bluuebunny/crossref_metadata_2025 huggingface dataset:
A Retrospective Analysis on Clinical Practice-Based Approaches Using Zolpidem and Lorazepam in Disorders of Consciousness
Authors: Zhang Bei , O’Brien Katherine , Won William , Li Sheng
Published: May 2021

This is a retrospective study to investigate the results of using zolpidem and lorazepam in persons with disorders of consciousness (DoC) and to provide practical information for clinical application and further studies. The cohort included 146 patients (11 hemorrhagic stroke, 87 traumatic brain injury (TBI), 48 anoxic brain injury (ABI)) admitted to a specialized DoC rehabilitation program. A positive trial indicated a patient responded to either zolpidem or lorazepam with prominent functional improvements necessitating routine use of the medication. Non-responders had equivocal or negative (i.e., went to sleep) responses. Eleven patients with a stroke who had either medication were all non-responders. Of the remaining 135 patients, 95 received at least one medication trial. The overall positive rate was 11.6% (11/95), with 6.3% (5/79) for zolpidem and 14.0% (6/43) for lorazepam. Among TBI patients, the positive rate of the zolpidem trial (10.2%, 5/49) was slightly higher than that of the lorazepam trial (6.9%, 2/29; p > 0.05). Among ABI patients, the positive rate of the lorazepam trial (28.6%, 4/14) was significantly higher than that of the zolpidem trial (0%, 0/30; p = 0.007). Following a positive trial, most patients were continued on the medications on a regular basis before eventual discontinuation. Our results suggested the etiology of DoC, considering traumatic vs. anoxic injuries, may serve in guiding the clinical application of these medications in the treatment of DoC and in future prospective studies. We advocate for screening all patients with DoC using zolpidem and/or lorazepam.
Apathy and Anhedonia: Clinical and Neurophysiological Assessment of a Romanian Cohort
Authors: Sipos-Lascu Diana , Vesa Ștefan-Cristian , Perju-Dumbravă Lăcrămioara
Published: May 2021

Background: Patients with Parkinson’s disease (PD) often have, besides the characteristic motor manifestations, a wide variety of non-motor symptoms. These include apathy and anhedonia, common issues in PD, which can be quantified with the help of evaluation scales recommended by the literature. There are sensory non-motor manifestations of PD, some of which are easy to detect through electrophysiological studies. Our aim was to investigate the possible association of apathy and anhedonia with the severity of the motor status in a sample of PD patients in Romania. We also examined the prevalence of latency changes in the P100 wave of visual evoked potentials (VEPs) and how they correlated with motor status, apathy, and anhedonia in PD patients. Methods: Thirty-four patients with PD participated in this study. All were assessed for motor status using the Unified Parkinson’s Disease Rating Scale (UPDRS) and were rated on the Hoehn and Yahr scales. The presence and severity of apathy and anhedonia were assessed using the Apathy Evaluation Scale (AES), the Dimensional Apathy Scale (DAS), the Lille Apathy Rating Scale (LARS), and the Snaith–Hamilton Pleasure Scale (SHAPS). The latency of the P100 wave of the VEP was measured in all the patients. Results: Apathy and anhedonia were common among the patients with PD (35% and 58.8%, respectively). The presence of apathy/anhedonia was correlated with the severity of motor symptoms, as assessed using the UPDRS scale (p < 0.001), and with the stage of the disease according to the Hoehn and Yahr scale (p < 0.001). A prolonged latency of the P100 wave of the VEP was observed among apathetic (p < 0.001)/anhedonic (p < 0.01) patients and those with increased disease severity (p < 0.001). Conclusion: Apathy and anhedonia are common in PD and may correlate with the severity of motor symptoms. There may be visual impairment in these patients, evidenced by a prolonged P100 latency, which correlates with the severity of disease. Significance: Scales for assessing apathy and anhedonia, as well as measuring VEP latency, could be useful in assessing the severity of disease.
Longitudinal Impact of Physical Activity on Brain Pulsatility Index and Cognition in Older Adults with Cardiovascular Risk Factors: A NIRS Study
Authors: Mohammadi Hanieh , Gagnon Christine , Vincent Thomas , Kassab Ali , Fraser Sarah , Nigam Anil , Lesage Frédéric , Bherer Louis
Published: May 2021

Recent studies have shown that optical indices of cerebral pulsatility, including cerebral pulse amplitude, are linked to cerebrovascular health. A chronically higher cerebral pulsatility is associated with cognitive decline. Although it is widely known that regular physical activity improves cognitive functions, little is known about the association between physical activity and the optical index of cerebral pulsatility. This study assessed the impact of 12 months of regular physical activity on the changes in the optical index of cerebral pulsatility and explored its association with cognition. A total of 19 older adults (aged 59–79 years) with cardiovascular risk factors (CVRF) completed the study. Low-intensity, short-duration walking as a brief cardiovascular challenge was used to study the impact of regular physical activity on post-walking changes in cerebral pulsatility index. The participants walked on a gym track while a near-infrared spectroscopy (NIRS) device recorded hemodynamics data from the frontal and motor cortex subregions. Our data indicated that 12 months of physical activity was associated with lower global cerebral pulse amplitude, which was associated with higher cognitive scores in executive functions. Further, the global cerebral pulsatility index was reduced after short-duration walking, and this reduction was greater after 12 months of regular physical activity compared with the baseline. This may be an indication of improvement in cerebrovascular response to the cardiovascular challenge after regular physical activity. This study suggests that 12 months of physical activity may support cognitive functions through improving cerebral pulsatility in older adults with CVRF.
Factors Affecting Occupants’ Satisfaction in Governmental Buildings: The Case of the Kingdom of Bahrain
Authors: Albuainain Noora , Sweis Ghaleb , AlBalkhy Wassim , Sweis Rateb , Lafhaj Zoubeir
Published: May 2021

Satisfaction is a very important factor in improving productivity and performance in the work environment. This study aims to investigate the levels of occupants’ satisfaction with the indoor environmental quality (IEQ) in the governmental buildings in the Kingdom of Bahrain and to investigate the impact of occupants’ demographics and building attributes (non-IEQ factors) on these levels. For these purposes, the study used a questionnaire that has 17 indoor environmental quality (IEQ) factors in addition to a group of non-IEQ factors. The questionnaire was distributed by hand or using email to 279 employees in the Bahraini governmental sector. The findings of the study revealed that occupants in the Bahraini governmental buildings are not strongly satisfied with IEQ factors, especially with sound privacy, followed by visual privacy and amount of space, and then noise levels. The findings also showed that for most IEQ factors, men are more satisfied than women are, those who work in enclosed private offices are more satisfied than those who work in open-plan offices, and those who have central air-conditioning at their workplace are more than those who have a wall-mounted air conditioner. The impact of age, nature of work, duration of working in the current building and at the current workstation, weekly working hours, and proximity to the window were also investigated. Accordingly, a group of recommendations was suggested aiming to improve the levels of occupants’ satisfaction.
A Nomogram-Based Prognostic Model for Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib: A Multicenter Study
Authors: Marasco Giovanni , Poggioli Francesco , Colecchia Antonio , Cabibbo Giuseppe , Pelizzaro Filippo , Giannini Edoardo , Marinelli Sara , Rapaccini Gian , Caturelli Eugenio , Di Marco Mariella , Biasini Elisabetta , Marra Fabio , Morisco Filomena , Foschi Francesco , Zoli Marco , Gasbarrini Antonio , Svegliati Baroni Gianluca , Masotto Alberto , Sacco Rodolfo , Raimondo Giovanni , Azzaroli Francesco , Mega Andrea , Vidili Gianpaolo , Brunetto Maurizia , Nardone Gerardo , Alemanni Luigina , Dajti Elton , Ravaioli Federico , Festi Davide , Trevisani Franco ,   on behalf of the Italian Liver Cancer (ITA.LI.CA.) Group
Published: May 2021

Among scores and staging systems used for HCC, none showed a good prognostic ability in patients with advanced HCC treated with Sorafenib. We aimed to evaluate predictive factors of overall survival (OS) and drug response in HCC patients undergoing Sorafenib included in the Italian Liver Cancer (ITA.LI.CA.) multicenter cohort. Patients in the ITA.LI.CA database treated with Sorafenib and updated on 30 June 2019 were included. Demographic and clinical data before starting Sorafenib treatment were considered. For the evaluation of predictive factors for OS, a time-dependent Cox proportional hazard model was used. A total of 1107 patients were included in our analysis. The mean age was 64.3 years and 81.7% were male. Most patients were staged as BCLC B (205, 18.9%) or C (706, 65.1%). The median time of Sorafenib administration was 4 months (interquartile range (IQR) 2–12), and the median OS was 10 months (IQR: 4–20). A total of 263 patients (33.8%) out of 780 with available evaluation experienced objective tumoral response to Sorafenib. The Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (hazard ratio (HR) 1.284), maximum tumoral diameter (HR 1.100), plasma total bilirubin (HR 1.119), aspartate amino transferase assessed as multiple of the upper normal value (HR 1.032), alpha-fetoprotein ≥200 ng/mL (HR 1.342), hemoglobin (HR 0.903) and platelet count (HR 1.002) were associated with OS at multivariate Cox regression analysis. Drug response was predicted by maximum tumoral diameter and platelet count. A novel prognostic nomogram for patients undergoing Sorafenib is hereby proposed. The novelty introduced is the comprehensive patient’s assessment using common markers of patient’s general status, liver damage and function and HCC biology. Further studies are required to test its accuracy and provide external validation.
Primary Gastrointestinal T/NK Cell Lymphoma
Authors: Kim Eun Kyung , Jang Mi , Yang Woo Ick , Yoon Sun Och
Published: May 2021

Primary gastrointestinal T/NK cell lymphoma (GI-TNKL) is an uncommon and heterogeneous group of lymphoid malignancies. We aimed to investigate their subtype distribution, clinicopathologic characteristics, and clinical outcomes. A total of 38 GI-TNKL cases and their clinical and pathological characteristics were analyzed. GI-TNKL occurred in adults with a median patient age in the sixth decade of life and showed a slight male predominance. The most common histologic type was extranodal NK/T-cell lymphoma, nasal type (ENKTL; 34.2%), followed by monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL; 31.6%), intestinal T-cell lymphoma, NOS (ITCL, NOS, 18.4%), anaplastic large cell lymphoma, ALK-negative (ALCL, ALK-; 13.2%). The small intestine was the primary affected region. More than 90% of patients complained of various GI symptoms and cases with advanced Lugano stage, high IPI score, or bowel perforation that required emergent operation were not uncommon. GI-TNKL also showed aggressive behavior with short progression-free survival and overall survival. This thorough clinical and pathological descriptive analysis will be helpful for accurate understanding, diagnosis, and treatment.
Modeling-Based Decision Support System for Radical Prostatectomy Versus External Beam Radiotherapy for Prostate Cancer Incorporating an In Silico Clinical Trial and a Cost–Utility Study
Authors: van Wijk Yvonka , Ramaekers Bram , Vanneste Ben G. L. , Halilaj Iva , Oberije Cary , Chatterjee Avishek , Marcelissen Tom , Jochems Arthur , Woodruff Henry C. , Lambin Philippe
Published: May 2021

The aim of this study is to build a decision support system (DSS) to select radical prostatectomy (RP) or external beam radiotherapy (EBRT) for low- to intermediate-risk prostate cancer patients. We used an individual state-transition model based on predictive models for estimating tumor control and toxicity probabilities. We performed analyses on a synthetically generated dataset of 1000 patients with realistic clinical parameters, externally validated by comparison to randomized clinical trials, and set up an in silico clinical trial for elderly patients. We assessed the cost-effectiveness (CE) of the DSS for treatment selection by comparing it to randomized treatment allotment. Using the DSS, 47.8% of synthetic patients were selected for RP and 52.2% for EBRT. During validation, differences with the simulations of late toxicity and biochemical failure never exceeded 2%. The in silico trial showed that for elderly patients, toxicity has more influence on the decision than TCP, and the predicted QoL depends on the initial erectile function. The DSS is estimated to result in cost savings (EUR 323 (95% CI: EUR 213–433)) and more quality-adjusted life years (QALYs; 0.11 years, 95% CI: 0.00–0.22) than randomized treatment selection.
Transcriptomic Profiling of the Liver Sinusoidal Endothelium during Cirrhosis Reveals Stage-Specific Secretory Signature
Authors: Manicardi Nicolò , Fernández-Iglesias Anabel , Abad-Jordà Laia , Royo Felix , Azkargorta Mikel , Ortega-Ribera Martí , Sanfeliu-Redondo David , Martínez-Alcocer Ana , Elortza Felix , Hessheimer Amelia J. , Fondevila Constantino , Lozano Juan José , García-Pagán Juan Carlos , Bosch Jaime , Cubero Francisco Javier , Albillos Agustín , Vaquero Javier , Falcón-Pérez Juan M. , Gracia-Sancho Jordi
Published: May 2021

The poor prognosis of chronic liver disease (CLD) generates the need to investigate the evolving mechanisms of disease progression, thus disclosing therapeutic targets before development of clinical complications. Considering the central role of liver sinusoidal endothelial cells (LSECs) in pre-neoplastic advanced CLD, the present study aimed at investigating the progression of CLD from an endothelial holistic perspective. RNAseq defined the transcriptome of primary LSECs isolated from three pre-clinical models of advanced CLD, during the progression of the disease, and from fresh human cirrhotic tissue. At each stage of the disease, the effects of LSECs secretome on neighboring cells and proteomic analysis of LSECs-derived extracellular vesicles (EVs) were also determined. CLD was associated with deep common modifications in the transcriptome of LSECs in the pre-clinical models. Pathway enrichment analysis showed predominance of genes related with pro-oncogenic, cellular communication processes, and EVs biogenesis during CLD progression. Crosstalk experiments revealed endothelial EVs as potent angiocrine effectors. The proteome of LSECs EVs showed stage-specific signatures, including over-expression of tropomyosin-1. Proof-of-principle experiments treating cirrhotic HSCs with recombinant tropomyosin-1 suggested de-activating effects. Our data provide the basis for discovering novel biomarkers and therapeutic targets for new disease-modifying treatments for patients with advanced CLD.
Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma
Authors: Popp Felix , Capino Ingracia , Bartels Joana , Damanakis Alexander , Li Jiahui , Datta Rabi , Löser Heike , Zhao Yue , Quaas Alexander , Lohneis Philipp , Bruns Christiane ,   on behalf of the PANCALYZE Study Group
Published: May 2021

Pancreatic cancer features elaborate mechanisms of immune evasion. The potential of new immune molecules was explored to restore the antitumor immune response. If these immune molecules are associated with poor survival, specific drugs could take effect. Here, we analyze the expression of VISTA, LAG3, IDO, and TIM3 on tumor-infiltrating lymphocytes (TILs) and its impact on patient survival. We analyzed 153 pancreatic cancer patients from the prospectively managed database of the multicentered PANCALYZE study. Immunohistochemistry on a tissue microarray assessed VISTA, LAG3, IDO, and TIM3 expression of TILs from the patients undergoing primary resection. Complementarily, we analyzed publicly available transcriptomic data (n = 903). Successful completion of chemotherapy, and lymph node status were independent predictors of survival in the multivariate analysis of the clinicopathologic parameters. Fifteen tumors were exclusively VISTA-positive, thirteen tumors expressed VISTA together with TIM3, and ten tumors expressed VISTA together with IDO. Patients featuring tumors with high numbers of IDO-positive TILs had better patient survival (p = 0.037). VISTA, LAG3, and TIM3 expression did not correlate with survival. The analysis of publicly available data did not show survival differences. Tumors rarely co-express more than two immune molecules at the same time, and VISTA is most frequently co-expressed. Although IDO generally inhibits T-cell proliferation, a high expression of IDO was associated with improved survival. We expect immune checkpoint inhibitors against VISTA, LAG3, and TIM3 to be inefficient in a clinical application.
Comparing the Effectiveness of a Wearable Activity Tracker in Addition to Counseling and Counseling Only to Reinforce Leisure-Time Physical Activity among Breast Cancer Patients: A Randomized Controlled Trial
Authors: Kong Sunga , Lee Jae Kyung , Kang Danbee , Kim Nayeon , Shim Young Mog , Park Won , Choi Dooho , Cho Juhee
Published: May 2021

This randomized controlled trial aimed to compare the effectiveness of a wearable activity tracker (WAT) in addition to counseling (WAT+counseling) and counseling only for reinforcing leisure-time physical activity (LTPA) among breast cancer patients during radiotherapy (RT). A total of 152 breast cancer patients who were planning to undergo radiation therapy (RT) after surgery participated in the study. The WAT+counseling group (n = 76) underwent physical activity (PA) self-monitoring using a WAT and participated in counseling. The counseling-only group (n = 76) received telephone counseling once a week during RT and did not receive WAT. The WAT+counseling group had increased relative change in self-reported LTPA (102.8) compared with the counseling-only group (57.8) immediately after RT compared to baseline. Although the relative changes of self-reported LTPA of the WAT+counseling group were higher at three and six months after the end of RT compared to in the counseling-only group, the results were not significant. The mean average daily step count of the WAT+counseling group was 9351.7, which increased to 11,592.2 during RT and 12,240.1 after RT. In the subgroup analysis, patients who did not perform regular PA before cancer diagnosis had significantly increased step counts. This study shows the feasibility of WAT with counseling to reinforce PA among breast cancer patients.
Burden and Needs of Patients with Severe GvHD from the Supportive and Palliative Care Perspective—A Literature Review
Authors: Wenzel Freya , Pralong Anne , Holtick Udo , Scheid Christoph , Herling Marco , Simon Steffen T
Published: May 2021

Graft-versus-host disease (GvHD) is a frequent, and often life-threatening, complication after an allogeneic, hematopoietic stem cell transplantation (allo-SCT). It can appear in an acute or a chronic form and presents different grades of severity. Particularly, the severe forms of GvHD are often responsible for a change of the curative intent for allo-SCT into a palliative goal of care. For this non-systematic review, we conducted a focused literature search in the MEDLINE database via PubMed to examine whether patients with severe forms of GvHD might have special needs and burdens from a supportive and palliative care perspective. To draw a comprehensive picture of this patient group, we included findings on quality of life (QoL) and physical symptoms and function as well as psychological and spiritual well-being. In most domains, patients with severe forms of GvHD showed greater impairment and a higher symptom burden compared to patients with milder forms of GvHD. However, we could not identify any studies that specifically investigated patients with severe forms of GvHD. Further research in this field is necessary to guarantee the highest standard of care for this very special patient group.
Uni-, Bi- or Trifocal Hepatocellular Carcinoma in Western Patients: Recurrence and Survival after Percutaneous Thermal Ablation
Authors: Preel Ancelin , Hermida Margaux , Allimant Carole , Assenat Eric , Guillot Chloé , Gozzo Cecilia , Aho-Glele Serge , Pageaux Georges-Philippe , Cassinotto Christophe , Guiu Boris
Published: May 2021

Multifocality is usually reported as a pejorative factor after percutaneous thermal ablation (PTA) of HCC but little is known in Western series. Recurrence and survival were extracted from a prospective database of all patients who underwent PTA for ≤3 cm HCC. From January 2015 to April 2020, we analyzed 281 patients with unifocal (n = 216), bifocal (n = 46) and trifocal (n = 16) HCC. PTA of bi- and trifocal HCC resulted in a high risk of very early (<6 months) distant recurrence (38.8% and 50%, respectively). Median RFS was 23.3 months (95% CI:18.6–30.4), 7.7 months (95% CI:5.1–11.43, p = 0.002) and 5.2 months (95% CI:3–12.3, p = 0.015), respectively, for uni-, bi- and trifocal HCC groups. In a multivariate analysis, both bifocal (HR = 2.46, p < 0.001) and trifocal (HR = 2.70, p = 0.021) vs. unifocal HCC independently predicted shorter RFS. Median OS in trifocal HCC group was 30.3 months (95 CI:19.3-not reached). Trifocal vs. unifocal HCC independently predicted shorter OS (HR = 3.30, p = 0.008), whereas bifocal vs. unifocal HCC did not (p = 0.27). Naïve patient (HR = 0.42, p = 0.007), AFP > 100 ng/mL (HR = 3.03, p = 0.008), MELD > 9 (HR = 2.84, p = 0.001) and steatotic HCC (HR = 0.12, p = 0.038) were also independent predictors of OS. In conclusion, multifocal HCCs in a Western population have a dramatically increased risk of distant recurrence. OS after PTA of trifocal HCC is significantly below what was expected after a curative treatment.
Rare Germline Variants in Chordoma-Related Genes and Chordoma Susceptibility
Authors: Yepes Sally , Shah Nirav N. , Bai Jiwei , Koka Hela , Li Chuzhong , Gui Songbai , McMaster Mary Lou , Xiao Yanzi , Jones Kristine , Wang Mingyi , Vogt Aurelie , Zhu Bin , Zhu Bin , Hutchinson Amy , Yeager Meredith , Hicks Belynda , Carter Brian , Freedman Neal D. , Beane-Freeman Laura , Chanock Stephen J. , Zhang Yazhuo , Parry Dilys M. , Yang Xiaohong R. , Goldstein Alisa M.
Published: May 2021

Background: Chordoma is a rare bone cancer with an unknown etiology. TBXT is the only chordoma susceptibility gene identified to date; germline single nucleotide variants and copy number variants in TBXT have been associated with chordoma susceptibility in familial and sporadic chordoma. However, the genetic susceptibility of chordoma remains largely unknown. In this study, we investigated rare germline genetic variants in genes involved in TBXT/chordoma-related signaling pathways and other biological processes in chordoma patients from North America and China. Methods: We identified variants that were very rare in general population and internal control datasets and showed evidence for pathogenicity in 265 genes in a whole exome sequencing (WES) dataset of 138 chordoma patients of European ancestry and in a whole genome sequencing (WGS) dataset of 80 Chinese patients with skull base chordoma. Results: Rare and likely pathogenic variants were identified in 32 of 138 European ancestry patients (23%), including genes that are part of notochord development, PI3K/AKT/mTOR, Sonic Hedgehog, SWI/SNF complex and mesoderm development pathways. Rare pathogenic variants in COL2A1, EXT1, PDK1, LRP2, TBXT and TSC2, among others, were also observed in Chinese patients. Conclusion: We identified several rare loss-of-function and predicted deleterious missense variants in germline DNA from patients with chordoma, which may influence chordoma predisposition and reflect a complex susceptibility, warranting further investigation in large studies.
Ubiquitin Specific Protease 29 Functions as an Oncogene Promoting Tumorigenesis in Colorectal Carcinoma
Authors: Chandrasekaran Arun Pandian , Suresh Bharathi , Sarodaya Neha , Ko Na-Re , Oh Seung-Jun , Kim Kye-Seong , Ramakrishna Suresh
Published: May 2021

Colorectal carcinoma is the third foremost cause of cancer-related deaths and accounts for 5.8% of all deaths globally. The molecular mechanisms of colon cancer progression and metastasis control are not well studied. Ubiquitin-specific protease 29 (USP29), a deubiquitinating enzyme, is involved in the occurrence and development of wide variety of cancers. However, its clinical significance and biological roles in colorectal carcinoma (CRC) remain unexplored. In this research, we observed that the rate of USP29 overexpression was higher in colon cancer patient tissues relative to its corresponding normal tissues. CRISPR-Cas9-mediated depletion of USP29 triggered DNA double strand breaks and delayed cell-cycle progression in HCT116 cells. We also demonstrated that USP29 depletion hampers the colony formation and increases apoptosis of HCT116 cells. USP29 knockdown significantly decreased CRC cell proliferation in vitro. Depletion of USP29 in HCT116 cells substantially reduced the tumor volume of mouse xenografts. In conclusion, our study shows that elevated expression of USP29 promotes malignancy in CRC, suggesting that USP29 could be a promising target for colon cancer therapy.
Prognostic Genetic Biomarkers Based on Oncogenic Signaling Pathways for Outcome Prediction in Patients with Oral Cavity Squamous Cell Carcinoma
Authors: Fan Wen-Lang , Yang Lan-Yan , Hsieh Jason Chia-Hsun , Lin Tsung-Chieh , Lu Mei-Yeh Jade , Liao Chun-Ta
Published: May 2021

Mutational profiling of patients’ tumors has suggested that the development of oral cavity squamous cell carcinoma (OCSCC) is driven by multiple genes in multiple pathways. This study aimed to examine the association between genomic alterations and clinical outcomes in patients with advanced stages OCSCC to facilitate prognostic stratification. We re-analyzed our previous whole-exome sequencing data from 165 long-term follow-ups of stages III and IV patients with OCSCC. Their frequent mutations were mapped to 10 oncogenic signaling pathways. Clinicopathological risk factors, relapse, and survival were analyzed to identify the genetic factors associated with advanced OCSCC. Frequent genetic alterations included point mutations in TP53, FAT1, NOTCH1, CASP8, CDKN2A, HRAS, PIK3CA, KMT2B (also known as MLL4), and LINC00273; amplified segments in CCND1, EGFR, CTTN, and FGFR1; and lost segments in CDKN2A, ADAM3A, and CFHR1/CFHR4. Comprehensive analysis of genetic alterations revealed that subgroups based on mutational signatures had a significant negative impact on disease-free survival (p = 0.0005) and overall survival (p = 0.0024). Several important signaling pathways were identified to be frequently genetically altered in our cohort. A specific subgroup of patients with alterations in NOTCH, RTK/RAS/MAPK, and TGF-beta pathways that had a significantly negative impact on disease-free survival (p = 0.0009). Thirty percent of samples had multiple targetable mutations in multiple pathways, indicating opportunities for novel therapy.
Rapid Progress in Immunotherapies for Multiple Myeloma: An Updated Comprehensive Review
Authors: Nishida Hiroko
Published: May 2021

Despite rapid advances in treatment approaches of multiple myeloma (MM) over the last two decades via proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs), their efficacies are limited. MM still remains incurable, and the majority of patients shortly relapse and eventually become refractory to existing therapies due to the genetic heterogeneity and clonal evolution. Therefore, the development of novel therapeutic strategies with different mechanisms of action represents an unmet need to achieve a deep and highly durable response as well as to improve patient outcomes. The antibody-drug conjugate (ADC), belanatmab mafadotin, which targets B cell membrane antigen (BCMA) on plasma cells, was approved for the treatment of MM in 2020. To date, numerous immunotherapies, including bispecific antibodies, such as bispecific T cell engager (BiTE), the duobody adoptive cellular therapy using a dendritic cell (DC) vaccine, autologous chimeric antigen (CAR)-T cells, allogeneic CAR-natural killer (NK) cells, and checkpoint inhibitors have been developed for the treatment of MM, and a variety of clinical trials are currently underway or are expected to be planned. In the future, the efficacy of combination approaches, as well as allogenic CAR-T or NK cell therapy, will be examined, and promising results may alter the treatment paradigm of MM. This is a comprehensive review with an update on the most recent clinical and preclinical advances with a focus on results from clinical trials in progress with BCMA-targeted immunotherapies and the development of other novel targets in MM. Future perspectives will also be discussed.
Texture Analysis of Fractional Water Content Images Acquired during PET/MRI: Initial Evidence for an Association with Total Lesion Glycolysis, Survival and Gene Mutation Profile in Primary Colorectal Cancer
Authors: Ganeshan Balaji , Miles Kenneth , Afaq Asim , Punwani Shonit , Rodriguez Manuel , Wan Simon , Walls Darren , Hoy Luke , Khan Saif , Endozo Raymond , Shortman Robert , Hoath John , Bhargava Aman , Hanson Matthew , Francis Daren , Arulampalam Tan , Dindyal Sanjay , Chen Shih-Hsin , Ng Tony , Groves Ashley
Published: May 2021

To assess the capability of fractional water content (FWC) texture analysis (TA) to generate biologically relevant information from routine PET/MRI acquisitions for colorectal cancer (CRC) patients. Thirty consecutive primary CRC patients (mean age 63.9, range 42–83 years) prospectively underwent FDG-PET/MRI. FWC tumor parametric images generated from Dixon MR sequences underwent TA using commercially available research software (TexRAD). Data analysis comprised (1) identification of functional imaging correlates for texture features (TF) with low inter-observer variability (intraclass correlation coefficient: ICC > 0.75), (2) evaluation of prognostic performance for FWC-TF, and (3) correlation of prognostic imaging signatures with gene mutation (GM) profile. Of 32 FWC-TF with ICC > 0.75, 18 correlated with total lesion glycolysis (TLG, highest: rs = −0.547, p = 0.002). Using optimized cut-off values, five MR FWC-TF identified a good prognostic group with zero mortality (lowest: p = 0.017). For the most statistically significant prognostic marker, favorable prognosis was significantly associated with a higher number of GM per patient (medians: 7 vs. 1.5, p = 0.009). FWC-TA derived from routine PET/MRI Dixon acquisitions shows good inter-operator agreement, generates biological relevant information related to TLG, GM count, and provides prognostic information that can unlock new clinical applications for CRC patients.
Techno-Economic and Environmental Analysis for Direct Catalytic Conversion of CO2 to Methanol and Liquid/High-Calorie-SNG Fuels
Authors: Atsbha Tesfalem Aregawi , Yoon Taeksang , Yoo Byung-Hoon , Lee Chul-Jin
Published: May 2021

Catalytic hydrogenation of CO2 has great potential to significantly reduce CO2 and contribute to green economy by converting CO2 into a variety of useful products. The goal of this study is to assess and compare the techno-economic and environmental measures of CO2 catalytic conversion to methanol and Fischer–Tropsch-based fuels. More specifically, two separate process models were developed using a process modeler: direct catalytic conversion of CO2 to Fischer–Tropsch-based liquid fuel/high-calorie SNG and direct catalytic conversion of CO2 to methanol. The unit production cost for each process was analyzed and compared to conventional liquid fuel and methanol production processes. CO2 emissions for each process were assessed in terms of global warming potential. The cost and environmental analyses results of each process were used to compare and contrast both routes in terms of economic feasibility and environmental friendliness. The results of both the processes indicated that the total CO2 emissions were significantly reduced compared with their respective conventional processes.
Stable Surface Technology for HER Electrodes
Authors: Kim Hong Soo , Kim Hwapyong , Flores Monica Claire , Jung Gyu-Seok , In Su-Il
Published: May 2021

With the rapid increase in energy consumption worldwide, the development of renewable and alternative energy sources can sustain long-term development in the energy field. Hydrogen (H2), which is one of the clean chemical fuels, has the highest weight energy density and its combustion byproduct is only water. Among the various methods of producing hydrogen source, water electrolysis is a process that can effectively produce H2. However, it is difficult for commercialization of water electrolysis for H2 production due to the high cost and low abundance of noble metal-based cathodic electrode used for highly efficiency. Several studies have been conducted to reduce noble metal loading and/or completely replace them with other materials to overcome these obstacles. Among them, stainless steel contains many components of transition metals (Ni, Cr, Co) but have sluggish reaction kinetics and small active surface area. In this study, the problem of stainless steel was to be solved by utilizing the electrocatalytic properties of silver nanoparticles on the electrode surface, and electrodes were easily fabricated through the electrodeposition process. In addition, the surface shape, elemental properties, and HER activity of the electrode was analyzed by comparing it with the commercialized silver nanoparticle-coated invasive electrodes from Inanos (Inano-Ag-IE) through the plasma coating process. As a result, silver nanoparticle-coated conventional electrode (Ag-CE) fabricated through electrodeposition confirmed high HER activity and stability. However, the Inano-Ag-IE showed low HER activity as silver nanoparticles were not found. We encourage further research on the production process of such products for sustainable energy applications.
Performance of Sulfide-Driven Fuel Cell Aerated by Venturi Tube Ejector
Authors: Beschkov Venko N. , Razkazova-Velkova Elena N. , Martinov Martin S. , Stefanov Stefan M.
Published: May 2021

Hydrogen sulfide is frequently met in natural waters, like mineral springs, but mostly it is found in marine water with low renewal rate. The Black Sea has extremely high hydrogen sulfide content. It can be utilized in different ways, but the most promising one is direct conversion into electricity. This result can be attained by a sulfide-driven fuel cell (SDFC), converting sulfide to sulfate thus releasing electric energy up to 24 GJ/t. One of the most important problems is the mass transfer limitation on oxygen transfer in the cathode space of the fuel cell. This problem can be solved using a gas diffusion electrode or highly efficient saturation by oxygen in an ejector of the Venturi tube type. This work presents experimental data in laboratory-scale SDFC for sulfide conversion into sulfate, sulfite and polysulfide releasing different amounts of electric energy. Two types of aeration are tested: direct air blow and Venturi-tube ejector. Besides pure graphite, two catalysts, i.e., cobalt spinel and zirconia-doped graphite were tested as anodes. Experiments were carried out at initial sulfide concentrations from 50 to 300 mg/L. Sulfate, sulfite and thiosulfate ions were detected in the outlet solutions from the fuel cell. The electrochemical results show good agreement with the chemical analyses. Most of the results show attained high efficiencies of the fuel cell, i.e., up to 80%. The practical applications of this method can be extended for other purposes, like treatment of polluted water together with utilization as energy.
The Loss of Polysialic Acid Impairs the Contractile Phenotype of Peritubular Smooth Muscle Cells in the Postnatal Testis
Authors: Hachem Nadim E. , Humpfle Luisa , Simon Peter , Kaese Miriam , Weinhold Birgit , Günther Juliane , Galuska Sebastian P. , Middendorff Ralf
Published: May 2021

In the testis, the germinal epithelium of seminiferous tubules is surrounded by contractile peritubular cells, which are involved in sperm transport. Interestingly, in postnatal testis, polysialic acid (polySia), which is also an essential player for the development of the brain, was observed around the tubules. Western blotting revealed a massive decrease of polySia from postnatal day 1 towards puberty, together with a fundamental reduction of the net-like intertubular polySia. Using polysialyltransferase knockout mice, we investigated the consequences of the loss of polySia in the postnatal testis. Compared to postnatal wild-type animals, polySia knockouts showed slightly reduced smooth muscle actin (SMA) immunostaining of peritubular smooth muscle cells (SMCs), while calponin, marking more differentiated SMCs, dramatically decreased. In contrast, testicular SMA and calponin immunostaining remained unchanged in vascular SMCs in all genotypes. In addition, the cGMP-dependent protein kinase PKG I, a key enzyme of SMC relaxation, was nearly undetectable in the peritubular SMCs. Cell proliferation in the peritubular layer increased significantly in the knockouts, as shown by proliferating cell nuclear anti (PCNA) staining. Taken together, in postnatal testis, the absence of polySia resulted in an impaired differentiation of peritubular, but not vascular, SMCs to a more synthetic phenotype. Thus, polySia might influence the maintenance of a differentiated phenotype of non-vascular SMCs.
Transcriptionally Active Chromatin—Lessons Learned from the Chicken Erythrocyte Chromatin Fractionation
Authors: Beacon Tasnim H. , Davie James R.
Published: May 2021

The chicken erythrocyte model system has been valuable to the study of chromatin structure and function, specifically for genes involved in oxygen transport and the innate immune response. Several seminal features of transcriptionally active chromatin were discovered in this system. Davie and colleagues capitalized on the unique features of the chicken erythrocyte to separate and isolate transcriptionally active chromatin and silenced chromatin, using a powerful native fractionation procedure. Histone modifications, histone variants, atypical nucleosomes (U-shaped nucleosomes) and other chromatin structural features (open chromatin) were identified in these studies. More recently, the transcriptionally active chromosomal domains in the chicken erythrocyte genome were mapped by combining this chromatin fractionation method with next-generation DNA and RNA sequencing. The landscape of histone modifications relative to chromatin structural features in the chicken erythrocyte genome was reported in detail, including the first ever mapping of histone H4 asymmetrically dimethylated at Arg 3 (H4R3me2a) and histone H3 symmetrically dimethylated at Arg 2 (H3R2me2s), which are products of protein arginine methyltransferases (PRMTs) 1 and 5, respectively. PRMT1 is important in the establishment and maintenance of chicken erythrocyte transcriptionally active chromatin.
Molecular Genetics in Neuroblastoma Prognosis
Authors: Lerone Margherita , Ognibene Marzia , Pezzolo Annalisa , Martucciello Giuseppe , Zara Federico , Morini Martina , Mazzocco Katia
Published: May 2021

In recent years, much research has been carried out to identify the biological and genetic characteristics of the neuroblastoma (NB) tumor in order to precisely define the prognostic subgroups for improving treatment stratification. This review will describe the major genetic features and the recent scientific advances, focusing on their impact on diagnosis, prognosis, and therapeutic solutions in NB clinical management.
Validation of the High-Altitude Wind and Rain Airborne Profiler during the Tampa Bay Rain Experiment
Authors: Coto Jonathan , Jones W. Linwood , Heymsfield Gerald M.
Published: May 2021

This paper deals with the validation of rain rate and wind speed measurements from the High-Altitude Wind and Rain Airborne Profiler (HIWRAP), which occurred in September 2013 when the NASA Global Hawk unmanned aerial vehicle passed over an ocean rain squall line in the Gulf of Mexico near the North Florida coast. The three-dimensional atmospheric rain distribution and the associated ocean surface wind vector field were simultaneously measured by two independent remote sensing and two in situ systems, namely the ground-based National Weather Service Next-Generation Weather Radar (NEXRAD); the European Space Agency satellite Advanced Scatterometer (ASCAT), and two instrumented weather buoys. These independent measurements provided the necessary data to calibrate the HIWRAP radar using the measured ocean radar backscatter and to validate the HIWRAP rain and wind vector retrievals against NEXRAD, ASCAT and ocean buoys observations. In addition, this paper presents data processing procedures for the HIWRAP instrument, including the development of a geometric model to collocate time-morphed rain rates from the NEXRAD radar with HIWRAP atmospheric rain profiles. Results of the rain rate intercomparison are presented, and they demonstrate excellent agreement with the NEXRAD time-interpolated rain volume scans. In our analysis, we find that HIWRAP produces wind and rain rates that are consistent with the supporting ground and satellite estimates, thereby providing validation of the geolocation, the calibration, and the geophysical retrieval algorithms for the HIWRAP instrument.
Corrosion Behavior and Mechanical Properties of a Nanocomposite Superhydrophobic Coating
Authors: Sebastian Divine , Yao Chun-Wei , Nipa Lutfun , Lian Ian , Twu Gary
Published: May 2021

In this work, a mechanically durable anticorrosion superhydrophobic coating is developed using a nanocomposite coating solution composed of silica nanoparticles and epoxy resin. The nanocomposite coating developed was tested for its superhydrophobic behavior using goniometry; surface morphology using scanning electron microscopy and atomic force microscopy; elemental composition using energy dispersive X-ray spectroscopy; corrosion resistance using atomic force microscopy; and potentiodynamic polarization measurements. The nanocomposite coating possesses hierarchical micro/nanostructures, according to the scanning electron microscopy images, and the presence of such structures was further confirmed by the atomic force microscopy images. The developed nanocomposite coating was found to be highly superhydrophobic as well as corrosion resistant, according to the results from static contact angle measurement and potentiodynamic polarization measurement, respectively. The abrasion resistance and mechanical durability of the nanocomposite coating were studied by abrasion tests, and the mechanical properties such as reduced modulus and Berkovich hardness were evaluated with the aid of nanoindentation tests.
Enhanced Anti-Corrosion Performances of Epoxy Resin Using the Addition of Sodium Dodecylbenzene Sulfonate-Modified Graphene
Authors: Li Jiehui , Liu Mukun , Niu Gang , Xiong Qingren , Ma Yanjie , An Ruihua , Bai Wei , Qin Changyi , Ren Wei
Published: May 2021

The improvement of anti-corrosive property of epoxy resin is significant for the development of coatings to avoid metal corrosion and thus to reduce the economic loss in many industries. The superior properties of graphene, a two-dimensional material, make it possibly suitable to fulfill this task. However, this is hindered by the easy agglomeration of graphene layers in solvents. In the present work, we report the modification and stabilization of graphene in water using sodium dodecylbenzene sulfonate (SDBS) and the enhancement of the anti-corrosive properties of epoxy resin by mixing such SDBS-modified graphene layers. The influence of the dosage of SDBS on the modification effect of graphene was studied in detail and an optimized dosage, i.e., 50 mg SDBS for 10 mg graphene, was obtained. The SDBS modification could effectively reduce graphene thickness, and the minimum thickness of the modified graphene was 3.50 nm. The modified graphene had increased layer spacing, and the maximum layer spacing was 0.426 nm. When the modified graphene was added into the epoxy resin, the electrochemical impedance modulus value evidently increased compared to pure epoxy resin and those incorporated by pure graphene, indicating that the anti-corrosion performance was significantly improved. These results clarified that SDBS could effectively modify graphene and the SDBS-modified graphene could subsequently largely improve the anti-corrosive property of epoxy resin, which is of significance for the anti-corrosive coatings.
Hybrid Approach for Wood Modification: Characterization and Evaluation of Weathering Resistance of Coatings on Acetylated Wood
Authors: Sandak Anna , Földvári-Nagy Edit , Poohphajai Faksawat , Diaz Rene Herrera , Gordobil Oihana , Sajinčič Nežka , Ponnuchamy Veerapandian , Sandak Jakub
Published: May 2021

Wood, as a biological material, is sensitive to environmental conditions and microorganisms; therefore, wood products require protective measures to extend their service life in outdoor applications. Several modification processes are available for the improvement of wood properties, including commercially available solutions. Among the chemical treatments, acetylation by acetic anhydride is one of the most effective methods to induce chemical changes in the constitutive polymers at the cellular wall level. Acetylation reduces wood shrinkage-swelling, increases its durability against biotic agents, improves UV resistance and reduces surface erosion. However, even if the expected service life for external cladding of acetylated wood is estimated to be 60 years, the aesthetics change rapidly during the first years of exposure. Hybrid, or fusion, modification includes processes where the positive effect of a single treatment can be multiplied by merging with additional follow-up modifications. This report presents results of the performance tests of wood samples that, besides the modification by means of acetylation, were additionally protected with seven commercially available coatings. Natural weathering was conducted in Northern Italy for 15 months. Samples were characterized with numerous instruments by measuring samples collected from the stand every three months. Superior performance was observed on samples that merged both treatments. It is due to the combined effect of the wood acetylation and surface coating. Limited shrinkage/swelling of the bulk substrate due to chemical treatment substantially reduced stresses of the coating film. Hybrid process, compared to sole acetylation of wood, assured superior visual performance of the wood surface by preserving its original appearance.