bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychophysiological Stress Reactivity in Monozygotic Twins with and without Takotsubo Syndrome
Authors: Princip Mary , Zuccarella-Hackl Claudia , Langraf-Meister Rebecca E. , Pazhenkottil Aju , Cammann Victoria L. , Templin Christian , Ghadri Jelena-Rima , von Känel Roland
Published: October 2022

Objective: Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction, often elevated myocardial enzymes, and electrocardiographic changes. Previous studies suggested that an overstimulation of the sympathetic nervous system might cause TTS. However, the pathogenesis of TTS is largely unknown. Therefore, we investigated physiological stress reactivity with a standardized stress test in monozygotic twin sisters, only one of whom had experienced TTS. Methods: The 60-year-old Caucasian monozygotic twins, one with and one without a previous episode of TTS, were recruited in the Department of Cardiology at the University Hospital Zurich, Switzerland. We applied the Trier Social Stress Test (TSST) to investigate stress reactivity six weeks after the TTS. Hemodynamic measures (heart rate (HR), blood pressure (BP)), heart rate variability (HRV), plasma norepinephrine and epinephrine and salivary cortisol levels were collected immediately before and after the TSST, and 15, 45, and 90 min after TSST. The monozygotic twins differed in their hemodynamic stress response with the TTS twin showing blunted HR and BP reactivity and vagal withdrawal beyond the acute phase of stress. In contrast, the TTS twin showed a higher catecholamine and cortisol stress response with a steady increase in norepinephrine during the recovery period from stress compared to her non-TTS twin sister. Conclusion: Large studies applying a case-control design are needed to confirm blunted hemodynamic reactivity, increased catecholamine reactivity, vagal withdrawal, and increased cortisol reactivity to stress in TTS. This may advance the knowledge of psychophysiological mechanisms in TTS.
Modulatory Effects of NBF1, an Algal Fiber-Rich Bioformula, on Adiponectin and C-Reactive Protein Levels, and Its Therapeutic Prospects for Metabolic Syndrome and Type-2 Diabetes Patients
Authors: Ngatu Nlandu Roger , Ikeda Mitsunori , Tonduangu Daniel Kuezina , Nangana Severin Luzitu , Hirao Tomohiro
Published: October 2022

An unhealthy diet can lead to the development of metabolic disorders. C-reactive protein (CRP) has been reported to be an inflammatory component of metabolic disorders. Additionally, reduced adiponectin (APN) levels is known as a predictor of metabolic disorders. We report on the beneficial effects of NBF1, an algal fiber-rich formula, on CRP, APN, and diabetes markers. Additionally, associations between dietary nutrients, CRP, and APN were investigated. A dietary survey that used a brief self-administered diet history questionnaire, a validated 58-item fixed-portion-type questionnaire, and a 4-week placebo-controlled dietary intervention were carried out. The latter consisted of a twice daily intake of 3 g of sujiaonori alga-based powder as a supplement (NBF1, n = 16), whereas the placebo group received the same amount of corn starch powder (n = 15). CRP and APN levels were assayed by ELISA. Clinical cases comprising three subjects with metabolic disorders treated with NBF1, including two type 2 diabetes mellitus patients and one subject with hypercholesterolemia, are also reported. They received 2.1g NBF1 once daily for 12 weeks. Intakes of algal fiber and n-3 PUFA were positively associated with the increase of APN, and n-3PUFA intake was inversely associated with CRP. All cases had improved metabolic health profile.
Radiologist versus Non-Radiologist Detection of Lymph Node Metastasis in Papillary Thyroid Carcinoma by Ultrasound: A Meta-Analysis
Authors: Issa Peter P. , Mueller Lauren , Hussein Mohammad , Albuck Aaron , Shama Mohamed , Toraih Eman , Kandil Emad
Published: October 2022

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer worldwide and is known to spread to adjacent neck lymphatics. Lymph node metastasis (LNM) is a known predictor of disease recurrence and is an indicator for aggressive resection. Our study aims to determine if ultrasound sonographers’ degree of training influences overall LNM detection. PubMed, Embase, and Scopus articles were searched and screened for relevant articles. Two investigators independently screened and extracted the data. Diagnostic test parameters were determined for all studies, studies reported by radiologists, and studies reported by non-radiologists. The total sample size amounted to 5768 patients and 10,030 lymph nodes. Radiologists performed ultrasounds in 18 studies, while non-radiologists performed ultrasounds in seven studies, corresponding to 4442 and 1326 patients, respectively. The overall sensitivity of LNM detection by US was 59% (95%CI = 58–60%), and the overall specificity was 85% (95%CI = 84–86%). The sensitivity and specificity of US performed by radiologists were 58% and 86%, respectively. The sensitivity and specificity of US performed by non-radiologists were 62% and 78%, respectively. Summary receiver operating curve (sROC) found radiologists and non-radiologists to detect LNM on US with similar accuracy (p = 0.517). Our work suggests that both radiologists and non-radiologists alike detect overall LNM with high accuracy on US.
Does a High-Risk (>1/50) Result for First-Trimester Combined Screening Always Entail Invasive Testing? Which Patients from This Group Might Benefit from cfDNA Testing?
Authors: García-Jiménez Rocío , Valero Irene , Corrales-Gutiérrez Isabel , Granell Reyes , Borrero Carlota , Sainz-Bueno José Antonio
Published: October 2022

Currently, cell-free DNA (cfDNA) is offered as part of a contingent screening for patients with a first-trimester combined test (FCT) risk between 1/50 and 1/250. However, most aneuploidies are within the group of patients with a risk above 1/10. An observational, retrospective, and multi-centric study was carried out, to evaluate the theorical performance of lowering the cut-off point for the high-risk group from 1/50 to 1/10. Out of the 25,920 patients included, 25,374 (97.9%) consented to the cfDNA contingent screening for aneuploidies. With the proposed strategy, knowing that the detection rate (DR) of cfDNA testing for trisomy 21 is 99.7%, the DR for trisomy 21 would have stayed in a 93.2%, just as it was with the current strategy. In this instance, 267 (1.1%) invasive tests would have been performed, while the current strategy had a total of 307 (1.2%). The false positive rate (FPR) rate would have stayed at 5.2% in both scenarios. In conclusion, the contingent screening of aneuploidies based in the result of the FCT, offering the analysis of cfDNA to patients with an intermediate risk after lowering the cut-off point from 1/50 to 1/10, is a valid alternative that might maintain the current detection rates and avoid the complications associated with invasive testing.
Unusual Mathematical Approaches Untangle Nervous Dynamics
Authors: Tozzi Arturo , Mariniello Lucio
Published: October 2022

The massive amount of available neurodata suggests the existence of a mathematical backbone underlying neuronal oscillatory activities. For example, geometric constraints are powerful enough to define cellular distribution and drive the embryonal development of the central nervous system. We aim to elucidate whether underrated notions from geometry, topology, group theory and category theory can assess neuronal issues and provide experimentally testable hypotheses. The Monge’s theorem might contribute to our visual ability of depth perception and the brain connectome can be tackled in terms of tunnelling nanotubes. The multisynaptic ascending fibers connecting the peripheral receptors to the neocortical areas can be assessed in terms of knot theory/braid groups. Presheaves from category theory permit the tackling of nervous phase spaces in terms of the theory of infinity categories, highlighting an approach based on equivalence rather than equality. Further, the physical concepts of soft-matter polymers and nematic colloids might shed new light on neurulation in mammalian embryos. Hidden, unexpected multidisciplinary relationships can be found when mathematics copes with neural phenomena, leading to novel answers for everlasting neuroscientific questions. For instance, our framework leads to the conjecture that the development of the nervous system might be correlated with the occurrence of local thermal changes in embryo–fetal tissues.
Direct Reprogramming of Mouse Subchondral Bone Osteoblasts into Chondrocyte-like Cells
Authors: Li Meihan , Zhang Lingzhi , Li Jing , Zhu Qing
Published: October 2022

Treatment of full-thickness articular cartilage defects with exposure of subchondral bone often seen in osteoarthritic conditions has long been a great challenge, especially with a focus on the feasibility of in situ cartilage regeneration through minimally invasive procedures. Osteoblasts that situate in the subchondral bone plate may be considered a potentially vital endogenous source of cells for cartilage resurfacing through direct reprogramming into chondrocytes. Microarray-based gene expression profiles were generated to compare tissue-specific transcripts between subchondral bone and cartilage of mice and to assess age-dependent differences of chondrocytes as well. On osteoblast cell lines established from mouse proximal tibial subchondral bone, sequential screening by co-transduction of transcription factor (TF) genes that distinguish chondrocytes from osteoblasts reveals a shortlist of potential reprogramming factors exhibiting combined effects in inducing chondrogenesis of subchondral bone osteoblasts. A further combinatorial approach unexpectedly identified two 3-TF combinations containing Sox9 and Sox5 that exhibit differences in reprogramming propensity with the third TF c-Myc or Plagl1, which appeared to direct the converted chondrocytes toward either a superficial or a deeper zone phenotype. Thus, our approach demonstrates the possibility of converting osteoblasts into two major chondrocyte subpopulations with two combinations of three genes (Sox9, Sox5, and c-Myc or Plagl1). The findings may have important implications for developing novel in situ regeneration strategies for the reconstruction of full-thickness cartilage defects.
The Role of Focal Therapy and Active Surveillance for Small Renal Mass Therapy
Authors: Matuszczak Milena , Kiljańczyk Adam , Salagierski Maciej
Published: October 2022

Small and low-grade renal cell carcinomas have little potential for metastasis and disease-related mortality. As a consequence, the main problem remains the use of appropriately tailored treatment for each individual patient. Surgery still remains the gold standard, but many clinicians are questioning this approach and present the advantages of focal therapy. The choice of treatment regimen remains a matter of debate. This article summarizes the current treatment options in the management of small renal masses.
Exploring the Antibacterial and Biosensing Applications of Peroxidase-Mimetic Ni0.1Cu0.9S Nanoflower
Authors: Liu Li , Lai Yayu , Cao Jinming , Peng Yu , Tian Tian , Fu Wensheng
Published: October 2022

Nanozymes, as artificial enzymes with the biological action of natural enzymes, have enormous potential in the fields of disease diagnosis, bacteriostasis, biosensing, etc. In this work, the Ni0.1Cu0.9S nanoflower was successfully synthesized through a one-step hydrothermal method. A combined strategy of Ni doping and morphology design was employed to adjust its electronic structure and active sites, endowing the Ni0.1Cu0.9S nanoflower with excellent peroxidase-like activity. Therefore, it can catalyze the decomposition of H2O2 to generate •OH with higher antibacterial activity, establishing a broad-spectrum antibacterial system based on the Ni0.1Cu0.9S nanoflower against E. coli and S. aureus, which avoids the harm of a high concentration of H2O2. Additionally, the colorless substrate TMB can be catalytically oxidized into blue ox-TMB via •OH. As a result, a colorimetric technique with rapid and accurate detection of ascorbic acid (AA) by the unaided eye was designed, in view of the specific inhibition effect towards the oxidation of TMB. This detection platform has a wide linear range (10~800 μM) with a low limit of detection (0.84 μM) and exhibits a satisfactory selectivity toward the detection of AA. This study sheds new light on the application of copper-containing nanozymes in the fields of biomedicine and bioassay.
Chemobrain, Olfactory and Lifestyle Assessment in Onco-Geriatrics: Sex-Mediated Differences between Chemotherapy and Immunotherapy
Authors: Invitto Sara , Leucci Mariangela , Accogli Giuseppe , Schito Andrea , Nestola Claudia , Ciccarese Vincenzo , Rinaldi Ross , Boscolo Rizzo Paolo , Spinato Giacomo , Leo Silvana
Published: October 2022

A possible link between chemotherapy and cognitive impairment has been identified. In the literature, this condition is usually called chemobrain and can mostly affect some memory domain but can lead also to other cognitive impairments. Olfaction, which is known to be linked with cognitive domain and the nociception system, can also be affected by chemotherapy. The aim of this study was to investigate the main cognitive and olfactory abilities and the functional and nutritional state of a cohort of chemotherapy and immunotherapy onco-geriatric patients and control geriatrics subjects. Cognitive, olfactory, geriatric and nutritional assessments were performed through the Mini Mental State Examination (MMSE), Sniffin’ Sticks Screening 12, G8 test and a questionnaire on the adherence of the Mediterranean diet, respectively. Our findings show a gender effect on the MMSE. Overall results indicate more pronounced impairments both at the cognitive and frailty level regardless of the type of therapy. On the other hand, the Sniffin’ Sticks performances highlight a significant decrease in olfactory perception ability of subjects following immunotherapy. Significant correlations between olfactory performance and MMSE and G8 scores were also found, as well as between MMSE and G8 measures.
Preserved Executive Control in Ageing: The Role of Literacy Experience
Authors: Pérez Ana I. , Fotiadou Georgia , Tsimpli Ianthi
Published: October 2022

Healthy ageing is commonly accompanied by cognitive decline affecting several domains such as executive control, whereas certain verbal skills remain relatively preserved. Interestingly, recent scientific research has shown that some intellectual activities may be linked to beneficial effects, delaying or even alleviating cognitive decline in the elderly. Thirty young (age: M = 23) and thirty old (age: M = 66) adults were assessed in executive control (switching) and literacy experience (print exposure). First, we tried to confirm whether healthy ageing was generally associated with deficits in switching by looking at mixing cost effects, to then investigate if individual differences in print exposure explained variation in that age-related mixing costs. Both accuracy and reaction times mixing cost indexes demonstrated larger cost in old (but not in young) adults when switching from local to global information. More importantly, this cost effect was not present in old adults with higher print exposure (reaction times). Our findings suggest literacy experience accumulated across the life-span may act as a cognitive reserve proxy to prevent executive control decline.
The Efficacy and Tolerability of Electroconvulsive Therapy in Psychiatric Patients with Arachnoid Cysts: A Retrospective Chart Study
Authors: Lu Ying , Tian Yu , Gan Yu , Fu Yixiao , Chen Qibin , Zou Lei , Zhao Bangshu , Yan Yu , Liu Shudong , Chen Xiaolu , Li Xiao
Published: October 2022

Electroconvulsive therapy (ECT) is an effective therapy for many psychiatric illnesses. However, intracranial occupying lesions are a relative contraindication to ECT. Arachnoid cysts are benign, congenital, and space-occupying lesions. Our study aimed to evaluate the efficacy and tolerability of ECT in psychiatric patients with arachnoid cysts. We retrospectively identified 62 psychiatric patients with arachnoid cysts; 43 of them underwent ECT and 19 did not. Their conditions were assessed by CGI-S and different scales depending on different diagnoses (PANSS for schizophrenia; HAMD for depression; YMRS for bipolar disorder). The side effect was assessed by TESS. Significant differences were shown in the reduced scores of the CGI-S between patients who underwent ECT and those who did not (p = 0.001), while, at the same time, there was no significant difference in their TESS score (p = 0.297). The current study found that ECT is an effective and tolerable therapy for psychiatric patients with arachnoid cysts.
Embryonic Deletion of TXNIP in GABAergic Neurons Enhanced Oxidative Stress in PV+ Interneurons in Primary Somatosensory Cortex of Aging Mice: Relevance to Schizophrenia
Authors: Xue Ting , Wang Xiaodan , Hu Ying , Cheng Ying , Li Han , Shi Yuan , Wang Lijun , Yin Dongmin , Cui Donghong
Published: October 2022

The brain is susceptible to perturbations of redox balance, affecting neurogenesis and increasing the risks of psychiatric disorders. Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of the thioredoxin antioxidant system. Its deletion or inhibition suggests protection for a brain with ischemic stroke or Alzheimer’s disease. Combined with conditional knockout mice and schizophrenia samples, we aimed to investigate the function of TXNIP in healthy brain and psychiatric disorders, which are under-studied. We found TXNIP was remarkedly expressed in the prefrontal cortex (PFC) during healthy mice’s prenatal and early postnatal periods, whereas it rapidly decreased throughout adulthood. During early life, TXNIP was primarily distributed in inhibitory and excitatory neurons. Contrary to the protective effect, the embryonic deletion of TXNIP in GABAergic (gamma-aminobutyric acid-ergic) neurons enhanced oxidative stress in PV+ interneurons of aging mice. The deleterious impact was brain region-specific. We also investigated the relationship between TXNIP and schizophrenia. TXNIP was significantly increased in the PFC of schizophrenia-like mice after MK801 administration, followed by oxidative stress. First episode and drug naïve schizophrenia patients with a higher level of plasma TXNIP displayed severer psychiatric symptoms than patients with a low level. We indicated a bidirectional function of TXNIP in the brain, whose high expression in the early stage is protective for development but might be harmful in a later period, associated with mental disorders.
Comparing Different Kinds of Influence on an Algorithm in Its Forecasting Process and Their Impact on Algorithm Aversion
Authors: Gubaydullina Zulia , Judek Jan René , Lorenz Marco , Spiwoks Markus
Published: October 2022

Although algorithms make more accurate forecasts than humans in many applications, decision-makers often refuse to resort to their use. In an economic experiment, we examine whether the extent of this phenomenon known as algorithm aversion can be reduced by granting decision-makers the possibility to exert an influence on the configuration of the algorithm (an influence on the algorithmic input). In addition, we replicate the study carried out by Dietvorst et al. (2018). This shows that algorithm aversion recedes significantly if the subjects can subsequently change the results of the algorithm—and even if this is only by a small percentage (an influence on the algorithmic output). The present study confirms that algorithm aversion is reduced significantly when there is such a possibility to influence the algorithmic output. However, exerting an influence on the algorithmic input seems to have only a limited ability to reduce algorithm aversion. A limited opportunity to modify the algorithmic output thus reduces algorithm aversion more effectively than having the ability to influence the algorithmic input.
Use of Heteroatom-Doped g-C3N4 Particles as Catalysts for Dehydrogenation of Sodium Borohydride in Methanol
Authors: Demirci Sahin , Sahiner Nurettin
Published: October 2022

Here, graphitic carbon nitride (g-C3N4) was synthesized from melamine, doped with heteroatoms, such as B, S, and P reported using boric acid, sulfur, and phosphorous red as dopants, respectively. The catalytic performances of g-C3N4, and heteroatom-doped g-C3N4 (H@g-C3N4 (H=B, S or P) particles as catalysts in the dehydrogenation of sodium borohydride (NaBH4) in methanol to generate hydrogen (H2) were investigated. The prepared g-C3N4-based structures were used as catalysts for hydrogen (H2) production in the dehydrogenation reaction of sodium borohydride (NaBH4) in methanol. The catalytic performance of H@g-C3N4 (H=B, S or P) structures in the dehydrogenation reaction of sodium borohydride (NaBH4) in methanol was determined to be higher than the catalytic performance of the bare g-C3N4 structure. The hydrogen generation rate (HGR) values were calculated for the reactions catalyzed by B@g-C3N4, P@g-C3N4, and S@g-C3N4 as 609 ± 48, 699 ± 48, and 429 ± 55 mL H2/g of cat.min, respectively, which is only 282 ± 11 mL H2/g of cat.min for the native g-C3N4-catalyzed one. The activation energies (Ea) were found to be relatively low, such as 31.2, 26.9, and 31.2 kJ/mol, for the reactions catalyzed by B@g-C3N4, P@g-C3N4, and S@g-C3N4, respectively. In addition, in the reuse studies, it was concluded that B@g-C3N4, P@g-C3N4, and S@g-C3N4 catalysts can readily complete the reaction with 100% conversion, even in five consecutive uses, and afforded promising potential with more than 80% activity for each use.
Advances in Chemotherapy and Targeted Therapies in Endometrial Cancer
Authors: Chambers Setsuko K.
Published: October 2022

Endometrial cancer is now recognized to be several diseases with differing biology and responses to treatment. Improved molecular characterization has furthered the development and testing of targeted therapies in the different cohorts of endometrial cancer. Lessons are being learned from other cancers that share similar molecular typing, and hence, potentially similar tumor behavior. This commentary serves as a broad overview of the types of advances to which our patients now have access.
Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas
Authors: Kyriakidis Ioannis , Mantadakis Elpis , Stiakaki Eftichia , Groll Andreas H. , Tragiannidis Athanasios
Published: October 2022

The aim of this review is to highlight mechanisms of immunosuppression for each agent, along with pooled analyses of infectious complications from the available medical literature. Rituximab confers no increase in grade ≥3 infectious risks, except in the case of patients with advanced-stage non-Hodgkin lymphoma. Gemtuzumab ozogamicin links with high rates of grade ≥3 infections which, however, are comparable with historical cohorts. Pembrolizumab exhibits a favorable safety profile in terms of severe infections. Despite high rates of hypogammaglobulinemia (HGG) with blinatumomab, low-grade ≥3 infection rates were observed, especially in the post-reinduction therapy of relapsed B-acute lymphoblastic leukemia. Imatinib and nilotinib are generally devoid of severe infectious complications, but dasatinib may slightly increase the risk of opportunistic infections. Data on crizotinib and pan-Trk inhibitors entrectinib and larotrectinib are limited. CAR T-cell therapy with tisagenlecleucel is associated with grade ≥3 infections in children and is linked with HGG and the emergence of immune-related adverse events. Off-label therapies inotuzumab ozogamicin, brentuximab vedotin, and venetoclax demonstrate low rates of treatment-related grade ≥3 infections, while the addition of bortezomib to standard chemotherapy in T-cell malignancies seems to decrease the infection risk during induction. Prophylaxis, immune reconstitution, and vaccinations for each targeted agent are discussed, along with comparisons to adult studies.
Machine Learning for Risk Prediction of Oesophago-Gastric Cancer in Primary Care: Comparison with Existing Risk-Assessment Tools
Authors: Briggs Emma , de Kamps Marc , Hamilton Willie , Johnson Owen , McInerney Ciarán D. , Neal Richard D.
Published: October 2022

Oesophago-gastric cancer is difficult to diagnose in the early stages given its typical non-specific initial manifestation. We hypothesise that machine learning can improve upon the diagnostic performance of current primary care risk-assessment tools by using advanced analytical techniques to exploit the wealth of evidence available in the electronic health record. We used a primary care electronic health record dataset derived from the UK General Practice Research Database (7471 cases; 32,877 controls) and developed five probabilistic machine learning classifiers: Support Vector Machine, Random Forest, Logistic Regression, Naïve Bayes, and Extreme Gradient Boosted Decision Trees. Features included basic demographics, symptoms, and lab test results. The Logistic Regression, Support Vector Machine, and Extreme Gradient Boosted Decision Tree models achieved the highest performance in terms of accuracy and AUROC (0.89 accuracy, 0.87 AUROC), outperforming a current UK oesophago-gastric cancer risk-assessment tool (ogRAT). Machine learning also identified more cancer patients than the ogRAT: 11.0% more with little to no effect on false positives, or up to 25.0% more with a slight increase in false positives (for Logistic Regression, results threshold-dependent). Feature contribution estimates and individual prediction explanations indicated clinical relevance. We conclude that machine learning could improve primary care cancer risk-assessment tools, potentially helping clinicians to identify additional cancer cases earlier. This could, in turn, improve survival outcomes.
Changes of Protein Expression after CRISPR/Cas9 Knockout of miRNA-142 in Cell Lines Derived from Diffuse Large B-Cell Lymphoma
Authors: Menegatti Jennifer , Nakel Jacqueline , Stepanov Youli K. , Caban Karolina M. , Ludwig Nicole , Nord Ruth , Pfitzner Thomas , Yazdani Maryam , Vilimova Monika , Kehl Tim , Lenhof Hans-Peter , Philipp Stephan E. , Meese Eckart , Fröhlich Thomas , Grässer Friedrich A. , Hart Martin
Published: October 2022

Background: As microRNA-142 (miR-142) is the only human microRNA gene where mutations have consistently been found in about 20% of all cases of diffuse large B-cell lymphoma (DLBCL), we wanted to determine the impact of miR-142 inactivation on protein expression of DLBCL cell lines. Methods: miR-142 was deleted by CRISPR/Cas9 knockout in cell lines from DLBCL. Results: By proteome analyses, miR-142 knockout resulted in a consistent up-regulation of 52 but also down-regulation of 41 proteins in GC-DLBCL lines BJAB and SUDHL4. Various mitochondrial ribosomal proteins were up-regulated in line with their pro-tumorigenic properties, while proteins necessary for MHC-I presentation were down-regulated in accordance with the finding that miR-142 knockout mice have a defective immune response. CFL2, CLIC4, STAU1, and TWF1 are known targets of miR-142, and we could additionally confirm AKT1S1, CCNB1, LIMA1, and TFRC as new targets of miR-142-3p or -5p. Conclusions: Seed-sequence mutants of miR-142 confirmed potential targets and novel targets of miRNAs can be identified in miRNA knockout cell lines. Due to the complex contribution of miRNAs within cellular regulatory networks, in particular when miRNAs highly present in RISC complexes are replaced by other miRNAs, primary effects on gene expression may be covered by secondary layers of regulation.
Radiotherapy-Related Gene Signature in Prostate Cancer
Authors: Kogionou Paraskevi , Fortis Sotirios , Goulielmaki Maria , Aubert Nicolas , Batsaki Panagiota , Ouzounis Sotirios , Cavouras Dionisis , Marodon Gilles , Stokidis Savvas , Gritzapis Angelos , Baxevanis Constantin
Published: October 2022

Radiotherapy for localized prostate cancer has increased the cure and survival rates of patients. Besides its local tumoricidal effects, ionizing radiation has been linked to mechanisms leading to systemic immune activation, a phenomenon called the abscopal effect. In this study, we performed gene expression analysis on peripheral blood from prostate cancer patients obtained post- radiotherapy and showed that 6 genes, including CCR7, FCGR2B, BTLA, CD6, CD3D, and CD3E, were down-regulated by a range of 1.5–2.5-fold as compared to pre-radiotherapy samples. The expression of the signature consisting of these six genes was also significantly lower post- vs. pre-radiotherapy. These genes are involved in various tumor-promoting immune pathways and their down-regulation post-radiotherapy could be considered beneficial for patients. This is supported by the fact that low mRNA expression levels for the 6-gene signature in the prostate tumor tissue was linked to better survival. Importantly, we report that this 6-gene signature strongly correlated with a favorable prognosis regardless of poor standard clinicopathological parameters (i.e., Gleason score ≥ 8 and T3 (including T3a and T3b). Our pioneering data open the possibility that the 6-gene signature identified herein may have a predictive value, but this requires further long-term studies.
Subtotal Pleurectomy with Intrathoracic Chemo Hyperthermia (HITHOC) for IVa Thymomas: De Novo Versus Recurrent Pleural Disease
Authors: Chappuy Benjamin , Drevet Gabrielle , Clermidy Hugo , Rosamel Pascal , Duruisseaux Mickael , Couraud Sebastien , Grima Renaud , Soldea Valentin , Chalabreysse Lara , Tronc François , Girard Nicolas , Maury Jean-Michel
Published: October 2022

Introduction: Stage IVa thymoma is a rare disease without a standard of care. Subtotal pleurectomy and HITHOC introduced in highly selected patients may provide interesting oncologic results. The purpose of this study was to distinguish de novo stage IVa tumors (DNT) from distant relapse (DR) with respect to post-operative and long-term outcomes to provide the procedure efficacy. Methods: From July 1997–December 2021, 40 patients with IVa pleural involvement were retrospectively analyzed. The surgical procedure was subtotal pleurectomy and HITHOC (cisplatin 50 mg/m2, mitomycin 25 mg/m2, 42 °C, 90 min). The post-operative outcome, disease-free interval (DFI) and overall survival (OS) were analyzed. Results: Mean age was 52 ± 12 years. B2 and B3 thymomas were preponderant (27; 67.5%). The median number of pleural nodes were nine (4–81) vs. five (1–36); p = 0.004 * in DNT and DR, respectively. Hospital mortality rate was 2.5%. There were four specific HITHOC complications (10%). DFI were 49 and 85 months (p = 0.02 *), OS were 94 and 118 months (NS), in DNT and DR, respectively. Conclusions: Subtotal pleurectomy with HITHOC in IVa offers satisfying results in highly selected patients, for both DNT and DR. Due to the disease rarity, multicentric studies are needed to define HITHOC as a standard of care.
Is There a Role for Exercise When Treating Patients with Cancer with Immune Checkpoint Inhibitors? A Scoping Review
Authors: Handford Jasmine , Chen Miaoqi , Rai Ridesh , Moss Charlotte L. , Enting Deborah , Peat Nicola , Karagiannis Sophia N. , Van Hemelrijck Mieke , Russell Beth
Published: October 2022

The impact of using exercise as a non-pharmacological intervention in patients with cancer receiving immune checkpoint inhibitors (ICIs) is not well known. Our objective was to determine the extent of, and identify gaps within, available literature addressing the effect of exercise on (a) oncological outcomes and (b) quality of life (QoL) in patients with cancer receiving ICIs, and (c) the underlying biological mechanisms for such effects. We conducted searches across EMBASE, APA PsycInfo and Ovid MEDLINE(R). Studies were eligible if they addressed at least one aspect of the objective and were available in the English language. Results were synthesised using a narrative approach and subsequently discussed with multidisciplinary stakeholders. As of the final search on 5 April 2022, 11 eligible studies were identified, of which 8 were preclinical and 3 were clinical. Clinical studies only focused on QoL-related outcomes. When studies were grouped by whether they addressed oncological outcomes (n = 7), QoL (n = 5) or biological mechanisms (n = 7), they were found to be heterogeneous in methodology and findings. Additional evidence, particularly in the clinical setting, is required before robust recommendations about whether, and how, to include exercise alongside ICI treatment can be made.
Metabolomic and Lipidomic Profiling of Gliomas—A New Direction in Personalized Therapies
Authors: Gaca-Tabaszewska Magdalena , Bogusiewicz Joanna , Bojko Barbara
Published: October 2022

In addition to being the most common primary brain tumor, gliomas are also among the most difficult to diagnose and treat. At present, the “gold standard” in glioma treatment entails the surgical resection of the largest possible portion of the tumor, followed by temozolomide therapy and radiation. However, this approach does not always yield the desired results. Additionally, the ability to cross the blood-brain barrier remains a major challenge for new potential drugs. Thus, researchers continue to search for targeted therapies that can be individualized based on the specific characteristics of each case. Metabolic and lipidomic research may represent two of the best ways to achieve this goal, as they enable detailed insights into the changes in the profile of small molecules in a biological system/specimen. This article reviews the new approaches to glioma therapy based on the analysis of alterations to biochemical pathways, and it provides an overview of the clinical results that may support personalized therapies in the future.
Immune Checkpoint Blockade: A Strategy to Unleash the Potential of Natural Killer Cells in the Anti-Cancer Therapy
Authors: Grottoli Melania , Carrega Paolo , Zullo Lodovica , Dellepiane Chiara , Rossi Giovanni , Parisi Francesca , Barletta Giulia , Zinoli Linda , Coco Simona , Alama Angela , Marconi Silvia , Parodi Monica , Orecchia Paola , Bassi Sara , Vitale Massimo , Mingari Maria Cristina , Pfeffer Ulrich , Genova Carlo , Pietra Gabriella
Published: October 2022

Immune checkpoint inhibitors (ICIs) immunotherapy has represented a breakthrough in cancer treatment. Clinical use of ICIs has shown an acceptable safety profile and promising antitumor activity. Nevertheless, some patients do not obtain clinical benefits after ICIs therapy. In order to improve and cure an increasing number of patients, the field has moved toward the discovery of new ICIs expressed by cells of innate immunity with an elevated inherent antitumor activity, such as natural killer cells. This review will focus on the recent findings concerning the role of classical and non-classical immune checkpoint molecules and receptors that regulate natural killer cell function, as potential targets, and their future clinical application.
Ferroptosis Induction and YAP Inhibition as New Therapeutic Targets in Gastrointestinal Stromal Tumors (GISTs)
Authors: Delvaux Marine , Hagué Perrine , Craciun Ligia , Wozniak Agnieszka , Demetter Pieter , Schöffski Patrick , Erneux Christophe , Vanderwinden Jean-Marie
Published: October 2022

GISTs are sarcomas of the gastrointestinal tract often associated with gain-of-function mutations in KIT or PDGFRA receptor genes. While most GISTs initially respond to tyrosine kinase inhibitors, relapses due to acquired resistance frequently occur. The induction of ferroptosis, an iron-dependent form of non-apoptotic cell death, emerged as a novel therapeutic approach in cancers and remains poorly characterized in GISTs. We studied hallmarks of ferroptosis, i.e., lipid peroxidation, iron and glutathione content, and GPX4 protein expression in imatinib-sensitive (GIST882) and -resistant (GIST48) GIST cell lines. GIST cells were highly sensitive to the induction of ferroptosis by RSL3, which was reversed by liproxstatin and deferoxamine. Lipid peroxidation and ferroptosis were mediated by VP and CA3 in GIST cells through a significant decrease in antioxidant defenses. Moreover, VP, but surprisingly not CA3, inhibited a series of target genes downstream of YAP in GIST cells. The ferroptosis marker TFRC was also investigated by immunohistochemistry in GIST tissue arrays. TFRC expression was observed in all samples. High TFRC expression was positively correlated with high-risk GISTs, elevated mitotic count, and YAP nuclear localization, reflecting YAP activation. This study highlights ferroptosis as a novel cell death mechanism in GISTs, and a potential therapeutic target to overcome resistance to tyrosine kinase inhibitors.
Metabolomics by NMR Combined with Machine Learning to Predict Neoadjuvant Chemotherapy Response for Breast Cancer
Authors: Cardoso Marcella R. , Silva Alex Ap. Rosini , Talarico Maria Cecília R. , Sanches Pedro H. Godoy , Sforça Maurício L. , Rocco Silvana A. , Rezende Luciana M. , Quintero Melissa , Costa Tassia B. B. C. , Viana Laís R. , Canevarolo Rafael R. , Ferracini Amanda C. , Ramalho Susana , Gutierrez Junier Marrero , Guimarães Fernando , Tasic Ljubica , Tata Alessandra , Sarian Luís O. , Cheng Leo L. , Porcari Andreia M. , Derchain Sophie F. M.
Published: October 2022

Neoadjuvant chemotherapy (NACT) is offered to patients with operable or inoperable breast cancer (BC) to downstage the disease. Clinical responses to NACT may vary depending on a few known clinical and biological features, but the diversity of responses to NACT is not fully understood. In this study, 80 women had their metabolite profiles of pre-treatment sera analyzed for potential NACT response biomarker candidates in combination with immunohistochemical parameters using Nuclear Magnetic Resonance (NMR). Sixty-four percent of the patients were resistant to chemotherapy. NMR, hormonal receptors (HR), human epidermal growth factor receptor 2 (HER2), and the nuclear protein Ki67 were combined through machine learning (ML) to predict the response to NACT. Metabolites such as leucine, formate, valine, and proline, along with hormone receptor status, were discriminants of response to NACT. The glyoxylate and dicarboxylate metabolism was found to be involved in the resistance to NACT. We obtained an accuracy in excess of 80% for the prediction of response to NACT combining metabolomic and tumor profile data. Our results suggest that NMR data can substantially enhance the prediction of response to NACT when used in combination with already known response prediction factors.
Understanding the Philosophy, Anatomy, and Surgery of the Extra-TME Plane of Locally Advanced and Locally Recurrent Rectal Cancer; Single Institution Experience with International Benchmarking
Authors: van Kessel Charlotte S. , Solomon Michael J.
Published: October 2022

Pelvic exenteration surgery has become a widely accepted procedure for treatment of locally advanced (LARC) and locally recurrent rectal cancer (LRRC). However, there is still unwarranted variation in peri-operative management and subsequently oncological outcome after this procedure. In this article we will elaborate on the various reasons for the observed differences based on benchmarking results of our own data to the data from the PelvEx collaborative as well as findings from 2 other benchmarking studies. Our main observation was a significant difference in extent of resection between exenteration units, with our unit performing more complete soft tissue exenterations, sacrectomies and extended lateral compartment resections than most other units, resulting in a higher R0 rate and longer overall survival. Secondly, current literature shows there is a tendency to use more neoadjuvant treatment such as re-irradiation and total neoadjuvant treatment and perform less radical surgery. However, peri-operative chemotherapy or radiotherapy should not be a substitute for adequate radical surgery and an R0 resection remains the gold standard. Finally, we describe our experiences with standardizing our surgical approaches to the various compartments and the achieved oncological and functional outcomes.
Inhibition of Phosphoglycerate Dehydrogenase Radiosensitizes Human Colorectal Cancer Cells under Hypoxic Conditions
Authors: Van de Gucht Melissa , Dufait Inès , Kerkhove Lisa , Corbet Cyril , de Mey Sven , Jiang Heng , Law Ka Lun , Gevaert Thierry , Feron Olivier , De Ridder Mark
Published: October 2022

Augmented de novo serine synthesis activity is increasingly apparent in distinct types of cancers and has mainly sparked interest by investigation of phosphoglycerate dehydrogenase (PHGDH). Overexpression of PHGDH has been associated with higher tumor grade, shorter relapse time and decreased overall survival. It is well known that therapeutic outcomes in cancer patients can be improved by reprogramming metabolic pathways in combination with standard treatment options, for example, radiotherapy. In this study, possible metabolic changes related to radioresponse were explored upon PHGDH inhibition. Additionally, we evaluated whether PHGDH inhibition could improve radioresponse in human colorectal cancer cell lines in both aerobic and radiobiological relevant hypoxic conditions. Dysregulation of reactive oxygen species (ROS) homeostasis and dysfunction in mitochondrial energy metabolism and oxygen consumption rate were indicative of potential radiomodulatory effects. We demonstrated that PHGDH inhibition radiosensitized hypoxic human colorectal cancer cells while leaving intrinsic radiosensitivity unaffected. In a xenograft model, the first hints of additive effects between PHGDH inhibition and radiotherapy were demonstrated. In conclusion, this study is the first to show that modulation of de novo serine biosynthesis enhances radioresponse in hypoxic colorectal cancer cells, mainly mediated by increased levels of intracellular ROS.
Surgical Tolerability and Frailty in Elderly Patients Undergoing Robot-Assisted Radical Prostatectomy: A Narrative Review
Authors: Yamada Yuta , Taguchi Satoru , Kume Haruki
Published: October 2022

Robot-assisted radical prostatectomy (RARP) has now become the gold standard treatment for localized prostate cancer. There are multiple elements in decision making for the treatment of prostate cancer. One of the important elements is life expectancy, which the current guidelines recommend as an indicator for choosing treatment options. However, determination of life expectancy can be complicated and difficult in some cases. In addition, surgical tolerability is also an important issue. Since frailty may be a major concern, it may be logical to use geriatric assessment tools to discriminate ‘surgically fit’ patients from unfit patients. Landmark studies show two valid models such as the phenotype model and the cumulative deficit model that allow for the diagnosis of frailty. Many studies have also developed geriatric screening tools such as VES-13 and G8. These tools may have the potential to directly sort out unfit patients for surgery preoperatively.
Assessment of a Euro VI Step E Heavy-Duty Vehicle’s Aftertreatment System
Authors: Giechaskiel Barouch , Selleri Tommaso , Gioria Roberto , Melas Anastasios D. , Franzetti Jacopo , Ferrarese Christian , Suarez-Bertoa Ricardo
Published: October 2022

The latest generation of heavy-duty vehicles (Euro VI step E) have to respect low emission limits both in the laboratory and on the road. The most challenging pollutants for diesel vehicles are NOx and particles; nevertheless, NH3 and N2O need attention. In this study, we measured regulated and unregulated pollutants of a Euro VI step E Diesel vehicle. Samples were taken downstream of (i) the engine, (ii) the Diesel oxidation catalyst (DOC) and catalyzed Diesel particulate filter (cDPF), and (iii) the selective catalytic reduction (SCR) unit for NOx with an ammonia slip catalyst (ASC). In addition to typical laboratory and real-world cycles, various challenging tests were conducted (urban driving with low payload, high-speed full-load driving, and idling) at 23 °C and 5 °C. The results showed high efficiencies of the DOC, DPF, and SCR under most testing conditions. Cold start cycles resulted in high NOx emissions, while high-temperature cycles resulted in high particle emissions. The main message of this study is that further improvements are necessary, also considering possible reductions in the emission limits in future EU regulations.
Direct One-Step Seedless Hydrothermal Growth of ZnO Nanostructures on Zinc: Primary Study for Photocatalytic Roof Development for Rainwater Purification
Authors: Le Pivert Marie , Piebourg Aurélie , Bastide Stéphane , Duc Myriam , Leprince-Wang Yamin
Published: October 2022

To shift towards the greener city, photocatalytic urban infrastructures have emerged as a promising solution for pollution remediation. To reach this goal, the large bandgap semiconductors, such as nontoxic Zinc Oxide (ZnO), already proved their excellent photocatalytic performances. However, integrating and developing cost-effective and greener photocatalytic surfaces with an easily scaled-up synthesis method and without energy and chemical product overconsumption is still challenging. Therefore, this work proposes to develop a depolluting Zinc (Zn) roof covered by ZnO nanostructures (NSs) using a one-step seedless hydrothermal growth method in 2 h. The feasibility of this synthesis was firstly studied on small areas of Zn (1.25 cm2) before being scaled up to medium-sized areas (25 cm2). The efficiency of this functionalization route for ZnO NSs grown without seed layer was attributed to the presence of Zn2+ sites and the native oxide film on the Zn surface. Their photocatalytic efficiency was demonstrated by removing in less than 3 h the Methylene Blue (MB) and Acid Red 14 (AR14) in both DI water and rainwater under UV-light. Promising results were also recorded under solar light. Therefore, the photocatalytic Zn roof functionalized by ZnO NSs is a promising route for rainwater purification by photocatalysis.
The Conversion of Waste Biomass into Carbon-Supported Iron Catalyst for Syngas to Clean Liquid Fuel Production
Authors: Amin Muhammad , Munir Saleem , Iqbal Naseem , Wabaidur Saikh , Iqbal Amjad
Published: October 2022

Syngas has been utilized in the production of chemicals and fuels, as well as in the creation of electricity. Feedstock impurities, such as nitrogen, sulfur, chlorine, and ash, in syngas have a negative impact on downstream processes. Fischer–Tropsch synthesis is a process that relies heavily on temperature to increase the production of liquid fuels (FTS). In this study, waste biomass converted into activated carbon and then a carbon-supported iron-based catalyst was prepared. The catalyst at 200 °C and 350 °C was used to investigate the influence of temperature on the subsequent application of syngas to liquid fuels. Potassium (K) was used as a structural promoter in the Fe-C catalyst to boost catalyst activity and structural stability (Fe-C-K). Low temperatures (200 °C) cause 60% and 80% of diesel generation, respectively, without and with potassium promoter. At high temperatures (350 °C), the amount of gasoline produced is 36% without potassium promoter, and 72% with promoter. Iron carbon-supported catalysts with potassium promoter increase gasoline conversion from 36.4% (Fe-C) to 72.5% (Fe-C-K), and diesel conversion from 60.8% (Fe-C) to 80.0% (Fe-C-K). As seen by SEM pictures, iron particles with potassium promoter were found to be equally distributed on the surface of activated carbon.