bluuebunny/crossref_metadata_2025 huggingface dataset:
Joint Production and Maintenance Optimization of a Series–Parallel System with Quality-Contingent Demand
Authors: Gao Zhenhua , Wang Hongjun , Zhou Chunliu , Zhang Hongliang
Published: July 2022

Making a reasonable and effective production plan is always an essential and challenging task in industrial production. A joint optimization model of production and maintenance is proposed in this paper, which considers the structural relationship between production units and the influence of the unit state on demand. A three-unit series–parallel system is selected to calculate the steady-state probability density function of the system, and the model is established by dividing different maintenance situations in one cycle. By analyzing the composition of expected cost and expected time in each situation, the expected cost rate is calculated by using renewal reward theory. The objective function of the model is to minimize the expected cost rate. The genetic algorithm is improved according to the model characteristics. The application of the model is illustrated by a case, and the sensitivity analysis is set to show the influence of different parameters on the decision-making results of the system, providing ideas for decision-makers. Finally, the contrast experiments show the advantages of the proposed model and method.
Algorithm for Locating the Datum Strand of a Suspension Bridge Considering the Influence of Friction and the Change in Tangent Point of the Cable Saddle
Authors: Zhou Xiangong , Han Heng , Zheng Xiaobo , Chen Yinghao , Liang Zhilei
Published: July 2022

In order to accurately simulate the position of the saddle in the analysis and calculation of a suspension bridge, and then obtain the accurate shape of the datum strand in the construction site, this paper puts forward a calculation method on the position of the saddle and the geometric shape of the datum strand on the basis of considering the friction between the main cable and the saddle. Firstly, the calculation method of friction between the main cable and cable saddle is proposed and the formula of the deviation between the coordinates of the initial position and that of the equilibrium position of the cable saddle is derived. Then, through theoretical derivation, the calculation program of cable geometric shape considering the change in saddle tangent point is compiled. Combined with the analytical algorithm, the concept of temperature telescopic bar is introduced, and a simulation method of the cable saddle and datum strand is given, which is suitable for the combination of finite element analysis and numerical algorithm. Finally, the reliability of the algorithm is verified by the comparison of a numerical example, and by changing the value of friction, the influence of friction on the saddle position and the datum strand geometric shape is analyzed.
Hybrid Meat Products: Incorporation of White Bean Flour in Lean Pork Burgers
Authors: Argel Natalia Soledad , Lorenzo Gabriel , Domínguez Rubén , Fraqueza Maria João , Fernández-López Juana , Sosa Maria Elena , Campagnol Paulo Cesar Bastianello , Lorenzo José Manuel , Andrés Silvina Cecilia
Published: July 2022

The effect of partial lean pork-meat replacement by white Phaseolus vulgaris L. flour in hybrid burgers was studied. A multivariate regression model was used to test different bean flour levels (BF: 8–15 g/100 g) and water/bean flour ratios (W/BF: 1.2, 1.6, and 1.8 g/g). Process yield, texture profile analysis, color parameters, thermal transitions, and microstructure of the systems were analyzed. Respond Surface Methodology was used to model the response behaviors and optimization. Burgers with BF showed yields higher than 88%. Hardness and cohesiveness decreased as the BF level increased, with a more noticeable effect when the W/BF ratio became larger. Regarding color, the higher the BF and the W/BF ratio in burgers, the higher the L* obtained. The desirability optimization predicted an optimum formulation consisting of 15 g BF/100 g and 1.36 g/g W/BF with similar attributes to a commercial pork burger. The thermal analysis showed an increase in the enthalpy associated with the myosin denaturation and the interactions between meat proteins and BF led to higher temperatures for the starch gelatinization and protein denaturation. The microstructure of BF burgers presented a more stable coarse gel matrix derived from coagulated meat proteins combined with the flour components. The mathematical procedure adequately predicted the hybrid burger quality attributes.
RGB-D-Based Robotic Grasping in Fusion Application Environments
Authors: Yin Ruochen , Wu Huapeng , Li Ming , Cheng Yong , Song Yuntao , Handroos Heikki
Published: July 2022

Although deep neural network (DNN)-based robot grasping has come a long way, the uncertainty of predicted results has prevented DNN-based approaches from meeting the stringent requirements of some industrial scenarios. To prevent these uncertainties from affecting the behavior of the robot, we break down the whole process into instance segmentation, clustering and planar extraction, which means we add some traditional approaches between the output of the instance segmentation network and the final control decision. We have experimented with challenging environments, and the results show that our approach can cope well with the challenging environment and achieve more stable and superior results than end-to-end grasping networks.
Current Topics in the Diagnostic Approach to Skin Diseases
Authors: Broggi Giuseppe , Caltabiano Rosario
Published: July 2022

The introduction of novel, non-invasive techniques capable of improving the diagnostic accuracy and sensibility of both inflammatory and neoplastic cutaneous diseases has always been one of the most practical objectives of dermatological research [...]
A Thermosiphon Photobioreactor for Photofermentative Hydrogen Production by Rhodopseudomonas palustris
Authors: Bosman Catharine Elizabeth , McClelland Pott Robert William , Bradshaw Steven Martin
Published: July 2022

A thermosiphon photobioreactor (TPBR) can potentially be used for biohydrogen production, circumventing the requirement for external mixing energy inputs. In this study, a TPBR is evaluated for photofermentative hydrogen production by Rhodopseudomonas palustris (R. palustris). Experiments were conducted in a TPBR, and response surface methodology (RSM), varying biomass concentration, and light intensity and temperature were employed to determine the operating conditions for the enhancement of both hydrogen production as well as biomass suspension. Biomass concentration was found to have had the most pronounced effect on both hydrogen production as well as biomass suspension. RSM models predicted maximum specific hydrogen production rates of 0.17 mol m−3h−1 and 0.21 mmol gCDW−1h−1 at R. palustris concentrations of 1.21 and 0.4 g L−1, respectively. The experimentally measured hydrogen yield was in the range of 45 to 77% (±3.8%), and the glycerol consumption was 8 to 19% (±0.48). At a biomass concentration of 0.40 g L−1, the highest percentage of biomass (72.3%), was predicted to remain in suspension in the TPBR. Collectively, the proposed novel photobioreactor was shown to produce hydrogen as well as passively circulate biomass.
Application of Tubular Reactor Technologies for the Acceleration of Biodiesel Production
Authors: Awogbemi Omojola , Kallon Daramy Vandi Von
Published: July 2022

The need to arrest the continued environmental contamination and degradation associated with the consumption of fossil-based fuels has continued to serve as an impetus for the increased utilization of renewable fuels. The demand for biodiesel has continued to escalate in the past few decades due to urbanization, industrialization, and stringent government policies in favor of renewable fuels for diverse applications. One of the strategies for ensuring the intensification, commercialization, and increased utilization of biodiesel is the adaptation of reactor technologies, especially tubular reactors. The current study reviewed the deployment of different types and configurations of tubular reactors for the acceleration of biodiesel production. The feedstocks, catalysts, conversion techniques, and modes of biodiesel conversion by reactor technologies are highlighted. The peculiarities, applications, merits, drawbacks, and instances of biodiesel synthesis through a packed bed, fluidized bed, trickle bed, oscillatory flow, and micro-channel tubular reactor technologies are discussed to facilitate a better comprehension of the mechanisms behind the technology. Indeed, the deployment of the transesterification technique in tubular reactor technologies will ensure the ecofriendly, low-cost, and large-scale production of biodiesel, a high product yield, and will generate high-quality biodiesel. The outcome of this study will enrich scholarship and stimulate a renewed interest in the application of tubular reactors for large-scale biodiesel production among biodiesel refiners and other stakeholders. Going forward, the use of innovative technologies such as robotics, machine learning, smart metering, artificial intelligent, and other modeling tools should be deployed to monitor reactor technologies for biodiesel production.
Feasibility of Implanting a Foot–Ankle Endoprosthesis within Skin in a Rabbit Model of Transtibial Amputation
Authors: Crouch Dustin L. , Hall Patrick T. , Stubbs Caleb , Billings Caroline , Pedersen Alisha P. , Burton Bryce , Greenacre Cheryl B. , Stephenson Stacy M. , Anderson David E.
Published: July 2022

Prosthetic limbs that are completely implanted within skin (i.e., endoprostheses) could permit direct, physical muscle–prosthesis attachment to restore more natural sensorimotor function to people with amputation. The objective of our study was to test, in a rabbit model, the feasibility of replacing the lost foot after hindlimb transtibial amputation by implanting a novel rigid foot–ankle endoprosthesis that is fully covered with skin. We first conducted a pilot, non-survival surgery in two rabbits to determine the maximum size of the skin flap that could be made from the biological foot–ankle. The skin flap size was used to determine the dimensions of the endoprosthesis foot segment. Rigid foot–ankle endoprosthesis prototypes were successfully implanted in three rabbits. The skin incisions healed over a period of approximately 1 month after surgery, with extensive fur regrowth by the pre-defined study endpoint of approximately 2 months post surgery. Upon gross inspection, the skin surrounding the endoprosthesis appeared normal, but a substantial subdermal fibrous capsule had formed around the endoprosthesis. Histology indicated that the structure and thickness of the skin layers (epidermis and dermis) were similar between the operated and non-operated limbs. A layer of subdermal connective tissue representing the fibrous capsule surrounded the endoprosthesis. In the operated limb of one rabbit, the subdermal connective tissue layer was approximately twice as thick as the skin on the medial (skin = 0.43 mm, subdermal = 0.84 mm), ventral (skin = 0.80 mm, subdermal = 1.47 mm), and lateral (skin = 0.76 mm, subdermal = 1.42 mm) aspects of the endoprosthesis. Our results successfully demonstrated the feasibility of implanting a fully skin-covered rigid foot–ankle endoprosthesis to replace the lost tibia–foot segment of the lower limb. Concerns include the fibrotic capsule which could limit the range of motion of jointed endoprostheses. Future studies include testing of endoprosthetics, as well as materials and pharmacologic agents that may suppress fibrous encapsulation.
Biosimilars: Harmonizing the Approval Guidelines
Authors: Niazi Sarfaraz K.
Published: July 2022

Biosimilar approval guidelines need rationalization and harmonization to remove the inconsistencies and misconceptions to enable faster, safer, and more cost-effective biosimilars. This paper proposes a platform for a model guideline based on the scientific evaluation of the regulatory filings of the 130+ products approved in the US, UK, and EU and hundreds more in the WHO member countries. Extensive literature survey of clinical data published and reported, including Clinicaltrials.gov, a review of all current guidelines in the US, UK and EU, and WHO, and detailed discussions with the FDA have confirmed that removing the animal and clinical efficacy testing and fixing other minor approaches will enable the creation of a harmonized guideline that will best suit an ICH designation.
Advancements in the Alcohol-Associated Liver Disease Model
Authors: Zhu Lin , Li Hai-Di , Xu Jie-Jie , Li Juan-Juan , Cheng Miao , Meng Xiao-Ming , Huang Cheng , Li Jun
Published: July 2022

Alcohol-associated liver disease (ALD) is an intricate disease that results in a broad spectrum of liver damage. The presentation of ALD can include simple steatosis, steatohepatitis, liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). Effective prevention and treatment strategies are urgently required for ALD patients. In previous decades, numerous rodent models were established to investigate the mechanisms of alcohol-associated liver disease and explore therapeutic targets. This review provides a summary of the latest developments in rodent models, including those that involve EtOH administration, which will help us to understand the characteristics and causes of ALD at different stages. In addition, we discuss the pathogenesis of ALD and summarize the existing in vitro models. We analyse the pros and cons of these models and their translational relevance and summarize the insights that have been gained regarding the mechanisms of alcoholic liver injury.
NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients: An Observational Study
Authors: Morimont Laure , Dechamps Mélanie , David Clara , Bouvy Céline , Gillot Constant , Haguet Hélène , Favresse Julien , Ronvaux Lorian , Candiracci Julie , Herzog Marielle , Laterre Pierre-François , De Poortere Julien , Horman Sandrine , Beauloye Christophe , Douxfils Jonathan
Published: July 2022

Background: Neutrophil extracellular traps’ (NETs’) formation is a mechanism of defense that neutrophils deploy as an alternative to phagocytosis, to constrain the spread of microorganisms. Aim: The aim was to evaluate biomarkers of NETs’ formation in a patient cohort admitted to intensive care unit (ICU) due to infection. Methods: Forty-six septic shock patients, 22 critical COVID-19 patients and 48 matched control subjects were recruited. Intact nucleosomes containing histone 3.1 (Nu.H3.1), or citrullinated histone H3R8 (Nu.Cit-H3R8), free citrullinated histone (Cit-H3), neutrophil elastase (NE) and myeloperoxidase (MPO) were measured. Results: Significant differences in Nu.H3.1 and NE levels were observed between septic shock and critical COVID-19 subjects as well as with controls (p-values < 0.05). The normalization of nucleosome levels according to the neutrophil count improved the discrimination between septic shock and critical COVID-19 patients. The ratio of Nu.Cit-H3R8 to Nu.H3.1 allowed the determination of nucleosome citrullination degree, presumably by PAD4. Conclusions: H3.1 and Cit-H3R8 nucleosomes appear to be interesting markers of global cell death and neutrophil activation when combined. Nu.H3.1 permits the evaluation of disease severity and differs between septic shock and critical COVID-19 patients, reflecting two distinct potential pathological processes in these conditions.
Campylobacter Species of the Oral Microbiota as Prognostic Factor for Cardiovascular Outcome after Coronary Artery Bypass Grafting Surgery
Authors: Schulz Susanne , Hofmann Britt , Grollmitz Julia , Friebe Lisa , Kohnert Michael , Schaller Hans-Günter , Reichert Stefan
Published: July 2022

Background: The oral microbiota has been implicated in a variety of systemic diseases, including cardiovascular (CV) disease. The main objective of this study (DRKS-ID: DRKS00015776) was to evaluate the prognostic importance of the oral microbiota for further CV events in patients undergoing coronary artery bypass grafting surgery (3-year follow-up). Methods: In this longitudinal cohort study, 102 CV patients were enrolled, of whom 95 completed the 3-year follow-up. The CV outcome was assessed using the major adverse cardiac and cerebrovascular events criteria. To evaluate subgingival colonization, 16S rRNA genes were amplified, targeting the V3/V4 region (Illumina MiSeq). Results: Regarding the specific number of operational taxonomic units (OTUs), no significant differences in CV outcome were determined (alpha diversity, Shannon index). In linear discriminant analyses and t-tests, the disease-specific differences in the beta diversity of the microbiota composition were evaluated. It was evident that bacteria species of the genus Campylobacter were significantly more prevalent in patients with a secondary CV event (p = 0.015). This hierarchical order also includes Campylobacter rectus, which is considered to be of comprehensive importance in both periodontal and CV diseases. Conclusions: Here, we proved that subgingival occurrence of Campylobacter species has prognostic relevance for cardiovascular outcomes in CV patients undergoing coronary artery bypass grafting.
Oral Microbiota, Its Equilibrium and Implications in the Pathophysiology of Human Diseases: A Systematic Review
Authors: Giordano-Kelhoffer Barbara , Lorca Cristina , March Llanes Jaume , Rábano Alberto , del Ser Teodoro , Serra Aida , Gallart-Palau Xavier
Published: July 2022

Imbalances of the oral microbiota and dysbiosis have traditionally been linked to the occurrence of teeth and oral diseases. However, recent findings indicate that this microbiota exerts relevant influence in systemic health. Dysbiosis of the oral microbiota is implicated in the apparition and progression of cardiovascular, neurodegenerative and other major human diseases. In fact, the oral microbiota are the second most diverse and largely populated microbiota of the human body and its relationships with systemic health, although widely explored, they still lack of proper integration. The purpose of this systematic review is thus to widely examine the implications of oral microbiota in oral, cardiovascular and neurodegenerative diseases to offer integrative and up-to-date interpretations. To achieve that aim, we identified a total of 121 studies curated in PUBMED from the time interval January 2003–April 2022, which after careful screening resulted in 79 studies included. The reviewed scientific literature provides plausible vias of implication of dysbiotic oral microbiota in systemic human diseases, and encourages further research to continue elucidating the highly relevant and still poorly understood implications of this niche microbiota in systemic health. PROSPERO Registration Number: CRD42022299692. This systematic review follows relevant PRISMA guidelines.
Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function
Authors: Sobral Daniel , Francisco Rita , Duro Laura , Videira Paula Alexandra , Grosso Ana Rita
Published: July 2022

Glycosylation is a fundamental cellular process affecting human development and health. Complex machinery establishes the glycan structures whose heterogeneity provides greater structural diversity than other post-translational modifications. Although known to present spatial and temporal diversity, the evolution of glycosylation and its role at the tissue-specific level is poorly understood. In this study, we combined genome and transcriptome profiles of healthy and diseased tissues to uncover novel insights into the complex role of glycosylation in humans. We constructed a catalogue of human glycosylation factors, including transferases, hydrolases and other genes directly involved in glycosylation. These were categorized as involved in N-, O- and lipid-linked glycosylation, glypiation, and glycosaminoglycan synthesis. Our data showed that these glycosylation factors constitute an ancient family of genes, where evolutionary constraints suppressed large gene duplications, except for genes involved in O-linked and lipid glycosylation. The transcriptome profiles of 30 healthy human tissues revealed tissue-specific expression patterns preserved across mammals. In addition, clusters of tightly co-expressed genes suggest a glycosylation code underlying tissue identity. Interestingly, several glycosylation factors showed tissue-specific profiles varying with age, suggesting a role in ageing-related disorders. In cancer, our analysis revealed that glycosylation factors are highly perturbed, at the genome and transcriptome levels, with a strong predominance of copy number alterations. Moreover, glycosylation factor dysregulation was associated with distinct cellular compositions of the tumor microenvironment, reinforcing the impact of glycosylation in modulating the immune system. Overall, this work provides genome-wide evidence that the glycosylation machinery is tightly regulated in healthy tissues and impaired in ageing and tumorigenesis, unveiling novel potential roles as prognostic biomarkers or therapeutic targets.
A New Approach to Imaging and Rapid Microbiome Identification for Prostate Cancer Patients Undergoing Radiotherapy
Authors: Maślak Ewelina , Miśta Wioletta , Złoch Michał , Błońska Dominika , Pomastowski Paweł , Monedeiro Fernanda , Buszewski Bogusław , Mrochem-Kwarciak Jolanta , Bojarska Katarzyna , Gabryś Dorota
Published: July 2022

(1) Background: Little is known about the impact of urinary microflora, in particular, its effects on side effects after radiotherapy. The use of mass spectrometry identification method (MALDI) may bring a new look at the issue of the composition and significance of the urinary microbiome. This study aimed to use the mass spectrometry identification method (MALDI) to identify the microbiome of urine samples collected from 50 irradiated prostate cancer patients. (2) Methods: Blood and urine samples were collected before gold marker implantation, at the start and last day of radiotherapy, 1, 4 months after. Patients do not always collect the urine from the midstream; therefore, samples were collected from the first void and midstream in 12 patients for MALDI analysis; in the remaining 38 patients—from the midstream void for MALDI and biochemical analysis. (3) Results: Microorganisms were present in 140/181 urine samples. We found 33 different species 3G(−) and 30G(+). The most frequently isolated strains were: Staphylococcus haemolyticus, Staphylococcus epidermidis, Staphylococcus hominis, Enterococcus faecalis, and Micrococcus luteus. When comparing the type of urine samples, bacteria were more common in samples from the first-void urine than from the midstream one. The absence of bacteria was found in 12.2% of samples from the first-void urine and in 24.7% from the midstream. There was no difference in the total incidence of species between streams (p = 0.85). Before fiducial implantation, the total number of detected bacterial species was significantly higher in comparison to the end of radiotherapy (p = 0.038), indicating that the administered therapy resulted in depleting the local microbiome. One month after radiotherapy, an increase in the number of isolated bacteria was observed. The number of bacterial species in urine did not correlate with blood parameters. The presence of leukocytes (p = 0.013) and proteins (p = 0.004) in urine was related to a greater variety of bacteria found in urine specimens. (4) Conclusions: We obtained a similar spectrum of bacteria from the initial and middle urine streams. We also showed that there is a change in bacteria species affected by the treatment of prostate cancer patients, with both antibiotics before gold fiducial implantation and radiotherapy.
Biological Sensing of Nitric Oxide in Macrophages and Atherosclerosis Using a Ruthenium-Based Sensor
Authors: Vidanapathirana Achini K. , Goyne Jarrad M. , Williamson Anna E. , Pullen Benjamin J. , Chhay Pich , Sandeman Lauren , Bensalem Julien , Sargeant Timothy J. , Grose Randall , Crabtree Mark J. , Zhang Run , Nicholls Stephen J. , Psaltis Peter J. , Bursill Christina A.
Published: July 2022

Macrophage-derived nitric oxide (NO) plays a critical role in atherosclerosis and presents as a potential biomarker. We assessed the uptake, distribution, and NO detection capacity of an irreversible, ruthenium-based, fluorescent NO sensor (Ru-NO) in macrophages, plasma, and atherosclerotic plaques. In vitro, incubation of Ru-NO with human THP1 monocytes and THP1-PMA macrophages caused robust uptake, detected by Ru-NO fluorescence using mass-cytometry, confocal microscopy, and flow cytometry. THP1-PMA macrophages had higher Ru-NO uptake (+13%, p < 0.05) than THP1 monocytes with increased Ru-NO fluorescence following lipopolysaccharide stimulation (+14%, p < 0.05). In mice, intraperitoneal infusion of Ru-NO found Ru-NO uptake was greater in peritoneal CD11b+F4/80+ macrophages (+61%, p < 0.01) than CD11b+F4/80− monocytes. Infusion of Ru-NO into Apoe−/− mice fed high-cholesterol diet (HCD) revealed Ru-NO fluorescence co-localised with atherosclerotic plaque macrophages. When Ru-NO was added ex vivo to aortic cell suspensions from Apoe−/− mice, macrophage-specific uptake of Ru-NO was demonstrated. Ru-NO was added ex vivo to tail-vein blood samples collected monthly from Apoe−/− mice on HCD or chow. The plasma Ru-NO fluorescence signal was higher in HCD than chow-fed mice after 12 weeks (37.9%, p < 0.05). Finally, Ru-NO was added to plasma from patients (N = 50) following clinically-indicated angiograms. There was lower Ru-NO fluorescence from plasma from patients with myocardial infarction (−30.7%, p < 0.01) than those with stable coronary atherosclerosis. In conclusion, Ru-NO is internalised by macrophages in vitro, ex vivo, and in vivo, can be detected in atherosclerotic plaques, and generates measurable changes in fluorescence in murine and human plasma. Ru-NO displays promising utility as a sensor of atherosclerosis.
Gene Ontology Analysis Highlights Biological Processes Influencing Non-Response to Anti-TNF Therapy in Rheumatoid Arthritis
Authors: Jezernik Gregor , Gorenjak Mario , Potočnik Uroš
Published: July 2022

Anti-TNF therapy has significantly improved disease control in rheumatoid arthritis, but a fraction of rheumatoid arthritis patients do not respond to anti-TNF therapy or lose response over time. Moreover, the mechanisms underlying non-response to anti-TNF therapy remain largely unknown. To date, many single biomarkers of response to anti-TNF therapy have been published but they have not yet been analyzed as a system of interacting nodes. The aim of our study is to systematically elucidate the biological processes underlying non-response to anti-TNF therapy in rheumatoid arthritis using the gene ontologies of previously published predictive biomarkers. Gene networks were constructed based on published biomarkers and then enriched gene ontology terms were elucidated in subgroups using gene ontology software tools. Our results highlight the novel role of proteasome-mediated protein catabolic processes (p = 2.91 × 10−15) and plasma lipoproteins (p = 4.55 × 10−11) in anti-TNF therapy response. The results of our gene ontology analysis help elucidate the biological processes underlying non-response to anti-TNF therapy in rheumatoid arthritis and encourage further study of the highlighted processes.
Setup and Characterization of a High-Throughput Luminescence-Based Serum Bactericidal Assay (L-SBA) to Determine Functionality of Human Sera against Shigella flexneri
Authors: Mancini Francesca , Micoli Francesca , Rossi Omar
Published: July 2022

Shigellosis represents a major public health problem worldwide. The morbidity of the disease, especially in children in developing countries, together with the increase of antimicrobial resistance make a vaccine against Shigella an urgent medical need. Several vaccines under development are targeting Shigella lipopolysaccharide (LPS), whose extreme diversity renders necessary the development of multivalent vaccines. Immunity against Shigella LPS can elicit antibodies capable of killing bacteria in a serotype-specific manner. Therefore, although a correlation of protection against shigellosis has not been established, demonstration of vaccine-elicited antibody bactericidal activity may provide one means of vaccine protection against Shigella. To facilitate Shigella vaccine development, we have set up a high-throughput serum bactericidal assay based on luminescence readout (L-SBA), which has been already used to determine the functionality of antibodies against S. sonnei in multiple clinical trials. Here we present the setup and intra-laboratory characterization of L-SBA against three epidemiologically relevant Shigella flexneri serotypes using human sera. We assessed the linearity, repeatability and reproducibility of the method, demonstrating high assay specificity to detect the activity of antibodies against each homologous strain without any heterologous aspecificity against species-related and non-species-related strains; this assay is ready to be used to determine bactericidal activity of clinical sera raised by multivalent vaccines and in sero-epidemiological studies.
Update on the Diagnosis and Management of Medullary Thyroid Cancer: What Has Changed in Recent Years?
Authors: Kaliszewski Krzysztof , Ludwig Maksymilian , Ludwig Bartłomiej , Mikuła Agnieszka , Greniuk Maria , Rudnicki Jerzy
Published: July 2022

Medullary thyroid carcinoma (MTC) is a neoplasm originating from parafollicular C cells. MTC is a rare disease, but its prognosis is less favorable than that of well-differentiated thyroid cancers. To improve the prognosis of patients with MTC, early diagnosis and prompt therapeutic management are crucial. In the following paper, recent advances in laboratory and imaging diagnostics and also pharmacological and surgical therapies of MTC are discussed. Currently, a thriving direction of development for laboratory diagnostics is immunohistochemistry. The primary imaging modality in the diagnosis of MTC is the ultrasound, but opportunities for development are seen primarily in nuclear medicine techniques. Surgical management is the primary method of treating MTCs. There are numerous publications concerning the stratification of particular lymph node compartments for removal. With the introduction of more effective methods of intraoperative parathyroid identification, the complication rate of surgical treatment may be reduced. The currently used pharmacotherapy is characterized by high toxicity. Moreover, the main limitation of current pharmacotherapy is the development of drug resistance. Currently, there is ongoing research on the use of tyrosine kinase inhibitors (TKIs), highly specific RET inhibitors, radiotherapy and immunotherapy. These new therapies may improve the prognosis of patients with MTCs.
Diagnosis and Treatment of Pineal Region Tumors in Adults: A EURACAN Overview
Authors: Lombardi Giuseppe , Poliani Pietro Luigi , Manara Renzo , Berhouma Moncef , Minniti Giuseppe , Tabouret Emeline , Razis Evangelia , Cerretti Giulia , Zagonel Vittorina , Weller Michael , Idbaih Ahmed
Published: July 2022

Pineal region tumors are rare intracranial tumors, accounting for less than 1% of all adult intracranial tumor lesions. These lesions represent a histologically heterogeneous group of tumors. Among these tumors, pineal parenchymal tumors and germ cell tumors (GCT) represent the most frequent types of lesions. According to the new WHO 2021 classification, pineal parenchymal tumors include five distinct histotypes: pineocytoma (PC), pineal parenchymal tumors of intermediate differentiation (PPTID), papillary tumor of the pineal region (PTPR), pinealoblastoma (PB), and desmoplastic myxoid tumor of the pineal region, SMARCB1-mutant; GCTs include germinoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, mixed GCTs. Neuroradiological assessment has a pivotal role in the diagnostic work-up, surgical planning, and follow-up of patients with pineal masses. Surgery can represent the mainstay of treatment, ranging from biopsy to gross total resection, yet pineal region tumors associated with obstructive hydrocephalus may be surgically managed via ventricular internal shunt or endoscopic third ventriculostomy. Radiotherapy remains an essential component of the multidisciplinary treatment approach for most pineal region tumors; however, treatment volumes depend on the histological subtypes, grading, extent of disease, and the combination with chemotherapy. For localized germinoma, the current standard of care is chemotherapy followed by reduced-dose whole ventricular irradiation plus a boost to the primary tumor. For pinealoblastoma patients, postoperative radiation has been associated with higher overall survival. For the other pineal tumors, the role of radiotherapy remains poorly studied and it is usually reserved for aggressive (grade 3) or recurrent tumors. The use of systemic treatments mainly depends on histology and prognostic factors such as residual disease and metastases. For pinealoblastoma patients, chemotherapy protocols are based on various alkylating or platinum-based agents, vincristine, etoposide, cyclophosphamide and are used in association with radiotherapy. About GCTs, their chemosensitivity is well known and is based on cisplatin or carboplatin and may include etoposide, cyclophosphamide, or ifosfamide prior to irradiation. Similar regimens containing platinum derivatives are also used for non-germinomatous GCTs with very encouraging results. However, due to a greater understanding of the biology of the disease’s various molecular subtypes, new agents based on targeted therapy are expected in the future. On behalf of the EURACAN domain 10 group, we reviewed the most important and recent developments in histopathological characteristics, neuro-radiological assessments, and treatments for pineal region tumors.
Comparative Multicentric Evaluation of Inter-Observer Variability in Manual and Automatic Segmentation of Neuroblastic Tumors in Magnetic Resonance Images
Authors: Veiga-Canuto Diana , Cerdà-Alberich Leonor , Sangüesa Nebot Cinta , Martínez de las Heras Blanca , Pötschger Ulrike , Gabelloni Michela , Carot Sierra José Miguel , Taschner-Mandl Sabine , Düster Vanessa , Cañete Adela , Ladenstein Ruth , Neri Emanuele , Martí-Bonmatí Luis
Published: July 2022

Tumor segmentation is one of the key steps in imaging processing. The goals of this study were to assess the inter-observer variability in manual segmentation of neuroblastic tumors and to analyze whether the state-of-the-art deep learning architecture nnU-Net can provide a robust solution to detect and segment tumors on MR images. A retrospective multicenter study of 132 patients with neuroblastic tumors was performed. Dice Similarity Coefficient (DSC) and Area Under the Receiver Operating Characteristic Curve (AUC ROC) were used to compare segmentation sets. Two more metrics were elaborated to understand the direction of the errors: the modified version of False Positive (FPRm) and False Negative (FNR) rates. Two radiologists manually segmented 46 tumors and a comparative study was performed. nnU-Net was trained-tuned with 106 cases divided into five balanced folds to perform cross-validation. The five resulting models were used as an ensemble solution to measure training (n = 106) and validation (n = 26) performance, independently. The time needed by the model to automatically segment 20 cases was compared to the time required for manual segmentation. The median DSC for manual segmentation sets was 0.969 (±0.032 IQR). The median DSC for the automatic tool was 0.965 (±0.018 IQR). The automatic segmentation model achieved a better performance regarding the FPRm. MR images segmentation variability is similar between radiologists and nnU-Net. Time leverage when using the automatic model with posterior visual validation and manual adjustment corresponds to 92.8%.
Vitamin D, Th17 Lymphocytes, and Breast Cancer
Authors: Filip-Psurska Beata , Zachary Honorata , Strzykalska Aleksandra , Wietrzyk Joanna
Published: July 2022

Vitamin D3, which is well known to maintain calcium homeostasis, plays an important role in various cellular processes. It regulates the proliferation and differentiation of several normal cells, including immune and neoplastic cells, influences the cell cycle, and stimulates cell maturation and apoptosis through a mechanism dependent on the vitamin D receptor. The involvement of vitamin D3 in breast cancer development has been observed in numerous clinical studies. However, not all studies support the protective effect of vitamin D3 against the development of this condition. Furthermore, animal studies have revealed that calcitriol or its analogs may stimulate tumor growth or metastasis in some breast cancer models. It has been postulated that the effect of vitamin D3 on T helper (Th) 17 lymphocytes is one of the mechanisms promoting metastasis in these murine models. Herein we present a literature review on the existing data according to the interplay between vitamin D, Th17 cell and breast cancer. We also discuss the effects of this vitamin on Th17 lymphocytes in various disease entities known to date, due to the scarcity of scientific data on Th17 lymphocytes and breast cancer. The presented data indicate that the effect of vitamin D3 on breast cancer development depends on many factors, such as age, menopausal status, or obesity. According to that, more extensive clinical trials and studies are needed to assess the importance of vitamin D in breast cancer, especially when no correlations seem to be obvious.
The Prediction of Cardiac Events Using Contemporary Risk Prediction Models after Radiation Therapy for Head and Neck Cancer
Authors: Alvi Raza M. , Quinaglia Thiago , Spahillari Aferdita , Suero-Abreu Giselle A. , Hassan Malek Z. O. , Gongora Carlos , Gilman Hannah K. , Nikolaidou Sofia , Sama Supraja , Wirth Lori J. , Chan Annie W. , Addison Daniel , Neilan Tomas G.
Published: July 2022

This study aims to evaluate the efficacy of the Pooled Cohort Equation (PCE), U.S. Preventative Services Task Force (USPSTF), and Framingham Risk Score (FRS) models in predicting ASCVD events among patients receiving radiation therapy (RT) for head and neck cancer (HNCA). From a large cohort of HNCA patients treated with RT, ASCVD events were adjudicated. Observed vs. predicted ASCVD events were compared. We compared rates by statin eligibility status. Regression models and survival analysis were used to identify the relationship between predicted risk and post-RT outcomes. Among the 723 identified patients, 274 (38%) were statin-eligible based on USPSTF criteria, 359 (49%) based on PCE, and 234 (32%) based on FRS. During follow-up, 17% developed an ASCVD, with an event rate of 27 per 1000 person-years, 68% higher than predicted (RR 1.68 (95% CI: 1.02, 2.12), p < 0.001). In multivariable regression, there was no difference in event rates by statin eligibility status (p > 0.05). Post-RT, the observed event rate was higher than the predicted ASCVD risk across all grades of predicted risk (p < 0.05) and the observed risk of an ASCVD event was high even among patients predicted to have a low risk of ASCVD. In conclusion, current ASCVD risk calculators significantly underestimate the risk for ASCVD among patients receiving RT for HNCA.
Leydig Cell Tumors of the Testis: An Update of the Imaging Characteristics of a Not So Rare Lesion
Authors: Maxwell Florian , Savignac Alexia , Bekdache Omar , Calvez Sandra , Lebacle Cédric , Arama Emmanuel , Garrouche Nada , Rocher Laurence
Published: July 2022

Pre-operative testicular tumor characterization is a challenge for radiologists and urologists. New data concerning imaging approaches or immunochemistry markers improve the management of patients presenting with a testicular tumor, sometimes avoiding radical orchiectomy. In the past 20 years, imaging modalities, especially ultrasound (US) and magnetic resonance imaging (MRI), improved, allowing for great progress in lesion characterization. Leydig cell tumors (LCT) are rare testicular tumors developing from the stromal tissue, with relatively scarce literature, as most of the studies focus on the much more frequent germ cell tumors. However, with the increase in testicular sonography numbers, the incidence of LCT appears much higher than expected, with some studies reporting up to 22% of small testicular nodules. Multimodal ultrasound using Doppler, Elastography, or injection of contrast media can provide crucial arguments to differentiate LCT from germ cell tumors. Multiparametric MRI is a second intention exam, but it allows for extraction of quantifiable data to assess the diagnosis of LCT. The aims of this article are to review the latest data regarding LCT imaging features, using multimodal ultrasound and multiparametric MRI, and to focus on the peculiar aspect of the testis of patients with Klinefelter’s syndrome. The possibility of an LCT should be raised in front of a small hypoechoic tumor with a marked corbelling hypervascularization in an otherwise normal testicular pulp. Ultrasonographic modules, such as ultrasensitive Doppler, contrast-enhanced ultrasonography, or elastography, can be used to reinforce the suspicion of LCT. MRI provides objective data regarding vascularization and enhancement kinetics.
Radiomic Signatures Associated with CD8+ Tumour-Infiltrating Lymphocytes: A Systematic Review and Quality Assessment Study
Authors: Ramlee Syafiq , Hulse David , Bernatowicz Kinga , Pérez-López Raquel , Sala Evis , Aloj Luigi
Published: July 2022

The tumour immune microenvironment influences the efficacy of immune checkpoint inhibitors. Within this microenvironment are CD8-expressing tumour-infiltrating lymphocytes (CD8+ TILs), which are an important mediator and marker of anti-tumour response. In practice, the assessment of CD8+ TILs via tissue sampling involves logistical challenges. Radiomics, the high-throughput extraction of features from medical images, may offer a novel and non-invasive alternative. We performed a systematic review of the available literature reporting radiomic signatures associated with CD8+ TILs. We also aimed to evaluate the methodological quality of the identified studies using the Radiomics Quality Score (RQS) tool, and the risk of bias and applicability with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Articles were searched from inception until 31 December 2021, in three electronic databases, and screened against eligibility criteria. Twenty-seven articles were included. A wide variety of cancers have been studied. The reported radiomic signatures were heterogeneous, with very limited reproducibility between studies of the same cancer group. The overall quality of studies was found to be less than desirable (mean RQS = 33.3%), indicating a need for technical maturation. Some potential avenues for further investigation are also discussed.
The Differential Metabolic Signature of Breast Cancer Cellular Response to Olaparib Treatment
Authors: Berardi Domenica , Hunter Yasmin , van den Driest Lisa , Farrell Gillian , Rattray Nicholas J. W. , Rattray Zahra
Published: July 2022

Metabolic reprogramming and genomic instability are key hallmarks of cancer, the combined analysis of which has gained recent popularity. Given the emerging evidence indicating the role of oncometabolites in DNA damage repair and its routine use in breast cancer treatment, it is timely to fingerprint the impact of olaparib treatment in cellular metabolism. Here, we report the biomolecular response of breast cancer cell lines with DNA damage repair defects to olaparib exposure. Following evaluation of olaparib sensitivity in breast cancer cell lines, we immunoprobed DNA double strand break foci and evaluated changes in cellular metabolism at various olaparib treatment doses using untargeted mass spectrometry-based metabolomics analysis. Following identification of altered features, we performed pathway enrichment analysis to measure key metabolic changes occurring in response to olaparib treatment. We show a cell-line-dependent response to olaparib exposure, and an increased susceptibility to DNA damage foci accumulation in triple-negative breast cancer cell lines. Metabolic changes in response to olaparib treatment were cell-line and dose-dependent, where we predominantly observed metabolic reprogramming of glutamine-derived amino acids and lipids metabolism. Our work demonstrates the effectiveness of combining molecular biology and metabolomics studies for the comprehensive characterisation of cell lines with different genetic profiles. Follow-on studies are needed to map the baseline metabolism of breast cancer cells and their unique response to drug treatment. Fused with genomic and transcriptomics data, such readout can be used to identify key oncometabolites and inform the rationale for the design of novel drugs or chemotherapy combinations.
Ni-H-Beta Catalysts for Ethylene Oligomerization: Impact of Parent Cation on Ni Loading, Speciation, and Siting
Authors: McCaig Joseph , Lamb H. Henry
Published: July 2022

Ni-H-Beta catalysts for ethylene oligomerization (EO) were prepared by ion exchange of NH4-Beta and H-Beta zeolites with aqueous Ni(NO3)2 and characterized by H2-temperature-programmed reduction (TPR), NH3-temperature-programmed desorption (TPD), and diffuse-reflectance infrared Fourier-transform spectroscopy (DRIFTS). Quadruple exchange of NH4-Beta at 70 °C resulted in 2.5 wt.% Ni loading corresponding to a Ni2+/framework aluminum (FAl) molar ratio of 0.52. [NiOH]+ and H+ are the primary charge-compensating cations in the uncalcined catalyst, as evidenced by TPR and DRIFTS. Subsequent calcination at 550 °C in air yielded a Ni-H-Beta catalyst containing primarily bare Ni2+ ions bonded to framework oxygens. Quadruple exchange of H-Beta at 70 °C gave 2.0 wt.% Ni loading (Ni2+/FAl = 0.41). After calcination at 550 °C, the resulting Ni-H-Beta catalyst comprises a mixture of bare Ni2+ ions: [NiOH]+ and NiO species. The relative abundance of [NiOH]+ increases with the number of exchanges. In situ pretreatment at 500 °C in flowing He converted the [NiOH]+ species to bare Ni2+ ions via dehydration. The bare Ni2+ ions interact strongly with the Beta framework as evidenced by a perturbed antisymmetric T-O-T vibration at 945 cm−1. DRIFT spectra of CO adsorbed at 20 °C indicate that the Ni2+ ions occupy two distinct exchange positions. The results of EO testing at 225 °C and 11 bar (ethylene) suggested that the specific Ni2+ species initially presented (e.g., bare Ni2+, [NiOH]+) did not significantly affect the catalytic performance.
Importance of the Microenvironment and Mechanosensing in Adipose Tissue Biology
Authors: Lecoutre Simon , Lambert Mélanie , Drygalski Krzysztof , Dugail Isabelle , Maqdasy Salwan , Hautefeuille Mathieu , Clément Karine
Published: July 2022

The expansion of adipose tissue is an adaptive mechanism that increases nutrient buffering capacity in response to an overall positive energy balance. Over the course of expansion, the adipose microenvironment undergoes continual remodeling to maintain its structural and functional integrity. However, in the long run, adipose tissue remodeling, typically characterized by adipocyte hypertrophy, immune cells infiltration, fibrosis and changes in vascular architecture, generates mechanical stress on adipose cells. This mechanical stimulus is then transduced into a biochemical signal that alters adipose function through mechanotransduction. In this review, we describe the physical changes occurring during adipose tissue remodeling, and how they regulate adipose cell physiology and promote obesity-associated dysfunction in adipose tissue.