bluuebunny/crossref_metadata_2025 huggingface dataset:
Salmonella enterica induces biogeography-specific changes in the gut microbiome of pigs
Authors: Gomes-Neto Joao Carlos , Pavlovikj Natasha , Korth Nate , Naberhaus Samantha A. , Arruda Bailey , Benson Andrew K. , Kreuder Amanda J.
Published: September 2023

Swine are a major reservoir of an array of zoonotic Salmonella enterica subsp. enterica lineage I serovars including Derby, Typhimurium, and 4,[5],12:i:- (a.k.a. Monophasic Typhimurium). In this study, we assessed the gastrointestinal (GI) microbiome composition of pigs in different intestinal compartments and the feces following infection with specific zoonotic serovars of S. enterica (S. Derby, S. Monophasic, and S. Typhimurium). 16S rRNA based microbiome analysis was performed to assess for GI microbiome changes in terms of diversity (alpha and beta), community structure and volatility, and specific taxa alterations across GI biogeography (small and large intestine, feces) and days post-infection (DPI) 2, 4, and 28; these results were compared to disease phenotypes measured as histopathological changes. As previously reported, only S. Monophasic and S. Typhimurium induced morphological alterations that marked an inflammatory milieu restricted to the large intestine in this experimental model. S. Typhimurium alone induced significant changes at the alpha- (Simpson’s and Shannon’s indexes) and beta-diversity levels, specifically at the peak of inflammation in the large intestine and feces. Increased community dispersion and volatility in colonic apex and fecal microbiomes were also noted for S. Typhimurium. All three Salmonella serovars altered community structure as measured by co-occurrence networks; this was most prominent at DPI 2 and 4 in colonic apex samples. At the genus taxonomic level, a diverse array of putative short-chain fatty acid (SCFA) producing bacteria were altered and often decreased during the peak of inflammation at DPI 2 and 4 within colonic apex and fecal samples. Among all putative SCFA producing bacteria, Prevotella showed a broad pattern of negative correlation with disease scores at the peak of inflammation. In addition, Prevotella 9 was found to be significantly reduced in all Salmonella infected groups compared to the control at DPI 4 in the colonic apex. In conclusion, this work further elucidates that distinct swine-related zoonotic serovars of S. enterica can induce both shared (high resilience) and unique (altered resistance) alterations in gut microbiome biogeography, which helps inform future investigations of dietary modifications aimed at increasing colonization resistance against Salmonella through GI microbiome alterations.
European Society of Organ Transplantation (ESOT) Consensus Report on Downstaging, Bridging and Immunotherapy in Liver Transplantation for Hepatocellular Carcinoma
Authors: Claasen Marco Petrus Adrianus Wilhelmus , Sneiders Dimitri , Rakké Yannick Sebastiaan , Adam René , Bhoori Sherrie , Cillo Umberto , Fondevila Constantino , Reig Maria , Sapisochin Gonzalo , Tabrizian Parissa , Toso Christian
Published: September 2023

Liver transplantation offers the best chance of cure for most patients with non-metastatic hepatocellular carcinoma (HCC). Although not all patients with HCC are eligible for liver transplantation at diagnosis, some can be downstaged using locoregional treatments such as ablation and transarterial chemoembolization. These aforementioned treatments are being applied as bridging therapies to keep patients within transplant criteria and to avoid them from dropping out of the waiting list while awaiting a liver transplant. Moreover, immunotherapy might have great potential to support downstaging and bridging therapies. To address the contemporary status of downstaging, bridging, and immunotherapy in liver transplantation for HCC, European Society of Organ Transplantation (ESOT) convened a dedicated working group comprised of experts in the treatment of HCC to review literature and to develop guidelines pertaining to this cause that were subsequently discussed and voted during the Transplant Learning Journey (TLJ) 3.0 Consensus Conference that took place in person in Prague. The findings and recommendations of the working group on Downstaging, Bridging and Immunotherapy in Liver Transplantation for Hepatocellular Carcinoma are presented in this article.
A Plant Disease Classification Algorithm Based on Attention MobileNet V2
Authors: Wang Huan , Qiu Shi , Ye Huping , Liao Xiaohan
Published: September 2023

Plant growth is inevitably affected by diseases, and one effective method of disease detection is through the observation of leaf changes. To solve the problem of disease detection in complex backgrounds, where the distinction between plant diseases is hindered by large intra-class differences and small inter-class differences, a complete plant-disease recognition process is proposed. The process was tested through experiments and research into traditional and deep features. In the face of difficulties related to plant-disease classification in complex backgrounds, the advantages of strong interpretability of traditional features and great robustness of deep features are fully utilized, and include the following components: (1) The OSTU algorithm based on the naive Bayes model is proposed to focus on where leaves are located and remove interference from complex backgrounds. (2) A multi-dimensional feature model is introduced in an interpretable manner from the perspective of traditional features to obtain leaf characteristics. (3) A MobileNet V2 network with a dual attention mechanism is proposed to establish a model that operates in both spatial and channel dimensions at the network level to facilitate plant-disease recognition. In the Plant Village open database test, the results demonstrated an average SEN of 94%, greater than other algorithms by 12.6%.
Tramadol vs. Lidocaine Administered Intraperitoneally and in Incisional Lines for the Intraoperative and Postoperative Pain Management of Romifidine-Telazol-Anesthetized Swine Undergoing Umbilical Hernia Repair
Authors: Costa Giovanna Lucrezia , Spadola Filippo , Di Pietro Simona , Nava Vincenzo , Licata Patrizia , Giudice Elisabetta , Leonardi Fabio , Bruno Fabio , Messina Laura , Macrì Francesco , Macrì Daniele , Ferrantelli Vincenzo , Tabbì Marco , Interlandi Claudia
Published: September 2023

The aim of the study was to compare the analgesic efficacy of tramadol and lidocaine for local anesthesia during umbilical hernia repair in swine. The study was performed on 66 large white crossbred swine. The swine received a mixture of tiletamine/zolazepam at 5 mg/kg and romifidine at 80 µg/kg, administered intramuscularly. Then, they were divided into three groups (n = 22) that received different treatments with lidocaine at 4 mg/kg and tramadol at 4 mg/kg. The LL group received lidocaine both by infiltration of the surgical planes and intraperitoneally. The LT group received lidocaine by infiltration of the surgical planes and tramadol intraperitoneally. The TT group received tramadol both by infiltration of the surgical planes and intraperitoneally. In all groups, the infiltration of the surgical planes into the umbilical region involved both the skin and muscle planes. Heart rate, noninvasive arterial blood pressure, and respiratory frequency were recorded during surgery. The response to the surgical stimulus was evaluated using a cumulative pain scale (the cut-off point for rescue analgesia was set to 10). Postoperative pain was assessed using the UNESP-Botucatu pig composite acute pain scale (the cut-off point was set to 4). The trend of physiological variables was adequate for patients under anesthesia. No subject required intraoperative and postoperative rescue analgesia. Tramadol could therefore be used for pain management in livestock.
Crucial but Neglected: Limited Availability of Animal Welfare Courses in Education of Wildlife Researchers
Authors: Zemanova Miriam A.
Published: September 2023

Animal welfare is a subject of increasing scientific and ethical concern in today’s society, crucial for the well-being of animals used in research and the integrity of scientific data. Equipping researchers in the life science disciplines with a science-based knowledge of animal welfare, behaviour, physiology, and health is, therefore, essential. Nevertheless, previous studies evaluating animal welfare education focused on veterinary, laboratory, or farm animal science. Consequently, the aim of this study was, for the very first time, to map the prevalence of animal welfare courses in the university education of ecologists, wildlife biologists, and conservation managers in Europe, Canada, the USA, Australia, and New Zealand. A comprehensive assessment of 1548 universities was conducted, resulting in the identification of 596 relevant programs at the bachelor’s and master’s levels. Analysis of the curricula revealed that only 1% of the programs offered a formal course on animal welfare, while 65% provided courses on animal behaviour, 59% on animal physiology, and 34% on animal health. However, the majority of these courses were listed as electives rather than mandatory components of the programs. These results underscore the need for universities to incorporate more formal and obligatory education in animal welfare in order to better prepare future ecologists, wildlife biologists, and conservation managers for the challenges of working with wildlife.
Modeling Gastrointestinal Tract Wet Pool Size in Small Ruminants
Authors: Ribeiro Paola R. , Gindri Marcelo , Macedo Junior Gilberto L. , Herbster Caio J. L. , Pereira Elzania S. , Biagioli Bruno , Teixeira Izabelle A. M. A.
Published: September 2023

The gastrointestinal tract (GIT) wet pool size (GITwps) refers to the total amount of wet contents in GIT, which in small ruminants can reach up to 19% of their body weight (BW). This study aimed to develop models to comprehensively predict GITwps in small ruminants using a meta-regression approach. A dataset was created based on 21 studies, comprising 750 individual records of sheep and goats. Various predictor variables, including BW, sex, breed, species, intake level, physiological states, stages and types of pregnancy, dry matter intake, and neutral detergent fiber intake (NDFI), were initially analyzed through simple linear regression. Subsequently, the variables were fitted using natural logarithm transformations, considering the random effect of the study and residual error, employing a supervised forward selection procedure. Overall, no significant relationship between GITwps and BW (p = 0.326) was observed for animals fed a milk-based diet. However, a strong negative linear relationship (p < 0.001) was found for animals on a solid diet, with the level of restriction influencing GITwps only at the intercept. Furthermore, the prediction of GITwps was independent of sex and influenced by species in cases where individuals were fed ad libitum. Pregnant females showed a noticeable reduction in GITwps, which was more pronounced in cases of multiple pregnancies, regardless of species (p < 0.01). The composition of the diet was found to be the primary factor affecting the modulation of GITwps, with NDFI able to override the species effect (p < 0.0001). Overall, this study sheds light on the factors influencing GITwps in small ruminants, providing valuable insights into their digestive processes and nutritional requirements.
To Treat or Not to Treat: Public Attitudes on the Therapeutic Use of Antibiotics in the Dairy Industry—A Qualitative Study
Authors: Knowlton Katharine F. , von Keyserlingk Marina A. G.
Published: September 2023

This paper describes the views of 779 U.S. residents on questions related to therapeutic antibiotic use in dairy cattle. An online survey was conducted with qualitative (open-ended) questions. Respondents were offered one of three scenarios with varying degrees of information describing a farmer with a sick cow that would benefit from antibiotic therapy. The text replies to the open-ended questions were analyzed by grouping responses with similar comments and identifying patterns or themes. Content analysis showed that many of the participants in this study provided farmers with the social license to treat sick cows with antibiotics; however, some participants commented on the social license not necessarily extending to antibiotic use for growth promotion or prophylactic use. Our findings are not generalizable, but may provide some insight that should be considered when developing policies and practices regarding the use of antibiotics on dairy farms that may promote improved alignment with societal values.
Glutamine Regulates Gene Expression Profiles to Increase the Proliferation of Porcine Intestinal Epithelial Cells and the Expansion of Intestinal Stem Cells
Authors: Zhu Min , Lai Weiming , Yao Lewen , Xu E , Chen Xiang , Zhang Yi-yu , Li Xiang-Guang
Published: September 2023

The intestinal epithelium is known for its rapid self-renewal, and glutamine is crucial in providing carbon and nitrogen for biosynthesis. However, understanding how glutamine affects gene expression in the intestinal epithelium is limited, and identifying the essential genes and signals involved in regulating intestinal epithelial cell growth is particularly challenging. In this study, glutamine supplementation exhibited a robust acceleration of intestinal epithelial cell proliferation and stem cell expansion. RNA sequencing indicated diverse transcriptome changes between the control and glutamine supplementation groups, identifying 925 up-regulated and 1152 down-regulated genes. The up-regulated DEGs were enriched in the KEGG pathway of cell cycle and GO terms of DNA replication initiation, regulation of phosphatidylinositol 3-kinase activity, DNA replication, minichromosome maintenance protein (MCM) complex, and ATP binding, whereas the down-regulated DEGs were enriched in the KEGG pathway of p53 signaling pathway, TNF signaling pathway, and JAK-STAT signaling pathway and GO terms of inflammatory response and intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress. Furthermore, GSEA analysis revealed a significant up-regulation of the cell cycle, DNA replication initiation, ATP-dependent RNA helicase activity, and down-regulation of the TNF signaling pathway. The protein–protein association network of the intersecting genes highlighted the significance of DNA replication licensing factors (MCM3, MCM6, and MCM10) in promoting intestinal epithelial growth in response to glutamine. Based on these findings, we propose that glutamine may upregulate DNA replication licensing factors, leading to increased PI3K/Akt signaling and the suppression of TNF, JAK-STAT, and p53 pathways. Consequently, this mechanism results in the proliferation of porcine intestinal epithelial cells and the expansion of intestinal stem cells.
Study on Dynamic Characteristics of Magnetic Coagulation of Fe-Based Fine Particles in Iron and Steel Industry
Authors: Xu Dengke , Hu Zuxiang , Zhang Li’an , Zhang Wenqing
Published: September 2023

Fine dust, represented by Fe-based fine particles and emitted from the production process of the iron and steel industry, is the primary factor causing many diseases represented by industrial pneumoconiosis, and ultra-low dust emission has always been a thorny problem to be solved urgently. To explore the magnetic coagulation effect of Fe-based fine particles in the magnetic field when removing them from industrial flue gas by the magnetic field effect in the iron and steel industry, using FLUENT software, magnetic dipole force was added between particles through user defined function (UDF) based on the computational fluid dynamics-discrete phase model (CFD-DPM) method so that the collision process of particles was then equivalent to their mutual trapping process. Next, the effects of particle size, particle volume fraction, external magnetic field strength, and particle magnetic susceptibility on the magnetic coagulation process were comprehensively studied. Meanwhile, the proton balance equation (PBE) was solved using the partition method on the basis of the computational fluid dynamics-population balance model (CFD-PBM) to compare the coagulation removal effect under random and aligned orientations of magnetic dipoles, respectively. The results showed that the magnetic coagulation strength under the random orientation of magnetic dipoles was greater than that under the aligned orientation. When the particle size of Fe-based fine particles increased from 0.5 μm to 1.5 μm, the magnetic coagulation coefficient decreased from 0.5414 to 0.2882, and the difference in the removal efficiency under the two different orientations of magnetic dipoles became smaller. When the particle volume fraction increased from 0.01 to 0.03, the magnetic coagulation coefficient increased from 0.2353 to 0.5061, and the difference in the removal efficiency under two orientations was enlarged. When the applied external magnetic field strength increased from 0.5 T to 1.0 T, the magnetic coagulation coefficient increased from 0.3940 to 0.5288, and the magnetic susceptibility increased from 0.0250 to 0.0500, the coagulation coefficient increased from 0.3940 to 0.5288, and the difference under two orientations basically stayed unchanged.
Multivariate CNN Model for Human Locomotion Activity Recognition with a Wearable Exoskeleton Robot
Authors: Son Chang-Sik , Kang Won-Seok
Published: September 2023

This study introduces a novel convolutional neural network (CNN) architecture, encompassing both single and multi-head designs, developed to identify a user’s locomotion activity while using a wearable lower limb robot. Our research involved 500 healthy adult participants in an activities of daily living (ADL) space, conducted from 1 September to 30 November 2022. We collected prospective data to identify five locomotion activities (level ground walking, stair ascent/descent, and ramp ascent/descent) across three terrains: flat ground, staircase, and ramp. To evaluate the predictive capabilities of the proposed CNN architectures, we compared its performance with three other models: one CNN and two hybrid models (CNN-LSTM and LSTM-CNN). Experiments were conducted using multivariate signals of various types obtained from electromyograms (EMGs) and the wearable robot. Our results reveal that the deeper CNN architecture significantly surpasses the performance of the three competing models. The proposed model, leveraging encoder data such as hip angles and velocities, along with postural signals such as roll, pitch, and yaw from the wearable lower limb robot, achieved superior performance with an inference speed of 1.14 s. Specifically, the F-measure performance of the proposed model reached 96.17%, compared to 90.68% for DDLMI, 94.41% for DeepConvLSTM, and 95.57% for LSTM-CNN, respectively.
Processing Adipose Tissue Samples in a GMP Environment Standardizes the Use of SVF in Cell Therapy Treatments: Data on 302 Patients
Authors: Cremona Martina , Rusconi Giulio , Ferrario Alessandro , Mariotta Luca , Gola Mauro , Soldati Gianni
Published: September 2023

Stromal vascular fraction (SVF) cells, together with adipose-derived mesenchymal stem cells, are becoming the tool of choice for many clinical applications. Currently, nearly 200 clinical trials are running worldwide to prove the efficacy of this cell type in treating many diseases and pathological conditions. To reach the goals of cell therapies and produce ATMPs as drugs for regenerative medicine, it is necessary to properly standardize GMP processes and, thus, collection methods, transportation strategies, extraction protocols, and characterization procedures, without forgetting that all the tissues of the human body are characterized by a wide inter-individual variability which is genetically determined and acquired during life. Here, we compare 302 samples processed under GMP rules to exclude the influence of the operator and of the anatomical site of collection. The influence of variability in the ages and genders of patients, along with laboratory parameters such as total cell number, cell viability, stem cell number, and other stromal vascular fraction cell subpopulations, has been compared. The results show that when the laboratory protocol is standardized, the variability of quantifiable cell parameters is widely statistically non-significant, meaning that we can take a further step toward standardized advanced cell therapy products.
From Brain Models to Robotic Embodied Cognition: How Does Biological Plausibility Inform Neuromorphic Systems?
Authors: Pham Martin Do , D’Angiulli Amedeo , Dehnavi Maryam Mehri , Chhabra Robin
Published: September 2023

We examine the challenging “marriage” between computational efficiency and biological plausibility—A crucial node in the domain of spiking neural networks at the intersection of neuroscience, artificial intelligence, and robotics. Through a transdisciplinary review, we retrace the historical and most recent constraining influences that these parallel fields have exerted on descriptive analysis of the brain, construction of predictive brain models, and ultimately, the embodiment of neural networks in an enacted robotic agent. We study models of Spiking Neural Networks (SNN) as the central means enabling autonomous and intelligent behaviors in biological systems. We then provide a critical comparison of the available hardware and software to emulate SNNs for investigating biological entities and their application on artificial systems. Neuromorphics is identified as a promising tool to embody SNNs in real physical systems and different neuromorphic chips are compared. The concepts required for describing SNNs are dissected and contextualized in the new no man’s land between cognitive neuroscience and artificial intelligence. Although there are recent reviews on the application of neuromorphic computing in various modules of the guidance, navigation, and control of robotic systems, the focus of this paper is more on closing the cognition loop in SNN-embodied robotics. We argue that biologically viable spiking neuronal models used for electroencephalogram signals are excellent candidates for furthering our knowledge of the explainability of SNNs. We complete our survey by reviewing different robotic modules that can benefit from neuromorphic hardware, e.g., perception (with a focus on vision), localization, and cognition. We conclude that the tradeoff between symbolic computational power and biological plausibility of hardware can be best addressed by neuromorphics, whose presence in neurorobotics provides an accountable empirical testbench for investigating synthetic and natural embodied cognition. We argue this is where both theoretical and empirical future work should converge in multidisciplinary efforts involving neuroscience, artificial intelligence, and robotics.
Brain Response to Interferential Current Compared with Alternating Current Stimulation
Authors: Xin Zonghao , Abe Yoshifumi , Kuwahata Akihiro , Tanaka Kenji F. , Sekino Masaki
Published: September 2023

Temporal interference (TI) stimulation, which utilizes multiple external electric fields with amplitude modulation for neural modulation, has emerged as a potential noninvasive brain stimulation methodology. However, the clinical application of TI stimulation is inhibited by its uncertain fundamental mechanisms, and research has previously been restricted to numerical simulations and immunohistology without considering the acute in vivo response of the neural circuit. To address the characterization and understanding of the mechanisms underlying the approach, we investigated instantaneous brainwide activation patterns in response to invasive interferential current (IFC) stimulation compared with low-frequency alternative current stimulation (ACS). Results demonstrated that IFC stimulation is capable of inducing regional neural responses and modulating brain networks; however, the activation threshold for significantly recruiting a neural response using IFC was higher (at least twofold) than stimulation via alternating current, and the spatial distribution of the activation signal was restricted. A distinct blood oxygenation level-dependent (BOLD) response pattern was observed, which could be accounted for by the activation of distinct types of cells, such as inhibitory cells, by IFC. These results suggest that IFC stimulation might not be as efficient as conventional brain modulation methods, especially when considering TI stimulation as a potential alternative for stimulating subcortical brain areas. Therefore, we argue that a future transcranial application of TI on human subjects should take these implications into account and consider other stimulation effects using this technique.
Prognostic Value of Necroptosis-Related Genes Signature in Oral Squamous Cell Carcinoma
Authors: Huang Ke , Gu Xiaoting , Xu Huimei , Li Hui , Shi Mingxuan , Wei Defang , Wang Shiqi , Li Yao , Liu Bin , Li Yi
Published: September 2023

The dual role of necroptosis in inhibiting and promoting tumor development has gradually received much attention because of its essential significance for targeted treatment. Accordingly, this study aims to explore the relationship between necroptosis and oral squamous cell carcinoma (OSCC), and search for novel prognostic factors for OSCC. RNA-seq data and clinical information were downloaded from TCGA and GTEx databases. The prognostic signature of necroptosis-related genes (NRGs) was constructed by univariate Cox regression analysis and the LASSO Cox regression model. Moreover, survival analyses, ROC curves, and nomograms were adopted to further analyze. GO and KEGG analyses and immune infiltration analyses were used for function enrichment and immune feature research in turn. The NRG prognostic signature expression was higher in OSCC tissues than in normal tissues, and the overall survival (OS) rate of the high-expression group was much lower. HPRT1 was proved to be an independent prognostic factor in OSCC. Furthermore, the function enrichment analyses revealed that NRGs were involved in necroptosis, apoptosis, inflammation, and immune reaction. The expression of NRGs was related to immunosuppression in OSCC. Furthermore, the knockdown of HPRT1 could suppress the proliferation and migration of OSCC. In conclusion, the high expression of NRG prognostic signature is associated with poor prognosis in OSCC, and HPRT1 can serve as a novel independent prognostic factor for OSCC.
CT Fluoroscopy-Guided Percutaneous Gastrostomy in the Palliative Management of Advanced and Relapsed Ovarian Cancer: The Charité Experiences and a Review of the Literature
Authors: Canaz Emel , Sehouli Jalid , Gebauer Bernhard , Segger Laura , Collettini Federico , Auer Timo Alexander
Published: September 2023

Peritoneal carcinomatosis-associated malignant bowel obstruction is a common feature that merits more attention in advanced and recurrent ovarian cancer. Decompressive gastrostomy is one of the most preferred methods to palliate distressing symptoms and maintain patients’ quality of life. We retrospectively identified 31 patients with ovarian cancer-associated MBO, who underwent decompressive CT fluoroscopy-guided percutaneous gastrostomy (CT-PG) between September 2015 and April 2023 at our institution. A systematic literature review was conducted for CT-guided gastrostomy in ovarian cancer. Prior to CT-PG, 27 (87%) patients underwent unsuccessful attempts at endoscopic gastrostomy or surgery due to bowel obstruction; a total of 55% had received ≥3 lines of chemotherapy. CT-PG could be successfully inserted in 25 of 31 (81%) patients without grade 4–5 complications. CT-PG insertion was feasible in 76% of patients with previous unsuccessful attempts of endoscopic gastrostomy. A total of 80% of patients with a successful insertion had considerable symptom relief and could tolerate fluid intake. Mean survival after the procedure was 44.4 days. Chemotherapy could be administered in 7 of 25 (28%) patients following the CT-PG insertion. CT-guided percutaneous gastrostomy is a safe procedure that effectively manages intractable symptoms of bowel obstruction in ovarian cancer. This minimally invasive technique should be emphasised as a routine instrument within the palliative management of MBO.
Selinexor in Combination with Decitabine Attenuates Ovarian Cancer in Mice
Authors: Stiff Patrick J. , Mehrotra Swati , Potkul Ronald K. , Banerjee Swarnali , Walker Christopher , Drakes Maureen L.
Published: September 2023

Background. High-grade serous ovarian cancer is a lethal gynecologic disease. Conventional therapies, such as platinum-based chemotherapy, are rendered inadequate for disease management as most advanced disease patients develop resistance to this therapy and soon relapse, leading to poor prognosis. Novel immunotherapy and targeted therapy are currently under investigation as treatment options for ovarian cancer, but so far with little success. Epigenetic changes, such as aberrant DNA methylation, have been reported in resistance to platinum-based therapy. Decitabine is a hypomethylating agent which is effective against platinum-resistant disease and also exhibits several anti-tumor immune functions. Selinexor is a selective inhibitor of nuclear protein export. It restored platinum sensitivity in patient-derived ovarian cancer cell lines and is currently in clinical trials for the treatment of platinum-resistant ovarian cancer. We hypothesized that these two agents used in combination could elicit more potent anti-tumor immune responses in vivo than either agent used alone. Methods. These studies were designed to investigate the efficacy of these two agents used in combination to treat ovarian cancer by assessing murine models for changes in disease pathology and in anti-tumor responses. Results. Decitabine priming followed by selinexor treatment significantly limited ascites formation and tumor size. This combination of agents also promoted T cell effector function as measured by granzyme B secretion. Treatment of mice with decitabine and selinexor led to the significant release of a broader range of macrophage and T cell cytokines and chemokines above control PBS and vehicle and above decitabine or selinexor treatment alone. Conclusions. These results reveal crucial information for the design of clinical trials which may advance therapy outcomes in ovarian cancer.
A Diagnostic Accuracy Study of Targeted and Systematic Biopsies to Detect Clinically Significant Prostate Cancer, including a Model for the Partial Omission of Systematic Biopsies
Authors: Morote Juan , Picola Natàlia , Muñoz-Rodriguez Jesús , Paesano Nahuel , Ruiz-Plazas Xavier , Muñoz-Rivero Marta V. , Celma Anna , Manuel Gemma García-de , Aisian Ignacio , Servian Pol , Abascal José M.
Published: September 2023

The primary objective of this study was to analyse the current accuracy of targeted and systematic prostate biopsies in detecting csPCa. A secondary objective was to determine whether there are factors predicting the finding of csPCa in targeted biopsies and, if so, to explore the utility of a predictive model for csPCa detection only in targeted biopsies. We analysed 2122 men with suspected PCa, serum PSA > 3 ng/mL, and/or a suspicious digital rectal examination (DRE), who underwent targeted and systematic biopsies between 2021 and 2022. CsPCa (grade group 2 or higher) was detected in 1026 men (48.4%). Discrepancies in csPCa detection in targeted and systematic biopsies were observed in 49.6%, with 13.9% of csPCa cases being detected only in systematic biopsies and 35.7% only in targeted biopsies. A predictive model for csPCa detection only in targeted biopsies was developed from the independent predictors age (years), prostate volume (mL), PI-RADS score (3 to 5), mpMRI Tesla (1.5 vs. 3.0), TRUS-MRI fusion image technique (cognitive vs. software), and prostate biopsy route (transrectal vs. transperineal). The csPCa discrimination ability of targeted biopsies showed an AUC of 0.741 (95% CI 0.721–0.762). The avoidance rate of systematic prostate biopsies went from 0.5% without missing csPCa to 18.3% missing 4.6% of csPCa cases. We conclude that the csPCa diagnostic accuracy of targeted biopsies is higher than that of systematic biopsies. However, a significant rate of csPCa remains detected only in systematic biopsies. A predictive model for the partial omission of systematic biopsies was developed.
Impact of a Tripartite Collaboration between Oncologist, Pharmacist and Diabetologist in the Management of Patients with Diabetes Starting Chemotherapy: The ONCODIAB Trial
Authors: Paris Justine , Legris Pauline , Devaux Madeline , Bost Stephanie , Gueneau Pauline , Rossi Cedric , Manfredi Sylvain , Bouillet Benjamin , Petit Jean-Michel , Pistre Pauline , Boulin Mathieu
Published: September 2023

Background: Diabetes negatively impacts cancer prognosis. The objective of this work was to evaluate a tripartite oncologist–pharmacist–diabetologist collaboration in the management of patients with diabetes starting chemotherapy. Patients and Methods: The prospective ONCODIAB study (NCT04315857) included 102 adults with diabetes starting chemotherapy by whom a continuous glucose monitoring device was worn for fourteen days from the first day of the first and second chemotherapy cycles. The primary outcome was to assess pharmacist and diabetologist interventions. The secondary outcome was to evaluate the impact of the ONCODIAB follow-up on individualized patient glycemic targets at 6 months. Results: A total of 191 (2 per patient) were made either by clinical pharmacists (n = 95) or diabetologists (n = 96) during the first two chemotherapy cycles. The anatomic therapeutic chemical drug classes most frequently involved in pharmacist interventions were cardiovascular system (23%), alimentary tract and metabolism (22%), and anti-infectives for systemic use (14%). Diabetologists modified the antidiabetic treatment in 58 (62%) of patients: dose reduction (34%), drug discontinuation (28%), drug addition (24%), and dose increase (15%). Glycated hemoglobin decreased from 7.6 ± 1.7% at baseline to 7.1 ± 1.1% at 6 months (p = 0.02). Compared to individualized targets, HbA1c was higher, in the interval, or lower in 29%, 44%, and 27% of patients at baseline vs. in 8%, 70%, and 22% of patients at 6 months, respectively (p < 10−3). Conclusions: In our study, a close collaboration between oncologists, pharmacists, and diabetologists helped by continuous glucose monitoring led to overall medication optimization and better glycemic control in patients with diabetes starting chemotherapy.
Midline Gliomas: A Retrospective Study from a Cancer Center in the Middle East
Authors: Al Sharie Sarah , Abu Laban Dima , Nazzal Jamil , Iqneibi Shahad , Ghnaimat Sura , Al-Ani Abdallah , Al-Hussaini Maysa
Published: September 2023

Midline gliomas are tumors that occur in midline structures and can be circumscribed or diffuse. Classical midline structures include the thalamus, brainstem, and spinal cord. Other midline structures include the corpus callosum, basal ganglia, ventricles, paraventricular structures, and cerebellum. Diffuse midline glioma (DMG) is a diffuse glioma that occurs in the classical midline structures, characterized by a specific genetic alteration, and associated with grim outcome. This study was conducted at King Hussein Cancer Center and reviewed the medical records of 104 patients with circumscribed and diffuse gliomas involving midline structures that underwent biopsy between 2005 and 2022. We included a final cohort of 104 patients characterized by a median age of 23 years and a male-to-female ratio of 1.59-to-1. Diffuse high-grade glioma (DHGG) was the most common pathological variant (41.4%), followed by DMG (28.9%). GFAP was positive in most cases (71.2%). Common positive mutations/alterations detected by surrogate immunostains included H3 K27me3 (28.9%), p53 (25.0%), and H3 K27M (20.2%). Age group, type of treatment, and immunohistochemistry were significantly associated with both the location of the tumor and tumor variant (all; p < 0.05). DMGs were predominantly found in the thalamus, whereas circumscribed gliomas were most commonly observed in the spinal cord. None of the diffuse gliomas outside the classical location, or circumscribed gliomas harbored the defining DMG mutations. The median overall survival (OS) for the entire cohort was 10.6 months. Only the tumor variant (i.e., circumscribed gliomas) and radiotherapy were independent prognosticators on multivariate analysis.
Associations between the Gut Microbiota, Race, and Ethnicity of Patients with Colorectal Cancer: A Pilot and Feasibility Study
Authors: Piawah Sorbarikor , Kyaw Than S. , Trepka Kai , Stewart Anita L. , Mora Rosa V. , Stanfield Dalila , Levine Kendall , Van Blarigan Erin L. , Venook Alan , Turnbaugh Peter J. , Nguyen Tung , Atreya Chloe E.
Published: September 2023

Background: Colorectal cancer (CRC) is more prevalent among some racial and ethnic minority and low socioeconomic status populations. Although the gut microbiota is a risk factor for CRC and varies with race and ethnicity, its role in CRC disparities remains poorly understood. Methods: We examined the feasibility of recruiting sociodemographically diverse CRC patients for a microbiome study involving a home stool collection. We also explored whether race and ethnicity were associated with gut microbiome composition. We recruited Black/African American, Hispanic/Latino, and non-Hispanic White patients who were receiving care for active CRC to complete a comprehensive dietary and lifestyle survey, self-collect a stool sample, and complete an exit interview. Gut microbial diversity and composition were analyzed using 16S rRNA gene sequencing. Results: 30 individuals consented (of 35 who were eligible and contacted) with 5 (17%) Black/African American, 11 (37%) Hispanic/Latino, and 14 (46%) non-Hispanic White. A total of 22 (73%) completed the dietary and lifestyle survey; 18 (63%) returned a stool sample. Even after controlling for socioeconomic, dietary, or treatment-related covariates, microbiome composition was associated with race and ethnicity. Fusobacteriota (a phylum associated with the development and progression of CRC) was significantly higher in the Black/African American group compared to others, and microbial diversity was higher in samples from non-Hispanic White individuals compared to Hispanic/Latino individuals. Conclusion: Our study shows that it is feasible to recruit and collect stool samples from diverse individuals with CRC and found significant associations in gut microbial structure with race and ethnicity.
Oral Complications from Oropharyngeal Cancer Therapy
Authors: Sankar Vidya , Xu Yuanming
Published: September 2023

Post-oropharyngeal cancer treatment complications include a multitude of oral side effects that impact overall survival and quality of life. These include acute and chronic conditions affecting the oral cavity and head and neck, such as mucositis, infection, xerostomia, dysgeusia, radiation caries, osteonecrosis, and trismus. This review will summarize the most common oral complications from oropharyngeal cancer therapy. The authors would like to point out that the literature cited frequently combines oropharyngeal and head and neck cancer results. If recommendations are made strictly related to oropharyngeal cancers, this will be highlighted.
Quality of Life for Head and Neck Cancer Patients: A 10-Year Bibliographic Analysis
Authors: Ghazali Siti Nur Akmal , Chan Caryn Mei Hsien , Nik Eezamuddeen Marfu’ah , Manan Hanani Abdul , Yahya Noorazrul
Published: September 2023

Head and neck cancers (HNCs) have a profound impact on patients, affecting not only their physical appearance but also fundamental aspects of their daily lives. This bibliometric study examines the landscape of scientific research pertaining to the quality of life (QoL) among head and neck cancer (HNC) patients. By employing data and bibliometric analysis derived from the Web of Science Core Collection (WOS-CC) and employing R-package and VOSviewer for visualization, the study assesses the current status of and prominent areas of focus within the literature over the past decade. The analysis reveals noteworthy countries, journals, and institutions that have exhibited notable productivity in this research domain between 2013 and 2022. Notably, the United States, the Supportive Care in Cancer journal, and the University of Pittsburgh emerged as the leading contributors. Moreover, there was a discernible shift, with an increasing focus on the significance of QoL within the survivorship context, exemplified by the emergence and subsequent peak of related keywords in 2020 and the subsequent year, respectively. The temporal analysis additionally reveals a transition towards specific QoL indices, such as dysphagia and oral mucositis. Therefore, the increasing relevance of survivorship further underscores the need for studies that address the associated concerns and challenges faced by patients.
Association between Contrast-Enhanced Computed Tomography Radiomic Features, Genomic Alterations and Prognosis in Advanced Lung Adenocarcinoma Patients
Authors: Rinaldi Lisa , Guerini Rocco Elena , Spitaleri Gianluca , Raimondi Sara , Attili Ilaria , Ranghiero Alberto , Cammarata Giulio , Minotti Marta , Lo Presti Giuliana , De Piano Francesca , Bellerba Federica , Funicelli Gianluigi , Volpe Stefania , Mora Serena , Fodor Cristiana , Rampinelli Cristiano , Barberis Massimo , De Marinis Filippo , Jereczek-Fossa Barbara Alicja , Orecchia Roberto , Rizzo Stefania , Botta Francesca
Published: September 2023

Non-invasive methods to assess mutational status, as well as novel prognostic biomarkers, are warranted to foster therapy personalization of patients with advanced non-small cell lung cancer (NSCLC). This study investigated the association of contrast-enhanced Computed Tomography (CT) radiomic features of lung adenocarcinoma lesions, alone or integrated with clinical parameters, with tumor mutational status (EGFR, KRAS, ALK alterations) and Overall Survival (OS). In total, 261 retrospective and 48 prospective patients were enrolled. A Radiomic Score (RS) was created with LASSO-Logistic regression models to predict mutational status. Radiomic, clinical and clinical-radiomic models were trained on retrospective data and tested (Area Under the Curve, AUC) on prospective data. OS prediction models were trained and tested on retrospective data with internal cross-validation (C-index). RS significantly predicted each alteration at training (radiomic and clinical-radiomic AUC 0.95–0.98); validation performance was good for EGFR (AUC 0.86), moderate for KRAS and ALK (AUC 0.61–0.65). RS was also associated with OS at univariate and multivariable analysis, in the latter with stage and type of treatment. The validation C-index was 0.63, 0.79, and 0.80 for clinical, radiomic, and clinical-radiomic models. The study supports the potential role of CT radiomics for non-invasive identification of gene alterations and prognosis prediction in patients with advanced lung adenocarcinoma, to be confirmed with independent studies.
Development of a Treatment Planning Framework for Laser Interstitial Thermal Therapy (LITT)
Authors: Lad Yash , Jangam Avesh , Carlton Hayden , Abu-Ayyad Ma’Moun , Hadjipanayis Constantinos , Ivkov Robert , Zacharia Brad E. , Attaluri Anilchandra
Published: September 2023

Purpose: Develop a treatment planning framework for neurosurgeons treating high-grade gliomas with LITT to minimize the learning curve and improve tumor thermal dose coverage. Methods: Deidentified patient images were segmented using the image segmentation software Materialize MIMICS©. Segmented images were imported into the commercial finite element analysis (FEA) software COMSOL Multiphysics© to perform bioheat transfer simulations. The laser probe was modeled as a cylindrical object with radius 0.7 mm and length 100 mm, with a constant beam diameter. A modeled laser probe was placed in the tumor in accordance with patient specific patient magnetic resonance temperature imaging (MRTi) data. The laser energy was modeled as a deposited beam heat source in the FEA software. Penne’s bioheat equation was used to model heat transfer in brain tissue. The cerebrospinal fluid (CSF) was modeled as a solid with convectively enhanced conductivity to capture heat sink effects. In this study, thermal damage-dependent blood perfusion was assessed. Pulsed laser heating was modeled based on patient treatment logs. The stationary heat source and pullback heat source techniques were modeled to compare the calculated tissue damage. The developed bioheat transfer model was compared to MRTi data obtained from a laser log during LITT procedures. The application builder module in COMSOL Multiphysics© was utilized to create a Graphical User Interface (GUI) for the treatment planning framework. Results: Simulations predicted increased thermal damage (10–15%) in the tumor for the pullback heat source approach compared with the stationary heat source. The model-predicted temperature profiles followed trends similar to those of the MRTi data. Simulations predicted partial tissue ablation in tumors proximal to the CSF ventricle. Conclusion: A mobile platform-based GUI for bioheat transfer simulation was developed to aid neurosurgeons in conveniently varying the simulation parameters according to a patient-specific treatment plan. The convective effects of the CSF should be modeled with heat sink effects for accurate LITT treatment planning.
Enhancing Lung Cancer Classification through Integration of Liquid Biopsy Multi-Omics Data with Machine Learning Techniques
Authors: Kwon Hyuk-Jung , Park Ui-Hyun , Goh Chul Jun , Park Dabin , Lim Yu Gyeong , Lee Isaac Kise , Do Woo-Jung , Lee Kyoung Joo , Kim Hyojung , Yun Seon-Young , Joo Joungsu , Min Na Young , Lee Sunghoon , Um Sang-Won , Lee Min-Seob
Published: September 2023

Early detection of lung cancer is crucial for patient survival and treatment. Recent advancements in next-generation sequencing (NGS) analysis enable cell-free DNA (cfDNA) liquid biopsy to detect changes, like chromosomal rearrangements, somatic mutations, and copy number variations (CNVs), in cancer. Machine learning (ML) analysis using cancer markers is a highly promising tool for identifying patterns and anomalies in cancers, making the development of ML-based analysis methods essential. We collected blood samples from 92 lung cancer patients and 80 healthy individuals to analyze the distinction between them. The detection of lung cancer markers Cyfra21 and carcinoembryonic antigen (CEA) in blood revealed significant differences between patients and controls. We performed machine learning analysis to obtain AUC values via Adaptive Boosting (AdaBoost), Multi-Layer Perceptron (MLP), and Logistic Regression (LR) using cancer markers, cfDNA concentrations, and CNV screening. Furthermore, combining the analysis of all multi-omics data for ML showed higher AUC values compared with analyzing each element separately, suggesting the potential for a highly accurate diagnosis of cancer. Overall, our results from ML analysis using multi-omics data obtained from blood demonstrate a remarkable ability of the model to distinguish between lung cancer and healthy individuals, highlighting the potential for a diagnostic model against lung cancer.