bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Adversity Affects Cerebellar Structure and Function—A Systematic Review of Human and Animal Studies
Authors: Mundorf Annakarina , Merklein Sarah A. , Rice Laura C. , Desmond John E. , Peterburs Jutta
Published: October 2024

Recent research has highlighted cerebellar involvement in cognition and several psychiatric conditions such as mood and anxiety disorders and schizophrenia. Attention‐deficit/hyperactivity disorder and autism spectrum disorder have been linked to reduced cerebellar volume as well. Cerebellar alterations are frequently present after early adversity in humans and animals, but a systematic integration of results is lacking. To this end, a systematic literature search was conducted in PubMed, Web of Science, and EBSCO databases using the keywords “early adversity OR early life stress” AND “cerebellum OR cerebellar.” A total of 45 publications met the inclusion criteria: 25 studies investigated human subjects and 20 reported results from animal models. Findings in healthy subjects show bilateral volume reduction and decreased functional connectivity within the cerebellum and between the cerebellum and frontal regions after adversity throughout life, especially when adversity was assessed with the Childhood Trauma Questionnaire. In clinical populations, adults demonstrate increased cerebellar volume and functional connectivity after adversity, whereas pediatric patients show reduced cerebellar volume. Animal findings reveal cerebellar alterations without necessarily co‐occurring pathological behavior, highlighting alterations in stress hormone receptor levels, cell density, and neuroinflammation markers. Cerebellar alterations after early adversity are robust findings across human and animal studies and occur independent of clinical symptoms.
Seascape Genetics and Distinct Intraspecific Diversification of the Decapod Nephrops norvegicus in the Adriatic Sea
Authors: Mašanović Marina , Žuvić Luka , Žužul Iva , Talijančić Igor , Šegvić‐Bubić Tanja
Published: October 2024

Norway lobster Nephrops norvegicus, a prized decapod crustacean species, is found at different depths across the East Atlantic Ocean and Mediterranean Sea. Despite management efforts, the stocks are globally characterised as overexploited. In the present study, the impact of biogeographical boundaries on the phylogeographical and demographic population status was investigated within the Adriatic Sea, addressing important genetic indices for decapod functional conservation management. Central Mediterranean, Adriatic Sea A total of 482 individuals of Nephrops divided into the 12 samples were collected across biogeographical range of the Adriatic Sea. Using the mtDNA D‐loop and microsatellite markers, methods of phylogeography and seascape genetics were applied to infer offshore versus coastal population divergence, demography and structure. Significant findings include genetic differentiation between offshore and coastal samples, with higher diversity indices in open waters. The limited gene flow observed between these two areas emphasises the self‐sustained nature of coastal populations. Recent demographic changes in coastal populations reflect geographical constraints, fishing pressures and fluctuations in self‐recruitment success. Additionally, the study reveals historical biogeographic events shaping the Adriatic populations, with evidence suggesting lineage divergence during the upper Pleistocene and postglacial recolonisation from southern Adriatic refugia. The role of biogeographical conditions in shaping genetic structure and limited gene flow between inshore and offshore areas underscore the need for improved management strategies, emphasising the importance of marine protected areas in conserving coastal populations and maintaining overall genetic diversity of the Norway lobster in the Adriatic Sea. Genomic monitoring within current management practices is recommended.
Trade‐Offs Between Forage Availability, Accessibility, and Predation Risk on Winter Foraging Strategies of Wood Bison (Bison bison athabascae)
Authors: Rawleigh Garrett J. , Edwards Mark A. , Epperson Darren , Nielsen Scott E.
Published: October 2024

Optimal foraging theory (OFT) and the energy maximization hypothesis (EMH) have long been essential when examining wildlife habitat selection. At high latitudes and altitudes, animals in winter face greater limitations in availability and accessibility of forage. Here we explore the foraging behavior of wood bison (Bison bison athabascae) during winter within the Ronald Lake bison herd in northeastern Alberta, Canada, and examine the trade‐offs they face due to limitations in forage abundance and availability (snow conditions), as well as the need to minimize predation risk. We used Global Positioning System (GPS) location data collected from 70 female wood bison to identify winter foraging sites and craters selected by bison to access forage beneath the snow. Within wetlands used by bison we selected 190 pairs of used (foraged) and random (available) sites to test eight a priori hypotheses explaining how bison traded‐off between forage availability, accessibility, and minimizing predation risk. We found with matched‐paired logistic regression that Carex atherodes was 1.21‐times more likely to be selected per unit increase in ground cover, compared to 1.17‐times per unit ground cover for C. aquatilis and C. utriculata. However, all Carex species showed an increase in selection when cover was > 50% cover within individual craters. While the importance of Carex was clear, forage site selection was still inversely related to snow depth. There is also a neutralizing combined effect of snow depth and Carex species ground cover which suggests that bison maximized their energy return by avoiding areas with deep snow (> 30 cm) that demanded intensive cratering, even when highly selected forage was accessible beneath. Avoidance of forage areas with deep snow demonstrates that wood bison employed a foraging strategy that considers both forage availability and environmental conditions, with snow depth being a limiting factor. We highlight the relationship between optimal foraging based on food availability and the trade‐offs within an energy restrictive winter season, furthering the understanding of how large herbivores forage strategically to maximize energy intake in northern environments.
Oligonucleotides Containing 8,1′‐Ethano‐2′‐deoxyadenosine: Synthesis and Properties
Authors: Hanashiro Honoka , Ito Yuta , Fuchi Yasufumi , Hari Yoshiyuki
Published: October 2024

Oligonucleotides containing 8,1′‐ethano‐2′‐deoxyadenosine (ethano‐dA) were synthesized in which the adenine base (ethA) is fixed in the syn conformation. Ethano‐dA phosphoramidite was synthesized by using a 1,5‐hydrogen‐atom transfer/radical cyclization process and introduced into oligonucleotides, which were successfully obtained by employing the 4,4′‐dimethoxytrityl‐off synthesis mode. The duplex‐forming ability of the oligonucleotides containing ethano‐dA was evaluated. In the antiparallel Watson–Crick duplex, the ethA formed stable base pairs with thymine and guanine, in which two Hoogsteen‐type hydrogen bonds could be formed. By contrast, the parallel Hoogsteen duplex containing the ethA:thymine base pair showed thermal stability comparable to that containing a natural adenine:thymine base pair because ethA and thymine can form two Watson–Crick‐type hydrogen bonds. These results indicated that ethano‐dA may be helpful for elucidating the function of adenine bases through the syn conformation in DNA.
Real meat shows good performance in maintaining colonic barrier function at a recommended amount of intake in mice
Authors: Xie Yunting , Cai Linlin , Ibeogu Isaiah Henry , Zhou Guanghong , Li Chunbao
Published: October 2024

This study aimed to investigate the effects and underlying mechanisms of real meat and plant‐based meat analogs on intestinal barrier function. Methods including PacBio sequencing, HPLC, histological observation, western blotting, and RT‐qPCR were jointly applied. The results indicated that the 20‐day intake of real meat and plant‐based meat analogs did not induce pathological changes in the colon of mice. However, when the feeding period was extended to 68 days, inflammatory infiltration was observed in the colon tissue of mice fed plant‐based meat analogs. In contrast, the intake of real meat for 68 days performed better in maintaining colonic barrier function by reducing cell apoptosis, increasing the number of goblet cells and mucin secretion, and upregulating the expression of tight junction proteins. High‐throughput sequencing revealed that the intake of real meat significantly altered the composition of the gut microbiota, reducing pro‐inflammatory bacteria (such as Bacteroides, Desulfovibrio, or Colidextribacter) or pathogenic bacteria (such as Mucispirillum and Helicobacter) while increasing beneficial bacteria (such as Lactobacillus, Bifidobacterium, or Roseburia). Additionally, the consumption of real meat markedly decreased protein fermentation in the colon, leading to lower levels of cadaverine, putrescine, and spermine. These changes associated with real meat consumption reduced the activation of the pro‐inflammatory pathway (lipopolysaccharide/Toll‐like receptor 4/nuclear factor kappa B), ultimately maintaining colonic homeostasis in mice. Collectively, the findings suggest that the proper intake of real meat is more beneficial for colon health in mice compared to plant‐based meat analogs.
Accessing the growth of heat‐resistant mold ascospores in potato dextrose agar, isolated from a processed fruit jam—Dependence of temperature, pH, and sugar concentration
Authors: Alam Mahabub , Sarkar Animesh , Sayem A. S. M. , Biswas Rahul , Hasan M. M. Mahdi
Published: October 2024

Heat‐resistant molds (HRM) pose a significant threat to food industries due to their ability to survive in high temperatures (pasteurization range) and grow in a variety of environments. To understand how inhibiting variables affect HRM growth, this study evaluated the impact of high sugar concentration (50–60°Brix), low pH (3.5–4.5), and temperature (5–15) on the time (tv) to develop detectable colonies (colony diameter = 2 mm) of three HRM strains (Byssochlamys nivea, Byssochlamys fulva, Neosartorya fischeri) isolated from mixed fruit products. The study found that all HRM strains had relatively short periods of time to develop detectable colonies at 50°Brix, while no visible growth was observed at 60°Brix. Byssochlamys nivea was found to be the most susceptible to low temperatures, requiring up to 43 days to develop detectable colonies at 10°C and unable to grow at colder temperatures. The tv varied from 6 to 27 days based on pH and isolates. HRM's resistance to high sugar concentrations and ability to grow in cold environments pose a threat to the microbiological safety of fruit products. The evaluated data were fitted to several statistical distribution models to support further research on the quantitative microbiological risk in processed fruit products. This study provides valuable insights into how inhibiting variables affect HRM growth and can inform efforts to minimize their impact on fruit‐based product quality and safety.
Exploring Jalisco's water quality: A comprehensive web tool for limnological and phytoplankton data
Authors: Camarena‐Orozco Cristofer , Carrillo Eduardo Juárez , González Martha Alicia Lara , Guerra‐Castro Edlin
Published: October 2024

This study presents a comprehensive dataset of hydrological information gathered from five key eastern basins in Jalisco, Mexico. The dataset encompasses approximately 50 limnological variables and phytoplankton counts specifically for one of these basins. Water‐quality data were collected by the State Water Commission of Jalisco, adhering to the methods outlined in the Official Mexican Norm ‘NOM‐127’. Monthly samplings were conducted to assess environmental variables such as pH, temperature, oxygen, nutrients and heavy metals. Monitoring has been ongoing for three basins since 2009, while the remaining two basins have been monitored since 2015 and 2020. Phytoplankton data were obtained from monthly samples taken by the University of Guadalajara between 2014 and 2019 in Lake Cajititlán. The original data were cleaned and organized using tidy data principles, with codes accessible on GitHub. To facilitate data exploration and visualization, we developed a user‐friendly web application with the Shiny package in R. This application enables users to explore the dataset through summary statistics tables, time series plots and phytoplankton community analysis. The dataset is accessible on Zenodo. The presented data hold significance for environmental and water‐quality assessment and applications in machine learning, neural network models, community ecology and broader environmental research. Notably, the raw data, publicly accessible from the State Water Commission of Jalisco, have been previously utilized for these purposes. This dataset offers value due to its diverse limnological and phytoplankton variables, an extended time frame of availability, a curated and streamlined accessibility process and the inclusion of a web application for intuitive exploration and visualization.
Solid‐phase synthesis of silicalite‐1 molecular sieve based on fly ash and its CO2 adsorption performance
Authors: Wu Xianglian , Nulahong Aisha , Miao Conghui , Liu Qinghua , Li Jiangyuan , Tuo Changmin
Published: October 2024

In this work, an alkali melting‐pickling assisted solid phase synthesis method of S‐1 zeolite molecular sieve with excellent adsorption properties for CO2 was successfully developed by using solid waste fly ash. SiO2 with a purity of up to 97.84% was successfully extracted by using alkaline fusion activation, high temperature calcination and pickling. The CO2 adsorption capacity of the prepared SiO2 was 0.51 mmol/g at 298 K and 1 bar. Silicalite‐1 molecular sieve was prepared by solid phase synthesis method using SiO2 extracted from fly ash as silicon source. The results showed that the prepared Silicalite‐1 had good morphology and relatively high crystallinity. The specific surface area is 623.30 m2/g, and the total pore volume is 0.31 cm3/g. In addition, the adsorption capacity of CO2 was 2.05 mmol/g at 298 K and 1 bar. Compared with the prepared SiO2, the adsorption capacity of CO2 by Silicalite‐1 molecular sieve increased by four times. Moreover, under the test condition of 298 K, it has a high selectivity coefficient for CO2/N2 mixed gas, and after 10 times of adsorption‐desorption cycle tests, the adsorption capacity of Silicalite‐1 molecular sieve for CO2 does not change significantly, and its adsorption rate can still be as high as 89.31%. The results indicate that Silicalite‐1 molecular sieve prepared by solid phase synthesis method has good adsorption selectivity and adsorption–desorption cycle regeneration stability, and can be used in the field of CO2 adsorption, separation and purification. © 2024 Society of Chemical Industry and John Wiley & Sons, Ltd.
Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition
Authors: Grenville Zoe S. , Noor Urwah , Rinaldi Sabina , Gunter Marc J. , Ferrari Pietro , Agnoli Claudia , Amiano Pilar , Catalano Alberto , Chirlaque María Dolores , Christakoudi Sofia , Guevara Marcela , Johansson Matthias , Kaaks Rudolf , Katzke Verena , Masala Giovanna , Olsen Anja , Papier Keren , Sánchez Maria‐Jose , Schulze Matthias B. , Tjønneland Anne , Tong Tammy Y. N. , Tumino Rosario , Weiderpass Elisabete , Zamora‐Ros Raul , Key Timothy J. , Smith‐Byrne Karl , Schmidt Julie A. , Travis Ruth C.
Published: October 2024

Measuring pre‐diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case–control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography‐mass spectrometry. Multivariable‐adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high‐grade, aggressive. We corrected for multiple testing using the Benjamini–Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high‐grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow‐up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR1SD 0.80, 95% CI 0.66–0.96 and 0.76, 0.59–0.97, respectively) but were weaker after longer follow‐up (0.95, 0.82–1.10 and 0.85, 0.67–1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68–0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced‐stage disease.
Detection of anti‐EBV TCR CDR3s associated with better outcomes for EBV‐positive, Ugandan cases of Burkitt lymphoma
Authors: Jain Rahul , Huda Taha I. , Paul Srijit , Chobrutskiy Andrea , Chobrutskiy Boris I. , Baker Madeline C. , Goel Nandini , Blanck George
Published: October 2024

Burkitt lymphoma (BL) has a tight association with Epstein–Barr virus (EBV), especially in sub‐Saharan Africa. While the relationship between BL and EBV is well documented, the relationship between the anti‐EBV adaptive immune response, particularly in sub‐Saharan African cases, and disease course, has not been substantially investigated. An analysis of T‐cell receptor (TCR) complementarity determining region‐3 (CDR3) sequences, reported here, from EBV‐positive, Ugandan BL tumor samples revealed a correlation between the presence of anti‐EBV CDR3s and improved overall survival probabilities. Furthermore, chemical complementarity assessments demonstrated higher complementarity for TCR CDR3s and EBV epitopes in the cases where there had been a detection of the anti‐EBV CDR3 AA sequence matches in the BL tumor samples. Overall, the results reported here raise the question of whether EBV targeted immunotherapy would lead to better BL outcomes?
Visible Light Mediated CO2 Fixation Reactions to Produce Carbamates and Carbonates: A Comprehensive Review
Authors: Goswami Asmita , Verma Monika , Thakur Ajay , Bharti Ruchi , Sharma Renu
Published: October 2024

CO2 is a significant greenhouse gas, and is considered as a copious renewable carbon reagent. From a synthetic perspective, it can be used as a sustainable and substitute C1 building block because of its nontoxic, nonflammable, and abundant nature. The transformation of a wide range of organic molecules with CO2 into numerous efficient commodities is a defining feature of recent success in this sector. Because of its numerous applications, photocatalysts and visible light‐mediated synthesis of carbamates and cyclic carbonates using CO2 have drawn a lot of interest from researchers. This mini review mainly focusses on the different one‐pot reactions that are proven to be efficacious for chemical fixation of CO2 in producing industry‐based compounds of carbamates and carbonates with the creation of CO, CH, CC, and CN bonds.
A Comparative Study on the Consistency of Ultrasound and X‐Ray in Assessing Risser Sign
Authors: Xue Lina , Jiang Xuehong , Shan Tao , Wang Kai , Zhou Wei , Wang Xujie , Zhu Lili , Yu Bing , Wang Ajun , Dong Fenglin
Published: October 2024

Objectives

Adolescent idiopathic scoliosis (AIS) is a 3‐dimensional spinal deformity involving lateral curvature, sagittal plane imbalance, and vertebral rotation. In China, AIS affects over 3 million individuals, with 300,000 new cases annually. AIS impacts physical and psychological well‐being, necessitating tailored treatment plans based on growth risk factors. This study evaluates the consistency of ultrasound and X‐ray assessments of the Risser sign in AIS patients and explores correlations between iliac crest distance and pelvic rotation degree.

Methods

This prospective study enrolled 80 patients diagnosed with AIS from June to September 2023 at Changzhou Sports Hospital. Eligible participants were aged 10–18 with a Cobb angle >10°. Ultrasonographic examinations were conducted by 3 experienced physicians using the VINNO V10 portable ultrasound system. The primary outcome was the Risser stage determined by X‐ray and ultrasound, with secondary outcomes including thoracic and thoracic‐lumbar segment rotation angles. Statistical analyses included kappa statistics, correlation analyses, and multiple regression.

Results

Among the 77 valid cases, 154 iliac wings were evaluated, with a high concordance rate of 77% between ultrasound and X‐ray assessments. kappa values for left and right iliac crests were 0.723 and 0.808, respectively. Grouping Risser grades (0–1, 2–3, and 4–5) into 3 categories yielded kappa values of 0.93, 0.96, and 0.93, indicating high consistency. Significant correlations were found between iliac crest distances and rotation angles (left iliac crest distance and left thoracic rotation angle, r = 0.56, P < .001; right iliac crest distance and right thoracic‐lumbar rotation angle, r = 0.69, P < .001; right iliac crest distance and right thoracic rotation angle, r = 0.39, P < .01).

Conclusions

Ultrasound is a reliable, radiation‐free alternative to X‐ray for assessing the Risser sign in AIS patients. Despite observed inconsistencies in intermediate Risser grades, ultrasound's ability to reduce radiation exposure and provide consistent results makes it a valuable tool in clinical practice. Further research is needed to optimize ultrasound techniques and explore its potential for early detection and intervention in scoliosis management.
Can We Protect China's Northern Coast Wetlands From Tidal Dynamics by Restoring Native Species After Spartina alterniflora Is Eradicated? A Model‐Based Analysis
Authors: Liu Jiakai , Wang Jingwen , Zhao Shiqiang , Engel Bernard A. , Zhang Mingxiang , Zhang Zhenming
Published: October 2024

In recent years, the Chinese government has implemented a series of initiatives with the objective of eradicating the invasive Spartina alterniflora along the entire coastline. This has given rise to concerns about the potential for subsequent coastal erosion and salt marsh shrinkage. This study introduces a novel contribution in the form of a model‐based analysis, grounded in fieldwork from the Yellow River Delta, which assesses the potential of native Suaeda salsa as an alternative for coastal protection. Our approach is distinctive in that it not only compares the flow velocity reduction effects of S. alterniflora and S. salsa, but also evaluates the efficacy of three distinct planting patterns in managing tidal dynamics. In this study, we present a significant finding: while both species can mitigate tidal flow velocity, S. alterniflora shows superior performance, which represents a novel point of discussion in the field of coastal wetland management. Furthermore, our research indicates that dense aggregated planting patterns are particularly effective during storm surges, offering a strategic insight for future ecological engineering. However, we recognize the potential limitations of our approach, including the need for continuous management to control the spread of S. alterniflora and the necessity for further research to optimize the restoration potential of S. salsa under varying tidal conditions. Our findings highlight the importance of a balanced approach, suggesting the retention of a portion of S. alterniflora while also emphasizing the strategic planting of S. salsa in high‐density configurations to enhance coastal resilience.
Current approaches to facial nerve schwannoma surgery
Authors: Hernandez‐Montero Elena , Garcia‐Ibañez Luis , Jubes Sara , Salmeron Jorge , Garcia‐Ibañez Emilio , Larrosa Francisco
Published: October 2024

Background

Facial nerve schwannomas (FNSs) are exceedingly rare benign tumors. This study aims to report on a series of excised FNSs, providing clinical information and details on their surgical management, including novel approaches.

Methods

We retrospectively reviewed patients who underwent surgical excision of FNSs in a private otology clinic and public tertiary referral center. The main outcome measures were facial nerve function, complete tumor removal, postoperative complications, tumor recurrence, and hearing.

Results

Seventeen patients (10 men and 7 women) with a mean age of 44.23 years (SD, 12.21) underwent surgery during the study period. The most common symptom was facial nerve dysfunction (58.8%). Facial and otoneurologic symptoms (hearing loss, tinnitus, and vertigo) were observed in 88.8% and 77.7% of patients, respectively. The middle cranial fossa (MCF) was the most common approach (six patients, 35.2%), followed by translabyrinthine (TL), transmastoid (TM), and combined TM‐MCF (three patients, 17.6% each). Exclusive endoscopic transcanal suprageniculate (ETS) and mastoid combined with cervical approaches were applied once in two patients, 5.8% each. Total tumor removal was achieved in all cases. No significant postoperative complications were observed. The mean follow‐up period was 193.2 months (SD, 119.5) and no tumor recurrence was observed.

Conclusion

This study provides further evidence for the safety and efficacy of various surgical approaches for FNS, and incorporates the endoscopic transcanal approach.

Level of evidence

4.
Surface Cation Cross‐Locking Enables Non‐Destructive “On‐Demand” Synthesis of Anion‐Exchanged CsPbX3 Perovskite Nanocrystals
Authors: Huang Guangguang , Sun Kaiwei , Xiong Xinyang , Song Long , Liu Gaoke , Zheng Chaofang , Yu Feilong , Du Zuliang
Published: October 2024

Post‐synthetic halide anion exchange is considered a “double‐edged sword” for perovskite nanocrystals (PNCs), which offer unique access to color tunability while bringing about surface defects. Herein, a novel surface cation cross‐locking (SCCL) strategy is proposed to achieve the anion‐exchanged CsPbX3 PNCs (X is Cl, Br, I) with non‐destructive emissions. This is achieved using a dendritic ligand of Pentaerythritol tetrakis (3‐mercaptopropionate) (PETMP) as a surface cross‐locker, which can form the multiple coordination to the surface Pb cation of octahedral [PbX6]4− during the fast halide anion exchange via four end‐thiolates and four side‐carboxylates. As a result, the red‐ and blue‐emitting anion‐exchanged CsPbX3 PNCs exhibit high photoluminescence quantum yield (PLQY) values of >97%, close to the parent green‐emitting CsPbBr3 PNCs. Moreover, the “on‐demand” synthesis of anion‐exchanged CsPbX3 PNCs is also performed via autonomous robotic in‐flow experimentation. This work provides a new general post‐synthetic way for the full‐color CsPbX3 PNCs with compositions that are inaccessible via direct synthetic routes.
Silmitasertib in Combination With Cabozantinib Impairs Liver Cancer Cell Cycle Progression, Induces Apoptosis, and Delays Tumor Growth in a Preclinical Model
Authors: Haga Yuki , Ray Ranjit , Ray Ratna B.
Published: October 2024

The rising incidence of hepatocellular carcinoma (HCC) is a global problem. Several approved treatments, including immune therapy and multi‐tyrosine kinase inhibitors, are used for treatment, although the results are not optimum. There is an unmet need to develop highly effective chemotherapies for HCC. Targeting multiple pathways to attack cancer cells is beneficial. Cabozantinib is an orally available bioactive multikinase inhibitor and has a modest effect on HCC treatment. Silmitasertib is an orally bioavailable, potent CK2 inhibitor with a direct role in DNA damage repair and is in clinical trials for other cancers. In this study, we planned to repurpose these existing drugs on HCC treatment. We observed a stronger antiproliferative effect of these two combined drugs on HCC cells generated from different etiologies as compared to the single treatment. Global RNA‐seq analyses revealed a decrease in the expression of G2/M cell cycle transition genes in HCC cells following combination treatment, suggesting G2 phase cell arrest. We observed G2/M cell cycle phase arrest in HCC cells upon combination treatment compared to the single‐treated or vehicle‐treated control cells. The downregulation of CCNA2 and CDC25C following combination therapy further supported the observation. Subsequent analyses demonstrated that combination treatment inhibited 70 kDa ribosomal protein S6 kinase (p70S6K) phosphorylation, and increased Bim expression. Apoptosis of HCC cells were accompanied by increased poly (ADP‐ribose) polymerase cleavage and caspase‐9 activation. Next, we observed that a combination therapy significantly delayed the progression of HCC xenograft growth as compared to vehicle control. Together, our results suggested combining cabozantinib and silmitasertib would be a promising treatment option for HCC.
Determination of an optimum patch configuration in the repair of a center crack in thin aluminum sheet using polymer composite patch
Authors: Rasane Amol , Kumar Prashant , Khond Mohan
Published: October 2024

The formation of cracks and their growth is an issue of concern in structural applications incorporating thin metal sheets. Adhering cracked region with a patch of composite material has proved effective in repairing cracks. Determining an optimum configuration of composite patch is still a challenge as a shorter patch may not be effective and a larger patch leads to wastage of resources. An appropriate methodology is required for specifying an optimum patch configuration in terms of its length, width, and thickness. The work presented prescribes a methodology for obtaining an appropriate combination of geometrical parameters of the composite patch. The computational tools like finite element analysis and response surface method have been incorporated. This is an extensive work consisting of a number of iterations of numerical analyses carried out for different combinations of the length and width of the patch. The results were also obtained for three different patch thicknesses in which the number of plies were increased from a single ply to three plies. The optimum size was obtained for each of the three patch thicknesses. Finally, a methodology for obtaining the most appropriate patch configuration based on the practical constraint of a small available area is prescribed.

Highlights

The crack repair in a thin structural sheet using fiber reinforced polymer composite patch separates at the interface. The optimum size of the patch needs to be used for an effective repair.

The work consists of a combination of experiments and numerical simulations using finite element analysis.

Response surface methodology is employed in this optimization study.
Monitoring Pregnancies Exposed to Galcanezumab for Migraine in a United States Administrative Claims Database
Authors: Hoffman Sarah R. , Mawanda Francis , Crowe Christopher L. , Ruff Dustin D. , Lanes Stephan , Schroeder Krista
Published: October 2024

Purpose

Galcanezumab is a calcitonin gene‐related peptide monoclonal antibody indicated for migraine prevention in adults. Due to the long half‐life of galcanezumab and the prevalence of migraine in women of childbearing age, galcanezumab exposure may occur during pregnancy. However, real‐world use and safety of galcanezumab during pregnancy has not been fully described. To help fill this gap, galcanezumab has two ongoing pregnancy safety studies, one of which is an insurance claims database study.

Methods

This database study is actively identifying and following pregnancies exposed to galcanezumab using commercial claims from the Healthcare Integrated Research Database (HIRD). Patient accrual is planned from September 2018 to June 2026, with a final study report planned for December 2027. This study requires 430 galcanezumab‐exposed pregnancies with linked infants to reach power for comparative analysis of major congenital malformations.

Results

Recent monitoring of patient accrual, including data from 28 September 2018 to 31 January 2023, identified 207 galcanezumab‐exposed pregnancies in women with migraine in the HIRD, of which 110 were live births and 73 of which were linked to an infant. This represents an annual accrual rate of approximately 17 pregnancies linked to infants, which is substantially lower than the 55 required annually to reach target size within current regulatory‐committed study timelines.

Conclusions

The accrual of a sufficient number of galcanezumab‐exposed pregnancies represents a substantial, but not uncommon, barrier to conducting comparative analyses in pregnancy studies. Potential solutions that would allow for timely dissemination of important safety information to patients and providers may be available.
The Awareness of and Adherence to the Pregnancy Prevention Program for Oral Retinoids: A Questionnaire Survey in Denmark
Authors: Backran Dana , Ahmad Sophia , Hansen Johanne M. , Almarsdóttir Anna Birna , Jacobsen Ramune
Published: October 2024

Purpose

We aimed to investigate the awareness of oral retinoid teratogenicity and the adherence to the pregnancy prevention program (PPP) related to oral retinoid use by physicians, pharmacists, and patients in Denmark.

Methods

As part of the multi‐country survey, web‐based questionnaires were distributed among Danish dermatologists, general practitioners, community pharmacists, and women of childbearing age, who were using or had used oral retinoids within the past 5 years.

Results

A total of 62 physicians, 96 pharmacists, and 50 oral retinoid using women responded; 95%, 100%, and 98%, respectively, were aware of the teratogenic risks of oral retinoids. For physicians, the most applied PPP measures were the usage of the patient (44%) and the healthcare professional (19%) guides, while the least applied measure was signing medication risk awareness form (3%). Among the pharmacists, the warning sign on the outer medication package was the most used measure (45%). Among the women, a majority (90%) had read the patient information leaflet included in the medication package and 72% discussed the use of contraception with their healthcare provider, while risk awareness forms and patient cards were seen by only few.

Conclusions

In Denmark, physicians, pharmacists, and medicine users were aware about the teratogenic effects of oral retinoids. Adherence to pregnancy prevention measures varied, suggesting unwillingness to use the measures that require patients' signatures among physicians and a lack of awareness of pharmacy targeting measures. Accessibility of the latter measures need to be optimized to improve the safety of oral retinoid use.
Core Concepts in Pharmacoepidemiology: Quantitative Bias Analysis
Authors: Brown Jeremy P. , Hunnicutt Jacob N. , Ali M. Sanni , Bhaskaran Krishnan , Cole Ashley , Langan Sinead M. , Nitsch Dorothea , Rentsch Christopher T. , Galwey Nicholas W. , Wing Kevin , Douglas Ian J.
Published: October 2024

Pharmacoepidemiological studies provide important information on the safety and effectiveness of medications, but the validity of study findings can be threatened by residual bias. Ideally, biases would be minimized through appropriate study design and statistical analysis methods. However, residual biases can remain, for example, due to unmeasured confounders, measurement error, or selection into the study. A group of sensitivity analysis methods, termed quantitative bias analyses, are available to assess, quantitatively and transparently, the robustness of study results to these residual biases. These approaches include methods to quantify how the estimated effect would be altered under specified assumptions about the potential bias, and methods to calculate bounds on effect estimates. This article introduces quantitative bias analyses for unmeasured confounding, misclassification, and selection bias, with a focus on their relevance and application to pharmacoepidemiological studies.
Investigation of pelvic floor influence on prostate displacement in image‐guided radiotherapy
Authors: Chai Hongbo , Miyasaka Yuya , Hagiwara Yasuhito , Souda Hikaru , Ishizawa Miyu , Sato Hiraku , Iwai Takeo
Published: October 2024

Purpose

The uncertainty of target location during prostate cancer radiotherapy plays an important role in accurate dose delivery and radiation toxicity in adjacent organs. This study analyzed displacement correlations between the prostate and pelvic floor.

Methods and Materials

We retrospectively analyzed registration results from 467 daily cone‐beam computed tomography (CT) in 12 patients with prostate cancer who received radiation therapy. We analyzed prostate displacement and the pelvic floor relative to the pelvic bone's anatomy in the translational and rotational directions and identified statistical correlations.

Results

The systematic (Σ) and random (σ) displacements of the prostate in the three translational directions, anterior–posterior (AP), superior–inferior (SI), and right–left (RL), were 1.49 ± 1.45, 2.10 ± 1.40, and 0.24 ± 0.53 mm, respectively, and in the rotational directions of the pitch, roll, and yaw were 2.10 ± 2.02°, 0.42 ± 0.74°, and 0.42 ± 0.64°, respectively. The pelvic floor displacements were 2.37 ± 1.96, 2.71 ± 2.28, and 0.47 ± 0.84 mm in the AP, SI, and RL directions, respectively, and 0.93 ± 1.49°, 0.98 ± 1.28 °, and 0.87 ± 0.94° in the pitch, roll, and yaw directions, respectively. Additionally, there were statistically significant correlations between the displacement of the prostate and pelvic floor in the AP and SI directions, with correlation coefficients (r) of 0.74 (p < 0.001) and 0.69 (p < 0.001), respectively.

Conclusions

The movement of the pelvic floor may be an important factor that causes prostate displacement, affecting the accuracy of radiotherapy. Therefore, it is necessary to take appropriate measures to ensure that the pelvic floor muscle tension is as consistent as possible in the treatment’ CT scan and daily treatment.
Strategic lead compound design and development utilizing computer‐aided drug discovery (CADD) to address herbicide‐resistant Phalaris minor in wheat fields
Authors: Rani Priyanka , Rajak Bikash Kumar , Mahato Gopal Kumar , Rathore Ravindranath Singh , Chandra Girish , Singh Durg Vijay
Published: October 2024

Wheat (Triticum aestivum) is a vital cereal crop and a staple food source worldwide. However, wheat grain productivity has significantly declined as a consequence of infestations by Phalaris minor. Traditional weed control methods have proven inadequate owing to the physiological similarities between P. minor and wheat during early growth stages. Consequently, farmers have turned to herbicides, targeting acetyl‐CoA carboxylase (ACCase), acetolactate synthase (ALS) and photosystem II (PSII). Isoproturon targeting PSII was introduced in mid‐1970s, to manage P. minor infestations. Despite their effectiveness, the repetitive use of these herbicides has led to the development of herbicide‐resistant P. minor biotypes, posing a significant challenge to wheat productivity. To address this issue, there is a pressing need for innovative weed management strategies and the discovery of novel herbicide molecules. The integration of computer‐aided drug discovery (CADD) techniques has emerged as a promising approach in herbicide research, that facilitates the identification of herbicide targets and enables the screening of large chemical libraries for potential herbicide‐like molecules. By employing techniques such as homology modelling, molecular docking, molecular dynamics simulation and pharmacophore modelling, CADD has become a rapid and cost‐effective medium to accelerate the herbicide discovery process significantly. This approach not only reduces the dependency on traditional experimental methods, but also enhances the precision and efficacy of herbicide development. This article underscores the critical role of bioinformatics and CADD in developing next‐generation herbicides, offering new hope for sustainable weed management and improved wheat cultivation practices. © 2024 Society of Chemical Industry.
Surgical Strategies and Perioperative Outcomes of Robot‐Assisted Vena Cava Reconstruction
Authors: Cheng Gong , Xing Yifei , Jiang Guosong , Liang Huageng , Chen Zhaohui , Zhang Xiaoping
Published: October 2024

Background

This study aimed to describe robot‐assisted vena cava reconstruction by summarising surgical strategies and perioperative outcomes.

Methods

A retrospective review was performed on all robotic surgeries involving dissection and repair of the inferior vena cava (IVC) at our institution. Patient characteristics, operative reports, and follow‐up visits were analysed.

Results

Thirty‐nine patients underwent robot assisted surgery of the vena cava from 2016 to 2023. The median postoperative hospital stay of all patients was 7 days, and the median estimated blood loss (EBL) was 550 mL. The median IVC clamping time was 23 min, and IVC wall invasion was pathologically identified in five cases. No patients had liver or kidney dysfunction at the last follow‐up.

Conclusion

Our initial experiences demonstrate that it is safe and feasible for experienced surgeons to perform robot‐assisted vena cava reconstruction in highly selected patients.
Combining Biomarkers to Improve Diagnostic Accuracy in Detecting Diseases With Group‐Tested Data
Authors: Yang Jin , Zhang Wei , Albert Paul S. , Liu Aiyi , Chen Zhen
Published: October 2024

We consider the problem of combining multiple biomarkers to improve the diagnostic accuracy of detecting a disease when only group‐tested data on the disease status are available. There are several challenges in addressing this problem, including unavailable individual disease statuses, differential misclassification depending on group size and number of diseased individuals in the group, and extensive computation due to a large number of possible combinations of multiple biomarkers. To tackle these issues, we propose a pairwise model fitting approach to estimating the distribution of the optimal linear combination of biomarkers and its diagnostic accuracy under the assumption of a multivariate normal distribution. The approach is evaluated in simulation studies and applied to data on chlamydia detection and COVID‐19 diagnosis.
Effects of Ni Loadings on the Structure and Morphology of Carbon Nanotubes Using Nickel Doped Iron Oxide Catalysts
Authors: Gul Habiba , Bilal Muhammad , Hussain Tasleem , Din Israf Ud , Mubashir Muhammad , Nasir Qazi
Published: October 2024

Iron oxide and their different doped iron oxide catalyst have been used for decades and are considered as efficient catalysts in several synthesis schemes including synthesis of carbon nanotubes. The iron oxide of the catalyst is abundant in nature, high catalytic activity at low over potentials, stability in basic media and low cost, making it environmentally and economically attractive. Nickel doped iron oxide catalyst have not been reported in the literature. Doping of nickel over iron oxide catalyst, different percentage 1 %, 5 %, 10 % and 20 % were done by impregnation method. The samples were characterized by X‐Ray powder Diffraction (XRD), Fourier‐Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM), Energy Dispersive X‐ray (EDX) and Thermo Gravimetric Analysis (TGA). Nickel doped iron oxide was used as catalyst for the synthesis of carbon nanotubes (CNTs) and doping changed the morphology of carbon nanotube (CNTs). FTIR results confirmed the doping and presence of different functional groups. Chemical vapor deposition (CVD) was carried out for the synthesis of multiwall carbon nanotubes (MWCNTs) on nickel doped iron oxide catalyst for different percentage (1 %, 5 %, 10 % and 20 %) separately. CVD assembly was carried in tube furnace and the reaction was checked at two different temperature i.e 700 °C and 750 °C and using methane and compressed natural gas (CNG) as precursors. The catalyst was activated in the furnace at 800 °C for an hour. Methane and argon were used in proportion 2 : 1 inside the furnace. SEM showed formation of CNTs at 750 °C with CNG precursor. Formation of CNTs increased with increasing doping with this CNTs was confirmed by SEM.
Synthesis of para‐Carboxamidostilbene Derivatives as Antihyperglycemia Agents and Their In Silico ADMET and Molecular Docking Studies
Authors: Mahdi Babai , Abu Bakar Mohamad Hafizi , Che Omar Mohamad Tasyriq , Zahari Azeana , Ibrahim Mohammad. M. , Mikhaylov Andrey. A. , Azmi Mohamad Nurul
Published: October 2024

In this project, para‐carboxamidostilbene derivatives were synthesized using the Heck coupling reaction, confirmed through various analytical techniques such as FT‐IR, HRMS, and NMR analyses, and tested in vitro to evaluate their α‐amylase inhibitory activity. In silico molecular docking was employed to model the binding interactions of compounds with α‐amylase. Pharmacokinetic properties (ADME) and drug‐likeness were also examined. Structure activity relationship (SAR) analysis was conducted to establish the relationship between the chemical structure and α‐amylase inhibitory activity. The synthesized compounds exhibited significant α‐amylase inhibitory activity with IC50 values ranging from 15.0 to 37.5 µM in comparison with acarbose (IC50 = 30.2 ± 1.9 µM). Among them, compounds 6d–6f and 7c–7f demonstrated promising inhibitory activity. Furthermore, molecular docking studies revealed strong interactions between the studied molecules and the α‐amylase binding pocket. The drug‐likeness prediction results indicated that all synthesized compounds adhered to Lipinski's rule of five, suggesting their suitability as drug‐like molecules. Additionally, the assessment of ADMET properties indicated favorable absorption profiles, particularly in terms of human intestinal absorption (HIA). Overall, this study successfully identified several para‐carboxamidostilbene derivatives as potential α‐amylase inhibitors for the treatment of T2DM.
Enhanced Oxalic Acid Electroreduction Selectivity toward Glyoxylic Acid on Ti3+‐Self‐Doped TiO2 Nanotube Arrays
Authors: Wu Yukun , Ullah Siraj , Hu Shuozhen , Zhang Xinsheng
Published: October 2024

Electroreduction of oxalic acid (OX) to glyoxylic acid (GO) is an extremely important and promising application in organic electrosynthesis. Pb cathodes, which exhibits good selectivity, need to be replace due to the severe deactivation and harmful to the environment. Herein, self‐doped titanium dioxide nanotube arrays (H‐TiO2NTs‐2) are synthesized as an alternative cathode for OX electroreduction to GO. Benefiting from two‐step anodization, the synthesized nanotube arrays are highly ordered with oriented openings. The ordered structure promotes the mass transfer of both OX and GO to ensure efficiently providing OX reactants for the diffusion‐controlled OX electroreduction and removal of GO products from the electrode to prevent the over‐reduction to glycolic acid. Additionally, the electroreduction treatment introduces more Ti3+ active sites and modulates the conduction band position of H‐TiO2NTs‐2, thereby enhancing the reduction driving force. Owing to the unique structural advantages, the Faraday efficiency of generating GO from OX reaches up to 81.3 % in an oxalic acid saturated electrolyte at 20 °C with a current density of 1500 A m−2. This designed H‐TiO2NTs‐2 holds broad application prospects in OX electroreduction.