bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic analysis identifying PVT1/DUSP13 axis for microvascular invasion in hepatocellular carcinoma
Authors: Su Renyi , Zhang Huizhong , Zhang Lincheng , Khan Abdul Rehman , Zhang Xuanyu , Wang Rui , Shao Chuxiao , Wei Xuyong , Xu Xiao
Published: December 2022

Background

Microvascular invasion (MVI) is an independent detrimental risk factor for tumor recurrence and poor survival in hepatocellular carcinoma (HCC). Competitive endogenous RNA (ceRNA) networks play a pivotal role in the modulation of carcinogenesis and progression among diverse tumor types. However, whether the ceRNA mechanisms are engaged in promoting the MVI process in patients with HCC remains unknown.

Methods

A ceRNA regulatory network was constructed based on RNA‐seq data of patients with HCC from The Cancer Genome Atlas (TCGA) database. In total, 10 hub genes of the ceRNA network were identified using four algorithms: “MCC,” “Degree,” “Betweenness,” and “Stress.” Transcriptional expressions were verified by in situ hybridization using clinical samples. Interactions between ceRNA modules were validated by luciferase reporting assay. Logistic regression analysis, correlation analysis, enrichment analysis, promoter region analysis, methylation analysis, and immune infiltration analysis were performed to further investigate the molecular mechanisms and clinical transformation value.

Results

The ceRNA regulatory network featuring a tumor invasion phenotype consisting of 3 long noncoding RNAs, 3 microRNAs, and 93 mRNAs was constructed using transcriptional data from the TCGA database. Systemic analysis and experimentally validation identified a ceRNA network (PVT1/miR‐1258/DUSP13 axis) characterized by lipid regulatory potential, immune properties, and abnormal methylation states in patients with HCC and MVI. Meanwhile, 28 transcriptional factors were identified as potential promotors of PVT1 with 3 transcriptional factors MXD3, ZNF580, and KDM1A promising as therapeutic targets in patients with HCC and MVI. Furthermore, miR‐1258 was an independent predictor for MVI in patients with HCC.

Conclusion

The PVT1/DUSP13 axis is significantly associated with MVI progression in HCC patients. This study provides new insight into mechanisms related to lipids, immune phenotypes, and abnormal epigenetics in oncology research.
Novel malformations: Chiari type 1 and hydrocephalus in Zhu‐Tokita‐Takenouchi‐Kim syndrome and novel SON variants
Authors: Pavone Piero , Saia Federica , Pappalardo Xena , Barbagallo Massimo , Prato Adriana , Rizzo Renata
Published: December 2022

Zhu‐Tokita‐Tachenouchi‐Kim syndrome (ZTTK) is a recently recognized malformation syndrome presenting with craniofacial dysmorphism, developmental delay/intellectual disability, seizures, anomalies involving brain white matter, and other body‐organs. In humans, the disorder is linked to the loss‐of‐function variants in the SON gene (MIM# 617140). Herewith, a new case of this syndrome is reported in a 2‐year‐old Caucasian child who presented the classical clinical features of the ZTTK syndrome in association with hydrocephalus and Chiari malformations type 1 an anomaly previously unreported. Exome analysis showed a de novo heterozygous variant in SON gene. Literature review of similar cases is reported.
Strongyloides stercoralis: Uncommon yet not to be missed cause of eosinophilia
Authors: Boccucci Jacob M. , Cronley Apryl , Walsh David W.
Published: December 2022

Strongyloides stercoralis is a soil‐transmitted nematode that is estimated to infect millions of people per year worldwide. However, cases are less commonly seen in the United States. This report highlights the importance of when to include Strongyloides stercoralis in the differential diagnosis of patients presenting eosinophilia within the United States.
Comparative Analysis of Catalytic Cracking and Hydrocracking of Waste Plastic
Authors: Iqbal Faiza , Shafeeq Amir , Aslam Rabya , Rauf Abdul
Published: December 2022

Waste materials from various processes comprising of polyethylene and polystyrene were analyzed for the production of fuel using catalytic cracking and hydrocracking in an autoclave reactor. The composite catalyst USY/SBA‐16 was synthesized in the lab to be employed in the catalytic process because of its outstanding stability and regenerative capability. Each of the two processes produced a fuel with different quality and quantity. Catalytic cracking and hydrocracking of polystyrene and polyethylene were investigated at different temperatures by varying the percentage amount of catalyst and it was found that polystyrene yielded a fuel of better quality as compared to polyethylene.
Macrophytes’ Performance in Floating Treatment Wetlands for the Remediation of Ciprofloxacin‐Contaminated Water
Authors: Shah Syed Wajid Ali , Rehman Mujaddad ur , Anwar Samina , Hayat Azam , Shabir Ghulam , Tahseen Razia , Rahman Moazur , Islam Ejazul , Iqbal Samina , Afzal Muhammad
Published: December 2022

The presence of trace antibiotics in domestic and industrial effluents poses a risk of toxicity to fauna and flora. The application of floating treatment wetlands (FTWs) is a low‐cost and sustainable approach to remediate wastewater. In this study, the performance of different macrophytes vegetated in FTWs for the remediation of ciprofloxacin (CIP)‐contaminated water is investigated. Six macrophytes, Brachia mutica, Typha domingensis, Phragmites australis, Canna indica, Cyperus laevigatus, and Leptochloa fusca, are vegetated in FTWs for the removal of CIP (50 mg L−1) from water. The FTWs show the potential to remove 30–43.58 mg L−1 CIP from water in 28 days. They also reduce the chemical oxygen demand (118–138 mg L−1) and biochemical oxygen demand (35–45 mg L−1) of water. Among the macrophytes, C. indica removes maximum (43.58 mg L−1) and T. domingensis minimum (30 mg L−1) CIP. Canna indica and T. domingensis exhibit the maximum and minimum increase (30% and 12% of dry biomass) in growth, respectively. This study reveals that the FTWs vegetated with different plant species exhibit varying performances in removing CIP from water. This investigation is a step forward toward sustainable bioremediation of water contaminated with antibiotics.
Application of deep learning as an ancillary diagnostic tool for thyroid FNA cytology
Authors: Hirokawa Mitsuyoshi , Niioka Hirohiko , Suzuki Ayana , Abe Masatoshi , Arai Yusuke , Nagahara Hajime , Miyauchi Akira , Akamizu Takashi
Published: December 2022

Background

Several studies have used artificial intelligence (AI) to analyze cytology images, but AI has yet to be adopted in clinical practice. The objective of this study was to demonstrate the accuracy of AI‐based image analysis for thyroid fine‐needle aspiration cytology (FNAC) and to propose its application in clinical practice.

Methods

In total, 148,395 microscopic images of FNAC were obtained from 393 thyroid nodules to train and validate the data, and EfficientNetV2‐L was used as the image‐classification model. The 35 nodules that were classified as atypia of undetermined significance (AUS) were predicted using AI training.

Results

The precision‐recall area under the curve (PR AUC) was >0.95, except for poorly differentiated thyroid carcinoma (PR AUC = 0.49) and medullary thyroid carcinoma (PR AUC = 0.91). Poorly differentiated thyroid carcinoma had the lowest recall (35.4%) and was difficult to distinguish from papillary thyroid carcinoma, medullary thyroid carcinoma, and follicular thyroid carcinoma. Follicular adenomas and follicular thyroid carcinomas were distinguished from each other by 86.7% and 93.9% recall, respectively. For two‐dimensional mapping of the data using t‐distributed stochastic neighbor embedding, the lymphomas, follicular adenomas, and anaplastic thyroid carcinomas were divided into three, two, and two groups, respectively. Analysis of the AUS nodules showed 94.7% sensitivity, 14.4% specificity, 56.3% positive predictive value, and 66.7% negative predictive value.

Conclusions

The authors developed an AI‐based approach to analyze thyroid FNAC cases encountered in routine practice. This analysis could be useful for the clinical management of AUS and follicular neoplasm nodules (e.g., an online AI platform for thyroid cytology consultations).
Energy‐efficient multiple cooperative moving relay selection for heterogeneous nonorthogonal‐multiple access systems
Authors: Khan Mohd Javed , Chauhan Ram Chandra Singh , Singh Indrasen
Published: December 2022

In a high‐speed vehicular scenario, due to vehicle penetration loss (VPL) and fast signal fluctuations, frequent handovers occur, which results in more battery consumption. So power saving is a critical concern in high‐speed wireless networks. In the past, moving relay (MR)‐based heterogeneous network (HetNet) models were proposed and studied to overcome the effect of VPL, but the issue of power saving has not been studied till now for vehicular HetNet. In this paper, we propose an energy‐efficient algorithm that selects the best number of cooperative MRs among multiple MRs installed on the top of the train for efficient utilization of transmission power in a NOMA‐based wireless network. A half‐duplex amplify‐and‐forward relaying protocol is used for the investigation. We define the optimization problem of energy efficiency for cooperative MR. The problem of energy maximization is stated as an optimization problem, and an energy‐efficient MR selection algorithm is proposed as the solution to the optimization problem. The simulation results show that the proposed algorithm enhances the energy efficiency of vehicular and nonvehicular users and it also decreases the outage probability at fixed spectral efficiency in comparison with the fixed MR‐based selection combining and maximum ratio combining diversity techniques. This result will be beneficial in vehicular communication to achieve maximum energy efficiency.
The history of calcite diagenesis and origin of exceptionally negative oxygen isotope values in chalks of the Niobrara Formation, Denver Basin, USA
Authors: Simon Rebekah E. , Budd David A. , Snell Kathryn E.
Published: December 2022

The Niobrara Formation of north‐east Colorado, USA, has anomalously negative δ18O values compared to all other Cretaceous chalks. These unique δ18O values have been attributed to elevated heat flow and/or freshening of the Cretaceous Western Interior Seaway. This work utilises clumped isotopes of calcite (Δ47), peak burial temperatures estimated from pyrolysis data, and strontium and neodymium isotopes of carbonate to re‐evaluate the origin of the calcite's18O‐depletion. Peak temperatures indicate lateral variability in geothermal gradients ofca20°C/km at the tens of kilometre scale, and corroborate prior studies proposing locally elevated palaeotemperatures. Greater insight is provided by numerical models of calcite recrystallisation and oxygen isotope evolution that are constrained by measured Δ47‐derived temperatures, calcite δ18O values and inferences from the87Sr/86Sr and εNd values. The models indicate that (1) sea water in the seaway had normal marine δ18O values of −1 (VSMOW) except on the eastern margin of the basin where some freshwater dilution yielded −2 to −3‰ (VSMOW) water, and (2) the main driver of the anonymously negative calcite δ18O values was a semi‐open hydrologic system that provided a few percent by pore volume of meteoric groundwater derived from post‐Laramide recharge into the basin. Minor contributions were a Laramide‐aged heat pulse related to the underlying Colorado Mineral Belt, the thermal insulating effects of now eroded coals, and a small flux of compaction‐driven Cretaceous sea water evolved by smectite dehydration. However, those three factors alone were insufficient drivers of the calcites'18O depletion. High burial temperatures are interpreted to have caused clumped isotope reordering in at least one well, but those temperatures cannot yield the observed calcite δ18O values. The study illustrates the unique attributes of the Niobrara's diagenetic system that results in its anomalous δ18O values, and reaffirms the value of clumped isotopes in unravelling the diagenetic history of chalk systems.
Genomic divergence between two sister Ostrya species through linked selection and recombination
Authors: Zhang Jin , Zhang Shangzhe , Zheng Zeyu , Lu Zhiqiang , Yang Yongzhi
Published: December 2022

Studying the evolution of genomic divergence between lineages is a topical issue in evolutionary biology. However, the evolutionary forces that shape the heterogeneous divergence of the genomic landscape are still poorly understood. Here, two wind‐pollinated sister‐species (Ostrya japonica and O. chinensis) are used to explore what these potential forces might be. A total of 40 individuals from 16 populations across their main distribution areas in China were sampled for genome‐wide resequencing. Population demography analyses revealed that these two sister‐species diverged at 3.06–4.43 Mya. Both population contraction and increased gene flow were detected during glacial periods, suggesting secondary contact at those times. All three parameters (DXY, π, and ρ) decreased in those regions showing high levels of differentiation (FST). These findings indicate that linked selection and recombination played a key role in the genomic heterogeneous differentiation between the two Ostrya species. Genotype–environment association analyses showed that precipitation was the most important ecological factor for speciation. Such environmentally related genes and positive selection genes may have contributed to local adaptation and the maintenance of species boundaries.
Predicting habitat suitability for Townsend's big‐eared bats across California in relation to climate change
Authors: Hamilton Natalie M. , Morrison Michael L. , Harris Leila S. , Szewczak Joseph M. , Osborn Scott D.
Published: December 2022

Effective management decisions depend on knowledge of species distribution and habitat use. Maps generated from species distribution models are important in predicting previously unknown occurrences of protected species. However, if populations are seasonally dynamic or locally adapted, failing to consider population level differences could lead to erroneous determinations of occurrence probability and ineffective management. The study goal was to model the distribution of a species of special concern, Townsend's big‐eared bats (Corynorhinus townsendii), in California. We incorporate seasonal and spatial differences to estimate the distribution under current and future climate conditions. We built species distribution models using all records from statewide roost surveys and by subsetting data to seasonal colonies, representing different phenological stages, and to Environmental Protection Agency Level III Ecoregions to understand how environmental needs vary based on these factors. We projected species' distribution for 2061–2080 in response to low and high emissions scenarios and calculated the expected range shifts. The estimated distribution differed between the combined (full dataset) and phenologically explicit models, while ecoregion‐specific models were largely congruent with the combined model. Across the majority of models, precipitation was the most important variable predicting the presence of C. townsendii roosts. Under future climate scenarios, distribution of C. townsendii is expected to contract throughout the state, however suitable areas will expand within some ecoregions. Comparison of phenologically explicit models with combined models indicates the combined models better predict the extent of the known range of C. townsendii in California. However, life‐history‐explicit models aid in understanding of different environmental needs and distribution of their major phenological stages. Differences between ecoregion‐specific and statewide predictions of habitat contractions highlight the need to consider regional variation when forecasting species' responses to climate change. These models can aid in directing seasonally explicit surveys and predicting regions most vulnerable under future climate conditions.
Past, present, and future higher education predictions
Authors: Dennis Marguerite J.
Published: December 2022

Change is coming, whether you like it or not.

Greta Thunberg, Swedish global climate advocate
How to help your students get the most out of college
Authors: Felix Elliot
Published: December 2022

College is where students forge their identities, find their communities, chart the course of their careers, and learn the knowledge and skills to succeed. With tuition rising and student loan debt looming, the pandemic brought the question of the value of higher education to the forefront for students, parents, and institutions.
Montclair's Jordanna Maziarz: Taking the stress out of college applications
Authors: D'Orio Wayne
Published: December 2022

For many admissions officers, the big goals of their profession seemed fixed: increase applicants and ensure your college has a full freshman class. While it's true some schools are trying to increase class sizes while others are attempting to become more selective, the rules to follow seem pretty well defined in this space.
Systemic inflammation as a biomarker of seizure propensity and a target for treatment to reduce seizure propensity
Authors: Stredny Coral , Rotenberg Alexander , Leviton Alan , Loddenkemper Tobias
Published: December 2022

People with diabetes can wear a device that measures blood glucose and delivers just the amount of insulin needed to return the glucose level to within bounds. Currently, people with epilepsy do not have access to an equivalent wearable device that measures a systemic indicator of an impending seizure and delivers a rapidly acting medication or other intervention (e.g., an electrical stimulus) to terminate or prevent a seizure. Given that seizure susceptibility is reliably increased in systemic inflammatory states, we propose a novel closed‐loop device where release of a fast‐acting therapy is governed by sensors that quantify the magnitude of systemic inflammation. Here, we review the evidence that patients with epilepsy have raised levels of systemic indicators of inflammation than controls, and that some anti‐inflammatory drugs have reduced seizure occurrence in animals and humans. We then consider the options of what might be incorporated into a responsive anti‐seizure system.
Identification and clinical characteristics of a novel missense ADGRG1 variant in bilateral Frontoparietal Polymicrogyria: The electroclinical change from infancy to adulthood after Callosotomy in three siblings
Authors: Kuo Cheng‐Yen , Tsai Meng‐Han , Lin Hsi‐Hsien , Wang Yu‐Chi , Singh Abhishek Kumar , Chang Chih‐Chen , Lin Jainn‐Jim , Hung Po‐Cheng , Lin Kuang‐Lin
Published: December 2022

Objective

Bilateral frontoparietal polymicrogyria (BFPP) is a rare genetic‐related migration disorder. It has been attributed to loss‐of‐function of the ADGRG1 gene, which encodes an adhesion G protein‐coupled receptor, ADGRG1/GPR56. We report the EEG findings of BFPP in three Asian patients, and confirmed that change in protein function was caused by the novel missense variant (p.Leu290Pro).

Methods

We reviewed the medical records of three siblings with BFPP including one elder girl and two identical twin boys from birth to adulthood. The clinical symptoms, electroencephalography (EEG), brain MRI, whole‐exome sequencing, treatment including medications, neuromodulation, and epilepsy surgery, and clinical outcomes were reviewed. The protein structure of a novel missense variant (p.Leu290Pro) was predicted by in silico studies, and molecular analysis was performed via typical flow cytometry and Western blotting.

Results

The elder girl (Patient 1) was 22 years old and the twin boys (Patients 2 and 3) were 20 years old at the time of publication. All of them presented with typical clinical symptoms/signs and MRI findings of BFPP. Whole‐exome sequencing followed by Sanger confirmation showed that all three patients had compound heterozygous variants in the ADGRG1 gene. The missense variant (p.Leu290Pro) was confirmed to be related to a reduction in cell surface GPR56 expression. High‐amplitude rhythmic activity was noted in sleep EEG during infancy, which may have been due to excessive sleep spindle, and the rhythm disappeared when they were of pre‐school age. Partial callosotomy provided short‐term benefits in seizure control in Patients 1 and 2, and combined vagus nerve stimulation and partial callosotomy provided longer benefits in Patient 3.

Significance

Sleep EEG findings of high‐amplitude rhythmic activity in our BFPP cases were only noted during infancy and childhood. We also confirmed that the missense variant (p.Leu290Pro) led to loss of function due to a reduction in cell surface GPR56 expression.
Clinical outcomes of combined cervical and transthoracic surgical approaches in patients with advanced thyroid cancer
Authors: Shenson Jared A. , Zafereo Mark E. , Lee Mark , Contrera Kevin J. , Feng Lei , Boonsripitayanon Mongkol , Gross Neil , Goepfert Ryan , Maniakas Anastasios , Wang Jennifer Rui , Grubbs Libby , Vaporciyan Ara , Hofstetter Wayne , Swisher Stephen , Mehran Reza , Rice David , Sepesi Boris , Antonoff Mara , Cabanillas Maria , Busaidy Naifa , Dadu Ramona , Silver Natalie L.
Published: December 2022

Background

Advanced thyroid disease involving the mediastinum may be managed surgically with a combined transcervical and transthoracic approach. Contemporary analysis of this infrequently encountered cohort will aid the multidisciplinary team in personalizing treatment approaches.

Methods

Retrospective review of patients undergoing combined transcervical and transthoracic surgery for thyroid cancer at a single high‐volume institution from 1994 to 2015.

Results

Thirty‐eight patients with median age 59 years (range 28–76) underwent surgery without perioperative mortality. Most patients had primary disease. A majority had distant metastases outside the mediastinum but had locoregionally curable disease. Common complications were temporary (39%) and permanent (18%) hypoparathyroidism, and wound infection (13%). One‐year overall survival was 84%; 1‐year locoregional disease‐free survival was 64%. Median time to locoregional recurrence was 36 months. Only esophageal invasion was associated with worse oncologic outcomes.

Conclusions

Combined transcervical and transthoracic surgery for advanced thyroid cancer can be performed without mortality and with acceptable morbidity.
Linking evapotranspiration seasonal cycles to the water balance of headwater catchments with contrasting land uses
Authors: Peixoto Neto Alberto M. L. , Cartwright Ian , Silva Marcela R. F. , McHugh Ian , Dresel P. Evan , Teodosio Bertrand , Jovanovic Dusan , McCaskill Malcom R. , Webb John , Daly Edoardo
Published: December 2022

Land use affects evapotranspiration rates and is a primary driver of the catchment water balance. The water balance of two catchments in southeastern Australia dominated by either grazed pasture or blue gum (Eucalyptus globulus) plantation was studied, focusing on the patterns of evapotranspiration (ET) throughout the year. Rainfall, streamflow, and groundwater levels measured between 2015 and 2019 were combined to estimate annual ET using a water balance equation. In the pasture, eddy covariance was used to measure ET from the catchment. Sap flow measurements were used to estimate tree transpiration in May 2017–May 2018 and Feb 2019–Feb 2021 in two different plots within the plantation. The tree transpiration rates were added to interception, estimated as a percentage of annual rainfall, to calculate ET from the plantation catchment. ET in the pasture showed strong seasonal cycles with very low ET rates in summer and ET rates in spring that were larger than the transpiration rates in the plantation, where trees transpired consistently throughout the year. The estimated annual ET from the water balance equation was comparable to ET estimated from other measurements. In the pasture, ET on average accounted for 88% of annual rainfall, while ET in the plantation was on average 93% of rainfall, exceeding it in the years with annual rainfall lower than about 500 mm. The difference between the ET rates in the plantation and the pasture was approximately 30–50 mm y−1. The larger ET rates in the plantation were reflected in a gradual decrease in the groundwater storage. The larger ET rates were enough to cause a decrease in groundwater storage in the plantation but not in the pasture, where groundwater levels remained stable.
Probabilistic risk assessment of sustainable fish consumption at sediment sites
Authors: Ruffle Betsy , Pfeiffer Danielle , Morrison Emily , Kirkwood Gemma , Anderson Paul
Published: December 2022

A probabilistic risk assessment (PRA) using a range of sustainable usual fish consumption rates (SUFCRs) was performed to evaluate the potential health risks from consuming resident fish at two contaminated sediment sites. The analysis focused on the Portland Harbor Superfund Site, a large river in Oregon, and Koppers Pond, a small pond in New York. At both sites, the sediment cleanup remedy is driven by PCBs in resident fish. The PRA fit probability distributions to inputs used to develop a distribution of SUFCR, the long-term fish consumption rate sustainably supported by a fishery, and other exposure parameters to calculate the range and likelihood of cancer risks and noncancer hazards for adult anglers. At the 95th percentile, which is often considered a reasonable maximum exposure (RME), the SUFCRs calculated using site-specific inputs are six- to ten-fold lower than the point estimate fish consumption rates used in the deterministic baseline human health risk assessment conducted for each site. The combination of sustainable fish consumption rates and probabilistic methods results in a range of risks and thereby provides more information than the more commonly used deterministic approach. For over 99% of the resident fish-consuming population, the potential cancer risks and noncancer hazards calculated in the PRA are below the deterministic estimates for the RME adult consumer at each site. The combination of PRA with the estimation of SUFCRs is a novel application of these techniques at contaminated sediment sites that provides critical information for risk management decision-making. Integr Environ Assess Manag 2023;19:830–843. © 2022 AECOM Technical Services, Inc and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Mediation effect of intestinal microbiota on the relationship between fiber intake and colorectal cancer
Authors: Shimomura Yoshimitsu , Zha Ling , Komukai Sho , Narii Nobuhiro , Sobue Tomotaka , Kitamura Tetsuhisa , Shiba Satoshi , Mizutani Sayaka , Yamada Takuji , Sawada Norie , Yachida Shinichi
Published: December 2022

Higher fiber intake has been associated with a lower risk of colorectal cancer (CRC) and has been shown to protect against CRC based on probable evidence. Recent studies revealed a possible mechanism whereby the interaction between intestinal microbiota and fiber intake mediates CRC risk. However, the specific intestinal bacteria and the amount of these bacteria involved in this mechanism are not fully known. Therefore, this single‐center study aimed to determine whether specific intestinal bacteria mediated the relationship between fiber intake and CRC risk. We enrolled patients who received colonoscopy at National Cancer Center Hospital. This cross‐sectional study included 180 patients with clinically diagnosed CRC and 242 controls. We conducted a causal mediation analysis to assess the natural indirect effect and natural direct effect of specific intestinal bacteria on association between fiber intake and CRC risk. The median age was 64 (interquartile range, 54‐70) years, and 58% of the participants were males. We used metagenomics for profiling gut microbiomes. The relative abundance of each species in each sample was calculated. Among the candidate, Fusobacterium nucleatum and Gemella morbillorum had a significant natural indirect effect based on their highest fiber intake compared to the lowest fiber intake, with a risk difference (95% confidence interval, proportion of mediation effect) of −0.06 [−0.09 to −0.03, 23%] and −0.03 [−0.06 to −0.01, 10.5%], respectively. Other bacteria did not display natural indirect effects. In conclusion, Fusobacterium nucleatum and Gemella morbillorum were found to mediate the relationship between fiber intake and CRC risk.
Asiaticoside attenuates oxygen–glucose deprivation/reoxygenation‐caused injury of cardiomyocytes by inhibiting autophagy
Authors: Yao Mingyan , Wang Jie , Zhang Jing , Guo Yifang , Ni Zhiyu , Jia Xinwei , Feng Huiping
Published: December 2022

Asiaticoside is a natural triterpene compound derived from Centella asiatica, possessing confirmed cardioprotective property. However, the roles of asiaticoside in regulating oxygen–glucose deprivation/reoxygenation (OGD/R)‐caused cardiomyocyte dysfunction remain largely obscure. Human cardiomyocyte AC16 cells were stimulated with OGD/R to mimic myocardial ischemia/reperfusion injury and treated with asiaticoside. Cytotoxicity was investigated by CCK‐8 assay and lactate dehydrogenase (LDH) release analysis. Autophagy‐ and Wnt/β‐catenin signaling‐related protein levels were measured via western blotting. Asiaticoside (0–20 μM) did not induce cardiomyocyte cytotoxicity. Asiaticoside (20 μM) mitigated OGD/R‐induced autophagy, cytotoxicity, oxidative stress, and myocardial injury. Rapamycin, an autophagy inductor, reversed the influences of asiaticoside on autophagy, cytotoxicity, oxidative stress, and myocardial injury, whereas 3‐methyadanine, an autophagy inhibitor, played an opposite effect. Asiaticoside (20 μM) attenuated OGD/R‐induced Wnt/β‐catenin signaling inactivation, which was reversed after transfection with si‐β‐catenin. Transfection with si‐β‐catenin attenuated the influences of asiaticoside on autophagy, cytotoxicity, oxidative stress, and myocardial injury. In conclusion, asiaticoside protected against OGD/R‐induced cardiomyocyte cytotoxicity, oxidative stress, and myocardial injury via blunting autophagy through activating the Wnt/β‐catenin signaling, indicating the therapeutic potential of asiaticoside in myocardial ischemia/reperfusion injury.
A Quantification Method for Disorganized Bone Components: Application to the Femoral Shaft
Authors: Zebaze Roger , Shore‐Lorenti Catherine , Nguyen Hanh H , Chiang Cherie , Milat Frances , Ebeling Peter R
Published: December 2022

Based on the current paradigm, a healthy bone is one with adequate mass without microarchitectural decay. However, these two features may not be sufficient to ensure that a bone is healthy. In addition, components must be correctly assembled and aligned. This ensures “the right amount of bone, at the right place” and thus, an optimal cohesion or interplay between constituents. Disorganization may be an independent contributor to bone abnormalities including fragility fractures. Indeed, many bone diseases may be characterized by the presence of disorganized bone, including osteogenesis imperfecta, hypophosphatasia, and atypical femur fractures (AFFs). Despite its likely importance, currently, there are no tools to quantify disorganization in vivo. We address this unmet need by describing a novel method for quantifying bone disorganization from X‐ray images. Disorganization is quantified as variations in the orientation of bone components in relation to a target reference point. True disorganization created by disarranging (misplacing) pixels within the bone served as “gold standard.” To further validate the method in clinical settings, we compared disorganization in three groups of femurs: (i) femurs of women with AFFs (n = 9); (ii) fracture‐free femurs contralateral to AFFs (n = 9); and (iii) fracture‐free femurs from controls (n = 25). There was excellent agreement between measured disorganization and “gold standard,” with R2 values ranging from 0.84 to 0.99. Precision error ranged from 1.72% to 4.69%. Disorganization produced by abnormalities associated with AFFs was accurately captured. Disorganization level was lowest in fracture‐free control femurs, higher in fracture‐free contralateral femurs to AFFs, and highest in femurs with AFFs (all p < 0.0001). Quantification of disorganization, a novel biomarker, may provide novel insights into the pathogenesis of metabolic bone diseases beyond that provided by bone mineral density (BMD) or microarchitecture. We provide evidence that measurement of disorganization is likely to help identify patients at risk for fractures, especially in those poorly explained by BMD or microarchitecture such as AFFs. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Sensitive determination of ethosuximide in human fluids by electromembrane extraction coupled with high performance liquid chromatography ultraviolet spectroscopy
Authors: Nabizadeh Hassan , Mohammadi Ali , Dolatabadi Roshanak , Nojavan Saeed , Vahabizad Fahimeh
Published: December 2022

Ethosuximide (ETX) is a common antiepileptic drug in the first line of absence epilepsy. In this study, for the first time, an economical and efficient electro‐membrane (EME) method for determination of ETX in a complex biological matrix using HPLC‐UV has been developed. Factors affecting conventional EME were evaluated. 1‐Octanol was immobilized in a polypropylene membrane and a voltage of 35 V was applied between two platinum electrodes for 15 min. The pH of acceptor and donor phases for ionization of ETX was adjusted to 13 and 11, respectively. Under optimal microextraction conditions, the enrichment factor was 21.02 and the linear range of ETX was 0.25 to 8.00 μg/mL with an acceptable R2 ≥ 0.9986. Inter‐day and intra‐day precision and accuracy of the suggested method were calculated with RSD < 9.5% and relative error <7.0%, respectively. The mean relative recovery of ETX in the human saliva and plasma samples was 81.68% and 74.47, respectively; while limit of detection and quantification concentrations were 0.08 and 0.25 μg/mL, respectively. Furthermore, to evaluate the application of the method, plasma and saliva samples of volunteers administering a single dose of ETX were analyzed successfully by EME‐HPLC‐UV method.
Serum calprotectin can indicate current and future severity ofCOVID‐19
Authors: Shokri‐Afra Hajar , Moradi Mona , Musavi Hadis , Moradi‐Sardareh Hemen , Moradi poodeh Bahman , Kazemi Veisari Arash , Oladi Ziaeddin , Ebrahimi Mahboobe
Published: December 2022

Background

Predictive and prognostic biomarkers to guide 2019 novel coronavirus disease (COVID‐19) are critically evolving. Dysregulated immune responses are the pivotal cause of severity mainly mediated by neutrophil activation. Thus, we evaluated the association of calprotectin, neutrophil secretory protein, and other mediators of inflammation with the severity and outcomes of COVID‐19.

Methods

This two‐center prospective study focused on PCR‐proven COVID‐19 patients (n = 76) with different clinical presentations and SARS‐CoV‐2 negative control subjects (n = 24). Serum calprotectin (SC) was compared with IL‐6 and other laboratory parameters.

Results

Median levels of SC were significantly higher in COVID‐19 patients in comparison to the control group (3760 vs. 2100 ng/ml,p < 0.0001). Elevated SC was significantly respective of disease severity (3760 ng/ml in mild up to 5700 ng/ml in severe cases,p < 0.0001). Moreover, the significant positive and negative correlations of SC with disease severity and oxygenation status indicated disease progression and respiratory worsening, respectively. It was found that SC was high in severe patients during hospitalization and significantly declined to normal after recovery. The logistic analysis identified the independent predictive power of SC for respiratory status or clinical severity. Indeed, SC behaved as a better discriminator for both outcomes, as it exhibited the largest area under the curve (receiver operating curve analysis), with the highest specificity and sensitivity when the predictive value of inflammatory biomarkers was compared.

Conclusion

Calprotectin can be used as a reliable prognostic tool to predict the poor clinical outcomes of COVID‐19 patients.
Exposure–Response Analyses of Polysomnography and Subjective Sleep Efficacy End Points From the Phase 3 Trials of Lemborexant, a Dual Orexin Receptor Antagonist for the Treatment of Insomnia
Authors: Lalovic Bojan , Savant Landry Ishani , Moline Margaret , Reyderman Larisa , Hussein Ziad
Published: December 2022

This report describes polysomnography and sleep diary exposure–response analyses from Study E2006‐G000‐304 (Study 304), a 1‐month trial of 5‐ or 10‐mg lemborexant, zolpidem, or placebo; and Study E2006‐G000‐303 (Study 303), a 6‐month trial of 5‐ or 10‐mg lemborexant or placebo. Studies 304 and 303 included 1006 (86%) and 956 (68%) (female) participants, respectively; >40% were ≥65 years, with individual lemborexant exposures derived from a previously described pharmacokinetic model. Linear mixed‐effects analyses of polysomnography: latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) quantified the change from baseline given lemborexant exposure, time, and covariates, guided by consensus recommendations regarding clinical significance. A small impact of sex, body weight, and race was predicted for LPS and SE, irrespective of treatment. Effect of age on LPS was small; baseline SE was estimated to be 8% higher for a 50‐year‐old versus an 80‐year‐old, decreasing to 6% by 1 month. Baseline WASO was 13 minutes longer for Black versus White subjects, corresponding to a 5‐minute lower change from baseline at the end of the study. For subjective end points, the statistically significant covariate effects for age, sex, and race were not deemed therapeutically relevant, likely reflecting physiologic sleep pattern changes across age and study subgroups. Both polysomnography and subjective analyses indicated clinically meaningful differences from baseline for both lemborexant treatments, with effects being greater for 10‐mg versus 5‐mg lemborexant, while indicating that covariate‐specific lemborexant dose adjustments are not warranted.
Prevalence of Baseline Cardiac Arrhythmias in Participants with Overweight or Obesity in Phase 1 Clinical Trials: Analysis of 24‐Hour Holter Electrocardiogram Recordings
Authors: Skovgaard Dorthe , Haahr Poul‐Martin , Lester Robert , Clark Katherine , Paglialunga Sabina , Finer Nick , Friedrichsen Martin H. , Hjerpsted Julie B. , Engelmann Mads D.M.
Published: December 2022

Although estimates of the prevalence of cardiac arrhythmias in healthy volunteers exist, there is a lack of baseline data in other specific populations, such as people living with overweight and obesity, who are increasingly involved in clinical trials. This study investigated the baseline prevalence of arrhythmias in participants with overweight or obesity in 2 phase 1 trials of weight management medications (NCT03661879, NCT03308721). Participants aged 18–55 years, without a history of cardiovascular disease, and with body mass index (BMI) of 25.0–39.9 kg/m2, were screened for abnormalities in vital signs, electrocardiogram (ECG) recordings, and electrolytes. Baseline 24‐hour ECG (Holter) data were collected and manually reviewed by a cardiologist. The primary endpoint was the proportion of participants with ≥1 episode of the predefined cardiac arrhythmias. Continuous 12‐lead ECG data were obtained from 207 participants. Most arrhythmias occurred in <3% of participants. Atrioventricular blocks and other potentially malignant arrhythmias were uncommon. There were no associations with age, sex, or BMI. Prevalence of atrioventricular blocks, nonsustained ventricular tachycardia, and other potentially malignant arrhythmias mirrored those reported in healthy participants with normal weight. In clinical trials of weight management medication, knowledge of the baseline prevalence of arrhythmias in people with overweight and obesity may inform trial eligibility criteria, improve on‐trial decisions, and could be useful in discussions with health authorities. Baseline Holter readings and real‐time ECG telemetry monitoring should be considered in such trials if arrhythmia risk is intrinsic to the molecule, or when signals have been observed in preclinical studies.
HIV‐associated Burkitt lymphoma in the combination antiretroviral therapy era: Real‐world outcomes and prognostication
Authors: Wang Chaoyu , Liang Shunsi , Quan Xi , Guo Bingling , Huang Dehong , Li Jieping , Liu Yao
Published: December 2022

We performed a retrospective study to analyze the clinical characteristics and outcomes of human immunodeficiency virus–associated Burkitt's lymphoma in Chongqing University Cancer Hospital, southwest China, from March 2012 to February 2022. In the entire cohort, the median age was 36 years (range, 28–60 years), and more patients were male (82.4%). The median CD4+ T cell count was 214/μl (range, 54–601), of whom 47.1% had a CD4+ T cell count below 200/μl. Most patients had elevated lactate dehydrogenase (LDH), elevated β2‐MG, extranodal involvement and advanced Ann Arbor stage at diagnosis. With a median follow‐up of 11.5 months (range, 1.6–94.9 months), the overall 1‐year progression‐free survival and overall survival (OS) rates were 27.6% and 47.6%, respectively. The 1‐year OS times in the LDH < 3 upper limit of normal and LDH ≥ 3 upper limit of normal groups were 62.5% and 31.3%, respectively (p = 0.008). The 1‐year OS times in the received <4 cycles and ≥4 cycles groups were 0% and 77.8%, respectively (p < 0.001). These results demonstrated that LDH < 3 upper limit of normal and received ≥4 cycles of chemotherapy were significantly associated with improved outcomes. However, rituximab administration was not significantly associated with improved outcomes.
Synthesis and characterization of 2‐trifluoromethyl‐4(3H)‐quinazolinone derivatives with various 3‐substituents
Authors: Al‐Harbi Reem A. K. , Albadrani Raneem F. N. , Abbas Samir Y.
Published: December 2022

Due to the significant properties and applications of quinazolinones and fluorinated compounds, there is increasing interest in the design and synthesis of new quinazolinone structures and fluorinated compounds. So, new derivatives of 2‐trifluoromethyl‐4(3H)‐quinazolinone were synthesized. Reaction of 2‐trifluoromethyl‐3,1‐benzoxazine‐4‐one benzoxazine‐4‐one 1 with some aniline derivatives afforded 3‐aryl‐2‐trifluoromethyl‐4(3H)‐quinazolinone derivatives 3 in good yields. On the other hand, treatment of 3,1‐benzoxazine‐4‐one 1 with aliphatic binucleophile afforded bis‐benzamide derivative 5 rather than bisquinazolines derivative 4. The reaction of benzoxazine‐4‐one 1 with 1,4‐phenylenediamine afforded bisquinazoline derivative 6. Reaction of 3‐amino‐4(3H)‐quinazolinone 7 with aldehydes or isothiocyanates gave the corresponding Schiff's base 8 and thiourea 9 derivatives, respectively. The structures of newly synthesized 2,3‐disubstituted 4(3H)‐quinazolinone derivatives were demonstrated through NMR (proton carbon and fluorine) experiment as well as mass spectra and elemental analyses. Most of the synthesized compounds were obtained in excellent yields, so they will share in enrichment the chemical libraries.
Metabolic syndrome among treatment‐naïve people living with and without HIV in Zambia and Zimbabwe: a cross‐sectional analysis
Authors: Chihota Belinda V. , Mandiriri Ardele , Shamu Tinei , Muula Guy , Nyamutowa Hellen , Taderera Charlotte , Mwamba Daniel , Chilengi Roma , Bolton‐Moore Carolyn , Bosomprah Samuel , Egger Matthias , Chimbetete Cleophas , Wandeler Gilles ,   for IeDEA Southern Africa
Published: December 2022

Introduction

Chronic viral replication has been linked to an increased risk of cardiovascular and metabolic diseases in people living with HIV (PLWH), but few studies have evaluated this association in Southern Africa. We explored the determinants of metabolic syndrome (MetS) among treatment‐naïve adults living with and without HIV in Southern Africa.

Methods

Treatment‐naïve PLWH and people living without HIV (PLWOH) ≥30 years were consecutively enrolled from primary care clinics in Zambia and Zimbabwe. PLWOH were seronegative partners or persons presenting for HIV testing. We defined MetS as the presence of central obesity plus any two of the following: raised blood pressure, impaired fasting glucose, reduced high‐density lipoprotein cholesterol and raised triglycerides, as defined by the International Diabetes Federation. We used logistic regression to determine factors associated with MetS.

Results

Between August 2019 and March 2022, we screened 1285 adults and enrolled 420 (47%) PLWH and 481 (53%) PLWOH. The median age was similar between PLWH and PLWOH (40 vs. 38 years, p < 0.24). In PLWH, the median CD4+ count was 228 cells/mm3 (IQR 108–412) and the viral load was 24,114 copies/ml (IQR 277–214,271). Central obesity was present in 365/523 (70%) females and 57/378 males (15%). MetS was diagnosed in 172/901 (19%, 95% confidence interval [CI] 17–22%), and prevalence was higher among females than males (27% vs. 9%). In multivariable analyses, HIV status was not associated with MetS (adjusted odds ratio [aOR] 1.05, 95% CI 0.74–1.51). Risk factors for MetS included age older than 50 years (aOR 2.31, 95% CI 1.49–3.59), female sex (aOR 3.47, 95% CI 2.15–5.60), highest income (aOR 2.19, 95% CI 1.39–3.44) and less than World Health Organization recommended weekly physical activity (aOR 3.35, 95% CI 1.41–7.96).

Conclusions

We report a high prevalence of MetS and central obesity among females in urban Zambia and Zimbabwe. Lifestyle factors and older age appear to be the strongest predictors of MetS in our population, with no evident difference in MetS prevalence between treatment‐naïve PLWH and PLWOH.
Characterization of olivines and their metallic composition: Raman spectroscopy could provide an accurate solution for the active and future Mars missions
Authors: Torre‐Fdez Imanol , García‐Florentino Cristina , Huidobro Jennifer , Coloma Leire , Ruiz‐Galende Patricia , Aramendia Julene , Castro Kepa , Arana Gorka , Madariaga Juan Manuel
Published: December 2022

The presence of olivine and its geochemical composition (forsterite/fayalite ratio) are relevant factors for the study of Mars. The use of Raman spectrometers in the Mars 2020 and future missions opens new possibilities to assess the Mg/Fe ratios in the analyzed olivine bearing rocks. On the one hand, its presence indicates approximately where and when Mars had volcanic activity, due to the partial weathering of this mineral into other secondary minerals. On the other hand, the forsterite and fayalite content of olivine can be used to study the origin and evolution of its parent magma, since this mineral is one of the first to crystallize from it. In order to properly study the forsterite and fayalite ratio of olivines, this work proposes a new calibration model using Raman spectroscopy, doing a thorough literature review of previous studies in order to improve the calibration quality. The proposed model improves greatly the accuracy and uncertainty associated with the final result of forsterite and fayalite (around 2%) compared to those published earlier in the literature (around or above 10%). Using the new model, it will be possible to assess the forsterite and fayalite ratios of Martian olivines properly, providing relevant information about their parent magma.