bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary excretion profile of prednisolone and prednisone after rectal administration: Significance in antidoping analysis
Authors: Iannella Loredana , Comunità Fabio , Botrè Francesco , Colamonici Cristiana , Curcio Davide , de la Torre Xavier , Mazzarino Monica
Published: August 2022

The rectal administration of glucocorticoids, as well as any injectable, and oral ones, is currently prohibited by the World Anti‐Doping Agency when occurs “in competition.” A reporting level of 100 ng/ml for prednisolone and 300 ng/ml for prednisone was established to discriminate the allowed and the prohibited administration. Here, the urinary excretion profiles of prednisone and prednisolone were evaluated in five volunteers in therapy with glucocorticoid‐based rectal formulations containing prednisone or prednisolone caproate. The urinary levels of the excreted target compounds were determined by liquid chromatography–tandem mass spectrometry (LC‐MS/MS) following the procedure validated and currently in use in our laboratory to detect and quantitate glucocorticoids in urine. Predictably, the excretion trend of the analytes of interest were generally comparable with those obtained after oral administration, even if the excretion profile showed a broad interindividual variability, with the absorption rate and the systemic bioavailability after rectal administration being strongly influenced by the type of formulations (suppository or rectal cream, in our case) as well as the physiological conditions of the absorption area. Results showed that the target compounds were detectable for at least 30 h after drug administration. After suppository administration, prednisolone levels reached the maximum after 3 h from drug administration and then dropped below the reporting level after 15–21 h; prednisone reached the maximum after 3 h from drug administration, and then dropped below the reporting level after 12–15 h. After cream administration, both prednisone and prednisolone levels remained in a concentration below the reporting level throughout the entire monitored period.
Spatial and temporal processing difficulties in Chinese children with developmental dyslexia: An ERP study
Authors: Meng Ze‐Long , Liu Meng‐Lian , Bi Hong‐Yan
Published: August 2022

Magnocellular (M) deficit theory indicates that individuals with developmental dyslexia (DD) have low sensitivity to stimuli with high temporal frequencies (HTF) and low spatial frequencies (LSF). However, some studies found that temporal processing and spatial processing were correlated with different reading‐related skills. Chinese is a logographic language, and visual skills are particularly important for reading in Chinese. It is necessary to investigate the temporal and spatial processing abilities in the M pathway of Chinese children with DD. Using electrophysiological recordings, the present study examined the mean amplitude and latency of P1 during a grating direction judgment task in 13 children with DD and 13 age‐matched normal children. Dyslexic children showed a low amplitude and long latency of P1 in the HTF condition and LSF condition compared with age‐matched children. In the HTF condition, the amplitude of P1 correlated with phonological awareness, and the latency of P1 correlated with reading fluency and rapid naming of digits. The amplitude of P1 in the LSF condition correlated with reading accuracy. This result suggested that Chinese children with DD had difficulties in both temporal and spatial processing in the M pathway. However, temporal processing and spatial processing played different roles in Chinese reading.
Disease and weather induce rapid shifts in a rangeland ecosystem mediated by a keystone species (Cynomys ludovicianus)
Authors: Duchardt Courtney J. , Augustine David J. , Porensky Lauren M. , Beck Jeffrey L. , Hennig Jacob D. , Pellatz David W. , Scasta J. Derek , Connell Lauren C. , Davidson Ana D.
Published: August 2022

Habitat loss and changing climate have direct impacts on native species but can also interact with disease pathogens to influence wildlife communities. In the North American Great Plains, black‐tailed prairie dogs (Cynomys ludovicianus) are a keystone species that create important grassland habitat for numerous species and serve as prey for predators, but lethal control driven by agricultural conflict has severely reduced their abundance. Novel disease dynamics caused by epizootic plague (Yersinia pestis) within prairie dog colonies have further reduced prairie dog abundances, in turn destabilizing associated wildlife communities. We capitalized on a natural experiment, collecting data on prairie dog distributions, vegetation structure, avian abundance, and mesocarnivore and ungulate occupancy before (2015–2017) and after (2018–2019) a plague event in northeastern Wyoming, USA. Plague decimated black‐tailed prairie dog populations in what was then the largest extant colony complex, reducing colony cover in the focal area from more than 10,000 ha to less than 50 ha. We documented dramatic declines in mesocarnivore occupancy and raptor abundance post‐plague, with probability of occupancy or abundance approaching zero in species that rely on prairie dogs for a high proportion of their diet (e.g., ferruginous hawk [Buteo regalis], American badger [Taxidea taxus], and swift fox [Vulpes velox]). Following the plague outbreak, abnormally high precipitation in 2018 hastened vegetation recovery from prairie dog disturbance on colonies in which constant herbivory had formerly maintained shortgrass structure necessary for certain colony‐associates. As a result, we observed large shifts in avian communities on former prairie dog colonies, including near‐disappearance of mountain plovers (Charadrius montanus) and increases in mid‐grass associated songbirds (e.g., lark bunting [Calamospiza melanocorys]). Our research highlights how precipitation can interact with disease‐induced loss of a keystone species to induce drastic and rapid shifts in wildlife communities. Although grassland taxa have co‐evolved with high spatiotemporal variation, fragmentation of the remaining North American rangelands paired with higher‐than‐historical variability in climate and disease dynamics are likely to destabilize these systems in the future.
A retrospective cohort study examining health care utilization patterns in individuals diagnosed with an eating disorder in childhood and/or adolescence
Authors: Couturier Jennifer , Gayowsky Anastasia , Findlay Sheri , Webb Cheryl , Sami Sadaf , Chan Anthony K. C. , Chanchlani Rahul , Kurdyak Paul
Published: August 2022

Objective

This study examined a 2‐year period following an eating disorder (ED) diagnosis in order to determine patterns of health care utilization.

Method

We conducted a retrospective cohort study of children (n = 1560) diagnosed with an ED between 2000 and 2017. The ED diagnosis was made at a tertiary level hospital for children and adolescents presenting for outpatient assessment by specialist adolescent medicine physicians and recorded in a program database over this period of time. We then created three sex‐ and age‐matched comparison cohorts using provincial health administrative databases including: a general population cohort, a diabetes cohort (to compare nonmental health care utilization) and a mood disorder cohort (to compare mental health care utilization). Outcomes included hospitalizations, emergency department visits, as well as general practitioner, psychiatrist, and pediatrician visits. Odds ratios (dichotomous outcomes) and rate ratios (continuous outcomes) were calculated.

Results

Compared to the general population cohort, the ED cohort had higher odds and rates of all types of health care utilization. Compared to the diabetes cohort, the ED cohort had higher odds of nonmental health‐related admissions (OR 1.45, 95% CI 1.09–1.95) and higher rates of nonmental health‐related emergency department visits (RR 1.59, 95% CI 1.18–2.13). Compared to the mood disorder cohort, the ED cohort had higher rates of pediatrician visits, which were mental health‐related (RR 14.88, 95% CI 10.64–20.82), however most other types of mental health service utilization were lower.

Discussion

These patterns indicate that the service needs of young people diagnosed with EDs are higher than those with diabetes with respect to nonmental health admissions and emergency department visits, while in terms of mental health service utilization, there appears to be a lack of use of mental health services compared to youth with mood disorders with the exception of pediatrician mental health visits. These findings must be interpreted in the context of under‐detection and under‐treatment of EDs.

Public Significance Statement

Our study found that the health service needs of young people with EDs are higher than those with diabetes with respect to admissions and emergency department visits, while there appears to be a lack of use of mental health services compared to youth with mood disorders with the exception of pediatrician mental health visits.
Rapid elevational shifts of Switzerland's avifauna and associated species traits
Authors: Hallman Tyler A. , Guélat Jérôme , Antoniazza Sylvain , Kéry Marc , Sattler Thomas
Published: August 2022

Global change in climate and land use has profound effects on species' geographic and elevational distributions. In European birds, while species are predicted to track their climatic niches upslope, lowland agricultural intensification and high‐elevation land abandonment can drive elevational shifts. Species traits that can predict response to change in climate and land use can inform conservation, but a thorough examination of their relationships with elevational shifts in European birds is lacking. We estimate the change in the elevational distributions of 71 species from 1996 to 2016 in a region of the western Palearctic with wide elevational gradients (approximately 3000 m) and large changes in temperature. We model the relationships between elevational shifts and species traits associated with resource preference and adaptive capacity at five reference points including the cool edge, warm edge, and the core of species' elevational distributions. When intermediate reference points were removed, changes to the results were negligible, indicating that three reference points are likely sufficient. We found significant upslope and downslope shifts in 56% and 23% of our study species, respectively. Asymmetric rates of shifts in the cool and warm edges caused significant contractions in elevational extent in 30% of our study species. The effect of elevational preference (i.e., midpoint elevation) was habitat dependent. Movement in alpine birds was unidirectionally upslope, with nearly half displaying significant or apparent elevational range contractions. In woodland birds, asymmetries of shifts in reference points led to expansions in extent in low‐elevation species and contractions in high‐elevation species. Generally, migrants, species with smaller mass, smaller relative brain size, smaller hand‐wing index, and generalists in diet, habitat, and elevation had greater upslope shifts. While elevational shifts in European birds were heterogenous and species‐specific, many were rapid, and species traits associated with resource preference and adaptive capacity were associated with common patterns of elevation.
Sacubitril/valsartan in heart failure: efficacy and safety in and outside clinical trials
Authors: Abdin Amr , Schulz Martin , Riemer Uwe , Hadëri Bledar , Wachter Rolf , Laufs Ulrich , Bauersachs Johann , Kindermann Ingrid , Vukadinović Davor , Böhm Michael
Published: August 2022

Heart failure (HF) treatment has changed substantially over the last 30 years, leading to significant reductions in mortality and hospital admissions in patients with HF with reduced ejection fraction (HFrEF). Currently, the optimization of guideline‐directed chronic HF therapy remains the mainstay to further improve quality of life, mortality, and HF hospitalizations for patients with HFrEF. The angiotensin receptor‐neprilysin inhibitor sacubitril/valsartan (S/V) has an important role in the treatment of patients with HFrEF. The PARADIGM‐HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) randomized controlled trial has established solid evidence for the treatment of HFrEF in various subgroups. Apart from HFrEF, several studies have been conducted using S/V in various indications: patients hospitalized with acute decompensated HF, HF with preserved ejection fraction, acute myocardial infarction with reduced ejection fraction, uncontrolled and resistant hypertension, and chronic kidney disease. Data from the German Institute for Drug Use Evaluation reveal that implementation of S/V has increased steadily over time and, by the end of 2021, an estimated 266 000 patients were treated with S/V in Germany. The estimated cumulative real‐world patient exposure is >5.5 million patient‐treatment years worldwide. The number of patients treated with S/V largely exceeds the number of patients treated in clinical trials, and the current indication for S/V is larger than the strict inclusion/exclusion criteria of the randomized trials. Especially elderly patients, women, and patients with more and more severe comorbidities are underrepresented in the clinical trials. We therefore aimed to summarize the importance of S/V in HF in terms of efficacy and safety in clinical trials and daily clinical practice.
Low‐gradient magnetic separation of magnetic nanoparticles under continuous flow: Experimental study, transport mechanism and mathematical modelling
Authors: Tan Yee Win , Leong Sim Siong , Lim JitKang , Yeoh Wei Ming , Toh Pey Yi
Published: August 2022

Low‐gradient magnetic separation (LGMS) of magnetic nanoparticles (MNPs) has been proven as one of the techniques with great potential for biomedical and environmental applications. Recently, the underlying principle of particle capture by LGMS, through a process known as magnetophoresis, under the influence of hydrodynamic effect has been widely studied and illustrated. Even though the hydrodynamic effect is very substantial for batch processes, its impact on LGMS operated at continuous flow (CF) condition remained largely unknown. Hence, in this study, the dynamical behaviour of LGMS process operated under CF was being studied. First, the LGMS experiments using poly(sodium 4‐styrenesulfonate)‐functionalized‐MNP as modelled particle system were performed through batchwise (BW) and CF modes at different operating conditions. Here BW operation was used as a comparative study to elucidate the transport mechanism of MNP under the similar environment of CF‐LGMS process, and it was found out that the convection induced by magnetophoresis (timescale effective is ∼1200 s) is only significant at far‐from‐magnet region. Hence, it can be deduced that forced convection is more dominant on influencing the transport behaviour of CF‐LGMS (with resident time ≤240 s). Moreover, we found that the separation efficiency of CF‐LGMS process can be boosted by the higher number of magnets, the higher MNP concentration and the lower flowrate of MNP solution. To better illustrate the underlying dynamical behaviour of LGMS process, a mathematical model was developed to predict its kinetic profile and separation efficiency (with average error of ∼2.6% compared to the experimental results).
High‐entropy oxide: A future anode contender for lithium‐ion battery
Authors: Liu Xuefeng , Li Xuke , Li Yage , Zhang Haijun , Jia Quanli , Zhang Shaowei , Lei Wen
Published: August 2022

Revolutionary changes in energy storage technology have put forward higher requirements on next‐generation anode materials for lithium‐ion battery. Recently, a new class of materials with complex stoichiometric ratios, high‐entropy oxide (HEO), has gradually emerging into sight and embracing the prosperity. The ideal elemental adjustability and attractive synergistic effect make HEO promising to break through the integrated performance bottleneck of conventional anodes and provide new impetus for the design and development of electrochemical energy storage materials. Here, the research progress of HEO anodes is comprehensively reviewed. The driving force behind phase stability, the role of individual cations, potential mechanisms for controlling properties, as well as state‐of‐the‐art synthetic strategies and modification approaches are critically evaluated. Finally, we envision the future prospects and related challenges in this field, which will bring some enlightening guidance and criteria for researchers to further unlock the mysteries of HEO anodes.

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Optimization of synthesis parameters for molybdenum diselenide using hydrothermal method
Authors: Khichi Pardeep , Tripathi Rahul , Ohlan Anil
Published: August 2022

Transition metal dichalcogenides (MoSe2) have attracted significant attention because of their potential use for hydrogen evolution reactions and in other electronic and optoelectronic applications. However, the synthesis of layered MoSe2 through the hydrothermal route itself is an arduous task. Herein, we have observed that the selenium does not get easily dissolved during synthesis in water and ethanol. However, the same seems to partially dissolve in a solution containing sodium borohydride and hydrazine monohydrate. This complication leads to unreacted selenium in the reaction product, as confirmed by the X‐ray diffraction data. In the available literature, the authors have reported washing of as‐obtained Se‐rich MoSe2 with ethanol, acids and some have utilized annealing to remove unreacted selenium. However, we have adopted another method of removing the excess unreacted selenium powder from the synthesized product, thereby obtaining MoSe2. In addition, the reaction parameters such as temperature, duration of hydrothermal reaction and precursor are optimized.
Effects of Metformin and its Metabolite Guanylurea on Fathead Minnow (Pimephales promelas) Reproduction
Authors: Blackwell Brett R. , Ankley Gerald T. , Biales Adam D. , Cavallin Jenna E. , Cole Alexander R. , Collette Timothy W. , Ekman Drew R. , Hofer Rachel N. , Huang Weichun , Jensen Kathleen M. , Kahl Michael D. , Kittelson Ashley R. , Romano Shannon N. , See Mary Jean , Teng Quincy , Tilton Charlene B. , Villeneuve Daniel L.
Published: August 2022

Metformin, along with its biotransformation product guanylurea, is commonly observed in municipal wastewaters and subsequent surface waters. Previous studies in fish have identified metformin as a potential endocrine-active compound, but there are inconsistencies with regard to its effects. To further investigate the potential reproductive toxicity of metformin and guanylurea to fish, a series of experiments was performed with adult fathead minnows (Pimephales promelas). First, explants of fathead minnow ovary tissue were exposed to 0.001–100 µM metformin or guanylurea to investigate whether the compounds could directly perturb steroidogenesis. Second, spawning pairs of fathead minnows were exposed to metformin (0.41, 4.1, and 41 µg/L) or guanylurea (1.0, 10, and 100 µg/L) for 23 days to assess impacts on reproduction. Lastly, male fathead minnows were exposed to 41 µg/L metformin, 100 µg/L guanylurea, or a mixture of both compounds, with samples collected over a 96-h time course to investigate potential impacts to the hepatic transcriptome or metabolome. Neither metformin nor guanylurea affected steroid production by ovary tissue exposed ex vivo. In the 23 days of exposure, neither compound significantly impacted transcription of endocrine-related genes in male liver or gonad, circulating steroid concentrations in either sex, or fecundity of spawning pairs. In the 96-h time course, 100 µg guanylurea/L elicited more differentially expressed genes than 41 µg metformin/L and showed the greatest impacts at 96 h. Hepatic transcriptome and metabolome changes were chemical- and time-dependent, with the largest impact on the metabolome observed at 23 days of exposure to 100 µg guanylurea/L. Overall, metformin and guanylurea did not elicit effects consistent with reproductive toxicity in adult fathead minnows at environmentally relevant concentrations. Environ Toxicol Chem 2022;41:2708–2720. © 2022 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Predicting the Accumulation of Ionizable Pharmaceuticals and Personal Care Products in Aquatic and Terrestrial Organisms
Authors: Carter Laura J. , Armitage James M. , Brooks Bryan W. , Nichols John W. , Trapp Stefan
Published: August 2022

The extent to which chemicals bioaccumulate in aquatic and terrestrial organisms represents a fundamental consideration for chemicals management efforts intended to protect public health and the environment from pollution and waste. Many chemicals, including most pharmaceuticals and personal care products (PPCPs), are ionizable across environmentally relevant pH gradients, which can affect their fate in aquatic and terrestrial systems. Existing mathematical models describe the accumulation of neutral organic chemicals and weak acids and bases in both fish and plants. Further model development is hampered, however, by a lack of mechanistic insights for PPCPs that are predominantly or permanently ionized. Targeted experiments across environmentally realistic conditions are needed to address the following questions: (1) What are the partitioning and sorption behaviors of strongly ionizing chemicals among species? (2) How does membrane permeability of ions influence bioaccumulation of PPCPs? (3) To what extent are salts and associated complexes with PPCPs influencing bioaccumulation? (4) How do biotransformation and other elimination processes vary within and among species? (5) Are bioaccumulation modeling efforts currently focused on chemicals and species with key data gaps and risk profiles? Answering these questions promises to address key sources of uncertainty for bioaccumulation modeling of ionizable PPCPs and related contaminants. Environ Toxicol Chem 2024;43:502–512. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Optimization of ultrasound‐assisted extraction method for phytochemical compounds and antioxidant activities of sour jujube extracts
Authors: Wang Yanyan , Zhao Wan , Li Yixiang , Zhao Hang , Ye Xiaonan , Li Tingli , Wang Zhibin , Huang Lili
Published: August 2022

Ultrasonic‐assisted extraction is a rapid and effective extraction method that uses ultrasound energy and solvents to extract target compounds from various plant matrices. In this study, the ultrasonic‐assisted extraction conditions of sour jujube were optimized. A five‐level central composite design (CCD) with four variables was used to evaluate ultrasonic treatment variables influencing the total saponin content (TSC), total flavonoid content (TFC), and total phenolic content (TPC) extracted from sour jujube. The solvent concentration, extraction time, ultrasonic power, and solid‐to‐liquid (S/L) ratio were optimized using aqueous ethanol and methanol solutions as extraction solvents. A central composite design (CCD) was used for an in‐depth study, and then the optimal value that could produce the maximum TPC, TFC, TSC, and four in vitro antioxidant activities (scavenging activity of hydroxyl free radicals, ferric‐reducing antioxidant power (FRAP), phosphomolybdic acid reduction method, and 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical‐scavenging activity) was determined. Hydrogen peroxide‐induced oxidative stress experiment confirmed that the Jujube extract could have an antioxidant role in vivo. The relationship between the contents of three compounds and the antioxidant activity in vitro and in vivo was further studied. The results showed that optimizing methanol and ethanol extraction process parameters could improve target components’ extraction efficiency. Under the optimum conditions, the TFC and TPC yields of sour jujube by ethanol are better than methanol, while the yield of TSC by methanol is better than ethanol. In vivo data showed that Jujube extract protects against the adverse effects of oxidative stress and improves the life span of female and male Drosophila. This study provides a valuable reference for the full use of Ziziphus jujube, as well as a new direction in food development.
Therapeutic application of carvacrol: A comprehensive review
Authors: Imran Muhammad , Aslam Mahwish , Alsagaby Suliman A. , Saeed Farhan , Ahmad Ishtiaque , Afzaal Muhamamd , Arshad Muhammad Umair , Abdelgawad Mohamed A. , El‐Ghorab Ahmed H. , Khames Ahmed , Shariati Mohammad Ali , Ahmad Arslan , Hussain Muzamal , Imran Ali , Islam Saiful
Published: August 2022

Carvacrol is a major natural constituent and is significantly present as an essential oil in aromatic plants and is well known for its numerous biological activities. Therapeutic properties of carvacrol have been demonstrated as anti‐oxidant, anticancer, diabetes prevention, cardioprotective, anti‐obesity, hepatoprotective and reproductive role, antiaging, antimicrobial, and immunomodulatory properties. The carvacrol biosynthesis has been mediated through mevalonate pathway. Carvacrol has the anticancer ability against malignant cells via decreasing the expressions of matrix metalloprotease 2 and 9, inducing apoptosis, enhancing the expression of pro‐apoptotic proteins, disrupting mitochondrial membrane, suppressing extracellular signal‐regulated kinase 1/2 mitogen‐activated protein kinase signal transduction, and also decreasing the phosphoinositide 3‐kinase/protein kinase B. It also decreased the concentrations of alanine aminotransferase, alkaline phosphatase and aspartate aminotransferase, and gamma‐glutamyl transpeptidase as well as also restored liver function, insulin level, and plasma glucose level. Carvacrol also has been found to exert antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Coagulase‐negative staphylococcus, Salmonella spp., Enterococcus sp. Shigella, and Escherichia coli. The current review article summarizes the health‐promoting perspectives of carvacrol through various pathways.
Depressurization and heat transfer during leakage of supercritical CO2 from a pipeline
Authors: Chen Lei , Yan Xingqing , Hu Yanwei , Yang Kai , Yu Shuai , Yu Jianliang , Chen Shaoyun
Published: August 2022

The carbon capture, utilization and storage (CCUS) technology can effectively improve global climate change. Extensive pipelines are used in CCUS to transport large amounts of pure and impure supercritical CO2(S‐CO2) from captured sites to storage, owing to pipelines being an economical and efficient means of transportation. In the event of an accidental rupture of a supercritical CO2 pipeline, causing substantial economic losses and catastrophic consequences to surroundings. Hence, it is necessary that the study of the pressure variation and temperature distribution of CO2 during pipeline blowdown contributes to understanding fracture initiation and propagation, as well as designing reliable pipelines. A laboratory‐scale setup is used to investigate the evolution of leakage behaviours and analyze heat transfer of pure and impure supercritical CO2 with different release orifices. The depressurization process, variation of inner and wall of pipeline temperature were measured. Results show that the larger is the leakage orifice, the lower is the minimum temperature of the inner pipeline. The larger is the concentrations of nitrogen (N2) in supercritical CO2 mixture, the lower is the minimum temperature of the inner pipeline, and the higher is the risk of pipeline brittle fracture. During the entire release process, the Nusselt number (Nu) was determined based on measurements to discuss the process of heat transfer between the CO2 mixture and pipeline wall. © 2022 Society of Chemical Industry and John Wiley & Sons, Ltd.
Petrogenetic evolution of Lichi volcanics from Arunachal Himalaya, Northeast India: Insights from geochemical modelling
Authors: Sharma Neeta Moni , Phukon Purbajyoti , Bhattacharyya Pramathesh
Published: August 2022

The Lichi volcanic rocks crop out along the Main Boundary Thrust (MBT) of the Arunachal Himalaya, northeast India are comprised primarily of sub‐alkaline basalt (SiO2 ranges from 48.66 to 50.62 wt%), with minor trachy‐andesite (SiO2 ranges from 57% to 61.42 wt%). The distribution of incompatible trace elements, low concentrations of large‐ion lithophile elements, and REE behaviour suggests an enriched nature of the studied rocks and limited influence of the crustal contamination during their evolution. Linear distribution trends of major oxide, consistent patterns of trace elements, and REEs on primitive mantle‐ and chondrite‐normalized diagrams suggest the cogenetic nature of mafic basaltic rocks and intermediate trachy‐andesite. The variation in Ti/Y (256.00–469.95) and Zr/Y (7.65–36.96) ratios indicates that garnet was present in the source. The well‐defined geochemical trends on variation diagram and the sub‐parallel trends on the chondrite‐normalized REE patterns suggest that fractional crystallization processes have played a major role in the evolution of parental magma. Petrogenetic modelling implies that the sub‐alkaline basalts and intermediate rocks were derived from low‐degree partial melting (1%–5%) of a garnet bearing peridotite source. The melt further evolved by fractional crystallization. We conclude that the geochemical attributes of the Lichi volcanics of the Arunachal Himalaya imply their emplacement in a continental extensional regime and possibly resulted from the Cretaceous Kerguelen plume activities.
Needs assessment in head and neck surgical oncology training: A qualitative study of expert opinions
Authors: Givi Babak , Gordon Alex J. , Park Yoon Soo , Lydiatt William M. , Tekian Ara
Published: August 2022

Background

Few studies have investigated the needs of head and neck surgery trainees and areas for improvement of fellowship programs.

Methods

We conducted a qualitative study by interviewing a nationally representative sample of program directors and national leaders in head and neck surgery. We asked about the current state and strengths of training; and areas for further improvement. All interviews were independently coded and analyzed by two reviewers.

Results

All experts (100%) believed that the current training provides a strong foundation and furthermore, a standardized curriculum is beneficial. Multidisciplinary training (80%), participation in tumor boards (75%), and a syllabus (60%) were the most frequently mentioned components. Most believed that a formal certification process would be beneficial (73%), though there was no consensus on the format.

Conclusion

Experts in head and neck surgery are generally in favor of a standardized curriculum. Further discussions of a formal certification process might be warranted.
Differential requirement of Hippo cascade during CTNNB1 or AXIN1 mutation‐driven hepatocarcinogenesis
Authors: Liang Binyong , Wang Haichuan , Qiao Yu , Wang Xue , Qian Manning , Song Xinhua , Zhou Yi , Zhang Yi , Shang Runze , Che Li , Chen Yifa , Huang Zhiyong , Wu Hong , Monga Satdarshan P. , Zeng Yong , Calvisi Diego F. , Chen Xiaoping , Chen Xin
Published: August 2022

Background and Aims:

Gain‐of‐function (GOF) mutations of CTNNB1 and loss‐of‐function (LOF) mutations of AXIN1 are recurrent genetic alterations in hepatocellular carcinoma (HCC). We aim to investigate the functional contribution of Hippo/YAP/TAZ in GOF CTNNB1 or LOF AXIN1 mutant HCCs.

Approach and Results:

The requirement of YAP/TAZ in c‐Met/β‐Catenin and c‐Met/sgAxin1‐driven HCC was analyzed using conditional Yap, Taz, and Yap;Taz knockout (KO) mice. Mechanisms of AXIN1 in regulating YAP/TAZ were investigated using AXIN1 mutated HCC cells. Hepatocyte‐specific inducible TTR‐CreERT2
KO system was applied to evaluate the role of Yap;Taz during tumor progression. Cabozantinib and G007‐LK combinational treatment were tested in vitro and in vivo. Nuclear YAP/TAZ was strongly induced in c‐Met/sgAxin1 mouse HCC cells. Activation of Hippo via overexpression of Lats2 or concomitant deletion of Yap and Taz significantly inhibited c‐Met/sgAxin1 driven HCC development, whereas the same approaches had mild effects in c‐Met/β‐Catenin HCCs. YAP is the major Hippo effector in c‐Met/β‐Catenin HCCs, and both YAP and TAZ are required for c‐Met/sgAxin1‐dependent hepatocarcinogenesis. Mechanistically, AXIN1 binds to YAP/TAZ in human HCC cells and regulates YAP/TAZ stability. Genetic deletion of YAP/TAZ suppresses already formed c‐Met/sgAxin1 liver tumors, supporting the requirement of YAP/TAZ during tumor progression. Importantly, tankyrase inhibitor G007‐LK, which targets Hippo and Wnt pathways, synergizes with cabozantinib, a c‐MET inhibitor, leading to tumor regression in the c‐Met/sgAxin1 HCC model.

Conclusions:

Our studies demonstrate that YAP/TAZ are major signaling molecules downstream of LOF AXIN1 mutant HCCs, and targeting YAP/TAZ is an effective treatment against AXIN1 mutant human HCCs.
Mortality after transjugular intrahepatic portosystemic shunt in older adult patients with cirrhosis: A validated prediction model
Authors: Vizzutti Francesco , Celsa Ciro , Calvaruso Vincenza , Enea Marco , Battaglia Salvatore , Turco Laura , Senzolo Marco , Nardelli Silvia , Miraglia Roberto , Roccarina Davide , Campani Claudia , Saltini Dario , Caporali Cristian , Indulti Federica , Gitto Stefano , Zanetto Alberto , Di Maria Gabriele , Bianchini Marcello , Pecchini Maddalena , Aspite Silvia , Di Bonaventura Chiara , Citone Michele , Guasconi Tomas , Di Benedetto Fabrizio , Arena Umberto , Fanelli Fabrizio , Maruzzelli Luigi , Riggio Oliviero , Burra Patrizia , Colecchia Antonio , Villa Erica , Marra Fabio , Cammà Calogero , Schepis Filippo
Published: August 2022

Background and Aims:

Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) improves survival in patients with cirrhosis with refractory ascites and portal hypertensive bleeding. However, the indication for TIPS in older adult patients (greater than or equal to 70 years) is debated, and a specific prediction model developed in this particular setting is lacking. The aim of this study was to develop and validate a multivariable model for an accurate prediction of mortality in older adults.

Approach and Results:

We prospectively enrolled 411 consecutive patients observed at four referral centers with de novo TIPS implantation for refractory ascites or secondary prophylaxis of variceal bleeding (derivation cohort) and an external cohort of 415 patients with similar indications for TIPS (validation cohort). Older adult patients in the two cohorts were 99 and 76, respectively. A cause‐specific Cox competing risks model was used to predict liver‐related mortality, with orthotopic liver transplant and death for extrahepatic causes as competing events. Age, alcoholic etiology, creatinine levels, and international normalized ratio in the overall cohort, and creatinine and sodium levels in older adults were independent risk factors for liver‐related death by multivariable analysis.

Conclusions:

After TIPS implantation, mortality is increased by aging, but TIPS placement should not be precluded in patients older than 70 years. In older adults, creatinine and sodium levels are useful predictors for decision making. Further efforts to update the prediction model with larger sample size are warranted.
Learning shifts the preferred theta phase of gamma oscillations in CA1
Authors: Rayan Abdelrahman , Donoso José R. , Mendez‐Couz Marta , Dolón Laura , Cheng Sen , Manahan‐Vaughan Denise
Published: August 2022

Hippocampal neuronal oscillations reflect different cognitive processes and can therefore be used to dissect the role of hippocampal subfields in learning and memory. In particular, it has been suggested that encoding and retrieval is associated with slow gamma (25–55 Hz) and fast gamma (60–100 Hz) oscillations, respectively, which appear in a nested manner at specific phases of the ongoing theta oscillations (4–12 Hz). However, the relationship between memory demand and the theta phase of gamma oscillations remains unclear. Here, we assessed the theta phase preference of gamma oscillations in the CA1 region, at the starting and junction zones of a T‐maze, while rats were learning an appetitive task. We found that the theta phase preference of slow gamma showed a ~180° phase shift when animals switched from novice to skilled performance during task acquisition. This phase‐shift was not present at the junction zone, where animals chose a right or left turn within the T‐maze, suggesting that a recall/decision process had already taken place at the starting zone. Our findings indicate that slow gamma oscillations support both encoding and retrieval, depending on the theta phase at which they occur. These properties are particularly evident prior to cognitive engagement in an acquired spatial task.
A rare case of long‐term survival from metachronous bilateral adrenal metastasis of lung adenocarcinoma after combined surgical removal and immunochemotherapy
Authors: Tomiyama Nami , Naiki Taku , Naiki‐Ito Aya , Kawai Tatsuya , Etani Toshiki , Gonda Masakazu , Aoki Maria , Morikawa Toshiharu , Sugiyama Yosuke , Yasui Takahiro
Published: August 2022

Introduction

The prognosis of adrenal metastasis from non‐small cell lung cancer is very poor. A recent report described the efficacy of the surgical removal of adrenal metastasis when solitary. However, metachronous bilateral adrenal metastasis is extremely rare, and a treatment strategy has not been established.

Case presentation

Herein, we describe a 52‐year‐old Asian male who presented with a right adrenal metastasis of non‐small cell lung cancer 8 months after immunochemotherapy and surgical resection of the lung. He underwent combined systemic treatment and a laparoscopic right adrenalectomy; however, after 9 months, a metachronous left adrenal metastasis emerged. A subsequent laparoscopic left adrenalectomy and systemic treatment led to long‐term progression‐free survival.

Conclusion

The appropriate surgical indication and combined systemic treatment of a metachronous bilateral adrenal metastasis in non‐small cell lung cancer may extend the prognosis.
Commodity price forecasting via neural networks for coffee, corn, cotton, oats, soybeans, soybean oil, sugar, and wheat
Authors: Xu Xiaojie , Zhang Yun
Published: August 2022

Agricultural commodity price forecasting represents a key concern for market participants. We explore the usefulness of neural network modeling for forecasting problems in datasets of daily prices over periods of greater than 50 years for coffee, corn, cotton, oats, soybeans, soybean oil, sugar, and wheat. By investigating different model settings across the algorithm, delay, hidden neuron, and data‐splitting ratio, we arrive at models leading to a decent performance for each commodity, with the overall relative root mean square error ranging from 1.70% to 3.19%. These results have small advantages over no‐change models due to particular price adjustments in the prices considered here. Our results can be used on a standalone basis or combined with fundamental forecasts in forming perspectives of commodity price trends and conducting policy analysis. Our empirical framework should not be diffucult to implement, which is a critical consideration for many decision‐makers and has the potential to be generalized for price forecasts of more commodities.
Inhibiting AKT signaling pathway with cilostazol and meloxicam synergism for suppressing K562 cells in vitro
Authors: Naderbar Laya , Pazhang Yaghub , Rezaie Jafar
Published: August 2022

Despite advances in cancer treatment, chronic myeloid leukemia (CML) is still one of the leading causes of death in the world. Due to the role of inflammation in cancer promotion and progression, thus use of anti‐inflammatory agents may suppress cancer cell growth. In this study, we used two anti‐inflammatory drugs, cilostazol and meloxicam, for the treatment of CML. Cell viability was measured using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and the synergism occurrence was calculated by compusyn software. Annexin V/PI test and Hoechst staining were used to determine the apoptosis rate. To determine the pathway of apoptosis induction, the expression of BCL2 Associated X (Bax) and B‐cell lymphoma‐2 (Bcl‐2) apoptotic genes and caspases activity were evaluated. The cell cycle was analyzed by propidium iodide (PI) staining and flow cytometry. Western blot analysis and immunofluorescence were performed to estimate alterations in Ak strain transforming‐1 (AKT‐1), phosphprylated AKT‐1 (p‐AKT‐1), adenosine mono‐phosphate‐kinase (AMPK), and phosphorylated AMPK (p‐AMPK) proteins and BCR/ABL and c‐Myc distribution, respectively. Results showed that cilostazol, meloxicam, and their combination drug reduced cell viability (p < 0.05). Compared with control, expression of Bax and Bcl‐2 decreased in treated cells, respectively (p < 0.05). The caspase‐9 activity increased in treated cells compared to control cells (p < 0.001). The applied drugs decreased the protein level of p‐AKT‐1 while increasing the p‐AMPK protein level (p < 0.05). BCR/ABL and c‐Myc Protein distribution significantly decreased in treated cells. In conclusion, the combination drug had more cytotoxic effects than cilostazol and meloxicam alone and induced apoptosis by inhibiting AKT‐1 activation and c‐Myc reduction. Therefore using combination drugs effectively can treat cancers of CML origin.
Productive biofilms: from prokaryotic to eukaryotic systems
Authors: Schmeckebier Andrea , Zayed Ahmed , Ulber Roland
Published: August 2022

Biofilms have great potential for producing valuable products more efficiently than suspended cultivations when it comes to yield and productivity. In addition, biofilms have the advantage of cell protection and increased resistance to environmental influences. Therefore, productive biofilms are used in biofilm reactors to produce value‐added products. A summary of possible applications for biofilm reactors is given here. In addition, the surfaces on which biofilms are cultivated are briefly explained. The possibility of using biofilms is not limited to prokaryotic systems. Thus, eukaryotic systems can also be cultivated as biofilms to produce valuable products. Therefore, both prokaryotic and eukaryotic productive biofilms will be described in this review. In the case of eukaryotic systems, fungal biofilms and plant biofilms will be discussed. The biofilm formation of the different cell types is listed and the productivity of a cell line on a corresponding substrate is summarized. Finally, the investigation methods of biofilms are discussed, as these methods are essential to understanding biofilms. © 2022 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
The combined cartilage growth – calcification patterns in the wing‐fins of Rajidae (Chondrichthyes): A divergent model from endochondral ossification of tetrapods
Authors: Pazzaglia Ugo E. , Reguzzoni Marcella , Manconi Renata , Zecca Piero Antonio , Zarattini Guido , Campagnolo Monica , Raspanti Mario
Published: August 2022

The relationship between cartilage growth – mineralization patterns were studied in adult Rajidae with X‐ray morphology/morphometry, undecalcified resin‐embedded, heat‐deproteinated histology and scanning electron microscopy. Morphometry of the wing‐fins, nine central rays of the youngest and oldest specimens documented a significant decrement of radials mean length between inner, middle and outer zones, but without a regular progression along the ray. This suggests that single radial length growth is regulated in such a way to align inter‐radial joints parallel to the wing metapterygia curvature. Trans‐illumination and heat‐deproteination techniques showed polygonal and cylindrical morphotypes of tesserae, whose aligned pattern ranged from mono‐columnar, bi‐columnar, and multi‐columnar up to the crustal‐like layout. Histology of tessellated cartilage allowed to identify of zones of the incoming mineral deposition characterized by enhanced duplication rate of chondrocytes with the formation of isogenic groups, whose morphology and topography suggested a relationship with the impending formation of the radials calcified column. The morphotype and layout of radial tesserae were related to mechanical demands (stiffening) and the size/mass of the radial cartilage body. The cartilage calcification pattern of the batoids model shares several morphological features with tetrapods' endochondral ossification, that is, (chondrocytes' high duplication rate, alignment in rows, increased volume of chondrocyte lacunae), but without the typical geometry of the metaphyseal growth plates.

Research Highlights

1. The wing‐fins system consists of stiff radials, mobile inter‐radial joints and a flat inter‐radial membrane adapted to the mechanical demand of wing wave movement.

2. Growth occurs by forming a mixed calcified‐uncalcified cartilage texture, developing intrinsic tensional stresses documented by morphoanatomical data.
Characterization of protein complexes in extracellular vesicles by intact extracellular vesicle crosslinking mass spectrometry (iEVXL)
Authors: Bauzá‐Martinez Julia , Armony Gad , Pronker Matti F. , Wu Wei
Published: August 2022

Extracellular vesicles (EVs) are blood‐borne messengers that coordinate signalling between different tissues and organs in the body. The specificity of such crosstalk is determined by preferential EV docking to target sites, as mediated through protein‐protein interactions. As such, the need to structurally characterize the EV surface precedes further understanding of docking selectivity and recipient‐cell uptake mechanisms. Here, we describe an intact extracellular vesicle crosslinking mass spectrometry (iEVXL) method that can be applied for structural characterization of protein complexes in EVs. By using a partially membrane‐permeable disuccinimidyl suberate crosslinker, proteins on the EV outer‐surface and inside EVs can be immobilized together with their interacting partners. This not only provides covalent stabilization of protein complexes before extraction from the membrane‐enclosed environment, but also generates a set of crosslinking distance restraints that can be used for structural modelling and comparative screening of changes in EV protein assemblies. Here we demonstrate iEVXL as a powerful approach to reveal high‐resolution information, about protein determinants that govern EV docking and signalling, and as a crucial aid in modelling docking interactions.