bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo MCM6 variants in neurodevelopmental disorders: a recognizable phenotype related to zinc binding residues
Authors: Smits Daphne J. , Schot Rachel , Popescu Cristiana A. , Dias Kerith-Rae , Ades Lesley , Briere Lauren C. , Sweetser David A. , Kushima Itaru , Aleksic Branko , Khan Suliman , Karageorgou Vasiliki , Ordonez Natalia , Sleutels Frank J. G. T. , van der Kaay Daniëlle C. M. , Van Mol Christine , Van Esch Hilde , Bertoli-Avella Aida M. , Roscioli Tony , Mancini Grazia M. S.
Published: May 2023

The minichromosome maintenance (MCM) complex acts as a DNA helicase during DNA replication, and thereby regulates cell cycle progression and proliferation. In addition, MCM-complex components localize to centrosomes and play an independent role in ciliogenesis. Pathogenic variants in genes coding for MCM components and other DNA replication factors have been linked to growth and developmental disorders as Meier–Gorlin syndrome and Seckel syndrome. Trio exome/genome sequencing identified the same de novo MCM6 missense variant p.(Cys158Tyr) in two unrelated individuals that presented with overlapping phenotypes consisting of intra-uterine growth retardation, short stature, congenital microcephaly, endocrine features, developmental delay and urogenital anomalies. The identified variant affects a zinc binding cysteine in the MCM6 zinc finger signature. This domain, and specifically cysteine residues, are essential for MCM-complex dimerization and the induction of helicase activity, suggesting a deleterious effect of this variant on DNA replication. Fibroblasts derived from the two affected individuals showed defects both in ciliogenesis and cell proliferation. We additionally traced three unrelated individuals with de novo MCM6 variants in the oligonucleotide binding (OB)-fold domain, presenting with variable (neuro)developmental features including autism spectrum disorder, developmental delay, and epilepsy. Taken together, our findings implicate de novo MCM6 variants in neurodevelopmental disorders. The clinical features and functional defects related to the zinc binding residue resemble those observed in syndromes related to other MCM components and DNA replication factors, while de novo OB-fold domain missense variants may be associated with more variable neurodevelopmental phenotypes. These data encourage consideration of MCM6 variants in the diagnostic arsenal of NDD.
Nasogastric tube feeding improves nutritional status and physical state in esophageal cancer patients during chemoradiotherapy: a retrospective study
Authors: Wang Shu-an , Dai Wang-shu , Zhu Jia-yu , Gao Bo , Ren Wei , Chen Xiaotian
Published: May 2023

Objective

To compare the complication rates, nutritional status, and physical state between esophageal cancer (EC) patients managed by nasogastric tube (NGT) feeding versus those managed by oral nutritional supplementation (ONS) during chemoradiotherapy.

Methods

EC patients undergoing chemoradiotherapy managed by nonintravenous nutritional support in our institute were retrospectively recruited and divided into an NGT group and an ONS group based on the nutritional support method. The main outcomes, including complications, nutritional status, and physical state, were compared between groups.

Results

The baseline characteristics of EC patients were comparable. There were no significant differences in the incidence of treatment interruption (13.04% vs. 14.71%, P = 0.82), death (2.17% vs. 0.00%, P = 0.84), or esophageal fistula (2.17% vs. 1.47%, P = 1.00) between the NGT group and ONS group. Body weight loss and decrease in albumin level were significantly lower in the NGT group than in the ONS group (both P < 0.05). EC patients in the NGT group had significantly lower Nutritional Risk Screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) scores and significantly higher Karnofsky Performance Status (KPS) scores than patients in the ONS group (all P < 0.05). The rates of grade > 2 esophagitis (10.00% vs. 27.59%, P = 0.03) and grade > 2 bone marrow suppression (10.00% vs. 32.76%, P = 0.01) were significantly lower in the NGT group than in the ONS group. There were no significant differences in the incidence of infection and upper gastrointestinal disorders or therapeutic efficacy between groups (all P > 0.05).

Conclusions

EN through NGT feeding leads to significantly better nutritional status and physical state in EC patients during chemoradiotherapy than EN via ONS. NGT may also prevent myelosuppression and esophagitis..
Can Self-affirmation Encourage HIV-Prevention? Evidence from Female Sex Workers in Senegal
Authors: Haire Sara , Lépine Aurélia , Effron Daniel A. , Treibich Carole
Published: May 2023

We test an intervention aiming to increase condom usage and HIV testing in a stigmatized population at high risk of contracting HIV: female sex workers (FSWs) in Senegal. Some sex work is legal in Senegal, and condoms and HIV tests are freely available to registered FSWs—but FSWs may be reluctant to get tested and use condoms, in part because doing so would entail acknowledging their risk of contracting HIV and potentially expose them to stigma. Drawing on self-affirmation theory, we hypothesized that reflecting on a source of personal pride would help participants acknowledge their risk of HIV, intend to use condoms more frequently, and take an HIV test. Prior research suggests that similar self-affirmation interventions can help people acknowledge their health risks and improve their health behavior, especially when paired with information about effectively managing their health (i.e., self-efficacy information). However, such interventions have primarily been tested in the United States and United Kingdom, and their generalizability outside of these contexts is unclear. Our high-powered experiment randomly assigned participants (N = 592 FSWs; N = 563 in the final analysis) to a self-affirmation condition or a control condition and measured their risk perceptions, whether they took condoms offered to them, and whether (after randomly receiving or not receiving self-efficacy information) they took an HIV test. We found no support for any of our hypotheses. We discuss several explanations for these null results based on the stigma attached to sex work and HIV, cross-cultural generalizability of self-affirmation interventions, and robustness of previous findings.
Electrophysiological findings during re-do procedures after single-shot pulmonary vein isolation for atrial fibrillation with pulsed field ablation
Authors: Magni Federico Tancredi , Scherr Daniel , Manninger Martin , Sohns Christian , Sommer Philip , Hovakimyan Tatevik , Blaauw Yuri , Mulder Bart A.
Published: May 2023

Background

Pulsed field ablation (PFA) is a novel ablation technology recently adopted in the treatment of atrial fibrillation (AF). Currently, little is known about the durability of PFA ablation lesions.

Methods

We investigated patients who underwent redo-ablation due to recurrent AF/atrial-flutter or tachycardia (AFL/AT) following PVI with PFA. We report electrophysiological findings and ablation strategy during redo-ablation.

Results

Of 447 patients undergoing index PVI with PFA, 14 patients (age: 61.9±10.8 years; 7 (50.0%) males; left atrial volume index (n=10): 39.4±14.6 mL/m2) were referred for redo-ablation. Initial indication was paroxysmal-AF in 7 patients, persistent-AF in 6 and long-standing-persistent-AF in one patient. Mean time-to-recurrence was 4.9±1.9 months. Three patients received additional posterior-wall-isolation during index PFA. Twelve (85.7%) patients suffered AF recurrence and 5/12 had concomitant AFL. In the remaining 2 patients, one had a (box-dependent) AFL, and one had an atypical AT. No patients had all PVs reconnected. Reconnection in zero, one, two or three PVs was found in 35.7%, 21.4%, 14.3%, and 28.6% of patients, respectively. All 7 patients with zero or one reconnection with AF recurrence received additional/repeat posterior-wall-isolation during re-ablation, while in the others, PVs were re-isolated. Patients with only AFL/AT had no reconnection of PVs, and the substrate was successfully ablated.

Conclusions

Durable PVI (all PV’s isolated) was observed in over one-third of patients at re-do. The predominant recurrent arrhythmia following PVI-only was AF. Concomitant (35.7%) or isolated (14.3%) AFL/AT recurrence was observed in 50% of patients.
Evaluation of the susceptibility of Alphitobius diaperinus meal to infestations by major stored-product beetle species
Authors: Rigopoulou Marianna , Rumbos Christos , Athanassiou Christos
Published: May 2023

The projections for the production of insects as food and feed show an enormous increase for insect production in the near future, which will subsequently lead to the increase of the stored quantities of insect meals and related products. However, information on the susceptibility of insect meals to infestations by stored-product insects is rather limited. To this end, the objective of the present study was to evaluate the potential of major storage insect species to grow and reproduce on insect meals that are based on larvae of the lesser mealworm, Alphitobius diaperinus. The progeny production of thirteen stored-product insects on A. diaperinus meal, as well as their instantaneous rate of increase, as a measure of population growth, was recorded for each species. Based on the results, six out of the thirteen examined insect species (A. diaperinus, Tenebrio molitor, Trogoderma granarium, Lasioderma serricorne, Tribolium confusum, and Tribolium castaneum) were able to infest pure A. diaperinus meal, as they grew well and developed progeny on the insect meal substrate. Tribolium confusum, T. castaneum, and especially T. granarium gave the highest progeny production numbers in the A. diaperinus meal with the latter giving an instantaneous rate of increase of 0.067. Expecting the upcoming increase in the production of insect-based products globally, further research in this field is needed for improved production and storage facilities, detection and estimation methods, and technologies to minimize insect infestations without causing negative effects to farmed insects.
A p-Si/CoPc Hybrid Photodiode System for Looking at Frequency and Temperature Dependence on Dielectric Relaxation and AC Electrical Conductivity
Authors: Mostafa A. , Ashour A. , Balboul Basma A. A. , Assem E. E. , Mostafa Mostafa Y. A.
Published: May 2023

In this work, a heterojunction of Al/p-Si/CoPc/Au was fabricated using the thermal evaporation technique by depositing CoPc on the p-Si. Complex impedance spectroscopy was employed to investigate the impedance characteristics and the full band profile measurements of the fabricated heterojunction. Arrhenius fitting of double relaxation operations was utilized to determine the activation energy of the tested device. The studied device gains a negative temperature resistance coefficient as interpreted from the electrical conductivity and Cole–Cole fitting. The lifetimes of the excess minority carriers, the coefficients of carrier diffusion, and the charge carrier mobilities at the interfaces were measured and estimated.
Comments on: Nonparametric estimation in mixture cure models with covariates
Authors: Cao Ricardo
Published: May 2023

This paper discusses the invited paper by López-Cheda, Peng and Jácome on nonparametric mixture cure models with covariates. An alternative estimation procedure is proposed in this context. The situation when the two covariate vectors (the one in the incidence and in the latency parts) share some, but not all, their covariates is also considered. Some technical aspects in the assumptions, results and proofs of the invited paper are also discussed. Comments on the simulations and the real-data application are included. Finally, possible interesting topics for further research in this field are briefly discussed.
Stability and Conditioning of Immersed Finite Element Methods: Analysis and Remedies
Authors: de Prenter Frits , Verhoosel Clemens V. , van Brummelen E. Harald , Larson Mats G. , Badia Santiago
Published: May 2023

This review paper discusses the developments in immersed or unfitted finite element methods over the past decade. The main focus is the analysis and the treatment of the adverse effects of small cut elements. We distinguish between adverse effects regarding the stability and adverse effects regarding the conditioning of the system, and we present an overview of the developed remedies. In particular, we provide a detailed explanation of Schwarz preconditioning, element aggregation, and the ghost penalty formulation. Furthermore, we outline the methodologies developed for quadrature and weak enforcement of Dirichlet conditions, and we discuss open questions and future research directions.
Comprehensive analysis of ferroptosis-related genes for clinical and biological significance in hepatocellular carcinoma
Authors: Wu Qixian , Tan Zhenlin , Xiong Yu , Gu Chengxin , Zhou Jingdon , Yang Hui , Zhou Jiyuan
Published: May 2023

Objective

This study aims to build a prognostic model of hepatocellular carcinoma (HCC) with ferroptosis-associated genes and explore their molecular function.

Methods

Gene expression data and clinical information were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and the International Cancer Genome Consortium (ICGC). A ferroptosis-associated gene set was obtained from the FerrDb database to identify differentially expressed genes. Then, we performed pathway enrichment analysis and immune infiltration analysis. A combined model based on ferroptosis-associated genes for predicting the overall survival of HCC was built by univariate and multivariate Cox regression analyses. Quantitative real-time polymerase chain reaction, Western blotting, colony formation, CCK-8, and EdU incorporation assays were performed to clarify the function of CAPG in the regulation of cell proliferation in human HCC. Ferroptosis was evaluated by glutathione (GSH), malondialdehyde (MDA), and total iron detection.

Results

Forty-nine ferroptosis-related genes were significantly correlated with HCC, 19 of which had prognostic significance. CAPG, SLC7A11 and SQSTM1 were used to construct a novel risk model. The areas under the curves (AUCs) were 0.746 and 0.720 (1 year) in the training and validation groups, respectively. The survival analysis indicated that patients with high risk scores exhibited worse survival in the training and validation groups. The risk score was also identified as an independent prognostic factor of overall survival (OS), which established and validated the predictive abilities of the nomogram. The risk score was also significantly correlated with the expression of immune checkpoint genes. In vitro data showed that CAPG knockdown dramatically suppressed HCC cell proliferation, and the underlying molecular mechanisms might be that the silencing of CAPG reduced the expression of SLC7A11 and promoted ferroptosis.

Conclusion

The established risk model can be used to predict the prognosis of HCC. At the mechanistic level, CAPG may drive HCC progression by regulating SLC7A11, and ferroptosis activation in HCC patients with high CAPG expression may serve as a potential therapeutic strategy.
Numerical modelling of particle entrainment in the wheel–rail interface
Authors: Maramizonouz Sadaf , Nadimi Sadegh , Skipper William A. , Lewis Stephen R. , Lewis Roger
Published: May 2023

The process of applying sand particles to increase the traction between wheel and rail is reported to be less than 20% efficient. To better understand entrainment efficiency, the process is simulated using the Discrete Element Method. The simulation results are validated against full-scale experimental observations in terms of entrainment efficiency and particle velocity for ten case studies with different positioning of the sand nozzle. The numerical simulations confirm the experimental observations wherein the highest efficiency can be achieved when the sander is aimed at the wheel/rail nip. When aiming the sander at the wheel, the values of entrainment efficiency from simulations and experiments show some discrepancy which can be related to the numerical assumptions. Calculating coefficients of traction between the rail and wheel from the simulation data for the four cases of an un-sanded contact, and with the sander aimed at the rail, the nip, and the wheel (all with the same angle) show an increase in the coefficient of traction for all sanded cases compared to the un-sanded case.
Edge General Position Sets in Fibonacci and Lucas Cubes
Authors: Klavžar Sandi , Tan Elif
Published: May 2023

A set of edges$$X\subseteq E(G)$$X⊆E(G)of a graphGis an edge general position set if no three edges fromXlie on a common shortest path inG. The cardinality of a largest edge general position set ofGis the edge general position number ofG. In this paper, edge general position sets are investigated in partial cubes. In particular, it is proved that the union of two largest$$\Theta $$Θ-classes of a Fibonacci cube or a Lucas cube is a maximal edge general position set.
Die Seele Trajans
Authors: Roling Bernd
Published: May 2023

Zu den scheinbaren Curiosa, mit denen sich schon die mittelalterliche, vor allem aber die frühneuzeitliche Theologie auseinandersetzen mußte, gehörte die Legende, Gregor der Große habe die Seele Trajans durch seine Fürbitten aus der Hölle befreien können. Die gut bezeugte und reich ventilierte hagiographische Tradition war mit erheblichem Skandalisierungspotential verbunden, torpedierte sie doch die strenge Teilung von Fegefeuer und Hölle, die für die Eschatologie spätestens mit dem 12. Jahrhundert unerlässlich war. Doppelt komplex gestaltete sich die Gemengelage nach der Reformation, denn denkbar leicht ließ sich in der interkonfessionellen Kontroverse von Seiten der Protestanten die scheinbare Befreiung Trajans als Musterbeispiel einer irregeleiteten Werkgerechtigkeit instrumentalisieren. Die Konfliktlinien, die hier zwischen Erzähl- und Exempelliteratur auf der einen Seite und der streng definitorisch argumentierenden Theologie auf der anderen verliefen, werden in diesem Beitrag an einigen Beispielen rekonstruiert, mit dem Ziel, eine Fallstudie für den (schwierigen) Dialog zwischen Literatur und Theologie vorzulegen, die vor allem auch ihre unterschiedlichen Textgattungen in ihrem Selbstverständnis in den Blick nehmen soll. Zugleich wird exemplarisch nachvollzogen, wie sich eine mittelalterliche Debatte in der Konfrontation der Konfessionen in der Frühen Neuzeit neu konfigurieren konnte.
Contingency, Sociality, and Moral Progress
Authors: LEFFLER OLOF
Published: May 2023

A debate has recently appeared regarding whether non-naturalism is better than other metaethical views at explaining moral progress. I shall take the occasion of this debate to present a novel debunking dilemma for moral non-naturalists, extending Sharon Street's Darwinian one. I will argue that moral progress indicates that our moral attitudes tend to reflect contingent sociocultural and psychological factors. For non-naturalists, there is then either a relation between these factors and the moral facts, non-naturalistically construed, or there is not. If there is no relation, the contingent factors are unlikely to lead to moral knowledge. If there is a relation, they must be likely to lead to non-naturalist-style moral knowledge, but no theoretically virtuous explanation of moral progress is likely to accommodate non-naturalist commitments. It follows that non-naturalist moral realism cannot explain our moral knowledge. I call this a contingentist challenge to non-naturalism.
Regulation by Design and the Governance of Technological Futures
Authors: Almada Marco
Published: May 2023

Regulation by design is an increasingly common approach in the governance of digital technologies. Under this approach, the developers of digital systems must adopt technical measures that implement the specific requirements mandated by law in their software. Some jurisdictions, notably the European Union (EU), have turned to regulation by design as a mechanism to automatically enforce legal requirements, but this article argues that such an approach can have important implications for long-term governance. Drawing from examples of regulation by design in EU law, it shows that by-design provisions delegate rule-making power to software designers, whose interpretations of the law become entrenched in digital systems. This delegation process suffers from legitimacy deficits, which are compounded whenever digital systems continue to enforce the designer-made rules as they operate for years and, sometimes, decades. Yet, these legitimacy deficits are not unavoidable, as regulation by design can be used to force designers to adopt technical and organisational practices that mitigate the risks of rule entrenchment to future generations. By mapping the long-term risks of regulation by design and potential solutions to them, this article provides a first step towards approaches to regulation by design that do not sacrifice the future for present interests.
First isolation of Echinococcus granulosus sensu lato genotype 7 in the archipelago of Cape Verde
Authors: Gonçalves Baptista Lara , Laurimäe Teivi , Muchaamba Gillian , Cathomas Laura , Barros Olende Ana Lina , Mata dos Santos Iolanda , Lobo de Pina Ângela , Deplazes Peter
Published: May 2023

There are no scientific data available on the occurrence of the Echinococcus granulosus sensu lato (s.l.) cluster in definitive hosts (domestic dogs), intermediate hosts (domestic livestock) nor humans in Cape Verde. In this pilot study, environmental dog fecal samples (n = 369) were collected around food markets, official slaughterhouses, as well as home and small business slaughter spots in 8 of the 9 inhabited islands from the Cape Verde archipelago, between June 2021 and March 2022. Additionally, during the same period, 40 cysts and tissue lesions were opportunistically collected from 5 islands, from locally slaughtered cattle (n = 7), goats (n = 2), sheep (n = 1) and pigs (n = 26). Genetic characterization by a multiplex polymerase chain reaction assay targeting the 12S rRNA gene confirmed the presence of E. granulosus s.l. in fecal and tissue material. In total, 17 cyst samples from Santiago (n = 9), Sal (n = 7) and São Vicente (n = 1) and 8 G6/G7-positive dog fecal samples from Santiago (n = 4) and Sal (n = 4) were identified as E. granulosus s.l. G7 by sequence analysis (nad2, nad5 and nad1 genes). This study discloses the transmission of E. granulosus s.l. G7, in pig, cattle and dog in Cape Verde.
Reappraising Prokofiev's Operas
Authors: Bedford Joshua
Published: May 2023

Sergei Prokofiev's operatic career exhibits a multitude of exceptional successes and failures, political and cultural idiosyncrasies and compromises, and bold convictions and uncertainties. Prokofiev considered himself an opera composer and showed his affinity for it from an early age, completing his first opera by age nine and continuing his work in the art form for the remainder of his life and career. Each opera takes on vastly different subjects, topics and time periods, evidence of his diverse selection of libretto sources. For his mature works, Prokofiev adapted literary works from Russia's nineteenth-century greats (Dostoyevsky and Tolstoy), a Russian twentieth-century symbolist author (Bryusov) and two socialist-realist authors (Katayev and Polevoy). He adapted two other operas from the eighteenth century with Richard Brinsley Sheridan's comic opera libretto forThe Duennaand Carlo Gozzi's fiabaL'amore delle tre melarance.
Hydrologic Controls on Individual Ostracode Stable Isotopes in a Desert Lake: A Modern Baseline for Lake Turkana
Authors: Thirumalai K. , Cohen A. S. , Taylor D.
Published: May 2023

Stable carbon (δ13C) and oxygen (δ18O) isotope measurements in lacustrine ostracodes are widely used as paleolimnological indicators of past climate change. Previous work has used individual ostracode valves to resolve seasonal and subdecadal paleohydrological signals, yet replicated assessments of co‐occurring specimens from modern samples are rare. Here we focus on ostracodes from sediments collected in 1979 from Lake Turkana, an alkaline desert lake in tropical eastern Africa. Sourced from the Ethiopian highlands, the Omo River is the dominant inflow into this lake. We present individual ostracode valve analyses (IOVA) of δ13C and δ18O measurements (n = 329) of the extant benthic ostracode Sclerocypris clavularis from 17 sites spanning the entire lake (navg = ∼19 specimens/site). We demonstrate that the pooled statistics of individual valve measurements at each site are shaped by lake hydrology, superimposed over inter‐individual isotopic variations. Within‐site variance in IOVA‐δ13C is larger (∼60%) than that of IOVA‐δ18O. Yet, site‐based averages exhibit a systematic pattern, with higher δ values toward the southern part of the lake, away from Omo River inflow. We suggest that the latitudinal δ13C gradient may arise from low riverine δ13C and low organic matter δ13C as a productivity response to nutrient‐rich Omo River inflow toward the north. The δ18O pattern may be explained by the diminishing influence of Omo River inflows and more evaporation driving higher IOVA‐δ18O values toward the windier, southern basin. We conclude that pooled IOVA statistics in Omo‐Turkana sediments can aid interpretations of past regional paleohydrology and its variability in this basin.
Raising Hazard Awareness at the Foot of One of the World’s Most Dangerous Volcanoes
Authors: Makoni Munyaradzi
Published: May 2023

In the shadow of a deadly eruption in 2021, students in Goma, Democratic Republic of Congo, are learning about future hazards.
Constraints on MTZ Water Content From Joint Inversion of Diurnal Variations and Magnetospheric Signals
Authors: Zhang H. , Egbert G. D. , Huang Q.
Published: May 2023

Electrical conductivity of mantle minerals is highly sensitive to water content, so estimates of this physical parameter based on long‐period electromagnetic induction data can help to constrain mantle hydration. Reliable constraints require conductivity model with sufficient resolution at relevant depths, as well as a comprehensive uncertainty analysis. In this global induction study, we combine data from the primarily ionospheric diurnal variation and longer‐period magnetospheric ring current bands. Joint inversion of these two data sources allows significantly improved vertical resolution of radial conductivity variations, especially in the mantle transition zone (MTZ). We then evaluate how uncertainties in the resulting conductivity model, in thermal models, and in laboratory results affect water content estimates, focusing on the MTZ. Our analysis suggests that the conductivity model is best explained by a dry MTZ with pyrolitic composition. Considering the uncertainties, an upper bound on average water content in the MTZ is 0.3 wt.% of water.
Spatial and Temporal Redox Heterogeneity Controlled by a Fe(II), Anoxic Upwelling System in the Early Mesoproterozoic Ocean
Authors: Ye Mingze , Zhang Shuichang , Ye Yuntao , Wu Minghao , Wang Xiaomei
Published: May 2023

The availability of oxygen and nutrients during the Mesoproterozoic (1.6–1.0 Ga) is thought to influence the rate of eukaryote evolution. The cause of the transition from low productivity in the upper Wumishan Formation to organic‐rich sediments in the Hongshuizhuang Formation remains unknown. We report FeHR/FeT, Fepy/FeHR, MoEF, UEF, VEF, and [Ce/Ce*]SN in one core of the Yanliao Basin to study the redox evolution and compare it with other sections in different depths of the Yanliao Basin to get clues of the spatial and temporal redox heterogeneity. Mo‐U covariation, low Co × Mn and CoEF × MnEF, and distribution patterns of trace metals indicate the upwelling events. An upwelling system could fuel nutrients to promote productivity levels in surface water and contribute to anoxic deep waters. The uniformly positive δ15N values are interpreted as sufficient NO3− reduction via denitrification and dissimilatory nitrate reduction to ammonium in a ferruginous upwelling condition.
Phase‐Field Simulation of Texture Evolution in Magmatic Rocks
Authors: Kundin J. , Steinbach I. , Chakraborty S.
Published: May 2023

The tool of phase‐field modeling for the prediction of chemical as well as microstructural evolution during crystallization from a melt in a mineralogical system has been developed in this work. We provide a compact theoretical background and introduce new aspects such as the treatment of anisotropic surface energies that are essential for modeling mineralogical systems. These are then applied to two simple model systems—the binary olivine‐melt and plagioclase‐melt systems ‐ to illustrate the application of the developed tools. In one case crystallization is modeled at a constant temperature and undercooling while in the other the process of crystallization is tracked for a constant cooling rate. These two examples serve to illustrate the capabilities of the modeling tool. The results are analyzed in terms of crystal size distributions (CSD) and with a view toward applications in diffusion chronometry; future possibilities are discussed. The modeling results demonstrate that growth at constant rates may be expected only for limited extents of crystallization, that breaks in slopes of CSD‐plots should be common, and that the lifetime of a given crystal of a phase is different from the lifetime of this phase in a magmatic system. The last aspect imposes an inherent limit to timescales that may be accessed by diffusion chronometry. Most significantly, this tool provides a bridge between CSD analysis and diffusion chronometry—two common tools that are used to study timescales of magmatic processes.
Multiple virus sorting based on aptamer-modified microspheres in a TSAW device
Authors: Liu Xianglian , Chen Xuan , Dong Yangchao , Zhang Chuanyu , Qu Xiaoli , Lei Yingfeng , Jiang Zhuangde , Wei Xueyong
Published: May 2023

Due to the overlapping epidemiology and clinical manifestations of flaviviruses, differential diagnosis of these viral diseases is complicated, and the results are unreliable. There is perpetual demand for a simplified, sensitive, rapid and inexpensive assay with less cross-reactivity. The ability to sort distinct virus particles from a mixture of biological samples is crucial for improving the sensitivity of diagnoses. Therefore, we developed a sorting system for the subsequent differential diagnosis of dengue and tick-borne encephalitis in the early stage. We employed aptamer-modified polystyrene (PS) microspheres with different diameters to specifically capture dengue virus (DENV) and tick-borne encephalitis virus (TBEV), and utilized a traveling surface acoustic wave (TSAW) device to accomplish microsphere sorting according to particle size. The captured viruses were then characterized by laser scanning confocal microscopy (LSCM), field emission scanning electron microscopy (FE-SEM) and reverse transcription-polymerase chain reaction (RT‒PCR). The characterization results indicated that the acoustic sorting process was effective and damage-free for subsequent analysis. Furthermore, the strategy can be utilized for sample pretreatment in the differential diagnosis of viral diseases.
Targeting strategies for bone diseases: signaling pathways and clinical studies
Authors: Xu Hao , Wang Wentao , Liu Xin , Huang Wei , Zhu Chen , Xu Yaozeng , Yang Huilin , Bai Jiaxiang , Geng Dechun
Published: May 2023

Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has been considered a promising therapeutic approach for handling such drawbacks. With the deepening understanding of bone biology, improvements in some established bone-targeted drugs and novel therapeutic targets for drugs and deliveries have emerged on the horizon. In this review, we provide a panoramic summary of recent advances in therapeutic strategies based on bone targeting. We highlight targeting strategies based on bone structure and remodeling biology. For bone-targeted therapeutic agents, in addition to improvements of the classic denosumab, romosozumab, and PTH1R ligands, potential regulation of the remodeling process targeting other key membrane expressions, cellular crosstalk, and gene expression, of all bone cells has been exploited. For bone-targeted drug delivery, different delivery strategies targeting bone matrix, bone marrow, and specific bone cells are summarized with a comparison between different targeting ligands. Ultimately, this review will summarize recent advances in the clinical translation of bone-targeted therapies and provide a perspective on the challenges for the application of bone-targeted therapy in the clinic and future trends in this area.
Global burden of hematologic malignancies and evolution patterns over the past 30 years
Authors: Zhang Nan , Wu Jinxian , Wang Qian , Liang Yuxing , Li Xinqi , Chen Guopeng , Ma Linlu , Liu Xiaoyan , Zhou Fuling
Published: May 2023

Hematologic malignancies are among the most common cancers, and understanding their incidence and death is crucial for targeting prevention, clinical practice improvement, and research resources appropriately. Here, we investigated detailed information on hematological malignancies for the period 1990–2019 from the Global Burden of Disease study. The age-standardized incidence rate (ASIR), the age-standardized death rate (ASDR), and the corresponding estimated annual percentage changes (EAPC) were calculated to assess temporal trends in 204 countries and territories over the past 30 years. Globally, incident cases of hematologic malignancies have been increasing since 1990, reaching 1343.85 thousand in 2019, but the ASDR for all types of hematologic malignancies has been declining. The ASDR for leukemia, multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma were 4.26, 1.42, 3.19, and 0.34 per 100,000 population in 2019, respectively, with Hodgkin lymphoma showing the most significant decline. However, the trend varies by gender, age, region, and the country’s economic situation. The burden of hematologic malignancies is generally higher in men, and this gender gap decreases after peaking at a given age. The regions with the largest increasing trend in the ASIR of leukemia, multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma were Central Europe, Eastern Europe, East Asia, and Caribbean, respectively. In addition, the proportion of deaths attributed to high body-mass index continued to rise across regions, especially in regions with high socio-demographic indices (SDI). Meanwhile, the burden of leukemia from occupational exposure to benzene and formaldehyde was more widespread in areas with low SDI. Thus, hematologic malignancies remain the leading cause of the global tumor burden, with growing absolute numbers but sharp among several age-standardized measures over the past three decades. The results of the study will inform analysis of trends in the global burden of disease for specific hematologic malignancies and develop appropriate policies for these modifiable risks.
All boreal forest successional stages needed to maintain the full suite of soil biodiversity, community composition, and function following wildfire
Authors: Porter Teresita M. , Smenderovac Emily , Morris Dave , Venier Lisa
Published: May 2023

Wildfire is a natural disturbance in boreal forest systems that has been predicted to increase in frequency, intensity, and extent due to climate change. Most studies tend to assess the recovery of one component of the community at a time but here we use DNA metabarcoding to simultaneously monitor soil bacteria, fungi, and arthropods along an 85-year chronosequence following wildfire in jack pine-dominated ecosites. We describe soil successional and community assembly processes to better inform sustainable forest management practices. Soil taxa showed different recovery trajectories following wildfire. Bacteria shared a large core community across stand development stages (~ 95–97% of their unique sequences) and appeared to recover relatively quickly by crown closure. By comparison fungi and arthropods shared smaller core communities (64–77% and 68–69%, respectively) and each stage appeared to support unique biodiversity. We show the importance of maintaining a mosaic ecosystem that represents each stand development stage to maintain the full suite of biodiversity in soils following wildfire, especially for fungi and arthropods. These results will provide a useful baseline for comparison when assessing the effects of human disturbance such as harvest or for assessing the effects of more frequent wildfire events due to climate change.
Iron functionalized silica particles as an ingenious sorbent for removal of fluoride from water
Authors: Kiprono Paul , Kiptoo Jackson , Nyawade Eunice , Ngumba Elijah
Published: May 2023

The paucity of safe drinking water remains a global concern. Fluoride is a pollutant prevalent in groundwater that has adverse health effects. To resolve this concern, we devised a silica-based defluoridation sorbent from pumice rock obtained from the Paka volcano in Baringo County, Kenya. The alkaline leaching technique was used to extract silica particles from pumice rock, which were subsequently modified with iron to enhance their affinity for fluoride. To assess its efficacy, selected borehole water samples were used. Scanning electron microscopy, X-ray diffraction, Fourier transform infrared and X-ray fluorescence spectroscopy was used to characterize the sorbent. The extracted silica particles were 96.71% pure and amorphous, whereas the iron-functionalized silica particles contained 93.67% SiO2 and 2.93% Fe2O3. The optimal pH, sorbent dose and contact time for defluoridation of a 20 mg/L initial fluoride solution were 6, 1 g and 45 min, respectively. Defluoridation followed pseudo-second-order kinetics and fitted Freundlich's isotherm. Fluoride levels in borehole water decreased dramatically; Intex 4.57–1.13, Kadokoi 2.46–0.54 and Naudo 5.39–1.2 mg/L, indicating that the silica-based sorbent developed from low-cost, abundant and locally available pumice rock is efficient for defluoridation.
Development of a deep learning system to detect glaucoma using macular vertical optical coherence tomography scans of myopic eyes
Authors: Kim Ji-Ah , Yoon Hanbit , Lee Dayun , Kim MoonHyun , Choi JoonHee , Lee Eun Ji , Kim Tae-Woo
Published: May 2023

Myopia is one of the risk factors for glaucoma, making accurate diagnosis of glaucoma in myopic eyes particularly important. However, diagnosis of glaucoma in myopic eyes is challenging due to the frequent associations of distorted optic disc and distorted parapapillary and macular structures. Macular vertical scan has been suggested as a useful tool to detect glaucomatous retinal nerve fiber layer loss even in highly myopic eyes. The present study was performed to develop and validate a deep learning (DL) system to detect glaucoma in myopic eyes using macular vertical optical coherence tomography (OCT) scans and compare its diagnostic power with that of circumpapillary OCT scans. The study included a training set of 1416 eyes, a validation set of 471 eyes, a test set of 471 eyes, and an external test set of 249 eyes. The ability to diagnose glaucoma in eyes with large myopic parapapillary atrophy was greater with the vertical than the circumpapillary OCT scans, with areas under the receiver operating characteristic curves of 0.976 and 0.914, respectively. These findings suggest that DL artificial intelligence based on macular vertical scans may be a promising tool for diagnosis of glaucoma in myopic eyes.
The role of genetic polymorphisms of interleukin-1 (IL-1R1 and IL-1RN) in primary knee osteoarthritis in Indonesia
Authors: Budhiparama Nicolaas C. , Lumban-Gaol Imelda , Sudoyo Herawati , Magetsari Rahadyan , Wibawa Tri
Published: May 2023

This study aimed to evaluate the association of SNPs of the IL-1 family with the clinical severity of knee OA. This case‒control study was performed among 100 healthy knees and 130 osteoarthritis (OA) knees of people aged ≥ 50 years with a BMI ≥ 25 kg/m2. The possible correlations among clinical findings, radiographic evaluations, serum levels of IL-1R1 and IL-1Ra, and genotype analyses were evaluated. Three SNPs of IL-1R1, rs871659, rs3771202, and rs3917238, were associated with primary knee OA. Females with IL-1R1 SNP rs871659 allele A had a higher prevalence of primary knee OA. No correlation was found between SNPs of IL-1R1 and IL-1RN and clinical or radiologic severity or serum concentrations of IL-1R1 and IL-1Ra (p > 0.05). BMI and IL-1R1 rs3917238 genotype C/C were correlated with moderate-severe VAS scores. A correlation was also found between the EQ-5D-3L self-care dimension and obesity and between the EQ-5D-3L pain and usual activity dimensions and age ≥ 60 and obesity (p < 0.05). Radiologic severity was only associated with age ≥ 60 years (p < 0.05). We found the IL-1R1 SNPs rs871659, rs3771202, and rs3917238 to be predisposing factors for primary knee osteoarthritis. The clinical findings, radiographic severity, and serum concentrations of IL-1R1 and IL-1Ra were not correlated with these gene polymorphisms.
Genetic predictors of cultural values variation between societies
Authors: Marcus Justin , Cetin Ecesu
Published: May 2023

Associations between the STin2 and 5-HTTLPR polymorphisms within the serotonin transporter gene, SLC6A4, and culture across societies were examined. Based on an analysis of 75 primary studies (28,726 individuals), STin2 allelic frequencies were found to vary widely across countries, ranging from 26% in Germany to 85% in Singapore. Across 53 countries, and after controlling for all major environmental influences of culture, STin2 and 5-HTTLPR were found to explain 23.6% unique variance in monumentalism but none in individualism. Our findings evidence a significant role of genetics in predicting cross-societal cultural values variation, and potentially speak to the need for and importance of incorporating both nature and nurture in theories of cultural values variation across societies.
An enzyme-free technique enables the isolation of a large number of adipose-derived stem cells at the bedside
Authors: Yaylacı Seher , Kaçaroğlu Demet , Hürkal Özgür , Ulaşlı Alper Murat
Published: May 2023

Adipose tissue derived stromal cells (ADSCs) play a crucial role in research and applications of regenerative medicine because they can be rapidly isolated in high quantities. Nonetheless, their purity, pluripotency, differentiation capacity, and stem cell marker expression might vary greatly depending on technique and tools used for extraction and harvesting. There are two methods described in the literature for isolating regenerative cells from adipose tissue. The first technique is enzymatic digestion, which utilizes many enzymes to remove stem cells from the tissue they reside in. The second method involves separating the concentrated adipose tissue using non-enzymatic, mechanical separation methods. ADSCs are isolated from the stromal-vascular fraction (SVF) of processed lipoaspirate, which is the lipoaspirate's aqueous portion. The purpose of this work was to evaluate a unique device ‘microlyzer’ for generating SVF from adipose tissue using a mechanical technique that required minimal intervention. The Microlyzer was examined using tissue samples from ten different patients. The cells that were retrieved were characterized in terms of their cell survival, phenotype, proliferation capacity, and differentiation potential. The number of progenitor cells extracted only from the microlyzed tissue was in comparable amount to the number of progenitor cells acquired by the gold standard enzymatic approach. The cells that were collected from each group exhibit similar levels of viability as well as proliferation rates. In addition, the differentiation potentials of the cells derived from the microlyzed tissue were investigated, and it was discovered that cells isolated through microlyzer entered the differentiation pathways more quickly and displayed a greater level of marker gene expression than cells isolated by enzymatic methods. These findings suggest that microlyzer, particularly in regeneration investigations, will allow quick and high rate cell separation at the bedside.
A pilot study for development of a pulmonary function test induction jacket to automate effort in performing the forced vital capacity manoeuvre
Authors: Rajdeep Prashant , Poorey Ketaki , Patel R. K. , Oommen E. R.
Published: May 2023

The pulmonary function test (PFT) induction jacket was invented to make the process of performing the forced vital capacity (FVC) manoeuvre with a computerized spirometer effortless and productive for both the patient and the medical practitioner. The jacket is composed of three layers of PVC material sealed together to form a single jacket with two chambers. The inner chamber is formed between the inner layer and the middle layer, in which cold water at a temperature of 10 °C is circulated using a connected water unit when triggered. Similarly, the outer chamber is formed between the middle layer and the outer layer, in which air is pressurized using a connected air unit. Thirty volunteers performed the FVC manoeuvre with and without wearing the jacket. There was no difference between the results in spirometry parameters in the participants without a jacket and those with a jacket. However, use of the jacket significantly reduced the number of trials the participants had to undergo to perform spirometry. The jacket automated the FVC manoeuvre by triggering a physiological inspiratory gasp using cold water and circumscribing pressurized air for expiration. Additionally, subsequent advancements in the jacket have been suggested.
Comparison of partial nephrectomy and radical nephrectomy for cystic renal cell carcinoma: a SEER-based and retrospective study
Authors: Lin Wenhao , Yang Zhenggang , Yan Ling , Dai Jun , Fang Chen , Hao Yining , Xu Danfeng , Zhang Jin , Zhao Juping
Published: May 2023

Cystic renal cell carcinoma (cRCC) is uncommon and surgical indication remains controversial. We compared radical nephrectomy (RN) with partial nephrectomy (PN) in patients with cRCC using data from the Surveillance, Epidemiology and End Results (SEER) database and a retrospective cohort including 106 cRCC patients hospitalized in Ruijin and Renji Hospitals from 2013 to 2022. The baseline characteristics between RN and PN groups in both cohorts were adjusted by propensity score-matching (PSM). A total of 640 patients were included in the SEER cohort. Before PSM, PN group in the SEER cohort had a lower level of T stage (p < 0.001) and comprised more Caucasians (p < 0.001). After PSM, RN was associated with worse overall survival (p < 0.001) and cancer-specific survival (p = 0.006) in contrast to PN. In the Chinese cohort, 86 patients who underwent PN and 20 patients who underwent RN were finally included. The mean proportions of estimated glomerular filtration rate preserved after RN were worse than PN. Therefore, PN should be preferred in cRCC patients.