bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting epigenetic aberrations of sarcoma in CRISPR era
Authors: Tanaka Miwa , Nakamura Takuro
Published: March 2023

Sarcomas are rare malignancies that exhibit diverse biological, genetic, morphological, and clinical characteristics. Genetic alterations, such as gene fusions, mutations in transcriptional machinery components, histones, and DNA methylation regulatory molecules, play an essential role in sarcomagenesis. These mutations induce and/or cooperate with specific epigenetic aberrations required for the growth and maintenance of sarcomas. Appropriate mouse models have been developed to clarify the significance of genetic and epigenetic interactions in sarcomas. Studies using the mouse models for human sarcomas have demonstrated major advances in our understanding the developmental processes as well as tumor microenvironment of sarcomas. Recent technological progresses in epigenome editing will not only improve the studies using animal models but also provide a direct clue for epigenetic therapies. In this manuscript, we review important epigenetic aberrations in sarcomas and their representative mouse models, current methods of epigenetic editing using CRISPR/dCas9 systems, and potential applications in sarcoma studies and therapeutics.
Efficacy of minimally invasive pectopexy with concomitant I‐stop‐mini sling for women with pelvic organ prolapse and overt stress urinary incontinence: A retrospective cohort study
Authors: Chao Wei‐Ting , Liu Chia‐Hao , Yang Szu‐Ting , Chen Yi‐Jen , Wang Peng‐Hui , Horng Huann‐Cheng
Published: March 2023

Objective

To compare the efficacy of minimally invasive pectopexy with I‐stop‐mini (MPI) and minimally invasive sacrocolpopexy with Obtryx (MSO).

Methods

Women with pelvic organ prolapse quantification (POP‐Q) stage III or more and overt stress urinary incontinence from May 2018 to May 2021 were included. Patients with meshes fixed on the cervix or vaginal vault and bilateral pectineal ligament with I‐stop‐mini were classified into the MPI group, while those fixed on the apex and sacral promontory with Obtryx were classified into the MSO group. The primary outcomes were 1‐year‐postoperative POP‐Q stage, patient‐reported urinary and prolapse outcomes (Urogenital Distress Inventory‐6, International Consultation on Incontinence Questionnaire‐Short Form, and Pelvic Organ Prolapse Distress Inventory‐6), 1‐h pad test, and sexual life quality (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire). Secondary outcomes included operative data and adverse events.

Results

The efficacy of MPI was similar to that of MSO according to the primary outcomes. MPI had shorter operative times (133.4 ± 30.6 min versus 199.3 ± 20.9 min, P = 0.001) and lower incidence rate of abdominal pain (0% vs 20%, P = 0.02) and groin pain (8% vs 40%, P = 0.01) than MSO.

Conclusions

MPI showed similar efficacy to MSO, but demonstrated shorter operative times and lower incidence rates of abdominal and groin pain.
Risk factors associated with the failure of initial treatment for cesarean scar pregnancy
Authors: Yang Mengjia , Cao Lili , Yan Jinyu , Tang Yibo , Cao Nanyu , Huang Lili
Published: March 2023

Objective

To explore the factors related to cesarean scar pregnancy (CSP) treatment failure under different treatment strategies.

Methods

This is a cohort study that consecutively included 1637 patients with CSP. Characteristics including age, gravidity, parity, previous uterine curettages, time since the last cesarean section, gestational age, mean sac diameter, initial serum β‐human chorionic gonadotropin, distance between gestational sac and serosal layer, CSP subtype, classification of blood flow abundance, fetal heartbeat presence, and intraoperative bleeding were recorded. Four strategies were performed separately on these patients. Binary logistic regression analysis was used to analyze the risk factors for initial treatment failure (ITF) under the different treatment strategies.

Results

The treatment methods failed in 75 CSP patients, and succeeded in 1298 patients. The analysis found that the presence of a fetal heartbeat was significantly associated with ITF of strategy 1, 2 and 4 (P < 0.05); sac diameter was associated with ITF of strategy 1 and 2 (P < 0.05); gestational age was associated with initial treatment failure of strategy 2 (P < 0.05).

Conclusion

There was no difference of the failure rate between ultrasound‐guided evacuation and hysteroscopy‐guided evacuation for CSP treatment with or without uterine artery embolization pretreatment. Sac diameter, fetal heartbeat presence, and gestational age were all associated with CSP initial treatment failure.
Protein Tyrosine Phosphatases: Mighty oaks from little acorns grow
Authors: Tonks Nicholas K.
Published: March 2023

In October 2020, we were finally able to gather for a celebration of Eddy Fischer's 100th birthday. As with many other events, COVID had disrupted and restricted preparations for the gathering, which ultimately was held via ZOOM. Nevertheless, it was a wonderful opportunity to share a day with Eddy, an exceptional scientist and true renaissance man, and to appreciate his stellar contributions to science. Eddy Fischer, together with Ed Krebs, was responsible for the discovery of reversible protein phosphorylation, which launched the entire field of signal transduction. The importance of this seminal work is now being felt throughout the biotechnology industry with the development of drugs that target protein kinases, which have transformed the treatment of a wide array of cancers. I was privileged to have worked with Eddy both as a postdoc and a junior faculty member, during which time we laid the foundations for our current understanding of the protein tyrosine phosphatase (PTP) family of enzymes and their importance as critical regulators of signal transduction. This tribute to Eddy is based upon the talk I presented at the event, giving a personal perspective on Eddy's influence on my career, our early research efforts together in this area, and how the field has developed since then.
Anti‐inflammatory effects of sodium‐glucose cotransporter‐2 inhibitors in COVID‐19
Authors: Yaribeygi Habib , Maleki Mina , Atkin Stephen L. , Kesharwani Prashant , Jamialahmadi Tannaz , Sahebkar Amirhossein
Published: March 2023

The ongoing pandemic of COVID‐19 is intrinsically a systemic inflammatory disorder; hence, those patients suffering an underlying chronic inflammatory disease such as diabetes mellitus are at high risk of severe complications. Preventing or suppressing the inflammatory responses are of importance in diabetic patients. Sodium‐glucose cotransporters‐2 inhibitors (SGLT2i) are a newly introduced anti‐diabetic drugs that have hypoglycemic effects through the urinary excretion of glucose. They also have an anti‐inflammatory potential in diabetes patients, in addition to improving glycemic control, and while there is no direct data available in diabetic patients with COVID‐19 disease, there is evidence that suggests that SGLT2i can reduce systemic inflammation and diminish the cytokine storm effect via several cellular mechanisms. In the current review, our aim was to classify and describe the molecular and cellular pathways by which SGLT2i have anti‐inflammatory effects in diabetic patients with COVID‐19 disease.
Increased Bone Volume by Ixazomib in Multiple Myeloma: 3-Month Results from an Open Label Phase 2 Study
Authors: Diaz-delCastillo Marta , Gundesen Michael Tveden , Andersen Christian Walther , Nielsen Anne Lerberg , Møller Hanne Elisabeth Højsgaard , Vinholt Pernille Just , Asmussen Jon Thor , Kristensen Ida Bruun , Nyvold Charlotte Guldborg , Abildgaard Niels , Levin Andersen Thomas , Lund Thomas
Published: March 2023

Multiple myeloma (MM) is an incurable bone marrow cancer characterized by the development of osteolytic lesions due to the myeloma-induced increase in osteoclastogenesis and decrease in osteoblastic activity. The standard treatment of MM often involves proteasome inhibitors (PIs), which can also have a beneficial off-target bone anabolic effect. However, long-term treatment with PIs is unadvised due to their high side-effect burden and inconvenient route of administration. Ixazomib is a new-generation, oral PI that is generally well tolerated; however, its bone effect remains unknown. Here, we describe the 3-month results of a single-center phase II clinical trial investigating the effect of ixazomib treatment on bone formation and bone microstructure. Thirty patients with MM in stable disease not receiving antimyeloma treatment for ≥3 months and presenting ≥2 osteolytic lesions received monthly ixazomib treatment cycles. Serum and plasma samples were collected at baseline and monthly thereafter. Sodium 18F-Fluoride positron emission tomography (NaF-PET) whole-body scans and trephine iliac crest bone biopsies were collected before and after three treatment cycles. The serum levels of bone remodeling biomarkers suggested an early ixazomib-induced decrease in bone resorption. NaF-PET scans indicated unchanged bone formation ratios; however, histological analyses of bone biopsies revealed a significant increase in bone volume per total volume after treatment. Further analyses of bone biopsies showed unchanged osteoclast number and COLL1A1High-expressing osteoblasts on bone surfaces. Next, we analyzed the superficial bone structural units (BSUs), which represent each recent microscopic bone remodeling event. Osteopontin staining revealed that following treatment, significantly more BSUs were enlarged (>200,000 μm2), and the distribution frequency of their shape was significantly different from baseline. Overall, our data suggest that ixazomib induces overflow remodeling-based bone formation by decreasing the level of bone resorption and promoting longer bone formation events, making it a potentially valuable candidate for future maintenance treatment. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Experiential techniques and therapeutic relationship in the treatment of narcissistic personality disorder: The case of Laura
Authors: Centonze Antonella , Popolo Raffaele , Panagou Corinna , MacBeth Angus , Dimaggio Giancarlo
Published: March 2023

Experiential techniques can be used to address maladaptive interpersonal patterns in patients with personality disorders (PDs) as long as they are delivered minding about the therapeutic relationship. We present the case study of Laura, a 38‐year‐old woman presenting with covert narcissism, generalized anxiety disorder, depression, and complicated grief treated with metacognitive interpersonal therapy. Laura initially refused to engage in any experiential work out of fear of being judged and abandoned by her therapist. To navigate this therapeutic obstacle, the therapist focused on exploring and eventually repairing early alliance ruptures. Thereafter, Laura engaged in experiential work, which helped her address her narcissistic interpersonal patterns. After 2 years, Laura's symptoms and narcissistic problematic behaviors decreased. This case study can help us understand how experiential techniques can be successfully used in PD psychotherapy as long as attention to the therapy relationship is paid.
Understanding community‐ and system‐capacity change over time: A close look at changing social capital in Evidence2Success communities
Authors: Chilenski Sarah M. , Gayles Jochebed , Luneke Aaron , Lew Daphne , Villarruel Francisco , Penilla Mary Lisa , Henderson Charles , Wilson Hilder , Gary Lisa
Published: March 2023

Evidence in majority White and low‐population areas suggest that community prevention systems can create social capital that is needed to support high‐quality implementation and sustainability of evidence‐based programs. This study expands prior work by asking the question: How does community social capital change during the implementation of a community prevention system in low‐income, highly populated communities of color? Data were collected from Community Board members and Key Leaders in five communities. Linear mixed effect models analyzed data on reports of social capital over time, first as reported by Community Board members then by Key Leaders. Community Board members reported social capital improved significantly over time during the implementation of the Evidence2Success framework. Key Leader reports did not change significantly over time. These findings suggest that community prevention systems implemented in historically marginalized communities may help communities build social capital that is likely to support the dissemination and sustainability of evidence‐based programs.
Ballast water treatment by ozone nanobubbles
Authors: Seridou Petroula , Kotzia Eleftheria , Katris Konstantinos , Kalogerakis Nicolas
Published: March 2023

BACKGROUND

The uncontrolled discharge of untreated ballast water, which is essential for a ship's optimal operation, is one of the major causes of sea environmental pollution by shipping. Among the disinfection methods available for ballast water treatment, ozonation is a commonly used method, but its performance is limited by the rapid ozone auto‐decomposition rate. Nanobubbles (NBs) technology has attracted much scientific interest as it is characterized by a long residence time in the aqueous phase and a high surface area; therefore, ozone nanobubbles (OzNBs) are expected to enhance disinfection capacity and residual activity. The present study was designed to provide further insight into the inactivation of heterotrophic bacteria in saline water and to examine the use of OzNBs for disinfection of saline water.

RESULTS

The survival rate of Escherichia coli (E. coli), which was used as indicator microorganism, along with the ozone consumption at different salinities (1.5, 4, 8 and 15 PSU) and bacterial concentrations (107, 106, and 105 CFU mL−1) with and without supplementation of OzNBs were investigated. The results indicated a statistical difference in the residual concentration of total residual oxidants (TRO) with the presence of OzNBs at salinity level 1.5 PSU and at 4 PSU only at the lowest bacterial content. At a low salinity and high bacterial concentration, the concentration of TRO was 6‐fold higher in the presence of OzNBs.

CONCLUSION

The salinity of water has a strong impact on the residual concentration of ozone. When salinity is increased, ozone reacts more rapidly with the bromide and chloride ions. The use of OzNBs exhibited a greater disinfection performance and higher residual activity. © 2023 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
Clinical features of the first attack with leukodystrophy‐like phenotype in children with myelin oligodendrocyte glycoprotein antibody‐associated disorders
Authors: Jiang Yan , Tan Chengbing , Li Xiujuan , Jiang Li , Hong Siqi , Yuan Ping , Zheng Heling , Fan Xiao , Han Wei
Published: March 2023

Background

Myelin oligodendrocyte glycoprotein antibody‐associated disorders (MOGAD) is identified autoimmune disorder with a predominance in paediatric patients, and the disease spectrum has expanded with clinical and radiological patterns. The aim of the study was to describe the clinical characteristics of the first attack with leukodystrophy‐like phenotype with MOGAD in children.

Methods

Patients hospitalized at the Children's Hospital of Chongqing Medical University from June 2017 to October 2021 with positive MOG antibodies and phenotype of leukodystrophy‐like (symmetric white matter lesions) were retrospectively analyzed. Cell‐based assays (CBAs) were used to test MOG antibodies.

Results

Four cases from 143 MOGAD patients were recruited, with two females and two males. The age of onset is all under 6 years old. At the last follow‐up, four cases exhibited a monophasic course, including ADEM in three patients and encephalitis in one patient. The mean EDSS score at onset was 4.62 ± 2.93, and the modified Rankin score (mRS) was 3.00 ± 1.82. First‐attack symptoms include fever, headache, vomiting, seizure, loss of consciousness, emotional and behavioural disorder, and ataxia. The brain MRI showed prominent extensive and essentially symmetric distribution lesions in the white matter. All patients showed clinical and partial radiological improvement after intravenous immunoglobulin and/or glucocorticoid treatment.

Conclusion

The first attack with MOGAD onset of leukodystrophy‐like phenotype was more frequently seen in younger children than other phenotype patients. The patients may show impressive neurologic disorders, but most patients who receive immunotherapy have a good prognosis.
Acute metabolic responses of two marine brachyuran crabs to dilute seawater: The aerobic cost of hyper regulation
Authors: Rios Leonardo P. , Freire Carolina A.
Published: March 2023

Hepatus pudibundus(“flecked box crab”) is a stenohaline osmoconfomer, and restricted to marine habitats.Callinectes danae(“swimming crab Dana”) lives in coastal/estuarine waters and is a weak hyper regulator. There is no consensus on which strategy is more expensive metabolically face salinity challenges: conformation with higher dependence on cell volume regulation, or hyper regulation, alleviating the need for intense cell volume regulation. Crabs were probed for their acute response to dilute seawater through exposures to salinities 35‰, 30‰, 25‰, and 20‰ for 2, 4, and 6 h. Hemolymph osmolality, lactate, and ions (chloride, sodium, magnesium, potassium) were assayed, as well as muscle water content. Water dissolved oxygen, ammonia, and pH levels were also measured.H. pudibundusconformed for osmolality and displayed increase in muscle hydration along the decrease in salinity down to 25‰, whileC. danaeefficiently maintained hemolymph osmo ionic stability, consumed more oxygen, acidified more the water, and released more ammonia. In 25‰, both species spent energy:H. pudibundusputatively controlling cell volume, andC. danaeregulating hemolymph concentrations. In 20‰,H. pudibundusclosed itself, avoiding the contact of the interface epithelia with the external environment and producing much lactate, whereasC. danaespent more energy (aerobic) in extracellular osmo ionic stability. Under these conditions, anisosmotic extracellular regulation (together with additional cell volume regulation) is more oxygen consuming than osmoconformation with a putatively more intense challenge to cell volume. The exposure to hyposalinity limits the occupation of estuarine environments byH. pudibundusin short and middle term.
The negative handmade effect: How and why control deprivation thwarts desire for handmade products
Authors: Song Jiaqi (Flora) , He Dongjin , Jiang Yuwei
Published: March 2023

This research examines consumer reactions to handcrafted products under control deprivation. Four studies reveal that while a positive handmade effect exists among consumers whose sense of personal control is not threatened, a negative handmade effect appears for those consumers under control deprivation. That is, consumers show less favorable attitudes toward handcrafted products when their sense of personal control is threatened. This effect appears because the lower psychological ownership of handcrafted (vs. regular) products cannot instrumentally help restore consumers' sense of personal control. The negative handmade effect under control deprivation is mitigated when consumers can customize the product based on their own preferences. The current research is among the first to show how the handcrafted nature of products can backfire and lead to negative reactions among consumers (i.e., a negative handmade effect). Our findings also shed light on the antecedents and consequences of psychological product ownership and add to the current knowledge of personal control in the consumption domain.
Forage Fish Species Prefer Habitat within Designated Offshore Wind Energy Areas in the U.S. Northeast Shelf Ecosystem
Authors: Friedland Kevin D. , Adams Evan M. , Goetsch Chandra , Gulka Julia , Brady Damian C. , Rzeszowski Everett , Crear Daniel P. , Gaichas Sarah , Gill Andrew B. , McManus M. Conor , Methratta Elizabeth T. , Morano Janelle L. , Staudinger Michelle D.
Published: March 2023

As the world develops sources of renewable energy, there is an intensifying interest in offshore wind energy production. The Northeast U.S. Continental Shelf (NES) ecosystem has favorable wind dynamics, with active development of wind energy. In this study, we present species distribution models that consider both occupancy and biomass responses for a broad spectrum of fish and macroinvertebrate taxa (n = 177). Building upon prior analyses, habitat was differentiated into overall and core habitats based on statistical distributions of habitat scores. Overall habitat was used to show each species' regional distribution based on fishery-independent survey captures between 1976 and 2019, whereas core habitat represented where the focus of the species' abundance was located as a subset of overall habitat. Wind energy developments may modify the water column in ways that impact lower-trophic-level productivity; therefore, added attention was given to the response of forage species. Over 20% of species showed preferential use of putative and potential wind development areas, including a disproportionate number of forage taxa. Principal usage varied by season, with forage species like Atlantic Menhaden Brevoortia tyrannus and Atlantic Mackerel Scomber scombrus preferentially using the lease areas in spring and Round Herring Etrumeus teres and longfin inshore squid Doryteuthis pealeii using lease areas in autumn. For species with relatively low usage of the lease areas, there was a tendency for the usage related to overall habitat to be lower than usage for core habitat; in contrast, for species with high usage of the lease areas, that usage was higher for overall habitat than for core habitat. The area of habitat tended to have positive trends across species, with these positive trends being disproportionately higher among forage taxa. These results frame the importance of wind lease areas for species in the NES, particularly forage taxa that fulfill many important ecological functions.
Beyond biogeographic patterns: Processes shaping the microbial landscape in soils and sediments along the Yangtze River
Authors: Wan Wenjie , Gadd Geoffrey M. , Gu Ji‐Dong , Liu Wenzhi , Chen Peng , Zhang Quanfa , Yang Yuyi
Published: March 2023

Deciphering biogeographic patterns of microorganisms is important for evaluating the maintenance of microbial diversity with respect to the ecosystem functions they drives. However, ecological processes shaping distribution patterns of microorganisms across large spatial‐scale watersheds remain largely unknown. Using Illumina sequencing and multiple statistical methods, we characterized distribution patterns and maintenance diversity of microorganisms (i.e., archaea, bacteria, and fungi) in soils and sediments along the Yangtze River. Distinct microbial distribution patterns were found between soils and sediments, and microbial community similarity significantly decreased with increasing geographical distance. Physicochemical properties showed a larger effect on microbial community composition than geospatial and climatic factors. Archaea and fungi displayed stronger species replacements and weaker environmental constraints in soils than that in sediments, but opposite for bacteria. Archaea, bacteria, and fungi in soils showed broader environmental breadths and stronger phylogenetic signals compared to those in sediments, suggesting stronger environmental adaptation. Stochasticity dominated community assemblies of archaea and fungi in soils and sediments, whereas determinism dominated bacterial community assembly. Our results have therefore highlighted distinct microbial distribution patterns and diversity maintenance mechanisms between soils and sediments, and emphasized important roles of species replacement, environmental adaptability, and ecological assembly processes on microbial landscape. Our findings are helpful in predicting loss of microbial diversity in the Yangtze River Basin, and might assist the establishment of environmental policies for protecting fragile watersheds.
Some recent finite volume schemes for one and two layers shallow water equations with variable density
Authors: Mohamed Kamel , Sahmim Slah , Benkhaldoun Fayssal , Abdelrahman Mahmoud A. E.
Published: March 2023

We propose a class of finite volume algorithms that are both simple and efficient for solving numerically the shallow water equations with varying densities; shallow water flows in single and two layers are considered. In these flow regimes, variable horizontal or vertical density is taken into account. The shallow water equations for the hydraulic variables are coupled with a suspended sediment transport equation for the concentration variable to construct the model. To approximate the numerical solution of the models under consideration, a generalized Rusanov method is proposed; this method avoids solving Riemann problems during the time integration process, and it is simple and accurate. The proposed method is divided into two stages: predictor and corrector; the presented finite volume approach is well balanced, conservative, and simple. Non‐oscillatory and suitable for shallow water equations when Riemann problems are challenging to solve. Several test problems for single‐layer and two‐layer shallow water flows are applied to the proposed method. The numerical results show that the proposed finite volume approach has high resolution and that it is capable of simulating shallow water equations with variable density in flow regimes with strong shocks accurately.
Agricultural contribution with respect to water challenges
Authors: Cardenas Alejandra G.
Published: March 2023

As our population continues to grow, the demand of a more efficient agriculture system heightens. We work to produce the highest yield possible to cover demands. Are we compromising our water quality for mass food production? In past years, the West Coast growers had been facing increasing struggles to farm with their allotted water often turning to groundwater use. California had to adopt measurements to regulate groundwater usage to protect the environment. The East Coast rain on the other hand faces with increasing amounts of algal blooms product of agricultural runoff derived from the consistent amount of rain received in that part of the country. Different approaches are being used to help reduce agricultural runoff like studies maintaining increased microbial activity in the soil to increase phosphorus uptake and preventing it from reaching waterways. California has passed the Sustainable Groundwater Management Act as an effort to encourage more conscious planning of water available.
Fabrication of wafer‐level double‐sided microlens array using injection compression molding
Authors: Cheng Ting‐Yu , Ke Kun‐Cheng , Yang Sen‐Yeu
Published: March 2023

Double‐sided microlens arrays (MLAs) are the key optical components of the optical component. To enhance microlens fabrication productivity, a wafer‐level, double‐sided MLA was designed and fabricated using injection compression molding (ICM). First, the Moldex3D simulation analysis results show that the design of the disc mold saves material and representation time than the multi‐cavity mold. The 4‐inch disc mold with a 4 × 4 double‐sided MLA of two inserts was used to do the study. The L9 orthogonal Taguchi method was employed to find the best combination of molding parameters. For molding experiments, 2 mold inserts with 4 × 4 convex and concave lens arrays were machined by the ultraprecision diamond turning. They were mounted into molds in one of two locations, either close to the gate or far from the gate. The molding experiment results confirmed that the ICM‐molded MLA was better than the injection molding (IM)‐molded one, with higher precision and lower residual stress. The results were similar to the simulations. The ICM molded MLA has a focal length of 2.549 mm and a spot size of 50 μm and the total deviation percentage is less than 1%. This study proves the feasibility of fabricating a wafer‐level, double‐sided MLA disc using ICM.
Prediction of gastric pH‐mediated drug exposure using physiologically‐based pharmacokinetic modeling: A case study of itraconazole
Authors: Yang Eunsol , Yu Kyung‐Sang , Lee SeungHwan
Published: March 2023

Abnormal gastric acidity, including achlorhydria, can act as a significant source of variability in orally administered drugs especially with pH‐sensitive solubility profiles, such as weak bases, potentially resulting in an undesirable therapeutic response. This study aimed to evaluate the utility of physiologically‐based pharmacokinetic (PBPK) modeling in the prediction of gastric pH‐mediated drug exposure by using itraconazole, a weak base, as a case. An itraconazole PBPK model was developed on the mechanistic basis of its absorption kinetics in a middle‐out manner from a stepwise in vitro‐in vivo extrapolation to in vivo refinement. Afterward, an independent prospective clinical study evaluating gastric pH and itraconazole pharmacokinetics (PKs) under normal gastric acidity and esomeprazole‐induced gastric hypoacidity was conducted for model validation. Validation was performed by comparing the predicted data with the clinical observations, and the valid model was subsequently applied to predict PK changes under achlorhydria. The developed itraconazole PBPK model showed reasonable reproducibility for gastric pH‐mediated exposure observed in the clinical investigation. Based on the model‐based simulations, itraconazole exposure was expected to be decreased up to 65% under achlorhydria, and furthermore, gastric pH‐mediated exposure could be mechanistically interpreted according to sequential variation in total solubility, dissolution, and absorption. This study suggested the utility of PBPK modeling in the prediction of gastric pH‐mediated exposure, especially for drugs whose absorption is susceptible to gastric pH. Our findings will serve as a leading model for further mechanistic assessment of exposure depending on gastric pH for various drugs, ultimately contributing to personalized pharmacotherapy.
Pyro‐Phototronic Effect in n‐Si/p‐MoO3−x Heterojunction: an Approach to Improve the Photoresponse of the Ultraviolet Photodetector
Authors: Bhatt Vishwa , Sahare Sanjay , Kumar Manjeet , Lee Shern-Long , Kumar Sunil , Yun Ju-Hyung
Published: March 2023

The pyro‐phototronic effect plays a crucial role in UV photodetection to enhance the overall device performance. Herein, the pyro‐phototronic effect is demonstrated for the first time in n‐Si/MoO3−x heterostructures. Vertically grown 2D‐MoO3−x microstructures are synthesized that show a centrosymmetric structure. Commonly, non‐centrosymmetric structures show a pyroelectric polarization effect; however, in the present work, authors have shown such a synergetic effect in a centrosymmetric MoO3−x‐based heterojunction. The fabricated device depicts a type I heterojunction that helps to reduce the response time and consequently minimizes charge‐carrier recombination losses. UV photodetection is measured with very low power, and significant device performances are observed under varying light intensities. The maximum responsivity and detectivity are attained up to 4.4 mA W−1 and 5.5  1010 Jones under photoelectric effects. Additionally, the maximum responsivity and detectivity are attained up to 7.82 mA W−1 and 1011 Jones under the pyro‐phototronic effect. Herein, an in‐depth understanding of the pyro‐phototronic effect in working phenomenon in type I heterojunction is provided. Such a mechanism can be explored in different heterojunctions to enhance photodetection performance in ultrafast light communications.
Quantification of follow‐up time in oncology clinical trials with a time‐to‐event endpoint: Asking the right questions
Authors: Rufibach Kaspar , Grinsted Lynda , Li Jiang , Weber Hans Jochen , Zheng Cheng , Zhou Jiangxiu
Published: March 2023

For the analysis of a time‐to‐event endpoint in a single‐arm or randomized clinical trial it is generally perceived that interpretation of a given estimate of the survival function, or the comparison between two groups, hinges on some quantification of the amount of follow‐up. Typically, a median of some loosely defined quantity is reported. However, whatever median is reported, is typically not answering the question(s) trialists actually have in terms of follow‐up quantification. In this paper, inspired by the estimand framework, we formulate a comprehensive list of relevant scientific questions that trialists have when reporting time‐to‐event data. We illustrate how these questions should be answered, and that reference to an unclearly defined follow‐up quantity is not needed at all. In drug development, key decisions are made based on randomized controlled trials, and we therefore also discuss relevant scientific questions not only when looking at a time‐to‐event endpoint in one group, but also for comparisons. We find that different thinking about some of the relevant scientific questions around follow‐up is required depending on whether a proportional hazards assumption can be made or other patterns of survival functions are anticipated, for example, delayed separation, crossing survival functions, or the potential for cure. We conclude the paper with practical recommendations.
Neuroadaptive tracking control for uncertain pure‐feedback systems under dynamic constraints
Authors: Cheng Hong , Song Yongduan
Published: March 2023

This paper presents a neuroadaptive tracking control method for a class of pure‐feedback nonlinear systems in the presence of dynamic constraints and unmodeled dynamics simultaneously. By introducing a nonlinear mapping (NM), the tracking control problem for constrained pure‐feedback system is recast into a regulation problem of the converted system without constraints. Such transformation allows the states to be confined within given regions directly, this is in contrast to the commonly used Barrier Lyapunov Function method that relies on the upper bound of the virtual control errors. To handle the unmodeled dynamics in the system, a dynamic compensation signal is introduced. It is shown that in the proposed scheme the neural networks (NN) not only act as a universal approximator to deal with unknown nonlinearity, but also function as a decoupler to cope with the coupling effects between state and the new variable arising from the introduction of the NM and the backstepping design. Simulation results also confirm the effectiveness of the proposed method.
Spaceborne LiDAR for characterizing forest structure across scales in the European Alps
Authors: Mandl Lisa , Stritih Ana , Seidl Rupert , Ginzler Christian , Senf Cornelius
Published: March 2023

The launch of NASA's Global Ecosystem Dynamics Investigation (GEDI) mission in 2018 opens new opportunities to quantitatively describe forest ecosystems across large scales. While GEDI's height‐related metrics have already been extensively evaluated, the utility of GEDI for assessing the full spectrum of structural variability—particularly in topographically complex terrain—remains incompletely understood. Here, we quantified GEDI's potential to estimate forest structure in mountain landscapes at the plot and landscape level, with a focus on variables of high relevance in ecological applications. We compared five GEDI metrics including relative height percentiles, plant area index, cover and understory cover to airborne laser scanning (ALS) data in two contrasting mountain landscapes in the European Alps. At the plot level, we investigated the impact of leaf phenology and topography on GEDI's accuracy. At the landscape‐scale, we evaluated the ability of GEDIs sample‐based approach to characterize complex mountain landscapes by comparing it to wall‐to‐wall ALS estimates and evaluated the capacity of GEDI to quantify important indicators of ecosystem functions and services (i.e., avalanche protection, habitat provision, carbon storage). Our results revealed only weak to moderate agreement between GEDI and ALS at the plot level (R2 from 0.03 to 0.61), with GEDI uncertainties increasing with slope. At the landscape‐level, however, the agreement between GEDI and ALS was generally high, with R2 values ranging between 0.51 and 0.79. Both GEDI and ALS agreed in identifying areas of high avalanche protection, habitat provision, and carbon storage, highlighting the potential of GEDI for landscape‐scale analyses in the context of ecosystem dynamics and management.
Human activities rather than climate dominated the grassland net primary production in the three basins of the Hexi Corridor, North‐Western China
Authors: Wang Yutao , Dou Tianbao
Published: March 2023

Actual net primary production (ANPP) is affected by both natural conditions and human activities in many areas, while the contributions of these factors to NPP remain unknown because it is difficult to isolate their effects. This knowledge gap hinders our implementation of environmental protection and restoration. In this study, we selected three basins of the Hexi Corridor, North‐western China, as the study area. Based on the monthly growth of grassland and field observations, we identified the undisturbed grids and then calculated the potential net primary productivity (PNPP) of these grids. Using the Carnegie‐Ames‐Stanford‐Approach (CASA) model, we calculated the ANPP in these areas. The influence of human activities on NPP (HNPP) was then calculated as the difference between ANPP and PNPP. The results showed that from 2001 to 2017, the mean grassland HNPP was −236.25 gC m−2 a−1. The area with a relative contribution index (RCI) of human activity greater than 0.5 accounted for more than 50% of the total, indicating that human activities were a dominant factor in the NPP change. After the implementation of ecological governance projects in the Hexi Corridor in 2006, HNPP exhibited a negative weakening rate of 2.79 gC m−2 a−1 (p < 0.05), and the RCI decreased from 0.708 at the beginning of the study period to 0.522 at the end (p < 0.01), indicating that reducing human interference with nature was an effective measure for ecological restoration. Based on these findings, we concluded that the changes in NPP in the three basins of the Hexi Corridor was dominated by human activities. Our results suggest that future studies pertaining to the response of NPP to climate change should consider the impact of human activities in semi‐arid regions.
High‐Activity Fe3C as pH‐Universal Electrocatalyst for Boosting Oxygen Reduction Reaction and Zinc‐Air Battery
Authors: Ruan Qi‐Dong , Feng Rui , Feng Jiu‐Ju , Gao Yi‐Jing , Zhang Lu , Wang Ai‐Jun
Published: March 2023

Transition metal catalysts are regarded as one of promising alternatives to replace traditional Pt‐based catalysts for oxygen reduction reaction (ORR). In this work, an efficient ORR catalyst is synthesized by confining Fe3C nanoparticles into N, S co‐doped porous carbon nanosheets (Fe3C/N,S‐CNS) via high‐temperature pyrolysis, in which 5‐sulfosalicylic acid (SSA) demonstrates as an ideal complexing agent for iron (ΙΙΙ) acetylacetonate while g‐C3N4 behaves as a nitrogen source. The influence of the pyrolysis temperature on the ORR performance is strictly examined in the controlled experiments. The obtained catalyst exhibits excellent ORR performance (E1/2 = 0.86 V; Eonset = 0.98 V) in alkaline electrolyte, coupled by exhibiting the superior catalytic activity and stability (E1/2 = 0.83 V, Eonset = 0.95 V) to Pt/C in acidic media. In parallel, its ORR mechanism is carefully illustrated by the density functional theory (DFT) calculations, especially the role of the incorporated Fe3C played in the catalytic process. The catalyst‐assembled Zn‐air battery also exhibits a much higher power density (163 mW cm–2) and ultralong cyclic stability in the charge–discharge test for 750 h with a gap increase down to 20 mV. This study provides some constructive insights for preparation of advanced ORR catalysts in green energy conversion units correlated systems.
Moisture‐Adaptive Contractile Biopolymer‐Derived Fibers for Wound Healing Promotion
Authors: Dong Lizhong , Zhang Wei , Ren Ming , Li Yuxuan , Wang Yulian , Zhou Yurong , Wu Yulong , Zhang Zhijun , Di Jiangtao
Published: March 2023

The advancement in thermosensitive active hydrogels has opened promising opportunities to dynamic full‐thickness skin wound healing. However, conventional hydrogels lack breathability to avoid wound infection and cannot adapt to wounds with different shapes due to the isotropic contraction. Herein, a moisture‐adaptive fiber that rapidly absorbs wound tissue fluid and produces a large lengthwise contractile force during the drying process is reported. The incorporation of hydroxyl‐rich silica nanoparticles in the sodium alginate/gelatin composite fiber greatly improves the hydrophilicity, toughness, and axial contraction performance of the fiber. This fiber exhibits a dynamic contractile behavior as a function of humidity, generating ≈15% maximum contraction strain or ≈24 MPa maximum isometric contractile stress. The textile knitted by the fibers features excellent breathability and generates adaptive contraction in the target direction during the natural desorption of tissue fluid from the wounds. In vivo animal experiments further demonstrate the advantages of the textiles over traditional dressings in accelerating wound healing.
Peripheral cord insertion is associated with adverse pregnancy outcome only when accompanied by clinically significant placental pathology
Authors: Stapleton D. , Darmonkow A. , Ravi Chandran A. , Milligan N. , Saghian R. , Shinar S. , Whitehead C. L. , Hobson S. R. , Serghides L. , Macgowan C. K. , Sled J. G. , Kingdom J. C. , Baschat A. A. , Parks W. T. , Cahill L. S.
Published: March 2023

Objective

To examine the relationship between umbilical cord insertion site, placental pathology and adverse pregnancy outcome in a cohort of normal and complicated pregnancies.

Methods

Sonographic measurement of the cord insertion and detailed placental pathology were performed in 309 participants. Associations between cord insertion site, placental pathology and adverse pregnancy outcome (pre‐eclampsia, preterm birth, small‐for‐gestational age) were examined.

Results

A total of 93 (30%) participants were identified by pathological examination to have a peripheral cord insertion site. Only 41 of the 93 (44%) peripheral cords were detected by prenatal ultrasound. Peripherally inserted cords were associated significantly (P < 0.0001) with diagnostic placental pathology (most commonly with maternal vascular malperfusion (MVM)); of which 85% had an adverse pregnancy outcome. In cases of isolated peripheral cords, without placental pathology, the incidence of adverse outcome was not statistically different when compared to those with central cord insertion and no placental pathology (31% vs 18%; P = 0.3). A peripheral cord with an abnormal umbilical artery (UA) pulsatility index (PI) corresponded to an adverse outcome in 96% of cases compared to 29% when the UA‐PI was normal.

Conclusions

This study demonstrates that peripheral cord insertion is often part of the spectrum of findings of MVM disease and is associated with adverse pregnancy outcome. However, adverse outcome was uncommon when there was an isolated peripheral cord insertion and no placental pathology. Therefore, additional sonographic and biochemical features of MVM should be sought when a peripheral cord is observed. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Effect of type of polymerization catalyst system on the degradation and stabilization of polyethylenes in the melt state—Part 4: Comparative antioxidant effectiveness on organoleptic extractables
Authors: Allen Norman S. , del Teso Sánchez Karmele , Edge Michele , Liauw Christopher M. , Hussain Sajid , Hall Keith
Published: March 2023

Several polyethylene resins using Ziegler, metallocene, and Phillips catalyst technologies were examined to obtain more detailed information about the effect of different polymerization catalyst systems on the production of extractable thermo‐oxidative degradation products formed during melt processing cycles. This produces volatile organoleptic components (VOCs and extractable) such as hydrocarbons, alcohols, aldehydes, ketones, and carboxylic acids. Although some of the oxidation products are in‐chain bound, many are produced as free, easily extractable entities or volatile components. The purpose of this study is to identify the nature of the products by gas chromatography–mass spectrometry (GC–MS) and FTIR analysis. The identity of the VOCs formed is necessary to modify the product's quality or establish which are toxic and/or leachable with food products. The results show that the evolution of carbonyl products, nature, and quantity is influenced significantly by the polymer type and catalyst used. Over 300 organoleptics low molar mass degradation products, such as alkane, alkene, carbonyl, and alcohol functionalities were detected by GC–MS analysis coupled with FTIR analysis on hexane extractables. Certain stabilizers can control the generation of certain functionalities and inhibit others. Of importance was the discovery of the relationship between additive activity and structure and inhibition of the formation of specific types of oxidation functionalities to a particular catalyst system.
Application of sustainable treatments to fiber surface for performance improvement of elastomeric polyurethane reinforced with basalt fiber
Authors: Tayfun Ümit
Published: March 2023

In order to overcome compatibility leakage between composite phases, which is a significant challenge in multidimensional composite applications, it is crucial to optimize the chemical nature of additives. The surface of basalt fiber (BF) was chemically enriched via biobased epoxy resin sizing and functional silanization process to improve its interfacial adhesion to the ecograde elastomeric polyurethane (EPU) matrix. The surface properties of BF were examined with the help of scanning electron microscopy X‐ray spectroscopy (SEM/EDX) and Fourier‐transformed infrared spectroscopy (FTIR) analyses. Impacts of surface modifications were compared based on mechanical, morphological, thermomechanical, and melt‐flow behaviors of composites involving pristine and modified BF. Findings revealed that surface‐modified BF inclusions improved the tensile strength and Shore‐hardness values of composites. Tensile strength of EPU raised from 27.1 to 37.1 MPa after compounding with epoxy‐sized BF. Additionally, the resin‐coated BF incorporation exhibited a two‐fold increase in the tensile modulus of EPU. Thermomechanical response of EPU exhibited an increasing trend by BF inclusions regardless of treatment type. Glass transition temperature of EPU shifted to 5 units higher value with modified BF loadings. SEM investigations confirmed the increased interfacial interaction between the EPU matrix and surface‐sized BF. The chemically enriched surface of BF improves composite performance by improving adhesion at the EPU‐BF interface. The results of this study confirmed that enhanced interfacial adhesion led to performance improvements for BF‐loaded EPU composites.
The emergence of delta shock in the limit process for two‐dimensional steady nonisentropic relativistic Euler flow onto a straight wedge
Authors: Cheng Jie , Chen Fangqi , Wang Zejun
Published: March 2023

In this paper, we mainly study the limit of solutions to the two‐dimensional steady nonisentropic relativistic Euler flow onto a straight wedge. It turns out that the sequence of shock solutions tends to a delta wave adhering to the wedge surface when the velocity of the incident flow goes to the speed of light and the adiabatic index tends to 1 in turn. Meanwhile, it also verifies that the pressure coefficient in the limit case is consistent with the Newtonian sin‐squared law when the speed of light tends to infinity. To this end, we also derive the generalized Bernoulli equation, Taub adiabat (or the generalized Hugoniot adiabat) and a shock polar, and so forth. Furthermore, we give the construction of the delta wave by the definition of weak solution.