bluuebunny/crossref_metadata_2025 huggingface dataset:
EEG Correlates of Active Stopping and Preparation for Stopping in Chronic Tic Disorder
Authors: Zea Vera Alonso , Pedapati Ernest V. , Larsh Travis R. , Kohmescher Kevin , Miyakoshi Makoto , Huddleston David A. , Jackson Hannah S. , Gilbert Donald L. , Horn Paul S. , Wu Steve W.
Published: January 2022

Motor inhibition is an important cognitive process involved in tic suppression. As the right frontal lobe contains important inhibitory network nodes, we characterized right superior, middle, and inferior frontal gyral (RSFG, RMFG, RIFG) event-related oscillations during motor inhibition in youth with chronic tic disorders (CTD) versus controls. Fourteen children with CTD and 13 controls (10–17 years old) completed an anticipated-response stop signal task while dense-array electroencephalography was recorded. Between-group differences in spectral power changes (3–50 Hz) were explored after source localization and multiple comparisons correction. Two epochs within the stop signal task were studied: (1) preparatory phase early in the trial before motor execution/inhibition and (2) active inhibition phase after stop signal presentation. Correlation analyses between electrophysiologic data and clinical rating scales for tic, obsessive-compulsive symptoms, and inattention/hyperactivity were performed. There were no behavioral or electrophysiological differences during active stopping. During stop preparation, CTD participants showed greater event-related desynchronization (ERD) in the RSFG (γ-band), RMFG (β, γ-bands), and RIFG (θ, α, β, γ-bands). Higher RSFG γ-ERD correlated with lower tic severity (r = 0.66, p = 0.04). Our findings suggest RSFG γ-ERD may represent a mechanism that allows CTD patients to keep tics under control and achieve behavioral performance similar to peers.
The Role of Walking Experience in the Emergence of Gait Harmony in Typically Developing Toddlers
Authors: De Bartolo Daniela , Zandvoort Coen S. , Goudriaan Marije , Kerkman Jennifer N. , Iosa Marco , Dominici Nadia
Published: January 2022

The ability to walk without support usually develops in the first year of a typically developing toddler’s life and matures further in the following years. Mature walking is characterized by the correct timing of the different gait phases that make up a full gait cycle formed by stance, swing, and double support phases. The harmony of mature walking is given by a specific self-similar structure of the ratios between the durations of these phases (stride/stance, stance/swing, swing/double support), that in adults all converge to the golden ratio (phi, about 1.618). The aim of this longitudinal, prospective, experimental study was to investigate the evolution of this gait harmonic structure in the transition from supported to independent walking. In total, 27 children were recruited and recorded at various stages of locomotor development, ranging from neonatal stepping up to an independent walking experience of about six months. Differently from walking speed that progressively increased with age, the gait phase ratios started to converge to golden value only after the first independent steps, suggesting a relation to the maturation of the walking experience. The independent walking experience seems to represent a trigger for the evolution of a locomotor harmonic pattern in toddlers learning to walk.
Relationships between Diffusion Tensor Imaging and Resting State Functional Connectivity in Patients with Schizophrenia and Healthy Controls: A Preliminary Study
Authors: Hoptman Matthew J. , Tural Umit , Lim Kelvin O. , Javitt Daniel C. , Oberlin Lauren E.
Published: January 2022

Schizophrenia is widely seen as a disorder of dysconnectivity. Neuroimaging studies have examined both structural and functional connectivity in the disorder, but these modalities have rarely been integrated directly. We scanned 29 patients with schizophrenia and 25 healthy control subjects, and we acquired resting state fMRI and diffusion tensor imaging. We used the Functional and Tractographic Connectivity Analysis Toolbox (FATCAT) to estimate functional and structural connectivity of the default mode network. Correlations between modalities were investigated, and multimodal connectivity scores (MCS) were created using principal component analysis. Of the 28 possible region pairs, 9 showed consistent (>80%) tracts across participants. Correlations between modalities were found among those with schizophrenia for the prefrontal cortex, posterior cingulate, and lateral temporal lobes, with frontal and parietal regions, consistent with frontotemporoparietal network involvement in the disorder. In patients, MCS correlated with several aspects of the Positive and Negative Syndrome Scale, with higher multimodal connectivity associated with outward-directed (externalizing) behavior and lower multimodal connectivity related to psychosis per se. In this preliminary sample, we found FATCAT to be a useful toolbox to directly integrate and examine connectivity between imaging modalities. A consideration of conjoint structural and functional connectivity can provide important information about the network mechanisms of schizophrenia.
Clinical Cognitive Motor Dissociation: A Case Report Showing How Pitfalls Can Hinder Early Clinical Detection of Awareness
Authors: Jöhr Jane , Aureli Viviana , Meyer Ivo , Cossu Giulia , Diserens Karin
Published: January 2022

This study presents the case of a brain-injured patient whose pathological awakening after coma and absence of interaction led to a diagnosis of lack of consciousness when standard clinical scales were administered. However, we were able to demonstrate conscious perception in this patient from initial clinical assessments using the Motor Behaviour Tool in the acute stage, complemented by a systematic search for potential obstacles blocking his execution of motor responses (pitfalls). This refinement of the diagnosis enabled prediction of a favourable outcome despite the severity of the lesions, with the patient’s evolution confirming our prediction. Faced with an unresponsive patient, every specialist should go beyond the absence of response with the standard scores, consider the possibility of a hidden consciousness and look for rigorous ways of proving it.
Bifrontal Osteoplastic Flap: An Option to Decrease Infection in Bifrontal Craniotomies with Skull Base Osteotomies
Authors: Ortiz Torres Michael , Ziu Endrit , Agunbiade Samiat , Carr Steven B. , Litofsky N. Scott
Published: January 2022

Infection can be a common complication following bifrontal craniotomy with skull base osteotomies given the potential violation of sinuses and entry into the nasal structures. Our objective was to examine our series of patients who underwent a bifrontal craniotomy with skull base osteotomies and describe the infection rate. We propose the bifrontal osteoplastic flap as an adjunct to infection prevention. A retrospective single-center study of a patient database was performed. Twenty patients were identified. Fifty-five percent were male. The mean age was 55.7 ± 13.9 years. The most common indications for surgery were esthesioneuroblastomas (35%) and anterior skull base meningiomas (30%). Six patients (30%) developed an infection, 1 patient (5%) developed a CSF leak, and no patients developed a mucocele. All 6 infected cases had nasal pathology with intracranial extension, they all received chemoradiation post-operatively and were all combined cases with otorhinolaryngology. Eighty-three percent of these patients required a craniectomy and all of them required long-term IV antibiotics. Infection is not uncommon after a bifrontal craniotomy with skull base osteotomies and the use of the bifrontal osteoplastic flap in cases where the risk of infection is high, i.e., esthesioneuroblastomas surgery, may help reduce said risk and lead to better patient outcomes.
The Relationship between Personality Traits and COVID-19 Anxiety: A Mediating Model
Authors: Kumar V. Vineeth , Tankha Geetika
Published: January 2022

The COVID-19 pandemic has created a lot of fear and anxiety globally. The current study attempted to investigate the association among the big five personality traits and the two factors of COVID-19 pandemic anxiety (fear and somatic concern). Further, sleep quality as a mediator between personality traits and pandemic anxiety was also assessed. The study involved a cross-sectional sample of 296 adult Indians who were administered the 10-item short version of BFI along with the COVID-19 Pandemic Anxiety Scale and Sleep Quality Scale. Path analysis was used to test the theoretical model that we proposed. The overall model has explained 6% and 36% of the variance, respectively, for the factors of fear and somatic concern of COVID-19 pandemic anxiety. The path analysis model indicated that only the trait of neuroticism showed a significant direct and indirect effect on pandemic anxiety in the sample. Those scoring high on neuroticism indicated high levels of fear as well as somatic concern. Neuroticism also showed partial mediation through sleep quality on the factor of somatic concern. Agreeableness was the only other personality trait that indicated a significantly negative relationship with the factor of somatic concern. These relationships were independent of age, gender, and occupational status. These findings provide a preliminary insight into the slightly different relationship which has emerged between personality and COVID-19 pandemic anxiety in comparison to general anxiety.
The State of Web Accessibility for People with Cognitive Disabilities: A Rapid Evidence Assessment
Authors: Gartland Sara , Flynn Paul , Carneiro Maria Ana , Holloway Greg , Fialho Jose de Sousa , Cullen Joe , Hamilton Emma , Harris Amy , Cullen Clare
Published: January 2022

Increased digitisation of day-to-day activities was occurring prior to the COVID-19 pandemic. The pandemic only accelerated the virtual shift, making web accessibility an urgent issue, especially for marginalised populations. Despite decades of work to develop, refine, and implement web accessibility standards, people with cognitive disabilities regularly experience many barriers to web accessibility. To inform ongoing work to improve web accessibility for people with cognitive disabilities, a systematic review was conducted. The main question guiding this review is: what are the state-of-the-art of interventions that support web accessibility for citizens, 9 years of age and up, living with cognitive impairment? A set of 50 search strings were entered into three academic databases: SCOPUS, ProQuest, and Web of Science. Systematic screening procedures narrowed the search returns to a total of 45 included papers. A data analysis revealed themes associated with the lived experiences of people with cognitive disabilities, tools for improving web accessibility, and methodological best practices for involving people with cognitive disabilities in research. These findings have immediate implications for ongoing research and the development of meaningful solutions to the problem of web accessibility for people with cognitive disabilities.
Effects of the Design Parameters of Ridge Vents on Induced Buoyancy-Driven Ventilation
Authors: Chen Ching-Mei , Lin Yi-Pin , Chung Sung-Chin , Lai Chi-Ming
Published: January 2022

With ridge vents that are commonly used in building ventilation applications as the research object, this study analyzed how design parameters affect the efficiency of thermal buoyancy-driven ventilation induced by ridge vents through computational fluid dynamics (CFD). The design parameters of ridge vents include the width S, height H, and eave overhang E. In consideration of engineering practices, the parameter ranges were set as follows: S = 1.2, 1.8, 2.4, and 3 m; H = 0.3, 0.6, 0.9, and 1.2 m; and E = 0, 0.3, and 0.6 m. The results show that when a ridge vent is under buoyancy-driven ventilation, the height H serves as the dominant design parameter. Correlation equations of the induced ventilation rates with the relevant ridge vent design parameters are provided.
Train-Induced Vibration Predictions Based on Data-Driven Cascaded State-Space Model
Authors: Tao Ziyu , Hu Zihao , Wu Ganming , Huang Conghui , Zou Chao , Ying Zhiyun
Published: January 2022

Over-track buildings above metro depots have become common in megacities due to urban land shortages. The transmission of vibrations into the over-track buildings during routine train operations has the potential to adversely impact the occupants in terms of perceptible vibration and noise. There is a need to quantify the potential impacts before construction for planning and design purposes. Train-induced vibration measurements were carried out on a six-story over-track building at the Luogang metro depot in Guangzhou, China, which is located adjacent to the tracks. The measurements were used to develop a data-driven cascaded state-space model, which can be applied to planned over-track buildings located in track areas to predict and assess whether train-induced vibrations would adversely affect the buildings’ future occupants. Vibration levels in the platform of the building’s columns were used as inputs to the models, thereby avoiding the complexity of modeling the transfer behavior of the platform. The predicted vibration levels corresponded with measurements in the existing building. This comparison validated the use of the model for future residential buildings where the predictions indicate that the impacts on its occupants will be within the applicable criteria.
Application of Multi-Criteria Analytic Methods in the Assessment of the Technical Conditions of Small Hydraulic Structures
Authors: Hämmerling Mateusz , Kałuża Tomasz , Zawadzki Paweł , Zaborowski Stanisław , Sojka Mariusz , Liberacki Daniel , Ptak Mariusz
Published: January 2022

Increasing water demand, combined with unfavourable climate change, creates a need for well-thought-out water management. Such goals are realised thanks to appropriate hydrotechnical infrastructure, the efficiency and functionality of which depend on its technical condition. In the literature, there is no method for the assessment of the technical condition of small damming structures, including sluice gates. The aim of this article was to present the possibility of using the multi-criteria AHP decision support method to assess the technical condition of small damming structures. The assessment included both concrete elements (spillways, abutments, and apron) and steel elements (gates and hoisting equipment). The analyses considered the effects of growing vegetation, the condition of concrete surfaces (e.g., cracks, cavities, exposed rebar) and steel elements (corrosion, deterioration). A hybrid method was used to study the assessment of the technical condition of water structures. It consisted of a modified Zawadzki’s method and weights which were determined by different groups of respondents with industry backgrounds (university students and experts) using the AHP method. The obtained results show that the factors related to the holes and corrosion of the gate elements had the highest value of the matrix solution vector. The last level of the tree structure indicated that the condition of the spillway and gate is the most important factor in the technical condition assessment. As the assessment considers commonly available parameters, the proposed method is universal and can be used in the assessment of other structures of this type in different regions of the world, which is important in terms of their functioning, planned repairs, and optimal use in water resource management.
Benchmark Numerical Model for Progressive Collapse Analysis of RC Beam-Column Sub-Assemblages
Authors: El-Ariss Bilal , Elkholy Said , Shehada Ahmed
Published: January 2022

The pertinence of the fiber element approach to enable thorough numerical investigation on the potential for progressive collapse of reinforced concrete (RC) frame structures owing to interior column exclusion is examined using twenty-nine RC sub-assemblages with five different test setups and three different test scales. A qualitative examination of the results reveals a good agreement between the test results and the outcomes of the fiber-element-based numerical model using the finite element package SeismoStruct. Moreover, minor discrepancies between the test and numerical data demonstrate the capability of the fiber-element-based model to accurately simulate the behavior of RC elements with various boundary conditions and scales under the context of progressive collapse. Given the costly nature of experimental research, test errors, and the lengthy testing process, the proposed numerical model based on the fiber element approach can be considered a viable option for analyzing structures under progressive collapse due to the interior column exclusion scenario. Engineers and researchers can use the conclusions and comments highlighted in the study as a guide to create accurate models for the analysis of RC structures subjected to progressive collapse.
Investigation of Indoor Asymmetric Thermal Radiation in Tibet Plateau: Case Study of a Typical Office Building
Authors: Wang Meilin , Shen Pengyuan
Published: January 2022

The unique climate in cold plateaus leads to long and cold winters, which result in the characteristics and creation of an indoor thermal environment different from that of plain areas. However, there is a lack of detailed research on and evaluation of indoor temperature distributions. This study took an office building in Lhasa as an example to study the indoor non-uniform temperature distributions with radiator and solar radiation. The indoor and outdoor thermal environment parameters were tested. Next, a numerical model was established and verified. On a typical winter weather day, although the average indoor air temperature and radiation temperature in Lhasa are higher than those in Beijing (both are cold areas), the temperature in both is lower than comfortable levels. The indoor vertical air temperature differences are below 3 °C, with a 5% dissatisfaction most of the time. Solar radiation and radiators seriously affect the uniformity of the indoor thermal environment. The radiation asymmetry in Lhasa is significant, and the maximum radiation temperature asymmetry can reach 8.73 °C. In addition, the setting of north-facing windows should be avoided as far as possible in Tibetan areas. Suitable design and evaluation standards should pay attention to the obvious phenomenon of uneven indoor temperature distribution.
Management of Early-Stage Cervical Cancer: A Literature Review
Authors: Guimarães Yasmin Medeiros , Godoy Luani Rezende , Longatto-Filho Adhemar , Reis Ricardo dos
Published: January 2022

Cervical cancer (CC) remains a public health issue worldwide despite preventive measures. Surgical treatment in the early-stage CC has evolved during the last decades. Our aim was to review the advances in the literature and summarize the ongoing studies on this topic. To this end, we conducted a literature review through PubMed focusing on English-language articles on the surgical management of early-stage CC. The emergent topics considered here are the FIGO 2018 staging system update, conservative management with less radical procedures for selected patients, lymph node staging, fertility preservation, preferred surgical approach, management of tumors up to 2 cm, and prognosis. In terms of updating FIGO, we highlight the inclusion of lymph node status on staging and the possibility of imaging. Regarding the preferred surgical approach, we emphasize the LACC trial impact worldwide in favor of open surgery; however, we discuss the controversial application of this for tumors < 2 cm. In summary, all topics show a tendency to provide patients with tailored treatment that avoids morbidity while maintaining oncologic safety, which is already possible in high-income countries. We believe that efforts should focus on making this a reality for low-income countries as well.
The Hematology of Tomorrow Is Here—Preclinical Models Are Not: Cell Therapy for Hematological Malignancies
Authors: Arranz Lorena
Published: January 2022

The purpose of this review is to present the current knowledge on the clinical use of several forms of cell therapy in hematological malignancies and the preclinical models available for their study. In the context of allogeneic hematopoietic stem cell transplants, mesenchymal stromal cells are pursued to help stem cell engraftment and expansion, and control graft versus host disease. We further summarize the status of promising forms of cellular immunotherapy including CAR T cell and CAR NK cell therapy aimed at eradicating the cells of origin of leukemia, i.e., leukemia stem cells. Updates on other forms of cellular immunotherapy, such as NK cells, CIK cells and CAR CIK cells, show encouraging results in AML. The considerations in available in vivo models for disease modelling and treatment efficacy prediction are discussed, with a particular focus on their strengths and weaknesses for the study of healthy and diseased hematopoietic stem cell reconstitution, graft versus host disease and immunotherapy. Despite current limitations, cell therapy is a rapidly evolving field that holds the promise of improved cure rates, soon. As a result, we may be witnessing the birth of the hematology of tomorrow. To further support its development, improved preclinical models including humanized microenvironments in mice are urgently needed.
Prognostic Impact of Total Lesion Glycolysis (TLG) from Preoperative 18F-FDG PET/CT in Stage II/III Colorectal Adenocarcinoma: Extending the Value of PET/CT for Resectable Disease
Authors: Lee Sea-Won , Park Hye Lim , Yoon Nara , Kim Ji Hoon , Oh Jin Kyoung , Buyn Jae Ho , Choi Eun Kyoung , Hong Ji Hyung
Published: January 2022

We investigated the prognostic role of metabolic parameters from preoperative 18F-FDG PET/CT in stage II/III colorectal adenocarcinoma. A total of 327 stage II/III colorectal adenocarcinoma patients who underwent curative resection were included. The maximal standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were analyzed for optimal cut-offs and their effect on DFS. Differences in DFS rates and hazard ratios for DFS between cut-offs were statistically significant in SUVmax, MTV2.5, MTV3, TLG 2.5, TLG3, and TLG30%. Factors significantly related to DFS in univariate Cox regression were age, sex, stage, preoperative CEA, SUVmax, MTV2.5, MTV3, TLG2.5, TLG3, and TLG30%. Age, sex, preoperative CEA, and TLG2.5 (p = 0.009) sustained statistically significant difference in multivariate analysis. The 1-, 3-, and 5-year DFS rates for TLG2.5 ≤ 448.5 were 98.1%, 79.6%, and 74.8%, significantly higher than 78.4%, 68.5%, and 61.1% of TLG2.5 > 448.5, respectively (p = 0.012). TLG, a parameter indicating both the metabolic activity and metabolic volume, was the strongest predictor independently associated with DFS, among several PET parameters with statistical significance. These results suggest the potential prognostic value of preoperative 18F-FDG PET/CT in stage II/III resectable colorectal cancer.
Risk of Non-Hodgkin Lymphoma among Patients with Hepatitis B Virus and Hepatitis C Virus in Taiwan: A Nationwide Cohort Study
Authors: Lai Yung-Rung , Chang Ya-Lan , Lee Chiu-Hsiang , Tsai Tung-Han , Huang Kuang-Hua , Lee Chien-Ying
Published: January 2022

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with an increased risk of developing non-Hodgkin lymphoma (NHL); however, adequate data corroborating these associations are lacking. Therefore, a study based on the national database was performed to investigate the correlation between HBV and HCV with NHL in Taiwan. This research was a retrospective cohort study using a nationally representative database established by the Health and Welfare Data Science Center of the Ministry of Health and Welfare, Taiwan. The participants were patients with HBV and HCV, analyzed using the propensity score matching method. The study results indicated that the incidence rate of NHL (0.13%) was significantly higher than that in patients from the general population. After controlling related variables, the hazard ratio (HR) of the incidence of NHL in patients with hepatitis was 2.37 (95% CI, 1.93–2.91). Furthermore, the incidence of NHL in patients with HBV was significantly higher than in patients from the general population (HR, 2.49; 95% CI, 1.94–3.19). The incidence of NHL in patients with HCV was significantly higher than in patients from the general population (HR, 2.36; 95% CI, 1.73–3.22). This study indicated that HBV and HCV significantly increase the risk of NHL.
Unveiling the Potential of Liquid Biopsy in HER2-Positive Breast Cancer Management
Authors: Godoy-Ortiz Ana , Alba-Bernal Alfonso , Pascual Javier , Comino-Méndez Iñaki , Alba Emilio
Published: January 2022

Invasive breast cancer (BC) is the most common cancer in women with a slightly increasing yearly incidence. BC immunohistochemical characterisation is a crucial tool to define the intrinsic nature of each tumour and personalise BC patients’ clinical management. In this regard, the characterisation of human epidermal growth factor receptor 2 (HER2) status guides physicians to treat with therapies tailored to this membrane receptor. Standardly, a tumour solid biopsy is therefore required, which is an invasive procedure and has difficulties to provide the complete molecular picture of the tumour. To complement these standard-of-care approaches, liquid biopsy is a validated methodology to obtain circulating tumour components such as circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) from body fluids in an easy-to-perform minimal-invasive manner. However, its clinical validity in cancer is still to be demonstrated. This review focusses on the utilisation of both ctDNA and CTCs in early and metastatic HER2-positive BC tumours. We discuss recently published studies deciphering the capacity of liquid biopsy to determine the response to neoadjuvant and adjuvant therapies as well as to predict patients’ outcomes.
Caveolae-Associated Molecules, Tumor Stroma, and Cancer Drug Resistance: Current Findings and Future Perspectives
Authors: Low Jin-Yih , Laiho Marikki
Published: January 2022

The discovery of small, “cave-like” invaginations at the plasma membrane, called caveola, has opened up a new and exciting research area in health and diseases revolving around this cellular ultrastructure. Caveolae are rich in cholesterol and orchestrate cellular signaling events. Within caveola, the caveola-associated proteins, caveolins and cavins, are critical components for the formation of these lipid rafts, their dynamics, and cellular pathophysiology. Their alterations underlie human diseases such as lipodystrophy, muscular dystrophy, cardiovascular disease, and diabetes. The expression of caveolins and cavins is modulated in tumors and in tumor stroma, and their alterations are connected with cancer progression and treatment resistance. To date, although substantial breakthroughs in cancer drug development have been made, drug resistance remains a problem leading to treatment failures and challenging translation and bench-to-bedside research. Here, we summarize the current progress in understanding cancer drug resistance in the context of caveola-associated molecules and tumor stroma and discuss how we can potentially design therapeutic avenues to target these molecules in order to overcome treatment resistance.
Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors
Authors: Fabro Federica , Lamfers Martine L. M. , Leenstra Sieger
Published: January 2022

Despite clinical intervention, glioblastoma (GBM) remains the deadliest brain tumor in adults. Its incurability is partly related to the establishment of drug resistance, both to standard and novel treatments. In fact, even though small kinase inhibitors have changed the standard clinical practice for several solid cancers, in GBM, they did not fulfill this promise. Drug resistance is thought to arise from the heterogeneity of GBM, which leads the development of several different mechanisms. A better understanding of the evolution and characteristics of drug resistance is of utmost importance to improve the current clinical practice. Therefore, the development of clinically relevant preclinical in vitro models which allow careful dissection of these processes is crucial to gain insights that can be translated to improved therapeutic approaches. In this review, we first discuss the heterogeneity of GBM, which is reflected in the development of several resistance mechanisms. In particular, we address the potential role of drug resistance mechanisms in the failure of small kinase inhibitors in clinical trials. Finally, we discuss strategies to overcome therapy resistance, particularly focusing on the importance of developing in vitro models, and the possible approaches that could be applied to the clinic to manage drug resistance.
Coping Strategies in Elderly Colorectal Cancer Patients
Authors: Vargas-Román Keyla , Tovar-Gálvez María Isabel , Liñán-González Antonio , Cañadas de la Fuente Guillermo Arturo , de la Fuente-Solana Emilia Inmaculada , Díaz-Rodríguez Lourdes
Published: January 2022

In Spain, 34,331 new cases of colorectal cancer were diagnosed in 2018 and 15,923 individuals died from this disease in the same year. The highest incidence of colorectal cancer is among individuals aged 65–75 years and the physiological consequences of aging, alongside the effects of the disease and its treatment, can exacerbate their physical deterioration and cognitive impairment and reduce their social relationships. The learning of coping strategies may help to improve the quality of life of patients after cancer diagnosis. To test the hypothesis that the utilization of coping strategies can improve the quality of life of elderly patients with colorectal cancer, PubMed and EBSCO databases were searched, up to 2021, using the following terms: “coping strategies and colorectal cancer” with “anxiety”, “quality of life”, “depression”, “unmet needs”, “optimism”, “intimacy”, “distress”, “self-efficacy” and “self-esteem” with Boolean operators “AND”, “OR”. The literature search retrieved 641 titles/abstracts written in English. After an exhaustive analysis, only 7 studies met the inclusion criteria. Randomized evidence was scant and was reported only in 3/7 of the studies analyzed. Data from available randomized evidence support that patients improved on their depression and quality of life and felt more prepared to deal with their cancer. Coping strategies in patients with colorectal cancer were effective in improving patient adaptation to their new situation. Healthcare professionals working with these patients should receive training in this complementary treatment, to be able to conduct comprehensive care in order to improve the quality of life of these patients.
Neoadjuvant Therapy Is Associated with Improved Chemotherapy Delivery and Overall Survival Compared to Upfront Resection in Pancreatic Cancer without Increasing Perioperative Complications
Authors: Deig Christopher Ryan , Sutton Thomas Lee , Beneville Blake , Trone Kristin , Stratton Amanda , Gunesch Ali N. , Liu Amy Ivy , Alrohaibani Alaaeddin , Mohebnasab Maedeh , Bassale Solange , Grossblatt-Wait Alison , Keith Dove , Attia Fouad , Gilbert Erin W. , Lopez Charles D. , Kardosh Adel , Chen Emerson Y. , Bensch Kenneth G. , Nabavizadeh Nima , Thomas Charles R. , Mayo Skye C. , Sheppard Brett C. , Grossberg Aaron
Published: January 2022

The role of neoadjuvant chemoradiotherapy and/or chemotherapy (neoCHT) in patients with pancreatic ductal adenocarcinoma (PDAC) is poorly defined. We hypothesized that patients who underwent neoadjuvant therapy (NAT) would have improved systemic therapy delivery, as well as comparable perioperative complications, compared to patients undergoing upfront resection. This is an IRB-approved retrospective study of potentially resectable PDAC patients treated within an academic quaternary referral center between 2011 and 2018. Data were abstracted from the electronic medical record using an institutional cancer registry and the National Surgical Quality Improvement Program. Three hundred and fourteen patients were eligible for analysis and eighty-one patients received NAT. The median overall survival (OS) was significantly improved in patients who received NAT (28.6 vs. 20.1 months, p = 0.014). Patients receiving neoCHT had an overall increased mean duration of systemic therapy (p < 0.001), and the median OS improved with each month of chemotherapy delivered (HR = 0.81 per month CHT, 95% CI (0.76–0.86), p < 0.001). NAT was not associated with increases in early severe post-operative complications (p = 0.47), late leaks (p = 0.23), or 30–90 day readmissions (p = 0.084). Our results show improved OS in patients who received NAT, driven largely by improved chemotherapy delivery, without an apparent increase in early or late perioperative complications compared to patients undergoing upfront resection.
The Central Role of the Ubiquitin–Proteasome System in EBV-Mediated Oncogenesis
Authors: Pei Yonggang , Robertson Erle S.
Published: January 2022

Deregulation of the ubiquitin–proteasome system (UPS) plays a critical role in the development of numerous human cancers. Epstein–Barr virus (EBV), the first known human tumor virus, has evolved distinct molecular mechanisms to manipulate the ubiquitin–proteasome system, facilitate its successful infection, and drive opportunistic cancers. The interactions of EBV antigens with the ubiquitin–proteasome system can lead to oncogenesis through the targeting of cellular factors involved in proliferation. Recent studies highlight the central role of the ubiquitin–proteasome system in EBV infection. This review will summarize the versatile strategies in EBV-mediated oncogenesis that contribute to the development of specific therapeutic approaches to treat EBV-associated malignancies.
Pharmacogenomics of Vincristine-Induced Peripheral Neuropathy in Children with Cancer: A Systematic Review and Meta-Analysis
Authors: Uittenboogaard Aniek , Neutel Céline L. G. , Ket Johannes C. F. , Njuguna Festus , Huitema Alwin D. R. , Kaspers Gertjan J. L. , van de Velde Mirjam E.
Published: January 2022

Vincristine-induced peripheral neuropathy (VIPN) is a debilitating side-effect of vincristine. It remains a challenge to predict which patients will suffer from VIPN. Pharmacogenomics may explain an individuals’ susceptibility to side-effects. In this systematic review and meta-analysis, we describe the influence of pharmacogenomic parameters on the development of VIPN in children with cancer. PubMed, Embase and Web of Science were searched. In total, 1597 records were identified and 21 studies were included. A random-effects meta-analysis was performed for the influence of CYP3A5 expression on the development of VIPN. Single-nucleotide polymorphisms (SNPs) in transporter-, metabolism-, cytoskeleton-, and hereditary neuropathy-associated genes and SNPs in genes previously unrelated to vincristine or neuropathy were associated with VIPN. CYP3A5 expression status was not significantly associated with VIPN. The comparison and interpretation of the results of the included studies was limited due to heterogeneity in the study population, treatment protocol and assessment methods and definitions of VIPN. Independent replication is essential to validate the clinical significance of the reported associations. Future research should aim for prospective VIPN assessment in both a discovery and a replication cohort. Ultimately, the goal would be to screen patients upfront to determine optimal vincristine dosage with regards to efficacy and risk of VIPN.
Immune Microenvironment Characteristics of Urachal Carcinoma and Its Implications for Prognosis and Immunotherapy
Authors: Zhang Xinke , Wang Suijing , Nie Run-Cong , Qu Chunhua , Chen Jierong , Yang Yuanzhong , Cai Muyan
Published: January 2022

Urachal carcinoma (UrC) is an exceedingly rare tumor and lacks effective treatment. Herein, we characterized an immune microenvironment characteristic of UrC in detail and identified its implications for prognosis and immunotherapy. In total, 37 resections of UrC were stained for CD20, CD3, CD4, CD8, FOXP3, CD68, HLA-DR, CD163, PD1, and PD-L1, as well as mismatch repair protein including MSH2, MSH6, MLH1, and PMS2 by immunohistochemistry. Intratumoral and peritumoral immune cell densities or the proportion of PD1 and PD-L1 expression alongside MSH2, MSH6, MLH1, and PMS2 status were manually evaluated using the whole slide. UrC patients with the number of tertiary lymphoid structures (TLS) per slide tended to be higher in tumors with dMMR (p = 0.1919), and tumors with higher number of TLS tended to have longer OS (p = 0.0940) and DFS (p = 0.0700). High densities of CD3+ T, CD8+ T, and CD68+ cells were significantly associated with worse OS and DFS (both p<0.05). Increased intratumoral (p = 0.0111) and peritumoral (p = 0.0485) CD8+ T cell densities were significantly associated with PD-L1 expression or increasing proportion of PD-L1 expression on immune cells. Similarly, increased intratumoral (p = 0.0008) and peritumoral (p = 0.063) CD8+ T cell densities were significantly associated with increasing proportion of PD1 expression on immune cells. Tumors with PD-L1 positive expression on immune cells had a significantly increased proportion of PD1 expression (p = 0.0121). High peritumoral CD8+ T cell density (>73.7/mm2) was significantly associated with worse OS (p = 0.0120) and DFS (p = 0.00095). The number of TLS seems to be considered not only as histopathological characteristics in predicting MMR status of UrC, but also as a prognostic or therapeutic biomarker, and we also provide some important suggestions for targeting PD-1/PD-L1 checkpoint in UrC.
Blood Count Recovery Following Induction Therapy for Acute Myeloid Leukemia in Children Does Not Predict Survival
Authors: Pommert Lauren , Cooper Todd M. , Gerbing Robert B. , Brodersen Lisa , Loken Michael , Gamis Alan , Aplenc Richard , Alonzo Todd A. , Kolb Edward Anders
Published: January 2022

International Working Group (IWG) and European LeukemiaNet (ELN) response definitions are utilized to evaluate the efficacy of new agents for childhood acute myeloid leukemia (AML) for regulatory purposes. However, these criteria are not consistent with definitions used in pediatric AML trials or with standard pediatric practice to proceed with subsequent therapy cycles prior to IWG/ELN-defined count recovery. We retrospectively analyzed data from the two most recent Phase 3 pediatric AML clinical trials conducted by the Children’s Oncology Group (COG) to assess the incidence, timing, and prognostic significance of count recovery following induction chemotherapy. Of the patients with fewer than 5% bone marrow blasts at the end of first induction, 21.5% of patients proceeded to a second induction cycle prior to achieving ANC ≥ 500 cells/μL and platelets ≥ 50,000 cells/μL, both well below the IWG/ELN thresholds of ANC > 1000 cells/μL and platelets > 100,000 cells/μL. In these two sequential childhood AML Phase 3 trials, neither ANC nor platelet recovery predicted survival. Intensification of treatment through the initiation of subsequent therapy cycles prior to attainment of IWG/ELN-defined CR is common practice in clinical trials for children with AML, suggesting that updated response definitions are needed for pediatric AML.
Genomic Mechanisms Influencing Outcome in Chronic Myeloid Leukemia
Authors: Fernandes Adelina , Shanmuganathan Naranie , Branford Susan
Published: January 2022

Chronic myeloid leukemia (CML) represents the disease prototype of genetically based diagnosis and management. Tyrosine kinase inhibitors (TKIs), that target the causal BCR::ABL1 fusion protein, exemplify the success of molecularly based therapy. Most patients now have long-term survival; however, TKI resistance is a persistent clinical problem. TKIs are effective in the BCR::ABL1-driven chronic phase of CML but are relatively ineffective for clinically defined advanced phases. Genomic investigation of drug resistance using next-generation sequencing for CML has lagged behind other hematological malignancies. However, emerging data show that genomic abnormalities are likely associated with suboptimal response and drug resistance. This has already been supported by the presence of BCR::ABL1 kinase domain mutations in drug resistance, which led to the development of more potent TKIs. Next-generation sequencing studies are revealing additional mutations associated with resistance. In this review, we discuss the initiating chromosomal translocation that may not always be a straightforward reciprocal event between chromosomes 9 and 22 but can sometimes be accompanied by sequence deletion, inversion, and rearrangement. These events may biologically reflect a more genomically unstable disease prone to acquire mutations. We also discuss the future role of cancer-related gene mutation analysis for risk stratification in CML.
A Bibliometric Analysis and Review of Pullulan-Degrading Enzymes—Past and Current Trends
Authors: Kahar Ummirul Mukminin , Latif Nurriza Ab , Amran Syazwani Itri , Liew Kok Jun , Goh Kian Mau
Published: January 2022

Starch and pullulan degrading enzymes are essential industrial biocatalysts. Pullulan-degrading enzymes are grouped into pullulanases (types I and type II) and pullulan hydrolase (types I, II and III). Generally, these enzymes hydrolyse the α-1,6 glucosidic bonds (and α-1,4 for certain enzyme groups) of substrates and form reducing sugars such as glucose, maltose, maltotriose, panose or isopanose. This review covers two main aspects: (i) bibliometric analysis of publications and patents related to pullulan-degrading enzymes and (ii) biological aspects of free and immobilised pullulan-degrading enzymes and protein engineering. The collective data suggest that most publications involved researchers within the same institution or country in the past and current practice. Multi-national interaction shall be improved, especially in tapping the enzymes from unculturable prokaryotes. While the understanding of pullulanases may reach a certain extend of saturation, the discovery of pullulan hydrolases is still limited. In this report, we suggest readers consider using the next-generation sequencing technique to fill the gaps of finding more new sequences encoding pullulan-degrading enzymes to expand the knowledge body of this topic.
In Situ Partial Sulfidation for Preparing Cu/Cu2−xS Core/Shell Nanorods with Enhanced Photocatalytic Degradation
Authors: Cheng Li , Zhong Yu-Ting , Wang Qu-Quan , Zhou Li
Published: January 2022

Herein, we report an approach to prepare Cu/Cu2−xS core/shell nanorods by in situ sulfidation of copper nanorods. Firstly, copper nanorods with tunable longitudinal surface plasmon resonances were synthesized by a seed-mediated method using Au nanoparticles as seeds. A convenient in situ sulfidation method was then applied to convert the outermost layer of Cu nanorods into Cu2−xS, to increase their stability and surface activity in photocatalytic applications. The thickness of Cu2−xS layer can be adjusted by controlling the amount of S source. The Cu/Cu2−xS core/shell nanorods exhibits two characteristic surface plasmon resonances located in visible and near-infrared regions, respectively. The photocatalytic performances of Cu nanorods and their derivatives were evaluated by measuring the degradation rate of methyl orange dyes. Compared with Cu nanorods, the Cu/Cu2−xS core/shell nanorods demonstrate more than a 13.6-fold enhancement in the degradation rate at 40 min. This work suggests a new direction for constructing derivative nanostructures of copper nanorods and exploring their applications.
Catalytic Enantioselective Diels Alder Reaction: Application in the Synthesis of Antiviral Agents
Authors: Grillo Alessandro , Bizzarri Bruno Mattia
Published: January 2022

The Diels–Alder reaction (DAR) is one of the most effective and reliable strategies for the construction of six-membered carbocyclic and heterocyclic rings, and it is widely used in the synthesis of organic molecules and drugs. Due to the high regio- and stereo-selectivity and its versatility, DARs have represented a powerful tool for organic chemistry for many years. In addition, the asymmetric DAR has become a fundamental synthetic approach in the preparation of optically active six-membered rings and natural compounds. The COVID-19-related pandemic requires continuous research; DAR represents an useful method to obtain optically active intermediates for the synthesis of antiviral agents under different catalytic conditions. We would like to highlight an intriguing synthetic procedure applied to the development of novel synthetic protocols that are potentially useful against a large panel of viruses and other unmet diseases.
Zeolites and Related Materials as Catalyst Supports for Hydrocarbon Oxidation Reactions
Authors: Martins Angela , Nunes Nelson , Carvalho Ana P. , Martins Luísa M. D. R. S.
Published: January 2022

Catalytic oxidation is a key technology for the conversion of petroleum-based feedstocks into useful chemicals (e.g., adipic acid, caprolactam, glycols, acrylates, and vinyl acetate) since this chemical transformation is always involved in synthesis processes. Millions of tons of these compounds are annually produced worldwide and find applications in all areas of chemical industries, ranging from pharmaceutical to large-scale commodities. The traditional industrial methods to produce large amounts of those compounds involve over-stoichiometric quantities of toxic inorganic reactants and homogeneous catalysts that operate at high temperature, originating large amounts of effluents, often leading to expensive downstream processes, along with nonrecovery of valuable catalysts that are loss within the reactant effluent. Due to the increasingly stringent environmental legislation nowadays, there is considerable pressure to replace these antiquate technologies, focusing on heterogeneous catalysts that can operate under mild reactions conditions, easily recovered, and reused. Parallelly, recent advances in the synthesis and characterization of metal complexes and metal clusters on support surfaces have brought new insights to catalysis and highlight ways to systematic catalysts design. This review aims to provide a comprehensive bibliographic examination over the last 10 years on the development of heterogeneous catalysts, i.e., organometallic complexes or metal clusters immobilized in distinct inorganic supports such as zeolites, hierarchical zeolites, silicas, and clays. The methodologies used to prepare and/or modify the supports are critically reviewed, as well as the methods used for the immobilization of the active species. The applications of the heterogenized catalysts are presented, and some case-studies are discussed in detail.