bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Dose Escalation on the Efficacy of Salvage Radiotherapy for Recurrent Prostate Cancer—A Risk-Adjusted, Matched-Pair Analysis
Authors: Böhmer Dirk , Siegmann Alessandra , Scharl Sophia , Ruf Christian , Wiegel Thomas , Krafcsik Manuel , Thamm Reinhard
Published: March 2022

Previous randomized trials have not provided conclusive evidence about dose escalations and associated toxicities for salvage radiotherapy (SRT) in prostate cancer. Here, we retrospectively analyzed whether dose escalations influenced progression-free survival in 554 patients that received salvage radiotherapy for relapses or persistently elevated prostate cancer antigen (PSA) after a radical prostatectomy. Patients received SRT between 1997 and 2017 at two University Hospitals in Germany. We compared patient groups that received radiation doses <7000 cGy (n = 225) or ≥7000 cGy (n = 329) to analyze the influence of radiation dose on progression-free survival. In a second matched-pair analysis of 216 pairs, we evaluated prognostic factors (pT2 vs. pT3–4, Gleason score [GS] ≤ 7 vs. GS ≥ 8, R0 vs. R1, and pre-SRT PSA <0.5 vs. ≥0.5 ng/mL). After a median follow-up of 6.8 (4.2–9.2) years, we found that escalated doses significantly improved progression-free survival (p = 0.0042). A multivariate analysis indicated that an escalated dose, lower tumor stages (pT2 vs. pT3/4), and lower GSs (≤7 vs. 8–10) were associated with improved progression-free survival. There was no significant effect on overall survival. Our data suggested that escalating the radiation dose to ≥7000 cGy for SRT after a prostatectomy significantly improved progression-free survival. Longer follow-ups are needed for a comprehensive recommendation.
Prognostic Impact of High Baseline Stromal Tumor-Infiltrating Lymphocytes in the Absence of Pathologic Complete Response in Early-Stage Triple-Negative Breast Cancer
Authors: Abuhadra Nour , Sun Ryan , Litton Jennifer K. , Rauch Gaiane M. , Yam Clinton , Chang Jeffrey T. , Seth Sahil , Bassett Roland , Lim Bora , Thompson Alastair M. , Mittendorf Elizabeth , Adrada Beatriz E. , Damodaran Senthil , White Jason , Ravenberg Elizabeth , Candelaria Rosalind , Arun Banu , Ueno Naoto T. , Santiago Lumarie , Saleem Sadia , Abouharb Sausan , Murthy Rashmi K. , Ibrahim Nuhad , Sahin Aysegul A. , Valero Vicente , Symmans William Fraser , Tripathy Debu , Moulder Stacy , Huo Lei
Published: March 2022

High stromal tumor-infiltrating lymphocytes (sTILs) are associated with an improved pathologic complete response (pCR) and survival in triple-negative breast cancer (TNBC). We hypothesized that high baseline sTILs would have a favorable prognostic impact in TNBC patients without a pCR after neoadjuvant chemotherapy (NACT). In this prospective NACT study, pretreatment biopsies from 318 patients with early-stage TNBC were evaluated for sTILs. Recursive partitioning analysis (RPA) was applied to search for the sTIL cutoff best associated with a pCR. With ≥20% sTILs identified as the optimal cutoff, 33% patients had high sTILs (pCR rate 64%) and 67% had low sTILs (pCR rate 29%). Patients were stratified according to the sTIL cutoff (low vs. high) and response to NACT (pCR vs. residual disease (RD)). The primary endpoint was event-free survival (EFS), with hazard ratios calculated using the Cox proportional hazards regression model and the 3-year restricted mean survival time (RMST) as primary measures. Within the high-sTIL group, EFS was better in patients with a pCR compared with those with RD (HR 0.05; 95% CI 0.01–0.39; p = 0.004). The difference in the 3-year RMST for EFS between the two groups was 5.6 months (95% CI 2.3–8.8; p = 0.001). However, among patients with RD, EFS was not significantly different between those with high sTILs and those with low sTILs (p = 0.7). RNA-seq analysis predicted more CD8+ T cells in the high-sTIL group with favorable EFS compared with the high-sTIL group with unfavorable EFS. This study did not demonstrate that high baseline sTILs confer a benefit in EFS in the absence of a pCR.
High-Throughput Monoclonal Antibody Discovery from Phage Libraries: Challenging the Current Preclinical Pipeline to Keep the Pace with the Increasing mAb Demand
Authors: Zambrano Nicola , Froechlich Guendalina , Lazarevic Dejan , Passariello Margherita , Nicosia Alfredo , De Lorenzo Claudia , Morelli Marco J. , Sasso Emanuele
Published: March 2022

Monoclonal antibodies are among the most powerful therapeutics in modern medicine. Since the approval of the first therapeutic antibody in 1986, monoclonal antibodies keep holding great expectations for application in a range of clinical indications, highlighting the need to provide timely and sustainable access to powerful screening options. However, their application in the past has been limited by time-consuming and expensive steps of discovery and production. The screening of antibody repertoires is a laborious step; however, the implementation of next-generation sequencing-guided screening of single-chain antibody fragments has now largely overcome this issue. This review provides a detailed overview of the current strategies for the identification of monoclonal antibodies from phage display-based libraries. We also discuss the challenges and the possible solutions to improve the limiting selection and screening steps, in order to keep pace with the increasing demand for monoclonal antibodies.
Circulating Cell-Free DNA Reflects the Clonal Evolution of Breast Cancer Tumors
Authors: Kujala Jouni , Hartikainen Jaana M. , Tengström Maria , Sironen Reijo , Auvinen Päivi , Kosma Veli-Matti , Mannermaa Arto
Published: March 2022

Liquid biopsy of cell-free DNA (cfDNA) is proposed as a potential method for the early detection of breast cancer (BC) metastases and following the clonal evolution of BC. Though the use of liquid biopsy is a widely discussed topic in the field, only a few studies have demonstrated such usage so far. We sequenced the DNA of matched primary tumor and metastatic sites together with the matched cfDNA samples from 18 Eastern Finnish BC patients and investigated how well cfDNA reflected the clonal evolution of BC interpreted from tumor DNA. On average, liquid biopsy detected 56.2 ± 7.2% of the somatic variants that were present either in the matched primary tumor or metastatic sites. Despite the high discordance observed between matched samples, liquid biopsy was found to reflect the clonal evolution of BC and identify novel driver variants and therapeutic targets absent from the tumor DNA. Tumor-specific somatic variants were detected in cfDNA at the time of diagnosis and 8.4 ± 2.4 months prior to detection of locoregional recurrence or distant metastases. Our results demonstrate that the sequencing of cfDNA may be used for the early detection of locoregional and distant BC metastases. Observed discordance between tumor DNA sequencing and liquid biopsy supports the parallel sequencing of cfDNA and tumor DNA to yield the most comprehensive overview for the genetic landscape of BC.
Safety and Feasibility of Lung Cancer Surgery under the COVID-19 Circumstance
Authors: Berzenji Lawek , Vercauteren Leonie , Yogeswaran Suresh K. , Lauwers Patrick , Hendriks Jeroen M. H. , Van Schil Paul E.
Published: March 2022

The current coronavirus disease 2019 (COVID-19) pandemic has forced healthcare providers worldwide to adapt their practices. Our understanding of the effects of COVID-19 has increased exponentially since the beginning of the pandemic. Data from large-scale, international registries has provided more insight regarding risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and has allowed us to delineate specific subgroups of patients that have higher risks for severe complications. One particular subset of patients that have significantly higher risks of SARS-CoV-2 infection with higher morbidity and mortality rates are those that require surgical treatment for lung cancer. Earlier studies have shown that COVID-19 infections in patients that underwent lung cancer surgery is associated with higher rates of respiratory failure and mortality. However, deferral of cancer treatments is associated with increased mortality as well. This creates difficult situations in which healthcare providers are forced to weigh the benefits of surgical treatment against the possibility of SARS-CoV-2 infections. A number of oncological and surgical organizations have proposed treatment guidelines and recommendations for patients planned for lung cancer surgery. In this review, we summarize the latest data and recommendations for patients undergoing lung cancer surgery in the COVID-19 circumstance.
Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia
Authors: Fiñana Claudia , Gómez-Molina Noel , Alonso-Moreno Sandra , Belver Laura
Published: March 2022

Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative neoplasm of early childhood. Most of JMML patients experience an aggressive clinical course of the disease and require hematopoietic stem cell transplantation, which is currently the only curative treatment. JMML is characterized by RAS signaling hyperactivation, which is mainly driven by mutations in one of five genes of the RAS pathway, including PTPN11, KRAS, NRAS, NF1, and CBL. These driving mutations define different disease subtypes with specific clinico-biological features. Secondary mutations affecting other genes inside and outside the RAS pathway contribute to JMML pathogenesis and are associated with a poorer prognosis. In addition to these genetic alterations, JMML commonly presents aberrant epigenetic profiles that strongly correlate with the clinical outcome of the patients. This observation led to the recent publication of an international JMML stratification consensus, which defines three JMML clinical groups based on DNA methylation status. Although the characterization of the genomic and epigenomic landscapes in JMML has significantly contributed to better understand the molecular mechanisms driving the disease, our knowledge on JMML origin, cell identity, and intratumor and interpatient heterogeneity is still scarce. The application of new single-cell sequencing technologies will be critical to address these questions in the future.
A Novel and Automated Approach to Classify Radiation Induced Lung Tissue Damage on CT Scans
Authors: Szmul Adam , Chandy Edward , Veiga Catarina , Jacob Joseph , Stavropoulou Alkisti , Landau David , Hiley Crispin T. , McClelland Jamie R.
Published: March 2022

Radiation-induced lung damage (RILD) is a common side effect of radiotherapy (RT). The ability to automatically segment, classify, and quantify different types of lung parenchymal change is essential to uncover underlying patterns of RILD and their evolution over time. A RILD dedicated tissue classification system was developed to describe lung parenchymal tissue changes on a voxel-wise level. The classification system was automated for segmentation of five lung tissue classes on computed tomography (CT) scans that described incrementally increasing tissue density, ranging from normal lung (Class 1) to consolidation (Class 5). For ground truth data generation, we employed a two-stage data annotation approach, akin to active learning. Manual segmentation was used to train a stage one auto-segmentation method. These results were manually refined and used to train the stage two auto-segmentation algorithm. The stage two auto-segmentation algorithm was an ensemble of six 2D Unets using different loss functions and numbers of input channels. The development dataset used in this study consisted of 40 cases, each with a pre-radiotherapy, 3-, 6-, 12-, and 24-month follow-up CT scans (n = 200 CT scans). The method was assessed on a hold-out test dataset of 6 cases (n = 30 CT scans). The global Dice score coefficients (DSC) achieved for each tissue class were: Class (1) 99% and 98%, Class (2) 71% and 44%, Class (3) 56% and 26%, Class (4) 79% and 47%, and Class (5) 96% and 92%, for development and test subsets, respectively. The lowest values for the test subsets were caused by imaging artefacts or reflected subgroups that occurred infrequently and with smaller overall parenchymal volumes. We performed qualitative evaluation on the test dataset presenting manual and auto-segmentation to a blinded independent radiologist to rate them as ‘acceptable’, ‘minor disagreement’ or ‘major disagreement’. The auto-segmentation ratings were similar to the manual segmentation, both having approximately 90% of cases rated as acceptable. The proposed framework for auto-segmentation of different lung tissue classes produces acceptable results in the majority of cases and has the potential to facilitate future large studies of RILD.
Measuring Walking Speed Failed to Predict Early Death and Toxicity in Elderly Patients with Metastatic Non-Small-Cell Lung Cancer (NSCLC) Selected for Undergoing First-Line Systemic Treatment: An Observational Exploratory Study
Authors: Aregui Amélie , Pluvy Johan , Sanchez Manuel , Israel Theresa , Esnault Hélène , Guyard Alice , Meyer Marie , Khalil Antoine , Zalcman Gérard , Raynaud Simon Agathe , Gounant Valérie
Published: March 2022

Walking speed (WS) has emerged as a potential predictor of mortality in elderly cancer patients, yet data involving non-small-cell lung cancer (NSCLC) patients are scarce. Our prospective exploratory study sought to determine whether WS would predict early death or toxicity in patients with advanced NSCLC receiving first-line systemic intravenous treatment. Overall, 145 patients of ≥70 years were diagnosed with NSCLC over 19 months, 91 of whom displayed locally-advanced or metastatic cancer. As first-line treatment, 21 (23%) patients received best supportive care, 13 (14%) targeted therapy, and 57 (63%) chemotherapy or immunotherapy. Among the latter, 38 consented to participate in the study (median age: 75 years). Median cumulative illness rating scale for geriatrics (CIRS-G) was 10 (IQR: 8–12), and median WS 1.09 (IQR: 0.9–1.31) m/s. Older age (p = 0.03) and comorbidities (p = 0.02) were associated with Grade 3–4 treatment-related adverse events or death within 6 months of accrual. Overall survival was 14.3 (IQR: 6.1-NR) months for patients with WS < 1 m/s versus 17.3 (IQR: 9.2–26.5) for those with WS ≥ 1 m/s (p = 0.78). This exploratory study revealed WS to be numerically, yet not significantly, associated with early mortality in older metastatic NSCLC patients. Following these hypothesis-generating results, a larger prospective, multicenter study appears to be required to further investigate this outcome.
A Target Animal Effectiveness Study on Adjuvant Peptide-Based Vaccination in Dogs with Non-Metastatic Appendicular Osteosarcoma Undergoing Amputation and Chemotherapy
Authors: Marconato Laura , Melacarne Alessia , Aralla Marina , Sabattini Silvia , Tiraboschi Luca , Ferrari Valentina , Zeira Offer , Balboni Andrea , Faroni Eugenio , Guerra Dina , Pisoni Luciano , Ghezzi Erica , Pettinari Letizia , Rescigno Maria
Published: March 2022

Despite efforts to develop novel treatment strategies, human and canine osteosarcomas continue to have poor prognosis and limited overall survival. The aim of this clinical trial was to test the antitumor effect and safety of multiple dermal administrations of a peptide-based anticancer vaccine in dogs with non-metastatic appendicular osteosarcoma undergoing standard of care (SOC), consisting of limb amputation and adjuvant chemotherapy. Salmonella-infected canine osteosarcoma cells were induced to release immunogenic peptides in the extracellular space via Cx43 hemichannels opening; the secretome was collected and constituted the vaccine. Dogs with non-metastatic appendicular osteosarcoma were eligible for recruitment. Following limb amputation and adjuvant carboplatin, dogs were vaccinated on a monthly basis for six times and followed up with serial thoracic radiographs. A population of dogs undergoing SOC treatment (amputation and adjuvant carboplatin) before the vaccine was available served as controls. Primary endpoints were time to metastasis (TTM) and tumor-specific survival (TSS). Secondary endpoints were feasibility, toxicity, T-cell and humoral immune responses. A total of 20 dogs were vaccinated along with SOC and 34 received SOC only. Vaccine-specific humoral and T-cell responses were observed; their amplitude correlated with TSS. Vaccine-associated toxicity was not recorded. TTM and TSS were significantly longer in vaccinated versus unvaccinated dogs (TTM: 308 vs. 240 days, respectively; p = 0.010; TSS: 621 vs. 278 days, respectively; p = 0.002). In dogs with non-metastatic osteosarcoma undergoing SOC, the addition of a bacteria-based vaccination strategy increased TTM, thereby prolonging survival, while maintaining a safe profile. Additionally, vaccinated dogs developed a long-term tumor-specific response, as documented by the immunomonitoring of these patients over time. These results hold promise for future management of canine osteosarcoma.
Advancements in Oncology with Artificial Intelligence—A Review Article
Authors: Vobugari Nikitha , Raja Vikranth , Sethi Udhav , Gandhi Kejal , Raja Kishore , Surani Salim R.
Published: March 2022

Well-trained machine learning (ML) and artificial intelligence (AI) systems can provide clinicians with therapeutic assistance, potentially increasing efficiency and improving efficacy. ML has demonstrated high accuracy in oncology-related diagnostic imaging, including screening mammography interpretation, colon polyp detection, glioma classification, and grading. By utilizing ML techniques, the manual steps of detecting and segmenting lesions are greatly reduced. ML-based tumor imaging analysis is independent of the experience level of evaluating physicians, and the results are expected to be more standardized and accurate. One of the biggest challenges is its generalizability worldwide. The current detection and screening methods for colon polyps and breast cancer have a vast amount of data, so they are ideal areas for studying the global standardization of artificial intelligence. Central nervous system cancers are rare and have poor prognoses based on current management standards. ML offers the prospect of unraveling undiscovered features from routinely acquired neuroimaging for improving treatment planning, prognostication, monitoring, and response assessment of CNS tumors such as gliomas. By studying AI in such rare cancer types, standard management methods may be improved by augmenting personalized/precision medicine. This review aims to provide clinicians and medical researchers with a basic understanding of how ML works and its role in oncology, especially in breast cancer, colorectal cancer, and primary and metastatic brain cancer. Understanding AI basics, current achievements, and future challenges are crucial in advancing the use of AI in oncology.
Oligometastatic Disease in Non-Small-Cell Lung Cancer: An Update
Authors: Chen Yi-Hsing , Ho Ue-Cheung , Kuo Lu-Ting
Published: March 2022

Oligometastatic non-small-cell lung cancer (NSCLC) is a distinct entity that is different from localized and disseminated diseases. The definition of oligometastatic NSCLC varies across studies in past decades owing to the use of different imaging modalities; however, a uniform definition of oligometastatic NSCLC has been proposed, and this may facilitate trial design and evaluation of certain interventions. Patients with oligometastatic NSCLC are candidates for curative-intent management, in which local ablative treatment, such as surgery or stereotactic radiosurgery, should be instituted to improve clinical outcomes. Although current guidelines recommend that local therapy for thoracic and metastatic lesions should be considered for patients with oligometastatic NSCLC with stable disease after systemic therapy, optimal management strategies for different oligometastatic sites have not been established. Additionally, the development of personalized therapies for individual patients with oligometastatic NSCLC to improve their quality of life and overall survival should also be addressed. Here, we review relevant articles on the management of patients with oligometastatic NSCLC and categorize the disease according to the site of metastases. Ongoing trials are also summarized to determine future directions and expectations for new treatment modalities to improve patient management.
Diagnostic Accuracy of Contrast-Enhanced, Spectral Mammography (CESM) and 3T Magnetic Resonance Compared to Full-Field Digital Mammography plus Ultrasound in Breast Lesions: Results of a (Pilot) Open-Label, Single-Centre Prospective Study
Authors: Ferranti Francesca , Vasselli Federica , Barba Maddalena , Sperati Francesca , Terrenato Irene , Graziano Franco , Vici Patrizia , Botti Claudio , Vidiri Antonello
Published: March 2022

Introduction: To assess the diagnostic accuracy of CESM and 3T MRI compared to full-field digital mammography (FFDM), plus US, in the evaluation of advanced breast lesions. Materials and Methods: Consenting women with suspicious findings underwent FFDM, US, CESM and 3T MRI. Breast lesions were histologically assessed, with histology being the gold standard. Two experienced breast radiologists, blinded to cancer status, read the images. Diagnostic accuracy of (1) CESM as an adjunct to FFDM and US, and (2) 3T MRI as an adjunct to CESM compared to FFDM and US, was assessed. Measures of accuracy were sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). Results: There were 118 patients included along with 142 histologically characterized lesions. K agreement values were 0.69, 0.68, 0.63 and 0.56 for concordance between the gold standard and FFDM, FFDM + US, CESM and MRI, respectively (p < 0.001, for all). K concordance for CESM was 0.81 with FFDM + US and 0.73 with MRI (p value < 0.001 for all). Conclusions: CESM may represent a valuable alternative and/or an integrating technique to MRI in the evaluation of breast cancer patients.
The Clinical Utility and Impact of Next Generation Sequencing in Gynecologic Cancers
Authors: Maruthi Vijaya Kadam , Khazaeli Mahyar , Jeyachandran Devi , Desouki Mohamed Mokhtar
Published: March 2022

Next generation sequencing (NGS) has facilitated the identification of molecularly targeted therapies. However, clinical utility is an emerging challenge. Our objective was to identify the clinical utility of NGS testing in gynecologic cancers. A retrospective review of clinico-pathologic data was performed on 299 gynecological cancers where NGS testing had been performed to identify (1) recognition of actionable targets for therapy, (2) whether the therapy changed based on the findings, and (3) the impact on survival. High grade serous carcinoma was the most common tumor (52.5%). The number of genetic alterations ranged from 0 to 25 with a mean of 2.8/case. The most altered genes were TP53, PIK3CA, BRCA1 and BRCA2. Among 299 patients, 100 had actionable alterations (79 received a targeted treatment (Group1), 29 did not receive treatment (Group 2), and there were no actionable alterations in 199 (Group3). The death rate in groups 1, 2 and 3 was 54.4%, 42.8% and 50.2%, with an average survival of 18.6, 6.6 and 10.8 months, respectively (p = 0.002). In summary, NGS testing for gynecologic cancers detected 33.4% of actionable alterations with a high clinical action rate. Along with the high clinical utility of NGS, testing also seemed to improve survival for patients who received targeted treatment.
Comprehensive Analysis of the Prognosis and Drug Sensitivity of Differentiation-Related lncRNAs in Papillary Thyroid Cancer
Authors: Wang Wenlong , Bai Ning , Li Xinying
Published: March 2022

Dedifferentiation is the main concern associated with radioactive iodine (RAI) refractoriness in patients with papillary thyroid cancer (PTC), and the underlying mechanisms of PTC dedifferentiation remain unclear. The present work aimed to identify a useful signature to indicate dedifferentiation and further explore its role in prognosis and susceptibility to chemotherapy drugs. A total of five prognostic-related DR-lncRNAs were selected to establish a prognostic-predicting model, and corresponding risk scores were closely associated with the infiltration of immune cells and immune checkpoint blockade. Moreover, we built an integrated nomogram based on DR-lncRNAs and age that showed a strong ability to predict the 3- and 5-year overall survival. Interestingly, drug sensitivity analysis revealed that the low-risk group was more sensitive to Bendamustine and TAS-6417 than the high-risk group. In addition, knockdown of DR-lncRNAs (DPH6-DT) strongly promoted cell proliferation, invasion, and migration via PI3K-AKT signal pathway in vitro. Furthermore, DPH6-DT downregulation also increased the expression of vimentin and N-cadherin during epithelial-mesenchymal transition. This study firstly confirms that DR-lncRNAs play a vital role in the prognosis and immune cells infiltration in patients with PTC, as well as a predictor of the drugs’ chemosensitivity. Based on our results, DR-lncRNAs can serve as a promising prognostic biomarkers and treatment targets.
EGFR Mutation-Harboring Lung Cancer Cells Produce CLEC11A with Endothelial Trophic and Tumor-Promoting Activities
Authors: Lin Tzu-Yin , Yang Chi-Hwa , Chou Hsiao-Chin , Cheng Chun-Mei , Liu Ya-Wen , Wang Jiz-Yuh , Huang Li-Rung , Tsai Shih-Feng , Huang Shiu-Feng , Chen Yi-Rong
Published: March 2022

The formation of new blood vessels in solid tumors is regulated by various endothelial trophic factors. We identified that CLEC11A, an extracellular C-type lectin, was over-expressed in lung cancer cell lines harboring mutated EGFR. CLEC11A expression was also frequently elevated in lung adenocarcinoma (LAC) tissues with EGFR mutation. CLEC11A-expressing H1299 cells formed larger tumors in nude mice than did the control cells. The CLEC11A-expressing tumors contained more CD31-positive cells, suggesting that they had a higher angiogenic activity. CLEC11A per se did not induce blood vessel formation, but enhanced angiogenesis triggered by VEGF-A or basic FGF in vivo. Additionally, the expression of small hairpin RNA against CLEC11A (shCLEC11A) in HCC827 LAC cells suppressed their tumorigenic ability. Purified CLEC11A exhibited a chemotactic ability, which is dependent on its integrin-binding RGD and LDT motifs, toward endothelial cells. This chemotactic activity was not affected by the presence of a VEGFR inhibitor. Conditioned medium produced by HCC827-shCLEC11A cells had diminished chemotactic ability toward endothelial cells. CLEC11A treatments increased the levels of active integrin β1 that were not associated with activation of focal adhesion kinases in endothelial cells. Our results indicated that CLEC11A was a factor of angiogenic potential and was involved in lung cancer tumorigenesis.
Bifunctional CuO-Ag/KB Catalyst for the Electrochemical Reduction of CO2 in an Alkaline Solid-State Electrolysis Cell
Authors: Zignani Sabrina Campagna , Lo Faro Massimiliano , Palella Alessandra , Spadaro Lorenzo , Trocino Stefano , Lo Vecchio Carmelo , Aricò Antonino Salvatore
Published: March 2022

The conversion of carbon dioxide into value-added products is progressively gaining momentum. Several strategies have been used to develop technologies that reduce the net emissions of CO2. The utilisation of CO2 could either contribute to carbon recycling. In this paper, the transformation of CO2 was investigated in a coelectrolysis cell constituted of a solid polymer electrolyte, a carbon-supported CuO-Ag composite cathode and NiFeOx anode. Noncritical raw materials were synthesised according to the oxalate method and investigated in an alkaline environment. Low-carbon alcohols were obtained with a specific selectivity for ethanol and methanol over the CuO-Ag/KB cathode. The reaction rates at 1.6 V and 1.8 V cell voltages have been determined in steady-state experiments using NaHCO3 supporting electrolyte recirculated at the anode.
Polyaromatic Carboxylate Ligands Based Zn(II) Coordination Polymers for Ultrasound-Assisted One-Pot Tandem Deacetalization–Knoevenagel Reactions
Authors: Karmakar Anirban , Soliman Mohamed M. A. , Alegria Elisabete C. B. A. , da Silva Maria Fátima C. Guedes , Pombeiro Armando J. L.
Published: March 2022

Solvothermal reactions between the polyaromatic group containing carboxylic acid pro-ligands 5-{(pyren-1-ylmethyl)amino}isophthalic acid (H2L1) and 5-{(anthracen-9-ylmethyl)amino}isophthalic acid (H2L2) with Zn(NO3)2·6H2O led to the formation of the new 1D coordination polymer [Zn(L1)(NMF)]n (1) and four other coordination polymers, [Zn(L1)(DMF)]n (2), [Zn(L1)(4,4′-Bipy)]n (3), [Zn(L2)(DMF)(H2O)2]n·n(H2O) (4) and [Zn2(L2)2(DMF)(CH3OH)]n (5), which were previously reported by our group. Single crystal X-ray diffraction analyses revealed that the CP 1 has a one-dimensional (1D) double-chain-type structure similar to that of CP 2. For CP 3, the assembly of the Zn(II) ion with a deprotonated L12− ligand and 4,4′-bipyridine produces a 3D network. CP 4 and 5 exhibit 1D linear and 2D layered-type structures. The ultrasound-assisted tandem reactions promoted by CPs have not yet been well studied. Thus, in the present work, we have investigated the catalytic activities of the newly synthesized CP 1, as well as of the other CPs 2–5, towards the tandem deacetalization–Knoevenagel condensation reactions of various acetals under ultrasonic irradiation. They proved to be highly efficient, with special emphasis on catalyst 1, which completely converted the substrate (benzaldehyde dimethyl acetal) into the desired product (2-benzylidenemalononitrile) after 2 h. The stability of the catalysts, namely regarding the action of ultrasonic radiation, was demonstrated by their reuse, where only a slight loss of activity was observed after four cycles. Heterogeneity was also demonstrated, and no leaching was detected over the various cycles.
One-Pot Synthesis of TiO2/Hectorite Composite and Its Photocatalytic Degradation of Methylene Blue
Authors: Yang Dingqing , Chen Jinyang , Hong Xiaomin , Cui Jingying , Li Lingzhen
Published: March 2022

TiO2/hectorite composite photocatalysts with different molar ratios of lithium, magnesium, and silicon were synthesized by a one-pot hydrothermal method. The samples were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), N2 adsorption-desorption isotherms, and ultraviolet-visible diffuse reflectance spectra (UV-Vis DRS). When the molar ratio of lithium, magnesium, and silicon was 1.32:5.34:8 (TH-2), the composite showed the highest UV photocatalytic degradation of methylene blue (MB). The apparent rate constant of TH-2 was 0.04361 min−1, which was about 3.12 times that of EVONIK Degussa commercial TiO2 of AEROXIDE P25. The improvement of photocatalytic efficiency of the composite was mainly due to its high specific surface area, light trapping ability, and effective separation of electrons (e−) and holes (h+). At the same time, the F element of hectorite is beneficial to the formation of Ti3+ in TiO2, thus enhancing the photocatalytic activity. After five cycles, the removal rate of MB with TH-2 still reached 87.9%, indicating its excellent reusability.
Satellite Glial Cells and Neurons in Trigeminal Ganglia Are Altered in an Itch Model in Mice
Authors: Cohen Meytal , Feldman-Goriachnik Rachel , Hanani Menachem
Published: March 2022

Itch (pruritus) is a common chronic condition with a lifetime prevalence of over 20%. The mechanisms underlying itch are poorly understood, and its therapy is difficult. There is recent evidence that following nerve injury or inflammation, intercellular communications in sensory ganglia are augmented, which may lead to abnormal neuronal activity, and hence to pain, but there is no information whether such changes take place in an itch model. We studied changes in neurons and satellite glial cells (SGCs) in trigeminal ganglia in an itch model in mice using repeated applications of 2,4,6-trinitro-1-chlorobenzene (TNCB) to the external ear over a period of 11 days. Treated mice showed augmented scratching behavior as compared with controls during the application period and for several days afterwards. Immunostaining for the activation marker glial fibrillary acidic protein in SGCs was greater by about 35% after TNCB application, and gap junction-mediated coupling between neurons increased from about 2% to 13%. The injection of gap junction blockers reduced scratching behavior, suggesting that gap junctions contribute to itch. Calcium imaging studies showed increased responses of SGCs to the pain (and presumed itch) mediator ATP. We conclude that changes in both neurons and SGCs in sensory ganglia may play a role in itch.
Diagnostic and Prognostic Power of Active DNA Demethylation Pathway Intermediates in Acute Myelogenous Leukemia and Myelodysplastic Syndromes
Authors: Skalska-Bugala Aleksandra , Starczak Marta , Szukalski Łukasz , Gawronski Maciej , Siomek-Gorecka Agnieszka , Szpotan Justyna , Labejszo Anna , Zarakowska Ewelina , Szpila Anna , Jachalska Anna , Szukalska Adriana , Kruszewski Marcin , Sadowska Anna , Wasilow Aleksandra , Baginska Patrycja , Czyz Jaroslaw , Olinski Ryszard , Rozalski Rafal , Gackowski Daniel
Published: March 2022

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are characterized by genomic instability, which may arise from the global hypomethylation of the DNA. The active DNA demethylation process may be linked with aberrant methylation and can be involved in leukemogenesis. The levels of 5-methylcytosine oxidation products were analyzed in minimally invasive material: the cellular DNA from peripheral blood cells and urine of patients with AML and MDS along with the control group, using isotope-dilution two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry. The receiver operating characteristic curve analysis was used for the assessment of the ability to discriminate patients’ groups from the control group, and AML from MDS. The most diagnostically useful for discriminating AML patients from the control group was the urinary excretion of 5-hydroxymethylcytosine (AUC = 0.918, sensitivity: 85%, and specificity: 97%), and 5-(hydroxymethyl)-2′-deoxyuridine (0.873, 74%, and 92%), while for MDS patients 5-(hydroxymethyl)-2′-deoxycytidine in DNA (0.905, 82%, and 98%) and urinary 5-hydroxymethylcytosine (0.746, 66%, and 92%). Multi-factor models of classification trees allowed the correct classification of patients with AML and MDS in 95.7% and 94.7% of cases. The highest prognostic value of the analyzed parameters in predicting the transformation of MDS into AML was observed for 5-carboxy-2′-deoxycytidine (0.823, 80%, and 97%) and 5-(hydroxymethyl)-2′-deoxyuridine (0.872, 100%, and 75%) in DNA. The presented research proves that the intermediates of the active DNA demethylation pathway determined in the completely non-invasive (urine) or minimally invasive (blood) material can be useful in supporting the diagnostic process of patients with MDS and AML. The possibility of an early identification of a group of MDS patients with an increased risk of transformation into AML is of particular importance.
Revealing the Roles of MOAP1 in Diseases: A Review
Authors: Su Yanfang , Wang Weixia , Meng Xianfang
Published: March 2022

Modulator of apoptosis protein1 (MOAP1), also known as MAP1 and PNMA4, belongs to the PNMA gene family consisting of at least 15 genes located on different chromosomes. MOAP1 interacts with the BAX protein, one of the most important apoptosis regulators. Due to its critical role in a few of disease-associated pathways, MOAP1 is associated with many diseases such as cancers and neurological diseases. In this study, we introduced MOAP1 and its biological functions and reviewed the associations between MOAP1 and a few diseases including cancers, neurological diseases, and other diseases such as inflammation and heart diseases. We also explained possible biological mechanisms underlying the associations between MOAP1 and these diseases, and discussed a few future directions regarding MOAP1, especially its potential roles in neurodegenerative disorders. In summary, MOAP1 plays a critical role in the development and progression of cancers and neurological diseases by regulating a few genes related to cellular apoptosis such as BAX and RASSF1A and interacting with disease-associated miRNAs, including miR-25 and miR1228.
KCNQ2 Selectivity Filter Mutations Cause Kv7.2 M-Current Dysfunction and Configuration Changes Manifesting as Epileptic Encephalopathies and Autistic Spectrum Disorders
Authors: Lee Inn-Chi , Yang Jiann-Jou , Liou Ying-Ming , Wong Swee-Hee
Published: March 2022

KCNQ2 mutations can cause benign familial neonatal convulsions (BFNCs), epileptic encephalopathy (EE), and mild-to-profound neurodevelopmental disabilities. Mutations in the KCNQ2 selectivity filter (SF) are critical to neurodevelopmental outcomes. Three patients with neonatal EE carry de novo heterozygous KCNQ2 p.Thr287Ile, p.Gly281Glu and p.Pro285Thr, and all are followed-up in our clinics. Whole-cell patch-clamp analysis with transfected mutations was performed. The Kv7.2 in three mutations demonstrated significant current changes in the homomeric-transfected cells. The conduction curves for V1/2, the K slope, and currents in 3 mutations were lower than those for the wild type (WT). The p.Gly281Glu had a worse conductance than the p.Thr287Ile and p.Pro285Thr, the patient compatible with p.Gly281Glu had a worse clinical outcome than patients with p.Thr287Ile and p.Pro285Thr. The p.Gly281Glu had more amino acid weight changes than the p.Gly281Glu and p.Pro285Thr. Among 5 BFNCs and 23 EE from mutations in the SF, the greater weight of the mutated protein compared with that of the WT was presumed to cause an obstacle to pore size, which is one of the most important factors in the phenotype and outcome. For the 35 mutations in the SF domain, using changes in amino acid weight between the WT and the KCNQ2 mutations to predict EE resulted in 80.0% sensitivity and 80% specificity, a positive prediction rate of 96.0%, and a negative prediction rate of 40.0% (p = 0.006, χ2 (1, n = 35) = 7.56; odds ratio 16.0, 95% confidence interval, 1.50 to 170.63). The findings suggest that p.Thr287Ile, p.Gly281Glu and p.Pro285Thr are pathogenic to KCNQ2 EE. In mutations in SF, a mutated protein heavier than the WT is a factor in the Kv7.2 current and outcome.
A Mechanistic Theory of Development-Aging Continuity in Humans and Other Mammals
Authors: Walker Richard F.
Published: March 2022

There is consensus among biogerontologists that aging occurs either as the result of a purposeful genome-based, evolved program or due to spontaneous, randomly occurring, maladaptive events. Neither concept has yet identified a specific mechanism to explain aging’s emergence and acceleration during mid-life and beyond. Presented herein is a novel, unifying mechanism with empirical evidence that describes how aging becomes continuous with development. It assumes that aging emerges from deterioration of a regulatory process that directs morphogenesis and morphostasis. The regulatory system consists of a genome-wide “backbone” within which its specific genes are differentially expressed by the local epigenetic landscapes of cells and tissues within which they reside, thereby explaining its holistic nature. Morphostasis evolved in humans to ensure the nurturing of dependent offspring during the first decade of young adulthood when peak parental vitality prevails in the absence of aging. The strict redundancy of each morphostasis regulatory cycle requires sensitive dependence upon initial conditions to avoid initiating deterministic chaos behavior. However, when natural selection declines as midlife approaches, persistent, progressive, and specific DNA damage and misrepair changes the initial conditions of the regulatory process, thereby compromising morphostasis regulatory redundancy, instigating chaos, initiating senescence, and accelerating aging thereafter.
Surface-Enhanced Raman Spectroscopy for the Investigation of Chromogenic Motion Picture Films: A Preliminary Study
Authors: Longoni Margherita , Ferretti Francesco , Zucca Sofia , Caielli Letizia , Bruni Silvia
Published: March 2022

In the present work, surface-enhanced Raman spectroscopy (SERS) is proposed for the identification of dyes in chromogenic films. These substances, which are generated within the film itself during the colour development process, are first studied on reference molecules synthesised for the purpose and, subsequently, on dyes extracted from a chromogenic film. SERS spectroscopy proved to be an efficient technique for their investigation, providing a proof of concept for its applicability for further studies on this complex topic. SERS spectra of the reference molecules were also compared with normal Raman spectra, acquired with a spectrometer based on SSE™ technology. Furthermore, the excellent SERS properties of anisotropic nanomaterials, such as silver nanostars, have been confirmed.
Study of Orofacial Function in Preschool Children Born Prematurely
Authors: Chang Mei-Chen , Liu Hsiu-Yueh , Huang Shun-Te , Chen Hsiu-Lin
Published: March 2022

Children born prematurely often exhibit orofacial dysfunction. We conducted Nordic Orofacial Test Screening and analyzed chewing and swallowing functions of 243 children aged 3–5 years, consisting of 142 and 101 children born full-term and preterm, respectively, to evaluate the orofacial function of preschool premature children. Categorical variables were analyzed using chi-square test for a comparison. The univariate analysis of variance was used to analyze the effects of birth weight, gestational age, intubation at birth, use of nasal continuous positive airway pressure support after birth, and use of nasogastric tube on the chewing and swallowing functions of children born prematurely. In this survey, term-born children had a higher incidence of bad oral habits, grinding teeth while sleeping, and abnormal gulping compared to preterm-born children. Preterm-born children had a higher incidence of choking, decreased mouth opening (<30 mm), abnormal dental arch form, abnormal palatal vault, and dysarthria compared to term-born children.
Socio-Economic and Environmental Determinants of Malnutrition in under Three Children: Evidence from PDHS-2018
Authors: Shahid Muhammad , Cao Yang , Shahzad Muhammad , Saheed Rafit , Rauf Umara , Qureshi Madeeha Gohar , Hasnat Abdullah , Bibi Asma , Ahmed Farooq
Published: March 2022

Objectives: This research investigates the association of malnutrition with social and economic factors in general and environmental factors in specific such as sanitation facilities and drinking water sources for Pakistan. Methods: Authors used the latest data of 1010 Under-Three children from Pakistan Demographic and Health Survey (PDHS) 2017–2018. Cumulative Index of Anthropometric Failure (CIAF) was developed to measure the malnutrition status among children based on z-scores of WHZ, WAZ, and HAZ, respectively. The study has applied the discrete-choice logistic methodology to find the relationship of malnutrition with socio-economic characteristics. The interaction terms of drinking water source and sanitation facility have been measured to see the impact of environmental factors on child malnutrition. Results: The study results depict that the likelihood of malnutrition increases when the child had diarrhea recently and the child belongs to the deprived region such as KPK, Sind, and Baluchistan. However, the chances of child malnutrition drop with (1) an escalation of mothers’ education, (2) a rise in wealth status of the household, and (3) the improved water source and sanitation facility in the household. The only water-improved sanitation category of the interaction term is significant in the model which depicts that households having both improved water and improved sanitation facilities had very fewer chances of malnutrition among their children. Conclusion: Authors conclude that malnutrition in younger children is associated with improved water as well as sanitation facilities, maternal education, and household wealth in Pakistan.
Use of a Novel Manikin for Neonatal Resuscitation Ventilation Training
Authors: Chang Catherine , Perlman Jeffrey , Abramson Erika
Published: March 2022

All providers who attend deliveries independently should be well versed in the performance of effective ventilation, assessment of the quality of ventilation/interventions supplied and able to troubleshoot in situations where these may be ineffective. A novel manikin serves as a unique ventilation-focused training tool to practice these clinical skills and decision-making. The data generated by the manikin, with the aid of a facilitator, may be used for formative and summative feedback on an individual level or curricular development on a larger level. This communication describes the importance of focused ventilation training for front-line providers and illustrates how this manikin can be incorporated into an individualized ventilation training program.
Lifestyle Changes and Baseball Activity among Youth Baseball Players before and during the First COVID-19 Pandemic in Japan
Authors: Kuratsubo Ryota , Kawabata Masashi , Nakamura Emi , Yoshimoto Masumi , Tsunoda Satoshi , Takazawa Yuji , Watanabe Hiroyuki
Published: March 2022

This cross-sectional study aimed to clarify the changes in lifestyle and baseball activity before and during the COVID-19 pandemic among youth baseball players. Participants were 99 youth baseball players (ages 9.6 ± 1.5 years, height 137.8 ± 9.4 cm, weight 35.3 ± 12.4 kg) in Japan. They completed an online survey between April 6 and 20, 2021, on their demographic characteristics, lifestyle (recreational screen, sleep, and study times), and baseball activity (frequency of team practice time and voluntary exercise-related baseball) at two-time points: before the pandemic (before March 2020) and during the state of emergency declared in Japan (from April to May 2020). The changes in outcomes between the two-time points were evaluated for significance. Recreational screen time and sleeping time during the state of emergency were significantly increased compared to those before the pandemic (p < 0.001). The frequency of team practice time on weekends during the state of emergency was significantly reduced, and voluntary exercise-related baseball was significantly increased compared to that before the pandemic (p < 0.01). We found that the COVID-19 pandemic changed behaviors concerning activities and exercise among youth baseball players and recommended that such behavioral changes be carefully monitored.