bluuebunny/crossref_metadata_2025 huggingface dataset:
Usefulness of genotyping APC gene for individualizing management of patients with familial adenomatous polyposis
Authors: Mori Yoshiko , Ishida Hideyuki , Chika Noriyasu , Ito Tetsuya , Amano Kunihiko , Chikatani Kenichi , Takeuchi Yoji , Kono Mitsuhiro , Shichijo Satoki , Chino Akiko , Nagasaki Toshiya , Takao Akinari , Takao Misato , Nakamori Sakiko , Sasaki Kazuhito , Akagi Kiwamu , Yamaguchi Tatsuro , Tanakaya Kohji , Naohiro Tomita , Ajioka Yoichi
Published: June 2023

Background
Colorectal polyp burden is crucial for the management of patients with familial adenomatous polyposis (FAP). However, accurate evaluation of polyp burden is difficult to standardize. This study aimed to examine the possible utility of genotype-oriented management of colorectal neoplasms in patients with FAP.
Methods
Clinicopathological data from genetically proven patients with FAP was analyzed using the database of a nationwide retrospective Japanese multicenter study. The cumulative incidence of CRC was evaluated between different genotype groups. Genotype-1 were defined as germline variants on attenuated FAP associated regions (codons 1-177, alternative splice site of exon 10 (codon 312), 1581–2843) and Genotype-2 as the other variants. Weibull and Joinpoint analyses were performed to determine the annual percentage changes in CRC risk.
Results
Overall, 69 men and 102 women were included. Forty-eight patients underwent colorectal resection for the first CRC, and five patients underwent resection for first cancer in the remnant anorectal segment after prophylactic surgery. The 70-year cumulative incidence of CRC in all patients was 59.3%. Patients with Genotype-1 (n = 23) demonstrated a lower risk of CRC stage II-IV than those with Genotype-2 (n = 148, P = 0.04). The risk of stage II-IV CRC was estimated to increase markedly at the age of 49 years in the Genotype-1 patients and 34 years in the Genotype-2 patients, respectively.
Conclusions
Different interventional strategies based on genotypes may be proposed for the clinical management of patients with FAP. This policy needs to be validated in further prospective studies focusing on long-term endoscopic intervention and optimal age at prophylactic (procto)colectomy.
Role of nestin/14-3-3/mTOR signaling in airway smooth muscle cell proliferation and airway remodeling
Authors: Tang Dale , Liao Guoning , Wu Yidi , Wang Ruping , Maheshwari Neelam , Penn Raymond
Published: June 2023

Airway smooth muscle (ASM) cell proliferation plays a critical role in the progression of asthma. Asthma is characterized by airway remodeling, a cardinal feature of which is aberrant ASM cell proliferation. ASM hyperplasia leads to thickening of the airway wall, which exacerbates airway hyperresponsiveness and narrowing during asthma attacks. Although Th2 cytokines are prominent drivers of asthma pathogenesis, they do not drive ASM hyperplasia in asthma. Here, we discover that nestin, a type VI intermediate filament protein, regulates human ASM cell proliferation via 14-3-3/mechanistic target of rapamycin (mTOR) signaling. More importantly, nestin is upregulated in asthmatic human ASM, an epigenetic effect dependent on ten-eleven translocation methylcytosine dioxygenase 1-mediated 5-hydroxymethylcytosine. Smooth muscle conditional nestin knockout reduces airway smooth muscle thickening, airway hyperresponsiveness, inflammation, and mucus hypersecretion in an allergen-induced murine model of asthma. Moreover, comprehensive in vivo studies demonstrate nestin drives ASM hyperplasia and airway remodeling via 14-3-3/mTOR signaling.
Study on PTFE Superhydrophobic Coating Modified by IC@dMSNs and its Enhanced Antibacterial Effect
Authors: Zhang Weixing , Du Juan , Zhu Tonghe , Wang Ruilan , Aslam Mehwish , Kanwal Fariha , Rehman Muhammad Fayyaz ur
Published: June 2023

Objective:
Vascular catheter-related infections and thrombosis are common and may lead to serious complications after catheterization. Reducing the incidence of such infections has become a significant challenge. This study aims to develop a super hydrophobic nanocomposite drug-loaded vascular catheter that can effectively resist bacterial infections and blood coagulation.
Methods:
In this study, a SiO2 nanocoated PTFE (Polytetrafluoroethylene) catheter (PTFE-SiO2) was prepared and further optimized to prepare a SiO2 nanocoated PTFE catheter loaded with imipenem/cilastatin sodium (PTFE-IC@dMSNs). The catheters were characterized for performance, cell compatibility, anticoagulant performance, in vitro and in vivo antibacterial effect and biological safety.
Result:
PTFE-IC@dMSNs catheter has efficient drug loading performance and drug release rate and has good cell compatibility and anticoagulant effect in vitro. Compared with the PTFE-SiO2 catheter, the inhibition ring of the PTFE-IC@dMSNs catheter against Escherichia coli increased from 3.985 mm2 to 4.561 mm2, and the antibacterial rate increased from about 50.8% to 56.9%, with significant difference (p<0.05). The antibacterial zone against Staphylococcus aureus increased from 8.633 mm2 to 11.735 mm2, and the antibacterial rate increased from approximately 83.5% to 89.3%, showing a significant difference (p<0.05). PTFE-IC@dMSNs catheter also has good biocompatibility in vivo.
Conclusion:
Compared with PTFE, PTFE-SiO2 and PTFE-IC@dMSNs catheters have good characterization performance, cell compatibility, and anticoagulant properties. PTFE SiO2 and PTFE-IC@dMSNs catheters have good antibacterial performance and tissue safety against E. coli and S. aureus. Relatively, PTFE-SiO2 and PTFE-IC@dMSNs catheter has better antibacterial properties and histocompatibility and has potential application prospects in anti-bacterial catheter development and anticoagulation.
Assessment of in vitro anti-skin ageing activities of Giant Indian Gooseberry (Phyllanthus indofischeri Bennet) extracts for dermatological health and aesthetic applications
Authors: Boonpisuttinant Korawinwich , Ruksiriwanich Warintorn , Chutoprapat Romchat , Udompong Sarinporn , Kansawang Rattiya , Sangsee Jinapa , Chompoo Wirinda , Samothai Kitrawi , Srisut Ratakorn
Published: June 2023

Giant Indian Gooseberry (GIG) are commercially cultivated and commonly used herbs in Traditional medicine especially in Thailand. The aim of this study was to assess the potential of the GIG extracts on anti-aging activities to be a dermatological application. The juice, meat residues, and seeds of GIG collected from Sra Kaeo Province, Thailand, were extracted by the Boiling method (B) and the Maceration process (M) by using 95% ethanol as a solvent. The GIG extracts gave the total phenolic (TPC) and total flavonoid contents (TFC), quercetin contents, as well as exhibited the anti-oxidative activities. The GIG-R-B extract inhibited tyrosinase activity and had the highest anti-melanogenesis activity on B16F10 cells of 31.63 ± 0.70%. The GIG-S-B, GIG-S-M, and GIG-R-M extracts demonstrated the highest collagen biosynthesis, which was comparable to vitamin C (p < 0.05), whereas the GIG-R-B extracts gave the highest stimulation of anti-ageing genes (SIRT1 and FOXO1). All extracts at the concentration of 0.1 mg/mL showed no cytotoxicity on human skin fibroblasts. Therefore, the GIG-S-B extract was discovered to be a promising natural anti-ageing agent for dermatological health and aesthetic applications, that can be further developed in cosmetic, functional food and food supplement industries.
Integrability, lump solutions, breather solutions and hybird solutions for the (2+1)-dimensional variable coefficient Korteweg-de Vries equation
Authors: Chu Jingyi , Chen Xin , Liu Yaqing
Published: June 2023

This paper focuses on the integrability and exact solutions of a (2+1)-dimensional variable coefficient Korteweg-de Vries equation. The bilinear form, Bäcklund transformations, and Lax pair of this equation are obtained using the Bell polynomial method. Soliton solutions, including lump solitons, breather solitons, and hybrid solutions, are constructed by assuming different auxiliary functions in the bilinear ansatz method. Additionally, the soliton solutions are presented as figures for different variable coefficient functions and undetermined items under appropriate parameter choices. The Bäcklund transformations also lead to Lax pair and the infinity conservation laws that ensure the integrability of the nonlinear system under study.
Data-Driven Decision Support for Post-Hospitalization Diabetes Case Management Referral: A Predictive Analysis
Authors: Lee Seung-Yup , Hayes Leslie , Ozaydin Bunyamin , Howard Steven , Garretson Alison , Bradley Heather , Land Andrew , Pritchett Amy , Furr Amanda , Allgood Ashleigh , Wyatt Matthew , Hall Allyson , Banaszak-Holl Jane , DeLaney Erin
Published: June 2023

Background
While diabetes cases become more complex with increasing age and comorbidity, social determinants of health (SDoH), including food security, medication availability, and transportation, act as a significant source of disparities in diabetes risk and outcomes. However, with the existing supply-demand mismatch in diabetes case management, current case management referrals are primarily based on the most apparent clinical information. Data-driven decision support that learns from large-scale electronic health records (EHRs) encompassing the SDoH is a promising approach to helping prioritize demand and alleviate disparities through the identification of patients at highest risk.
Methods
This protocol is for a predictive analysis study to develop a proactive risk assessment decision support (PRADS) model incorporating the SDoH data to stratify urgency of needed case management among diabetic patients by identifying patients that are likely to utilize extensive resources including hospitalizations and emergency department (ED) visits. We will collect EHR data spanning from January 2018 to February 2023 from a Level 1 Trauma Center in Southeast (where diabetes and disparities have been prevalent), including demographics, SDoH, comorbidities, laboratory test results, access to care, medications, and the outcome variables (i.e., readmissions and ED visits). The dataset includes 65,821 unique inpatients that account for 132,273 inpatient encounters. 70% of the data observations will be utilized to train a Survival Decision Tree model, and the rest to generate prediction outcomes (probability of readmission or ED visit). The model will be validated in a quantitative manner by evaluating performance evaluation metrics and in a qualitative manner by conducting a three-phase modified Delphi method that involves the case management, clinician, and quality and patient safety teams.
Discussion
Despite the multifaceted disparities among diabetic patients, e.g., comorbidities and social support, the current case management referral process does not involve a comprehensive assessment of patient information. Data-driven decision support that learns from a wide range of SDoH and clinical information can help better identify high-risk patients for effective utilization of the current workforce. The PRADS model may demonstrate the value of SDoH in estimating diabetes risk factors, potential for system implementation, and improvement in utilizing the case management workforce.
Pharmacological fingerprint of antipsychotic drugs at the serotonin 5-HT2A receptor
Authors: Gaitonde Supriya A. , Shahraki Aida , Pastor Adrian Morales , Talagayev Valerij , Robledo Patricia , Kolb Peter , Selent Jana , Bouvier Michel
Published: June 2023

The intricate involvement of the serotonin 5-HT2A receptor (5-HT2AR) both in schizophrenia and in the activity of antipsychotic drugs is widely acknowledged. The currently marketed antipsychotic drugs, although effective in managing the symptoms of schizophrenia to a certain extent, are not without their repertoire of serious side effects. There is a need for better therapeutics to treat schizophrenia for which understanding the mechanism of action of the current antipsychotic drugs is imperative. With bioluminescence resonance energy transfer (BRET) assays, we trace the signaling signature of six antipsychotic drugs belonging to three generations at the 5-HT2AR for the entire spectrum of signaling pathways activated by serotonin (5-HT). The antipsychotic drugs display previously unidentified pathway preference at the level of the individual Gα subunits and β-arrestins. In particular, risperidone, clozapine, olanzapine and haloperidol showed G protein-selective inverse agonist activity. In addition, G protein-selective partial agonism was found for aripiprazole and cariprazine. Pathway-specific apparent dissociation constants determined from functional analyses revealed distinct coupling-modulating capacities of the tested antipsychotics at the different 5-HT-activated pathways. Computational analyses of the pharmacological and structural fingerprints supports a mechanistically based clustering that recapitulate the clinical classification (typical/first generation, atypical/second generation, third generation) of the antipsychotic drugs. The study provides a new framework to functionally classify antipsychotics that should represent a useful tool for the identification of better and safer neuropsychiatric drugs and allows formulating hypotheses on the links between specific signaling cascades and in the clinical outcomes of the existing drugs.
Evaluation of anti-biofilm properties of Mentha piperita essential oils loaded in chitosan nanoparticles against Acinetobacter baumannii in the Catheter surface
Authors: Shakib Pegah , Ashrafi Behnam , Rezaei Faranak , Delfani Somayeh
Published: June 2023

Background Multidrug-resistant (MDR) Gram-negative bacteria such as Acinetobacter baumannii pose an increasingly severe threat. Finding new therapeutic strategies such as herbal remedies is a vital priority, especially in combination with nano gels which have recently been widely used in medical purposes and drug delivery systems.Objective In this study, evaluated the physicochemical properties and effects of mutagenicity synthesizing Mentha Piperita Essential Oils loaded in chitosan nanoparticles (MPEO- CsNPs), which is referred to as an antimicrobial agent for inhibiting biofilm formation of Acinetobacter baumannii on the catheter surface.Method Mentha piperita essential oils loaded in chitosan nanoparticles (MPEO- CsNPs) and the physicochemical properties of MPEO-CsNPs were analyzed by Scanning Electron Microscopy (SEM) and Differential Calorimetry Scanning (DCS). The Minimum Inhibitory Concentration (MIC), the Minimum Bactericidal Concentration (MBC), and the Inhibitory Concentration (MBIC50) of MPEO- CsNPs against the standard strain of Acinetobacter baumannii were investigated. The amount of biofilm formation in the presence and absence of MPEO- CsNPs on the catheter surface was analyzed. The bap gene expression was studied as the primary leading indicator of biofilm formation using the real-time PCR technique. The effects of mutagenicity according to the Ames test were investigated.Results The results showed that the synthesized MPEO- CsNPs at equivalent concentrations had lower MIC than sodium azide. MIC and MBC levels were reported to be 3.12 and 12.48 µg / ml, respectively. MBIC50 was calculated to be 2.69%, which it was approximately twofold compared to the control that was treated with no MPEO concentration. The adherence of bacterial cells to the catheter surface had high sensitivity to the MPEO- CsNPs, while when treated with unloaded CNPs, it had no inhibitory effect on adherence activity. It was observed that with increasing the concentration of the MPEO- CsNPs, expression of the bap gene decreased.Conclusion This study showed that chitosan-peppermint nanoparticles could be used as a safe, compatible, and preventive coating in the design and manufacture of hospital catheters and other medical devices.
Targeted metabolomic profiling as a tool for diagnostics of patients with non- small-cell lung cancer
Authors: Shestakova Ksenia M. , Moskaleva Natalia E. , Boldin Andrey A. , Rezvanov Pavel M. , Shestopalov Alexandr V. , Rumyantsev Sergey A. , Zlatnik Elena Yu. , Novikova Inna A. , Sagakyants Alexander B. , Timofeeva Sofya V. , Simonov Yuriy , Baskhanova Sabina N. , Tobolkina Elena , Rudaz Serge , Appolonova Svetlana A.
Published: June 2023

Lung cancer is referred to as the second most common cancer worldwide and is mainly associated with poor diagnostics and the absence of personalized therapy. Metabolomics may provide significant insights into the improvement of lung cancer diagnostics and treatment through identification of the specific biomarkers or biomarker panels that characterize the pathological state of the patient. We performed targeted metabolomic profiling of plasma samples from individuals with non-small cell lung cancer (NSLC, n = 100) and individuals without any cancer or chronic pathologies (n = 100) to identify the relationship between plasma endogenous metabolites and NSLC by means of modern comprehensive bioinformatics tools, including univariate analysis, multivariate analysis, partial correlation network analysis and machine learning. Through the comparison of metabolomic profiles of patients with NSCLC and noncancer individuals, we identified significant alterations in the concentration levels of metabolites mainly related to tryptophan metabolism, the TCA cycle, the urea cycle and lipid metabolism. Additionally, partial correlation network analysis revealed significantly changed new ratios of the analyzed metabolites. Using the identified significantly altered metabolites and their ratios, we developed a machine learning classification model with an ROC AUC value equal to 0.96. The developed machine learning lung cancer model may serve as a prototype of the approach for the in-time diagnostics of lung cancer that in the future may be introduced in routine clinical use. Overall, we have demonstrated that the combination of metabolomics and up-to-date bioinformatics can be used as a potential tool for proper diagnostics of patients with NSCLC.
Coaxial electrospun Ag-NPs-loaded endograft membrane with long-term antibacterial function treating mycotic aortic aneurysm.
Authors: Hu Qingxi , Huang Zhenwei , zhang haiguang , Ma Pengcheng , Feng Jiaxuan , Feng Rui
Published: June 2023

Endovascular stent-graft has been widely used in the treatment of aortic pathologies. The stent-graft is consisted of two main parts: one is artificial vascular membrane which was used to exclude the lesions, and the other is the nitinol stent skeleton. But the current endograft membrane which was PET or ePTFE has a poor ability to inhibit bacterial colonization, it is not fit for endovascular treatment of mycotic aneurysms, as the infection is prone to progress after endograft implantation. And even after endovascular repair for non-mycotic aortic pathologies, endografts could become infected in short term or in long term, especially for patients with diabetes mellitus or in immune insufficiency conditions. In order to solve the problem that aneurysms cannot resist infection for a long time in clinic, in this study, a kind of silver nanoparticles (Ag-NPs) -loaded endograft membrane was prepared for coating the outer layer of the current stent-graft. The Ag-NPs-loaded membrane adopts coaxial electrospinning technique, with Polycaprolactone (PCL) as the shell, Chitosan (CS), Polyethylene oxide (PEO) and Ag-NPs with broad-spectrum antibacterial effect as the core, forming fibers with core-shell structure. A series of physical and chemical properties and biological properties of the Ag-NPs-loaded membrane were characterized: The formation of the core-shell structure was confirmed by TEM; The drug release experiment revealed that the membrane could effectively control the release rate of Ag-NPs; The bacteriostasis experiment proved that the membrane coating had an obvious inhibitory effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Animal experiments confirmed that the Ag-NPs-loaded membrane is basically non-toxic, has good biocompatibility, and can play an effective antibacterial role in the mycotic aortic aneurysm model in porcine. In conclusion, the Ag-NPs-loaded membrane prepared by coaxial electrospinning had optimal anti-infection function and it realized slow-releasing of Ag-NPs to achieve long-term bacteriostasis. Thus, the Ag-NPs-loaded membrane might have potential in preventing infection progression and treating mycotic aortic aneurysm in endovascular way.
Examining the Changes in Patient Adherence to Diabetic Footwear Using a Grounded Theory Approach
Authors: Mufti Yusuf , Hartman Anthony , Hayes Corey , Berry Armand , Peterson Blaire , Roser Mark
Published: June 2023

Background

Foot ulceration is one of the most debilitating complications of diabetes, often leading to further injury and eventual amputation. Specialized prescriptive footwear is a common modality for treatment and prevention of diabetic foot ulcers. However, footwear adherence is abysmally low in most cases, nullifying the therapeutic efficacy of this critical treatment. Little research has been done to ascertain the motivations and perspectives of those who utilize diabetic footwear, with this being the first qualitative study in the United States that seeks to understand the perspectives of those suffering from foot ulceration on therapeutic footwear.

Methods

In-depth interviews with fifteen diabetic individuals on their preferences and experiences with prescriptive footwear were conducted. A coding scheme was then iteratively generated and applied to interview transcripts using a grounded theory approach in order to elucidate key concepts.

Results

Three main categories by which patients evaluated prescription footwear emerged: style, utility, and efficacy. In the interviews, many common themes were found in the temporal progression of an individual’s attitude towards diabetic footwear . Based on these findings we found that there is a tripartite progression model of patient attitudes towards footwear, with individuals first emphasizing style early in the disease course, then footwear comfort, and, after a watershed moment such as an amputation, therapeutic efficacy.

Conclusions

This study has important implications for the design of future diabetic footwear. Using the tripartite model of progression, clinicians can tailor therapy to match patient preferences through the course of their disease, maximizing adherence.
Three-nucleate Rhizoctonia AG-E - a new subgroup within binucleate Rhizoctonia spp.
Authors: Moliszewska Ewa , Maculewicz Dagna , Stępniewska Hanna
Published: June 2023

The article presents a brief review of binucleate Rhizoctonia (BNR) within the Rhizoctonia genus. The genus Rhizoctonia has been classified into two main groups according to the number of nuclei. Binucleate Rhizoctonia strains have two nuclei in each cell, whereas multinucleate Rhizoctonia fungi were observed to have a variable number of nuclei ranging from 4 to 16 in each cell. The study was carried out on 12 BNR isolates originating in southern Poland. Comparison of the ITS1-5,8S-ITS2 sequences of the rDNA of tested isolates with sequences deposited in the GenBank revealed their affiliation to AG-E. Their affiliation to AG was confirmed by anastomosis reactions with tester isolates. The number of nuclei was counted with DAPI staining under a fluorescent microscope, and the diameter of hyphae was also measured. Not all AG-E isolates had the same number of nuclei in their cells: one group among these fungi produced cells with a diverse number of nuclei, usually 3; however, this number ranged from 2 to 4, making the average number of nuclei close to 3. It can be assumed that all isolates with three nuclei belong to this group, which may greatly facilitate the preliminary identification of binucleate isolates of Rhizoctonia spp. belonging to AG-E. This feature may also be a prerequisite for the separation of a new subgroup within AG-E, a subgroup of trinucleate strains (AG-E-3n). The thiamine requirement is not helpful in classifying and describing the AG-E strains.
Investigation of land use and land cover dynamics, drivers, and their consequences in south-central Ethiopia, with special emphasis on the contrasting agro-ecological settings of the Satame and Legabora watersheds
Authors: Mariye Mehari , Jianhua Li , Maryo Melesse , Tsegaye Gedion , Yigez Belayneh
Published: June 2023

Identifying the causes and drivers of land change is one of the main objectives of the land use and cover change investigation. Land use and cover change data are crucial for managing water resources and land preservation. This study examined the trends, driving factors, and implications of land use and land cover dynamics in contrasting agro-ecologies to provide empirical evidence about increases and losses in land use classes. Landsat images of MSS (1976), TM (1991 and 2001), ETM+ (2011), and OLI (2022) were used to study LULC dynamics. To identify the potential driving forces and impacts, field observations, discussions with key informants, analysis of land use policy, and focus group discussions (FGDs) were undertaken. The analysis of remote sensing data revealed that there was an increasing tendency for croplands, settlements, and forest lands at the expense of grasslands and shrublands. In Satame, shrub land and grassland decreased annually by –128.7 and –139.9 ha per year, while grassland and shrub cover reduced annually by –248.2 and –144.5 ha per year in Legabora, respectively. The Local communities perceived agricultural expansion, population growth, settlement expansion, and poverty as the main drivers of LULC changes, while deforestation, land degradation, low production and loss of biodiversity were the major consequences. From this study, it can be inferred that LULC has undergone significant changes over the past 45 years, with both positive and negative impacts. Hence, this study provides a foundation for land management policies and strategies in this watershed and other watersheds facing similar problems.
Absence of post-treatment changes in sentinel lymph nodes does not translate into increased regional recurrence rate in initially node positive breast cancer patients
Authors: Pislar Nina , Gasljevic Gorana , Ratosa Ivica , Kovac Anja , Zgajnar Janez , Perhavec Andraz
Published: June 2023

Purpose: To determine whether the absence of post-treatment changes in the negative sentinel lymph nodes (SLN) in the neoadjuvant setting for biopsy-proven cN+ disease results in an increased regional recurrence (RR) rate in patients after SLN biopsy (SLNB) only.
Methods: Breast cancer patients with biopsy-proven cN+ disease who converted to node-negative disease after neoadjuvant systemic treatment (NAST) and underwent SLNB only were included. Retrospective analysis was performed for patients diagnosed between 2008 and 2021. Patohistological specimens were reviewed for the presence of post-treatment changes in the SLNs. Patients with negative SLNs (ypN0) were divided into 2 groups: i) with post-treatment changes, ii) without post-treatment changes. Patients' characteristics were compared between groups. Crude RR rates were compared using the log-rank test. Recurrence-free (RFS) and overall survival (OS) for the entire cohort were calculated using Kaplan-Meier.
Results: Of 437 patients with cN+ disease, 95 underwent SLNB only. 82 were ypN0, 57 with post-treatment changes (group 1), 30 without post-treatment changes (group 2). During the median follow-up of 37 months (range 6–148), 1 isolated regional recurrence occurred in group 2 (RR rate 0% for group 1 vs. 4% for group 2, p=0.167). 3-year RFS and 3-year OS were 90.2% and 96.3%, respectively.
Conclusion: Absent post-treatment changes in negative SLNs for biopsy-proven cN+ disease that covert to node-negative after NAST did not result in increased regional recurrence rates in our cohort. Multidisciplinary input is essential to determine whether additional treatment is needed in these patients.
Caspase 8 protects pancreatic neoplasia from KRAS-driven necroptotic priming
Authors: Tishina Sofya , Dahlhaus Alina , Androulidaki Ariadne , Kotliar Michael , Mulalic Lejla , Rakhsh-Khorshid Hassan , Hocher Florian , Stroh Jenny , Beck Julia , Manik Marta , Williams Riley , Gülcüler Gülce , Abdallah Ali , Bebber Christina , Reese Moritz , Lim Jonathan , Trauzold Anna , Quaas Alexander , Brägelmann Johannes , Beleggia Filippo , Pasparakis Manolis , Liccardi Gianmaria , Balachandran Siddharth , Astsaturov Igor , Von Karstedt Silvia
Published: June 2023

Caspase 8 regulates normal tissue homeostasis by executing apoptosis and protecting from necroptosis. Several aggressive cancers express high levels of caspase 8, yet its function in neoplastic disease remains poorly explored. Here, we find that oncogenic KRAS-driven neoplastic transformation induces a transcriptional state of necroptotic priming, but necroptosis itself is kept in check by co-upregulation of caspase 8. Mice in which caspase 8 is deleted in the pancreas manifested a drastic decrease in precursor lesion formation in a KRASG12D-driven model of pancreatic cancer. Co-deletion of the essential necroptosis effector MLKL reversed the protective effects of caspase 8 ablation, and promoted metastasis. Mechanistically, oncogenic KRAS induced a STING-dependent type I interferon response, resulting in upregulation of necroptosis pathway components. High caspase 8 expression in precursor lesions was a result of co-selection to prevent necroptosis. Therefore, triggering necroptosis by blocking caspase 8 activity was therapeutically highly efficacious in models of genetically engineered PDAC in vivo. These results assign a tumor-protective function to caspase 8 in PDAC and show that overcoming caspase 8 activity has therapeutic benefit in this incurable malignancy.
Protective effects of butorphanol in oleic acid-endotoxin “two-hit” induced rat lung injury by suppression of inflammation and apoptosis
Authors: Zheng Yanlei , Hu Ronghua , Hu Jinrong , Feng Lina , Li Shi
Published: June 2023

Butorphanol is widely used as an anesthetic drug, whether butorphanol could reduce organ injury and protecting lung tissue is unknown. This study explored the effects of butorphanol on ALI and investigated its underlying mechanisms. We established a “two-hit” rat model and “two-hit” cell model to prove our hypothesis. Rats were divided into four groups [control, “two-hit” (OA + LPS), “two-hit” + butorphanol (4 mg/kg and 8 mg/kg) (OA + LPS + B1 and OA + LPS + B2)]. RPMVE cells were divided into four groups [control, “two-hit” (OA + LPS), “two-hit” + butorphanol (4 µM and 8 µM) (OA + LPS + 4 µM and OA + LPS + 8 µM)]. Inflammatory injury was assessed by the histopathology and W/D ratio, inflammatory cytokines, and arterial blood gas analysis. Apoptosis was assessed by Western blotting and flow cytometry. The effect of NF-κB p65 was detected by ELISA. Butorphanol could relieve the “two-hit” induced lung injury, the expression of TNF, IL-1β, IL-6, and improve lung ventilation. In addition, butorphanol decreased Bax and cleaved caspase-3, increased an antiapoptotic protein (Bcl-2), and inhibited the “two-hit” cell apoptosis ratio. Moreover, butorphanol suppressed NF-κB p65 activity in rat lung injury. Our research showed that butorphanol may attenuate “two-hit”-induced lung injury by regulating the activity of NF-κB p65, which may supply more evidence for ALI treatment.
Dual role of striatal astrocytes in behavioral flexibility and metabolism in the context of obesity
Authors: Montalban Enrica , Chao Daniela Herrera Moro , Ansoult Anthony , Pham Cuong , Contini Andrea , Castel Julien , Hassouna Rim , Hardonk Marene , Petitbon Anna , Foppen Ewout , Gangarossa Giuseppe , Trifilieff Pierre , Li Dongdong , Martin Claire , Luquet Serge
Published: June 2023

Brain circuits involved in metabolic control and reward-associated behaviors are potent drivers of feeding behavior and are both dramatically altered in obesity, a multifactorial disease resulting from genetic and environmental factors. In both mice and humans, exposure to calorie-dense food has been associated with increased astrocytes reactivity and pro-inflammatory response in the brain. Although our understanding of how astrocytes regulate brain circuits has recently flourish, whether and how striatal astrocytes contribute in regulating food-related behaviors and whole-body metabolism is still unknown. In this study, we show that exposure to enriched food leads to profound changes in neuronal activity and synchrony. Chemogenetic manipulation of astrocytes activity in the dorsal striatum was sufficient to restore the defect in flexible behaviors induced by obesity, while manipulation of astrocytes in the nucleus accumbens led to acute change in whole-body substrate utilization and energy expenditure. Altogether, this work reveals a yet unappreciated role for striatal astrocyte as a direct operator of reward-driven behavior and metabolic control.
Guideline Adherence for Cardiometabolic Monitoring of Patients Prescribed Antipsychotic Medications in UK primary care: A Retrospective Observational study
Authors: Ali Ruba Saleh Azfr , Jalal Zahraa , Johal Jaspal , Paudyal Vibhu
Published: June 2023

Background
The adverse effects of antipsychotics on cardiometabolic function are well documented despite their known effectiveness. Despite guidelines promoting routine monitoring, practices appear to be suboptimal.
Aim
The present study investigated the level of adherence to guidelines for cardiovascular and metabolic monitoring among healthcare professionals in primary care and factors that may influence monitoring patterns.
Method
Data were collected for patients with mental illness and prescribed antipsychotics at two general practices in England (February 2016-February 2021). The main outcome measures were the proportion of patients with evidence of monitoring for cardiometabolic parameters (body compositions, anthropometrics, lipids, glucose outcomes). Regression analysis was used to explore the factors predicting the monitoring practices.
Results
Data from 497 patients were included. The proportion of patients receiving cardiometabolic monitoring at least once yearly varied across different parameters. Patients were mostly monitored for BP (92%), body weight (BMI; >85%) and HDL (72%), but to a lesser extent for other lipid parameters (non-HDL ≈ 2%) and blood glucose (≈ 2%). Old age (OR:2.0–7.0, p < 0.001) and chronic conditions (e.g., CVD and DM, p < 0.05) were associated with cardiometabolic monitoring. Conversely, high metabolic risks antipsychotics (olanzapine), antipsychotic polypharmacy and cardiometabolic dysregulations (e.g., dyslipidaemias) did not improve monitoring practices.
Conclusions
Cardiometabolic health monitoring was generally infrequent, irregular, and did not change in response to abnormal test results or antipsychotic treatment with high cardiometabolic risks, suggesting more efforts need to be made to ensure the guidelines for cardiometabolic monitoring are followed. Monitoring Practices need to be evaluated across more general practices in the UK.
Systemic biochemical changes in pepper (Capsicum annuum L.) against Rhizoctonia solani by kale (Brassica oleracea var. acephala L.) green manure application
Authors: Rodríguez Víctor M. , Velasco Pablo , Cartea María Elena , Poveda Jorge
Published: June 2023

Background
In the search for new alternatives to avoid the problems associated with the use of chemical fungicides in agriculture, the use of green manure (GrM) could help to combat fungal diseases of crops, such as those produced by the necrotrophic pathogen Rhizoctonia solani. In the case of the use of brassica-tissues as GrM, could have an elicitor capacity of systemic plant resistance.
Results
We used kale-leaves as GrM and applied to pepper plants infected with R. solani. Application of freeze-dried kale-tissues to roots of pepper plants produced a systemic activation of foliar defenses via the salicylic acid (SA) and ethylene (ET) pathways, significantly reducing pathogen damage. In addition, this systemic response led to the accumulation of secondary defense metabolites in leaves, such as pipecolic acid, hydroxycoumarin or gluconic acid, among others. Remarkably, pepper plants treated with lyophilized kale-GrM accumulate glucosinolates when infected with R. solani. We also confirm that autoclaving removed part of the glucobrassicin (GBS) (85%) and sinigrin (19%) content of the kale-tissues.
Conclusions
GrM kale-tissues are able to activate systemic defenses in bell pepper against foliar pathogens through SA/ET hormonal pathways, accumulating secondary defense metabolites.
Single-Center Experience with Catheter-Directed Thrombolysis and Balloon Angioplasty for Acute Upper-Extremity Deep Vein Thrombosis: A Case Series Study
Authors: Jenab Yaser , Tofighi Saeed , Ayati Aryan , Rezvanimehr Ali , Moosavi Najme-sadat , Jalaie Houman , Barbati Mohammad Esmaeil
Published: June 2023

Background
Effective treatment of upper extremity deep vein thrombosis (UEDVT) is crucial to prevent further complications. Various treatments, including percutaneous mechanical thrombectomy (PMT), catheter-directed thrombolysis (CDT), decompression surgery, and venoplasty are suggested for UEDVT. However, no prospective study has yet favored any of these treatments. This study presents a review of our experience with CDT followed by balloon venoplasty in patients with acute primary UEDVT.
Methods
We enrolled all patients diagnosed with acute UEDVT from January 2020 to June 2021. Subjects with UEDVT due to secondary causes like malignancies, indwelling catheters, or leads were excluded. CDT was performed through brachial vein access, using a perfusion catheter, and rt-PA administration. Balloon venoplasty was performed if the treated segment had severe stenosis >50% after CDT. Patients were followed up at the vein clinic for any signs and symptoms in the upper extremity and lifestyle changes. Follow-up ultrasonography was done 12 months after discharge.
Results
Twelve patients with a mean age of 41.08 ± 14.0 were included in the study. The mean duration of CDT was 25.00±10.56 hours. After CDT, all patients had more than 50% stenosis, with seven having total occlusion. However, after balloon venoplasty, no patient had significant (more than 50%) stenosis. There was no serious complication after both procedures. Patients were followed up for a mean duration of twelve months after their admission, with a mean time of maintenance anticoagulation was 10.73±5.77 months. Only one patient had recurrent symptoms in his target limb, while the rest were free of symptoms in their treated extremity. No subject developed pulmonary emboli (PE) during admission or the follow-up period. There was no evidence of hospital readmission for any reason. Upper extremity color-doppler sonography of the patients at twelve months after their procedure showed normal venous flow without any significant stenosis in 8 (66.7%), and partially normal flow with patent target vein in 4 (33.3%) patients.
Conclusions
CDT followed by balloon venoplasty may be an effective treatment for selected patients with acute primary UEDVT, providing desirable long-term results and potentially avoiding the need for decompression surgery in the short or long term.
Are Youtube videos useful for students about Neurocranium Bones Anatomy?
Authors: Cuglan Songül , Gas Selin
Published: June 2023

Purpose
This study aims to evaluate the content, quality and functionality of YouTube videos on the anatomy of Neurocranium bones and to measure educational usefullness of the videos.
Methods
In this cross-sectional study, searches were made using the keywords "Neurocranium bones" and "Skull anatomy" in the YouTube search tab. Demographic data such as type, source, duration, upload date, and view rates of the videos were recorded. The quality and content of the videos were evaluated using the total content score (TCS), modified DISCERN scale, JAMA and Global Quality Scale (GQS). SPSS 26.0 software was used for statistical analysis.
Results
A statistically significant high correlation was observed between the GQS scores and the DISCERN scores (r = 0.813, p < 0.001). There was a high statistically significant positive correlation between the total content score and GQS (r = 0.887, p < 0.001) and between total content score and modified DISCERN (r = 0.691, p < 0.001). Also, there was a statistically significant positive moderate correlation between GQS scores and JAMA scores (r = 0.507, p < 0.05). A statistically significant moderate correlation was observed between JAMA and DISCERN scores (r = 0.521, p < 0.001), video length (r = 0,416, p < 0,05), comments (r = 0,457, p < 0,05), likes (r = 0,608, p < 0,001). There was a moderate statistically significant positive correlation between total content score and JAMA (r = 0,431, p < 0,05).
Conclusion
The majority of YouTube videos have insufficient information on neurocranium bones in the medical and dental school curriculum. Anatomists and institutions should be encouraged to prepare and present YouTube videos with assessment systems such as DISCERN, JAMA, GQS, and TCS in line with the current anatomy education curriculum.
Identification of PC4 as a diagnostic and prognostic biomarker in hepatocellular carcinoma
Authors: Bai Liangliang , Liu Guan , Dou Gang , He Xiaojun , Gong Chenyu , Zhang Hongbin , Tan Kai , Du Xilin
Published: June 2023

Background
Human positive cofactor 4 (PC4) is associated with the development and therapeutic resistance of several malignancies. Nonetheless, the role of PC4 in HCC remains obscure, warranting further investigation.
Methods
PC4 differential expression between HCC and normal tissues and its association with the clinicopathological characteristics of HCC patients were explored in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. Subsequently, the prognostic and diagnostic significance of PC4 in HCC patients was analyzed. Functional enrichment analyses were conducted by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene set enrichment analysis (GSEA) analysis to explore the biological functions of PC4. The CIBERSORT algorithm was used for immune infiltration analysis. The risk signature based on PC4-related genes was constructed by LASSO-COX regression and validated with the International Cancer Genome Consortium (ICGC) dataset. The qRT-PCR was used to verify the expression levels of all genes. Tumor Immune Dysfunction and Exclusion (TIDE) analysis evaluated the correlation between PC4 level and risk score and immunotherapy response in HCC patients. Finally, based on online databases, PC4-related ceRNA networks were constructed to explore the regulatory mechanism of PC4 in HCC.
Results
PC4 levels were significantly upregulated in HCC compared to normal tissues and positively correlated with the pathological grade and clinical stage. The PC4-high expression group showed a worse prognosis. In addition, PC4 could help distinguish tumor tissues from normal ones with an area under the curve (AUC) of 0.965. The PC4 level was associated with immune checkpoints and immune cell infiltration. In the training and validation sets, the eight-gene risk signature (Risk score = 0.074*CEP55 + 0.091*TRIP13 + 0.100*BRIX1 + 0.081*STIP1 + 0.191*PIGU + 0.038*CFL1 + 0.017*RBM17 + 0.178*OLA1) was strongly correlated with HCC patient prognosis and was considered as an independent prognostic factor. TIDE analysis showed that patients in both the PC4-low and low-risk groups were more likely to benefit from immunotherapy. Finally, the lncRNAs/miRNA-101-3p/PC4 network was constructed.
Conclusion
We confirmed PC4 as a diagnostic and prognostic marker in HCC patients. And, we developed and validated an 8-gene risk signature, which could help for clinical decision-making. The CeRNA network could help explore the regulatory mechanism of the PC4 gene in HCC.
Breast cancer histopathology image-based gene expression prediction using spatial transcriptomics data and deep learning
Authors: Rahaman Md Mamunur , Millar Ewan K. A. , Meijering Erik
Published: June 2023

Tumour heterogeneity in breast cancer poses challenges in predicting outcome and response to therapy. Spatial transcriptomics technologies may address these challenges, as they provide a wealth of information about gene expression at the cell level, but they are expensive, hindering their use in large-scale clinical oncology studies. Predicting gene expression from hematoxylin and eosin stained histology images provides a more affordable alternative for such studies. Here we present BrST-Net, a deep learning framework for predicting gene expression from histopathology images using spatial transcriptomics data. Using this framework, we trained and evaluated 10 state-of-the-art deep learning models without utilizing pretrained weights for the prediction of 250 genes. To enhance the generalisation performance of the main network, we introduce an auxiliary network into the framework. Our methodology outperforms previous studies, with 237 genes identified with positive correlation, including 24 genes with a median correlation coefficient greater than 0.50. This is a notable improvement over previous studies, which could predict only 102 genes with positive correlation, with the highest correlation values ranging from 0.29 to 0.34.
Balloon Kyphoplasty Is Unable to Improve Low Health-Related Quality of Life in Imbalanced Patients: A Longitudinal Cohort Study
Authors: Teraguchi Masatoshi , Enyo Yoshio , Minetama Masakazu , Yamamoto Yoshio , Nakagawa Masafumi , Nakatani Tomohiro , Nakagawa Yukihiro
Published: June 2023

Introduction: Osteoporotic vertebral compression fracture (OVCF) is a major public health concern, affecting the quality of life (QOL) of patients, particularly older adults. Balloon kyphoplasty (BKP) is a minimally invasive surgical treatment for OVCFs, with good clinical outcomes reported in short-term investigations. However, the impact of BKP on health-related QOL in the long term remains unclear. This study aimed to evaluate the effects of BKP on global sagittal balance and alignment and to determine the association between predictive factors before BKP and health-related QOL in the long term. Methods: A longitudinal cohort study was conducted on 62 patients (13 men and 49 women) diagnosed with OVCF who underwent BKP and were followed up for more than 12 months. Spinopelvic parameters, including sagittal vertical axis (SVA), thoracic kyphosis (TK), pelvic incidence (PI) minus lumbar lordosis (LL), and low back pain (LBP) severity, were measured preoperatively, at 3 months post-BKP, and at final follow-up. Multivariate logistic regression analysis was performed to identify predictive factors for unhealthy condition after BKP, with adjustment for age, sex, and duration from onset of back pain to BKP. Results: The mean follow-up duration was 20.7 months. The mean SVA values were 7.42 cm preoperatively, 7.62 cm at 3 months post-BKP, and 8.01 cm at final follow-up. The mean self-reported numerical rating scale scores for LBP were 8.4 preoperatively, 0.4 post-BKP, 0.6 at 3 months post-BKP, and 1.0 at final follow-up. Imbalanced spine (SVA ≥ 5.0 cm) and PI-LL mismatch (PI-LL ≥ 20°) before BKP were significantly associated with unhealthy condition (EuroQol 5 dimensions 5-level < 0.65) (odds ratio and 95% confidence intervals: imbalanced spine, 4.76 and 1.32–17.2; PI-LL mismatch, 3.78 and 1.18–12.1, respectively). Conclusions: BKP did not improve global spinopelvic parameters or health-related QOL in imbalanced patients. Higher SVA measurements and PII-LL mismatch before BKP were associated with lower health-related QOL after BKP. Therefore, BKP for imbalanced patients did not improve low health-related QOL.