serum (NTS) nephritis (NTN). NTN was induced in three-week old wild-type mice. On day 3, half of the mice were treated with MMF (100 mg/kgBW/d p.o.) for one week. On day 10, we performed proteomic analysis of glomeruli as well as super-resolution imaging of the slit diaphragm. For multiphoton imaging of Ca2+concentration ([Ca2+]i), the experimental design was repeated in mice expressing podocyte-specific Ca2+sensor. MMF ameliorated the proteinuria and crescent formation induced by NTS. We identified significant changes in the abundance of proteins involved in Ca2+signaling and actin cytoskeleton regulation, which was further confirmed by direct [Ca2+]iimaging in podocytes showing decreased Ca2+levels after MMF treatment. This was associated with a tendency to restoration of podocyte foot process structure. Here, we provide evidence that MPA has a substantial direct effect on podocytes. MMF contributes to improvement of [Ca2+]iand amelioration of the disorganized actin cytoskeleton in podocytes. These data extend the knowledge of direct effects of immunosuppressants on podocytes that may contribute to a more effective treatment of proteinuric glomerulopathies with the least possible side effects.
Attention U-net for automated pulmonary fissure integrity analysis in lung computed tomography images
Authors: Althof Zachary W. , Gerard Sarah E. , Eskandari Ali , Galizia Mauricio S. , Hoffman Eric A. , Reinhardt Joseph M.
Published: August 2023

Computed Tomography (CT) imaging is routinely used for imaging of the lungs. Deep learning can effectively automate complex and laborious tasks in medical imaging. In this work, a deep learning technique is utilized to assess lobar fissure completeness (also known as fissure integrity) from pulmonary CT images. The human lungs are divided into five separate lobes, divided by the lobar fissures. Fissure integrity assessment is important to endobronchial valve treatment screening. Fissure integrity is known to be a biomarker of collateral ventilation between lobes impacting the efficacy of valves designed to block airflow to diseased lung regions. Fissure integrity is also likely to impact lobar sliding which has recently been shown to affect lung biomechanics. Further widescale study of fissure integrity’s impact on disease susceptibility and progression requires rapid, reproducible, and noninvasive fissure integrity assessment. In this paper we describe IntegrityNet, an attention U-Net based automatic fissure integrity analysis tool. IntegrityNet is able to predict fissure integrity with an accuracy of 95.8%, 96.1%, and 89.8% for left oblique, right oblique, and right horizontal fissures, compared to manual analysis on a dataset of 82 subjects. We also show that our method is robust to COPD severity and reproducible across subject scans acquired at different time points.
Optimization of heterogeneous vehicle logistics scheduling with multi-objectives and multi-centers
Authors: He Zhaolei , Zhang Miaohan , Chen Qiyong , Chen Shiyun , Pan Nan
Published: August 2023

Industrial enterprises have high requirements on timeliness and cost when delivering industrial products to their customers. For this reason, this paper studies the vehicle routing problem (VRP) of different vehicle models in multiple distribution centers. First of all, we consider the multi-dimensional constraints in the actual distribution process such as vehicle load and time window, and build a multi-objective optimization model for product distribution with the goal of minimizing the distribution time and cost and maximizing the loading rate of vehicles. Furthermore, an Improved Life-cycle Swarm Optimization (ILSO) algorithm is proposed based on the life cycle theory. Finally, we use the order data that Yunnan Power Grid Company needs to deliver to the customer (municipal power supply bureau) on a certain day to conduct a dispatching experiment. The simulation and application results show that the transportation cost of transportation obtained by the ILSO algorithm is reduced by 0.8% to 1.6% compared with the other five algorithms. Therefore, ILSO algorithm has advantages in helping enterprises reduce costs and improve efficiency.
Designing super-fast trimodal sponges using recycled polypropylene for organics cleanup
Authors: Saleem Junaid , Moghal Zubair Khalid Baig , McKay Gordon
Published: August 2023

Sorbent pads and films have been commonly used for environmental remediation purposes, but designing their internal structure to optimize access to the entire volume while ensuring cost-effectiveness, ease of fabrication, sufficient strength, and reusability remains challenging. Herein, we report a trimodal sorbent film from recycled polypropylene (PP) with micropores, macro-voids, and sponge-like 3D cavities, developed through selective dissolution, thermally induced phase separation, and annealing. The sorbent has hundreds of cavities per cm2 that are capable of swelling up to twenty-five times its thickness, allowing for super-fast saturation kinetics (within 30 s) and maximum oil sorption (97 g/g). The sorption mechanism follows a pseudo-second-order kinetic model. Moreover, the sorbent is easily compressible, and its structure is retained during oil sorption, desorption, and resorption, resulting in 96.5% reuse efficiency. The oil recovery process involves manually squeezing the film, making the cleanup process efficient with no chemical treatment required. The sorbent film possesses high porosity for effective sorption with sufficient tensile strength for practical applications. Our integrated technique results in a strengthened porous polymeric structure that can be tailored according to end-use applications. This study provides a sustainable solution for waste management that offers versatility in its functionality.