bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Atlas of the Myelin Basic Protein Interaction Landscape
Authors: Smirnova Evgeniya V. , Rakitina Tatiana V. , Ziganshin Rustam H. , Arapidi Georgij P. , Saratov George A. , Kudriaeva Anna A. , Belogurov Alexey A.
Published: November 2021

Intrinsically disordered myelin basic protein (MBP) is one of the key autoantigens in autoimmune neurodegeneration and multiple sclerosis particularly. MBP is highly positively charged and lacks distinct structure in solution and therefore its intracellular partners are still mostly enigmatic. Here we used combination of formaldehyde-induced cross-linking followed by immunoprecipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the interaction network of MBP in mammalian cells and provide the list of potential MBP interacting proteins. Our data suggest that the largest group of MBP-interacting proteins belongs to cellular proteins involved in the protein translation machinery, as well as in the spatial and temporal regulation of translation. MBP interacts with core ribosomal proteins, RNA helicase Ddx28 and RNA-binding proteins STAU1, TDP-43, ADAR-1 and hnRNP A0, which are involved in various stages of RNA biogenesis and processing, including specific maintaining MBP-coding mRNA. Among MBP partners we identified CTNND1, which has previously been shown to be necessary for myelinating Schwann cells for cell-cell interactions and the formation of a normal myelin sheath. MBP binds proteins MAGEB2/D2 associated with neurotrophin receptor p75NTR, involved in pathways that promote neuronal survival and neuronal death. Finally, we observed that MBP interacts with RNF40–a component of heterotetrameric Rnf40/Rnf20 E3 ligase complex, recruited by Egr2, which is the central transcriptional regulator of peripheral myelination. Concluding, our data suggest that MBP may be more actively involved in myelination not only as a main building block but also as a self-regulating element.
Effect of Methyl Jasmonate Doped Nanoparticles on Nitrogen Composition of Monastrell Grapes and Wines
Authors: Gil-Muñoz Rocío , Giménez-Bañón María José , Moreno-Olivares Juan Daniel , Paladines-Quezada Diego Fernando , Bleda-Sánchez Juan Antonio , Fernández-Fernández José Ignacio , Parra-Torrejón Belén , Ramírez-Rodríguez Gloria Belén , Delgado-López José Manuel
Published: November 2021

Nitrogen composition on grapevines has a direct effect on the quality of wines since it contributes to develop certain volatile compounds and assists in the correct kinetics of alcoholic fermentation. Several strategies can be used to ensure nitrogen content in grapes and one of them could be the use of elicitors such as methyl jasmonate. The use of this elicitor has been proven to be efficient in the production of secondary metabolites which increases the quality of wines, but its use also has some drawbacks such as its low water solubility, high volatility, and its expensive cost. This study observes the impact on the amino acid and ammonium composition of must and wine of Monastrell grapes that have been treated with methyl jasmonate (MeJ) and methyl jasmonate n-doped calcium phosphate nanoparticles (MeJ-ACP). The first objective of this study was to compare the effect of these treatments to determine if the nitrogenous composition of the berries and wines increased. The second aim was to determine if the nanoparticle treatments showed similar effects to conventional treatments so that the ones which are more efficient and sustainable from an agricultural point of view can be selected. The results showed how both treatments increased amino acid composition in grapes and wines during two consecutive seasons and as well as the use of MeJ-ACP showed better results compared to MeJ despite using less quantity (1 mM compared to 10 mM typically). So, this application form of MeJ could be used as an alternative in order to carry out a more efficient and sustainable agriculture.
An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases
Authors: Marra Federica , Lunetti Paola , Curcio Rosita , Lasorsa Francesco Massimo , Capobianco Loredana , Porcelli Vito , Dolce Vincenza , Fiermonte Giuseppe , Scarcia Pasquale
Published: November 2021

Neuromuscular diseases (NMDs) are dysfunctions that involve skeletal muscle and cause incorrect communication between the nerves and muscles. The specific causes of NMDs are not well known, but most of them are caused by genetic mutations. NMDs are generally progressive and entail muscle weakness and fatigue. Muscular impairments can differ in onset, severity, prognosis, and phenotype. A multitude of possible injury sites can make diagnosis of NMDs difficult. Mitochondria are crucial for cellular homeostasis and are involved in various metabolic pathways; for this reason, their dysfunction can lead to the development of different pathologies, including NMDs. Most NMDs due to mitochondrial dysfunction have been associated with mutations of genes involved in mitochondrial biogenesis and metabolism. This review is focused on some mitochondrial routes such as the TCA cycle, OXPHOS, and β-oxidation, recently found to be altered in NMDs. Particular attention is given to the alterations found in some genes encoding mitochondrial carriers, proteins of the inner mitochondrial membrane able to exchange metabolites between mitochondria and the cytosol. Briefly, we discuss possible strategies used to diagnose NMDs and therapies able to promote patient outcome.
Galectin-1 Cooperates with Yersinia Outer Protein (Yop) P to Thwart Protective Immunity by Repressing Nitric Oxide Production
Authors: Jofre Brenda Lucila , Eliçabe Ricardo Javier , Silva Juan Eduardo , Pérez Sáez Juan Manuel , Paez Maria Daniela , Callegari Eduardo , Mariño Karina Valeria , Di Genaro María Silvia , Rabinovich Gabriel Adrián , Davicino Roberto Carlos
Published: November 2021

Yersinia enterocolitica (Ye) inserts outer proteins (Yops) into cytoplasm to infect host cells. However, in spite of considerable progress, the mechanisms implicated in this process, including the association of Yops with host proteins, remain unclear. Here, we evaluated the functional role of Galectin-1 (Gal1), an endogenous β-galactoside-binding protein, in modulating Yop interactions with host cells. Our results showed that Gal1 binds to Yops in a carbohydrate-dependent manner. Interestingly, Gal1 binding to Yops protects these virulence factors from trypsin digestion. Given that early control of Ye infection involves activation of macrophages, we evaluated the role of Gal1 and YopP in the modulation of macrophage function. Although Gal1 and YopP did not influence production of superoxide anion and/or TNF by Ye-infected macrophages, they coordinately inhibited nitric oxide (NO) production. Notably, recombinant Gal1 (rGal1) did not rescue NO increase observed in Lgals1−/− macrophages infected with the YopP mutant Ye ∆yopP. Whereas NO induced apoptosis in macrophages, no significant differences in cell death were detected between Gal1-deficient macrophages infected with Ye ∆yopP, and WT macrophages infected with Ye wt. Strikingly, increased NO production was found in WT macrophages treated with MAPK inhibitors and infected with Ye wt. Finally, rGal1 administration did not reverse the protective effect in Peyer Patches (PPs) of Lgals1−/− mice infected with Ye ∆yopP. Our study reveals a cooperative role of YopP and endogenous Gal1 during Ye infection.
Anticancer Platinum Drugs Update
Authors: Ciarimboli Giuliano
Published: November 2021

The discovery of the anticancer properties of platinum derivatives by Rosenberg represents a milestone in the development of chemotherapeutic protocols for tumor treatment [...]
Comparison of Two Alternative Procedures to Obtain Packed Red Blood Cells for β-Thalassemia Major Transfusion Therapy
Authors: Schiroli Davide , Merolle Lucia , Quartieri Eleonora , Chicchi Roberta , Fasano Tommaso , De Luca Tiziana , Molinari Giuseppe , Pulcini Stefano , Pertinhez Thelma A. , Di Bartolomeo Erminia , Biguzzi Rino , Baricchi Roberto , Marraccini Chiara
Published: November 2021

β-thalassemia major (βTM) patients require frequent blood transfusions, with consequences that span from allogenic reactions to iron overload. To minimize these effects, βTM patients periodically receive leucodepleted packed red blood cells (P-RBCs) stored for maximum 14 days. The aim of this study was to compare two alternative routine procedures to prepare the optimal P-RBCs product, in order to identify differences in their content that may somehow affect patients’ health and quality of life (QoL). In method 1, blood was leucodepleted and then separated to obtain P-RBCs, while in method 2 blood was separated and leucodepleted after removal of plasma and buffycoat. Forty blood donors were enrolled in two independent centers; couples of phenotypically matched whole blood units were pooled, divided in two identical bags and processed in parallel following the two methods. Biochemical properties, electrolytes and metabolic composition were tested after 2, 7 and 14 days of storage. Units prepared with both methods were confirmed to have all the requirements necessary for βTM transfusion therapy. Nevertheless, RBCs count and Hb content were found to be higher in method-1, while P-RBCs obtained with method 2 contained less K+, iron and storage lesions markers. Based on these results, both methods should be tested in a clinical perspective study to determine a possible reduction of transfusion-related complications, improving the QoL of βTM patients, which often need transfusions for the entire lifespan.
A Review of Sustained Drug Release Studies from Nanofiber Hydrogels
Authors: Bayer Ilker S.
Published: November 2021

Polymer nanofibers have exceptionally high surface area. This is advantageous compared to bulk polymeric structures, as nanofibrils increase the area over which materials can be transported into and out of a system, via diffusion and active transport. On the other hand, since hydrogels possess a degree of flexibility very similar to natural tissue, due to their significant water content, hydrogels made from natural or biodegradable macromolecular systems can even be injectable into the human body. Due to unique interactions with water, hydrogel transport properties can be easily modified and tailored. As a result, combining nanofibers with hydrogels would truly advance biomedical applications of hydrogels, particularly in the area of sustained drug delivery. In fact, certain nanofiber networks can be transformed into hydrogels directly without the need for a hydrogel enclosure. This review discusses recent advances in the fabrication and application of biomedical nanofiber hydrogels with a strong emphasis on drug release. Most of the drug release studies and recent advances have so far focused on self-gelling nanofiber systems made from peptides or other natural proteins loaded with cancer drugs. Secondly, polysaccharide nanofiber hydrogels are being investigated, and thirdly, electrospun biodegradable polymer networks embedded in polysaccharide-based hydrogels are becoming increasingly popular. This review shows that a major outcome from these works is that nanofiber hydrogels can maintain drug release rates exceeding a few days, even extending into months, which is an extremely difficult task to achieve without the nanofiber texture. This review also demonstrates that some publications still lack careful rheological studies on nanofiber hydrogels; however, rheological properties of hydrogels can influence cell function, mechano-transduction, and cellular interactions such as growth, migration, adhesion, proliferation, differentiation, and morphology. Nanofiber hydrogel rheology becomes even more critical for 3D or 4D printable systems that should maintain sustained drug delivery rates.
Corpus Callosotomy in 3 Cavalier King Charles Spaniel Dogs with Drug-Resistant Epilepsy
Authors: Asada Rikako , Mizuno Satoshi , Yu Yoshihiko , Hamamoto Yuji , Anazawa Tetsuya , Ito Daisuke , Kitagawa Masato , Hasegawa Daisuke
Published: November 2021

Corpus callosotomy (CC) is an established palliative surgery for human patients with drug-resistant epilepsy (DRE), especially those with generalized seizures and multiple or unknown epileptogenic focus. However, there are no reports to describe CC in canine patients with epilepsy. Three client-owned Cavalier King Charles Spaniels with DRE are included in this case series. In presurgical evaluations, an apparent epileptogenic zone was not detected in each dog and CC was conducted. Total CC was performed in one dog, whereas the other two received partial CC. One dog recovered from surgery without any complications, but died suddenly by an unknown cause at 10 h after surgery. For the other two dogs, postoperative evaluations including seizure outcomes, complications, and quality of life of the dogs and owners were assessed for at least 12 months. Both dogs showed a remarkable decrease in seizure frequency (averaged 80.3% reduction) and severity after surgery. The antiseizure medications were maintained, and not only the mentation and activity of the dogs, but also the quality of life of dogs and owners were improved postoperatively. Although technical improvement and more large-scale studies are needed, CC is a treatment option for dogs with DRE in veterinary medicine.
Progression in Ph-Chromosome-Negative Myeloproliferative Neoplasms: An Overview on Pathologic Issues and Molecular Determinants
Authors: Sabattini Elena , Pizzi Marco , Agostinelli Claudio , Bertuzzi Clara , Sagramoso Sacchetti Carlo Alberto , Palandri Francesca , Gianelli Umberto
Published: November 2021

Progression in Ph-chromosome-negative myeloproliferative neoplasms (MPN) develops with variable incidence and time sequence in essential thrombocythemia, polycythemia vera, and primary myelofibrosis. These diseases show different clinic-pathologic features and outcomes despite sharing deregulated JAK/STAT signaling due to mutations in either the Janus kinase 2 or myeloproliferative leukemia or CALReticulin genes, which are the primary drivers of the diseases, as well as defined diagnostic criteria and biomarkers in most cases. Progression is defined by the development or worsening of marrow fibrosis or the progressive increase in the marrow blast percentage. Progression is often related to additional genetic aberrations, although some can already be detected during the chronic phase. Detailed scoring systems for clinical usage that are mostly applied in patients with primary myelofibrosis have been defined, and the most recent ones include cytogenetic and molecular parameters with prognostic significance. Additional different clinic-pathologic changes have been reported that may occur during the course of the disease and that are, at present, classified as WHO-defined types of progression, although they likely represent such an event. The present review is meant to provide an updated overview on progression in Ph-chromosome-negative MPN, with a major focus on the pathologic side.
PI3Kδ Inhibitors as Immunomodulatory Agents for the Treatment of Lymphoma Patients
Authors: Tarantelli Chiara , Argnani Lisa , Zinzani Pier Luigi , Bertoni Francesco
Published: November 2021

The development of small molecules able to block specific or multiple isoforms of phosphoinositide 3-kinases (PI3K) has already been an active field of research for many years in the cancer field. PI3Kδ inhibitors are among the targeted agents most extensively studied for the treatment of lymphoma patients and PI3Kδ inhibitors are already approved by regulatory agencies. More recently, it became clear that the anti-tumor activity of PI3K inhibitors might not be due only to a direct effect on the cancer cells but it can also be mediated via inhibition of the kinases in non-neoplastic cells present in the tumor microenvironment. T-cells represent an important component of the tumor microenvironment and they comprise different subpopulations that can have both anti- and pro-tumor effects. In this review article, we discuss the effects that PI3Kδ inhibitors exert on the immune system with a particular focus on the T-cell compartment.
Tumor Glucose Metabolism and Its Heterogeneity on F-18 FDG PET/CT Provide Better Prognostication in Nonmetastatic Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma
Authors: Cho Hojin , Kim Soyoung , Jo Kwanhyeong , Jeong Yong Hyu , Kang Won Jun
Published: November 2021

Background: We aimed to evaluate the prognostic role of metabolic parameters on baseline F-18 fluorodeoxyglucose (FDG) PET/CT in patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). Methods: We retrospectively reviewed patients who were diagnosed with nonmetastatic HPV-related OPSCC using the 8th TNM staging system from 2010 to 2015 and underwent baseline F-18 FDG PET/CT. Tumor SUVmax to liver SUVmean ratio (SUVmax-TLR), metabolic tumor volume (MTV), tumor total lesion glycolysis to liver SUVmean ratio (TLG-TLR), and coefficient of variation (CV) of the primary tumor were measured. Patients were primarily treated with surgery or radiotherapy. Endpoints were progression-free survival (PFS) and overall survival (OS). Results: Ninety consecutive patients (male, 72; female, 18) were enrolled. They were followed up for a median of 77.4 months (interquartile range, 48.4–106.4). Sixteen patients progressed, and 13 died. Multivariate analysis revealed that patients with advanced age, overall stage, and higher SUVmax-TLR or CV had poorer PFS and OS. Conclusion: Higher SUVmax-TLR and CV of the primary tumor on baseline F-18 FDG PET/CT were associated with poorer PFS and OS in patients with nonmetastatic HPV-related OPSCC. Further study is warranted to address the possible implications of F-18 FDG PET/CT on treatment de-intensification in these patients.
Pd on the Composite of Perlite and Allylamine-N-isopropylacrylamide Copolymer: A Thermo-Responsive Catalyst for Hydrogenation of Nitroarenes under Mild Reaction Condition
Authors: Abedian-Dehaghani Neda , Heravi Majid M. , Sadjadi Samahe
Published: November 2021

A novel thermo-responsive catalyst for the hydrogenation of nitroarenes under mild reaction condition was devised. To prepare the catalyst, a thermo-responsive polymer was first synthesized through the co-polymerization of N-isopropylacrylamide and allylamine and then covalently grafted on the Cl-functionalized perlite. The resulting composite was subsequently utilized as a support for the stabilization of Pd nanoparticles. Investigation of the catalytic activity of the catalyst approved its high catalytic activity at a temperature above the lower critical solution temperature. More precisely, 0.03 g of the catalyst can promote the reaction of 1 mmol of nitro-compounds in H2O/EtOH (1:1) at 45 °C to furnish the corresponding products in 70–100% yields. This issue was assigned to the collapse of the polymeric component and formation of a hydrophobic environment that was beneficial for the mass-transfer of the hydrophobic nitroarenes. Notably, the catalytic activity of the catalyst was higher than that of palladated perlite and thermos-responsive polymer due to the synergistic effects between the perlite and polymeric moiety. Furthermore, the study of the substrate scope confirmed that a wide range of substrates with different steric and electronic properties could tolerate hydrogenation reaction. Moreover, the catalyst was highly selective toward hydrogenation of the nitro group and could be recycled up to seven runs with insignificant Pd leaching and loss of catalytic activity. The hot filtration test also confirmed the heterogeneous nature of the catalysis.
Scientific Validation and Clinical Application of Lung Cancer Organoids
Authors: Lee Dahye , Kim Yoonjoo , Chung Chaeuk
Published: November 2021

Lung cancer organoid (LCO) is a novel model of lung cancer that facilitates drug screening. However, the success rate of LCOs varies from 7% to 87%, and the culture medium compositions are markedly different. Airway organoid media can be used for LCO cultures, but this promotes the overgrowth of normal cell organoids especially in LCOs from intrapulmonary lesions. Several modified media are specifically utilized for promoting the cancer cell’s growth. For culturing high-purity LCOs, cancer cells from metastatic lesions and malignant effusions are used. Recently, single-cell RNA sequencing has identified previously unknown cell populations in the lungs and lung cancer. This sequencing technology can be used to validate whether the LCO recapitulates the heterogeneity and functional hierarchy of the primary tumor. Several groups have attempted to culture LCOs with mesenchymal cells and immune cells to recapitulate the tumor microenvironment. Disease modeling using LCO provides novel insight into the pathophysiology of lung cancer and enables high-throughput screening for drug discovery and prognosis prediction. An LCO model would help to identify new concepts as a basis for lung cancer targeting by discovering innovative therapeutic targets.
Fine-Tuning of mTOR mRNA and Nucleolin Complexes by SMN
Authors: Gabanella Francesca , Barbato Christian , Fiore Marco , Petrella Carla , de Vincentiis Marco , Greco Antonio , Minni Antonio , Corbi Nicoletta , Passananti Claudio , Di Certo Maria Grazia
Published: November 2021

Increasing evidence points to the Survival Motor Neuron (SMN) protein as a key determinant of translation pathway. Besides its role in RNA processing and sorting, several works support a critical implication of SMN in ribosome biogenesis. We previously showed that SMN binds ribosomal proteins (RPs) as well as their encoding transcripts, ensuring an appropriate level of locally synthesized RPs. SMN impacts the translation machinery in both neural and non-neural cells, in agreement with the concept that SMN is an essential protein in all cell types. Here, we further assessed the relationship between SMN and translation-related factors in immortalized human fibroblasts. We focused on SMN-nucleolin interaction, keeping in mind that nucleolin is an RNA-binding protein, highly abundant within the nucleolus, that exhibits a central role in ribosomes production. Nucleolin may also affects translation network by binding the mammalian target of rapamycin (mTOR) mRNA and promoting its local synthesis. In this regard, for the first time we provided evidence that SMN protein itself associates with mTOR transcript. Collectively, we found that: (1) SMN coexists with nucleolin–mTOR mRNA complexes at subcellular level; (2) SMN deficiency impairs nucleolar compartmentalization of nucleolin, and (3) this event correlates with the nuclear retention of mTOR mRNA. These findings suggest that SMN may regulate not only structural components of translation machinery, but also their upstream regulating factors.
Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies
Authors: Mueller Anna-Lena , Payandeh Zahra , Mohammadkhani Niloufar , Mubarak Shaden M. H. , Zakeri Alireza , Alagheband Bahrami Armina , Brockmueller Aranka , Shakibaei Mehdi
Published: November 2021

Rheumatoid arthritis (RA) is considered a chronic systemic, multi-factorial, inflammatory, and progressive autoimmune disease affecting many people worldwide. While patients show very individual courses of disease, with RA focusing on the musculoskeletal system, joints are often severely affected, leading to local inflammation, cartilage destruction, and bone erosion. To prevent joint damage and physical disability as one of many symptoms of RA, early diagnosis is critical. Auto-antibodies play a pivotal clinical role in patients with systemic RA. As biomarkers, they could help to make a more efficient diagnosis, prognosis, and treatment decision. Besides auto-antibodies, several other factors are involved in the progression of RA, such as epigenetic alterations, post-translational modifications, glycosylation, autophagy, and T-cells. Understanding the interplay between these factors would contribute to a deeper insight into the causes, mechanisms, progression, and treatment of the disease. In this review, the latest RA research findings are discussed to better understand the pathogenesis, and finally, treatment strategies for RA therapy are presented, including both conventional approaches and new methods that have been developed in recent years or are currently under investigation.
Adult Neural Stem Cells from Midbrain Periventricular Regions Show Limited Neurogenic Potential after Transplantation into the Hippocampal Neurogenic Niche
Authors: Fauser Mareike , Loewenbrück Kai F , Rangnick Johannes , Brandt Moritz D , Hermann Andreas , Storch Alexander
Published: November 2021

The regulation of adult neural stem or progenitor cell (aNSC) proliferation and differentiation as an interplay of cell-intrinsic and local environmental cues remains in part unclear, impeding their role in putative regenerative therapies. aNSCs with all major properties of NSCs in vitro have been identified in a variety of brain regions beyond the classic neurogenic niches, including the caudal periventricular regions (PVRs) of the midbrain, though active neurogenesis is either limited or merely absent in these regions. To elucidate cell-intrinsic properties of aNSCs from various PVRs, we here examined the proliferation and early differentiation capacity of murine aNSCs from non-neurogenic midbrain PVRs (PVRMB) compared to aNSCs from the neurogenic ventricular-subventricular zone (PVRV-SVZ) 7 days after transplantation into the permissive pro-neurogenic niche of the dentate gyrus (DG) of the hippocampus in mice. An initial in vitro characterization of the transplants displayed very similar characteristics of both aNSC grafts after in vitro expansion with equal capacities of terminal differentiation into astrocytes and Tuj1+ neurons. Upon the allogenic transplantation of the respective aNSCs into the DG, PVRMB grafts showed a significantly lower graft survival and proliferative capacity compared to PVRV-SVZ transplants, whereby the latter are exclusively capable of generating new neurons. Although these differences might be—in part—related to the transplantation procedure and the short-term study design, our data strongly imply important cell-intrinsic differences between aNSCs from neurogenic compared to non-neurogenic PVRs with respect to their neurogenic potential and/or their sensitivity to neurogenic cues.
Investigation of Duplex Brass Membranes with Metallography, Permeability and Treatments: Work-Hardening, Annealing and Quenching
Authors: Kavafaki Sofia , Bomis George , Drakaki Kyriaki , Varoutoglou Athanasios , Kiourtzidis Konstantinos , Kyzas George Z. , Mitropoulos Athanasios C.
Published: November 2021

This paper consists of the fabrication and investigation of metal membranes and the study of their behaviour and applications in gas separation processes. The scope is to produce and characterize the porous crystal structure of brass alloy (standardization: DIN 17660) membranes and measure their permeability with helium as a penetrant medium. Another part of this study is to alter the brass alloy’s structure throughout metallurgical treatments and investigate how the permeability is allied to the structure’s alteration. This work merges the knowledge and technology of inorganic porous materials science in metallurgy. The novelty of the current research resides in the process to alternate the brass alloy structure throughout metallurgical treatments and how it is allied to the permeability of the membrane, which is of interest to be investigated. The results of the research are analysed and compared conducting the final inferences. All metallurgical treatments resulted in low permeability values when compared to a non-treated specimen. Specifically, the drop in permeance ranged from 76 up to 99.56%. It is noted that consecutive treatments contributed to even further decreases.
Ultrasensitive Leaky Surface Acoustic Wave Immunosensor for Real-Time Detection of Alpha-Fetoprotein in Biological Fluids
Authors: Rauf Sana , Qazi Hafiz Imran Ahmad , Luo Jingting , Fu Chen , Tao Ran , Rauf Sajid , Yang Lei , Li Honglang , Fu Yongqing
Published: November 2021

We propose an ultrasensitive leaky surface acoustic wave (LSAW) immunosensor based on molybdenum disulfide @ cuprous oxide—gold (MoS2@Cu2O-Au) nanoparticles and subsequent gold staining for the detection of alpha-fetoprotein (AFP). MoS2@Cu2O-Au nanoparticles, with their large specific surface area and good biocompatibility, not only capture the secondary antibodies (Ab2) but also amplify the mass loading effect of the acoustic wave sensor in the detection of AFP. The immunosensor signals are further amplified upon injection of gold staining solution. The developed immunosensor achieved a low detection limit of 5.5 and 25.0 pg/mL with and without gold staining, respectively. The immunosensor demonstrated its efficiency for the quantitative detection of AFP in complex biological fluids, including human serum and saliva samples, with excellent selectivity and long-term stability, showing great potential for the quantification of AFP in clinical diagnosis.
Assessment of Parents’ Perceptions of Childhood Immunization: A Cross-Sectional Study from Pakistan
Authors: Hussain Azhar , Zahid Anam , Malik Madeeha , Ansari Mukhtar , Vaismoradi Mojtaba , Aslam Adeel , Hayat Khezar , Gajdács Márió , Jamshed Shazia
Published: November 2021

Immunization is one of the most cost-effective public health interventions, with considerable impacts on people’s health. Parents’ perception of their knowledge, attitude, and satisfaction is an important factor, as they may be targeted by interventions for better immunization coverage. Therefore, this study aimed to assess parents’ perceptions in terms of their knowledge, attitude, and satisfaction of the immunization of their children aged less than two years of age, in two cities of Pakistan. A descriptive cross-sectional study was conducted in the vicinity of Rawalpindi and Islamabad from March to August 2019. A semi-structured questionnaire was used for the data collection on a convenient sample of parents. The questionnaire was hand-delivered to the parents by data collectors. Descriptive and inferential statistics were used for data analysis via SPSS version 22. A total of n = 382 respondents were included in the data analysis. Statistically significant differences were found between the parents’ knowledge scores and their education levels and monthly incomes (p < 0.05). Parents with master’s education degrees and low monthly incomes had significantly better knowledge (p < 0.05). Additionally, 96.85% of the respondents believed that child immunization was important. In addition, more than half of the respondents (57.58%) thought that the affordability of vaccines was a principal factor for delays in immunization. Although the parents’ knowledge regarding the immunization of their children was not adequate, they had positive perceptions toward it.
Effects of Caudal Autotomy on the Locomotor Performance of Micrablepharus Atticolus (Squamata, Gymnophthalmidae)
Authors: Silva Naiane Arantes , Caetano Gabriel Henrique de Oliveira , Campelo Pedro Henrique , Cavalcante Vitor Hugo Gomes Lacerda , Godinho Leandro Braga , Miles Donald Bailey , Paulino Henrique Monteiro , da Silva Júlio Miguel Alvarenga , de Souza Bruno Araújo , da Silva Hosmano Batista Ferreira , Colli Guarino Rinaldi
Published: November 2021

Caudal autotomy is a striking adaptation used by many lizard species to evade predators. Most studies to date indicate that caudal autotomy impairs lizard locomotor performance. Surprisingly, some species bearing the longest tails show negligible impacts of caudal autotomy on sprint speed. Part of this variation has been attributed to lineage effects. For the first time, we model the effects of caudal autotomy on the locomotor performance of a gymnophthalmid lizard, Micrablepharus atticolus, which has a long and bright blue tail. To improve model accuracy, we incorporated the effects of several covariates. We found that body temperature, pregnancy, mass, collection site, and the length of the regenerated portion of the tail were the most important predictors of locomotor performance. However, sprint speed was unaffected by tail loss. Apparently, the long tail of M. atticolus is more useful when using undulation amidst the leaf litter and not when using quadrupedal locomotion on a flat surface. Our findings highlight the intricate relationships among physiological, morphological, and behavioral traits. We suggest that future studies about the impacts of caudal autotomy among long-tailed lizards should consider the role of different microhabitats/substrates on locomotor performance, using laboratory conditions that closely mimic their natural environments.
The Transition Period Updated: A Review of the New Insights into the Adaptation of Dairy Cows to the New Lactation
Authors: Mezzetti Matteo , Cattaneo Luca , Passamonti Matilde Maria , Lopreiato Vincenzo , Minuti Andrea , Trevisi Erminio
Published: November 2021

Recent research on the transition period (TP) of dairy cows has highlighted the pivotal role of immune function in affecting the severity of metabolic challenges the animals face when approaching calving. This suggests that the immune system may play a role in the etiology of metabolic diseases occurring in early lactation. Several studies have indicated that the roots of immune dysfunctions could sink way before the “classical” TP (e.g., 3 weeks before and 3 weeks after calving), extending the time frame deemed as “risky” for the development of early lactation disorders at the period around the dry-off. Several distressing events occurring during the TP (i.e., dietary changes, heat stress) can boost the severity of pre-existing immune dysfunctions and metabolic changes that physiologically affect this phase of the lactation cycle, further increasing the likelihood of developing diseases. Based on this background, several operational and nutritional strategies could be adopted to minimize the detrimental effects of immune dysfunctions on the adaptation of dairy cows to the new lactation. A suitable environment (i.e., optimal welfare) and a balanced diet (which guarantees optimal nutrient partitioning to improve immune functions in cow and calf) are key aspects to consider when aiming to minimize TP challenges at the herd level. Furthermore, several prognostic behavioral and physiological indicators could help in identifying subjects that are more likely to undergo a “bad transition”, allowing prompt intervention through specific modulatory treatments. Recent genomic advances in understanding the linkage between metabolic disorders and the genotype of dairy cows suggest that genetic breeding programs aimed at improving dairy cows’ adaptation to the new lactation challenges (i.e., through increasing immune system efficiency or resilience against metabolic disorders) could be expected in the future. Despite these encouraging steps forward in understanding the physiological mechanisms driving metabolic responses of dairy cows during their transition to calving, it is evident that these processes still require further investigation, and that the TP—likely extended from dry-off—continues to be “the final frontier” for research in dairy sciences.
Structured Reporting of Computed Tomography and Magnetic Resonance in the Staging of Pancreatic Adenocarcinoma: A Delphi Consensus Proposal
Authors: Granata Vincenza , Morana Giovanni , D'Onofrio Mirko , Fusco Roberta , Coppola Francesca , Grassi Francesca , Cappabianca Salvatore , Reginelli Alfonso , Maggialetti Nicola , Buccicardi Duccio , Barile Antonio , Rengo Marco , Bortolotto Chandra , Urraro Fabrizio , La Casella Giorgia Viola , Montella Marco , Ciaghi Eleonora , Bellifemine Francesco , De Muzio Federica , Danti Ginevra , Grazzini Giulia , Barresi Carmelo , Brunese Luca , Neri Emanuele , Grassi Roberto , Miele Vittorio , Faggioni Lorenzo
Published: November 2021

Background: Structured reporting (SR) in radiology has been recognized recently by major scientific societies. This study aims to build structured computed tomography (CT) and magnetic resonance (MR)-based reports in pancreatic adenocarcinoma during the staging phase in order to improve communication between the radiologist and members of multidisciplinary teams. Materials and Methods: A panel of expert radiologists, members of the Italian Society of Medical and Interventional Radiology, was established. A modified Delphi process was used to develop the CT-SR and MRI-SR, assessing a level of agreement for all report sections. Cronbach’s alpha (Cα) correlation coefficient was used to assess internal consistency for each section and to measure quality analysis according to the average inter-item correlation. Results: The final CT-SR version was built by including n = 16 items in the “Patient Clinical Data” section, n = 11 items in the “Clinical Evaluation” section, n = 7 items in the “Imaging Protocol” section, and n = 18 items in the “Report” section. Overall, 52 items were included in the final version of the CT-SR. The final MRI-SR version was built by including n = 16 items in the “Patient Clinical Data” section, n = 11 items in the “Clinical Evaluation” section, n = 8 items in the “Imaging Protocol” section, and n = 14 items in the “Report” section. Overall, 49 items were included in the final version of the MRI-SR. In the first round for CT-SR, all sections received more than a good rating. The overall mean score of the experts was 4.85. The Cα correlation coefficient was 0.85. In the second round, the overall mean score of the experts was 4.87, and the Cα correlation coefficient was 0.94. In the first round, for MRI-SR, all sections received more than a good rating. The overall mean score of the experts was 4.73. The Cα correlation coefficient was 0.82. In the second round, the overall mean score of the experts was 4.91, and the Cα correlation coefficient was 0.93. Conclusions: The CT-SR and MRI-SR are based on a multi-round consensus-building Delphi exercise derived from the multidisciplinary agreement of expert radiologists in order to obtain more appropriate communication tools for referring physicians.
Challenges Encountered When Evaluating an Antibody-Detecting Point-of-Care Test for Taeniosis in an Endemic Community in Zambia: A Prospective Diagnostic Accuracy Study
Authors: Mubanga Chishimba , Trevisan Chiara , Van Damme Inge , Schmidt Veronika , Phiri Isaac K. , Zulu Gideon , Noh John , Handali Sukwan , Mambo Richard , Chembensofu Mwelwa , Masuku Maxwell , Reynders Dries , Jansen Famke , Bottieau Emmanuel , Magnussen Pascal , Winkler Andrea S. , Dorny Pierre , Mwape Kabemba E. , Gabriel Sarah
Published: November 2021

Taenia solium taeniosis diagnosis is challenging because current tests perform sub-optimally and/or are expensive, require sophisticated equipment, infrastructure and trained manpower, and therefore are not community deployable. A recently-developed, multi-strip, T. solium point-of-care test (TS POC) for simultaneous detection of tapeworm (TS POC T) and cysticercus (TS POC CC) human antibodies was evaluated for diagnostic accuracy on consecutively recruited community participants in Sinda district, Zambia. All participants were tested using the TS POC test. All test-positives and 20% of the test-negative participants were invited to give a blood and stool sample for reference testing. Three different reference tests were used for taeniosis diagnosis: recombinant rES33 enzyme-linked immunoelectrotransfer blot (rES33 EITB), copro PCR and copro Ag ELISA. Bayesian analysis with probabilistic constraints was used to estimate sensitivity and specificity. In total, 1254 participants were tested with the TS POC test, of whom 13 tested positive using the TS POC T. Based on 161 participants with complete data, the estimated sensitivity and specificity for the TS POC T test were 38% (95% CI: 5–93%) and 99% (95% CI: 98–100%), respectively. The challenge of highly variable inter-assay performance is highlighted. We recommend either increasing the sensitivity or redesigning the test.
IsoMAG—An Automated System for the Immunomagnetic Isolation of Squamous Cell Carcinoma-Derived Circulating Tumor Cells
Authors: Gribko Alena , Stiefel Janis , Liebetanz Lana , Nagel Sophie Madeleine , Künzel Julian , Wandrey Madita , Hagemann Jan , Stauber Roland H. , Freese Christian , Gül Désirée
Published: November 2021

Background: detailed information about circulating tumor cells (CTCs) as an indicator of therapy response and cancer metastasis is crucial not only for basic research but also for diagnostics and therapeutic approaches. Here, we showcase a newly developed IsoMAG IMS system with an optimized protocol for fully automated immunomagnetic enrichment of CTCs, also revealing rare CTC subpopulations. Methods: using different squamous cell carcinoma cell lines, we developed an isolation protocol exploiting highly efficient EpCAM-targeting magnetic beads for automated CTC enrichment by the IsoMAG IMS system. By FACS analysis, we analyzed white blood contamination usually preventing further downstream analysis of enriched cells. Results: 1 µm magnetic beads with tosyl-activated hydrophobic surface properties were found to be optimal for automated CTC enrichment. More than 86.5% and 95% of spiked cancer cells were recovered from both cell culture media or human blood employing our developed protocol. In addition, contamination with white blood cells was minimized to about 1200 cells starting from 7.5 mL blood. Finally, we showed that the system is applicable for HNSCC patient samples and characterized isolated CTCs by immunostaining using a panel of tumor markers. Conclusion: Herein, we demonstrate that the IsoMAG system allows the detection and isolation of CTCs from HNSCC patient blood for disease monitoring in a fully-automated process with a significant leukocyte count reduction. Future developments seek to integrate the IsoMAG IMS system into an automated microfluidic-based isolation workflow to further facilitate single CTC detection also in clinical routine.
Immunoprofiling of 4-1BB Expression Predicts Outcome in Chronic Lymphocytic Leukemia (CLL)
Authors: Kaban Kübra , Greiner Sarah M. , Holzmayer Samuel , Tandler Claudia , Meyer Sophie , Hinterleitner Clemens , Salih Helmut R. , Märklin Melanie , Heitmann Jonas S.
Published: November 2021

Recent success of novel therapies has improved treatment of chronic lymphocytic leukemia (CLL) patients, but most of them still require several treatment regimes. To improve treatment choice, prognostic markers suitable for prediction of disease outcome are required. Several molecular/genetic markers have been established, but accessibility for the entirety of all patients is limited. We here evaluated the relevance of GITR/4-1BB as well as their ligands for the prognosis of CLL patients. Surface expression of GITR/GITRL and 4-1BB/4-1BBL was correlated with established prognostic markers. Next, we separated our patient population according to GITR/GITRL and 4-1BB/4-1BBL expression in groups with high/low expression levels and performed Kaplan-Meier analyses. Interestingly, no correlation was observed with the defined prognostic markers. Whereas no significant difference between high and low expression of GITR, GITRL and 4-1BBL was observed, high 4-1BB levels on leukemic cells were associated with significantly shorter survival. Thereby we identify 4-1BB as prognostic marker for CLL.
Modulated Electro-Hyperthermic (mEHT) Treatment in the Therapy of Inoperable Pancreatic Cancer Patients—A Single-Center Case-Control Study
Authors: Petenyi Flora Greta , Garay Tamas , Muhl Dorottya , Izso Blanka , Karaszi Adam , Borbenyi Erika , Herold Magdolna , Herold Zoltan , Szasz Attila Marcell , Dank Magdolna
Published: November 2021

Our present oncological treatment arsenal has limited treatment options for pancreatic ductal adenocarcinoma (PDAC). Extended reviews have shown the benefits of hyperthermia for PDAC, supporting the perspectives with the improvements of the treatment possibilities. METHODS: A retrospective single-center case-control study was conducted with the inclusion of 78 inoperable PDAC patients. Age-, sex-, chemotherapy-, stage-, and ascites formation-matched patients were assigned to two equal groups based on the application of modulated electro-hyperthermia (mEHT). The EHY2030 mEHT device was used. RESULTS: A trend in favor of mEHT was found in overall survival (p = 0.1420). To further evaluate the potential beneficial effects of mEHT, the presence of distant metastasis or ascites in the patients’ oncological history was investigated. Of note, mEHT treatment had a favorable effect on patients’ overall survival in metastatic disease (p = 0.0154), while less abdominal fluid responded to the mEHT treatment in a more efficient way (p ≤ 0.0138). CONCLUSION: mEHT treatment was associated with improved overall survival in PDAC in our single-center retrospective case-control study. The outcome measures encourage us to design a randomized prospective clinical study to further confirm the efficiency of mEHT in this patient cohort.
Expand-and-Randomize: An Algebraic Approach to Secure Computation
Authors: Zhao Yizhou , Sun Hua
Published: November 2021

We consider the secure computation problem in a minimal model, where Alice and Bob each holds an input and wish to securely compute a function of their inputs at Carol without revealing any additional information about the inputs. For this minimal secure computation problem, we propose a novel coding scheme built from two steps. First, the function to be computed is expanded such that it can be recovered while additional information might be leaked. Second, a randomization step is applied to the expanded function such that the leaked information is protected. We implement this expand-and-randomize coding scheme with two algebraic structures—the finite field and the modulo ring of integers, where the expansion step is realized with the addition operation and the randomization step is realized with the multiplication operation over the respective algebraic structures.
Does Income Inequality Create Excessive Threats to the Sustainable Development of Russia? Evidence from Intercountry Comparisons via Analysis of Inequality Heatmaps
Authors: Dorofeev Mikhail Lvovitch
Published: November 2021

The paper explored the problem of income inequality in Russia in the context of the sustainable development of Russia. The research starts from the historical analysis of income inequality dynamics in Russia. Then, we discussed the problem of the inconsistency of data, comparing different sources (official data from the Rosstat database and alternative data from the World inequality database). The purpose of this research was to assess Russian specifics of income inequality and answer the question of if the income inequality in Russia is excessively high and needs extra government regulation in order to reach the trajectory of advanced sustainable development. To this end, we made intercountry comparisons and used the method of building income inequality heatmaps basing on a dataset from the World Inequality Database. Our sample includes the per-adult equivalent of household market income distribution in 27 developed and developing countries and world regions. The result of the research was that there are many countries in the world wherein the differentiation of income exceeds Russia’s. Russian income inequality is lower than the world average, but the structure of the Russian household income distribution stands out by an extreme concentration of national income in the hands of the top 1%. We supported our results via the independent data from the Credit Suisse wealth inequality report, connecting a record level of wealth inequality in Russia with its problem of top 1% income inequality. It is recommended to gradually increase marginal tax rates on the income and wealth of the top 1% and continue developing an effective progressive tax system in Russia.