bluuebunny/crossref_metadata_2025 huggingface dataset:
A Modified Generalized Analytic Feynman Integral Associated with the Bounded Linear Operator
Authors: Chung Hyun Soo
Published: December 2022

In this paper, we define a modified and generalized analytic Feynman integral associated with the bounded linear operator on abstract Wiener spaces. We then prove its existence. We also establish some modified and generalized analytic Feynman integration formulas and relationships involving the generalized Cameron–Storvick theorem. Finally, we give some examples to explain the usefulness of our research.
Prevalence of Escherichia coli Producing Extended Spectrum Beta-Lactamase (ESBL) Driven Septicaemia in Children Aged 0–2 Years in Two Districts Hospitals in Yaounde, Cameroon
Authors: Djuikoue Cécile Ingrid , Djouela Djoulako Paule Dana , Wouambo Rodrigue Kamga , Lacmago Suzie Titsamp , Dayomo Audrey , Kamga Hortense Gonsu , Thumamo Pokam Benjamin D. , Apalata Teke
Published: December 2022

Septicaemia is public health problem worldwide with a high rate of mortality among children. Epidemiological data on this phenomenon in Cameroon are still scarce. This study aimed to determine the prevalence and associated factors to septicaemia due to E. coli strains producing extended spectrum beta-lactamase (ESBL) in two hospitals in Yaoundé, Cameroon. A prospective, cross-sectional study was conducted on infants aged 0 to 2 years old at the consultation and neonatology care unit of two district hospitals of Yaoundé (UTHY and YGOPH) during a period of seven months (from August 2019 to March 2020). Each blood sample collected per infant was cultured in hemoline performance vials, and bacterial strains were identified using the Api-20 E system. In addition, an antibiotic resistant profile of isolates as well as the ESBL production were performed in accordance with the recommendations of the Antibiogram committee of the French Society of Microbiology 2019. Data were analysed in Epi-Info7.0 and for p less than 0.05, the difference was statistically significant. Of the 300 children enrolled, 130 (43.33%) were blood culture positive, and E. coli. was the most prevalent (69.23% (90/130)). Then antibiotic susceptibility test revealed that 77 over 90 E. coli strains were resistant to penicillin (with 85.55% to amoxicillin), and 34.44% were producing ESBL. Factors such as immunodeficiency, being on antibiotics, and particularly taking β-lactam were significantly associated with E. coli ESBL production ([aOR = 19.93; p = 0.0001], [aOR = 1.97; p = 0.04], and [aOR = 3.54; p = 0.01], respectively). Moreover, co-resistance to aminoglycosides, quinolones, fluoroquinolones, and cotrimoxazole were also found. This study highlighted a high prevalence of E. coli ESBL in blood samples of children aged 0–2 years in Yaoundé and prompts the development of more efficient strategies against E. coli ESBL associated mortality in infants in Cameroon.
Innovative Business Process Reengineering Adoption: Framework of Big Data Sentiment, Improving Customers’ Service Level Agreement
Authors: Susanto Heru , Sari Aida , Leu Fang-Yie
Published: December 2022

Social media is now regarded as the most valuable source of data for trend analysis and innovative business process reengineering preferences. Data made accessible through social media can be utilized for a variety of purposes, such as by an entrepreneur who wants to learn more about the market they intend to enter and uncover their consumers’ requirements before launching their new products or services. Sentiment analysis and text mining of telecommunication businesses via social media posts and comments are the subject of this study. A proposed framework will be utilized as a guideline, and it will be tested for sentiment analysis. Lexicon-based sentiment categorization is used as a model training dataset for a supervised machine learning support vector machine. The result is very promising. The accuracy and the quantity of the true sentiments it can detect are compared. This result signifies the usefulness of text mining and sentiment analysis on social media data, while the use of machine learning classifiers for predicting sentiment orientation provides a useful tool for operations and marketing departments. The availability of large amounts of data in this digitally active society is advantageous for sectors such as the telecommunication industry. These companies can be two steps ahead with their strategy and develop a more cohesive company that can make customers happier and mitigate problems easily with the use of text mining and sentiment analysis for further adopting innovative business process reengineering for service improvements within the telecommunications industry.
Rat Model of Quadriceps Contracture by Joint Immobilization
Authors: Suwankanit Kanokwan , Shimizu Miki
Published: December 2022

Muscle contracture is an abnormal pathologic process resulting in fibrosis and muscle atrophy, which can lead to limitation of joint motion. To establish a diagnostic method to detect muscle contracture and a method to control its progression, we investigated an appropriate method to create an animal model of quadriceps contracture using rats. Eighteen Wistar rats were divided into three groups, and bilateral hindlimbs were immobilized with either a cast (Group I), a Velcro hook-and-loop fastener (Group V), or steel wire (Group S) with the knee and ankle joints in extension position for two weeks. Five rats in a control group (Group C) were not immobilized. After two weeks, the progression of quadriceps contracture was assessed by measuring the range of joint motion and pathohistological changes. Muscle atrophy and fibrosis were observed in all immobilization groups. The knee joint range of motion, quadriceps muscle weight, and muscle fiber size decreased only in Group S compared to the other immobilization groups. Stress on rats due to immobilization was less in Group S. These results indicate that Group S is the superior quadriceps contracture model. This model aids research investigating diagnostic and therapeutic methods for muscle contracture in humans and animals.
Plant Microbiome Engineering: Hopes or Hypes
Authors: Afridi Muhammad Siddique , Ali Sher , Salam Abdul , César Terra Willian , Hafeez Aqsa , Sumaira  , Ali Baber , S. AlTami Mona , Ameen Fuad , Ercisli Sezai , Marc Romina Alina , Medeiros Flavio H. V. , Karunakaran Rohini
Published: December 2022

Rhizosphere microbiome is a dynamic and complex zone of microbial communities. This complex plant-associated microbial community, usually regarded as the plant’s second genome, plays a crucial role in plant health. It is unquestioned that plant microbiome collectively contributes to plant growth and fitness. It also provides a safeguard from plant pathogens, and induces tolerance in the host against abiotic stressors. The revolution in omics, gene-editing and sequencing tools have somehow led to unravel the compositions and latent interactions between plants and microbes. Similarly, besides standard practices, many biotechnological, (bio)chemical and ecological methods have also been proposed. Such platforms have been solely dedicated to engineer the complex microbiome by untangling the potential barriers, and to achieve better agriculture output. Yet, several limitations, for example, the biological obstacles, abiotic constraints and molecular tools that capably impact plant microbiome engineering and functionality, remained unaddressed problems. In this review, we provide a holistic overview of plant microbiome composition, complexities, and major challenges in plant microbiome engineering. Then, we unearthed all inevitable abiotic factors that serve as bottlenecks by discouraging plant microbiome engineering and functionality. Lastly, by exploring the inherent role of micro/macrofauna, we propose economic and eco-friendly strategies that could be harnessed sustainably and biotechnologically for resilient plant microbiome engineering.
Corticotropin-Releasing Hormone: Biology and Therapeutic Opportunities
Authors: Caruso Alessandra , Gaetano Alessandra , Scaccianoce Sergio
Published: December 2022

In 1981, Wylie Vale, Joachim Spiess, Catherine Rivier, and Jean Rivier reported on the characterization of a 41-amino-acid peptide from ovine hypothalamic extracts with high potency and intrinsic activity stimulating the secretion of adrenocorticotropic hormone and β-endorphin by cultured anterior pituitary cells. With its sequence known, this neuropeptide was determined to be a hormone and consequently named corticotropin-releasing hormone (CRH), although the term corticotropin-releasing factor (CRF) is still used and preferred in some circumstances. Several decades have passed since this seminal contribution that opened a new research era, expanding the understanding of the coding of stress-related processes. The characterization of CRH receptors, the availability of CRH agonists and antagonists, and advanced immunocytochemical staining techniques have provided evidence that CRH plays a role in the regulation of several biological systems. The purpose of this review is to summarize the present knowledge of this 41-amino-acid peptide.
Oxidative Stress-Induced HMGB1 Translocation in Myenteric Neurons Contributes to Neuropathy in Colitis
Authors: Stavely Rhian , Sahakian Lauren , Filippone Rhiannon T. , Stojanovska Vanesa , Bornstein Joel C. , Sakkal Samy , Nurgali Kulmira
Published: December 2022

High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern released by dying cells to stimulate the immune response. During cell death, HMGB1 is translocated from the nucleus to the cytoplasm and passively released. High levels of secreted HMGB1 are observed in the faeces of inflammatory bowel disease (IBD) patients, indicating its role in IBD pathophysiology and potential as a non-invasive IBD biomarker. HMGB1 is important in regulating neuronal damage in the central nervous system; its pathological activity is intertwined with oxidative stress and inflammation. In this study, HMGB1 expression in the enteric nervous system and its relevance to intestinal neuroinflammation is explored in organotypic cultures of the myenteric plexus exposed to oxidative stimuli and in Winnie mice with spontaneous chronic colitis. Oxidative stimuli induced cytoplasmic translocation of HMGB1 in myenteric neurons in organotypic preparations. HMGB1 translocation correlated with enteric neuronal loss and oxidative stress in the myenteric ganglia of Winnie mice. Inhibition of HMGB1 by glycyrrhizic acid ameliorated HMGB1 translocation and myenteric neuronal loss in Winnie mice. These data highlight modulation of HMGB1 signalling as a therapeutic strategy to reduce the consequences of enteric neuroinflammation in colitis, warranting the exploration of therapeutics acting on the HMGB1 pathway as an adjunct treatment with current anti-inflammatory agents.
A Novel and Validated 8-Pyroptosis-Related Genes Based Risk Prediction Model for Diffuse Large B Cell Lymphoma
Authors: Ma Junrui , Wang Wenhan , Ma Jiao , Xu Zizhen
Published: December 2022

Background: Diffuse large B-cell lymphoma (DLBCL), the most common type of Non-Hodgkin’s Lymphoma (NHL), has a lethal nature. Thus, the establishment of a novel model to predict the prognosis of DLBCL and guide its therapy is an urgency. Meanwhile, pyroptosis is engaged in the progression of DLBCL with further investigations required to reveal the underlying mechanism. Methods: LASSO regression was conducted to establish a risk model based on those PRGs. External datasets, RT-qPCR and IHC images from The Human Protein Alta (HPA) database were utilized to validate the model. ssGSEA was utilized to estimate the score of immune components in DLBCL. Results: A model based on 8 PRGs was established to generate a risk score. Validation of the model confirmed its robust performance. The risk score was associated with advanced clinical stages and shorter overall survivals. Two novel second-line chemotherapies were found to be potential treatments for high-risk patients. The risk score was also found to be correlated with immune components in DLBCL. Conclusion: This novel model can be utilized in clinical practices to predict the prognosis of DLBCL and guide the treatment of patients at high risk, providing an overview of immune regulatory program via pyroptosis in DLBCL.
Determination of the Assigned Values of Blood Cells by an Impedance Method for Hematological Reference Samples Used in Hematology External Quality Assessment (EQA) Programs
Authors: Vo Ngoc Nguyen , Tran Huu Tam , Nguyen Thi Hong Phuong , Vu Dinh Dung , Vo Thanh Sang , Nguyen Thuy Huong
Published: December 2022

The research into and production of hematological reference samples used to implement an external quality assessment (EQA) to check the quality of hematology tests are necessary for hematology laboratories in Vietnam. In this research, the study team determined the assessment values of blood cell count (human RBCs, pseudo-leucocytes, and pseudo-platelets) by the impedance method used in hematology EQA programs. The hematological reference samples were controlled at three concentration levels: low, normal, and high. Determination of the assigned value (mean ± 2SD) was performed for the following hematology analyzer series by impedance method: ABX Micros 60, Celldyn 1700, and Mindray BC 2000. Each device was sent to 10 different laboratories for evaluation. Research results for assigned values of each model (ABX Micros 60, Celldyn 1700, and Mindray BC 2000) were determined at the three concentrations. For the ABX Micros 60 and Celldyn 1700 series, 80% of laboratories had analytical results within assigned values. For the Mindray BC 2000 series, 100% of laboratories had analytical results within assigned values. The measurement results for the number of human RBCs, pseudo-leucocytes, and pseudo-platelets on each analyzer were similar between the 10 laboratories; the results of the three hematology analyzer series using the impedance method were different and the difference was statistically significant (p < 0.05). Thus, hematological reference samples for measuring the number of blood cells meeting the standards so that they can evaluate the results of laboratories using the impedance method: ABX, Celldyn 1700, Mindray BC 2000.
A Missense Variant in PDK1 Associated with Severe Neurodevelopmental Delay and Epilepsy
Authors: Vaz Raquel , Wincent Josephine , Elfissi Najla , Rosengren Forsblad Kristina , Pettersson Maria , Naess Karin , Wedell Anna , Wredenberg Anna , Lindstrand Anna , Ygberg Sofia
Published: December 2022

The pyruvate dehydrogenase complex (PDC) is responsible for the conversion of pyruvate into acetyl-CoA, which is used for energy conversion in cells. PDC activity is regulated by phosphorylation via kinases and phosphatases (PDK/PDP). Variants in all subunits of the PDC and in PDK3 have been reported, with varying phenotypes including lactic acidosis, neurodevelopmental delay, peripheral neuropathy, or seizures. Here, we report a de novo heterozygous missense variant in PDK1 (c.1139G > A; p.G380D) in a girl with developmental delay and early onset severe epilepsy. To investigate the role of PDK1G380D in energy metabolism and neuronal development, we used a zebrafish model. In zebrafish embryos we show a reduced number of cells with mitochondria with membrane potential, reduced movements, and a delay in neuronal development. Furthermore, we observe a reduction in the phosphorylation of PDH-E1α by PDKG380D, which suggests a disruption in the regulation of PDC activity. Finally, in patient fibroblasts, a mild reduction in the ratio of phosphorylated PDH over total PDH-E1α was detected. In summary, our findings support the notion that this aberrant PDK1 activity is the cause of clinical symptoms in the patient.
Disclosure of Genetic Risk Factors for Alzheimer’s Disease to Cognitively Healthy Individuals—From Current Practice towards a Personalised Medicine Scenario
Authors: Galluzzi Samantha , Pievani Michela , Zanetti Orazio , Benussi Luisa ,   The Italian-DIAfN Working Group, Frisoni Giovanni B. , Di Maria Emilio
Published: December 2022

Alzheimer’s disease (AD) is a genetically complex disorder. In addition to the relatively small number of pathogenic variants causing autosomal dominant AD, many others have been associated with the much more common sporadic form. The E4 allele of the Apolipoprotein E (APOE) is the first discovered genetic risk factor for AD. In addition, more than 70 genetic risk loci contributing to AD have been identified. Current guidelines do not recommend AD susceptibility genetic testing in cognitively healthy adults because the implications for clinical care are limited. However, secondary prevention clinical trials of disease-modifying therapies enrol individuals based on genetic criteria, and participants are often informed of APOE testing results. Moreover, the availability of direct-to-consumer genetic testing allows individuals to learn their own AD genetic risk profile without medical supervision. A number of research protocols for AD susceptibility genetic testing have been proposed. In Italy, disclosure processes and protocols beyond those developed for inherited dementia have not been established yet. We reviewed the literature on the current practice and clinical issues related to disclosing AD genetic risk to cognitively healthy individuals and provide suggestions that may help to develop specific guidelines at the national level.
Role of Matrix Metalloproteinases and Their Inhibitors in Locally Invasive Papillary Thyroid Cancer
Authors: Ivković Irena , Limani Zgjim , Jakovčević Antonia , Huić Dražen , Prgomet Drago
Published: December 2022

Locally invasive papillary thyroid carcinoma (PTC) protrudes beyond the thyroid capsule and invades local structures. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in local invasion and metastasis in PTC. The aim of our study was to determine expression levels of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 in tissue specimens of invasive and non-invasive PTC. Our hypothesis was that expression levels of these biomarkers correlate with the development of locally invasive PTC. In our single-center study we retrospectively investigated MMP and TIMP expression levels in 50 samples of thyroid tissue diagnosed as locally invasive papillary carcinoma (study group) and 30 samples of thyroid tissue diagnosed as non-invasive, non-metastatic papillary carcinoma (control group). Tissue specimens were immunohistochemically stained with primary monoclonal antibodies against MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2. When correlating expression levels of MMPs and TIMPs in thyroid tissue, statistically significant differences were found for MMP-1 and TIMP-1 expression (p < 0.001; Mann–Whitney U test) with the highest levels of expression in the invasive PTC group. Although expression of MMP-9 and TIMP-2 was higher in invasive PTC, the differences were not statistically significant. Elevated expression of MMP-1 and TIMP-1 in tumor tissue can predict invasiveness for PTC.
Enzymes of Fibrosis in Chronic Liver Disease
Authors: Tsomidis Ioannis , Notas George , Xidakis Costas , Voumvouraki Argyro , Samonakis Dimitrios N , Koulentaki Mairi , Kouroumalis Elias
Published: December 2022

Introduction: Liver fibrosis has been extensively studied at the cellular and molecular level, but very few data exist on the final enzymatic stages of collagen synthesis (prolyl hydroxylase, PH) and degradation (matrix metalloproteinases, MMPs), particularly in primary biliary cholangitis (PBC). Aim: We studied enzyme activities in liver tissue from patients with chronic liver diseases and compared them to normal livers. Patients: Eighteen patients with PBC of early and late stages (Ludwig’s classification) and seven on treatment with ursodeoxycholate (UDCA) were studied and compared to 34 patients with alcoholic liver disease (ALD), 25 patients with chronic viral liver disease and five normal biopsies. Sera were available from a total of 140 patients. Methods: The tritiated water released from the tritiated proline was measured in PH assessment. 14C intact and heat-denatured collagen substrates were used to measure collagenase and gelatinases, respectively. 3H Elastin was the substrate for elastase. In serum, ELISAs were used for MMP-1, TIMP-1, and TIMP-2 measurements while MMP-2 and MMP-9 were estimated by zymography. Results: PH was significantly increased in early and late PBC. Collagenase was reduced only in the late stages (p < 0.01), where the ratio PH/collagenase was increased. UDCA treatment restored values to almost normal. Gelatinases were reduced in late stages (p < 0.05). In contrast to PBC and ALD fibrosis, collagen synthesis is not increased in viral fibrosis. The balance shifted towards collagen deposition due to reduced degradation. Interestingly, gelatinolytic activity is not impaired in ALD. Elastase was similar to controls in all diseases studied. TIMP-1 was reduced in early PBC and viral and alcoholic hepatitis and cirrhosis (p < 0.001). Conclusions: (1) There is evidence that collagen synthesis increases in the early stages of PBC, but the collagenolytic mechanism may compensate for the increased synthesis. (2) In viral disease, fibrosis may be due to decreased degradation rather than increased synthesis. (3) The final biochemical stages of liver fibrosis may be quantitatively different according to underlying etiology.
Axonal Regeneration: Underlying Molecular Mechanisms and Potential Therapeutic Targets
Authors: Akram Rabia , Anwar Haseeb , Javed Muhammad Shahid , Rasul Azhar , Imran Ali , Malik Shoaib Ahmad , Raza Chand , Khan Ikram Ullah , Sajid Faiqa , Iman Tehreem , Sun Tao , Han Hyung Soo , Hussain Ghulam
Published: December 2022

Axons in the peripheral nervous system have the ability to repair themselves after damage, whereas axons in the central nervous system are unable to do so. A common and important characteristic of damage to the spinal cord, brain, and peripheral nerves is the disruption of axonal regrowth. Interestingly, intrinsic growth factors play a significant role in the axonal regeneration of injured nerves. Various factors such as proteomic profile, microtubule stability, ribosomal location, and signalling pathways mark a line between the central and peripheral axons’ capacity for self-renewal. Unfortunately, glial scar development, myelin-associated inhibitor molecules, lack of neurotrophic factors, and inflammatory reactions are among the factors that restrict axonal regeneration. Molecular pathways such as cAMP, MAPK, JAK/STAT, ATF3/CREB, BMP/SMAD, AKT/mTORC1/p70S6K, PI3K/AKT, GSK-3β/CLASP, BDNF/Trk, Ras/ERK, integrin/FAK, RhoA/ROCK/LIMK, and POSTN/integrin are activated after nerve injury and are considered significant players in axonal regeneration. In addition to the aforementioned pathways, growth factors, microRNAs, and astrocytes are also commendable participants in regeneration. In this review, we discuss the detailed mechanism of each pathway along with key players that can be potentially valuable targets to help achieve quick axonal healing. We also identify the prospective targets that could help close knowledge gaps in the molecular pathways underlying regeneration and shed light on the creation of more powerful strategies to encourage axonal regeneration after nervous system injury.
Colocalization Analysis of Cytoplasmic Actin Isoforms Distribution in Endothelial Cells
Authors: Shakhov Anton S. , Kovaleva Polina A. , Churkina Alexandra S. , Kireev Igor I. , Alieva Irina B.
Published: December 2022

Actin cytoskeleton is an essential component of living cells and plays a decisive role in many cellular processes. In mammals, β- and γ-actin are cytoplasmic actin isoforms in non-muscle cells. Despite minor differences in the amino acid sequence, β- and γ-actin localize in different cell structures and perform different functions. While cytoplasmic β-actin is involved in many intracellular processes including cell contraction, γ-actin is responsible for cell mobility and promotes tumor transformation. Numerous studies demonstrate that β- and γ-actin are spatially separated in the cytoplasm of fibroblasts and epithelial cells; this separation is functionally determined. The spatial location of β/γ-actin in endothelial cells is still a subject for discussion. Using super-resolution microscopy, we investigated the β/γ-actin colocalization in endotheliocytes and showed that the β/γ-actin colocalization degree varies widely between different parts of the marginal regions and near the cell nucleus. In the basal cytoplasm, β-actin predominates, while the ratio of isoforms evens out as it moves to the apical cytoplasm. Thus, our colocalization analysis suggests that β- and γ-actin are segregated in the endotheliocyte cytoplasm. The segregation is greatly enhanced during cell lamella activation in the nocodazole-induced endothelial barrier dysfunction, reflecting a different functional role of cytoplasmic actin isoforms in endothelial cells.
The Role of the Microbiome in Connective-Tissue-Associated Interstitial Lung Disease and Pulmonary Vasculitis
Authors: Drakopanagiotakis Fotios , Stavropoulou Elisavet , Tsigalou Christina , Nena Evangelia , Steiropoulos Paschalis
Published: December 2022

The microbiome can trigger and maintain immune-mediated diseases and is associated with the severity and prognosis of idiopathic pulmonary fibrosis, which is the prototype of interstitial lung diseases (ILDs). The latter can be a major cause of morbidity and mortality in patients with connective-tissue diseases (CTD). In the present review, we discuss the current evidence regarding microbiome in CTD-ILD and pulmonary vasculitis. In patients with rheumatoid arthritis (RA) the BAL microbiota is significantly less diverse and abundant, compared to healthy controls. These changes are associated with disease severity. In systemic sclerosis (SSc), gastrointestinal (GI)-dysbiosis is associated with ILD. Butyrate acid administration as a means of restoration of GI-microbiota has reduced the degree of lung fibrosis in animal models. Although related studies are scarce for SLE and Sjögren’s syndrome, studies of the gut, oral and ocular microbiome provide insights into the pathogenesis of these diseases. In ANCA-associated vasculitis, disease severity and relapses have been associated with disturbed nasal mucosa microbiota, with immunosuppressive treatment restoring the microbiome changes. The results of these studies suggest however no causal relation. More studies of the lung microbiome in CTD-ILDs are urgently needed, to provide a better understanding of the pathogenesis of these diseases.
NURR1 Is Differentially Expressed in Breast Cancer According to Patient Racial Identity and Tumor Subtype
Authors: Shaik Shahensha , Campbell Ha’reanna , Williams Christopher
Published: December 2022

Breast carcinoma (BCa) remains the second most common cause of cancer-related death among American women. Whereas estrogen receptor (ER) expression is typically regarded as a favorable prognostic indicator, a significant proportion of ER(+) patients still experience either de novo or acquired endocrine resistance. Previously, we have shown that the loss of orphan nuclear receptor NURR1 expression is associated with neoplastic transformation of the breast epithelium and shorter relapse-free survival (RFS) among systemically treated breast cancer (BCa) patients. Here, we further ascertain the prognostic value of NURR1 in BCa, and its differential expression among Black and White female BCa patients. We assessed the expression of NURR1 mRNA in BCa patients using the Cancer Genome Atlas (TGCA) and compared the occurrence of basal-like cancer and luminal A breast cancer subtypes. Expression levels were further stratified according to racial identity of the patient. We next assessed the correlation of NURR1 expression with Oncotype DX prognostic markers, and the association of NURR1 expression with relapse free survival in patients treated with endocrine therapy. Our study shows that NURR1 mRNA expression is differentially correlated with luminal A vs. basal-like cancer BCa and is predictive of poor relapse-free survival, confirming a similar trend observed in our previous studies using microarray data. NURR1 expression was positively correlated with expression of Oncotype DX biomarkers associated with estrogen responsiveness, while being inversely correlated with biomarkers associated with cell proliferation. Furthermore, we observed that NURR1 expression was positively associated with greater relapse-free survival at 5 years among patients treated with endocrine therapy. Interestingly, we found that among Black women with luminal A BCa, NURR1 expression was repressed in comparison to White women with the same subtype.
Template Free Anisotropically Grown Gold Nanocluster Based Electrochemical Immunosensor for Ultralow Detection of Cardiac Troponin I
Authors: Nisar Sumaya , Chansi  , Mathur Ashish , Basu Tinku , Singh Kshitij RB , Singh Jay
Published: December 2022

Anisotropic gold nanostructures have fascinated with their exceptional electronic properties, henceforth exploited for the fabrication of electrochemical sensors. However, their synthesis approaches are tedious and often require a growth template. Modern lifestyle has caused an upsurge in the risk of heart attack and requires urgent medical attention. Cardiac troponin I can serve as a biomarker in identification of suspected myocardial infection (heart attack). Hence the present work demonstrates the fabrication of a sensing platform developed by assimilating anisotropic gold nanoclusters (AuNCs) with anti cTnI antibody (acTnI) for the detection of cardiac troponin I (cTnI). The uniqueness and ease of synthesis by a template-free approach provides an extra edge for the fabrication of AuNC coated electrodes. The template-free growth of anisotropic AuNCs onto the indium tin oxide (ITO) glass substrates offers high sensitivity (2.2 × 10−4 A ng−1 mL cm−2) to the developed sensor. The immunosensor was validated by spiking different concentrations of cTnI in artificial serum with negligible interference under optimized conditions. The sensor shows a wide range of detection from 0.06–100 ng/mL with an ultralow detection limit. Thus, it suggests that the template-free immunosensor can potentially be used to screen the traces of cTnI present in blood serum samples, and the AuNCs based platform holds great promise as a transduction matrix, hence it can be exploited for broader sensing applications.
Current Status and Future Perspectives of Lactate Dehydrogenase Detection and Medical Implications: A Review
Authors: Zhou Yangzhe , Qi Min , Yang Minghui
Published: December 2022

The demand for glucose uptake and the accompanying enhanced glycolytic energy metabolism is one of the most important features of cancer cells. Unlike the aerobic metabolic pathway in normal cells, the large amount of pyruvate produced by the dramatic increase of glycolysis in cancer cells needs to be converted to lactate in the cytoplasm, which cannot be done without a large amount of lactate dehydrogenase (LDH). This explains why elevated serum LDH concentrations are usually seen in cancer patient populations. LDH not only correlates with clinical prognostic survival indicators, but also guides subsequent drug therapy. Besides their role in cancers, LDH is also a biomarker for malaria and other diseases. Therefore, it is urgent to develop methods for sensitive and convenient LDH detection. Here, this review systematically summarizes the clinical impact of lactate dehydrogenase detection and principles for LDH detection. The advantages as well as limitations of different detection methods and the future trends for LDH detection were also discussed.
Visual and Ultrasensitive Detection of a Coronavirus Using a Gold Nanorod Probe under Dark Field
Authors: Qian Xuejia , Shen Yuanzhao , Yuan Jiasheng , Yang Chih-Tsung , Zhou Xin
Published: December 2022

Porcine epidemic diarrhea virus (PEDV), a coronavirus that causes highly infectious intestinal diarrhea in piglets, has led to severe economic losses worldwide. Rapid diagnosis and timely supervision are significant in the prophylaxis of PEDV. Herein, we proposed a gold-nanorod (GNR) probe-assisted counting method using dark field microscopy (DFM). The antibody-functionalized silicon chips were prepared to capture PEDV to form sandwich structures with GNR probes for imaging under DFM. Results show that our DFM-based assay for PEDV has a sensitivity of 23.80 copies/μL for simulated real samples, which is very close to that of qPCR in this study. This method of GNR probes combined with DFM for quantitative detection of PEDV not only has strong specificity, good repeatability, and a low detection limit, but it also can be implemented for rapid on-site detection of the pathogens.
Au Nanoparticles (NPs) Decorated Co Doped ZnO Semiconductor (Co400-ZnO/Au) Nanocomposites for Novel SERS Substrates
Authors: Zhai Yan , Zhao Xiaoyu , Ma Zhiyuan , Guo Xiaoyu , Wen Ying , Yang Haifeng
Published: December 2022

Au nanoparticles were decorated on the surface of Co-doped ZnO with a certain ratio of Co2+/Co3+ to obtain a novel semiconductor-metal composite. The optimal substrate, designated as Co400-ZnO/Au, is beneficial to the promotion of separation efficiency of electron and hole in a semiconductor excited under visible laser exposure, which the enhances localized surface plasmon resonance (LSPR) of the Au nanoparticles. As an interesting finding, during Co doping, quantum dots of ZnO are generated, which strengthen the strong semiconductor metal interaction (SSSMI) effect. Eventually, the synergistic effect effectively advances the surface enhancement Raman scattering (SERS) performance of Co400-ZnO/Au composite. The enhancement mechanism is addressed in-depth by morphologic characterization, UV-visible, X-ray diffraction, photoluminescence, X-ray photoelectron spectroscopy, density functional theory, and finite difference time domain (FDTD) simulations. By using Co400-ZnO/Au, SERS detection of Rhodamine 6G presents a limit of detection (LOD) of 1 × 10−9 M. As a real application, the Co400-ZnO/Au-based SERS method is utilized to inspect tyramine in beer and the detectable concentration of 1 × 10−8 M is achieved. In this work, the doping strategy is expected to realize a quantum effect, triggering a SSSMI effect for developing promising SERS substrates in future.
Common Data Elements Reported in Mechanical Thrombectomy for Acute Ischemic Stroke: A Systematic Review of Active Clinical Trials
Authors: Ghozy Sherief , Hardy Nicole , Sutphin Daniel J. , Kallmes Kevin M. , Kadirvel Ramanathan , Kallmes David F.
Published: December 2022

Background: New trials are planned regularly to provide the highest quality of evidence and invade new occlusion territories, which requires a pre-defined reporting strategy with consistent, common data elements for more straightforward collective evidence synthesis. We sought to review all active endovascular thrombectomy trials to investigate their patient selection criteria, intervention description, and reported outcomes. Methods: A literature search was systematically conducted on clinicaltrials.gov for active trials and all intervention, inclusion criteria, and outcomes reported were extracted. A qualitative synthesis of the frequency of study design types and data elements are graphically and narratively presented. Results: A total of 32 studies were tagged and included in the final qualitative analysis. The inclusion criteria were highly variable, including different cut-offs for the last well-known baseline National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and modified Rankin scale (mRS). Half of the studies (16/32) mentioned “thrombectomy” without defining which technique or device was used, and the final thrombolysis in cerebral infarction scale was provided in 19 (59.4%) studies. Heterogeneity was also present among the studies reporting a first-pass effect, both in how studies defined the outcome and in used ranges for mRS. Mortality and intracerebral hemorrhage (ICH) were more homogenous in their presentation and follow-up. Conclusions: There is a great degree of heterogeneity in the active thrombectomy trials concerning inclusion criteria, interventions used, and how outcomes are being reported.
Altered Functional Connectivity and Complexity in Major Depressive Disorder after Musical Stimulation
Authors: Qiu Pintao , Dai Jinxiao , Wang Ting , Li Hangcheng , Ma Cunbin , Xi Xugang
Published: December 2022

Major depressive disorder (MDD) is a common mental illness. This study used electroencephalography (EEG) to explore the effects of music therapy on brain networks in MDD patients and to elucidate changes in functional brain connectivity in subjects before and after musical stimulation. EEG signals were collected from eight MDD patients and eight healthy controls. The phase locking value was adopted to calculate the EEG correlation of different channels in different frequency bands. Correlation matrices and network topologies were studied to analyze changes in functional connectivity between brain regions. The results of the experimental analysis found that the connectivity of the delta and beta bands decreased, while the connectivity of the alpha band increased. Regarding the characteristics of the EEG functional network, the average clustering coefficient, characteristic path length and degree of each node in the delta band decreased significantly after musical stimulation, while the characteristic path length in the beta band increased significantly. Characterized by the average clustering coefficient and characteristic path length, the classification of depression and healthy controls reached 93.75% using a support vector machine.
Endoscopic Endonasal Skull Base Surgery Complication Avoidance: A Contemporary Review
Authors: Porras Jose L. , Rowan Nicholas R. , Mukherjee Debraj
Published: December 2022

The endoscopic endonasal approach (EEA) provides a direct trajectory to ventral skull base lesions, avoidance of brain retraction, and clear visualization of cranial nerves as they exit skull base foramina. Despite these benefits, the EEA is not without complications. Here, we review published literature highlighting complications associated with the EEA including cerebrospinal fluid (CSF) leak, cranial nerve (CN) dysfunction, pituitary gland dysfunction, internal carotid artery (ICA) injury, infection, and others; we place special emphasis on discussing the prevention of these complications. As widespread adoption of the EEA continues, it becomes critical to educate surgeons regarding potential complications and their prevention while identifying gaps in the current literature to guide future research and advances in clinical care.
The Application of Graph in BIM/GIS Integration
Authors: Zhu Junxiang , Chong Heap-Yih , Zhao Hongwei , Wu Jeremy , Tan Yi , Xu Honglei
Published: December 2022

Information exchange between building information modelling (BIM) and geographic information system (GIS) is problematic, especially in terms of semantic information. Graph-based technologies, such as the resource description framework (RDF) and the labelled property graph (LPG), are promising in solving this problem. These two technologies are different but have not been systematically investigated in the context of BIM/GIS integration. This paper presents our systematic investigation into these two technologies, trying to propose the proper one for BIM/GIS data integration. The main findings are as follows. (1) Both LPG-based databases and RDF-based databases can be generally considered graph databases, but an LPG-based database is considered a native graph database, while an RDF-based database is not. (2) RDF suits applications focusing more on linking data and sharing data, and (3) LPG-based graph database suits applications focusing more on data query and analysis. An LPG-based graph database is thus proposed for BIM/GIS data integration. This review can facilitate the use of graph technology in BIM/GIS integration.
Post-buckling Partial Similitude Scaled Model for Stiffened Cylinders under Axial Compression by Energy Method
Authors: Yu Wei , Du Siyu , Zhu Wanxu , Zhang Chuntao
Published: December 2022

Considering the geometric nonlinearity and geometric imperfection of stiffened cylinders, the generalized similitude conditions and scaling laws for axial compression post-buckling are established by applying the similitude transformation to the total energy of the structure. The post-buckling similarity of stiffened cylinders is numerically analyzed, and scale laws, through innovative application of the stiffness formulas and deformation scale factor. Based on three type geometrical imperfections, the effects of radius to effective thickness ratios, stiffened cross-sections, boundary conditions and imperfection coefficients are investigated by post-buckling partial similarity simulation of stiffened cylinders under axial compression. The results show that the partial similarity can be well realized by changing other parameters or selecting a model with a similar Poisson’s ratio for the prototypical material on the premise of invariant stiffness scale factors. Partial similarity simulation of axial compression post-buckling of stiffened cylinders is not affected by radius to effective thickness ratios (23.76–268.95), classical simply supported and fixed support boundary conditions, rectangular or T-type stiffened cross-sections and three type of geometric imperfections.
Leading New Frontiers in Vulva Cancer to Build Personalized Therapy
Authors: Corrado Giacomo , Garganese Giorgia
Published: December 2022

Approximately 3 in 1000 women will receive a diagnosis of vulvar cancer at some point in their lives [...]
The Emerging Role of uORF-Encoded uPeptides and HLA uLigands in Cellular and Tumor Biology
Authors: Jürgens Lara , Wethmar Klaus
Published: December 2022

Recent technological advances have facilitated the detection of numerous non-canonical human peptides derived from regulatory regions of mRNAs, long non-coding RNAs, and other cryptic transcripts. In this review, we first give an overview of the classification of these novel peptides and summarize recent improvements in their annotation and detection by ribosome profiling, mass spectrometry, and individual experimental analysis. A large fraction of the novel peptides originates from translation at upstream open reading frames (uORFs) that are located within the transcript leader sequence of regular mRNA. In humans, uORF-encoded peptides (uPeptides) have been detected in both healthy and malignantly transformed cells and emerge as important regulators in cellular and immunological pathways. In the second part of the review, we focus on various functional implications of uPeptides. As uPeptides frequently act at the transition of translational regulation and individual peptide function, we describe the mechanistic modes of translational regulation through ribosome stalling, the involvement in cellular programs through protein interaction and complex formation, and their role within the human leukocyte antigen (HLA)-associated immunopeptidome as HLA uLigands. We delineate how malignant transformation may lead to the formation of novel uORFs, uPeptides, or HLA uLigands and explain their potential implication in tumor biology. Ultimately, we speculate on a potential use of uPeptides as peptide drugs and discuss how uPeptides and HLA uLigands may facilitate translational inhibition of oncogenic protein messages and immunotherapeutic approaches in cancer therapy.
Radiomics-Based Prediction of Future Portal Vein Tumor Infiltration in Patients with HCC—A Proof-of-Concept Study
Authors: Stoehr Fabian , Kloeckner Roman , Pinto dos Santos Daniel , Schnier Mira , Müller Lukas , Mähringer-Kunz Aline , Dratsch Thomas , Schotten Sebastian , Weinmann Arndt , Galle Peter Robert , Mittler Jens , Düber Christoph , Hahn Felix
Published: December 2022

Portal vein infiltration (PVI) is a typical complication of HCC. Once diagnosed, it leads to classification as BCLC C with an enormous impact on patient management, as systemic therapies are henceforth recommended. Our aim was to investigate whether radiomics analysis using imaging at initial diagnosis can predict the occurrence of PVI in the course of disease. Between 2008 and 2018, we retrospectively identified 44 patients with HCC and an in-house, multiphase CT scan at initial diagnosis who presented without CT-detectable PVI but developed it in the course of disease. Accounting for size and number of lesions, growth type, arterial enhancement pattern, Child–Pugh stage, AFP levels, and subsequent therapy, we matched 44 patients with HCC who did not develop PVI to those developing PVI in the course of disease (follow-up ended December 2021). After segmentation of the tumor at initial diagnosis and texture analysis, we used LASSO regression to find radiomics features suitable for PVI detection in this matched set. Using an 80:20 split between training and holdout validation dataset, 17 radiomics features remained in the fitted model. Applying the model to the holdout validation dataset, sensitivity to detect occurrence of PVI was 0.78 and specificity was 0.78. Radiomics feature extraction had the ability to detect aggressive HCC morphology likely to result in future PVI. An additional radiomics evaluation at initial diagnosis might be a useful tool to identify patients with HCC at risk for PVI during follow-up benefiting from a closer surveillance.
Prognostic Evaluation of Metastatic Castration Resistant Prostate Cancer and Neuroendocrine Prostate Cancer with [68Ga]Ga DOTATATE PET-CT
Authors: Bilen Mehmet Asim , Akintayo Akinyemi , Liu Yuan , Abiodun-Ojo Olayinka , Kucuk Omer , Carthon Bradley C. , Schuster David M. , Parent Ephraim E.
Published: December 2022

Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, [68Ga]Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of [68Ga]Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: [68Ga]Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those, 2/17 had NePC. A semiquantitative analysis with standardized uptake values (SUV) (e.g., SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. [68Ga]Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastatic lesion with identifiable [68Ga]Ga-DOTATATE uptake. Marked [68Ga]Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. Three patients had mild [68Ga]Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after [68Ga]Ga-DOTATATE imaging. Conclusions: [68Ga]Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with [68Ga]Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.