bluuebunny/crossref_metadata_2025 huggingface dataset:
The Y831C Mutation of the POLG Gene in Dementia
Authors: Borgione Eugenia , Lo Giudice Mariangela , Santa Paola Sandro , Giuliano Marika , Lanza Giuseppe , Cantone Mariagiovanna , Ferri Raffaele , Scuderi Carmela
Published: April 2023

Background: The POLG gene encodes the catalytic subunit of DNA polymerase γ, which is crucial for mitochondrial DNA (mtDNA) repair and replication. Gene mutation alters the stability of mtDNA and is associated with several clinical presentations, such as dysarthria and ophthalmoplegia (SANDO), progressive external ophthalmoplegia (PEO), spinocerebellar ataxia and epilepsy (SCAE), Alpers syndrome, and sensory ataxic neuropathy. Recent evidence has also indicated that POLG mutations may be involved in some neurodegenerative disorders, although systematic screening is currently lacking. Methods: To investigate the frequency of POLG gene mutations in neurodegenerative disorders, we screened a group of 33 patients affected by neurodegenerative diseases, including Parkinson’s disease, some atypical parkinsonisms, and dementia of different types. Results: Mutational analysis revealed the presence of the heterozygous Y831C mutation in two patients, one with frontotemporal dementia and one with Lewy body dementia. The allele frequency of this mutation reported by the 1000 Genomes Project in the healthy population is 0.22%, while in our group of patients, it was 3.03%, thus showing a statistically significant difference between the two groups. Conclusions: Our results may expand the genotype-phenotype spectrum associated with mutations in the POLG gene and strengthen the hypothesis of a pathogenic role of the Y831C mutation in neurodegeneration.
Urine Dipstick Analysis on Automated Platforms: Is a Reliable Screening Tool for Proteinuria? An Experience from Umberto I Hospital in Rome
Authors: Terracina Sergio , Pallaria Antonio , Lucarelli Marco , Angeloni Antonio , De Angelis Annarita , Ceci Flavio Maria , Caronti Brunella , Francati Silvia , Blaconà Giovanna , Fiore Marco , Ferraguti Giampiero
Published: April 2023

Urinalysis is commonly used as a screening tool for kidney disease. In many cases, the dipstick urine assay includes the assessment of albumin/protein and creatinine; consequently, the value of their ratio is available on the urine section report. Identification of albuminuria/proteinuria at early stages is an important issue to prevent or at least delay the onset of chronic kidney disease (CKD), kidney failure, and the progression of cardiovascular damage linked to the kidney’s loss of function. Sensitive and specific diagnostic methods are required for the assessment of such an important biomarker: urine albumin, creatinine, and their ratio (ACR) measured with quantitative assays are considered the gold standard. Routine dipstick methods (more rapid and at a lower cost) are intended for wide population screening. The aim of our study was to verify the reliability of an automated urinalysis dipstick method by comparing the results with the quantitative test of creatinine and albumin performed on a clinical chemistry platform. The first-morning voids of 249 patients who arrived from different departments were analyzed in the Central Laboratory of the University Hospital Policlinico Umberto I in Rome. We found a good correlation between the two assays, even though we observed that the dipstick assessment tends to overestimate the ACR’s value, disclosing a higher number of false positives if compared to the reference method. As an important novelty in this study, we analyzed our data considering age (starting from pediatric to geriatric patients) and sex as variables for a sub-stratification of the participants. Our results show that positive values need to be confirmed with quantitative methods, especially in women and younger people, and that from samples that resulted as diluted at the dipstick assay, the ACR’s values can be obtained if they are reanalyzed with quantitative assays. Moreover, patients with microalbuminuria (ACR 30–300 mg/g) or severe albumin urinary excretion (ACR > 300 mg/g) should be reanalyzed using quantitative methods to obtain a more reliable calculation of the ACR.
Effects of Blood Contamination and Decontamination Protocol on Reverse Torque Value of Abutment Screws in Dental Implants: An In Vitro Study
Authors: Adawi Hafiz A. , Dewan Harisha , Khawaji Arwa , Akkam Hadeel , Hakami Areej , Wasli Bashair , Hakami Maram , Alali Maimonah , Chohan Hitesh
Published: April 2023

Background and Objective: Loosening of abutment screws in dental implants is a mechanical complication that affects prosthetic treatments and hence, patient satisfaction. Blood contamination of abutment screws may play a role in this phenomenon. However, only limited research attention has been given to this issue. In the present study, we determined the effect of blood contamination and decontamination protocol on the reverse torque value (RTV) of abutment screws. Materials and Methods: A questionnaire-based survey was sent to 210 implantologists requesting feedback on their attitude to the blood contamination issue and the decontamination protocols used. The survey responses were used in a selection of the decontamination solutions that were used in the subsequent in vitro study on the effects of blood decontamination protocol on the RTV of abutment screws. Thus, three study groups were used (n = 20 abutment screws in each group): Group 1 (control group; blood-contaminated screws); Group 2 (screws decontaminated with 5.25% sodium hypochlorite (NaOCl) solution); and Group 3 (screws decontaminated with normal saline solution (0.9%)). Then, each of the connections were subjected to thermocycling, and RTVs of the screw were measured using a digital torque meter. Intragroup and intergroup RTVs were analyzed for significance using analysis of variance (ANOVA) and Tukey’s honestly significant difference (HSD) tests. Results: 48% of the implantologists responded to the survey; 80% of them were concerned with blood contamination in the implant connection, especially before abutment loading and 85% of them used either chlorhexidine solution or normal saline solution as the decontamination agent. The mean RTV for Group 2 screws (30.27 ± 2.8 N.cm) was significantly greater than that for Group 3 screws (26.02 ± 1.99 N.cm) which, in turn, was significantly greater than that for Group 1 screws (23.64 ± 1.84 N.cm). Conclusion: Decontamination of blood-covered connections using 5.25% NaOCl solution or normal saline solution restores the RTV of abutment screws. This finding may have clinical relevance in that the decontaminated screws may contribute to the low incidence of screw loosening and, ultimately, improved patient satisfaction.
Systematic Review of Single-Agent vs. Multi-Agent Chemotherapy for Advanced Pancreatic Adenocarcinoma in Elderly vs. Younger Patients
Authors: Lewis Alison , Nagrial Adnan
Published: April 2023

Purpose: To systematically review all studies comparing multi-agent to single-agent chemotherapy in the first and second-line setting for unresectable pancreatic adenocarcinoma, so as to compare the outcomes of young and elderly patients. Methods: This review searched three databases for relevant studies. The inclusion criteria were diagnosis of locally advanced or metastatic pancreatic adenocarcinoma, comparison of an elderly versus young population, comparison of single-agent versus multi-agent chemotherapy, data on survival outcomes, and randomised controlled trials. The exclusion criteria were phase I trials, incomplete studies, retrospective analyses, systematic reviews, and case reports. A meta-analysis was performed on second-line chemotherapy in elderly patients. Results: Six articles were included in this systematic review. Three of these studies explored first-line treatment and three explored second-line treatment. In the subgroup analysis, the meta-analysis showed statistically improved overall survival for elderly patients receiving single-agent second-line treatment. Conclusions: This systematic review confirmed that combination chemotherapy improved survival in the first-line treatment of advanced pancreatic adenocarcinoma, regardless of age. The benefit of combination chemotherapy in second-line studies for elderly patients with advanced pancreas cancer was less clear.
Last Resort from Nursing Shortage? Comparative Cost Analysis of Open vs. Robot-Assisted Partial Nephrectomies with a Focus on the Costs of Nursing Care
Authors: Zeuschner Philip , Böttcher Carolin , Hager Lutz , Linxweiler Johannes , Stöckle Michael , Siemer Stefan
Published: April 2023

Despite perioperative advantages, robot-assisted surgery is associated with high costs. However, the lower morbidity of robotic surgery could lead to a lower nursing workload and cost savings. In this comparative cost analysis of open retroperitoneal versus robot-assisted transperitoneal partial nephrectomies (PN), these possible cost savings, including other cost factors, were quantified. Therefore, patient, tumor characteristics, and surgical results of all PN within two years at a tertiary referral center were retrospectively analyzed. The nursing effort was quantified by the local nursing staff regulation and INPULS® intensive care and performance-recording system. Out of 259 procedures, 76.4% were performed robotically. After propensity score matching, the median total nursing time (2407.8 vs. 1126.8 min, p < 0.001) and daily nursing effort (245.7 vs. 222.6 min, p = 0.025) were significantly lower after robotic surgery. This resulted in mean savings of EUR 186.48 in nursing costs per robotic case, in addition to savings of EUR 61.76 due to less frequent administrations of erythrocyte concentrates. These savings did not amortize the higher material costs for the robotic system, causing additional expenses of EUR 1311.98 per case. To conclude, the nursing effort after a robotic partial nephrectomy was significantly lower compared to open surgery; however, this previously unnoticed savings mechanism alone could not amortize the overall increased costs.
Special Issue of Cancers: “Retinoblastoma: Current Challenges and Promising New Approaches”
Authors: Munier Francis L.
Published: April 2023

Despite being a rare pediatric cancer arising in the developing retina from red/green cone precursors, retinoblastoma is the most common eye cancer worldwide and occupies an emblematic position in oncology and human genetics for the following reasons:-Historically, the discovery of RB1 and the recessive nature of its mutations led to the prototypic description of anti-oncogenes or tumor suppressor genes [...]
TGF-β as Predictive Marker and Pharmacological Target in Lung Cancer Approach
Authors: Ramundo Valeria , Palazzo Maria Luisa , Aldieri Elisabetta
Published: April 2023

Lung cancer (LC) represents the leading cause of cancer incidence and mortality worldwide. LC onset is strongly related to genetic mutations and environmental interactions, such as tobacco smoking, or pathological conditions, such as chronic inflammation. Despite advancement in knowledge of the molecular mechanisms involved in LC, this tumor is still characterized by an unfavorable prognosis, and the current therapeutic options are unsatisfactory. TGF-β is a cytokine that regulates different biological processes, particularly at the pulmonary level, and its alteration has been demonstrated to be associated with LC progression. Moreover, TGF-β is involved in promoting invasiveness and metastasis, via epithelial to mesenchymal transition (EMT) induction, where TGF-β is the major driver. Thus, a TGF-β-EMT signature may be considered a potential predictive marker in LC prognosis, and TGF-β-EMT inhibition has been demonstrated to prevent metastasis in various animal models. Concerning a LC therapeutic approach, some TGF-β and TGF-β-EMT inhibitors could be used in combination with chemo- and immunotherapy without major side effects, thereby improving cancer therapy. Overall, targeting TGF-β may be a valid possibility to fight LC, both in improving LC prognosis and cancer therapy, via a novel approach that could open up new effective strategies against this aggressive cancer.
Radiomics of Tumor Heterogeneity in 18F-FDG-PET-CT for Predicting Response to Immune Checkpoint Inhibition in Therapy-Naïve Patients with Advanced Non-Small-Cell Lung Cancer
Authors: Ventura David , Schindler Philipp , Masthoff Max , Görlich Dennis , Dittmann Matthias , Heindel Walter , Schäfers Michael , Lenz Georg , Wardelmann Eva , Mohr Michael , Kies Peter , Bleckmann Annalen , Roll Wolfgang , Evers Georg
Published: April 2023

We aimed to evaluate the predictive and prognostic value of baseline 18F-FDG-PET-CT (PET-CT) radiomic features (RFs) for immune checkpoint-inhibitor (CKI)-based first-line therapy in advanced non-small-cell lung cancer (NSCLC) patients. In this retrospective study 44 patients were included. Patients were treated with either CKI-monotherapy or combined CKI-based immunotherapy–chemotherapy as first-line treatment. Treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). After a median follow-up of 6.4 months patients were stratified into “responder” (n = 33) and “non-responder” (n = 11). RFs were extracted from baseline PET and CT data after segmenting PET-positive tumor volume of all lesions. A Radiomics-based model was developed based on a Radiomics signature consisting of reliable RFs that allow classification of response and overall progression using multivariate logistic regression. These RF were additionally tested for their prognostic value in all patients by applying a model-derived threshold. Two independent PET-based RFs differentiated well between responders and non-responders. For predicting response, the area under the curve (AUC) was 0.69 for “PET-Skewness” and 0.75 predicting overall progression for “PET-Median”. In terms of progression-free survival analysis, patients with a lower value of PET-Skewness (threshold < 0.2014; hazard ratio (HR) 0.17, 95% CI 0.06–0.46; p < 0.001) and higher value of PET-Median (threshold > 0.5233; HR 0.23, 95% CI 0.11–0.49; p < 0.001) had a significantly lower probability of disease progression or death. Our Radiomics-based model might be able to predict response in advanced NSCLC patients treated with CKI-based first-line therapy.
The Prevalence of Back Pain in Patients Operated on Due to Colorectal Cancer Depending on the Type of Surgical Procedure Performed
Authors: Głowacka-Mrotek Iwona , Jankowski Michał , Skonieczny Bartosz , Tarkowska Magdalena , Ratuszek-Sadowska Dorota , Lewandowska Anna , Nowikiewicz Tomasz , Ogurkowski Karol , Zegarski Wojciech , Mackiewicz-Milewska Magdalena
Published: April 2023

Purpose: Low back pain presents a serious challenge for numerous medical specialties. The purpose of this study was to assess disability due to low back pain in patients operated on due to colorectal cancer depending on the type of surgery performed. Methods: This prospective observational study was carried out in the period of July 2019 through March 2020. Included in the study were patients with colorectal cancer for scheduled surgeries including anterior resection of rectum (AR), laparoscopic anterior resection of rectum (LAR), Hartmann’s procedure (HART), or abdominoperineal resection of rectum (APR). The Oswestry Low Back Pain Disability Questionnaire was used as the research tool. The study patients were surveyed at three time points: before surgery, six months after surgery, and one year after surgery. Results: The analysis of study results revealed that an increase in the degree of disability and functioning impairment occurred in all groups between time points I and II, with the differences being statistically significant (p < 0.05). The inter-group comparative analysis of the total Oswestry questionnaire scores revealed statistically significant differences, with the impairment of function being most severe within the APR group and least severe within the LAR group. Conclusion: The study results showed that low back pain contributes to impaired functioning of patients operated on due to colorectal cancer regardless of the type of procedure performed. A reduction in the degree of disability due to low back pain was observed one year after the procedure in patients having undergone LAR.
An Aptamer That Rapidly Internalizes into Cancer Cells Utilizes the Transferrin Receptor Pathway
Authors: Song Xirui , Yu Haixiang , Sullenger Cynthia , Gray Bethany Powell , Yan Amy , Kelly Linsley , Sullenger Bruce
Published: April 2023

Strategies to direct drugs specifically to cancer cells have been increasingly explored, and significant progress has been made toward such targeted therapy. For example, drugs have been conjugated into tumor-targeting antibodies to enable delivery directly to tumor cells. Aptamers are an attractive class of molecules for this type of drug targeting as they are high-affinity/high-specificity ligands, relatively small in size, GMP manufacturable at a large-scale, amenable to chemical conjugation, and not immunogenic. Previous work from our group revealed that an aptamer selected to internalize into human prostate cancer cells, called E3, can also target a broad range of human cancers but not normal control cells. Moreover, this E3 aptamer can deliver highly cytotoxic drugs to cancer cells as Aptamer-highly Toxic Drug Conjugates (ApTDCs) and inhibit tumor growth in vivo. Here, we evaluate its targeting mechanism and report that E3 selectively internalizes into cancer cells utilizing a pathway that involves transferrin receptor 1 (TfR 1). E3 binds to recombinant human TfR 1 with high affinity and competes with transferrin (Tf) for binding to TfR1. In addition, knockdown or knockin of human TfR1 results in a decrease or increase in E3 cell binding. Here, we reported a molecular model of E3 binding to the transferrin receptor that summarizes our findings.
Myeloid NGS Analyses of Paired Samples from Bone Marrow and Peripheral Blood Yield Concordant Results: A Prospective Cohort Analysis of the AGMT Study Group
Authors: Jansko-Gadermeir Bettina , Leisch Michael , Gassner Franz J. , Zaborsky Nadja , Dillinger Thomas , Hutter Sonja , Risch Angela , Melchardt Thomas , Egle Alexander , Drost Manuel , Larcher-Senn Julian , Greil Richard , Pleyer Lisa
Published: April 2023

Background: Next generation sequencing (NGS) has become indispensable for diagnosis, risk stratification, prognostication, and monitoring of response in patients with myeloid neoplasias. Guidelines require bone marrow evaluations for the above, which are often not performed outside of clinical trials, indicating a need for surrogate samples. Methods: Myeloid NGS analyses (40 genes and 29 fusion drivers) of 240 consecutive, non-selected, prospectively collected, paired bone marrow/peripheral blood samples were compared. Findings: Very strong correlation (r = 0.91, p < 0.0001), high concordance (99.6%), sensitivity (98.8%), specificity (99.9%), positive predictive value (99.8%), and negative predictive value (99.6%) between NGS analyses of paired samples was observed. A total of 9/1321 (0.68%) detected mutations were discordant, 8 of which had a variant allele frequency (VAF) ≤ 3.7%. VAFs between peripheral blood and bone marrow samples were very strongly correlated in the total cohort (r = 0.93, p = 0.0001) and in subgroups without circulating blasts (r = 0.92, p < 0.0001) or with neutropenia (r = 0.88, p < 0.0001). There was a weak correlation between the VAF of a detected mutation and the blast count in either the peripheral blood (r = 0.19) or the bone marrow (r = 0.11). Interpretation: Peripheral blood samples can be used to molecularly classify and monitor myeloid neoplasms via NGS without loss of sensitivity/specificity, even in the absence of circulating blasts or in neutropenic patients.
Photocatalytic Activity and Stability of Organically Modified Layered Perovskite-like Titanates HLnTiO4 (Ln = La, Nd) in the Reaction of Hydrogen Evolution from Aqueous Methanol
Authors: Kurnosenko Sergei A. , Voytovich Vladimir V. , Silyukov Oleg I. , Rodionov Ivan A. , Zvereva Irina A.
Published: April 2023

Two series of hybrid inorganic–organic materials, prepared via interlayer organic modification of protonated Ruddlesden–Popper phases HLnTiO4 (Ln = La, Nd) with n-alkylamines and n-alkoxy groups of various lengths, have been systematically studied with respect to photocatalytic hydrogen evolution from aqueous methanol under near-ultraviolet irradiation for the first time. Photocatalytic measurements were organized in such a way as to control a wide range of parameters, including the hydrogen generation rate, quantum efficiency of the reaction, potential dark activity of the sample, its actual volume concentration in the suspension, pH of the medium and stability of the photocatalytic material under the operating conditions. The insertion of the organic modifiers into the interlayer space of the titanates allowed obtaining new, more efficient photocatalytic materials, being up to 68 and 29 times superior in the activity in comparison with the initial unmodified compounds HLnTiO4 and a reference photocatalyst TiO2 P25 Degussa, respectively. The hydrogen evolution rate over the samples correlates with the extent of their interlayer hydration, as in the case of the inorganic–organic derivatives of other layered perovskites reported earlier. However, the HLnTiO4-based samples demonstrate increased stability with regard to the photodegradation of the interlayer organic components as compared with related H2Ln2Ti3O10-based hybrid materials.
Application of Laccase Catalysis in Bond Formation and Breakage: A Review
Authors: Lin Huan , Yu Zongjiang , Wang Qian , Liu Yaojie , Jiang Long , Xu Chao , Xian Mo
Published: April 2023

Laccase belongs to the superfamily of multicopper oxidases and has been widely investigated in recent decades. Due to its mild and efficient oxidation of substrates, laccase has been successfully applied in organic catalytic synthesis, the degradation of harmful substances, and other green catalytic fields. Nevertheless, there are few reports on the green catalysis with laccase. This review focuses on reporting and collating some of the latest interesting laccase-catalyzed bond formation and breakage research. This is discussed with a focus on the effects of the medium system on the laccase-catalyzed reaction, as well as the formation and the breakage of C–N, C–C, and C–O bonds catalyzed by laccase. It provides abundant references and novel insights for furthering the industrial applications of laccase.
Multiple Roles of cAMP in Vertebrate Retina
Authors: Erofeeva Natalia , Meshalkina Darya , Firsov Michael
Published: April 2023

cAMP is a key regulatory molecule that controls many important processes in the retina, including phototransduction, cell development and death, growth of neural processes, intercellular contacts, retinomotor effects, and so forth. The total content of cAMP changes in the retina in a circadian manner following the natural light cycle, but it also shows local and even divergent changes in faster time scales in response to local and transient changes in the light environment. Changes in cAMP might also manifest or cause various pathological processes in virtually all cellular components of the retina. Here we review the current state of knowledge and understanding of the regulatory mechanisms by which cAMP influences the physiological processes that occur in various retinal cells.
Differential Expression of Non-Coding RNAs in Stem Cell Development and Therapeutics of Bone Disorders
Authors: Mishra Anurag , Kumar Rishabh , Mishra Satya Narayan , Vijayaraghavalu Sivakumar , Tiwari Neeraj Kumar , Shukla Girish C. , Gurusamy Narasimman , Kumar Munish
Published: April 2023

Stem cells’ self-renewal and multi-lineage differentiation are regulated by a complex network consisting of signaling factors, chromatin regulators, transcription factors, and non-coding RNAs (ncRNAs). Diverse role of ncRNAs in stem cell development and maintenance of bone homeostasis have been discovered recently. The ncRNAs, such as long non-coding RNAs, micro RNAs, circular RNAs, small interfering RNA, Piwi-interacting RNAs, etc., are not translated into proteins but act as essential epigenetic regulators in stem cells’ self-renewal and differentiation. Different signaling pathways are monitored efficiently by the differential expression of ncRNAs, which function as regulatory elements in determining the fate of stem cells. In addition, several species of ncRNAs could serve as potential molecular biomarkers in early diagnosis of bone diseases, including osteoporosis, osteoarthritis, and bone cancers, ultimately leading to the development of new therapeutic strategies. This review aims to explore the specific roles of ncRNAs and their effective molecular mechanisms in the growth and development of stem cells, and in the regulation of osteoblast and osteoclast activities. Furthermore, we focus on and explore the association of altered ncRNA expression with stem cells and bone turnover.
The Regulation and Double-Edged Roles of the Deubiquitinase OTUD5
Authors: Fu Lin , Lu Kun , Jiao Qian , Chen Xi , Jia Fengju
Published: April 2023

OTUD5 (OTU Deubiquitinase 5) is a functional cysteine protease with deubiquitinase activity and is a member of the ovarian tumor protease (OTU) family. OTUD5 is involved in the deubiquitination of many key proteins in various cellular signaling pathways and plays an important role in maintaining normal human development and physiological functions. Its dysfunction can affect physiological processes, such as immunity and DNA damage repair, and it can even lead to tumors, inflammatory diseases and genetic disorders. Therefore, the regulation of OTUD5 activity and expression has become a hot topic of research. A comprehensive understanding of the regulatory mechanisms of OTUD5 and its use as a therapeutic target for diseases is of great value. Herein, we review the physiological processes and molecular mechanisms of OTUD5 regulation, outline the specific regulatory processes of OTUD5 activity and expression, and link OTUD5 to diseases from the perspective of studies on signaling pathways, molecular interactions, DNA damage repair and immune regulation, thus providing a theoretical basis for future studies.
Timing of Interleukin-4 Stimulation of Macrophages Determines Their Anti-Microbial Activity during Infection with Salmonella enterica Serovar Typhimurium
Authors: Brigo Natascha , Neumaier Emely , Pfeifhofer-Obermair Christa , Grubwieser Philipp , Engl Sabine , Berger Sylvia , Seifert Markus , Reinstadler Vera , Oberacher Herbert , Weiss Günter
Published: April 2023

Priming of macrophages with interferon-gamma (IFNγ) or interleukin-4 (IL-4) leads to polarisation into pro-inflammatory or anti-inflammatory subtypes, which produce key enzymes such as inducible nitric oxide synthase (iNOS) and arginase 1 (ARG1), respectively, and in this way determine host responses to infection. Importantly, L-arginine is the substrate for both enzymes. ARG1 upregulation is associated with increased pathogen load in different infection models. However, while differentiation of macrophages with IL-4 impairs host resistance to the intracellular bacterium Salmonella enterica serovar Typhimurium (S.tm), little is known on the effects of IL-4 on unpolarised macrophages during infection. Therefore, bone-marrow-derived macrophages (BMDM) from C57BL/6N, Tie2Cre+/−ARG1fl/fl (KO), Tie2Cre−/−ARG1fl/fl (WT) mice were infected with S.tm in the undifferentiated state and then stimulated with IL-4 or IFNγ. In addition, BMDM of C57BL/6N mice were first polarised upon stimulation with IL-4 or IFNγ and then infected with S.tm. Interestingly, in contrast to polarisation of BMDM with IL-4 prior to infection, treatment of non-polarised S.tm-infected BMDM with IL-4 resulted in improved infection control whereas stimulation with IFNγ led to an increase in intracellular bacterial numbers compared to unstimulated controls. This effect of IL-4 was paralleled by decreased ARG1 levels and increased iNOS expression. Furthermore, the L-arginine pathway metabolites ornithine and polyamines were enriched in unpolarised cells infected with S.tm and stimulated with IL-4. Depletion of L-arginine reversed the protective effect of IL-4 toward infection control. Our data show that stimulation of S.tm-infected macrophages with IL-4 reduced bacterial multiplication via metabolic re-programming of L-arginine-dependent pathways.
Effect of Rigid Xanthan Gums (RXGs) on Flow and Pressure Drops to Improve Drag Reduction Rates in Horizontal Pipe Flow
Authors: Kadhim Bashar J. , Mahdy Omar S. , Alsaedi Sajda S. , Majdi Hasan S. , Shnain Zainab Y. , Alwaiti Asawer A. , AbdulRazak Adnan A.
Published: April 2023

Drag reduction in turbulent flow may be significantly reduced by adding tiny quantities of fiber, polymer, and surfactant particles to the liquid. Different drag-reduction agents have proven to be effective in enhancing the flowability of the liquid when added. This study investigated the potential of decreasing the drag, turbulent flow, and pressure drop in horizontal pipe flow by using a mixture of modified xanthan gums (XGs). Xanthan gums are an environmentally friendly natural polymer complex. They can be extracted from xanthan gum plants and utilized to formulate different concentrations of complexes. The flowability of the xanthan gum was experimentally investigated in a 1-m-long pipe by using addition concentrations of 300 to 950 ppm, an inner diameter of 0.254 inches, and four different flow rates. The results revealed that the pressure drop was reduced considerably with an increase in the concentration of the additives. The mixture (xanthan gums plus water) resulted a favorable reduction in the pressure, which reached 65% at a concentration of 950 ppm. The results of the computational fluid dynamic simulation using the COMSOL simulator showed a change in the fluid velocity profiles, which became more parabolic. This occurred because of an increase in the mean fluid velocity due to the addition of the drag-reducing polymers.
A Novel Highly Sensitive Chemiluminescence Enzyme Immunoassay with Signal Enhancement Using Horseradish Peroxidase-Luminol-Hydrogen Peroxide Reaction for the Quantitation of Monoclonal Antibodies Used for Cancer Immunotherapy
Authors: Darwish Ibrahim , Alzoman Nourah , Khalil Nehal
Published: April 2023

The development and validation of a novel enhanced chemiluminescence enzyme immunoassay (CLEIA) with excellent sensitivity for the quantification of monoclonal antibodies (mAbs) used for immunotherapy of cancer are described in this paper for the first time. The 96-microwell plates were used for the assay procedures, which involved the non-competitive binding reaction to a specific antigen. The immune complex of the antigen-mAb formed on the internal surface of the plate wells was quantified by a novel chemiluminescence (CL)-producing horseradish peroxidase (HRP) reaction. The reaction employed 4-(imidazol-1-yl)phenol (IMP) as a highly potent signal enhancer for the HRP-luminol–hydrogen peroxide (H2O2) CL reaction. The proposed CLEIA was developed for bevacizumab (BEV), as a representative example for mAbs. The CLEIA was validated in accordance with the immunoassay validation for bioanalysis standards, and all of the validation criteria were met. The assay’s limit of detection (LOD) and limit of quantitation (LOQ) were 9.3 and 28.2 pg mL−1, respectively, with a working dynamic range of 10–400 pg mL−1. The assay enables the accurate and precise quantitation of mAbs in human plasma samples without any interference from endogenous substances and/or plasma matrix. The novel CLEIA was compared in terms of dynamic range and sensitivity with other pre-validated enzyme-linked immunosorbent assay (ELISA) using HRP/colorimetric substrate as a detection system and the observed differences were explained. The CLEIA protocol’s ease of use, high throughput, and simplicity allows to analyze numerous samples in clinical settings. The proposed CLEIA has a significant benefit in the assessment of mAbs in clinical settings for the evaluation of their pharmacokinetics, pharmacodynamics, therapeutic drug monitoring, and refining their safety profiles, opening a new era for a better understanding of pharmacodynamics at the cellular level.
Elsberg Syndrome with Mixed Presentation as Meningitis Retention Syndrome: A Pediatric Case Report and Comprehensive Review of the Literature
Authors: Hsu Mandy , El Seblani Nader , Zhu Zahra , Ramisetty Bhuvaneswari , Day Christopher , Zachariah Jikku , Kaur Divpreet , Kumar Ashutosh , Paudel Sita , Paul Dustin , Kochar Puneet , Carney Paul , Naik Sunil
Published: April 2023

Elsberg syndrome is a typically infectious syndrome that may cause acute or subacute bilateral lumbosacral radiculitis and sometimes lower spinal cord myelitis. Patients often present with various neurological symptoms involving the lower extremities, including numbness, weakness, and urinary disturbances such as retention. A 9-year-old girl with no significant past medical history presented with altered mental status, fever, urinary retention, and anuria and was found to have encephalomyelitis. An extensive diagnostic workup led to ruling out possible etiologies until identifying Elsberg syndrome. In this report, we describe a case of Elsberg syndrome caused by West Nile virus (WNV). To the best of our knowledge, this is the first reported case of its kind in the pediatric population. Utilizing PubMed and Web of Science databases, we reviewed the literature to describe the neurogenic control of the urinary system in correlation to a multitude of neurologic pathologies.
Impact of Metal Accumulation on Photosynthetic Pigments, Carbon Assimilation, and Oxidative Metabolism in Mangroves Affected by the Fundāo Dam Tailings Plume
Authors: D’Addazio Veronica , Tognella Monica Maria Pereira , Fernandes Adriano Alves , Falqueto Antelmo Ralph , da Rosa Marcelo Barcellos , Gontijo Ivoney , de Oliveira Marcelo Antônio
Published: April 2023

The effects of iron, manganese, zinc, copper, and lead on the chlorophyll content, carbon assimilation, and the antiradical activity of Rhizophora mangle and Laguncularia racemosa were evaluated in regions affected by the Fundão dam disruption in Brazil. The mine waste which settled and accumulated in the sediments could represent long-term contamination. It can be expected that the iron oxyhydroxides deposited in the sediments will be solubilized, leading to chronic contamination by trace metals and the accumulation of these metals in the biota. In this sense, biological indicators prove to be important tools to assess this type of damage. The different bioaccumulation of metals by the species revealed that R. mangle was more impacted by Mn and Cu and that L. racemosa showed alterations in its physiological responses in the presence of Cu, Zn, and Fe. The concentration of these metals in the leaves, with values above previous local reference limits, was associated with reductions in the chlorophyll-a and chlorophyll-b content and carbon assimilation, mainly in L. racemosa. The antiradical activity was also altered, suggesting a lower ability of both species to eliminate reactive oxygen species (ROS). A possible reason for the symptoms of oxidative stress may be due to the reduced efficiency of antioxidant defense by Cu2+ and Zn2+. In addition, the presence of Pb in the leaf tissue may be toxic to the fauna and the bioaccumulation of this metal and trace elements can be a way to transfer them into the food web by biomagnification.
First Observation of Protomicelles in the System with a Non-Colloidal Surfactant
Authors: Rusanov Anatoly I. , Movchan Tamara G. , Plotnikova Elena V.
Published: April 2023

A spectrophotometric study of the system heptanol—Nile red (NR)—water was carried out, where, for the first time for such studies, a non-colloidal surfactant that does not form micelles was taken as a surfactant. The dependence of the solubility of NR on the concentration of heptanol in an aqueous solution was studied. The experiments were carried out at a given chemical potential of NR, which was provided by an excess of the solid phase of NR. The existence of a solubilization effect has been theoretically and experimentally established: An increase in the solubility of NR with an increase in the concentration of heptanol in solution. It was found that heptanol protomicelles with a solubilization core as an NR molecule are formed in such a system, so that in the absence of micelles, the protomicelles take on the entire solubilization load. From the experimental data, the concentration of protomicelle formation was calculated, which can also be taken as the concentration of NR monomerization in an aqueous solution, since the formation of protomicelles prevents the dye aggregation. Based on the results obtained, the following generalizations were made: (1) non-colloidal surfactants, although they do not give micelles, are capable of forming protomicelles; and (2) non-colloidal surfactants can serve as a practical means of dye monomerization.
Effects of Focused Ion Beam Lithography on La2−xSrxCuO4 Single Crystals
Authors: Caruso Roberta , Camino Fernando , Gu Genda , Tranquada John M. , Han Myung-Geun , Zhu Yimei , Bollinger Anthony T. , Božović Ivan
Published: April 2023

Focused ion beam (FIB) milling is a mask-free lithography technique that allows the precise shaping of 3D materials on the micron and sub-micron scale. The recent discovery of electronic nematicity in La2−xSrxCuO4 (LSCO) thin films triggered the search for the same phenomenon in bulk LSCO crystals. With this motivation, we have systematically explored FIB patterning of bulk LSCO crystals into micro-devices suitable for longitudinal and transverse resistivity measurements. We found that several detrimental factors can affect the result, ultimately compromising the possibility of effectively using FIB milling to fabricate sub-micrometer LSCO devices, especially in the underdoped regime.
Molecular Beam Epitaxy of Twin-Free Bi2Se3 and Sb2Te3 on In2Se3/InP(111)B Virtual Substrates
Authors: Wickramasinghe Kaushini S. , Forrester Candice , Tamargo Maria C.
Published: April 2023

Three-dimensional topological insulators (3D-TIs) are a new generation of materials with insulating bulk and exotic metallic surface states that facilitate a wide variety of ground-breaking applications. However, utilization of the surface channels is often hampered by the presence of crystal defects, such as antisites, vacancies, and twin domains. For terahertz device applications, twinning is shown to be highly deleterious. Previous attempts to reduce twins using technologically important InP(111) substrates have been promising, but have failed to completely suppress twin domains while preserving high structural quality. Here we report growth of twin-free molecular beam epitaxial Bi2Se3 and Sb2Te3 structures on ultra-thin In2Se3 layers formed by a novel selenium passivation technique during the oxide desorption of smooth, non-vicinal InP(111)B substrates, without the use of an indium source. The formation of un-twinned In2Se3 provides a favorable template to fully suppress twin domains in 3D-TIs, greatly broadening novel device applications in the terahertz regime.
Influence of the Arene/Perfluoroarene Ratio on the Structure and Non-Covalent Interactions in Crystals of Cd(II), Cd(II)-Tb(III) and Cu(II) Compounds
Authors: Voronina Julia K. , Yambulatov Dmitriy S. , Chistyakov Aleksander S. , Bolot’ko Alena E. , Efromeev Leonid M. , Shmelev Maxim A. , Sidorov Alexey A. , Eremenko Igor L.
Published: April 2023

The influence of arene/perfluoroarene ratio on the structure and crystal packing of carboxylate and nitrate-carboxylate complexes of Cd, Cd-Tb and Cu was studied, using the following compounds: pentafluorobenzoate (pfb) and 4-allyl-2,3,5,6-tetrabenzoate (Afb) anions and 1,10-phenanthroline (phen) composition [Cd(pfb)2(phen)]n (1), [Cd(NO3)(pfb)(phen)]n (2), [Tb2Cd2(pfb)10(phen)2]. 3MeCN]n (3), [Tb2Cd2(NO3)2(pfb)8(phen)2.1.5MeCN]n (4), [Cu2(Afb)4(phen)2] (5), [Cu2(NO3)2(Afb)2(phen)2] (6). It is shown that the main contribution to the stabilization of the crystal packing of coordination polymers 1–4 and molecular binuclear complexes 5 and 6 can be attributed to non-covalent π···π, C-H···F, and C-F···π interactions. It was found that the partial exchange of pfb or Afb anions on compact NO3− anions leads to a decrease in steric hindrance, a more efficient overlap of aromatic fragments, and a significant change in the geometry of complexes. Synthesized compounds were characterized by X-ray diffraction analysis, IR spectroscopy, and CHN analysis. The thermal stability of complexes 1 and 2 was studied. Non-covalent interactions were analyzed using the Hirshfeld surface method.
Understanding Real-World Treatment Patterns and Clinical Outcomes among Metastatic Melanoma Patients in Alberta, Canada
Authors: O’Sullivan Dylan E. , Boyne Devon J. , Gogna Priyanka , Brenner Darren R. , Cheung Winson Y.
Published: April 2023

Immunotherapy and targeted therapies have been shown to considerably improve long-term survival outcomes in metastatic melanoma patients. Real-world evidence on the uptake of novel therapies and outcomes for this patient population in Canada are limited. We conducted a population-based retrospective cohort study of all metastatic melanoma patients diagnosed in Alberta, Canada (2015–2018) using electronic medical records and administrative data. Information on BRAF testing for patients diagnosed in 2017 or 2018 was obtained through chart abstraction. In total, 434 metastatic melanoma patients were included, of which 110 (25.3%) were de novo metastatic cases. The median age at diagnosis was 66 years (IQR: 57–76) and 70.0% were men. BRAF testing was completed for the majority of patients (88.7%). Among all patients, 60.4%, 19.1%, and 6.0% initiated first-line, second-line, and third-line systemic therapy. The most common therapies were anti-PD-1 and targeted therapies. The two-year survival probability from first-line therapy, second-line therapy, and third-line therapy was 0.50 (95% CI: 0.44–0.57), 0.26 (95% CI: 0.17–0.40), and 0.14 (95% CI: 0.40–0.46), respectively. In the first-line setting, survival was highest for patients that received ipilimumab or ipilimumab plus nivolumab, while targeted therapy had the highest survival in the second-line setting. This study indicates that novel therapies improve survival in the real world but a considerable proportion of patients do not receive treatment with systemic therapy.
De-Implementation of Axillary Staging and Radiotherapy in Low-Risk Breast Cancer Patients Aged 70–79 Years from Six Italian Cancer Institutes
Authors: Bucchi Lauro , Ravaioli Alessandra , Dal Maso Luigino , Falcini Fabio , Mangone Lucia , Massarut Samuele , Schirosi Laura , Crispo Anna , Vici Patrizia , Franceschi Silvia
Published: April 2023

In women aged ≥70 with low-risk breast cancer (BrC), some major international guidelines recommend against sentinel lymph node biopsy (for example, those from the Society of Surgical Oncology, U.S.) and post-lumpectomy radiotherapy (for example, those from the National Comprehensive Cancer Network, U.S.). We assessed the frequency of both procedures in six National Cancer Institutes (IRCCSs) in the North, the Centre, and the South of Italy. Data on tumour characteristics and treatment were obtained from each centre. Patients aged 70–79 years diagnosed with a pT1–pT2, clinically axillary lymph node-negative, oestrogen and/or progesterone receptor-positive, and human epidermal growth factor receptor 2-negative BrC between 2015 and 2020 were eligible for the study. Factors associated with the omission of the two procedures were evaluated using binary penalised logistic regression models. Axillary staging was omitted in 33/1000 (3.3%) women. After simultaneous adjustment for the centre of treatment and all other key variables, axillary staging was omitted more often in 2015–2016 vs. 2017–2020 (odds ratio (OR): 2.7; 95% CI: 1.0–7.5), in women aged 75–79 vs. 70–74 years (OR: 2.3; 95% CI: 1.1–4.9), and in those who had mastectomy vs. breast-conserving surgery (OR: 3.3; 95% CI: 1.2–9.0). The higher the histological grade was, the less frequent were the omissions (OR for grade 3 vs. grade 1: 0.2; 95% CI: 0.0–0.7). Post-lumpectomy radiotherapy was omitted in 56/651 (8.6%) women with no significant association with age, period, tumour stage, and tumour grade. In conclusion, the omission of axillary staging and post-lumpectomy radiotherapy in low-risk older BrC patients was rare in the Italian IRCCSs. Although women included in the study cannot be considered a nationally representative sample of BrC patients in Italy, our findings can serve as a baseline to monitor the impact of future guidelines. To do that, the recording and storage of hospital-based information should be improved.
Invasion Consequences in Communities Maintained by Niche and Intransitive Coexistence Mechanisms
Authors: Zhang Bozhong , Guo Xiaolong , Bao Liping , Yang Yinghui
Published: April 2023

Understanding invasion mechanisms or identifying their potential outcomes has been a longstanding objective of invasion. Many recent empirical and theoretical works tend to frame a perspective of invasion biology within the field of coexistence theory. With increasing emphasis on indirect competitions, more researches hold that niche departure, intransitive loop structure or the integration of these two would be the potential mechanisms to promote native coexistence. But how invasion dynamics rely on these key properties of native competitive network is seldom investigated. Here, we introduce one alien species to a three-species competition system. By setting the structure of coexistence coefficient matrix, we consider three native coexistence mechanisms. After analyzing the equilibrium consequences of alien species invasion under these three mechanisms, we have found that (1) in the native communities supported by strong niche differentiation, alien species can certainly establish their population but would not pose great destruction to native species. (2) Invasion exclusion would happen in the community maintained by intransitive competition loop. However, whether alien species coexist with or exclude resident populations depends on both intraspecific and interspecific competition of invader. (3) The community assembled by the combination of these two mechanisms are most resistant to invasion, and where invasion consequences are more diverse. (4) Finally, the species long-term steady state and short-term respond always keep consistent. We have explicitly situated invasion process within the recent coexistence framework. Our results would broaden the understanding of invasion mechanisms and provide insights into the combination of invasion and coexistence theory.