bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between beta‐blocker atenolol use and prostate cancer upgrading in active surveillance1
Authors: Zahalka Ali H. , Fram Ethan , Garden Evan , Howard Lauren , Wiggins Emily , Babar Mustufa , Annam Jay , Reagan Allison , Eilender Benjamin , de Hoedt Amanda , Freedland Stephen J. , Tewari Ash , Watts Kara L.
Published: October 2024

Objectives

The objective of this study is to investigate the association between the use of beta‐adrenergic antagonist atenolol and risk of pathologic upgrade in patients on active surveillance, considering growing literature implicating adrenergic innervation with disease progression mediated through beta‐adrenergic signalling.

Patients and Methods

Men with low‐risk or favourable intermediate‐risk prostate cancer who were placed on an active surveillance protocol between 2006 and 2020 across three diverse urban hospitals were included. Exposure was duration of atenolol use, and outcome was pathologic grade group upgrading (to GG ≥ 3) on final prostate biopsy. Cox proportional hazard regression models were used to determine the associations between atenolol use and risk of upgrading with time, on a per‐examination basis.

Results

A total of 467 men with initial GG ≤ 2 were included. Postdiagnosis atenolol use was associated with a decreased risk of pathologic upgrade to GG ≥ 3 on final repeat biopsy (HR 0.81, 95% CI 0.39–0.98). Longer duration of postdiagnosis atenolol use (>2 years) and greater cumulative atenolol dose (>730 defined daily doses) were associated with a more pronounced decreased risk of upgrade to GG ≥ 3 (HR 0.41, 95% CI 0.05–0.88, and HR 0.32, 95% CI 0.15–0.99, respectively). Initiation of atenolol use prior to prostate cancer diagnosis had a slightly greater protective effect than drug initiation postdiagnosis (HR 0.79, 95% CI 0.43–0.98, and HR 0.83, 95% CI 0.30–0.99, respectively).

Conclusions

Beta‐adrenergic blockade with atenolol use in men on active surveillance is associated with a reduced risk for clinically significant grade group pathologic upgrade.
Selecting Endogenous Promoters for Improving Biosynthesis of Squalene in Schizochytrium sp.
Authors: Nong Fang‐Tong , Zhang Zi‐Xu , Xu Lu‐Wei , Du Fei , Ma Wang , Yang Guang , Sun Xiao‐Man
Published: October 2024

Squalene (C30H50) is an acyclic triterpenoid compound renowned for its myriad physiological functions, such as anticancer and antioxidative properties, rendering it invaluable in both the food and pharmaceutical sectors. Due to the natural resource constraints, microbial fermentation has emerged as a prominent trend. Schizochytrium sp., known to harbor the intact mevalonate acid (MVA) pathway, possesses the inherent capability to biosynthesize squalene. However, there is a dearth of reported key genes in both the MVA and the squalene synthesis pathways, along with the associated promoter elements for their modification. This study commenced by cloning and characterizing 13 endogenous promoters derived from transcriptome sequencing data. Subsequently, five promoters exhibiting varying expression intensities were chosen from the aforementioned pool to facilitate the overexpression of the squalene synthase gene squalene synthetase (SQS), pivotal in the MVA pathway. Ultimately, a transformed strain designated as SQS‐3626, exhibiting squalene production 2.8 times greater than that of the wild‐type strain, was identified. Finally, the optimization of nitrogen source concentrations and trace element contents in the fermentation medium was conducted. Following 120 h of fed‐batch fermentation, the accumulated final squalene yield in the transformed strain SQS‐3626 reached 2.2 g/L.
Thermoresponsive and Supramolecular Polymers: Interesting Biomaterials for Drug Delivery
Authors: Darvishi Ahmad , Ansari Mojtaba
Published: October 2024

How to use and deliver drugs to diseased and damaged areas has been one of the main concerns of pharmacologists and doctors for a long time. With the efforts of researchers, the advancement of technology, and the involvement of engineering in the health field, diverse and promising approaches have been studied and used to achieve this goal. A better understanding of biomaterials and the ability of production equipment led researchers to offer new drug delivery systems to the world. In recent decades, responsive polymers (exclusively to temperature and pH) and supramolecular polymers have received much attention due to their unique capabilities. Although this field of research still needs to be scrutinized and studied more, their recognition, examination, and use as drug delivery systems is a start for a promising future. This review study, focusing on temperature‐responsive and supramolecular biomaterials and their application as drug delivery systems, deals with their structure, properties, and role in the noninvasive and effective delivery of medicinal agents.
Development of a Human Recombinant Collagen for Vat Polymerization‐Based Bioprinting
Authors: Schlauch Domenic , Ebbecke Jan Peter , Meyer Johanna , Fleischhammer Tabea Marie , Pirmahboub Hamidreza , Kloke Lutz , Kara Selin , Lavrentieva Antonina , Pepelanova Iliyana
Published: October 2024

In light‐based 3D‐bioprinting, gelatin methacrylate (GelMA) is one of the most widely used materials, as it supports cell attachment, and shows good biocompatibility and degradability in vivo. However, as an animal‐derived material, it also causes safety concerns when used in medical applications. Gelatin is a partial hydrolysate of collagen, containing high amounts of hydroxyproline. This causes the material to form a thermally induced gel at ambient temperatures, a behavior also observed in GelMA. This temperature‐dependent gelation requires precise temperature control during the bioprinting process to prevent the gelation of the material. To avoid safety concerns associated with animal‐derived materials and reduce potential issues caused by thermal gelation, a recombinant human alpha‐1 collagen I fragment was expressed in Komagataella phaffii without hydroxylation. The resulting protein was successfully modified with methacryloyl groups and underwent rapid photopolymerization upon ultraviolet light exposure. The developed material exhibited slightly slower polymerization and lower storage modulus compared to GelMA, while it showed higher stretchability. However, unlike the latter, the material did not undergo physical gelation at ambient temperatures, but only when cooled down to below 10°C, a characteristic that has not been described for comparable materials so far. This gelation was not caused by the formation of triple‐helical structures, as shown by the absence of the characteristic peak at 220 nm in CD spectra. Moreover, the developed recombinant material facilitated cell adherence with high cell viability after crosslinking via light to a 3D structure. Furthermore, desired geometries could be easily printed on a stereolithographic bioprinter.
The efficacy of first and second immunotherapy exposure in patients with recurrent or metastatic cervical cancer
Authors: Ju Mingxiu , Pan Baoyue , Huang Yongwen , Zhou Yun , Chen Jieping , Xiang Huiling , Xu Shije , Chen Siyu , Lan Chunyan , Li Jundong , Zheng Min
Published: October 2024

Objective

Immunotherapy has led to changes in cervical cancer guidelines. Therefore, additional biomarkers to identify the ideal patient who would experience the most benefit may be important.

Methods

We retrospectively collected 208 patients with R/M CC and recorded clinicopathologic information, peripheral blood markers and treatments to analyze the prognostic factors of clinical outcomes. Response rate comparison, univariate, and multivariate analyses were performed to assess the efficacy of different factors.

Results

A total of 43.27% patients achieved objective responses, including 18 with complete response and 72 with partial response. Patients receiving first‐line immunotherapy had much higher objective response rate (ORR) than the remaining patients (53.8% vs. 34.8%, p = 0.006). CRP >3 ECOG ≥1 and recurrence in 6 months predicted shorter progression free survival (PFS). CRP >3, GLU >6.1 independently predicted unfavorable overall survival (OS). Compared with no antiangiogenic therapy, previous antiangiogenic therapy reduced the median OS by nearly 14 months. Immunotherapy rechallenge was still effective after first immunotherapy failure, and combined with dual‐immunotherapy or bevacizumab combined with chemoradiotherapy resulted in a 60.00% or 62.50% ORR, respectively. Patients with squamous cell carcinoma, with stable disease or objective response in the first immunotherapy or without chemotherapy in second immunotherapy had favorable clinical outcome.

Conclusion

The baseline CRP levels in serum was an independent factor for PFS and OS of R/M CC patients treated with immunotherapy, and previous antiangiogenic therapy was associated with poor OS. Patients still show response to immunotherapy rechallenge and combined treatment with bevacizumab or candonilimab showed higher response rate than anti‐PD‐1 after immunotherapy failure.
Edodes Cultured Extract Regulates Immune Stress During Puberty and Modulates MicroRNAs Involved in Mammary Gland Development and Breast Cancer Suppression
Authors: Yasavoli‐Sharahi Hamed , Shahbazi Roghayeh , Alsadi Nawal , Robichaud Samuel , Kambli Darshan Babu , Izadpanah Amirhossein , Mohsenifar Zhaleh , Matar Chantal
Published: October 2024

Background

Immune stressors, such as lipopolysaccharides (LPS), profoundly affect microbiota balance, leading to gut dysbiosis. This imbalance disrupts the metabolic phenotype and structural integrity of the gut, increasing intestinal permeability. During puberty, a critical surge in estrogen levels is crucial for mammary gland development. However, inflammation originating from the gut in this period may interfere with this development, potentially heightening breast cancer risk later. The long‐term effects of pubertal inflammation on mammary development and breast cancer risk are underexplored. Such episodes can dysregulate cytokine levels and microRNA expression, altering mammary cell gene expression, and predisposing them to tumorigenesis.

Methods

This study hypothesizes that prebiotics, specifically Lentinula edodes Cultured Extract (AHCC), can counteract LPS's adverse effects. Using BALB/c mice, an acute LPS dose was administered at puberty, and breast cancer predisposition was assessed at 13 weeks. Cytokine and tumor‐related microRNA levels, tumor development, and cancer stem cells were explored through immunoassays and qRT‐PCR.

Results

Results show that LPS induces lasting effects on cytokine and microRNA expression in mammary glands and tumors. AHCC modulates cytokine expression, including IL‐1β, IL‐17A/F, and IL‐23, and mitigates LPS‐induced IL‐6 in mammary glands. It also regulates microRNA expression linked to tumor progression and suppression, particularly counteracting the upregulation of oncogenic miR‐21, miR‐92, and miR‐155. Although AHCC slightly alters some tumor‐suppressive microRNAs, these changes are modest, highlighting a complex regulatory role that warrants further study.

Conclusion

These findings underscore the potential of dietary interventions like AHCC to mitigate pubertal LPS‐induced inflammation on mammary gland development and tumor formation, suggesting a preventive strategy against breast cancer.
Preoperative Serum Glycan Levels Reflect Progression of Patients With Hepatocellular Carcinoma
Authors: Liu Sheng‐Sheng , Ye Lei , Dai Qing‐Qing , Gao Yi , Chen Guang‐Hou , Zhao Hong‐Chuan , Du Wei‐Dong
Published: October 2024

Background

Abnormal glycosylation is associated with tumors. The clinical value of serum glycans in assessing progression of hepatocellular carcinoma (HCC) patients remains a challenge.

Methods

A study dynamically comparing levels of fifteen lectin‐specific glycans between preoperative and postoperative serum of 65 HCC patients was conducted via lectin biochip technology. Multivariable logistic regression analysis was used to address associations between serum glycan levels and clinicopathological characteristics. Kaplan–Meier analysis was used to evaluate the impacts of serum glycan levels on overall survival (OS) and progression‐free survival (PFS) of the HCC patients.

Results

HCC patients presented significantly higher levels of the lectin‐specific glycans in preoperative serum than disease‐free individuals (p < 0.001 − p = 0.029), except ConA. The glycans in preoperative sera were significantly related to tumor size, pTNM, metastasis, BCLC stage, portal hypertension (PHT), and platelet count (PLT), respectively (p < 0.05). Multivariate logistic analyses indicated that tumor size and pTNM independently impact on glycan‐specific lectins either LTL, UEA‐I, VVL, NPL, WGA, PNA, MAL‐I, SNA, or PHA‐L (p = 0.003 − p = 0.044); BCLC stage and PLT were independent factors influencing the serum glycans recognizable DSA (p = 0.024) and SNA (p = 0.050), respectively. Surgical excision of tumor mass significantly reduced glycan levels in sera. Tumor differentiation, albumin, and ABO type significantly revealed independent influence on glycan‐specific lectins, such as RCA‐I (p = 0.024), VVL (p = 0.024), and Con A (p = 0.026) in the postoperative serum. HCC patients with high levels of VVL‐binding glycans significantly benefited from a longer OS time (p = 0.016, HR: 0.460, 95% CI: 0.237–0.892) and a better PFS time (p = 0.004; HR: 0.435, 95% CI: 0.237–0.799), respectively.

Conclusion

Serum glycans could reflect surgical outcomes in at‐risk patients and become valuable biomarkers in evaluating the progression of HCC patients.
Mutational Landscape of Gastric Adenocarcinoma of the Fundic Gland Type Revealed by Whole Genome Sequencing
Authors: Wei Hu , Chen Ze Min , Xue Xiu Fen , Xia Xi Li , Yang Gen Hua , Zhai Zhi Yong , Huang Zhao Yu , Zhou Ping , Bao Chong Ju , You Li Juan , Ou Yang Mei Ping , Xia Gui Li , Zeng Zhi Yu , Cui Xiao Bing , Pei Xiao Juan , Gong Wei
Published: October 2024

Background

Gastric adenocarcinoma of the fundic gland type (GA‐FG) is a newly described variant of gastric adenocarcinoma with lack of knowledges regarding its genetic features.

Methods

We performed whole‐genome sequencing (WGS) in formalin‐fixed paraffin‐embedded (FFPE) tumor tissues and matched adjacent noncancerous specimens from 21 patients with GA‐FG, and integrated published datasets from 1105 patients with traditional gastric adenocarcinoma with the purpose of dissecting genetic determinants both common to conventional gastric adenocarcinoma and unique to GA‐FG disease.

Results

We characterized the genomic architecture of GA‐FG disease, revealing the predominant proportion of C > T substitution among the six types of SNVs. GNAS was the most significantly mutated driver gene (14.29%). 42.8% of samples harbored “Kataegis.” Distinct genomic alterations between GA‐FG and conventional gastric cancer were identified. Specifically, low mutational burden and relatively moderate mutational frequencies of significantly mutated driver genes, coupled with the absence of non‐silent alterations of formerly well‐known drivers such as TP53, PIK3CA and KRAS were identified in GA‐FG patients. Oncogenic signaling pathway analysis revealed mutational processes associated with focal adhesions and proteoglycans in cancer, highlighting both common and specific procedures during the development of GA‐FG and conventional gastric cancer.

Conclusion

Our study is the first to comprehensively depict the genomic landscape highlighting the multidimensional perturbations in GA‐FG patients. These discoveries offered mechanistic insights for novel diagnostic and therapeutic strategies for patients with such disease.
Unveiling the Clinical Path of Microinvasive Breast Cancer: A Comparative Study With Tis‐T1 Breast Cancer
Authors: Song Ran , Lee Dong‐Eun , Jung So‐Youn , Lee Seeyoun , Kang Han‐Sung , Han Jai Hong , Woo Jaeyeon , Lee Eun‐Gyeong
Published: October 2024

Purpose

The prognosis of microinvasive breast cancer (MIBC) is controversial, with a high reported rate of local recurrence (LR). This study aimed to evaluate the characteristics, treatments, and prognosis of patients with MIBC compared to those with carcinoma in situ (CIS) or early invasive cancer.

Methods

Patients who diagnosed with CIS or stage I breast cancer were retrospectively enrolled. Using the Kaplan–Meier method, local recurrence‐free survival (LRFS), systemic recurrence‐free survival (SRFS), and cancer‐specific survival (CSS) were compared according to T stage. The prognostic factors associated with LRFS were identified using the Cox proportional hazards model.

Results

According to T stage, 517 (21.6%), 200 (8.4%), 207 (8.7%), 363 (15.2%), and 1101 (46.1%) patients had Tis, T1mi, T1a, T1b, and T1c tumors, respectively. The proportion of human epidermal growth factor receptor 2‐positive tumors was significantly higher in patients with MIBC (p < 0.0001). The administered adjuvant treatments also showed differences according to T stage (p < 0.0001). During the 73‐month median follow‐up period, patients with MIBC showed significantly worse LRFS than those with T1a or T1c tumors (p = 0.002). There was no significant difference in SRFS and CSS. In the Cox regression analysis, tumor multiplicity (p = 0.017), Ki‐67 (p = 0.025), cancer subtype (p = 0.034), adjuvant endocrine therapy (p = 0.003), and adjuvant radiation therapy (p < 0.0001) were significant prognostic factors associated with LRFS.

Conclusion

The risk of LR was higher in patients with MIBC than in those with small invasive breast cancer. Therefore, if indicated, adjuvant endocrine and radiation therapies should be administered to prevent undertreatment in patients with MIBC.
Chemical enhanced oil recovery from shale‐rich tight carbonate reservoirs using 2‐butoxyethanol as a mutual solvent and diluted seawater
Authors: Nowrouzi Iman , Mohammadi Amir H. , Khaksar Manshad Abbas
Published: October 2024

Oil production from tight reservoirs due to their very low permeability and high capillary pressure requires complex operations and materials, so that hydraulic fracturing in these reservoirs is recommended before any chemical injection. This operation turns the reservoir into a fractured one that can produce more oil by activating the imbibition mechanism. The interfacial tension (IFT) of oil and water and reservoir rock wettability as key parameters of overproduction from this type of reservoir can affect this mechanism. In this study, the potential of 2‐butoxyethanol as a mutual solvent for enhanced oil recovery (EOR) was investigated with a focus on the oil production under imbibition in this type of reservoir through performing experiments and calculations of IFT, oil swelling, contact angle, and oil production. The analysis of the results shows that the mechanisms of IFT reduction, wettability alteration, and oil swelling, which all directly affect the oil production under imbibition, reached the desired values using 2‐butoxyethanol in the appropriate concentration along with the dilution of seawater. The lowest values for interfacial tension and contact angle at 0.03 M concentration of the solvent and 5000 ppm salinity at 90°C temperature were 1.315 mN/m and 71.57°, respectively. These values are much lower compared to the values obtained by similar additives, while solvents, unlike 2‐butoxyethanol, are effective in much higher volume ratios. The oil swelling increased by about 14% using 2‐butoxyethanol due to its mass transfer between water and oil phases through the interface. Finally, the oil recovery factors of 42% and 59% were achieved under one‐ and multi‐dimensional spontaneous imbibition (ODSI and MDSI), respectively.
Environmental, social, and governance, board gender diversity, and firm efficiency: Evidence from the global mining industry pre‐ and post‐COVID‐19 pandemic
Authors: Lu Wen‐Min , Kuo Kuo‐Cheng , Kweh Qian Long , Ganbaatar Oyunchimeg
Published: October 2024

We examine (i) the impacts of environmental, social, and governance (ESG) on firm efficiency and (ii) how board gender diversity (BGD) moderates these impacts in mining multinational enterprises (MNCs). We first employ a two‐stage network data envelopment analysis (DEA) approach to estimate eco‐efficiency (EE) and profitability efficiency (PE), and a network‐based ranking model to rank the mining MNCs. Second, we utilize multivariate regression analysis on 294 firm‐year observations of 49 global MNCs spanning from 2016 to 2021 to achieve our research objectives. Based on our findings, it appears that mining MNCs have a bigger room for improvement when it comes to their profitability efficiency than their eco‐efficiency. The DEA average efficiency scores for EE and PE stand at around 83% and 50%, respectively. Moreover, our regression results reveal that ESG significantly and positively influences EE but insignificantly affects PE. Environmental pillar score (EPS), social pillar score (SPS), and governance pillar score insignificantly influence EE, whereas EPS and SPS significantly affect PE. In addition, BGD significantly moderates the effect of ESG on EE. BGD significantly moderates only the impact of SPS on PE. Overall, this study emphasizes the significance of focusing on BGD when examining the relationship between ESG and firm efficiency, which thus provides crucial insights for stakeholders in the global mining industry, including investors, policymakers, and researchers.
Genetic Structure of Monochamus alternatus (Hope) in Qinling‐Daba Mountains and Expansion Trend: Implications for Pest Prevention and Management
Authors: Qi Jingyu , Nan Junke , Zhao Xiaogu , Liang Chaoqiong , Fan Jiangbin , He Hong
Published: October 2024

Pine wilt disease (PWD), caused by Bursaphelenchus xylophilus, severely threatens global pine forests. Monochamus alternatus is the primary vector of B. xylophilus in East Asia. Understanding the population structure and evolutionary forces of vector insects is critical for establishing effective PWD management strategies. The present work explores the genetic structure and phylogenetic relationships of 20 populations of M. alternatus from the Qinling‐Daba Mountains (QDM) in China using the mitochondria DNA dataset, supplemented by ecological niche modeling (ENM). All M. alternatus populations were categorized into three phylogeographic clusters (Clade A, Clade B, and Clade C), with Clade A and Clade B corresponding to the western and eastern QDM, respectively. The results of divergence time estimation concur with environmental changes induced by Quaternary glacial climate oscillations in QDM of China. M. alternatus populations exhibited significant genetic differentiation, with expansion in their population size. Ecological niche modeling (ENM) demonstrated that precipitation and temperature significantly influence the distribution of M. alternatus and the species is anticipated to grow into higher latitude and higher altitude regions in the future. In a nutshell, exploring the genetic structure and evolutionary dynamics of M. alternatus can provide valuable insights into the prevention and occurrence of B. xylophilus. These findings also serve as a reference for research on population differentiation and phylogeography of other species in QDM and adjacent areas.
The Sinking Dead—Arctic Deep‐Sea Scavengers' Diet Suggests Nekton as Vector in Benthopelagic Coupling
Authors: Schmittmann Lara , Schindler Sophie V. , Bayer Till , Fuss Janina , Havermans Charlotte , Merten Véronique , Hoving Henk‐Jan T.
Published: October 2024

Many benthic deep‐sea animals rely on carcasses from the overlying water column that sink to the seafloor and form local organic enrichments known as food falls. This flux of organic carbon from the shallow pelagic to the deep sea is part of the biological carbon pump (BCP) and as such contributes to carbon sequestration. For a complete understanding of local carbon budgets, it is crucial to identify the diversity and distribution of sinking carcasses which are difficult to detect by observational methods. Here, we analyzed the diet of the abundant amphipod scavenger, Eurythenes gryllus, by DNA metabarcoding to assess their potential to identify food falls in the Fram Strait, a gateway to the Arctic. E. gryllus scavenges on nekton but so far it was not certain whether this represents their main diet. We detected dietary taxa (26 in total) in 20 out of 101 analyzed amphipods. We found that amphipods primarily fed on larger nekton including fish, cephalopods, and mammals, with bony fish being the most targeted food source in terms of diversity and abundance. Only one amphipod had fed on a gelatinous organism. These results support the hypothesis that E. gryllus targets mostly nekton food falls. The diversity of dietary taxa differed between the Eastern and Western Fram Strait, which suggests regional variability in food falls availability. We also detected, for the first time in E. gryllus, infections with the parasitic dinoflagellate Hematodinium. This detection demonstrates the potential of metabarcoding for revealing both food web dynamics and host–parasite interactions in the deep sea. E. gryllus seems a promising “natural sampler” to monitor the diversity of deep‐sea food falls which will help to investigate the importance of medium‐sized food falls in local vertical carbon export in a rapidly changing Arctic Ocean.
Relational Systems Evaluation rubrics as tools for building and measuring evaluation capacity
Authors: Urban Jennifer Brown , Postlewaite Elyse L. , Davis Bekki , Les Elaine , Buckley Jane , Hargraves Monica
Published: October 2024

Evaluation capacity building (ECB) is still an emerging area of study in the field of evaluation. The purpose of ECB is to assist program practitioners with implementing higher‐quality evaluation; however, we need better tools and resources to effectively assess ECB efforts. Existing measures typically depend on self‐report as opposed to assessing the artifacts of ECB training. Among the few non‐self‐report tools that support the assessment of ECB efforts are Relational Systems Evaluation rubrics designed to evaluate logic models, pathway models, and evaluation plans. These rubrics were first developed and tested several years ago. The purpose of the current study is to update the Relational Systems Evaluation rubrics to reflect current ECB knowledge. The updated rubrics have good to excellent inter‐rater reliability and high internal consistency. The results of this study contribute to the ECB field by providing measurement tools for assessing the quality of ECB artifacts. The rubrics can also be used by organizations and funders who need a systematic approach for assessing (and comparing) the quality of evaluation plans and visual theory of change models (e.g., logic models).
Guidelines for anti‐inflammatory assays in RAW264.7 cells
Authors: Wu Xincheng
Published: October 2024

In recent years, research on various bioactive compounds with anti‐inflammation effects has become increasingly active. Evaluating anti‐inflammatory activity is well established in cell models represented by RAW264.7 cells. Methylthiazolyldiphenyl‐tetrazolium bromide (MTT) and cell counting kit‐8 (CCK‐8) assays are commonly used to detect the effects of drugs or deleterious substances on cytotoxicity, cell viability, and survival. RAW264.7 cells release nitric oxide (NO) when exposed to inflammatory stimuli, so their anti‐inflammatory capacity can be assessed by detecting the NO content in cell culture supernatants, and the Griess method is one of the commonly used methods for determining NO concentration. RAW264.7 cells release a variety of inflammation‐associated cytokines, such as the TNF‐α and IL‐1β, with ELISA being the standard method to detect the release of these inflammatory factors. For mRNA expression levels of genes associated with inflammation, real‐time PCR (Quantitative Real‐time PCR, qPCR) is commonly used. In addition, the well‐known western blotting assay can be used to detect the expression levels of proteins associated with inflammatory signaling pathways. In this guideline, we discuss the basic principles and practices of the above experimental methods, which provide a valuable reference for the anti‐inflammatory experimental methods in cellular models such as the RAW264.7 cells.
Experimental study on the effects of integrating phase change material with a solar updraft tower
Authors: Qasim Ali Abdulrahman , Mussa Munther Abdullah
Published: October 2024

The solar updraft tower power plant presents a promising renewable energy solution but faces limitations in thermal efficiency and energy production during nonsunny hours. This study addresses a critical gap in the literature by investigating the integration of latent heat storage systems utilizing paraffin wax as phase change materials (PCMs) to enhance solar updraft tower (SUT) performance. Two identical small‐scale SUTs were constructed, both using the same tank configuration; however, the PCM device was filled with paraffin wax as a PCM, while the non‐PCM device contained only atmospheric air. Three scenarios were explored, featuring varying PCM tank heights of 2, 4, and 6 cm (the full capacity of the PCM tank). Results indicated that, from 3 p.m. until sunset, the PCM‐integrated SUT in Case 3 (with 6 cm of PCM) achieved the best performance, with an average absorber temperature rise of 25°C, compared with 12°C for the non‐PCM device. During the same period, the average air velocity at the tower neck, where a wind turbine could be installed, was 1.21 m/s for the PCM device, versus 0.82 m/s for the non‐PCM device. Notably, the nocturnal operating time extended significantly with PCM use, rising from 90 min for the 2 cm case to 125 min for the 6 cm case. In contrast, the non‐PCM device exhibited no operational time after sunset. This research not only demonstrates the effectiveness of PCM in improving the thermal performance and operational longevity of SUTs but also introduces a novel tank configuration that allows for flexible PCM integration, representing a significant advancement in the development of more efficient SUT systems.
Evaluating the yield of digital single operator cholangioscopy in posttransplant biliary strictures after unsuccessful guidewire placement with ERCP
Authors: Ng Jonathan , Chandran Sujievvan , Be Kim Hay , Zorron Cheng Tao Pu Leonardo , Choi Kevin Kyung Ho , Saxena Payal , Kaffes Arthur John , Vaughan Rhys , Efthymiou Marios
Published: October 2024

Background and Aims

Strictures are the most common biliary complication after liver transplantation, and endoscopic retrograde cholangiopancreatography (ERCP) is considered the gold standard in its management. Failure to cross the biliary anastomosis requires a repeated attempt with ERCP, referral for percutaneous transhepatic cholangiography (PTC) or surgery. We present our experience with the digital single operator cholangioscope (D‐SOC) in achieving guidewire access in a liver transplant cohort with difficult biliary strictures who have failed conventional ERCP methods.

Methods

This was a retrospective study involving two adult liver transplant centers servicing the two most populated states in Australia. Deceased‐donor liver transplant recipients undergoing D‐SOC for biliary strictures who have failed conventional methods to achieve biliary access were included.

Results

Between July 2017 to April 2022, eighteen patients underwent D‐SOC after failing to achieve guidewire placement through standard ERCP techniques. Thirteen out of eighteen (72%) had successful guidewire placement with index D‐SOC. Five of eighteen patients (28%) had unsuccessful guidewire placement with D‐SOC. In two of these patients, use of D‐SOC informed further endoscopic management, with one avoiding PTC and the other avoiding surgery. Two of the five patients required PTC and one patient was left unstented. Three patients developed post D‐SOC cholangitis.

Conclusions

D‐SOC is effective at achieving guidewire access in post‐liver transplant patients who fail conventional ERCP techniques and should be considered in the treatment algorithm as a step before PTC and surgery.
“Between the Lines”: Perceptions of Poetry With Authorship Attributed to Artificial Intelligence or Humans – A Comparative Analysis
Authors: Stanko‐Kaczmarek Maja , Dera Lilianna , Koscielska Halszka
Published: October 2024

In the rapidly evolving field of artificial intelligence (AI) literature generation, understanding how society perceives AI‐generated content, compared with human‐produced literature is of paramount importance. This study investigated societal perceptions and biases toward AI‐generated versus human‐produced poetry. A sample of 123 participants was subjected to a controlled experiment in which they evaluated a human‐generated poem that was randomly attributed to either a human, an AI, or an unspecified author. The assessment metrics comprised five categories: originality, aesthetic appeal, emotional engagement, coherence, and interpretive difficulty. An analysis of variance was used to analyze the survey results. Our findings revealed that poems attributed to an AI consistently received lower scores for originality, aesthetic appeal, and emotional engagement compared to those attributed to a human author. However, AI‐generated content was perceived as more complex and was rated higher in terms of interpretive difficulty. Interestingly, perceived authorship did not significantly influence coherence as a metric. When the poem was believed to be AI‐generated, it faced more critical evaluations than when it was human‐attributed. When authorship was ambiguous, feedback was distributed uniformly across negative, positive, and neutral sentiments, suggesting a potential mitigating effect of ambiguity on bias.
Inactivation of Tnf‐α/Tnfr signaling attenuates progression of intervertebral disc degeneration in mice
Authors: Tao Chu , Lin Sixiong , Shi Yujia , Gong Weiyuan , Chen Mingjue , Li Jianglong , Zhang Peijun , Yao Qing , Qian Dongyang , Ling Zemin , Xiao Guozhi
Published: October 2024

Background

Intervertebral disc degeneration (IVDD) is a major cause of low back pain (LBP), worsened by chronic inflammatory processes associated with aging. Tumor necrosis factor alpha (Tnf‐α) and its receptors, Tnf receptor type 1 (Tnfr1) and Tnf receptor type 2 (Tnfr2), are upregulated in IVDD. However, its pathologic mechanisms remain poorly defined.

Methods

To investigate the role of Tnfr in IVDD, we generated global Tnfr1/2 double knockout (KO) mice and age‐matched control C57BL/6 male mice, and analyzed intervertebral disc (IVD)‐related phenotypes of both genotypes under physiological conditions, aging, and lumbar spine instability (LSI) model through histological and immunofluorescence analyses and μCT imaging. Expression levels of key extracellular matrix (ECM) proteins in aged and LSI mice, especially markers of cell proliferation and apoptosis, were evaluated in aged (21‐month‐old) mice.

Results

At 4 months, KO and control mice showed no marked differences of IVDD‐related parameters. However, at 21 months of age, the loss of Tnfr expression significantly alleviated IVDD‐like phenotypes, including a significant increase in height of the nucleus pulposus (NPs) and reductions of endplates (EPs) porosity and histopathological scores, when compared to controls. Tnfr deficiency promoted anabolic metabolism of the ECM proteins and suppressed ECM catabolism. Tnfr loss largely inhibited hypertrophic differentiation, and, in the meantime, suppressed cell apoptosis and cellular senescence in the annulus fibrosis, NP, and EP tissues without affecting cell proliferation. Similar results were observed in the LSI model, where Tnfr deficiency significantly alleviated IVDD and enhanced ECM anabolic metabolism while suppressing catabolism.

Conclusion

The deletion of Tnfr mitigates age‐related and LSI‐induced IVDD, as evidenced by preserved IVD structure, and improved ECM integrity. These findings suggest a crucial role of Tnf‐α/Tnfr signaling in IVDD pathogenesis in mice. Targeting this pathway may be a novel strategy for IVDD prevention and treatment.
CANVAR: A Tool for Clinical Annotation of Variants Using ClinVar Databases
Authors: Vestergaard Lau K. , Lopacinska‐Jørgensen Joanna , Høgdall Estrid V.
Published: October 2024

Background

Genomic medicine has transformed clinical genetics by utilizing high‐throughput sequencing technologies to analyze genetic variants associated with diseases. Accurate variant classification is crucial for diagnosis and treatment decisions, and various tools and software such as the Ion Reporter Software and the Illumina Nirvana Software often used in a clinical setting utilize information from the ClinVar database/archive to aid in variant interpretation. However, these existing annotation tools may lack access to the latest ClinVar data, necessitating manual variant inspection.

Aims

To address this gap in developing a tool providing the latest ClinVar data for variant annotation in clinical and research settings.

Materials and Methods

We introduce CANVAR, a Python‐based script that efficiently annotates variants identified from next‐generation sequencing in a clinical or research context, offering comprehensive information from the latest ClinVar database.

Results

CANVAR provides accurate, up‐to‐date variant annotations, streamlining variant analysis.

Discussion

The rise in genomic data requires accurate variant annotation for clinical decision‐making. Misclassification poses risks, and current tools may not always access the latest data, challenging variant interpretation.

Conclusion

CANVAR contributes to enhancing variant annotation by offering comprehensive information from the latest ClinVar database for genetic variants identified through next‐generation sequencing.
Curcumin Attenuates Dextran Sodium Sulfate Induced Colitis in Obese Mice
Authors: Kang Zeng‐Ping , Xiao Qiu‐Ping , Huang Jia‐Qi , Wang Meng‐Xue , Huang Jie , Wei Si‐Yi , Cheng Nian , Wang Hai‐Yan , Liu Duan‐Yong , Zhong You‐Bao , Zhao Hai‐Mei
Published: October 2024

Scope: Curcumin (Cur), with diverse pharmacological properties, shows anti‐obesity, immunomodulatory, and anti‐inflammatory effects. Its role in ulcerative colitis complicated by obesity remains unclear.

Methods and results: Here, colitis is induced in obese mice using dextran sulfate sodium (DSS), followed by administration of Cur at a dosage of 100 mg kg−1 for 14 days. Cur effectively alleviates DSS‐induced colitis in obese mice, accompanied by an increase in body weight and survival rate, reduction in disease activity index, elongation of the colon, decrease in colonic weight, and improvements in ulcer formation and inflammatory cell infiltration in colonic tissues. Additionally, Cur effectively improves lipid metabolism and the composition of the gut microbiota, and enhances mucosal integrity and boosts anti‐oxidative stress capacity in obese mice with colitis. Importantly, Cur is effective in improving the homeostasis of memory T cells in obese mice with colitis. Furthermore, Cur regulates inflammatory cytokines expression and inhibits activation of the JAK2/STAT signaling pathway in colonic tissues of obese mice with colitis.

Conclusions: Cur alleviates colitis in obese mice through a comprehensive mechanism that improves lipid metabolism, modulates gut microbiota composition, enhances mucosal integrity and anti‐oxidative stress, balances memory T cell populations, regulates inflammatory cytokines, and suppresses the JAK2/STAT signaling pathway.
A photonic sensor system for real-time monitoring of turbidity changes in aquaculture
Authors: Tolon Mustafa Tolga , Tokaç Adnan , Kostak Enis N. , Strehse Christoph
Published: October 2024

Objective

The objective of this study was to test the compatibility and performance of a developed photonic sensor system, which can serve as a dependable and practical device for continuous monitoring of turbidity changes in aquaculture tanks.

Methods

The fabricated photonic sensor system consisted of an integrated data logger and sensor probe. The sensor probe exhibited a precise emission of infrared light at a wavelength of 850 nm. Moreover, the sensor evaluates the ambient light across the red-green-blue spectrum. To ensure accuracy and reliability, the entire system underwent a thorough calibration process, referencing nephelometric turbidity unit values acquired through a specialized handheld turbidimeter. Rigorous trials were systematically conducted in 600-L seawater tanks featuring tubular sea cucumber Holothuria tubulosa and Gilt-head Sea Bream Sparus auratus to ensure the sensitivity and robustness of the photonic sensor system to the aquaculture environment.

Result

A calibration curve revealed a significant correlation between the infrared channel values of the sensor (photon counts) and the turbidity values measured by the turbidimeter. The photonic sensor effectively captured turbidity changes in the aquaculture tanks, with significant differences observed between the tanks. The sensor performance was evaluated in trials with Gilt-head Sea Bream, which showed sensitivity to high turbidity changes. The photonic sensor system accurately reflects turbidity changes continuously using its own active light source, independent of ambient light intensity, which is essential for turbid water conditions or for taking measurements in total darkness.

Conclusion

The photonic sensor is a reliable tool for the continuous and accurate monitoring of turbidity changes in aquaculture systems. However, there are specific usage limitations under low-turbidity conditions that can be improved in further studies.
An Analysis of the Otolaryngology Workforce in Pennsylvania
Authors: Sciscent Bao Y. , Chan Kimberly , Eberly Hänel W. , Goldenberg David , Goyal Neerav
Published: October 2024

Objective

This study aims to analyze the distribution of otolaryngologists between urban and rural counties in Pennsylvania.

Study Design

Retrospective database.

Setting

American Academy of Otolaryngology–Head and Neck Surgery (AAO‐HNS) database and Centers for Medicare and Medicaid Services (CMS) Database.

Methods

The AAO‐HNS database (Entnet.org) and the CMS Database were used to identify otolaryngologists, their primary location, and their state of training. The 2023 Rural‐Urban Continuum Codes were used to classify metropolitan (codes 1‐3) and nonmetropolitan counties (codes 4‐9) and determine county populations.

Results

A total of 388 otolaryngologists were identified across 67 Pennsylvania counties (33 metropolitan, 34 nonmetropolitan), 80% of which were male. There were 354 otolaryngologists in metropolitan counties serving 11.2 million people, with an average of 2.4 otolaryngologists per 100,000 people (/100 k). The majority of otolaryngologists (n = 235, 60.6%) are located in counties designated by code 1. There were 34 otolaryngologists in nonmetropolitan counties serving 1.8 million people, with an average of 2.4 otolaryngologists/100 k. Montour County (code 6) is home to a large academic center and accounts for 14/34 otolaryngologists in the nonmetropolitan counties. With the exception of Montour County, the remaining nonmetropolitan counties averaged 1.0 otolaryngologist/100 k. Only 3 metropolitan counties did not have otolaryngologists compared to 19 nonmetropolitan counties without otolaryngologists. Most otolaryngologists received their residency training in Pennsylvania (n = 177). New York (n = 35) and Maryland (n = 24) were the second most common states for training.

Conclusion

There is a lack of otolaryngologists in rural counties of Pennsylvania, except in counties home to large academic centers.
Postprocedure protocols after intraarticular orthobiologic injections—A scoping review
Authors: Kruse Ryan C. , Rossmiller Kristina D. , Fleagle Timothy R.
Published: October 2024

Osteoarthritis is a chronic degenerative disease affecting 500 million people throughout the world. Although orthobiologics have been proposed as a symptom and disease modifying treatment for osteoarthritis, there is significant heterogeneity in the results of the orthobiologic procedures in the literature. One possible explanation for the heterogeneity is the inconsistent reporting and description of the postorthobiologic protocols. The goal of this scoping review was to identify the current literature on the use of orthobiologics for osteoarthritis and critically evaluate the postorthobiologic protocol within these studies. A total of 200 identified studies met inclusion criteria. In 37.5% of studies, there was no mention of a postorthobiologic protocol. Of the 125 studies that did mention a postorthobiologic protocol, only 38.4% included a rehabilitation protocol, 21.6% included postprocedure weightbearing restrictions, and only 2 (1.6%) mentioned the use of durable medical equipment. Nonsteroidal anti‐inflammatory drug restriction was described in 91.2% of study protocols, whereas corticosteroids and immunosuppressants were restricted in 84.8% and 19.2% of protocols, respectively. The results of this scoping review demonstrate the inconsistent reporting of postorthobiologic procedure protocols in the literature, with significant heterogeneity in those that are described. These findings highlight the need for future research and improved reporting of postorthobiologic protocols.
Incidence of lymphedema among adults with cerebral palsy
Authors: Gettys Christine R. , Smith Sean , Rauch Kimberly K. , Whitney Daniel G.
Published: October 2024

Background

Lymphedema is a chronic and progressive condition but is understudied among adults with cerebral palsy (CP).

Objective

To compare the 2‐year incidence of lymphedema between adults with versus without CP before and after accounting for multimorbidity, cancer diagnosis/treatment, and lymph node/channel surgery.

Design

Retrospective cohort study.

Setting

Nationwide commercial claims data from January 1, 2011 to December 31, 2017.

Participants

Adults ≥18 years old with and without CP with at least 12 months of continuous health plan enrollment, defined as the baseline period, were included for analysis. The 12‐month baseline period was used to establish information on preexisting lymphedema (for exclusion), presence of cancer, including radiation treatment and lymph node surgery, and the Whitney Comorbidity Index (WCI).

Interventions

Not applicable.

Main Outcome Measure

The 2‐year incidence rate (IR) and IR ratio (IRR) of lymphedema were evaluated. Cox regression estimated the hazard ratio (HR) of 2‐year lymphedema after adjusting for age, gender, WCI, cancer diagnosis/treatment, and lymph node/channel surgery.

Results

The 2‐year IR of lymphedema was 5.73 (95% confidence interval [CI] = 4.59–6.88) for adults with CP (n = 9922) and 1.81 (95% CI = 1.79–1.83) for adults without CP (n = 12,932,288); the IRR was 3.17 (95% CI = 2.59–3.87) and the adjusted HR was 2.43 (95% CI = 1.98–2.98). There was evidence of effect modification by gender, age, and WCI score. All HRs were elevated, but men with versus without CP had higher HRs than women with versus without CP; HRs for adults with versus without CP were higher for younger participants and those with lower WCI scores.

Conclusions

Adults with CP had a higher 2‐year rate of lymphedema compared with those without CP. Men with CP had a disproportionately higher rate than women with CP when compared with their gender‐based reference cohorts without CP.