bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Molecular Signature of Cancer-Associated Fibroblasts Predicts Prognosis and Immunotherapy Response in Pancreatic Cancer
Authors: Ge Weiyu , Yue Ming , Wang Yanling , Wang Yongchao , Xue Shengbai , Shentu Daiyuan , Mao Tiebo , Zhang Xiaofei , Xu Haiyan , Li Shumin , Ma Jingyu , Wang Liwei , Cui Jiujie
Published: December 2022

Cancer-associated fibroblasts (CAFs), a prominent population of stromal cells, play a crucial role in tumor progression, prognosis, and treatment response. However, the relationship among CAF-based molecular signatures, clinical outcomes, and tumor microenvironment infiltration remains largely elusive in pancreatic cancer (PC). Here, we collected multicenter PC data and performed integrated analysis to investigate the role of CAF-related genes (CRGs) in PC. Firstly, we demonstrated that α-SMA+ CAFs were the most prominent stromal components and correlated with the poor survival rates of PC patients in our tissue microarrays. Then, we discriminated two diverse molecular subtypes (CAF clusters A and B) and revealed the significant differences in the tumor immune microenvironment (TME), four reported CAF subpopulations, clinical characteristics, and prognosis in PC samples. Furthermore, we analyzed their association with the immunotherapy response of PC patients. Lastly, a CRG score was constructed to predict prognosis, immunotherapy responses, and chemosensitivity in pancreatic cancer patients. In summary, these findings provide insights into further research targeting CAFs and their TME, and they pave a new road for the prognosis evaluation and individualized treatment of PC patients.
Lessons on Drug Development: A Literature Review of Challenges Faced in Nonalcoholic Fatty Liver Disease (NAFLD) Clinical Trials
Authors: Chen Joel Yeh Siang , Chua Damien , Lim Carissa Odelia , Ho Wan Xi , Tan Nguan Soon
Published: December 2022

NAFLD is the most common chronic liver disease worldwide, occurring in both obese and lean patients. It can lead to life-threatening liver diseases and nonhepatic complications, such as cirrhosis and cardiovascular diseases, that burden public health and the health care system. Current care is weight loss through diet and exercise, which is a challenging goal to achieve. However, there are no FDA-approved pharmacotherapies for NAFLD. This review thoroughly examines the clinical trial findings from 22 drugs (Phase 2 and above) and evaluates the future direction that trials should take for further drug development. These trialed drugs can broadly be categorized into five groups—hypoglycemic, lipid-lowering, bile-pathway, anti-inflammatory, and others, which include nutraceuticals. The multitude of challenges faced in these yet-to-be-approved NAFLD drug trials provided insight into a few areas of improvement worth considering. These include drug repurposing, combinations, noninvasive outcomes, standardization, adverse event alleviation, and the need for precision medicine with more extensive consideration of NAFLD heterogenicity in drug trials. Understandably, every evolution of the drug development landscape lies with its own set of challenges. However, this paper believes in the importance of always learning from lessons of the past, with each potential improvement pushing clinical trials an additional step forward toward discovering appropriate drugs for effective NAFLD management.
Diversity in Genetic Regulation of Bacterial Fimbriae Assembled by the Chaperone Usher Pathway
Authors: Gahlot Dharmender K. , Taheri Nayyer , MacIntyre Sheila
Published: December 2022

Bacteria express different types of hair-like proteinaceous appendages on their cell surface known as pili or fimbriae. These filamentous structures are primarily involved in the adherence of bacteria to both abiotic and biotic surfaces for biofilm formation and/or virulence of non-pathogenic and pathogenic bacteria. In pathogenic bacteria, especially Gram-negative bacteria, fimbriae play a key role in bacteria–host interactions which are critical for bacterial invasion and infection. Fimbriae assembled by the Chaperone Usher pathway (CUP) are widespread within the Enterobacteriaceae, and their expression is tightly regulated by specific environmental stimuli. Genes essential for expression of CUP fimbriae are organised in small blocks/clusters, which are often located in proximity to other virulence genes on a pathogenicity island. Since these surface appendages play a crucial role in bacterial virulence, they have potential to be harnessed in vaccine development. This review covers the regulation of expression of CUP-assembled fimbriae in Gram-negative bacteria and uses selected examples to demonstrate both dedicated and global regulatory mechanisms.
Scion-to-Rootstock Mobile Transcription Factor CmHY5 Positively Modulates the Nitrate Uptake Capacity of Melon Scion Grafted on Squash Rootstock
Authors: Hou Shu’an , Zhu Yulei , Wu Xiaofang , Xin Ying , Guo Jieying , Wu Fang , Yu Hanqi , Sun Ziqing , Xu Chuanqiang
Published: December 2022

It is generally recognized that the root uptake capacity of grafted plants strongly depends on the rootstocks’ well-developed root system. However, we found that grafted plants showed different nitrate uptake capacities when different varieties of oriental melon scion were grafted onto the same squash rootstock, suggesting that the scion regulated the nitrate uptake capacity of the rootstock root. In this study, we estimated the nitrate uptake capacity of grafted plants with the different oriental melon varieties’ seedlings grafted onto the same squash rootstocks. The results indicated a significant difference in the nitrate uptake rate and activity of two heterologous grafting plants. We also showed a significant difference in CmoNRT2.1 expression in the roots of two grafting combinations and verified the positive regulation of nitrate uptake by CmoNRT2.1 expression. In addition, the two varieties of oriental melon scion had highly significant differences in CmHY5 expression, which was transported to the rootstock and positively induced CmoHY5-1 and CmoHY5-2 expression in the rootstock roots. Meanwhile, CmHY5 could positively regulate CmoNRT2.1 expression in the rootstock roots. Furthermore, CmoHY5-1 and CmoHY5-2 also positively regulated CmoNRT2.1 expression, respectively, and CmoHY5-1 dominated the positive regulation of CmoNRT2.1, while CmHY5 could interact with CmoHY5-1 and CmoHY5-2, respectively, to jointly regulate CmoNRT2.1 expression. The oriental melon scion regulated the nitrate uptake capacity of the melon/squash grafting plant roots, and the higher expression of CmHY5 in the oriental melon scion leaves, the more substantial the nitrate uptake capacity of squash rootstock roots.
Succinyl Chitosan-Colistin Conjugates as Promising Drug Delivery Systems
Authors: Dubashynskaya Natallia V. , Bokatyi Anton N. , Dobrodumov Anatoliy V. , Kudryavtsev Igor V. , Trulioff Andrey S. , Rubinstein Artem A. , Aquino Arthur D. , Dubrovskii Yaroslav A. , Knyazeva Elena S. , Demyanova Elena V. , Nashchekina Yuliya A. , Skorik Yury A.
Published: December 2022

The growth of microbial multidrug resistance is a problem in modern clinical medicine. Chemical modification of active pharmaceutical ingredients is an attractive strategy to improve their biopharmaceutical properties by increasing bioavailability and reducing drug toxicity. Conjugation of antimicrobial drugs with natural polysaccharides provides high efficiency of these systems due to targeted delivery, controlled drug release and reduced toxicity. This paper reports a two-step synthesis of colistin conjugates (CT) with succinyl chitosan (SucCS); first, we modified chitosan with succinyl anhydride to introduce a carboxyl function into the polymer molecule, which was then used for chemical grafting with amino groups of the peptide antibiotic CT using carbodiimide chemistry. The resulting polymeric delivery systems had a degree of substitution (DS) by CT of 3–8%, with conjugation efficiencies ranging from 54 to 100% and CT contents ranging from 130–318 μg/mg. The size of the obtained particles was 100–200 nm, and the ζ-potential varied from −22 to −28 mV. In vitro release studies at pH 7.4 demonstrated ultra-slow hydrolysis of amide bonds, with a CT release of 0.1–0.5% after 12 h; at pH 5.2, the hydrolysis rate slightly increased; however, it remained extremely low (1.5% of CT was released after 12 h). The antimicrobial activity of the conjugates depended on the DS. At DS 8%, the minimum inhibitory concentration (MIC) of the conjugate was equal to the MIC of native CT (1 µg/mL); at DS of 3 and 5%, the MIC increased 8-fold. In addition, the developed systems reduced CT nephrotoxicity by 20–60%; they also demonstrated the ability to reduce bacterial lipopolysaccharide-induced inflammation in vitro. Thus, these promising CT-SucCS conjugates are prospective for developing safe and effective nanoantibiotics.
CRISPR/Cas9-Induced Inactivation of the Autism-Risk Gene setd5 Leads to Social Impairments in Zebrafish
Authors: Gabellini Chiara , Pucci Cecilia , De Cesari Chiara , Martini Davide , Di Lauro Caterina , Digregorio Matteo , Norton William , Zippo Alessio , Sessa Alessandro , Broccoli Vania , Andreazzoli Massimiliano
Published: December 2022

Haploinsufficiency of the SETD5 gene, encoding a SET domain-containing histone methyltransferase, has been identified as a cause of intellectual disability and Autism Spectrum Disorder (ASD). Recently, the zebrafish has emerged as a valuable model to study neurodevelopmental disorders because of its genetic tractability, robust behavioral traits and amenability to high-throughput drug screening. To model human SETD5 haploinsufficiency, we generated zebrafish setd5 mutants using the CRISPR/Cas9 technology and characterized their morphological, behavioral and molecular phenotypes. According to our observation that setd5 is expressed in adult zebrafish brain, including those areas controlling social behavior, we found that setd5 heterozygous mutants exhibit defective aggregation and coordination abilities required for shoaling interactions, as well as indifference to social stimuli. Interestingly, impairment in social interest is rescued by risperidone, an antipsychotic drug used to treat behavioral traits in ASD individuals. The molecular analysis underscored the downregulation of genes encoding proteins involved in the synaptic structure and function in the adult brain, thus suggesting that brain hypo-connectivity could be responsible for the social impairments of setd5 mutant fishes. The zebrafish setd5 mutants display ASD-like features and are a promising setd5 haploinsufficiency model for drug screening aimed at reversing the behavioral phenotypes.
Lipoprotein(a): Cardiovascular Disease, Aortic Stenosis and New Therapeutic Option
Authors: Maloberti Alessandro , Fabbri Saverio , Colombo Valentina , Gualini Elena , Monticelli Massimiliano , Daus Francesca , Busti Andrea , Galasso Michele , De Censi Lorenzo , Algeri Michela , Merlini Piera Angelica , Giannattasio Cristina
Published: December 2022

Atherosclerosis is a chronic and progressive inflammatory process beginning early in life with late clinical manifestation. This slow pathological trend underlines the importance to early identify high-risk patients and to treat intensively risk factors to prevent the onset and/or the progression of atherosclerotic lesions. In addition to the common Cardiovascular (CV) risk factors, new markers able to increase the risk of CV disease have been identified. Among them, high levels of Lipoprotein(a)—Lp(a)—lead to very high risk of future CV diseases; this relationship has been well demonstrated in epidemiological, mendelian randomization and genome-wide association studies as well as in meta-analyses. Recently, new aspects have been identified, such as its association with aortic stenosis. Although till recent years it has been considered an unmodifiable risk factor, specific drugs have been developed with a strong efficacy in reducing the circulating levels of Lp(a) and their capacity to reduce subsequent CV events is under testing in ongoing trials. In this paper we will review all these aspects: from the synthesis, clearance and measurement of Lp(a), through the findings that examine its association with CV diseases and aortic stenosis to the new therapeutic options that will be available in the next years.
Temporomandibular Joint Osteoarthritis: Pathogenic Mechanisms Involving the Cartilage and Subchondral Bone, and Potential Therapeutic Strategies for Joint Regeneration
Authors: Cardoneanu Anca , Macovei Luana Andreea , Burlui Alexandra Maria , Mihai Ioana Ruxandra , Bratoiu Ioana , Rezus Ioana Irina , Richter Patricia , Tamba Bogdan-Ionel , Rezus Elena
Published: December 2022

The temporomandibular joint (TMJ) is a specialized synovial joint that is crucial for the movement and function of the jaw. TMJ osteoarthritis (TMJ OA) is the result of disc dislocation, trauma, functional overburden, and developmental anomalies. TMJ OA affects all joint structures, including the articular cartilage, synovium, subchondral bone, capsule, ligaments, periarticular muscles, and sensory nerves that innervate the tissues. The present review aimed to illustrate the main pathomechanisms involving cartilage and bone changes in TMJ OA and some therapeutic options that have shown potential restorative properties regarding these joint structures in vivo. Chondrocyte loss, extracellular matrix (ECM) degradation, and subchondral bone remodeling are important factors in TMJ OA. The subchondral bone actively participates in TMJ OA through an abnormal bone remodeling initially characterized by a loss of bone mass, followed by reparative mechanisms that lead to stiffness and thickening of the condylar osteochondral interface. In recent years, such therapies as intraarticular platelet-rich plasma (PRP), hyaluronic acid (HA), and mesenchymal stem cell-based treatment (MSCs) have shown promising results with respect to the regeneration of joint structures or the protection against further damage in TMJ OA. Nevertheless, PRP and MSCs are more frequently associated with cartilage and/or bone repair than HA. According to recent findings, the latter could enhance the restorative potential of other therapies (PRP, MSCs) when used in combination, rather than repair TMJ structures by itself. TMJ OA is a complex disease in which degenerative changes in the cartilage and bone develop through intricate mechanisms. The regenerative potential of such therapies as PRP, MSCs, and HA regarding the cartilage and subchondral bone (alone or in various combinations) in TMJ OA remains a matter of further research, with studies sometimes obtaining discrepant results.
Hydroxysafflower Yellow A Inhibits Vascular Adventitial Fibroblast Migration via NLRP3 Inflammasome Inhibition through Autophagy Activation
Authors: Liu Lin , Cui Qingzhuo , Song Junna , Yang Yang , Zhang Yixin , Qi Jiapeng , Zhao Jingshan
Published: December 2022

Inflammation is closely associated with progression of vascular remodeling. The NLRP3 inflammasome is the key molecule that promotes vascular remodeling via activation of vascular adventitia fibroblast (VAF) proliferation and differentiation. VAFs have a vital effect on vascular remodeling that could be improved using hydroxysafflower yellow A (HSYA). However, whether HSYA ameliorates vascular remodeling through inhibition of NLRP3 inflammasome activation has not been explored in detail. Here, we cultured primary VAFs and analyzed the migration of VAFs induced by angiotensin II (ANG II) to determine the potential effects and mechanism of HSYA on VAF migration. The results thereof showed that HSYA remarkably inhibited ANG II-induced VAF migration, NLRP3 inflammasome activation, and the TLR4/NF-κB signaling pathway in a dose-dependent manner. In addition, it is worth noting that LPS promoted ANG II-induced VAF migration and NLRP3 inflammasome assembly, which could be significantly reversed using HSYA. Moreover, HSYA could be used to inhibit NLRP3 inflammasome activation by promoting autophagy. In conclusion, HSYA could inhibit ANG II-induced VAF migration through autophagy activation and inhibition of NLRP3 inflammasome activation through the TLR4/NF-κB signaling pathway.
IL-20 Activates ERK1/2 and Suppresses Splicing of X-Box Protein-1 in Intestinal Epithelial Cells but Does Not Improve Pathology in Acute or Chronic Models of Colitis
Authors: Moniruzzaman Md. , Wong Kuan Yau , Wang Ran , Symon Hamish , Mueller Alexandra , Rahman M. Arifur , Hasnain Sumaira Z.
Published: December 2022

The cytokine Interleukin (IL)-20 belongs to the IL-10 superfamily. IL-20 levels are reported to increase in the intestines of Ulcerative Colitis (UC) patients, however not much is known about its effects on intestinal epithelial cells. Here, we investigated the influence of IL-20 on intestinal epithelial cell lines and primary intestinal organoid cultures. By using chemical-induced (dextran sodium sulphate; DSS) colitis and a spontaneous model of colitis (Winnie mice), we assess whether recombinant IL-20 treatment is beneficial in reducing/improving pathology. Following stimulation with IL-20, intestinal primary organoids from wild-type and Winnie mice increased the expression of ERK1/2. However, this was lost when cells were differentiated into secretory goblet cells. Importantly, IL-20 treatment significantly reduced endoplasmic reticulum (ER) stress, as measured by spliced-XBP1 in epithelial cells, and this effect was lost in the goblet cells. IL-20 treatment in vivo in the DSS and Winnie models had minimal effects on pathology, but a decrease in macrophage activation was noted. Taken together, these data suggest a possible, but subtle role of IL-20 on epithelial cells in vivo. The therapeutic potential of IL-20 could be harnessed by the development of a targeted therapy or combination therapy to improve the healing of the mucosal barrier.
Usefulness of Molecular Methods for Helicobacter pylori Detection in Pediatric Patients and Their Correlation with Histopathological Sydney Classification
Authors: Bogiel Tomasz , Mikucka Agnieszka , Szaflarska-Popławska Anna , Grzanka Dariusz
Published: December 2022

Helicobacter pylori infections, as one of the most prevalent among humans, are generally acquired during childhood, and are one of the main causes of chronic gastritis and peptic ulcer disease. A bacterial culture from a gastric biopsy is the gold standard and is the only method that has 100% specificity. However, its sensitivity varies, depending on experience of the laboratory staff, applied culture media, specimen transport conditions, biopsy site, and quality of the sample. The same factors compromise all invasive methods and a culture-based H. pylori infection diagnostic, as well as a recent intake of antibiotics, bismuth-containing compounds, and proton pump inhibitors. Molecular methods have been used for clinical microbiology investigation since the beginning of the 21st century. However, their usefulness for H. pylori infections diagnosis remains unclear, especially in pediatric patients. The aim of the study was to assess the incidence of H. pylori infections in a group of 104 pediatric patients and to compare the results of the PCR test with the corresponding histopathological investigation effects. Among the biopsy samples collected from 104 children, 44 (42.3%) were positive in PCR, while 43 (41.3%) and 39 (37.5%) presented histologically-confirmed signs of inflammation and H. pylori colonization, respectively. Moreover, the mean grades of the parameters of the histopathological examination were higher in the group of PCR-positive samples. The compatibility of both research methods was confirmed, emphasizing the usefulness of molecular methods for detecting H. pylori infections in pediatric patients. Considering that the PCR-based method gives reliable results and is less time-consuming and costly, it is worth discussing this method as a new standard in the diagnosis of H. pylori infections, at least among pediatric patients, for which culture-based diagnostics is not sufficient or histopathological examination is negative, while inflammation signs are observed macroscopically.
A Closer Look at Machine Learning Effectiveness in Android Malware Detection
Authors: Giannakas Filippos , Kouliaridis Vasileios , Kambourakis Georgios
Published: December 2022

Nowadays, with the increasing usage of Android devices in daily life activities, malware has been increasing rapidly, putting peoples’ security and privacy at risk. To mitigate this threat, several researchers have proposed different methods to detect Android malware. Recently, machine learning based models have been explored by a significant mass of researchers checking for Android malware. However, selecting the most appropriate model is not straightforward, since there are several aspects that must be considered. Contributing to this domain, the current paper explores Android malware detection from diverse perspectives; this is achieved by optimizing and evaluating various machine learning algorithms. Specifically, we conducted an experiment for training, optimizing, and evaluating 27 machine learning algorithms, and a Deep Neural Network (DNN). During the optimization phase, we performed hyperparameter analysis using the Optuna framework. The evaluation phase includes the measurement of different performance metrics against a contemporary, rich dataset, to conclude with the most accurate model. The best model was further interpreted by conducting feature analysis, using the Shapley Additive Explanations (SHAP) framework. Our experiment results showed that the best model is the DNN consisting of four layers (two hidden), using the Adamax optimizer, as well as the Binary Cross-Entropy (loss), and the Softsign activation functions. The model succeeded with 86% prediction accuracy, while the balanced accuracy, the F1-score, and the ROC-AUC metrics were at 82%.
Potential of Entomopathogenic Nematode HbSD as a Candidate Biocontrol Agent against Spodoptera frugiperda
Authors: Chen Yuan , Long Haibo , Jin Tao , Peng Zhengqiang , Sun Yanfang , Feng Tuizi
Published: December 2022

Spodoptera frugiperda is a highly destructive and polyphagous pest that causes severe damage to various crops, especially maize. The wide use of chemical insecticides to control S. frugiperda results in resistance against commonly used chemicals and resistant mutations will expand in populations accompanied by a spread to vulnerable areas. Consequently, more effective and friendly strategies must be explored to minimize losses caused by S. frugiperda. Entomopathogenic nematodes (EPN) are good candidates for the biological control of different species of insect pests, including S. frugiperda. In the current study, the infective capabilities of the EPN species HbSD, belonging to Hetrerorhabditis bacteriophora, were evaluated against S. frugiperda under laboratory, greenhouse and field conditions. In laboratory assays, HbSD was highly virulent against 3rd/5th instar larvae, which was related to HbSD concentration and exposure durations. In greenhouse assays, spraying aqueous HbSD also showed good performance in killing larvae on maize leaves. However, the virulence of HbSD decreased in field trials where many adverse factors affecting survival and efficacy were encountered by HbSD. Overall, our study provides an alternative EPN for the biological control of S. frugiperda with the potential to be developed as a sustainable option for efficient pest management.
Evidence for Reconsidering the Taxonomic Status of Closely Related Oligonychus Species in punicae Complex (Acari: Prostigmata: Tetranychidae)
Authors: Mushtaq Hafiz Muhammad Saqib , Kamran Muhammad , Saleh Amgad A. , Alatawi Fahad Jaber
Published: December 2022

To elucidate the taxonomic problems in species delineation within the Oligonychus punicae complex (O. punicae, O. mangiferus, and O. vitis) (Acari: Prostigmata: Tetranychidae), we performed morphological and molecular investigations on mite samples, collected from different hosts/countries. Thirty-nine samples of punicae complex, collected from Egypt, Pakistan, and Saudi Arabia (SA), did not show any considerable morphological differences in females and males. All 39 samples of the punicae complex resembled the original description of O. punicae, while the claimed Mexican O. punicae was distinctively different based on male aedeagus. Molecularly, the low nucleotide diversity ranged from 0% to 2.1% (ITS2-rDNA) and 0% to 1% (COI-mtDNA), and was observed among various DNA sequences of the punicae complex from Egypt, India, Israel, Pakistan, and SA, confirming their identity as one species. The high genetic divergence ranged from 17.2% to 18.8% (ITS2) and 9.2% to 10.2% (COI), observed between the claimed Mexican O. punicae and all other sequences of the punicae complex, indicating that the Mexican sample do not belong to O. punicae. Basing our findings on both morphological and molecular data, we can conclude that O. mangiferus and O. vitis are synonymized with O. punicae. Additionally, this study reveals that the claimed Mexican O. punicae needs to be re-identified.
The Leaf Color and Trichome Density Influence the Whitefly Infestation in Different Cassava Cultivars
Authors: Pastório Marcelo A. , Hoshino Adriano T. , Kitzberger Cíntia S. G. , Bortolotto Orcial C. , de Oliveira Luciano M. , dos Santos Adevanir Martins , Lima Wilmar F. , Menezes Junior Ayres de O. , Androcioli Humberto G.
Published: December 2022

The whitefly species Bemisia tuberculata and Aleurotrixus aepim (Hemiptera: Aleyrodidae) are considered important cassava (Manihot esculenta) pests. Leaf color and other morphological characteristics can influence the pest’s interactions with the host plants. Thus, this study aimed to identify the relationship between whitefly occurrence and trichome density and leaf color in different cassava cultivars. The study was conducted in the field during the 2014/2015 and 2016/2017 crop seasons. The whitefly occurrence was surveyed in the cultivars, IAPAR 19, IPR Upira, IPR União, IAC 576-70, IAC 14, IAC 90, Catarina Branca, Santa Helena and Baianinha. The whitefly nymph quantification was correlated with non-glandular trichome density, luminosity (L*) and chroma (a* and b*) of the cassava leaves. IAPAR 19 and IAC 14 were less infested by whitefly nymphs when contrasted with IPR União, IPR Upira and Baianinha, which were the most infested. The lowest B. tuberculata infestations were correlated with lesser trichome density, highest light reflection and highest chroma in the sprout and the plant’s superior third portion leaves. Low A. aepim infestation in both crop seasons made it impossible to verify its correlation with the studied cassava plant characteristics. The cultivars IAPAR 19 and IAC 14 could contribute towards B. tuberculata management in regions with a history of whitefly infestation.
Cost-Effective PCR-Based Identification of Tunga penetrans (Siphonaptera) Larvae Extracted from Soil Samples Containing PCR Inhibitor-Rich Material
Authors: Amugune Billy L. , Matharu Abneel K. , Ouma Paul , Mutebi Francis , Elson Lynne , Fillinger Ulrike , Krücken Jürgen
Published: December 2022

Tungiasis is a neglected tropical disease caused by skin-penetrating female Tunga penetrans fleas. Although tungiasis causes severe health problems, its ecology is poorly understood and morphological descriptions of the larvae are unavailable. To identify T. penetrans immature stages and sites where they develop, diagnostic PCRs are required. However, flea larvae feed on soil organic matter rich in PCR inhibitors. Here, three DNA preparation methods, including a soil DNA kit that removes inhibitors, a simple ammonium acetate precipitation approach (AmAcet) and a crude lysate of larvae (CL), were combined with amplification by the highly processive FIREPol® Taq or the inhibitor-resistant Phusion® polymerase. Independent of the polymerase used, the frequency of successful amplification, Cq values and PCR efficacies for the low-cost CL and AmAcet methods were superior to the commercial kit for amplification of a 278 bp partial internal transcribed spacer-2 (ITS-2) and a 730 bp pan-Siphonaptera cytochrome oxidase II PCR. For the CL method combined with Phusion® polymerase, the costs were approximately 20-fold lower than for the methods based on the soil DNA kit, which is a considerable advantage in resource-poor settings. The ITS-2 PCR did not amplify Ctenocephalides felis genomic or Tunga trimammilata ITS-2 plasmid DNA, meaning it can be used to specifically identify T. penetrans.
Emerging Risk of Cross-Species Transmission of Honey Bee Viruses in the Presence of Invasive Vespid Species
Authors: Rodríguez-Flores María Shantal , Mazzei Maurizio , Felicioli Antonio , Diéguez-Antón Ana , Seijo María Carmen
Published: December 2022

The increase in invasive alien species is a concern for the environment. The establishment of some of these species may be changing the balance between pathogenicity and host factors, which could alter the defense strategies of native host species. Vespid species are among the most successful invasive animals, such as the genera Vespa, Vespula and Polistes. Bee viruses have been extensively studied as an important cause of honey bee population losses. However, knowledge about the transmission of honey bee viruses in Vespids is a relevant and under-researched aspect. The role of some mites such as Varroa in the transmission of honey bee viruses is clearer than in the case of Vespidae. This type of transmission by vectors has not yet been clarified in Vespidae, with interspecific relationships being the main hypotheses accepted for the transmission of bee viruses. A majority of studies describe the presence of viruses or their replicability, but aspects such as the symptomatology in Vespids or the ability to infect other hosts from Vespids are scarcely discussed. Highlighting the case of Vespa velutina as an invader, which is causing huge losses in European beekeeping, is of special interest. The pressure caused by V. velutina leads to weakened hives that become susceptible to pathogens. Gathering this information is necessary to promote further research on the spread of bee viruses in ecosystems invaded by invasive species of Vespids, as well as to prevent the decline of bee populations due to bee viruses.
Sub-Lethal Effects of Bifenthrin and Imidacloprid on Megacephala carolina carolina L. (Coleoptera: Carabidae) in Turfgrass
Authors: Joseph Shimat
Published: December 2022

The tiger beetle, Megacephala carolina carolina L. (Coleoptera: Carabidae), is a common predator in turfgrass and ornamental landscapes in Georgia, USA. Among insecticides used in turfgrass to control foliar and root-feeding insect pests, bifenthrin and imidacloprid are routinely used. It was unclear whether sub-lethal doses of bifenthrin and imidacloprid could cause nontarget effects on larvae and M. carolina carolina adults. Thus, the objective was to determine the sub-lethal effects of bifenthrin and imidacloprid on larvae and M. carolina carolina adults. The results show that M. carolina carolina larvae actively hunt for passing prey by waiting at the hole of the tunnel during the day and nighttime. This larval behavior was affected by sub-lethal doses (up to 25% of full label rate) of bifenthrin but not of imidacloprid. The walking behavior of adult M. carolina carolina was also altered when exposed to sub-lethal doses of bifenthrin as they traveled further distances at greater velocities than the nontreated control. The results imply that turfgrass managers should avoid treating lawns where tiger beetles have actively colonized.
Aphelinus nigritus Howard (Hymenoptera: Aphelinidae) Preference for Sorghum Aphid, Melanaphis sorghi (Theobald, 1904) (Hemiptera: Aphididae), Honeydew Is Stronger in Johnson Grass, Sorghum halepense, Than in Grain Sorghum, Sorghum bicolor
Authors: Wright Crys , Helms Anjel M. , Bernal Julio S. , Grunseich John M. , Medina Raul F.
Published: December 2022

How aphid parasitoids of recent invasive species interact with their hosts can affect the feasibility of biological control. In this study, we focus on a recent invasive pest of US grain sorghum, Sorghum bicolor, the sorghum aphid (SA), Melanaphis sorghi. Understanding this pest’s ecology in the grain sorghum agroecosystem is critical to develop effective control strategies. As parasitoids often use aphid honeydew as a sugar resource, and honeydew is known to mediate parasitoid–aphid interactions, we investigated the ability of SA honeydew to retain the parasitoid Aphelinus nigritus. Since SAs in the US have multiple plant hosts, and host–plant diet can modulate parasitoid retention (a major component in host foraging), we measured SA honeydew sugar, organic acid, and amino acid profiles, then assessed via retention time A. nigritus preference for honeydew produced on grain sorghum or Johnson grass, Sorghum halepense. Compared to a water control, A. nigritus spent more time on SA honeydew produced on either host plant. Despite similar honeydew profiles from both plant species, A. nigritus preferred honeydew produced on Johnson grass. Our results suggest the potential for SA honeydew to facilitate augmentation strategies aimed at maintaining A. nigritus on Johnson grass to suppress SAs before grain sorghum is planted.
The Role of Anti-U1 RNP Antibody in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis
Authors: Xiang Weizhen , Dong Rongrong , Li Meiqi , Liu Baocheng , Ma Zhenzhen , Yang Qingrui
Published: December 2022

Connective tissue disease (CTD) patients may suffer from pulmonary arterial hypertension (PAH), a serious complication, and anti-U1 ribonucleoprotein (RNP) antibodies can be used as a potential indicator for the development and prognosis of CTD-associated PAH (CTD-PAH). However, there are still some controversies; thus, a systematic review and meta-analysis were performed. We searched PubMed, Embase, Cochrane Library, and Scopus for eligible studies and assessed their quality using Newcastle–Ottawa scales or Agency for Healthcare Research and Quality indicators according to the type of research. Odds ratio (OR) was adopted as a measure of effect in risk factor analysis, and hazard ratio (HR) was adopted for prognostic factor analysis. Publication bias was evaluated using the Egger’s test. Thirteen studies were finally included. Anti-U1 RNP antibody was proved as a risk factor for PAH among CTD patients (OR = 5.30, 95%CI 2.96–9.48, p < 0.05) and a protective factor against mortality among CTD-PAH patients (HR = 0.55, 95%CI 0.36–0.83, p < 0.05). CTD patients with positive anti-U1 RNP antibodies are at high risk for PAH, so routine screening examinations, including echocardiography, are recommended. Additionally, anti-U1 RNP positivity has been linked to decreased mortality in patients with CTD-PAH.
Preference and Adherence to a Fixed-Dose Combination of Bisoprolol–Aspirin and Blood Pressure Control: Results of an Open-Label, Multicentre Study
Authors: Gaciong Zbigniew
Published: December 2022

This study assessed blood pressure (BP) control and adherence in patients given a fixed-dose combination (FDC) of bisoprolol (BIS) + aspirin (ASA) compared to those given these two drugs as separate tablets. Patients with hypertension and/or coronary heart disease treated with two-pill BIS (5–10 mg) and ASA (75–100 mg) were switched to FDC BIS + ASA (either 5/75 mg or 10/75 mg) ≥4 weeks prior to study initiation. Adherence was estimated from pill counts and patients’ diaries (1–2 months and 3 months after inclusion) and using Morisky’s Medication Adherence Scale (MMAS) at 3 months. BP control with the two treatments was compared. A total of 356 patients were enrolled (mean (SD) age: 64.3 ± 11.9 years, 56.5% male). Mean (SD) duration of prior treatment with two-pill BIS and ASA was 17.8 ± 26.6 months. FDC adherence was excellent or good (≥76%) in 98.3% and 98.0% of patients based on pill counts and patients’ diaries, respectively. Overall MMAS score was 3.1 ± 1.0. A significant decrease was observed in mean systolic BP, mean diastolic BP and heart rate over the 3-month period (all p < 0.001). FDC BIS + ASA was associated with excellent adherence and improved BP control. The majority (78.7%) of patients preferred the FDC.
Incidence and Associations of Acute Kidney Injury after General Thoracic Surgery: A System Review and Meta-Analysis
Authors: Yu Yang , Xu Shanshan , Yan Bing , Tang Xiaodong , Zhang Honggang , Pan Caifei , Zhu Shengmei
Published: December 2022

(1) Background: Acute kidney injury (AKI) is related to adverse outcomes in critical illness and cardiovascular surgery. In this study, a systematic literature review and meta-analysis was carried out to evaluate the incidence and associations of AKI as a postoperative complication of thoracic (including lung resection and esophageal) surgical procedures. (2) Methods: Adopting a systematic strategy, the electronic reference databases (PubMed, EMBASE, and Cochrane Library) were searched for articles researching postoperative renal outcomes that were diagnosed using RIFLE, AKIN or KDIGO consensus criteria in the context of a thoracic operation. A random-effects model was applied to estimate the incidence of AKI and, where reported, the pooled relative risk of mortality and non-renal complications after AKI. The meta-analysis is registered in PROSPERO under the number CRD42021274166. (3) Results: In total, 20 studies with information gathered from 34,826 patients after thoracic surgery were covered. Comprehensively, the incidence of AKI was estimated to be 8.8% (95% CI: 6.7–10.8%). A significant difference was found in the mortality of patients with and without AKI (RR = 2.93, 95% CI: 1.79–4.79, p < 0.001). Additionally, in patients experiencing AKI, cardiovascular and respiratory complications were more common (p = 0.01 and p < 0.001, respectively). (4) Conclusions: AKI is a common complication associated with adverse outcomes following general thoracic surgery. An important issue in perioperative care, AKI should be considered as a highly significant prognostic indicator and an attractive target for potential therapeutic interventions, especially in high-risk populations.
Advances in Understanding the Genetic Mechanisms of Zebrafish Renal Multiciliated Cell Development
Authors: Wesselman Hannah M. , Nguyen Thanh Khoa , Chambers Joseph M. , Drummond Bridgette E. , Wingert Rebecca A.
Published: December 2022

Cilia are microtubule-based organelles that project from the cell surface. In humans and other vertebrates, possession of a single cilium structure enables an assortment of cellular processes ranging from mechanosensation to fluid propulsion and locomotion. Interestingly, cells can possess a single cilium or many more, where so-called multiciliated cells (MCCs) possess apical membrane complexes with several dozen or even hundreds of motile cilia that beat in a coordinated fashion. Development of MCCs is, therefore, integral to control fluid flow and/or cellular movement in various physiological processes. As such, MCC dysfunction is associated with numerous pathological states. Understanding MCC ontogeny can be used to address congenital birth defects as well as acquired disease conditions. Today, researchers used both in vitro and in vivo experimental models to address our knowledge gaps about MCC specification and differentiation. In this review, we summarize recent discoveries from our lab and others that have illuminated new insights regarding the genetic pathways that direct MCC ontogeny in the embryonic kidney using the power of the zebrafish animal model.
Wool Keratin Nanofibers for Bioinspired and Sustainable Use in Biomedical Field
Authors: Sanchez Ramirez Diego Omar , Vineis Claudia , Cruz-Maya Iriczalli , Tonetti Cinzia , Guarino Vincenzo , Varesano Alessio
Published: December 2022

Keratin is a biocompatible and biodegradable protein as the main component of wool and animal hair fibers. Keratin-based materials support fibroblasts and osteoblasts growth. Keratin has been extracted by sulphitolysis, a green method (no harmful chemicals) with a yield of 38–45%. Keratin has been processed into nanofibers from its solutions by electrospinning. Electrospinning is a versatile and easy-to-use technique to generate nanofibers. It is an eco-friendly and economical method for the production of randomly and uniaxially oriented polymeric nanofibers. Thanks to their high specific surface area, nanofibers have great potential in the biomedical field. Keratin nanofibers have received significant attention in biomedical applications, such as tissue engineering and cell growth scaffolds, for their biocompatibility and bio-functionality. Accordingly, we propose an extensive overview of recent studies focused on the optimization of keratinbased nanofibers, emphasizing their peculiar functions for cell interactions and the role of additive phases in blends or composite systems to particularize them as a function of specific applications (i.e., antibacterial).
Auguring Fake Face Images Using Dual Input Convolution Neural Network
Authors: Bhandari Mohan , Neupane Arjun , Mallik Saurav , Gaur Loveleen , Qin Hong
Published: December 2022

Deepfake technology uses auto-encoders and generative adversarial networks to replace or artificially construct fine-tuned faces, emotions, and sounds. Although there have been significant advancements in the identification of particular fake images, a reliable counterfeit face detector is still lacking, making it difficult to identify fake photos in situations with further compression, blurring, scaling, etc. Deep learning models resolve the research gap to correctly recognize phony images, whose objectionable content might encourage fraudulent activity and cause major problems. To reduce the gap and enlarge the fields of view of the network, we propose a dual input convolutional neural network (DICNN) model with ten-fold cross validation with an average training accuracy of 99.36 ± 0.62, a test accuracy of 99.08 ± 0.64, and a validation accuracy of 99.30 ± 0.94. Additionally, we used ’SHapley Additive exPlanations (SHAP) ’ as explainable AI (XAI) Shapely values to explain the results and interoperability visually by imposing the model into SHAP. The proposed model holds significant importance for being accepted by forensics and security experts because of its distinctive features and considerably higher accuracy than state-of-the-art methods.
Meningeal Sporotrichosis Due to Sporothrix brasiliensis: A 21-Year Cohort Study from a Brazilian Reference Center
Authors: Lima Marco A. , Freitas Dayvison F. S. , Oliveira Raquel V. C. , Fichman Vivian , Varon Andréa G. , Freitas Andréa D. , Lamas Cristiane C. , Andrade Hugo B. , Veloso Valdilea G. , Almeida-Paes Rodrigo , Almeida-Silva Fernando , Zancopé-Oliveira Rosely Maria , de Macedo Priscila M. , Valle Antonio C. F. , Silva Marcus T. T. , Araújo Abelardo Q. C. , Gutierrez-Galhardo Maria C.
Published: December 2022

Meningeal sporotrichosis is rare and occurs predominantly in immunosuppressed individuals. This retrospective study explored clinical and laboratory characteristics, treatment, and prognosis of patients with disseminated sporotrichosis who underwent lumbar puncture (LP) at a Brazilian reference center from 1999 to 2020. Kaplan–Meier and Cox regression models were used to estimate overall survival and hazard ratios. Among 57 enrolled patients, 17 had meningitis. Fifteen (88.2%) had HIV infection, and in 6 of them, neurological manifestations occurred because of the immune reconstitution inflammatory syndrome (IRIS). The most frequent symptom was headache (88.2%). Meningeal symptoms at first LP were absent in 7/17 (41.2%) patients. Sporothrix was diagnosed in cerebrospinal fluid either by culture or by polymerase chain reaction in seven and four patients, respectively. All but one patient received prolonged courses of amphotericin B formulations, and seven received posaconazole, but relapses were frequent. Lethality among patients with meningitis was 64.7%, with a higher chance of death compared to those without meningitis (HR = 3.87; IC95% = 1.23;12.17). Meningeal sporotrichosis occurs mostly in people with HIV and can be associated with IRIS. Screening LP is indicated in patients with disseminated disease despite the absence of neurological complaints. Meningitis is associated with poor prognosis, and better treatment strategies are needed.
Agreement between Wedged Hepatic Venous Pressure and Portal Pressure in Hepatic Sinusoidal Obstruction Syndrome
Authors: Cheng Yang , Gu Lihong , Yin Xiaochun , Wang Xixuan , Xiao Jiangqiang , Wang Yi , Zhang Wei , Wang Lei , Zou Xiaoping , Zhang Ming , Zhuge Yuzheng , Zhang Feng
Published: December 2022

Background: Wedge hepatic vein pressure (WHVP) accurately estimates the portal pressure (PP) in chronic sinusoidal portal hypertension patients. Whether this applies to patients with acute portal hypertension due to hepatic sinusoidal obstruction syndrome (HSOS) is unclear. Our aim was to assess the agreement between WHVP and PP in patients with HSOS by comparing them to decompensated cirrhosis patients. Methods: From December 2013 to December 2021, patients with pyrrolidine alkaloid-induced HSOS (PA-HSOS) receiving hepatic venous pressure gradient (HVPG) measurement and transjugular intrahepatic portosystem shunt (TIPS) were retrospectively collected and matched with those of patients with virus- or alcohol-related cirrhosis as a cirrhosis group. Pearson’s correlation (R), intraclass correlation coefficient (ICC), scatter plots, and the Bland–Altman method were performed for agreement evaluation. Results: A total of 64 patients were analyzed (30 PA-HSOS and 34 cirrhosis groups). The correlation between WHVP and PP was moderate in the PA-HSOS group (R: 0.58, p = 0.001; ICC: 0.68, p = 0.002) but good in the cirrhosis group (R: 0.81, p < 0.001; ICC: 0.90, p < 0.001). The percentage of patients with inconsistent WHVP and PP in the two groups was 13 (43.3%) and 15 (26.5%) (p = 0.156), respectively, and an overestimation of PP was more common in the PA-HSOS group (33.3% vs. 2.9%, p = 0.004). HVPG and portal pressure gradient (PPG) consistency was poor in both groups (R: 0.51 vs. 0.26; ICC: 0.65 vs. 0.41; p < 0.05). Conclusions: WHVP in patients with PA-HSOS did not estimate PP as accurately as in patients with virus- or alcohol-related cirrhosis, which was mainly due to PP overestimation.
Cytokines and Hepatocellular Carcinoma: Biomarkers of a Deadly Embrace
Authors: Pocino Krizia , Stefanile Annunziata , Basile Valerio , Napodano Cecilia , D’Ambrosio Francesca , Di Santo Riccardo , Callà Cinzia Anna Maria , Gulli Francesca , Saporito Raffaele , Ciasca Gabriele , Equitani Francesco , Basile Umberto , Marino Mariapaola
Published: December 2022

Hepatocellular carcinoma (HCC) represents a worldwide health matter with a major care burden, high prevalence, and poor prognosis. Its pathogenesis mainly varies depending on the underlying etiological factors, although it develops from liver cirrhosis in the majority of cases. This review summarizes the role of the most interesting soluble factors as biomarkers for early diagnosis and as recommended targets for treatment in accordance with the new challenges in precision medicine. In the premalignant environment, inflammatory cells release a wide range of cytokines, chemokines, growth factors, prostaglandins, and proangiogenic factors, making the liver environment more suitable for hepatocyte tumor progression that starts from acquired genetic mutations. A complex interaction of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory cytokines (TGF-α and -β), pro-angiogenic molecules (including the Angiopoietins, HGF, PECAM-1, HIF-1α, VEGF), different transcription factors (NF-kB, STAT-3), and their signaling pathways are involved in the development of HCC. Since cytokines are expressed and released during the different stages of HCC progression, their measurement, by different available methods, can provide in-depth information on the identification and management of HCC.