bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neuropsychology of Emotion and Emotion Regulation: The Role of Laterality and Hierarchy
Authors: Turnbull Oliver Hugh , Salas Christian Eduardo
Published: August 2021

Over the last few decades, work in affective neuroscience has increasingly investigated the neural basis of emotion. A central debate in the field, when studying individuals with brain damage, has been whether emotional processes are lateralized or not. This review aims to expand this debate, by considering the need to include a hierarchical dimension to the problem. The historical journey of the diverse literature is presented, particularly focusing on the need to develop a research program that explores the neural basis of a wide range of emotional processes (perception, expression, experience, regulation, decision making, etc.), and also its relation to lateralized cortical and deep-subcortical brain structures. Of especial interest is the study of the interaction between emotional components; for example, between emotion generation and emotion regulation. Finally, emerging evidence from lesion studies is presented regarding the neural basis of emotion-regulation strategies, for which the issue of laterality seems most relevant. It is proposed that, because emotion-regulation strategies are complex higher-order cognitive processes, the question appears to be not the lateralization of the entire emotional process, but the lateralization of the specific cognitive tools we use to manage our feelings, in a range of different ways.
Chimeric Anterolateral Thigh Flap in Skull Base Reconstruction: A Case-Based Update and Literature Review
Authors: Auricchio Anna Maria , Mazzucchi Edoardo , Rapisarda Alessandro , Sabatino Giovanni , Della Pepa Giuseppe Maria , Visconti Giuseppe , Salgarello Marzia , Olivi Alessandro , La Rocca Giuseppe
Published: August 2021

Oncologic and traumatic neurosurgery may have to cope with the issue of skull base defects, which are associated with increased risk of meningitis, epidural abscess and cerebro-spinal fluid (CSF) leak. The aim of skull base reconstruction is to repair the dural exposure and to separate the intracranial contents from the nonsterile sino-nasal cavities and extracranial space. Currently, many different surgical techniques have been described, and one of the most performed is the use free flap. In the present paper we performed a case-based update and literature review of the use of chimeric anterolateral thigh free flap harvested from rectus femoris, reporting the case of a 68-year-old man with recurrent spheno-ethmoidalis plane meningioma.
Neuroimaging Guided Transcranial Electrical Stimulation in Enhancing Surgical Skill Acquisition. Comment on Hung et al. The Efficacy of Transcranial Direct Current Stimulation in Enhancing Surgical Skill Acquisition: A Preliminary Meta-Analysis of Randomized Controlled Trials. Brain Sci. 2021, 11, 707
Authors: Walia Pushpinder , Kumar Kavya Narendra , Dutta Anirban
Published: August 2021

Surgical skill acquisition may be facilitated with a safe application of transcranial direct current stimulation (tDCS). A preliminary meta-analysis of randomized control trials showed that tDCS was associated with significantly better improvement in surgical performance than the sham control; however, meta-analysis does not address the mechanistic understanding. It is known from skill learning studies that the hierarchy of cognitive control shows a rostrocaudal axis in the frontal lobe where a shift from posterior to anterior is postulated to mediate progressively abstract, higher-order control. Therefore, optimizing the transcranial electrical stimulation to target surgical task-related brain activation at different stages of motor learning may provide the causal link to the learning behavior. This comment paper presents the computational approach for neuroimaging guided tDCS based on open-source software pipelines and an open-data of functional near-infrared spectroscopy (fNIRS) for complex motor tasks. We performed an fNIRS-based cortical activation analysis using AtlasViewer software that was used as the target for tDCS of the motor complexity-related brain regions using ROAST software. For future studies on surgical skill training, it is postulated that the higher complexity laparoscopic suturing with intracorporeal knot tying task may result in more robust activation of the motor complexity-related brain areas when compared to the lower complexity laparoscopic tasks.
Influence of Aerobic Fitness on White Matter Integrity and Inhibitory Control in Early Adulthood: A 9-Week Exercise Intervention
Authors: Zhu Hao , Zhu Lina , Xiong Xuan , Dong Xiaoxiao , Chen Dandan , Wang Jingui , Cai Kelong , Wang Wei , Chen Aiguo
Published: August 2021

Previous cross-sectional studies have related aerobic fitness to inhibitory control and white matter (WM) microstructure in young adults, but there is no longitudinal study to confirm whether these relationships exist. We carried out a longitudinal study comparing aerobic fitness, inhibitory control, and WM integrity across time points, before versus after completing an exercise intervention in young adults (18–20 years old) relative to a control group. The exercise group (n = 35) participated in a 9-week exercise protocol, while the control group (n = 24) did not receive any regular exercise training. Behavioral data and diffusion tensor imaging (DTI) data were collected prior to and following the intervention. After the exercise intervention, aerobic fitness and inhibitory control performance were significantly improved for the exercise group, but not for the control group. Analyses of variance (ANOVA) of the DTI data demonstrated significantly increased fractional anisotropy (FA) in the right corticospinal tract and significantly decreased FA in the left superior fronto-occipital fasciculus in the exercise group after the intervention versus before. The enhanced aerobic fitness induced by exercise was associated with better inhibitory control performance in the incongruent condition and lower FA in the Left superior fronto-occipital fasciculus (SFOF). Regression analysis of a mediation model did not support Left SFOF FA as a mediator of the relationship between improvements in aerobic fitness and inhibitory control. The present data provide new evidence of the relationship between exercise-induced changes in aerobic fitness, WM integrity, and inhibitory control in early adulthood. Longer-duration intervention studies with larger study cohorts are needed to confirm and further explore the findings obtained in this study.
Therapeutic Strategies for Mutant SPAST-Based Hereditary Spastic Paraplegia
Authors: Mohan Neha , Qiang Liang , Morfini Gerardo , Baas Peter W.
Published: August 2021

Mutations of the SPAST gene that encodes the microtubule-severing enzyme called spastin are the chief cause of Hereditary Spastic Paraplegia. Growing evidence indicates that pathogenic mutations functionally compromise the spastin protein and endow it with toxic gain-of-function properties. With each of these two factors potentially relevant to disease etiology, the present article discusses possible therapeutic strategies that may ameliorate symptoms in patients suffering from SPAST-based Hereditary Spastic Paraplegia, which is usually termed SPG4-HSP.
Neuroplasticity within and between Functional Brain Networks in Mental Training Based on Long-Term Meditation
Authors: Guidotti Roberto , Del Gratta Cosimo , Perrucci Mauro Gianni , Romani Gian Luca , Raffone Antonino
Published: August 2021

(1) The effects of intensive mental training based on meditation on the functional and structural organization of the human brain have been addressed by several neuroscientific studies. However, how large-scale connectivity patterns are affected by long-term practice of the main forms of meditation, Focused Attention (FA) and Open Monitoring (OM), as well as by aging, has not yet been elucidated. (2) Using functional Magnetic Resonance Imaging (fMRI) and multivariate pattern analysis, we investigated the impact of meditation expertise and age on functional connectivity patterns in large-scale brain networks during different meditation styles in long-term meditators. (3) The results show that fMRI connectivity patterns in multiple key brain networks can differentially predict the meditation expertise and age of long-term meditators. Expertise-predictive patterns are differently affected by FA and OM, while age-predictive patterns are not influenced by the meditation form. The FA meditation connectivity pattern modulated by expertise included nodes and connections implicated in focusing, sustaining and monitoring attention, while OM patterns included nodes associated with cognitive control and emotion regulation. (4) The study highlights a long-term effect of meditation practice on multivariate patterns of functional brain connectivity and suggests that meditation expertise is associated with specific neuroplastic changes in connectivity patterns within and between multiple brain networks.
The Good, the Bad and the Blend: The Strategic Role of the “Middle Leadership” in Work-Family/Life Dynamics during Remote Working
Authors: Spagnoli Paola , Manuti Amelia , Buono Carmela , Ghislieri Chiara
Published: August 2021

The ongoing epidemiological crisis has suddenly steered us towards a new futuristic work scenario in which most service sector employees work remotely, which could be a permanent reality for most service sector employees. This paper focuses on the strategic role that leadership could play in the radical change process that is taking place in work environments. Particular attention was paid to the role of ‘middle managers’ who perform an important function as a link between the strategic vision of top management and the workforce. In addition, special attention was paid to gender differences in work-life dynamics, which are particularly relevant in countries with traditional cultural identities. As this is a conceptual contribution, the most recent studies on this specific role of middle managers have been taken into account and embedded in the current scenario. Therefore, the main contribution in terms of originality was that the current review aimed to leverage such a legacy of knowledge and create a system of evidence-based practical implications for effectively supporting change in organizational culture through the identification of the most appropriate middle management leadership models for remote working that could prevent and/or limit any psychosocial risks (e.g., workaholism and technostress) and longer-term outcomes such as sustainable work-life interface.
Architectural Education in the Current of Deep Ecology and Sustainability
Authors: Cisek Ewa , Jaglarz Anna
Published: August 2021

As a result of the experience and scientific research of the authors on the deep ecology and sustainability process, academic courses were created that are run at two stages of educating architecture students. The authors aimed at demonstrating the effectiveness and quality of the courses as well as the rationality of the assumptions and educational methods adopted for their implementation. One of them was the survey method, as a didactic and scientific experiment and didactic tool. The innovative educational methodology presented in the work may be implemented by other educators at architectural universities in order to improve the quality of teaching design in the spirit of pro-ecological and sustainable development. The result is a long-term action which constitutes a tool to combat the ecological crisis. It consists of bottom-up activities, both in the open landscape (ecovillages) and in the urban context (housing complexes with elements of urban farms and environmental education parks). This is connected with the application of the educational system from the pre-school level in the place of residence up to in-depth academic education.
20th-Century Award-Winning Buildings in Lisbon (Portugal). Study of Plasters, Rendering, and Concrete Materials Aiming Their Sustainable Preservation
Authors: Almeida Luís , Silva António Santos , Veiga Maria do Rosário , Mirão José , Vieira Manuel
Published: August 2021

Conservation, increasing the useful life period of existing significant buildings with minimum consumption of new materials, as much as possible of low-embodied energy, is an important step towards sustainable rehabilitation, while also contributing to the preservation of the cultural heritage. In the context of 20th-century buildings’ conservation, the knowledge of construction techniques and applied materials is essential to pursue sustainable preservation and rehabilitation actions. This paper presents the main construction types and characteristics of a set of architecture award-winning buildings in Lisbon (Portugal) between 1903 and 2002 along with an inspection of the main anomalies detected in renders, plasters, and concrete surfaces. The applied methodology made it possible to classify plasters, renders, and concrete materials according to their state of conservation. The study of 20th-century buildings is justified by the intense renovation activity in the city centres, which leads to the loss of their outer layers and their historical and original values. This study aims to contribute to future conservation actions that will guarantee better preservation concerning sustainable materials, i.e., compatible materials to the existing ones that enhance the durability of the old buildings and minimize the use of new materials.
Quantifying Critical Success Factors (CSFs) in Management of Investment-Construction Projects: Insights from Bayesian Model Averaging
Authors: Sobieraj Janusz , Metelski Dominik
Published: August 2021

The problem with evaluating investment projects is that there are many factors that determine the degree of their successful conclusion. Consequently, there has been an active debate for years as to which critical success factors (CSFs) contribute most to the performance of construction projects. This is because the practice of empirical research is based on two steps: first, researchers choose a particular model from the space of all possible models, and second, they act as if the chosen model is the only one that fits the data and describes the phenomenon under study. Hence, there are many CSF lists that can be found in the literature, owing to the uncertainty at the model selection stage, which is usually ignored. Alternatively, model averaging accounts for this model uncertainty. In this study, the Bayesian model averaging and data from a survey of Polish construction managers were used to investigate the potential of 28 factors describing a diverse set of characteristics in explaining the performance of construction projects in Poland. Determinants of successful completion of investment projects are categorized by their level of evidential strength, which is derived from posterior inclusion probabilities (PIPs), i.e., providing strong, medium and weak evidence.
Strategies of Design Concepts and Energy Systems for Nearly Zero-Energy Container Buildings (NZECBs) in Different Climates
Authors: Koke Johannes , Schippmann André , Shen Jingchun , Zhang Xingxing , Kaufmann Peter , Krause Stefan
Published: August 2021

Container-based lightweight buildings offer a high ecologic and economic potential when they are designed as nearly zero-energy container buildings (NZECBs). Thus, they are relevant to energy transition in achieving an almost climate-neutral building stock. This paper describes and applies design strategies for suitable building concepts and energy systems to be used in NZECBs for different climates. Therefore, different applications in representative climatic zones were selected. Initially, the global climate zones were characterized and analyzed with regard to their potential for self-sufficiency and renewable energies in buildings. The design strategies were further developed and demonstrated for three cases: a single-family house in Sweden, a multi-family house in Germany, and a small school building in rural Ethiopia. For each case, design guidelines were derived and building concepts were developed. On the basis of these input data, various energy concepts were developed in which solar and wind energy, as well as biomass, were integrated as renewable energy sources. All the concepts were simulated and analyzed with the Polysun® software. The various approaches were compared and evaluated, particularly with regard to energy self-sufficiency. Self-sufficiency rates up to 80% were achieved. Finally, the influence of different climate zones on the energy efficiency of the single-family house was studied as well as the influence of the size of battery storage and insulation.
Value of Combined PET Imaging with [18F]FDG and [68Ga]Ga-PSMA-11 in mCRPC Patients with Worsening Disease during [177Lu]Lu-PSMA-617 RLT
Authors: Khreish Fadi , Ribbat Kalle , Bartholomä Mark , Maus Stephan , Stemler Tobias , Hierlmeier Ina , Linxweiler Johannes , Schreckenberger Mathias , Ezziddin Samer , Rosar Florian
Published: August 2021

Despite the promising results of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) in metastatic castration-resistant prostate cancer (mCRPC), some patients show worsening disease during PSMA-RLT. We investigated the value of combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging in this setting. In n = 29 mCRPC patients with worsening disease after a median of four cycles of [177Lu]Lu-PSMA-617 RLT, combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging was performed to detect [18F]FDG-avid lesions with low or no PSMA expression (mismatch lesions). To evaluate prognostic implication of mismatch, survival analyses regarding presence, location, and [18F]FDG PET-derived parameters such as SUVmax, metabolic tumor volume (MTVm), and total lesion glycolysis (TLGm) of mismatch findings were performed. Seventeen patients (59%) showed at least one mismatch metastasis. From the time point of combined PET imaging, the median overall survival (OS) of patients with mismatch findings was significantly (p = 0.008) shorter than those without (3.3 vs. 6.1 mo). Patients with a high MTVm revealed a significantly (p = 0.034) shorter OS of 2.6 mo than patients with low MTVm (5.3 mo). Furthermore, patients with hepatic mismatch showed a significantly (p = 0.049) shorter OS than those without (2.9 vs. 5.3 mo). Difference in OS regarding SUVmax and TLGm was not significant. In mCRPC patients with worsening disease during PSMA-RLT, combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging is essential to identify mismatch findings, as these are associated with poor outcomes requiring a change in therapy management.
Therapeutic Advances Propelled by Deciphering Tumor Biology and Immunology—Highlights of the 8th Heidelberg Myeloma Workshop
Authors: Lutz Raphael , Friedrich Mirco , Raab Marc Steffen , Weinhold Niels , Goldschmidt Hartmut
Published: August 2021

The diagnostics and treatment of newly diagnosed and relapsed MM are continuously evolving. While advances in the field of (single cell) genetic analysis now allow for characterization of the disease at an unprecedented resolution, immunotherapeutic approaches and MRD testing are at the forefront of the current clinical trial landscape. Here, we discuss research progress aimed at gaining a better understanding of this heterogenous disease entity, presented at the 8th Heidelberg Myeloma Workshop. We address the questions of whether biology can guide treatment decisions in MM and how assessment for measurable residual disease can help physicians in clinical decision-making. Finally, we summarize current developments in immunotherapeutic approaches that promise improved patient outcomes for MM patients. Besides summarizing key developments in MM research, we highlight perspectives given by key opinion leaders in the field.
Molecular Mechanisms Associated with Brain Metastases in HER2-Positive and Triple Negative Breast Cancers
Authors: Bryan Sarah , Witzel Isabell , Borgmann Kerstin , Oliveira-Ferrer Leticia
Published: August 2021

Breast cancer (BC) is the most frequent cause of cancer-associated death for women worldwide, with deaths commonly resulting from metastatic spread to distant organs. Approximately 30% of metastatic BC patients develop brain metastases (BM), a currently incurable diagnosis. The influence of BC molecular subtype and gene expression on breast cancer brain metastasis (BCBM) development and patient prognosis is undeniable and is, therefore, an important focus point in the attempt to combat the disease. The HER2-positive and triple-negative molecular subtypes are associated with an increased risk of developing BCBM. Several genetic and molecular mechanisms linked to HER2-positive and triple-negative BC breast cancers appear to influence BCBM formation on several levels, including increased development of circulating tumor cells (CTCs), enhanced epithelial-mesenchymal transition (EMT), and migration of primary BC cells to the brain and/or through superior local invasiveness aided by cancer stem-like cells (CSCs). These specific BC characteristics, together with the ensuing developments at a clinical level, are presented in this review article, drawing a connection between research findings and related therapeutic strategies aimed at preventing BCBM formation and/or progression. Furthermore, we briefly address the critical limitations in our current understanding of this complex topic, highlighting potential focal points for future research.
Epigenetic Regulation of Immunotherapy Response in Triple-Negative Breast Cancer
Authors: Llinàs-Arias Pere , Íñiguez-Muñoz Sandra , McCann Kelly , Voorwerk Leonie , Orozco Javier I. J. , Ensenyat-Mendez Miquel , Sesé Borja , DiNome Maggie L. , Marzese Diego M.
Published: August 2021

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor and progesterone receptor and human epidermal growth factor receptor 2 (HER2) overexpression. This malignancy, representing 15–20% of breast cancers, is a clinical challenge due to the lack of targeted treatments, higher intrinsic aggressiveness, and worse outcomes than other breast cancer subtypes. Immune checkpoint inhibitors have shown promising efficacy for early-stage and advanced TNBC, but this seems limited to a subgroup of patients. Understanding the underlying mechanisms that determine immunotherapy efficiency is essential to identifying which TNBC patients will respond to immunotherapy-based treatments and help to develop new therapeutic strategies. Emerging evidence supports that epigenetic alterations, including aberrant chromatin architecture conformation and the modulation of gene regulatory elements, are critical mechanisms for immune escape. These alterations are particularly interesting since they can be reverted through the inhibition of epigenetic regulators. For that reason, several recent studies suggest that the combination of epigenetic drugs and immunotherapeutic agents can boost anticancer immune responses. In this review, we focused on the contribution of epigenetics to the crosstalk between immune and cancer cells, its relevance on immunotherapy response in TNBC, and the potential benefits of combined treatments.
Clearing up Clear Cell: Clarifying the Immuno-Oncology Treatment Landscape for Metastatic Clear Cell RCC
Authors: Doppalapudi Sai Krishnaraya , Leopold Zev R. , Thaper Akshay , Kaldany Alain , Chua Kevin , Patel Hiren V. , Srivastava Arnav , Singer Eric A.
Published: August 2021

Patients with advanced or malignant renal cell carcinoma at the time of diagnosis have historically had a poor prognosis. Immunonologic agents have significantly altered the therapeutic landscape and clinical outcomes of these patients. In this review, we highlight recent and upcoming clinical trials investigating the role of immunotherapies in clear cell RCC. In particular, we emphasize immunotherapy-based combinations, including immune checkpoint inhibitor (ICI) combinations, neoadjuvant, and adjuvant ICI, and ICI agents combined with anti-VEGF therapy.
Low-Field NMR Relaxometry for Intraoperative Tumour Margin Assessment in Breast-Conserving Surgery
Authors: Bitonto Valeria , Ruggiero Maria Rosaria , Pittaro Alessandra , Castellano Isabella , Bussone Riccardo , Broche Lionel M. , Lurie David J. , Aime Silvio , Baroni Simona , Geninatti Crich Simonetta
Published: August 2021

As conserving surgery is routinely applied for the treatment of early-stage breast cancer, the need for new technology to improve intraoperative margin assessment has become increasingly important. In this study, the potential of fast field-cycling 1H-NMR relaxometry as a new diagnostic tool was evaluated. The technique allows the determination of the tissue proton relaxation rates (R1), as a function of the applied magnetic field, which are affected by the changes in the composition of the mammary gland tissue occurring during the development of neoplasia. The study involved 104 small tissue samples obtained from surgical specimens destined for histopathology. It was found that a good accuracy in margin assessment, i.e., a sensitivity of 92% and a specificity of 85%, can be achieved by using two quantifiers, namely (i) the slope of the line joining the R1 values measured at 0.02 and 1 MHz and (ii) the sum of the R1 values measured at 0.39 and 1 MHz. The method is fast, and it does not rely on the expertise of a pathologist or cytologist. The obtained results suggest that a simplified, low-cost, automated instrument might compete well with the currently available tools in margin assessment.
Hypnosis Sedation Reduces the Duration of Different Side Effects of Cancer Treatments in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Authors: Berliere Martine , Piette Nathan , Bernard Marion , Lacroix Camille , Gerday Amandine , Samartzi Vasiliki , Coyette Maude , Roelants Fabienne , Docquier Marie-Agnes , Touil Nassim , Watremez Christine , Piette Philippe , Duhoux Fran×ois P.
Published: August 2021

Background: Reducing side effects of cancer treatments is a major challenge for clinicians involved in the management of breast cancer patients. Methods: We analyzed data from 63 patients (32 in the general anesthesia group and 31 in the hypnosis sedation group) who were included in 1 prospective non-randomized trial evaluating hypnosis sedation in breast cancer treatment. The patients were followed every 3 months for 2 years. All patients received neoadjuvant chemotherapy with 4 cycles of epirubicin and cyclophosphamide followed by taxanes. Thereafter, patients underwent surgery while on general anesthesia or while on hypnosis sedation. Radiotherapy was administered according to institutional guidelines. Endocrine therapy was prescribed if tumors expressed hormone receptors. Prevalence, intensity and duration of polyneuropathy, musculoskeletal pain, postoperative pain and cancer-related fatigue were assessed at each medical visit. Results: Symptoms duration was statistically reduced for polyneuropathy (p < 0.05), musculoskeletal pain (p < 0.05) postoperative pain and cancer-related fatigue (p < 0.05) in the hypnosis group. Conclusion: Despite the limitations of this study (lack of randomization and small size) we conclude that hypnosis sedation may exert a role on different side effects of breast cancer treatment in patients receiving neoadjuvant chemotherapy, mainly by reducing their duration.
Breast Cancer Risk Assessment and Primary Prevention Advice in Primary Care: A Systematic Review of Provider Attitudes and Routine Behaviours
Authors: Bellhouse Sarah , Hawkes Rhiannon E. , Howell Sacha J. , Gorman Louise , French David P.
Published: August 2021

Implementing risk-stratified breast cancer screening is being considered internationally. It has been suggested that primary care will need to take a role in delivering this service, including risk assessment and provision of primary prevention advice. This systematic review aimed to assess the acceptability of these tasks to primary care providers. Five databases were searched up to July–August 2020, yielding 29 eligible studies, of which 27 were narratively synthesised. The review was pre-registered (PROSPERO: CRD42020197676). Primary care providers report frequently collecting breast cancer family history information, but rarely using quantitative tools integrating additional risk factors. Primary care providers reported high levels of discomfort and low confidence with respect to risk-reducing medications although very few reported doubts about the evidence base underpinning their use. Insufficient education/training and perceived discomfort conducting both tasks were notable barriers. Primary care providers are more likely to accept an increased role in breast cancer risk assessment than advising on risk-reducing medications. To realise the benefits of risk-based screening and prevention at a population level, primary care will need to proactively assess breast cancer risk and advise on risk-reducing medications. To facilitate this, adaptations to infrastructure such as integrated tools are necessary in addition to provision of education.
Serum DJ-1 Is a Biomarker of Colorectal Cancer and DJ-1 Activates Mitophagy to Promote Colorectal Cancer Progression
Authors: Chen William Tzu-Liang , Yang Han-Bin , Ke Tao-Wei , Liao Wen-Ling , Hung Shih-Ya
Published: August 2021

Colorectal cancer is the second most common cancer and the third cancer-associated death in Taiwan. Currently used serum markers for detecting colorectal cancer lack excellent diagnostic accuracy, which results in colorectal cancer being often recognized too late for successful therapy. Mitophagy is the selective autophagic degradation of damaged or excessive mitochondria. DJ-1 is an antioxidant protein that attenuates oxidative stress and maintains mitochondrial quality through activating mitophagy. Mitophagy activation contributes to anti-cancer drug resistance. However, the role of DJ-1-induced mitophagy in colorectal cancer progression remains unclear. In the present study, we collected matched tumor and adjacent normal tissues and serum from patients and cancer cells to demonstrate the clinical value and physiological function of DJ-1 in colorectal cancer. We found that DJ-1 increased in tumor tissues and serum; it was positively correlated with TNM (tumor-node-metastasis) stages of colorectal cancer patients. Through stable knockdown DJ-1 expression in metastatic colorectal adenocarcinoma cells SW620, DJ-1 knockdown inhibited cancer cell survival, migration, and colony formation. In SW620 cells, DJ-1 knockdown induced an incomplete autophagic response that did not affect ATP production; DJ-1 knockdown enhanced intracellular reactive oxygen species generation and damaged mitochondrial accumulation and mitophagy inhibition. It suggests that DJ-1 knockdown inhibits mitophagy that causes metastatic colorectal adenocarcinoma cells to be unable to remove damaged mitochondria and further enhance cancer cell apoptosis. Our data indicate that DJ-1 might be clinically valuable as serum and tissue biomarkers for predicting the TNM stage in colorectal cancer patients. Since DJ-1-induced mitophagy promotes tumor progression, DJ-1 inhibition is a potential therapeutic strategy for colorectal cancer treatment.
The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients
Authors: Paolino Giovanni , Huber Veronica , Camerini Serena , Casella Marialuisa , Macone Alberto , Bertuccini Lucia , Iosi Francesca , Moliterni Elisa , Cecchetti Serena , Ruspantini Irene , Chiarotti Flavia , Vergani Elisabetta , Lalli Luca , Raggi Carla , Di Biase Antonella , Calvieri Stefano , Mercuri Santo Raffaele , Lugini Luana , Federici Cristina
Published: August 2021

The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is fundamental to increasing survival and therapeutic adjustment. In stages II–IV especially, additional indications for adjuvant therapy purposes after resection and for treatment of metastatic patients are urgently needed. We investigated whether the fatty acid (FA) and protein compositions of small extracellular vesicles (sEV) derived from the plasma of stage 0–I, II and III–IV melanoma patients (n = 38) could reflect disease stage. The subpopulation of sEV expressing CD81 EV marker (CD81sEV) was captured by an ad hoc immune affinity technique from plasma depleted of large EV. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA was detectable in patients with respect to healthy donors (HD). Moreover, a higher C18:0/C18:1 ratio, as a marker of cell membrane fluidity, distinguished early (stage 0–I) from late (III–IV) stages’ CD81sEV. Proteomics detected increases in CD14, PON1, PON3 and APOA5 exclusively in stage II CD81sEV, and RAP1B was decreased in stage III–IV CD81sEV, in comparison to HD. Our results suggest that stage dependent alterations in CD81sEV’ FA and protein composition may occur early after disease onset, strengthening the potential of circulating sEV as a source of discriminatory information for early diagnosis, prediction of metastatic behavior and following up of melanoma patients.
Magnesium Impregnated on NaX Zeolite Synthesized from Cogon Grass Silica for Fast Production of Fructose via Microwave-Assisted Catalytic Glucose Isomerization
Authors: Kulawong Sittichai , Youngjan Saran , Khemthong Pongtanawat , Chanlek Narong , Wittayakun Jatuporn , Osakoo Nattawut
Published: August 2021

Fructose is a crucial intermediate in the production of several chemical platforms. Fructose is mainly produced from glucose isomerization either through immobilized enzymes or heterogeneous catalysts using a conventional heating source, and this is time-consuming. Thus, this work discloses a fast production of fructose via microwave-assisted catalytic glucose isomerization using Mg catalysts supported on NaX zeolite from cogon grass silica. The catalysts were prepared by the impregnation of magnesium nitrate solution and subsequently transformed into MgO on NaX by calcination. The effect of 3, 6 and 9 wt.% Mg content on NaX on the performance of glucose isomerized to fructose was tested at 90 °C for 15 min. The best catalyst was selected for studying the effect of reaction times of 5, 15, 30 and 60 min. Results from X-ray diffraction (XRD), N2 sorption and CO2 temperature-programmed desorption (CO2-TPD) suggested that crystallinity, surface area and micropore volume decrease but basicity increases with Mg content. The X-ray photoelectron spectroscopy (XPS) result confirmed the presence of mixed phases of MgO and Mg2CO3 in all catalysts. The glucose conversion enhanced with the Mg loading but the fructose yield gave the highest value with Mg of 6 wt.%, probably due to the tuning of high active sites and surface area. The greatest fructose selectivity and yield (71.9% and 25.8%) were obtained within 15 min by microwave-assisted catalytic reaction, shorter than the reported value in the literature, indicating a suitable reaction time. Mg (6 wt.%)/NaX catalyst preserves the original catalytic performance up to three cycles, indicating that it is a promising catalyst for fructose production.
Immobilization of Mutant Phosphotriesterase on Fuller’s Earth Enhanced the Stability of the Enzyme
Authors: Latip Wahhida , Knight Victor Feizal , Khim Ong Keat , Mohd Kasim Noor Azilah , Wan Yunus Wan Md Zin , Mohamad Ali Mohd Shukuri , Mohd Noor Siti Aminah
Published: August 2021

Immobilization is a method for making an enzyme more robust in the environment, especially in terms of its stability and reusability. A mutant phosphotriesterase (YT PTE) isolated from Pseudomonas dimunita has been reported to have high proficiency in hydrolyzing the Sp and Rp-enantiomers of organophosphate chromophoric analogs and therefore has great potential as a decontamination agent and biosensor. This work aims to investigate the feasibility of using Fuller’s earth (FE) as a YT PTE immobilization support and characterize its biochemical features after immobilization. The immobilized YT PTE was found to show improvement in thermal stability with a half-life of 24 h compared to that of the free enzyme, which was only 8 h. The stability of the immobilized YT PTE allowed storage for up to 4 months and reuse for up to 6 times. The immobilized YT PTE showed high tolerance against all tested metal ions, Tween 40 and 80 surfactants and inorganic solvents. These findings showed that the immobilized YT PTE became more robust for use especially with regards to its stability and reusability. These features would enhance the future applicability of this enzyme as a decontamination agent and its use in other suitable industrial applications.
Investigation on the Cause of the SO2 Generation during Hot Gas Desulfurization (HGD) Process
Authors: Hwang Byungwook , Kim Jung Hwan , Lee Doyeon , Nam Hyungseok , Kim Ha Na , Baek Jeom In , Ryu Ho-Jung
Published: August 2021

In the integrated gasification combined cycle (IGCC) process, the sulfur compounds present in coal are converted to hydrogen sulfide (H2S) when the coal is gasified. Due to its harmful effects on sorbent/solvent and environmental regulations, H2S needs to be removed from the product gas stream. To simulate the H2S removal process, desulfurization was carried out using a dry sorbent as a fluidizing material within a bubbling, high-temperature fluidized bed reactor. The ZnO-based sorbent showed not only an excellent capacity of H2S removal but also long-term stability. However, unexpected SO2 gas at a concentration of several hundred ppm was detected during the desulfurization reaction. Thus, we determined that there is an unknown source that supplies oxygen to ZnS, and identified the oxygen supplier through three possibilities: oxygen by reactant (fresh sorbent, ZnO), byproduct (ZnSO4), and product (H2O). From the experiment results, we found that the H2O produced from the reaction reacts with ZnS, resulting in SO2 gas being generated during desulfurization. The unknown oxygen source during desulfurization was deduced to be oxygen from H2O produced during desulfurization. That is, the oxygen from produced H2O reacts with ZnS, leading to SO2 generation at high temperature.
Unraveling Human AQP5-PIP Molecular Interaction and Effect on AQP5 Salivary Glands Localization in SS Patients
Authors: Chivasso Clara , Nesverova Veronika , Järvå Michael , Blanchard Anne , Rose Kristie L , Öberg Fredrik Kryh , Wang Zhen , Martin Maud , Lhotellerie Florent , Zindy Egor , Junqueira Bruna , Leroy Karelle , Vanhollebeke Benoit , Delforge Valérie , Bolaky Nargis , Perret Jason , Soyfoo Muhammad Shahnawaz , Moscato Stefania , Baldini Chiara , Chaumont François , Mattii Letizia , Schey Kevin L , Myal Yvonne , Törnroth-Horsefield Susanna , Delporte Christine
Published: August 2021

Saliva secretion requires effective translocation of aquaporin 5 (AQP5) water channel to the salivary glands (SGs) acinar apical membrane. Patients with Sjögren’s syndrome (SS) display abnormal AQP5 localization within acinar cells from SGs that correlate with sicca manifestation and glands hypofunction. Several proteins such as Prolactin-inducible protein (PIP) may regulate AQP5 trafficking as observed in lacrimal glands from mice. However, the role of the AQP5-PIP complex remains poorly understood. In the present study, we show that PIP interacts with AQP5 in vitro and in mice as well as in human SGs and that PIP misexpression correlates with an altered AQP5 distribution at the acinar apical membrane in PIP knockout mice and SS hMSG. Furthermore, our data show that the protein-protein interaction involves the AQP5 C-terminus and the N-terminal of PIP (one molecule of PIP per AQP5 tetramer). In conclusion, our findings highlight for the first time the role of PIP as a protein controlling AQP5 localization in human salivary glands but extend beyond due to the PIP-AQP5 interaction described in lung and breast cancers.
Association of TP53 Alteration with Tissue Specificity and Patient Outcome of IDH1-Mutant Glioma
Authors: Murnyak Balazs , Huang L. Eric
Published: August 2021

Since the initial discovery of recurrent isocitrate dehydrogenase 1 (IDH1) mutations at Arg132 in glioma, IDH1 hotspot mutations have been identified in cholangiocarcinoma, chondrosarcoma, leukemia, and various other types of cancer of sporadic incidence. Studies in glioma and leukemia have helped promote the theory that IDH1 mutations are an oncogenic event that drives tumorigenesis in general. Through bioinformatic analysis of more than 45,000 human pan-cancer samples from three independent datasets, we show here that IDH1 mutations are rare events in human cancer but are exclusively prevalent in WHO grade II and grade III (lower-grade) glioma. Interestingly, alterations in the tumor-suppressor gene TP53 (tumor protein p53) co-occur significantly with IDH1 mutations and show a tendency of exclusivity to IDH2 mutations. The co-occurrence of IDH1 mutation and TP53 alteration is widespread in glioma, particularly in those harboring IDH1R132H, IDH1R132G, and IDH1R132S, whereas co-occurrence of IDH1R132C and TP53 alteration can be found sporadically in other cancer types. In keeping with the importance of p53 in tumor suppression, TP53 status is an independent predictor of overall survival irrespective of histological and molecular subgroups in lower-grade glioma. Together, these results indicate tissue specificity of IDH1 hotspot mutation and TP53 alteration and the importance of TP53 status as a predictor of patient outcome in lower-grade glioma.
Oleuropein Activates Neonatal Neocortical Proteasomes, but Proteasome Gene Targeting by AAV9 Is Variable in a Clinically Relevant Piglet Model of Brain Hypoxia-Ischemia and Hypothermia
Authors: El Demerdash Nagat , Chen May W. , O’Brien Caitlin E. , Adams Shawn , Kulikowicz Ewa , Martin Lee J. , Lee Jennifer K.
Published: August 2021

Cerebral hypoxia-ischemia (HI) compromises the proteasome in a clinically relevant neonatal piglet model. Protecting and activating proteasomes could be an adjunct therapy to hypothermia. We investigated whether chymotrypsin-like proteasome activity differs regionally and developmentally in the neonatal brain. We also tested whether neonatal brain proteasomes can be modulated by oleuropein, an experimental pleiotropic neuroprotective drug, or by targeting a proteasome subunit gene using recombinant adeno-associated virus-9 (AAV). During post-HI hypothermia, we treated piglets with oleuropein, used AAV-short hairpin RNA (shRNA) to knock down proteasome activator 28γ (PA28γ), or enforced PA28γ using AAV-PA28γ with green fluorescent protein (GFP). Neonatal neocortex and subcortical white matter had greater proteasome activity than did liver and kidney. Neonatal white matter had higher proteasome activity than did juvenile white matter. Lower arterial pH 1 h after HI correlated with greater subsequent cortical proteasome activity. With increasing brain homogenate protein input into the assay, the initial proteasome activity increased only among shams, whereas HI increased total kinetic proteasome activity. OLE increased the initial neocortical proteasome activity after hypothermia. AAV drove GFP expression, and white matter PA28γ levels correlated with proteasome activity and subunit levels. However, AAV proteasome modulation varied. Thus, neonatal neocortical proteasomes can be pharmacologically activated. HI slows the initial proteasome performance, but then augments ongoing catalytic activity. AAV-mediated genetic manipulation in the piglet brain holds promise, though proteasome gene targeting requires further development.
Innate Immune Responses to Herpesvirus Infection
Authors: O’Connor Christine M. , Sen Ganes C.
Published: August 2021

Infection of a host cell by an invading viral pathogen triggers a multifaceted antiviral response. One of the most potent defense mechanisms host cells possess is the interferon (IFN) system, which initiates a targeted, coordinated attack against various stages of viral infection. This immediate innate immune response provides the most proximal defense and includes the accumulation of antiviral proteins, such as IFN-stimulated genes (ISGs), as well as a variety of protective cytokines. However, viruses have co-evolved with their hosts, and as such, have devised distinct mechanisms to undermine host innate responses. As large, double-stranded DNA viruses, herpesviruses rely on a multitude of means by which to counter the antiviral attack. Herein, we review the various approaches the human herpesviruses employ as countermeasures to the host innate immune response.
New Activities of the Nuclear Pore Complexes
Authors: Wong Richard W.
Published: August 2021

Nuclear pore complexes (NPCs) at the surface of nuclear membranes play a critical role in regulating the transport of both small molecules and macromolecules between the cell nucleus and cytoplasm via their multilayered spiderweb-like central channel. During mitosis, nuclear envelope breakdown leads to the rapid disintegration of NPCs, allowing some NPC proteins to play crucial roles in the kinetochore structure, spindle bipolarity, and centrosome homeostasis. The aberrant functioning of nucleoporins (Nups) and NPCs has been associated with autoimmune diseases, viral infections, neurological diseases, cardiomyopathies, and cancers, especially leukemia. This Special Issue highlights several new contributions to the understanding of NPC proteostasis.
Patient-Specific Guided Osteotomy to Correct a Symptomatic Malunion of the Left Forearm
Authors: Schröder Femke F. , de Graaff Feike , Vochteloo Anne J. H.
Published: August 2021

We present a case report of a 12-year old female with a midshaft forearm fracture. Initial conservative treatment with a cast failed, resulting in a malunion. The malunion resulted in functional impairment for which surgery was indicated. A corrective osteotomy was planned using 3D analyses of the preoperative CT-scan. Subsequently, patient-specific guides were printed and used during the procedure to precisely correct the malunion. Three months after surgery, the radiographs showed full consolidation and the patient was pain-free with full range of motion and comparable strength in both forearms. The current case report shows that a corrective osteotomy with patient-specific guides based on preoperative 3D analyses can help surgeons to plan and precisely correct complex malunions resulting in improved functional outcomes.