bluuebunny/crossref_metadata_2025 huggingface dataset:
Acellular Biomaterials Associated with Autologous Bone Marrow-Derived Mononuclear Stem Cells Improve Wound Healing through Paracrine Effects
Authors: de Souza Isio Carvalho , Takejima Aline Luri , Simeoni Rossana Baggio , Gamba Luize Kremer , Ribeiro Victoria Stadler Tasca , Foltz Katia Martins , de Noronha Lucia , de Almeida Meila Bastos , Neto Jose Rocha Faria , de Carvalho Katherine Athayde Teixeira , da Silveira Paulo Cesar Lock , Pinho Ricardo Aurino , Francisco Julio Cesar , Guarita-Souza Luiz César
Published: March 2023

Wound healing is a complex process of repair that involves the interaction between different cell types and involves coordinated interactions between intracellular and extracellular signaling. Bone Marrow Mesenchymal Stem Cells (BMSCs) based and acellular amniotic membrane (AM) therapeutic strategies with the potential for treatment and regeneration of tissue. We aimed to evaluate the involvement of paracrine effects in tissue repair after the flap skin lesion rat model. In the full-thickness flap skin experiment of forty Wistar rats: A total of 40 male Wistar rats were randomized into four groups: group I: control (C; n = 10), with full-thickness lesions on the back, without (BMSCs) or AM (n = 10); group II: injected (BMSCs; n = 10); group III: covered by AM; group IV–injected (AM + BMSCs; n = 10). Cytokine levels, IL-1, and IL-10 assay kits, superoxide dismutase (SOD), glutathione reductase (GRs) and carbonyl activity levels were measured by ELISA 28th day, and TGF-β was evaluated by immunohistochemical, the expression collagen expression was evaluated by Picrosirius staining. Our results showed that the IL-1 interleukin was higher in the control group, and the IL-10 presented a higher mean when compared to the control group. The groups with BMSCs and AM showed the lowest expression levels of TGF-β. SOD, GRs, and carbonyl activity analysis showed a predominance in groups that received treatment from 80%. The collagen fiber type I was predominant in all groups; however, the AM + BMSCs group obtained a higher average when compared to the control group. Our findings suggest that the AM+ BMSCs promote skin wound healing, probably owing to their paracrine effect attributed to the promotion of new collagen for tissue repair.
Examination of Upper Limb Function and the Relationship with Gross Motor Functional and Structural Parameters in Patients with Spinal Muscular Atrophy
Authors: Bieniaszewska Aleksandra , Sobieska Magdalena , Steinborn Barbara , Gajewska Ewa
Published: March 2023

Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by the deletion or/and mutation in the survival motor neuron 1 (SMN1) gene on chromosome 5. Until now, only a few articles investigating the relationship between upper limb function and the gross motor function in untreated SMA patients have been published. However, there is still a lack of publications including the relationship between structural changes such as cervical rotation, trunk rotation and side trunk shortening, and upper limb function. The aim of the study was to examine the upper limb function in patients with spinal muscular atrophy and the relationship between the upper limb function, gross motor function, and structural parameters. We present an analysis of 25 SMA patients, divided into sitter and walker groups, undergoing pharmacological treatment (nusinersen or risdiplam), examined twice between the initial examination and evaluation after a 12-month period. The participants were tested using validated scales such as the Revised Upper Limb Module (RULM), the Hammersmith Functional Motor Scale—Extended (HFMSE), and the structural parameters. Our results showed that patients demonstrated greater improvement on the RULM scale than on the HFMSE scale. Moreover, persistent structural changes negatively affected both the upper limb function and gross motor skills.
Changes in the Localization of Polyamine Spermidine in the Rat Retina with Age
Authors: Ríos David S. , Malpica-Nieves Christian J. , Díaz-García Amanda , Eaton Misty J. , Skatchkov Serguei N.
Published: March 2023

Polyamines (PAs) in the nervous system has a key role in regeneration and aging. Therefore, we investigated age-related changes in the expression of PA spermidine (SPD) in the rat retina. Fluorescent immunocytochemistry was used to evaluate the accumulation of SPD in retinae from rats of postnatal days 3, 21, and 120. Glial cells were identified using glutamine synthetase (GS), whereas DAPI, a marker of cell nuclei, was used to differentiate between retinal layers. SPD localization in the retina was strikingly different between neonates and adults. In the neonatal retina (postnatal day 3-P3), SPD is strongly expressed in practically all cell types, including radial glia and neurons. SPD staining showed strong co-localization with the glial marker GS in Müller Cells (MCs) in the outer neuroblast layer. In the weaning period (postnatal day 21-P21), the SPD label was strongly expressed in all MCs, but not in neurons. In early adulthood (postnatal day 120-P120), SPD was localized in MCs only and was co-localized with the glial marker GS. A decline in the expression of PAs in neurons was observed with age while glial cells accumulated SPD after the differentiation stage (P21) and during aging in MC cellular endfoot compartments.
Recent Advances in Aptamer-Based Sensors for Sensitive Detection of Neurotransmitters
Authors: Park Joon-Ha , Eom Yun-Sik , Kim Tae-Hyung
Published: March 2023

In recent years, there has been an increased demand for highly sensitive and selective biosensors for neurotransmitters, owing to advancements in science and technology. Real-time sensing is crucial for effective prevention of neurological and cardiovascular diseases. In this review, we summarise the latest progress in aptamer-based biosensor technology, which offers the aforementioned advantages. Our focus is on various biomaterials utilised to ensure the optimal performance and high selectivity of aptamer-based biosensors. Overall, this review aims to further aptamer-based biosensor technology.
Outcome Comparison of Drug-Resistant Trigeminal Neuralgia Surgical Treatments—An Umbrella Review of Meta-Analyses and Systematic Reviews
Authors: Rapisarda Alessandro , Battistelli Marco , Izzo Alessandro , D’Ercole Manuela , D’Alessandris Quintino Giorgio , Polli Filippo Maria , Santi Samuele , Martinelli Renata , Montano Nicola
Published: March 2023

Medical treatment for trigeminal neuralgia (TN) is not always a feasible option due to a lack of full response or adverse effects. Open surgery or percutaneous procedures are advocated in these cases. Several articles have compared the results among different techniques. Nevertheless, the findings of these studies are heterogeneous. Umbrella reviews are studies sitting at the peak of the evidence pyramid. With this umbrella review, we provided a systematic review of the outcomes of the surgical procedures used for TN treatment. Only systematic reviews and meta-analyses were included following the PRISMA guidelines. Ten articles were enrolled for qualitative and quantitative assessment. Level of evidence was quantified using a specific tool (AMSTAR-2). Results were heterogenous in terms of outcome and measurements. Microvascular decompression (MVD) appeared to be the most effective procedure both in the short-term (pain relief in 85–96.6% of cases) and long-term follow-up (pain relief in 64–79% of cases), although showed the highest rate of complications. The results of percutaneous techniques were similar but radiosurgery showed the highest variation in term of pain relief and a higher rate of delayed responses. The use of the AMSTAR-2 tool to quantify the evidence level scored three studies as critically low and seven studies as low-level, revealing a lack of good quality studies on this topic. Our umbrella review evidenced the need of well-designed comparative studies and the utilization of validated scales in order to provide more homogenous data for pooled-analyses and meta-analyses in the field of TN surgical treatment.
French Students with Dyslexia Facing the Punctuation System: Insecurity, Inventory Use, and Error Studies
Authors: Mazur Audrey , Quignard Matthieu
Published: March 2023

Punctuation strongly contributes to the cohesion of the text. Despite this relevant role in written activity, this linguistic paradigm is too rarely observed. Moreover, it is all the more important to analyze its management as it is one of the difficulties declared by students with dyslexia. In that sense, the purpose of this paper is to analyze punctuation management during written text production by students with dyslexia, compared to matched control students. Previous English and Dutch studies confirm this feeling and reveal that students with dyslexia make many punctuation errors. That being said, there is no consensus; other studies do not reach this conclusion. For this present study, students with dyslexia and control students matched in age, university level, and gender were asked to produce spontaneous written and spoken narrative and expository texts. The written texts (N = 86) were collected using Eye and Pen© software with digitizing tablets. Results reveal that if students with dyslexia use the same inventory of punctuation marks as control students, they use fewer punctuation marks and make more errors than control students. These results are discussed and highlighted by the literature dealing with written production as a complex cognitive activity. They reveal that punctuation management is deficient for students with dyslexia, suggesting that the cohesion system can be impacted by dyslexia.
mTORC1-Dependent Protein and Parkinson’s Disease: A Mendelian Randomization Study
Authors: Tan Cheng , Ai Jianzhong , Zhu Ye
Published: March 2023

Background: The mTOR pathway is crucial in controlling the growth, differentiation, and survival of neurons, and its pharmacological targeting has promising potential as a treatment for Parkinson’s disease. However, the function of mTORC1 downstream proteins, such as RPS6K, EIF4EBP, EIF-4E, EIF-4G, and EIF4A, in PD development remains unclear. Methods: We performed a Mendelian randomization study to evaluate the causal relationship between mTORC1 downstream proteins and Parkinson’s disease. We utilized various MR methods, including inverse-variance-weighted, weighted median, MR–Egger, MR-PRESSO, and MR-RAPS, and conducted sensitivity analyses to identify potential pleiotropy and heterogeneity. Results: The genetic proxy EIF4EBP was found to be inversely related to PD risk (OR = 0.79, 95% CI = 0.67–0.92, p = 0.003), with the results from WM, MR-PRESSO, and MR-RAPS being consistent. The plasma protein levels of EIF4G were also observed to show a suggestive protective effect on PD (OR = 0.85, 95% CI = 0.75–0.97, p = 0.014). No clear causal effect was found for the genetically predicted RP-S6K, EIF-4E, and EIF-4A on PD risk. Sensitivity analyses showed no significant imbalanced pleiotropy or heterogeneity, indicating that the MR estimates were robust and independent. Conclusion: Our unbiased MR study highlights the protective role of serum EIF4EBP levels in PD, suggesting that the pharmacological activation of EIF4EBP activity could be a promising treatment option for PD.
Collateral Circulation and BNP in Predicting Outcome of Acute Ischemic Stroke Patients with Atherosclerotic versus Cardioembolic Cerebral Large-Vessel Occlusion Who Underwent Endovascular Treatment
Authors: Cao Ruoyao , Lu Yao , Qi Peng , Wang Yanyan , Hu Hailong , Jiang Yun , Chen Min , Chen Juan
Published: March 2023

Purpose: The aim of this study was to verify the value of collateral circulation and B-type natriuretic peptide (BNP) in predicting clinical outcomes of patients with acute ischemic stroke (AIS) and their biomarker value for stroke subtypes before endovascular treatment (EVT). Patients and Methods: In this retrospective study, 182 patients who underwent EVT for unilateral anterior circulation large-vessel occlusion between March 2016 and January 2022 were analyzed. The modified collateral circulation scoring system on four-dimensional computed tomography angiography (4D CTA-CS) was used to assess collateral status, and stroke subtypes were determined according to the TOAST classification criteria. Patients were divided into good (mRS ≤ 2) and poor outcome (mRS > 2) groups based on their modified Rankin Scale (mRS) score at 3 months. Results: 4D CTA-CS was an independent predictor of the clinical outcome for all AIS patients (odds ratio = 0.253; 95% CI, 0.147–0.437; p < 0.001), CE stroke patients (odds ratio = 0.513; 95% CI, 0.280–0.939; p = 0.030), and LAA stroke patients (odds ratio = 0.148; 95% CI, 0.049–0.447; p = 0.001). The BNP was a biomarker for clinical outcome prediction in CE (odds ratio = 1.004; 95% CI, 1.001–1.008; p = 0.005) but not in LAA patients. Combined with BNP, 4D CTA-CS improved predictive values for clinical outcomes (p < 0.05). Conclusion: Collateral status and BNP could be used as independent predictors of clinical outcomes in AIS patients and could determine stroke subtypes (CE stroke or LAA stroke). In addition, the model of 4D CTA-CS combined with BNP was the most effective in predicting clinical outcomes compared with collateral status or BNP alone.
Positive Touch Deprivation during the COVID-19 Pandemic: Effects on Anxiety, Stress, and Depression among Italian General Population
Authors: Bruno Francesco , Tagliaferro Carlotta , Canterini Sonia , Laganà Valentina , Contrada Marianna , Fioravanti Chiara , Altomari Natalia , Pistininzi Rebecca , Tarantino Francesca , Placanica Alessia , Greco Ersilia Martina , Capicotto Francesca , Spadea Saverio , Coscarella Anna Maria , Bonanno Martina , Scarfone Federica , Luchetta-Mattace Sara , Filice Alessia , Pettinato Annamaria , Avramovic Ana , Lau Chloe , Marunic Georgia , Chiesi Francesca
Published: March 2023

Physical distancing due to the COVID-19 Pandemic has limited the opportunities for family members, friends, and significant others to show physical affection (i.e., hugs, kisses, caresses, holding hands) during social interactions. The present study investigated the effects of positive touch and psychological distress in 991 Italian participants (Mage = 34.43, SD = 14.27). Results showed the frequency of hugs with the cohabiting partner significantly decreased the symptoms of depression (β = −1.187, p = 0.018, eβ = 0.30, 95% CI = 0.11–0.82), whereas the frequency of caresses with cohabiting relatives predicted the symptoms of anxiety (β = 0.575, p = 0.034, eβ = 1.78, 95% CI = 1.04–3.03). The frequency of hugs (β = −0.609, p = 0.049, eβ = 0.54, 95% CI = 0.30–1.00), and kisses (β = 0.663, p = 0.045, eβ = 1.94, 95% CI = 1.01–3.71) with non-cohabiting relatives predicted the symptoms of anxiety (χ2 = 1.35, df = 5, p = 0.93). These results suggest the importance of positive touch on psychological well-being in the social context.
Dynamic Characteristics and Evolution Analysis of Information Dissemination Theme of Social Networks under Emergencies
Authors: Zhang Yuan , Xie Yanxi , Shi Victor , Yin Ke
Published: March 2023

Social media has become an essential channel for the public to create and obtain information during emergencies. As the theme of public concern for emergencies changes over time, there is a lack of research on its dynamic evolution from its latent stage. This paper selects the Henan rainstorm event as a case study and extracts the theme characteristics by combining the life cycle theory and Latent Dirichlet Allocation (LDA) model. It integrates the Term Frequency–Inverse Document Frequency (TF-IDF) and Pointwise Mutual Information (PMI) algorithms as the theme-coding data source to build a dynamic theme propagation model for emergencies. Our research results showed that the theme coding effectively verified the assumption of latent development trends. The dynamic theme model could reveal the theme characteristics of different time series stages of emergencies, analyze the law of the theme evolution of the network’s public opinion, and provide practical and theoretical insights for the emergency management of urban cities.
Effects of Geogrid Reinforcement on the Backfill of Integral Bridge Abutments
Authors: Farhangi Visar , Zadehmohamad Mehdi , Monshizadegan Armaghan , Izadifar MohammadAli , Moradi Mohammad Javad , Dabiri Hamed
Published: March 2023

The construction of integral bridges is one of the most effective methods to reduce bridges’ construction and in-service costs. However, there are associated geotechnical problems with their abutments backfill due to the integrated abutments. The main goal of this study is to evaluate and quantify the benefits of geogrid reinforcement for reducing the backfill’s geotechnical problems. For this purpose, using small-scale physical modeling, the benefits of geogrid reinforcing of the backfill of an integral abutment bridge subjected to cyclic movements are evaluated. The results are then compared with a previous study performed on unreinforced backfill and two types of geocells. In this study, 120 loading cycles are applied to geogrid-reinforced soil to simulate the cyclic loadings on integral abutment backfill due to seasonal abutment displacement. The horizontal reaction load at the top of the wall, changes in pressure behind the wall, and deformation in backfill soil are measured during the test. Then the results are discussed in terms of equivalent peak lateral soil coefficient (Kpeak), lateral earth pressure coefficient (K*), and normalized settlement behind the wall (Sg/H). The derived lateral soil coefficients and settlement behind the abutment show that geogrid substantially reduces pressure and settlements after 120 cyclic loads. Based on the results, Kpeak and K* of the geogrid-reinforced backfill decrease by up to 36%, and Sg/H behind the wall decreases by 62%. In addition, the comparison of the results for geogrid with two geocell types shows that geogrid is more efficient in terms of lateral soil coefficients.
Seismic Retrofitting of Indonesian Masonry Using Bamboo Strips: An Experimental Study
Authors: Habieb Ahmad Basshofi , Rofiussan Farisal Akbar , Irawan Djoko , Milani Gabriele , Suswanto Budi , Widodo Amien , Soegihardjo Hidajat
Published: March 2023

Unreinforced masonry (UM) is well known as a vulnerable structure against earthquakes. However, it remains a popular structural system for low-rise residential housing in many high-seismicity areas, particularly in developing regions due to its low cost and easy construction. In the present study, a retrofitting strategy using locally available material, bamboo strips, was proposed. In addition to its fast-growing rate, the tensile strength of bamboo is considered high, nearly comparable to its steel counterpart. A series of experimental tests were performed in this study, including the bamboo tensile test, the mortar flexural test, the diagonal compressive shear test on the masonry assemblages, and the in-plane pushover test on masonry wall specimens without and with bamboo reinforcement. The retrofitted specimens with different volumes of bamboo reinforcement were also considered. The results show that the application of bamboo reinforcement, at a proper volume, significantly increases the ultimate strength and the ductility of the masonry wall. Such results indicate that the brittle failure of UM structures can be avoided by means of bamboo retrofitting.
Experimental Investigation of Self-Compacting Concrete with Recycled Concrete Aggregate
Authors: Ahmed Sayed , El-Zohairy Ayman , Eisa Ahmed , Mohamed Mohamed , Abdo Ayman
Published: March 2023

Due to the depletion of natural aggregates and raw materials for contemporary construction, the construction and demolition waste existing in old concrete structures is an imperative problem. Cutting down on exploiting natural aggregates and reusing construction and demolition waste in the concrete industry are solutions to this problem. This paper investigated the replacement of natural coarse aggregate (NCA) with recycled concrete aggregates (RCA) with different ratios (0%, 50%, 75%, and 100%) in producing self-compacting concrete (SCC). Different components of supplementary cementitious materials (SCMs), such as nano-silica (NS), fly ash (FA), and metakaolin (MK), as well as PVA fibers, were incorporated into the SCC mixtures. The fresh properties (slump flow, V-funnel, and L-box test) and hardened properties (compressive strength, splitting tensile strength, and flexural strength), as well as the flexural behavior of SCC beams (load-carrying capacity, crack pattern, mid-span deflection, and flexural stiffness), were studied for all SCC mixes. The results of fresh and hardened concrete confirmed that it is possible to produce SCC with a 100% replacement of RCA with minimal effects on the concrete properties. The mixture of SCC with 100% RCA replacement, 20% MK, and 22% FA was the optimum mixture with acceptable fresh properties that complied with the EFNARC specifications. For 100% RCA replacement, the compressive strength was reduced by 8.20%, and the ultimate load and flexural stiffness increased by 3.20 and 16.25%, respectively, compared with the control mixture.
Antibody Surface Profiling Identifies Glycoforms in Multiple Myeloma as Targets for Immunotherapy: From Antibody Derivatives to Mimetic Peptides for Killing Tumor Cells
Authors: Sioud Mouldy , Olberg Anniken
Published: March 2023

Despite therapeutic advances in recent years, there are still unmet medical needs for patients with multiple myeloma (MM). Hence, new therapeutic strategies are needed. Using phage display for screening a large repertoire of single chain variable fragments (scFvs), we isolated several candidates that recognize a heavily sulfated MM-specific glycoform of the surface antigen syndecan-1 (CD138). One of the engineered scFv-Fc antibodies, named MM1, activated NK cells and induced antibody-dependent cellular cytotoxicity against MM cells. Analysis of the binding specificity by competitive binding assays with various glycan ligands identified N-sulfation of glucosamine units as essential for binding. Additionally, site-directed mutagenesis revealed that the amino acids arginine and histidine in the complementarily determining regions (CDRs) 2 and 3 of the heavy chain are important for binding. Based on this observation, a heavy-chain antibody, known as a nanobody, and a peptide mimicking the CDR loop sequences were designed. Both variants exhibited high affinity and specificity to MM cells as compared to blood lymphocytes. Specific killing of MM cells was achieved by conjugating the CDR2/3 mimic peptide to a pro-apoptotic peptide (KLAKLAK)2. In a co-culture model, the fusion peptide killed MM cells, while leaving normal peripheral blood mononuclear cells unaffected. Collectively, the development of antibodies and peptides that detect tumor-specific glycoforms of therapeutic targets holds promise for improving targeted therapies and tumor imaging.
Targeting Mitochondria with ClpP Agonists as a Novel Therapeutic Opportunity in Breast Cancer
Authors: Wedam Rohan , Greer Yoshimi Endo , Wisniewski David J. , Weltz Sarah , Kundu Manjari , Voeller Donna , Lipkowitz Stanley
Published: March 2023

Breast cancer is the most frequently diagnosed malignancy worldwide and the leading cause of cancer mortality in women. Despite the recent development of new therapeutics including targeted therapies and immunotherapy, triple-negative breast cancer remains an aggressive form of breast cancer, and thus improved treatments are needed. In recent decades, it has become increasingly clear that breast cancers harbor metabolic plasticity that is controlled by mitochondria. A myriad of studies provide evidence that mitochondria are essential to breast cancer progression. Mitochondria in breast cancers are widely reprogrammed to enhance energy production and biosynthesis of macromolecules required for tumor growth. In this review, we will discuss the current understanding of mitochondrial roles in breast cancers and elucidate why mitochondria are a rational therapeutic target. We will then outline the status of the use of mitochondria-targeting drugs in breast cancers, and highlight ClpP agonists as emerging mitochondria-targeting drugs with a unique mechanism of action. We also illustrate possible drug combination strategies and challenges in the future breast cancer clinic.
Metabolomic Signatures of Scarff–Bloom–Richardson (SBR) Grade in Non-Metastatic Breast Cancer
Authors: Bailleux Caroline , Chardin David , Gal Jocelyn , Guigonis Jean-Marie , Lindenthal Sabine , Graslin Fanny , Arnould Laurent , Cagnard Alexandre , Ferrero Jean-Marc , Humbert Olivier , Pourcher Thierry
Published: March 2023

Purpose: Identification of metabolomic biomarkers of high SBR grade in non-metastatic breast cancer. Methods: This retrospective bicentric metabolomic analysis included a training set (n = 51) and a validation set (n = 49) of breast cancer tumors, all classified as high-grade (grade III) or low-grade (grade I–II). Metabolomes of tissue samples were studied by liquid chromatography coupled with mass spectrometry. Results: A molecular signature of the top 12 metabolites was identified from a database of 602 frequently predicted metabolites. Partial least squares discriminant analyses showed that accuracies were 0.81 and 0.82, the R2 scores were 0.57 and 0.55, and the Q2 scores were 0.44431 and 0.40147 for the training set and validation set, respectively; areas under the curve for the Receiver Operating Characteristic Curve were 0.882 and 0.886. The most relevant metabolite was diacetylspermine. Metabolite set enrichment analyses and metabolic pathway analyses highlighted the tryptophan metabolism pathway, but the concentration of individual metabolites varied between tumor samples. Conclusions: This study indicates that high-grade invasive tumors are related to diacetylspermine and tryptophan metabolism, both involved in the inhibition of the immune response. Targeting these pathways could restore anti-tumor immunity and have a synergistic effect with immunotherapy. Recent studies could not demonstrate the effectiveness of this strategy, but the use of theragnostic metabolomic signatures should allow better selection of patients.
Normal Pressure Hydrocephalus Following Cranial Radiation: Identification of Shunting Responders
Authors: Cayuela Nuria , Domínguez-Lizarbe Manuel , Plans Gerard , Alemany Montserrat , Sánchez Juan José , Andrés Begoña , Lucas Anna , Bruna Jordi , Simó Marta
Published: March 2023

Background: We examined cognitive, brain MRI, and lumbar infusion test (LIT) features to identify predictors of response to ventriculoperitoneal shunting (VPS) in long-term cancer survivors with suspected normal pressure hydrocephalus (NPH) following cranial radiotherapy (RT). Methods: Patients who completed cranial RT at least 2 years before with clinically suspected NPH and an Evans’ index (EI) ≥ 0.30 underwent a cognitive and a cerebrospinal fluid (CSF) volumetric (MRI) analysis (n = 36). For those in whom VPS was placed (n = 14), we explored whether adding a CSF volumetric analysis to classical MRI and LIT (Tap Test) features would better identify VPS responders. Results: Nearly 80% exhibited cognitive impairment. The CSF volume at NPH diagnoses was significantly larger in the group of VPS responders (p = 0.04). The addition of CSF volume to NPH diagnoses increased accuracy to 93%, with a positive and negative predictive value of 91% and 100%, respectively. Conclusion: The addition of a quantitative MRI analysis of CSF volume to classical MRI and LIT NPH criteria, along with a high clinical suspicion of NPH, may help to identify VPS responders, thus improving the clinical management and prognosis of long-term survivors.
Bowel Preparation for Colonoscopy Changes Serum Composition as Detected by Thermal Liquid Biopsy and Fluorescence Spectroscopy
Authors: Hermoso-Durán Sonia , Domper-Arnal María José , Roncales Pilar , Vega Sonia , Sanchez-Gracia Oscar , Ojeda Jorge L. , Lanas Ángel , Velazquez-Campoy Adrian , Abian Olga
Published: March 2023

(1) Background: About 50% of prescribed colonoscopies report no pathological findings. A secondary screening test after fecal immunochemical test positivity (FIT+) would be required. Considering thermal liquid biopsy (TLB) as a potential secondary test, the aim of this work was to study possible interferences of colonoscopy bowel preparation on TLB outcome on a retrospective study; (2) Methods: Three groups were studied: 1/514 FIT(+) patients enrolled in a colorectal screening program (CN and CP with normal and pathological colonoscopy, respectively), with blood samples obtained just before colonoscopy and after bowel preparation; 2/55 patients from the CN group with blood sample redrawn after only standard 8–10 h fasting and no bowel preparation (CNR); and 3/55 blood donors from the biobank considered as a healthy control group; (3) Results: The results showed that from the 514 patients undergoing colonoscopy, 247 had CN and 267 had CP. TLB parameters in these two groups were similar but different from those of the blood donors. The resampled patients (with normal colonoscopy and no bowel preparation) had similar TLB parameters to those of the blood donors. TLB parameters together with fluorescence spectra and other serum indicators (albumin and C-reactive protein) confirmed the statistically significant differences between normal colonoscopy patients with and without bowel preparation; (4) Conclusions: Bowel preparation seemed to alter serum protein levels and altered TLB parameters (different from a healthy subject). The diagnostic capability of other liquid-biopsy-based methods might also be compromised. Blood extraction after bowel preparation for colonoscopy should be avoided.
Microparticle Phosphatidylserine Mediates Coagulation: Involvement in Tumor Progression and Metastasis
Authors: Jing Haijiao , Wu Xiaoming , Xiang Mengqi , Wang Chengyue , Novakovic Valerie A. , Shi Jialan
Published: March 2023

Tumor progression and cancer metastasis has been linked to the release of microparticles (MPs), which are shed upon cell activation or apoptosis and display parental cell antigens, phospholipids such as phosphatidylserine (PS), and nucleic acids on their external surfaces. In this review, we highlight the biogenesis of MPs as well as the pathophysiological processes of PS externalization and its involvement in coagulation activation. We review the available evidence, suggesting that coagulation factors (mainly tissue factor, thrombin, and fibrin) assist in multiple steps of tumor dissemination, including epithelial–mesenchymal transition, extracellular matrix remodeling, immune escape, and tumor angiogenesis to support the formation of the pre-metastatic niche. Platelets are not just bystander cells in circulation but are functional players in primary tumor growth and metastasis. Tumor-induced platelet aggregation protects circulating tumor cells (CTCs) from the blood flow shear forces and immune cell attack while also promoting the binding of CTCs to endothelial cells and extravasation, which activates tumor invasion and sustains metastasis. Finally, in terms of therapy, lactadherin can inhibit coagulation by competing effectively with coagulation factors for PS binding sites and may similarly delay tumor progression. Furthermore, we also investigate the therapeutic potential of coagulation factor inhibitors within the context of cancer treatment. The development of multiple therapies targeting platelet activation and platelet–tumor cell interactions may not only reduce the lethal consequences of thrombosis but also impede tumor growth and spread.
Recent Progress in Electrocatalytic Reduction of CO2
Authors: Ren Chaojun , Ni Wei , Li Hongda
Published: March 2023

A stable life support system in the spacecraft can greatly promote long-duration, far-distance, and multicrew manned space flight. Therefore, controlling the concentration of CO2 in the spacecraft is the main task in the regeneration system. The electrocatalytic CO2 reduction can effectively treat the CO2 generated by human metabolism. This technology has potential application value and good development prospect in the utilization of CO2 in the space station. In this paper, recent research progress for the electrocatalytic reduction of CO2 was reviewed. Although numerous promising accomplishments have been achieved in this field, substantial advances in electrocatalyst, electrolyte, and reactor design are yet needed for CO2 utilization via an electrochemical conversion route. Here, we summarize the related works in the fields to address the challenge technology that can help to promote the electrocatalytic CO2 reduction. Finally, we present the prospective opinions in the areas of the electrocatalytic CO2 reduction, especially for the space station and spacecraft life support system.
Green Catalytic Conversion of Some Benzylic Alcohols to Acids by NiO2 Nanoparticles (NPNPs) in Water
Authors: Shoair Abdel Ghany F. , Shanab Mai M. A. H. , El-Ghamaz Nasser A. , Abou-Krisha Mortaga M. , Kenawy Sayed H. , Yousef Tarek A.
Published: March 2023

The aqueous basic systems NiSO4·6H2O/K2S2O8 (pH = 14) and NiSO4·6H2O/KBrO3 (pH = 11.5) were investigated for the catalytic conversion of benzyl alcohol and some para-substituted benzyl alcohols to their corresponding acids in 75–97% yields at room temperature. The active species was isolated and characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction, EDX and FT-IR techniques, and identified as comprising NiO2 nanoparticles (NPNPs). The SEM and TEM images of the Ni peroxide samples showed a fine spherical-like aggregation of NiO2 molecules with a nearly homogeneous partial size and confirmed the aggregation’s size to be in the range of 2–3 nm. The yields, turn over (TO) and turn over frequencies (TOF) were calculated. It was noticed that the aromatic alcohols containing para-substituted electron donation groups gave better yields than those having electron withdrawing groups. The optimum conditions for this catalytic reaction were studied using benzyl alcohol as a model. The mechanism of the catalytic conversion reaction was suggested, in which the produced NPNPs convert alcohols to acids in two steps through the formation of the corresponding aldehyde. The produced NiO because of this conversion is converted again to NPNPs by the excess of K2S2O8 or KBrO3. This catalytic cycle continues until all of the substrate is oxidized.
Straightforward and Efficient Deuteration of Terminal Alkynes with Copper Catalysis
Authors: Tarrach Xènia , Yang Jingzhou , Soleiman-Beigi Mohammad , Díez-González Silvia
Published: March 2023

The mild and effective preparation of deuterated organic molecules is an active area of research due to their important applications. Herein, we report an air-stable and easy to access copper(I) complex as catalyst for the deuteration of mono-substituted alkynes. Reactions were carried out in technical solvents and in the presence of air, to obtain excellent deuterium incorporation in a range of functionalised alkynes.
Cerebral Malaria Model Applying Human Brain Organoids
Authors: Silva-Pedrosa Rita , Campos Jonas , Fernandes Aline Marie , Silva Miguel , Calçada Carla , Marote Ana , Martinho Olga , Veiga Maria Isabel , Rodrigues Ligia R. , Salgado António José , Ferreira Pedro Eduardo
Published: March 2023

Neural injuries in cerebral malaria patients are a significant cause of morbidity and mortality. Nevertheless, a comprehensive research approach to study this issue is lacking, so herein we propose an in vitro system to study human cerebral malaria using cellular approaches. Our first goal was to establish a cellular system to identify the molecular alterations in human brain vasculature cells that resemble the blood–brain barrier (BBB) in cerebral malaria (CM). Through transcriptomic analysis, we characterized specific gene expression profiles in human brain microvascular endothelial cells (HBMEC) activated by the Plasmodium falciparum parasites. We also suggest potential new genes related to parasitic activation. Then, we studied its impact at brain level after Plasmodium falciparum endothelial activation to gain a deeper understanding of the physiological mechanisms underlying CM. For that, the impact of HBMEC-P. falciparum-activated secretomes was evaluated in human brain organoids. Our results support the reliability of in vitro cellular models developed to mimic CM in several aspects. These systems can be of extreme importance to investigate the factors (parasitological and host) influencing CM, contributing to a molecular understanding of pathogenesis, brain injury, and dysfunction.
Tau Transfer via Extracellular Vesicles Disturbs the Astrocytic Mitochondrial System
Authors: Perbet Romain , Zufferey Valentin , Leroux Elodie , Parietti Enea , Espourteille Jeanne , Culebras Lucas , Perriot Sylvain , Du Pasquier Renaud , Bégard Séverine , Deramecourt Vincent , Déglon Nicole , Toni Nicolas , Buée Luc , Colin Morvane , Richetin Kevin
Published: March 2023

Tauopathies are neurodegenerative disorders involving the accumulation of tau isoforms in cell subpopulations such as astrocytes. The origins of the 3R and 4R isoforms of tau that accumulate in astrocytes remain unclear. Extracellular vesicles (EVs) were isolated from primary neurons overexpressing 1N3R or 1N4R tau or from human brain extracts (progressive supranuclear palsy or Pick disease patients or controls) and characterized (electron microscopy, nanoparticle tracking analysis (NTA), proteomics). After the isolated EVs were added to primary astrocytes or human iPSC-derived astrocytes, tau transfer and mitochondrial system function were evaluated (ELISA, immunofluorescence, MitoTracker staining). We demonstrated that neurons in which 3R or 4R tau accumulated had the capacity to transfer tau to astrocytes and that EVs were essential for the propagation of both isoforms of tau. Treatment with tau-containing EVs disrupted the astrocytic mitochondrial system, altering mitochondrial morphology, dynamics, and redox state. Although similar levels of 3R and 4R tau were transferred, 3R tau-containing EVs were significantly more damaging to astrocytes than 4R tau-containing EVs. Moreover, EVs isolated from the brain fluid of patients with different tauopathies affected mitochondrial function in astrocytes derived from human iPSCs. Our data indicate that tau pathology spreads to surrounding astrocytes via EVs-mediated transfer and modifies their function.
Modeling the Effects of Cypermethrin Toxicity on Ovalbumin-Induced Allergic Pneumonitis Rats: Macrophage Phenotype Differentiation and p38/STAT6 Signaling Are Candidate Targets of Pirfenidone Treatment
Authors: Morsi Ahmed A. , Faruk Eman Mohamed , Mogahed Mysara Mohamed , Baioumy Bodour , Hussein Asmaa Y. A. , El-shafey Rabab Shaban , Mersal Ezat A. , Abdelmoneim Ahmed M. , Alanazi Mohammed M. , Elshazly Amal Mahmoud ElSafy
Published: March 2023

Although the classic form of asthma is characterized by chronic pneumonitis with eosinophil infiltration and steroid responsivity, asthma has multifactorial pathogenesis and various clinical phenotypes. Previous studies strongly suggested that chemical exposure could influence the severity and course of asthma and reduce its steroid responsiveness. Cypermethrin (CYP), a common pesticide used in agriculture, was investigated for the possible aggravation of the ovalbumin (OVA)-induced allergic pneumonitis and the possible induction of steroid resistance in rats. Additionally, it was investigated whether pirfenidone (PFD) could substitute dexamethasone, as an alternative treatment option, for the induced steroid resistance. Fifty-six male Wistar albino rats were randomly divided into seven groups: control, PFD alone, allergic pneumonitis, CYP alone, allergic pneumonitis/CYP-exposed, allergic pneumonitis/CYP/dexamethasone (Dex), and allergic pneumonitis/CYP/PFD-treated groups. Allergic pneumonitis was induced by three intraperitoneal OVA injections administered once a week, followed by an intranasal OVA instillation challenge. CYP (25 mg/kg/d), Dex (1 mg/kg/d), and PFD (100 mg/kg/d) were administered orally from day 15 to the end of the experiment. Bronchoalveolar lavage fluid (BALF) was analyzed for cytokine levels. Hematoxylin and eosin (H&E) and periodic acid Schiff (PAS)-stained lung sections were prepared. Immunohistochemical identification of p38 MAPK and lung macrophages was performed. The inflammatory/oxidative status of the lung and PCR-quantification of the STAT6, p38 MAPK, MUC5AC, and IL-13 genes were carried out. The allergic pneumonitis-only group showed eosinophil-mediated inflammation (p < 0.05). Further CYP exposure aggravated lung inflammation and showed steroid-resistant changes, p38 activation, neutrophil-mediated, M1 macrophage-related inflammation (p < 0.05). All changes were reversed (p < 0.05) by PFD, meanwhile not by dexamethasone treatment. Pirfenidone could replace dexamethasone treatment in the current rat model of CYP-induced severe steroid-resistant asthma via inhibiting the M1 macrophage differentiation through modulation of the STAT6/p38 MAPK pathway.
Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish
Authors: Gopal Udhayakumar , Monroe Jerry D. , Marudamuthu Amarnath S. , Begum Salma , Walters Bradley J. , Stewart Rodney A. , Washington Chad W. , Gibert Yann , Zachariah Marcus A.
Published: March 2023

Leptomeningeal disease occurs when cancer cells migrate into the ventricles of the brain and spinal cord and then colonize the meninges of the central nervous system. The triple-negative subtype of breast cancer often progresses toward leptomeningeal disease and has a poor prognosis because of limited treatment options. This is due, in part, to a lack of animal models with which to study leptomeningeal disease. Here, we developed a translucent zebrafish casper (roy-/-; nacre-/-) xenograft model of leptomeningeal disease in which fluorescent labeled MDA-MB-231 human triple-negative breast cancer cells are microinjected into the ventricles of zebrafish embryos and then tracked and measured using fluorescent microscopy and multimodal plate reader technology. We then used these techniques to measure tumor area, cell proliferation, and cell death in samples treated with the breast cancer drug doxorubicin and a vehicle control. We monitored MDA-MB-231 cell localization and tumor area, and showed that samples treated with doxorubicin exhibited decreased tumor area and proliferation and increased apoptosis compared to control samples.
Derivation and Preclinical Characterization of CYT-303, a Novel NKp46-NK Cell Engager Targeting GPC3
Authors: Arulanandam Antonio , Lin Liang , Chang Hao-Ming , Cerutti Martine , Choblet Sylvie , Gao Peng , Rath Armin , Bensussan Armand , Kadouche Jean , Teper Daniel , Mandelboim Ofer , Li Wei
Published: March 2023

Glypican-3 (GPC3) is an oncofetal antigen that is highly expressed in multiple solid tumors, including hepatocellular carcinoma, and is barely expressed in adult normal tissues except the placenta. NKp46 activation receptor is expressed in all-natural killer (NK) cells, including tumor-infiltrating NK cells. FLEX-NKTM is a platform for the production of tetravalent multifunctional antibody NK cell engagers (NKE). CYT-303 was designed using the FLEX-NK scaffold, incorporating a novel humanized NKp46 binder that does not induce NKp46 internalization and a humanized GPC3 binder that targets the membrane-proximal lobe to mediate NK cell-redirected killing of HCC tumors. CYT-303 shows sub-nanomolar binding affinities to both GPC3 and NKp46. CYT-303 was highly potent and effective in mediating NK cell-redirected cytotoxicity against multiple HCC tumor cell lines and tumor spheroids. More interestingly, it can reverse the dysfunction induced in NK cells following repeated rounds of serial killing of tumors. It also mediated antibody-dependent cellular phagocytosis (ADCP) and complement-dependent cytotoxicity against GPC3-expressing HCC tumors. In vivo, CYT-303 showed no toxicity or cytokine release in cynomolgus monkeys up to the highest dose (60 mg/kg), administered weekly by intravenous infusion for 28 days. These results demonstrate the potential of CYT-303 to be a safe and effective therapy against HCC.
The Performance of Microfiltration Using Hydrophilic and Hydrophobic Membranes for Phenol Extraction from a Water Solution
Authors: Hussein Tamara Kawther , Jasim Nidaa Adil , Al-Madhhachi Abdul-Sahib T.
Published: March 2023

Two types of membranes, for hydrophilic and hydrophobic microfiltration, were prepared as flat sheets to treat a phenol-contaminated water solution. The membranes were fabricated using four synthetic polymers: polysulfone, polyethylene oxide, dimethylacetamide, and N-methyl-2-pyrrolidone. Scanning electron microscope measurements of the top-surface and cross-section images of the produced membranes were used to characterize them physically. Distilled water and water contaminated with phenol were used to evaluate the membrane’s performance based on the flux results depending on pressure, the concentration of phenol, and temperature variables. Meanwhile, the rejection performance was evaluated using the phenol-contaminated water solution. The results show that the flux increased with increases in pressure and temperature and decreased with increases in phenol concentration. Distilled water gave far higher results than water contaminated with phenol. The flux of distilled water ranged from 52.18 to 73.15 L/m2/h for the hydrophilic type and from 72.27 to 97.46 L/m2/h for the hydrophobic type, whereas the flux of water contaminated with phenol solution ranged from 26.58 to 61.55 L/m2/h for the hydrophilic type and from 29.98 to 80.55 L/m2/h for the hydrophobic type. Meanwhile, the phenol solution’s rejection was 60% when using a hydrophilic membrane, whereas it was only 45% when a hydrophobic membrane was used. The hydrophobic membrane showed high fluxes and low rejection. Thus, transport through this membrane is closer to having viscous behavior than that through the hydrophilic membrane; in contrast, the permeability through the hydrophilic membrane is less because the pore size decreases the viscous flow mechanism.
Heterogeneous Photodegradation Reaction of Phenol Promoted by TiO2: A Kinetic Study
Authors: Broccoli Francesco , Paparo Rosanna , Iesce Maria Rosaria , Di Serio Martino , Russo Vincenzo
Published: March 2023

Phenol is widely used in industry. Due to its high stability and toxicity, it represents a threat to the environment and human health. In this study, a kinetic investigation of phenol heterogeneous photodegradation was conducted using commercial Aeroxide P-25, performing experiments in a wide range of conditions. In detail, a negligible adsorption effect was detected. An activation energy of Ea = 14.3 ± 0.5 kJ mol−1 was measured, and the catalyst loading effect indicated an optimal condition due to the shield of the catalyst particles to the UV irradiation. The catalyst was most active at pH = 7 and it was stable for 25 h of reaction time; thus, it will be worth to investigate its application in flow.
Preterm Birth, Developmental Smoke/Nicotine Exposure, and Life-Long Pulmonary Sequelae
Authors: Kurihara Chie , Kuniyoshi Katherine M. , Rehan Virender K.
Published: March 2023

This review delineates the main pulmonary issues related to preterm birth, perinatal tobacco/nicotine exposure, and its effects on offspring, focusing on respiratory health and its possible transmission to subsequent generations. We review the extent of the problem of preterm birth, prematurity-related pulmonary effects, and the associated increased risk of asthma later in life. We then review the impact of developmental tobacco/nicotine exposure on offspring asthma and the significance of transgenerational pulmonary effects following perinatal tobacco/nicotine exposure, possibly via its effects on germline epigenetics.