bluuebunny/crossref_metadata_2025 huggingface dataset:
No Change in Inhibitory Control or P3 Following Different High-Intensity Interval Exercise Modalities
Authors: Drollette Eric S. , Johnson Megan N. , Meadows Caroline C.
Published: January 2022

Acute aerobic high-intensity interval exercise (HIIE) has demonstrated positive effects on inhibitory control and P3 event-related potential (ERP) in young adults. However, the evidence is not well established regarding the effects of different HIIE modalities that incorporate aerobic-resistance training on these cognitive and neurocognitive outcomes. The purpose of this investigation was to examine the transient effects of HIIE-aerobic and HIIE-aerobic/resistance on P3 and Flanker task performance. Participants (n = 24; 18–25 years old) completed the Flanker task at two time points (30 min and 85 min) following 9 min of HIIE-aerobic (intermittent bouts of walking and running at 90% of maximal heart rate), HIIE-aerobic/resistance (intermittent bouts of walking and high-intensity calisthenics), and seated rest on three separate counterbalanced days. Results revealed no changes in Flanker performance (i.e., reaction time and response accuracy) or P3 (latency and mean amplitude) following either HIIE conditions compared to seated rest. Together, these data suggest inhibitory control and neuroelectric underpinnings are not affected by different modalities of HIIE at 30 min and 85 min post-exercise. Such findings reveal that engaging in short bouts of different HIIE modalities for overall health neither improves nor diminishes inhibitory control and brain function for an extended period throughout the day.
Gender Differences in the Correlations between Childhood Trauma, Schizotypy and Negative Emotions in Non-Clinical Individuals
Authors: Thomas Elizabeth H. X. , Rossell Susan L. , Gurvich Caroline
Published: January 2022

Early life trauma has a negative impact on the developing brain, and this can lead to a wide range of mental illnesses later in life. Childhood trauma is associated with increased psychotic symptoms and negative emotions such as depressive, anxiety, and stress symptoms in adulthood. Childhood trauma has also been shown to influence sub-clinical ‘schizotypy’ characteristics of psychosis in the general population. As it has been reported that mental health outcomes after early life trauma exposure are influenced by gender, the current study aimed to investigate the gender differences in the relationship between childhood trauma, schizotypy and negative emotions. Sixty-one non-clinical participants (33 men and 28 women) aged between 18 and 45 completed self-report questionnaires to measure early life trauma, schizotypy and negative emotions. Despite similar levels of childhood trauma in men and women, early life trauma in women was associated with increased schizotypy personality characteristics (Cognitive Disorganisation) and increased depression, anxiety and stress later in life, but no correlations were observed in men. Our findings suggest that the sociocultural and biological processes affected by early life adversities may differ between the genders. Women may be more vulnerable to the influence of childhood trauma, which may be associated with increased psychopathology later in life.
Performance Comparison of Different Building Shapes Using a Wind Tunnel and a Computational Model
Authors: Sari Dany Perwita , Cho Kang-Pyo
Published: January 2022

A building-integrated wind turbine (BIWT) is an alternative way to assess renewable energy. BIWTs produces their own energy without relying on fossil fuels. However, only a few researchers have studied BIWTs. Greater wind velocity (V) results in greater potential energy (P). The aerodynamic design has an important role to play in increasing wind velocity and reducing turbulence intensity. CFD simulations taken from previous research have revealed that round-shaped buildings increase velocity up to 30%. This study focuses on the wind response of square and top-rounded-shaped building models, and their optimization based on variations in wind velocity. Wind tunnel studies were conducted to study wind flow around the building, followed by a computer simulation to verify the results. In a wind tunnel, three BIWT models (1:150 in scale) located in Seoul, South Korea (terrain B), were evaluated. The results of the study show that the streamline should be followed when installing wind turbines on rectangular rooves with flat surfaces. This method allows wind speed to be elevated significantly, when compared to a turbine at a higher height. In addition, round corners can produce wind velocity that is up to 34% greater than sharp corners beside a building. In summary, this paper presents a five-step analysis framework that can be used by researchers who wish to analyze BIWTs through wind tunnel experiments and CFD.
Potential Application of BIM in RFI in Building Projects
Authors: Morales Francisca , Herrera Rodrigo F. , Rivera Felipe Muñoz-La , Atencio Edison , Nuñez Manuel
Published: January 2022

Requests for information (RFIs) are frequently used by the architecture, engineering, construction, and operation (AECO) industry to resolve doubts and inaccuracies and to request complimentary information. However, they can be inefficient due to the lag between issuance and response, generating delays and cost overruns. The building information modeling (BIM) methodology allows for the integration of information by using virtual models and facilitating the control and management of RFIs; however, the full potential of BIM is not being exploited. Therefore, this work aims to analyze the RFIs of 17 high-rise building projects in conjunction with the application of BIM for their mitigation. To achieve this, categories of RFI categories were identified, the issuance and response process was analyzed, the building projects’ RFIs were classified, the most frequent problems were identified, the BIM uses that would allow for a reactive or preventive action were identified, and, finally, the potential benefits of BIM use for the reduction of RFIs were analyzed. The research showed that the correct use of BIM applications focusing on RFIs allows for an effective information review, generating preventive or reactive management of problems. Thus, it is possible to identify the recurrent causes of RFIs and those specialties issuing the most RFIs, with the objective of mitigating RFI submission in construction projects.
Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases
Authors: Mekhaeil Marianna , Dev Kumlesh Kumar , Conroy Melissa Jane
Published: January 2022

Over the past decade, Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors have arisen as a novel and promising targeted therapy for breast cancer gene (BRCA)-mutated ovarian and breast cancer patients. Therapies targeting the enzyme, PARP-1, have since established their place as maintenance drugs for cancer. Here, we present existing evidence that implicates PARP-1 as a player in the development and progression of both malignancy and demyelinating disease. These findings, together with the proven clinical efficacy and marketed success of PARP-1 inhibitors in cancer, present the repurposing of these drugs for demyelinating diseases as a desirable therapeutic concept. Indeed, PARP-1 inhibitors are noted to demonstrate neuroprotective effects in demyelinating disorders such as multiple sclerosis and Parkinson’s disease, further supporting the use of these drugs in demyelinating, neuroinflammatory, and neurodegenerative diseases. In this review, we discuss the potential for repurposing PARP-1 inhibitors, with a focus on rare demyelinating diseases. In particular, we address the possible use of PARP-1 inhibitors in examples of rare leukodystrophies, for which there are a paucity of treatment options and an urgent need for novel therapeutic approaches.
Denonvilliers’ Fascia: The Prostate Border to the Outside World
Authors: Tzelves Lazaros , Protogerou Vassilis , Varkarakis Ioannis
Published: January 2022

The fascial structure around the prostate has been a controversial issue for several decades, but its role in radical prostatectomy is crucial to achieving successful nerve-sparing surgery. One of the fasciae surrounding the prostate is Denonvilliers’ fascia, forming its posterior border with the rectum and enclosing along its layers several fibers of the neurovascular bundle. This review focuses on embryological and anatomical points of Denonvilliers’ fascia, aiming to provide a summary for the operating general surgeons and urologists of this area.
Dynamic Prediction of Near-Term Overall Survival in Patients with Advanced NSCLC Based on Real-World Data
Authors: Wang Xuechen , Kerrigan Kathleen , Puri Sonam , Shen Jincheng , Akerley Wallace , Haaland Benjamin
Published: January 2022

Patients with terminal cancers commonly receive aggressive and sub-optimal treatment near the end of life, which may not be beneficial in terms of duration or quality of life. To improve end-of-life care, it is essential to develop methods that can accurately predict the short-term risk of death. However, most prediction models for patients with cancer are static in the sense that they only use patient features at a fixed time. We proposed a dynamic prediction model (DPM) that can incorporate time-dependent predictors. We apply this method to patients with advanced non-small-cell lung cancer from a real-world database. Inverse probability of censoring weighted AUC with bootstrap inference was used to compare predictions among models. We found that increasing ECOG performance status and decreasing albumin had negative prognostic associations with overall survival (OS). Moreover, the negative prognostic implications strengthened over the patient disease course. DPMs using both time-independent and time-dependent predictors substantially improved short-term prediction accuracy compared to Cox models using only predictors at a fixed time. The proposed model can be broadly applied for prediction based on longitudinal data, including an estimation of the dynamic effects of time-dependent features on OS and updating predictions at any follow-up time.
Fecal Microbiota Transplant for Hematologic and Oncologic Diseases: Principle and Practice
Authors: Bou Zerdan Maroun , Niforatos Stephanie , Nasr Sandy , Nasr Dayana , Ombada Mulham , John Savio , Dutta Dibyendu , Lim Seah H.
Published: January 2022

Understanding of the importance of the normal intestinal microbial community in regulating microbial homeostasis, host metabolism, adaptive immune responses, and gut barrier functions has opened up the possibility of manipulating the microbial composition to modulate the activity of various intestinal and systemic diseases using fecal microbiota transplant (FMT). It is therefore not surprising that use of FMT, especially for treating relapsed/refractory Clostridioides difficile infections (CDI), has increased over the last decade. Due to the complexity associated with and treatment for these diseases, patients with hematologic and oncologic diseases are particularly susceptible to complications related to altered intestinal microbial composition. Therefore, they are an ideal population for exploring FMT as a therapeutic approach. However, there are inherent factors presenting as obstacles for the use of FMT in these patients. In this review paper, we discussed the principles and biologic effects of FMT, examined the factors rendering patients with hematologic and oncologic conditions to increased risks for relapsed/refractory CDI, explored ongoing FMT studies, and proposed novel uses for FMT in these groups of patients. Finally, we also addressed the challenges of applying FMT to these groups of patients and proposed ways to overcome these challenges.
Neuro-Oncology Patients as Human Research Subjects: Ethical Considerations for Cognitive and Behavioral Testing for Research Purposes
Authors: Kaur Jasleen , Egladyous Andrew , Valdivia Claudia , Daniel Andy G. S. , Krishna Saritha , Aabedi Alexander A. , Brang David , Hervey-Jumper Shawn L.
Published: January 2022

Language, cognition, and behavioral testing have become a fundamental component of standard clinical care for brain cancer patients. Many existing publications have identified and addressed potential ethical issues that are present in the biomedical setting mostly centering around the enrollment of vulnerable populations for therapeutic clinical trials. Well-established guides and publications have served as useful tools for clinicians; however, little has been published for researchers who share the same stage but administer tests and collect valuable data solely for non-therapeutic investigational purposes derived from voluntary patient participation. Obtaining informed consent and administering language, cognition, and behavioral tasks for the sole purpose of research involving cancer patients that exhibit motor speech difficulties and cognitive impairments has its own hardships. Researchers may encounter patients who experience emotional responses during tasks that challenge their existing impairments. Patients may have difficulty differentiating between clinical testing and research testing due to similarity of task design and their physician’s dual role as a principal investigator in the study. It is important for researchers to practice the proposed methods emphasized in this article to maintain the overall well-being of patients while simultaneously fulfilling the purpose of the study in a research setting.
Biopsy and Margins Optimize Outcomes after Thermal Ablation of Colorectal Liver Metastases
Authors: Vasiniotis Kamarinos Nikiforos , Vakiani Efsevia , Gonen Mithat , Kemeny Nancy E. , Sigel Carlie , Saltz Leonard B. , Brown Karen T. , Covey Anne M. , Erinjeri Joseph P. , Brody Lynn A. , Ziv Etay , Yarmohammadi Hooman , Kunin Henry , Barlas Afsar , Petre Elena N. , Kingham Peter T. , D’Angelica Michael I. , Manova-Todorova Katia , Solomon Stephen B. , Sofocleous Constantinos T.
Published: January 2022

Background: Thermal ablation is a definitive local treatment for selected colorectal liver metastases (CLM) that can be ablated with adequate margins. A critical limitation has been local tumor progression (LTP). Methods: This prospective, single-group, phase 2 study enrolled patients with CLM < 5 cm in maximum diameter, at a tertiary cancer center between November 2009 and February 2019. Biopsy of the ablation zone center and margin was performed immediately after ablation. Viable tumor in tissue biopsy and ablation margins < 5 mm were assessed as predictors of 12-month LTP. Results: We enrolled 107 patients with 182 CLMs. Mean tumor size was 2.0 (range, 0.6–4.6) cm. Microwave ablation was used in 51% and radiofrequency ablation in 49% of tumors. The 12- and 24-month cumulative incidence of LTP was 22% (95% confidence interval [CI]: 17, 29) and 29% (95% CI: 23, 36), respectively. LTP at 12 months was 7% (95% CI: 3, 14) for the biopsy tumor-negative ablation zone with margins ≥ 5 mm vs. 63% (95% CI: 35, 85) for the biopsy-positive ablation zone with margins < 5 mm (p < 0.001). Conclusions: Biopsy-proven complete tumor ablation with margins of at least 5 mm achieves optimal local tumor control for CLM, regardless of the ablation modality used.
From Interferon to Checkpoint Inhibition Therapy—A Systematic Review of New Immune-Modulating Agents in Bacillus Calmette–Guérin (BCG) Refractory Non-Muscle-Invasive Bladder Cancer (NMIBC)
Authors: Deininger Susanne , Törzsök Peter , Mitterberger Michael , Pallauf Maximilian , Oswald David , Deininger Christian , Lusuardi Lukas
Published: January 2022

Background: In Bacillus Calmette–Guérin (BCG) refractory non-muscle-invasive bladder cancer (NMIBC), radical cystectomy is the gold standard. The advent of immune checkpoint inhibitors (CPIs) has permanently changed the therapy landscape of bladder cancer (BC). This article presents a systematic review of immune-modulating (IM) therapies (CPIs and others) in BCG-refractory NMIBC. Methods: In total, 406 articles were identified through data bank research in PubMed/Medline, with data cutoff in October 2021. Four full-text articles and four additional congress abstracts were included in the review. Results: Durvalumab plus Oportuzumab monatox, Pembrolizumab, and Nadofaragene firadenovec (NF) show complete response (CR) rates of 41.6%, 40.6%, and 59.6% after 3 months, with a long-lasting effect, especially for NF (12-month CR rate of 30.5%). Instillations with oncolytic viruses such as NF and CG0070 show good efficacy without triggering significant immune-mediated systemic adverse events. Recombinant BCG VPM1002BC could prove to be valid as an alternative to BCG in the future. The recombinant pox-viral vector vaccine PANVAC™ is not convincing in combination with BCG. Interleukin mediating therapies, such as ALT-803, are currently being studied. Conclusion: CPIs and other IM agents now offer an increasing opportunity for bladder-preserving strategies. Studies on different substances are ongoing and will yield new findings.
Stereotactic Radiotherapy after Radical Prostatectomy in Patients with Prostate Cancer in the Adjuvant or Salvage Setting: A Systematic Review
Authors: Schröder Christina , Tang Hongjian , Windisch Paul , Zwahlen Daniel Rudolf , Buchali André , Vu Erwin , Bostel Tilman , Sprave Tanja , Zilli Thomas , Murthy Vedang , Förster Robert
Published: January 2022

(1) Background: Prostate cancer is the most common cancer in men and can be treated with radical prostatectomy (RPE) or radiotherapy in the primary setting. Stereotactic radiotherapy (SBRT) has proven to be effective and well tolerated in this setting. However, if SBRT is an equally promising treatment option if applied in the adjuvant or salvage setting after RPE remains unknown. (2) Methods: We searched the PubMed and Embase databases with the following full-text queries in August 2021 for any combination of the terms “SBRT”, “prostate”, “adjuvant”, “postoperative”, “salvage”, “stereotactic radiotherapy”, “prostate bed”. There were no limitations regarding publication date or language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. (3) Results: We identified 11 individual studies that were included in this systematic review. Three publications included patients without prior radiotherapy and the remaining eight patients with prior radiotherapy. In all but two publications the radiation target was the macroscopic recurrence. SBRT was overall well tolerated with acceptable rates of acute and late gastrointestinal or genitourinary toxicity. Quality of life was published for two phase I trials with good results. There was a very heterogeneous reporting on biochemical control after SBRT. (4) Conclusions: At this point, ultra-hypofractionated RT using SBRT to the prostate bed remains experimental and its use should be restricted to clinical trials. Given the biological rationale for extreme hypofractionation in patients with prostate cancer and the acceptable toxicity rates that have been reported, further exploration of this field is warranted.
The Genomics of Hairy Cell Leukaemia and Splenic Diffuse Red Pulp Lymphoma
Authors: Oscier David , Stamatopoulos Kostas , Mirandari Amatta , Strefford Jonathan
Published: January 2022

Classical hairy cell leukaemia (HCLc), its variant form (HCLv), and splenic diffuse red pulp lymphoma (SDRPL) constitute a subset of relatively indolent B cell tumours, with low incidence rates of high-grade transformations, which primarily involve the spleen and bone marrow and are usually associated with circulating tumour cells characterised by villous or irregular cytoplasmic borders. The primary aim of this review is to summarise their cytogenetic, genomic, immunogenetic, and epigenetic features, with a particular focus on the clonal BRAFV600E mutation, present in most cases currently diagnosed with HCLc. We then reflect on their cell of origin and pathogenesis as well as present the clinical implications of improved biological understanding, extending from diagnosis to prognosis assessment and therapy response.
The Impact of Surgical Practice on Oncological Outcomes in Robot-Assisted Radical Hysterectomy for Early-Stage Cervical Cancer, Spanish National Registry
Authors: Fernandez-Gonzalez Sergi , Ponce Jordi , Martínez-Maestre María Ángeles , Barahona Marc , Gómez-Hidalgo Natalia R. , Díaz-Feijoo Berta , Casajuana Andrea , Gracia Myriam , Frias-Gomez Jon , Benavente Yolanda , Costas Laura , Martí Lola , Melero Lidia , Silvan Jose Manuel , Beiro Eva , Lobo Ignacio , De la Rosa Jesús , Coronado Pluvio J. , Gil-Moreno Antonio
Published: January 2022

This study aimed to assess whether surgical practice had a significant impact on oncological outcomes among women who underwent robot-assisted radical hysterectomy for early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009). The secondary objective was to audit the pre-surgical quality indicators (QI) proposed by the European Society of Gynaecological Oncology (ESGO). The top 5 of 10 centers in Spain and Portugal were included in the analysis. The hospitals were divided into group A (n = 118) and group B (n = 97), with recurrence rates of <10% and >10%, respectively. After balancing both groups using the propensity score, the ORs for all events were higher and statistically significant for group B (recurrences OR = 1.23, 95% CI = 1.13–1.15, p-value = 0.001; death OR = 1.10, 95% CI = 1.02–1.18, p-value = 0.012; disease-specific mortality ORr = 1.11, 95% CI = 1.04–1.19, p-value = 0.002). A higher surgical volume, higher participation in clinical trials, higher rate of MRI use for diagnosis, greater use of sentinel lymph node biopsies, and a favorable learning curve with low rates of early recurrences were observed among the centers with better oncological outcomes. These factors might have a significant impact on oncological outcomes not only after robot-assisted surgery, but also after laparoscopies and open surgeries in the treatment of cervical cancer.
Radiomic Phenotypes for Improving Early Prediction of Survival in Stage III Non-Small Cell Lung Cancer Adenocarcinoma after Chemoradiation
Authors: Luna José , Barsky Andrew , Shinohara Russell , Roshkovan Leonid , Hershman Michelle , Dreyfuss Alexandra , Horng Hannah , Lou Carolyn , Noël Peter , Cengel Keith , Katz Sharyn , Diffenderfer Eric , Kontos Despina
Published: January 2022

We evaluate radiomic phenotypes derived from CT scans as early predictors of overall survival (OS) after chemoradiation in stage III primary lung adenocarcinoma. We retrospectively analyzed 110 thoracic CT scans acquired between April 2012−October 2018. Patients received a median radiation dose of 66.6 Gy at 1.8 Gy/fraction delivered with proton (55.5%) and photon (44.5%) beam treatment, as well as concurrent chemotherapy (89%) with carboplatin-based (55.5%) and cisplatin-based (36.4%) doublets. A total of 56 death events were recorded. Using manual tumor segmentations, 107 radiomic features were extracted. Feature harmonization using ComBat was performed to mitigate image heterogeneity due to the presence or lack of intravenous contrast material and variability in CT scanner vendors. A binary radiomic phenotype to predict OS was derived through the unsupervised hierarchical clustering of the first principal components explaining 85% of the variance of the radiomic features. C-scores and likelihood ratio tests (LRT) were used to compare the performance of a baseline Cox model based on ECOG status and age, with a model integrating the radiomic phenotype with such clinical predictors. The model integrating the radiomic phenotype (C-score = 0.69, 95% CI = (0.62, 0.77)) significantly improved (p<0.005) upon the baseline model (C-score = 0.65, CI = (0.57, 0.73)). Our results suggest that harmonized radiomic phenotypes can significantly improve OS prediction in stage III NSCLC after chemoradiation.
Plasma Thymidine Kinase Activity as a Novel Biomarker in Metastatic Melanoma Patients Treated with Immune Checkpoint Inhibitors
Authors: Costa Svedman Fernanda , Jalsenius Marie , Höiom Veronica , Grozman Vitali , Bergqvist Mattias , Söderdahl Fabian , Eriksson Hanna , Rotstein Samuel , Ny Lars , Ascierto Paolo A. , Brage Suzanne Egyhazi , Helgadottir Hildur
Published: January 2022

Background. Immune checkpoint inhibitors (ICI) are effective in fractions of patients with disseminated melanoma. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a biomarker in melanoma patients. Methods. Plasma samples were collected prior to treatment start in patients with unresectable metastatic cutaneous melanoma, treated with ICI (anti-CTLA-4 and/or anti-PD-1). Plasma TK activity (TKa) levels were determined using the DiviTum TKa ELISA assay. TKa levels were correlated with patients’ baseline characteristics, response rate (RR), progression-free survival (PFS), and overall survival (OS). Results. In the 90 study patients, the median TKa level was 42 Du/L (range <20–1787 Du/L). A significantly higher plasma TKa was found in patients with ECOG performance status ≥1 (p = 0.003), M1c-d disease (p = 0.015), and elevated lactate dehydrogenase levels (p < 0.001). The RR was 63.2% and 30.3% in those with low or high TKa, respectively (p = 0.022). The median PFS was 19.9 and 12.6 months in patients with low or high TKa, respectively (hazard ratio (HR) 1.83 (95% CI, 1.08–3.08), p = 0.024). The median OS was >60 months and 18.5 months in patients with low or high TKa, respectively (HR: 2.25 (95% CI, 1.25–4.05), p = 0.011. Conclusions. High pretreatment plasma TKa levels were significantly associated with worse baseline characteristics and poor response and survival in ICI-treated melanoma patients. TKa is hence a novel and interesting plasma biomarker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease.
Exploring Posttraumatic Stress Symptoms and Posttraumatic Growth among Children Living beyond Cancer and Their Parents Using an Actor–Partner Interdependence Model
Authors: Wurz Amanda , Patton Michaela , Merz Erin L. , Hou Sharon H. J. , Cho Sara , Schulte Fiona
Published: January 2022

There is a growing focus on describing both negative and positive outcomes in the wake of childhood cancer. The purpose of this study was to describe and explore the relationships between posttraumatic stress symptoms (PTSS) and posttraumatic growth (PTG) among children living beyond cancer and one of their parents. As part of a larger online survey, 113 children (Mage at time of study = 15.82 (SD = 4.81); Mage at diagnosis = 5.86 (SD = 4.66)) and one of their parents completed questionnaires assessing PTSS and PTG. Descriptive statistics were used to describe the sample and levels of PTSS and PTG. Data were z-transformed and analyzed using bivariate correlations and t-tests. An actor–partner interdependence model (APIM) was used to test whether children’s and their parents’ PTSS was associated with their own PTG (actor effect) and the others’ PTG (partner effect). PTSS was low and PTG was moderate in this sample relative to scale ranges. There were no significant differences between the children’s and their parents’ PTSS (p = 0.535) or PTG (p = 0.534). Results from the APIM showed no significant actor effects (p = 0.185). A significant overall partner effect (p = 0.020) emerged. Lower PTSS for children was associated with greater PTG for their parents (b = −0.29, p = 0.018), but parent’s PTSS was not associated with children’s PTG (p = 0.434). This sample reported similar levels of PTSS and PTG to that which has been reported in the literature. Children and their parents’ scores on PTSS and PTG measures were not significantly different from one another. Children’s PTSS was negatively associated with their parents PTG, illuminating the ways in which PTSS and PTG may be related in the context of childhood cancer. Exploring family-based strategies to reduce PTSS and enhance PTG may be warranted, though further studies are required.
Long-Term Outcome in a Phase II Study of Regional Hyperthermia Added to Preoperative Radiochemotherapy in Locally Advanced and Recurrent Rectal Adenocarcinomas
Authors: Schem Baard-Christian , Pfeffer Frank , Ott Martin Anton , Wiig Johan N. , Sletteskog Nils , Frøystein Torbjørn , Myklebust Mette Pernille , Leh Sabine , Dahl Olav , Mella Olav
Published: January 2022

Hyperthermia was added to standard preoperative chemoradiation for rectal adenocarcinomas in a phase II study. Patients with T3-4 N0-2 M0 rectal cancer or local recurrences were included. Radiation dose was 54 Gy combined with capecitabine 825 mg/m2 × 2 daily and once weekly oxaliplatin 55 mg/m2. Regional hyperthermia aimed at 41.5–42.5 °C for 60 min combined with oxaliplatin infusion. Radical surgery with total or extended TME technique, was scheduled at 6–8 weeks after radiation. From April 2003 to April 2008, a total of 49 eligible patients were recruited. Median number of hyperthermia sessions were 5.4. A total of 47 out of 49 patients (96%) had the scheduled surgery, which was clinically radical in 44 patients. Complete tumour regression occurred in 29.8% of the patients who also exhibited statistically significantly better RFS and CSS. Rate of local recurrence alone at 10 years was 9.1%, distant metastases alone occurred in 25.6%, including local recurrences 40.4%. RFS for all patients was 54.8% after 5 years and CSS was 73.5%. Patients with T50 temperatures in tumours above median 39.9 °C had better RFS, 66.7% vs. 31.3%, p = 0.047, indicating a role of hyperthermia. Toxicity was acceptable.
Targeting GPCRs and Their Signaling as a Therapeutic Option in Melanoma
Authors: Raymond Jérémy H. , Aktary Zackie , Larue Lionel , Delmas Véronique
Published: January 2022

G-protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established. However, evidence of new functions of GPCRs directly in melanomagenesis has been highlighted in recent years. GPCRs are coupled, through their intracellular domains, to heterotrimeric G-proteins, which induce cellular signaling through various pathways. Such signaling modulates numerous essential cellular processes that occur during melanomagenesis, including proliferation and migration. GPCR-associated signaling in melanoma can be activated by the binding of paracrine factors to their receptors or directly by activating mutations. In this review, we present melanoma-associated alterations of GPCRs and their downstream signaling and discuss the various preclinical models used to evaluate new therapeutic approaches against GPCR activity in melanoma. Recent striking advances in our understanding of the structure, function, and regulation of GPCRs will undoubtedly broaden melanoma treatment options in the future.
Early-Stage Lung Adenocarcinoma MDM2 Genomic Amplification Predicts Clinical Outcome and Response to Targeted Therapy
Authors: Sinha Abhilasha , Zou Yong , Patel Ayushi S. , Yoo Seungyeul , Jiang Feng , Sato Takashi , Kong Ranran , Watanabe Hideo , Zhu Jun , Massion Pierre P. , Borczuk Alain C. , Powell Charles A.
Published: January 2022

Lung cancer is the most common cause of cancer-related deaths in both men and women, accounting for one-quarter of total cancer-related mortality globally. Lung adenocarcinoma is the major subtype of non-small cell lung cancer (NSCLC) and accounts for around 40% of lung cancer cases. Lung adenocarcinoma is a highly heterogeneous disease and patients often display variable histopathological morphology, genetic alterations, and genomic aberrations. Recent advances in transcriptomic and genetic profiling of lung adenocarcinoma by investigators, including our group, has provided better stratification of this heterogeneous disease, which can facilitate devising better treatment strategies suitable for targeted patient cohorts. In a recent study we have shown gene expression profiling identified novel clustering of early stage LUAD patients and correlated with tumor invasiveness and patient survival. In this study, we focused on copy number alterations in LUAD patients. SNP array data identified amplification at chromosome 12q15 on MDM2 locus and protein overexpression in a subclass of LUAD patients with an invasive subtype of the disease. High copy number amplification and protein expression in this subclass correlated with poor overall survival. We hypothesized that MDM2 copy number and overexpression predict response to MDM2-targeted therapy. In vitro functional data on a panel of LUAD cells showed that MDM2-targeted therapy effectively suppresses cell proliferation, migration, and invasion in cells with MDM2 amplification/overexpression but not in cells without MDM2 amplification, independent of p53 status. To determine the key signaling mechanisms, we used RNA sequencing (RNA seq) to examine the response to therapy in MDM2-amplified/overexpressing p53 mutant and wild-type LUAD cells. RNA seq data shows that in MDM2-amplified/overexpression with p53 wild-type condition, the E2F → PEG10 → MMPs pathway is operative, while in p53 mutant genetic background, MDM2-targeted therapy abrogates tumor progression in LUAD cells by suppressing epithelial to mesenchymal transition (EMT) signaling. Our study provides a potentially clinically relevant strategy of selecting LUAD patients for MDM2-targeted therapy that may provide for increased response rates and, thus, better survival.
Development of a Disease-Specific Health-Related Quality of Life Questionnaire (DTF-QoL) for Patients with Desmoid-Type Fibromatosis
Authors: Schut Anne-Rose W. , Lidington Emma , Timbergen Milea J. M. , Younger Eugenie , van der Graaf Winette T. A. , van Houdt Winan J. , Bonenkamp Johannes J. , Jones Robin L. , Grünhagen Dirk. J. , Sleijfer Stefan , Verhoef Cornelis , Gennatas Spyridon , Husson Olga
Published: January 2022

Sporadic desmoid-type fibromatosis (DTF) is a rare, non-metastasising soft-tissue tumour. Patients can experience a variety of disease-specific issues related to the unpredictable clinical course and aggressiveness of DTF, which negatively impacts health-related quality of life (HRQoL). These DTF-specific issues are not captured by generic HRQoL tools. A 102-item provisional DTF-specific HRQoL tool, the DTF-QoL, was previously developed. The aim of this study was to pre-test the psychometric properties of the DTF-QoL by administering it together with the EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) to 236 DTF patients from the United Kingdom and the Netherlands. Construct validity and reliability were determined based on factor analysis, multi-trait scaling analysis, Cronbach’s alpha, and correlations with the EORTC QLQ-C30 scales. Ninety-six items were selected, conceptualised into three symptom scales, eleven disease-impact scales and six single items, together forming the final DTF-QoL. Scaling assumptions were fully or moderately met for ten out of fourteen scales. Cronbach’s alpha ranged from 0.551–0.908. Most scales of the DTF-QoL were weakly or moderately correlated with the EORTC QLQ-C30. The DTF-QoL is a promising tool capturing the whole spectrum of DTF-specific issues. Implementation of the DTF-QoL in research and clinical practice will help to personalise HRQoL measurement and clinical care for DTF patients.
Psychosocial Needs and Preferences for Care among Adolescent and Young Adult Cancer Patients (Ages 15–39): A Qualitative Study
Authors: Avutu Viswatej , Lynch Kathleen A. , Barnett Marie E. , Vera Jacqueline A. , Glade Bender Julia L. , Tap William D. , Atkinson Thomas M.
Published: January 2022

Adolescents and young adults (AYAs) require a multidisciplinary approach to cancer care due to their complex biopsychosocial situations and varied developmental maturity. Currently, age and diagnosis determine referral to pediatric or adult oncology, with differing treatment paradigms and service utilization patterns, contributing to suboptimal improvements in outcomes. Understanding the unique perspectives of AYAs is essential to designing patient-centered AYA services. Thus, we conducted six focus groups with AYAs (n = 25) treated by medical or pediatric oncologists to evaluate: (1) the unique experiences of cancer care as an AYA; (2) AYA-specific information needs and communication preferences; and (3) recommendations for service provision, delivery and accommodations for AYAs. Transcripts were analyzed using inductive thematic content analysis and identified six major themes to inform clinically-actionable recommendations and the development of a patient-reported outcome measure: (1) AYAs experience social isolation and loss of independence; (2) AYAs have an uncertain sense of the future and need conversations around survivorship and long-term and late effects; (3) AYAs desire greater control over discussions with their care team; (4) AYAs need additional navigational and social/caregiver supports; (5) AYAs prefer an inclusive AYA space in the hospital; and (6) LGBTQ+ patients experience distinct concerns as AYA cancer patients. These will form the basis for specific and tailored clinical recommendations to improve AYA cancer care delivery.
External Validation of the FSAC Model Using On-Therapy Changes in Noninvasive Fibrosis Markers in Patients with Chronic Hepatitis B: A Multicenter Study
Authors: Lee Jae Seung , Lee Hyun Woong , Lim Tae Seop , Min In Kyung , Lee Hye Won , Kim Seung Up , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Kim Beom Kyung
Published: January 2022

Antiviral therapy (AVT) induces the regression of non-invasive fibrosis markers (NFMs) and reduces hepatocellular carcinoma (HCC) risk among chronic hepatitis B (CHB) patients. We externally validated the predictive performance of the FSAC prediction model for HCC using on-therapy NFM responses. Our multicenter study consecutively recruited treatment-naïve CHB patients (n = 3026; median age, 50.0 years; male predominant (61.3%); cirrhosis in 1391 (46.0%) patients) receiving potent AVTs for >18 months between 2007 and 2018. During follow-up (median 64.0 months), HCC developed in 303 (10.0%) patients. Patients with low FIB-4 or APRI levels at 12 months showed significantly lower HCC risk than those with high NFM levels at 12 months (all p < 0.05). Cumulative 3-, 5-, and 8-year HCC probabilities were 0.0%, 0.3% and 1.2% in the low-risk group (FSAC ≤ 2); 2.1%, 5.2%, and 11.1% in the intermediate-risk group (FSAC 3−8); and 5.2%, 15.5%, and 29.8% in the high-risk group (FSAC ≥ 9) (both p < 0.001 between each adjacent pair). Harrell’s c-index value for FSAC score (0.770) was higher than those for PAGE-B (0.725), modified PAGE-B (0.738), modified REACH-B (0.737), LSM-HCC (0.734), and CAMD (0.742). Our study showed that the FSAC model, which incorporates on-therapy changes in NFMs, had better predictive performance than other models using only baseline parameters.
New Approaches with Precision Medicine in Adult Brain Tumors
Authors: Leibetseder Annette , Preusser Matthias , Berghoff Anna Sophie
Published: January 2022

Primary central nervous system (CNS) tumors represent a heterogenous group of tumors. The 2021 fifth edition of the WHO Classification of Tumors of the CNS emphasizes the advanced role of molecular diagnostics with routine implementation of molecular biomarkers in addition to histologic features in the classification of CNS tumors. Thus, novel diagnostic methods such as DNA methylome profiling are increasingly used to provide a more precise diagnostic work-up of CNS tumors. In addition to these diagnostic precision medicine advantages, molecular alterations are also addressed therapeutically with targeted therapies. Like in other tumor entities, precision medicine has therefore also arrived in the treatment of CNS malignancies as the application of targeted therapies has shown promising response rates. Nevertheless, large prospective studies are currently missing as most targeted therapies were evaluated in single arm, basket, or platform trials. In this review, we focus on the current evidence of precision medicine in the treatment of primary CNS tumors in adults. We outline the pathogenic background and prevalence of the most frequent targetable genetic alterations and summarize the existing evidence of precision medicine approaches for the treatment of primary CNS tumors.
Management of Ground-Glass Nodules: When and How to Operate?
Authors: Kim Young Tae
Published: January 2022

With the increased popularity of low-dose computed tomography (LDCT), many patients present with pulmonary ground-glass nodules (GGNs), and the appropriate diagnostic and management strategy of those lesions make physicians be on the horn of the clinical dilemma. As there is not enough data available to set universally acceptable guidelines, the management of GGNs may be different. If GGN is an incidental finding through LDCT, the lesion should be followed according to the current guidelines. We recommend a multidisciplinary team discussion to be initiated if a new solid component develops or the solid portion size grows on follow-up CT as the risk of malignancy is high. Attempts to preoperatively biopsy solid components in part-solid GGNs are often not feasible and not helpful in clinical settings. Currently, if malignancy is suspected, a surgical biopsy with the guidance of various localization methods is recommended. If malignancy is confirmed, sub-lobar resection may provide an excellent oncologic outcome.
Bacterial Competition for the Anode Colonization under Different External Resistances in Microbial Fuel Cells
Authors: Godain Alexiane , Haddour Naoufel , Fongarland Pascal , Vogel Timothy M.
Published: January 2022

This study investigated the effect of external resistance (Rext) on the dynamic evolution of microbial communities in anodic biofilms of single-chamber microbial fuel cells fueled with acetate and inoculated with municipal wastewater. Anodic biofilms developed under different Rext (0, 330 and 1000 ohms, and open circuit condition) were characterized as a function of time during two weeks of growth using 16S rRNA gene sequencing, cyclic voltammetry (CV) and fluorescence microscopy. The results showed a drastic difference in power output of MFCs operated with an open circuit and those operated with Rext from 0 to 1000 ohms. Two steps during the bacterial community development of the anodic biofilms were identified. During the first four days, nonspecific electroactive bacteria (non-specific EAB), dominated by Pseudomonas, Acinetobacter, and Comamonas, grew fast whatever the value of Rext. During the second step, specific EAB, dominated by Geobacter and Desulfuromonas, took over and increased over time, except in open circuit MFCs. The relative abundance of specific EAB decreased with increasing Rext. In addition, the richness and diversity of the microbial community in the anodic biofilms decreased with decreasing Rext. These results help one to understand the bacterial competition during biofilm formation and suggest that an inhibition of the attachment of non-specific electroactive bacteria to the anode surface during the first step of biofilm formation should improve electricity production.
Diastereoselective Formation of Quaternary Stereocenters in Imidazole N-Oxide Cycloaddition with Fluoroalkenes
Authors: Bukowska Patrycja , Loska Rafał
Published: January 2022

Imidazole N-oxides are attractive starting materials for the preparation of complex molecules containing an imidazole ring. Dipolar cycloaddition between 1,1-difluoroalkenes and imidazole N-oxides bearing a chiral auxiliary performed in the presence of oxygen or nitrogen nucleophiles was found to provide access to esters and amides bearing a 2-azaheteroaryl substituent at the α position of the imidazole ring as mixtures of diastereomers that, in most cases, are readily separable. This three-component reaction introduces a new tertiary or quaternary all-carbon stereocenter into the heterocyclic ring at a position originally occupied by hydrogen. Importantly, products containing a trifluoromethyl group attached to this stereocenter are readily available as well.
Applying Hydrogenation to Stabilize N-TiO2 and Enhance Its Visible Light Photocatalytic Activity
Authors: Zhao Dongqiu , Tang Xiao , Qin Xuming , Tang Zhenjie , Yuan Di , Ju Lin
Published: January 2022

Up to now, the explanation for the origin of enhanced photocatalytic activity of N doped TiO2 (N-TiO2) with H incorporation, which is observed in experiment, is still lacking. In our work, the effects of hydrogenation on the stability and electronic properties of N-TiO2 have been systematically investigated by first-principles calculations. Our results of the study on stability demonstrate that, both full and part hydrogenation could stabilize N-TiO2 by largely reducing the formation energy of N doping under Ti-rich conditions. Moreover, the calculated results on the electronic structure show that, for the completely hydrogenated N-TiO2, band gap becomes slightly larger, which is caused by the full passivation for unpaired electron from N atom. However, for the partially hydrogenated N-TiO2, due to the interaction between hydrogenated and unhydrogenated N atoms, its valence band maximum shifts to higher energy by 0.32 eV and the valence band states mix with the wide band-gap states, which results in a higher light absorption capacity and carrier separation. Our results not only explain the enhancement of visible light photocatalytic activity experimentally found in N-TiO2 specimen with H incorporation, but also indicate that, tuning the hydrogenation degree is a hopeful routine to improve the photocatalytic performance of N-TiO2.
Mesenchymal Stem Cell-Based COVID-19 Therapy: Bioengineering Perspectives
Authors: Karakaş Nihal , Üçüncüoğlu Süleyman , Uludağ Damla , Karaoğlan Birnur Sinem , Shah Khalid , Öztürk Gürkan
Published: January 2022

The novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) are currently utilized in clinics for pulmonary inflammatory diseases, including acute respiratory distress syndrome and acute lung injury. Given that MSCs offer a promising treatment against COVID-19, they are being used against COVID-19 in more than 70 clinical trials with promising findings. Genetically engineered MSCs offer promising therapeutic options in pulmonary diseases. However, their potential has not been explored yet. In this review, we provide perspectives on the functionally modified MSCs that can be developed and harnessed for COVID-19 therapy. Options to manage the SARS-CoV-2 infection and its variants using various bioengineering tools to increase the therapeutic efficacy of MSCs are highlighted.