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This review paper presents the practical development of imaging biomarkers in the scope of the PRIMAGE (PRedictive In silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers) project, as a noninvasive and reliable way to improve the diagnosis and prognosis in pediatric oncology. The PRIMAGE project is a European multi-center research initiative that focuses on developing medical imaging-derived artificial intelligence (AI) solutions designed to enhance overall management and decision-making for two types of pediatric cancer: neuroblastoma and diffuse intrinsic pontine glioma. To allow this, the PRIMAGE project has created an open-cloud platform that combines imaging, clinical, and molecular data together with AI models developed from this data, creating a comprehensive decision support environment for clinicians managing patients with these two cancers. In order to achieve this, a standardized data processing and analysis workflow was implemented to generate robust and reliable predictions for different clinical endpoints. Magnetic resonance (MR) image harmonization and registration was performed as part of the workflow. Subsequently, an automated tool for the detection and segmentation of tumors was trained and internally validated. The Dice similarity coefficient obtained for the independent validation dataset was 0.997, indicating compatibility with the manual segmentation variability. Following this, radiomics and deep features were extracted and correlated with clinical endpoints. Finally, reproducible and relevant imaging quantitative features were integrated with clinical and molecular data to enrich both the predictive models and a set of visual analytics tools, making the PRIMAGE platform a complete clinical decision aid system. In order to ensure the advancement of research in this field and to foster engagement with the wider research community, the PRIMAGE data repository and platform are currently being integrated into the European Federation for Cancer Images (EUCAIM), which is the largest European cancer imaging research infrastructure created to date., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fluorescent lateral flow immunoassay (LFA), one tool in point of care testing (POCT) systems for breast cancer, has attracted attention because it is quick, simple, and convenient. However, samples and the constituent material exhibit autofluorescence in the visible region, which is a very large obstacle in the development of fluorescent LFAs. The autofluorescence of biological samples is scarcely found in the second near-infrared (NIR-II) range and samples scatter and absorb less NIR-II light than visible light. Here, we report an NIR-II QD-LFA platform using the NIR-II fluorescent Ag 2 Se quantum dots (QDs) with 1020 nm emission encapsulated into polystyrene beads as fluorescent probes. The NIR-II LFA platform was established to detect breast cancer tumour markers (CEA and CA153) within 15 min with a low limit of detection (CEA: 0.768 ng mL -1 , CA153: 1.192 U mL -1 ), high recoveries (93.7% ~ 108.8%), and relative standard deviations (RSDs) of less than 10%. This study demonstrated the potential of NIR-II Ag 2 Se polystyrene beads as a fluorescent probe in LFA for rapid and accurate identification of biomarkers. They are suited for use in professional situations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Postoperative pancreatic fistula (POPF) is one of the most critical complications of pancreaticoduodenectomy (PD). Studies on predictive factors for POPF that can be identified preoperatively are limited. Recent reports have highlighted the association between the preoperative nutritional status, including sarcopenia, and postoperative complications. We examined preoperative risk factors for POPF after PD, focusing on nutritional indicators., Methods: A total of 153 consecutive patients who underwent PD at our institution were enrolled in this study. Preoperative nutritional parameters, including hand grip strength (HGS) and skeletal muscle mass as components of sarcopenia, were incorporated into the analysis. POPFs were categorized according to the International Study Group of Pancreatic Fistula (ISGPF) definition as biochemical (grade A) or clinically relevant (CR-POPF; grades B and C)., Results: Thirty-seven of the 153 patients (24.1%) fulfilled the ISGPF definition of CR-POPF postoperatively. In the univariate analysis, the incidence of CR-POPF was associated with male sex, non-pancreatic tumor diseases, a high body mass index, a high HGS and a high skeletal muscle mass index. In the multivariate analysis, non-pancreatic tumor diseases and an HGS ≥23.0 kg were selected as independent risk factors for CR-POPF (P <0.05)., Conclusions: A high HGS, a screening tool for sarcopenia, was a risk factor for CR-POPF. It can accurately serve as a useful predictor of POPF risk in patients undergoing PD. These results highlight the potential of sarcopenia to reduce the incidence of POPF and highlight the need to clarify the mechanism of POPF occurrence., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To tackle cancer and provide prompt diagnoses and prognoses, the constantly evolving biosensing field is continuously on the lookout for novel markers that can be non-invasively analysed. Extracellular vesicles (EVs) may represent a promising biomarker that also works as a source of biomarkers. The augmented cellular activity of cancerous cells leads to the production of higher numbers of EVs, which can give direct information on the disease due to the presence of general and cancer-specific surface-tethered molecules. Moreover, the intravesicular space is enriched with other molecules that can considerably help in the early detection of neoplasia. Even though EV-targeted research has indubitably received broad attention lately, there still is a wide lack of practical and effective quantitative procedures due to difficulties in pre-analytical and analytical phases. This review aims at providing an exhaustive outline of the recent progress in EV detection using electrochemical and photoelectrochemical biosensors, with a focus on handling approaches and trends in the selection of bioreceptors and molecular targets related to EVs that might guide researchers that are approaching such an unstandardised field., (© 2023. The Author(s).)

Purpose: Implant placement in patients with cancer receiving high-dose antiresorptive medication (HDAR) is considered contraindicated. This prospective, feasibility study tested the hypothesis that dental implants can be placed in such patients by applying a staged implant placement protocol with submerged healing., Methods: Three groups of patients on HDAR were included as follows: group 1: patients who underwent tooth extraction, without the development of medication-related osteonecrosis of the jaws (MRONJ); group 2: patients with surgically treated MRONJ who had demonstrated clinical healing for at least 3 months; group 3: patients with established MRONJ who was planned for surgical resection and simultaneous implant placement., Results: A total of 49 implants were placed in 27 patients (group 1: 12, group 2: 7 and group 3: 8). HDAR included bisphosphonates and denosumab. The mean HDAR time was 25 months (SD: ± 18.4, range 3-68 months). An abutment operation was performed 4 months following the implant placement (SD: ± 1.9, range 3-14 months). All patients healed uneventfully., Conclusions: This study demonstrated that it is feasible to insert dental implants and perform an abutment surgery in patients with cancer on HDAR, without the development of MRONJ., Clinicaltrials: gov Identifier: NCT04741906., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Some of the cancer biomarkers often lack specificity and sensitivity; thus, simultaneous detection of multiple biomarkers can make the diagnosis more accurate. Also, simple sensing system without utilization of extra reagents like mediator or substrate during detection event is desirable for point-of-care testing. To address this, mediator and substrate-free amperometric biosensor for simultaneous detection of cancer biomarkers carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) have been demonstrated by designing two different redox-labelled detection probes. Colloidal nanoparticles of polyaniline-pectin conjugated with AFP antibody along with ferrocene and silver nanoparticles conjugated with CEA antibody along with anthraquinone were used as redox probes to bind with AFP and CEA during the detection event. Sensor constructed using carboxylic acid tethered polyaniline as immobilization matrix displayed 5 times wider linear range than conventional polyaniline for AFP and CEA detection by sandwich electrochemical assay. The detection limit was 30 pg mL -1 for AFP and 80 pg mL -1 for CEA. The biosensor displayed appropriate sensitivity, good specificity, and negligible cross-reactivity between the two targets. The proposed sensor was used to determine APF and CEA in human blood serum. The strategy demonstrated can be further extended for detection of panel of cancer biomarkers by designing appropriate redox probes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Doxorubicin (DOX) is a potent chemotherapeutic agent used against several cancer types. However, due to its cardiotoxic adverse effects, the use of this drug may be also life-threatening. Although most cancer patients are elderly, they are poorly represented and evaluated in pre-clinical and clinical studies. Considering this, the present work aims to evaluate inflammation and oxidative stress as the main mechanisms of DOX-induced cardiotoxicity, in an innovative approach using an experimental model constituted of elderly animals treated with a clinically relevant human cumulative dose of DOX. Elderly (18-20 months) CD-1 male mice received biweekly DOX administrations, for 3 weeks, to reach a cumulative dose of 9.0 mg/kg. One week (1W) or two months (2 M) after the last DOX administration, the heart was collected to determine both drug's short and longer cardiac adverse effects. The obtained results showed that DOX causes cardiac histological damage and fibrosis at both time points. In the 1W-DOX group, the number of nuclear factor kappa B (NF-κB) p65 immunopositive cells increased and a trend toward increased NF-κB p65 expression was seen. An increase of inducible nitric oxide synthase (iNOS) and interleukin (IL)-33 and a trend toward increased IL-6 and B-cell lymphoma-2-associated X (Bax) expression were seen after DOX. In the same group, a decrease in IL-1β, p62, and microtubule-associated protein 1A/1B-light chain 3 (LC3)-I, p38 mitogen-activated protein kinase (MAPK) expression was observed. Contrariwise, the animals sacrificed 2 M after DOX showed a significant increase in glutathione peroxidase 1 and Bax expression with persistent cardiac damage and fibrosis, while carbonylated proteins, erythroid-2-related factor 2 (Nrf2), NF-κB p65, myeloperoxidase, LC3-I, and LC3-II expression decreased. In conclusion, our study demonstrated that in an elderly mouse population, DOX induces cardiac inflammation, autophagy, and apoptosis in the heart in the short term. When kept for a longer period, oxidative-stress-linked pathways remained altered, as well as autophagy markers and tissue damage after DOX treatment, emphasizing the need for continuous post-treatment cardiac monitoring., (© 2023. The Author(s).)

CD47/SIRPα pathway is a new breakthrough in the field of tumor immunity after PD-1/PD-L1. While current monoclonal antibody therapies targeting CD47/SIRPα have demonstrated some anti-tumor effectiveness, there are several inherent limitations associated with these formulations. In the paper, we developed a predictive model that combines next-generation phage display (NGPD) and traditional machine learning methods to distinguish CD47 binding peptides. First, we utilized NGPD biopanning technology to screen CD47 binding peptides. Second, ten traditional machine learning methods based on multiple peptide descriptors and three deep learning methods were used to build computational models for identifying CD47 binding peptides. Finally, we proposed an integrated model based on support vector machine. During the five-fold cross-validation, the integrated predictor demonstrated specificity, accuracy, and sensitivity of 0.755, 0.764, and 0.772, respectively. Furthermore, an online bioinformatics tool called CD47Binder has been developed for the integrated predictor. This tool is readily accessible on http://i.uestc.edu.cn/CD47Binder/cgi-bin/CD47Binder.pl ., (© 2023. International Association of Scientists in the Interdisciplinary Areas.)

Heterogeneity of dose distribution has been shown at different spatial scales in diagnostic nuclear medicine. In cancer treatment using new radiopharmaceuticals with alpha-particle emitters, it has shown an extensive degree of dose heterogeneity affecting both tumour control and toxicity of organs at risk. This review aims to provide an overview of generalized internal dosimetry in nuclear medicine and highlight the need of consideration of the dose heterogeneity within organs at risk. The current methods used for patient dosimetry in radiopharmaceutical therapy are summarized. Bio-distribution and dose heterogeneities of alpha-particle emitting pharmaceutical 223 Ra (Xofigo) within bone tissues are presented as an example. In line with the strategical research agendas of the Multidisciplinary European Low Dose Initiative (MELODI) and the European Radiation Dosimetry Group (EURADOS), future research direction of pharmacokinetic modelling and dosimetry in patient radiopharmaceutical therapy are recommended., (© 2022. The Author(s).)

The present research was conducted to design and construct an electrochemical aptasensor for evaluating carbohydrate antigen 15-3 (CA15-3) as a biomarker for breast cancer. The aptasensor has been fabricated by a gold thin film (AuTF) electrodeposited on a cauliflower-like reduced graphene oxide-molybdenum sulfide nanocomposite (rGO-MoS 2 ). The modified electrode's surface was used to immobilize the thiolated aptamer, which was subsequently treated with CA 15-3 antigen. The aptasensor fabrication process was assessed using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). This research also applied EIS to the quantitative measurement of CA 15-3 antigen by the proposed aptasensor. The interfacial charge transfer resistance (R ct ) alteration before and after incubation of CA 15-3 by the immobilized aptamer was considered a signal for the quantitative measurement of CA 15-3. A linear concentration ranging from 5.0 to 200.0 U mL -1 with a detection limit of 3.0 × 10 -1 U mL -1 was obtained for CA 15-3 using the EIS method. This designed aptasensor indicates satisfactory repeatability and stability, good selectivity, and high sensitivity. Moreover, clinical samples were assayed by the prepared aptasensor and compared with the ELISA method, yielding acceptable results. The recovery and relative standard deviation (RSD) of CA 15-3 in human serum samples were in the range 95.0 to 107.0% and 3.5 to 7.5%, respectively., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. However, immune-related adverse events (irAEs) and undesired response patterns such as progression after the initial good response in a subset of patients pose a major challenge and drawback to ICIT. This paper provides deep insight into ICIT related bottlenecks and corresponding effective management and combat strategies for very complex complications., Methods: The relevant literatures from PubMed have been reviewed. Based on obtained information, rigorous and exhaustive analyses have been made to present novel methods and strategies against ICIT drawbacks and bottlenecks., Results: The results show that baseline biomarker tests are very crucial to identify suitable candidates for ICIT and frequent assessments throughout ICIT help to recognize possible irAEs at early stages. Equally important are the necessity for mathematical definitions for the ICIT success rate and optimum duration, and the development of combat mechanisms against loss of sensitivity within the tumor microenvironment (TME)., Conclusion: Rigorous management approaches are presented for mostly observed irAEs. Furthermore, for the first time in the literature, a non-linear mathematical model is invented to measure the ICIT success rate and to decide about the optimum ICIT duration. Finally, a strategy against tumor plasticity is introduced., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The nucleolus is considered the center of metabolic control and an important organelle for the biogenesis of ribosomal RNA (rRNA). Nucleolar and coiled-body phosphoprotein 1(NOLC1), which was originally identified as a nuclear localization signal-binding protein is a nucleolar protein responsible for nucleolus construction and rRNA synthesis, as well as chaperone shuttling between the nucleolus and cytoplasm. NOLC1 plays an important role in a variety of cellular life activities, including ribosome biosynthesis, DNA replication, transcription regulation, RNA processing, cell cycle regulation, apoptosis, and cell regeneration., Purpose: In this review, we introduce the structure and function of NOLC1. Then we elaborate its upstream post-translational modification and downstream regulation. Meanwhile, we describe its role in cancer development and viral infection which provide a direction for future clinical applications., Methods: The relevant literatures from PubMed have been reviewed for this article., Conclusion: NOLC1 plays an important role in the progression of multiple cancers and viral infection. In-depth study of NOLC1 provides a new perspective for accurate diagnosis of patients and selection of therapeutic targets., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Clinical pharmacy can reduce drug-related iatrogenesis by improving the management of adverse effects of drugs, limiting drug-drug interactions, and improving patient adherence. Given the vulnerability of cancer patients and the toxicity of injectable anticancer drugs, clinical pharmacy service (CPS) could provide a significant clinical benefit in cancer care. This review aims to synthesize existing evidence on clinical pharmacy's impact on patients treated with intravenous anticancer drugs., Methods: A comprehensive search was performed in the PubMed/Medline database from January 2000 to December 2021, associating the keywords: clinical pharmacy, pharmaceutical care, pharmacist, oncology, and chemotherapy. To be eligible for inclusion, studies have to report clinical pharmaceutical services for patients treated with intravenous chemotherapy with a clinical and/or economic impact., Results: Forty-one studies met the selection criteria. Various CPS were reported: medication reconciliation, medication review, and pharmaceutical interview with patient. There was a lack of randomized study (n = 3; 7.3%). In one randomized controlled trial, pharmaceutical intervention significantly improved quality of life of patients receiving pharmaceutical care during injectable anticancer drugs courses. Economical results appear to show positive impact of clinical pharmacy with cost savings reported from 3112.87$ to 249 844€. Although most studies were non-comparative, they highlighted that clinical pharmacy tend to limit chemotherapy side effects and drug-related problems, improve quality of life and satisfaction of patients and healthcare professional, and a positive economic impact., Conclusion: Clinical pharmacy can reduce adverse drug events in cancer patients. More robust and economic evaluations are still required to support its development in everyday practice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Exosomes are nanosized extracellular vesicles secreted by nearly all viable cells following the fusing of multivesicular bodies and the plasma membrane and discharged into the encircling bodily fluids. Exosomes can transport cell-specific components from the source cell to the target cell. Given the enormous potential of exosomes as non-invasive diagnostic biomarkers and therapeutic nanovehicles. Lately, accumulated evidence has demonstrated that exosomes serve an important role in prognosis, diagnosis, and even treatment strategies. While several reviews have collective information on the biomedical application of exosomes, a comprehensive review incorporating updated and improved methodologies for beneficial applications of such vesicles in cancer theranostics is indispensable. In the current review, we first provided a comprehensive review of the introduction of exosomes, featuring their discovery, separation, characterization, function, biogenesis, secretion. The implications of exosomes as promising nanovehicles for drug and gene delivery, application of exosome inhibitors in the management of cancers, completed and ongoing clinical trials on the biological relevance of exosomes are then discussed in detail. As the field of exosome research grows, a better understanding of the subcellular parts and mechanisms involved in exosome secretion and targeting of specific cells will help figure out what their exact physiological functions are in the body., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Major national and international oncological societies generally recommend treating a significant proportion of oncological patients in clinical trials to improve therapy strategies for cancer patients. At cancer centers, the recommendation about the appropriate therapy for the individual tumor patient is usually made in interdisciplinary case discussions in multidisciplinary tumor boards (MDT). In this study, we examined the impact of MDTs for the inclusion of patients in therapy trials., Methodology: A prospective, explorative study of the Comprehensive Cancer Center Munich (CCCM) was conducted at both university hospitals in 2019. In the first phase, various MDTs' case discussions about oncological situations and their decisions regarding possible therapy trials were recorded in a structured manner. In the second phase, the actual inclusion rates of patients in therapy trials and reasons for non-inclusion were examined. Finally, the data of the respective university hospitals were anonymized, pooled and analyzed., Results: A total of 1797 case discussions were reviewed. Therapy recommendations were made in 1527 case presentations. 38 (2.5%) of 1527 patients were already included in a therapy trial at the time of case presentation. The MDTs recommended inclusion of an additional 107 cases (7%), for a therapy trial. Of these patients, 41 were finally enrolled in a therapy trial which resulted in a total recruitment rate of 5.2%. Despite MDTs' recommendations, 66 patients were not included in a therapy trial. The main reason for non-inclusion was insufficient inclusion or existing exclusion criteria (n = 18, 28%). In 48% of all cases (n = 31), the reason for non-inclusion could not be determined., Conclusion: The potential of MDTs as an instrument for the inclusion of patients in therapy trials is high. To increase the enrollment of patients in oncological therapy trials, structural measures such as the central use of trial administration and MTB software in addition to standardized tumor board discussions must be established to ensure a seamless flow of information about actual recruiting trials and the current status of trial participation of patients., (© 2023. The Author(s).)

Over recent years, great efforts have been extensively documented in top scientific journals on the development of methods for early diagnosis, treatment, and monitoring of cancers which are prevalent critical diseases with a high mortality rate among men and women. The determination of cancer biomarkers using different optimum methodologies is one of the finest options for achieving these goals with more precision, speed, and at a lower cost than traditional clinical procedures. In this regard, while focusing on specific biomarkers, molecularly imprinted technology has enabled novel diagnostic techniques for a variety of diseases. Due to the well-known advantages of molecularly imprinted polymers (MIPs), this review focuses on the current trends of MIPs-based extraction/microextraction methods, specifically targeting cancer biomarkers from various matrices. These optimized methods have demonstrated high selectivity, accuracy, sorbent reusability, extraction recovery, and low limits of detection and quantification for a variety of cancer biomarkers, which are a powerful tool to provide early diagnosis, prognosis, and treatment monitoring, with potential clinical application expected soon. This review highlights the key progress, specific modifications, and strategies used for MIP synthesis. The future perspectives for cancer biomarkers purification and determination by fabricating MIP-based techniques are also discussed., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Recent research in the field of electrochemical biosensors equipped with peptides and nanomaterials have been categorized, reviewed, and critically analyzed. Indeed, using these innovative biosensors can revolutionize biomedical diagnostics in the future. Saving lives, time, and money in this field will be considered as some main benefits of this type of diagnosis. Here, these biosensors have been categorized and evaluated in four main sections. In the first section, the focus is on investigating the types of electrochemical peptide-based nanobiosensors applied to detect pathogenic microorganisms, microbial toxins, and viruses. In the second section, due to the importance of rapid diagnosis and prognosis of various cancers, the electrochemical peptide-based nanobiosensors designed to detect cancer biomarkers have been reviewed and analyzed. In the third section, the electrochemical peptide-based nanobiosensors, which were applied to detect the essential and effective biomolecules in the various diseases, and health control, including enzymes, hormones, biomarkers, and other biomolecules, have been considered. Finally, using a comprehensive analysis, all the used elements in these biosensors have been presented as conceptual diagrams that can effectively guide researchers in future developments. The essential factors in evaluating and analyzing these electrochemical peptide-based nanobiosensors such as analyte, peptide sequence, functional groups interacted between the peptide sequences and other biosensing components, the applied nanomaterials, diagnostic techniques, detection range, and limit of detection have also been included. Other analyzable items such as the type of used redox marker and the location of the peptide sequence against the signal transducer were also considered., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Cancer is a disease in which some cells of the body grow uncontrollably and occasionally spread to other parts of the body. With a group of more than 100 different types, cancer can start almost anywhere in the body. Defective cells may form a mass called a tumor which can be cancerous (malignant), which grows and spreads to other parts of the body, or benign that can grow but not spread throughout the body. In 2021, more than 10 million people died of cancer worldwide (1 out of 6 deaths). This paper has thoroughly investigated the cancer status in the Occupied Palestinian Territories (OPT), in terms of its various types; incidence; mortality; sex, age, and geography distribution; and potential causes. In the OPT, with a population of 5.35 million, cancer mortality was 14% in 2016, being the second cause of death after cardiovascular diseases accounting 30.6% of all causes of death. Cancer mortality in the OPT increased by 136% from 2000 to 2016, and by 14% from 2016 to 2020. In addition to other types of cancer in the OPT, its main types are lung (highest in males), breast (highest in females), colorectal (highest in both sexes), and leukemia (highest in children). The high rates of different types of cancer in the OPT can be attributed to various causes, including those related to environmental pollution, nutrition, stress, and lifestyle factors (smoking, lack of activity, increased dependence on technologies, etc.), whereas only 10-30% of cancer cases are attributed to genetics., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Flower-like core-shell nanostructures based on natural asphalt (NA) coated with nickel-layered double hydroxide nanosheets (Ni-LDH NSs) were synthesized for the first time. The synthetic nanostructures were successfully used as an efficient platform in the design of sarcosine (SAR) electrochemical aptasensor. SAR is considered an efficient biomarker for prostate cancer (PCa) diagnosis. However, the low concentration of SAR in urine, plasma, and tissue cells has limited the growth of SAR biosensors. The performance of the presented SAR aptasensor is very promising in being applied as a portable device in the identification of PCa. After drawing the calibration curve, the linear concentration range was obtained in two ranges from 5 pM to 100 nM and 100 nM to 7.9 μM, and the limit of detection (LOD) was calculated to be 1.6 pM. This study can provide a basis for wider research in various programs such as developing PCa diagnostic aptasensors and investigating the use of NA nanostructures in other electrochemical applications such as electrocatalysis and energy storage., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

In recent years, various types of radiosensitizers have been developed to address the challenges of cancer radiotherapy. Here, platinum-functionalized oxygenated single-walled carbon nanotubes (O-SWCNTs-Pt) coated with folic acid (FA) and bovine serum albumin (BSA) (O-SWCNTs-Pt-BSA-FA) were synthesized, characterized, and used as radiosensitizers to improve the therapeutic efficacy of X-rays in a mouse model of breast cancer (4T1) in vitro. The nanosensitizer was characterized by different techniques, such as transmission electron microscopy (TEM), selected area electron diffraction (SAED), dynamic light scattering (DLS), zeta potential, X-ray diffraction (XRD), ultraviolet-visible (UV-visible), and Fourier transform infrared (FTIR) spectrometry. The evaluation of cell viability with nanocarriers O-SWCNTs-BSA, O-SWCNTs-Pt-BSA, Pt-BSA-FA, and O-SWCNTs-Pt-BSA-FA is reported at the concentrations of 10, 30, and 90 μg/mL by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in the presence and absence of X-rays at 4 and 8 Gy. The results showed that administration of O-SWCNTs-BSA, O-SWCNTs-Pt-BSA, Pt-BSA-FA, and O-SWCNTs-Pt-BSA-FA + 8 Gy at a concentration of 90 μg/mL reduced survival by 75.31, 65.32, 67.35, and 60.35%, respectively. O-SWCNTs-Pt-BSA-FA has a hydrodynamic size of 88.57 nm and a surface charge of -29 mV, which indicates special stability. Compared with O-SWCNTs-BSA, O-SWCNTs-Pt-BSA, and Pt-BSA-FA, it has very strong cell-killing activity in the 4T1 cell line. It is also noteworthy that SWCNTs can act as a controlled release and delivery system for PtNPs due to their unique properties and easy penetration into biological membranes. As a result, the  new nanosensitizer may play a role in cancer treatment in conjunction with radiotherapy technology. Graphical abstract., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A sandwich-type photoelectrochemical (PEC) immunosensor was constructed on a screen-printed electrode (SPE) using gold-coated tin selenide quantum dots (Au-SnSe QDs) to determine the carbohydrate antigen 19 9 (CA19-9). Water-soluble Au-SnSe QDs were prepared by coating low-cost SnSe QDs, prepared by reacting tin(II) 2-ethyl hexanoate with selenium ions (HNaSe) without needing to add an external capping agent (SnSe QDs). SnSe-based QDs were characterized using high-resolution transmission electron microscopy (HR-TEM) and dynamic light scattering (DLS). DSP (dithio-bis (succinimidyl propionate)) as a linker was attached on Au@SnSe QDs and conjugated with CA19-9 monoclonal antibodies (Ab 2 -DSP-Au@SnSE QD). For capture probe assembling, an Au nano-layer was electrochemically deposited on a SPE by HAuCl 4 reduction using 12 cycles of cyclic voltammetry (0 to - 1.4 V) at the scan rate of 50 mV s -1 , then covered by self-assembly of DSP and covalent conjugation of CA19-9 Ab 1 . Our developed PEC immunosensor showed a significant photoelectrochemical response, recorded using chronoamperometry (0.3 V), for the presence of CA19-9 antigen in serum samples under light irradiation, with a detection limit (LOD) of 0.0011 U mL -1 and a dynamic range of 0.005-100 U mL -1 . The recovery of CA19-9 determination from serum samples was 101 to 113%., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objectives: High-dose bone-modifying agents (BMAs), such as bisphosphonates and denosumab, are essential for the treatment of cancer patients with bone metastases. The incidence of medication-related osteonecrosis of the jaw (MRONJ) is increasing. Inflammatory dental diseases could lead to MRONJ, and hence, they should be managed appropriately. Tooth extractions are commonly advised to prevent dental inflammation; however, the accurate indications for tooth extractions before starting BMA therapy have not been established. Hence, we assessed teeth with inflammatory dental diseases to identify indicators for prophylactic extraction before starting BMA therapy., Materials and Methods: We included 745 teeth with inflammatory dental diseases of 212 cancer patients on high-dose BMA therapy. We assessed the relationship between inflammatory dental disease and risk of MRONJ development. Multivariate Cox regression analysis was used for statistical analysis. The cumulative occurrence rate of MRONJ was calculated using the Kaplan-Meier method., Results: MRONJ occurred in 43 of 745 teeth. Teeth characteristics significantly correlated with MRONJ occurrence were mandible (p = 0.009), molar region (p = 0.005), radiopaque changes in bone surrounding the root on orthopantograms obtained at patients' first visits (p < 0.001), and tooth extractions after starting BMA therapy (p < 0.001)., Conclusions: Radiopaque changes in bone surrounding the root are an important radiographic finding that indicates the need for prophylactic tooth extractions before starting BMA therapy., Clinical Relevance: Our results suggest that the prophylactic extraction of teeth with radiopaque changes in bone surrounding the root before starting BMA therapy could prevent the onset of MRONJ.

Reactive oxygen species (ROS) are involved in drug-induced cytotoxicity by regulating cell signaling, inducing oxidative stress, and damaging the DNA and proteins. Examining ROS production in cells under the stimulation of chemotherapeutic drugs is of great importance for understanding the ROS roles and identifying the mechanism of drug-induced cytotoxicity. Here, a silver/gold (Ag/Au) nanoshell-based colorimetric and surface-enhanced Raman spectroscopy (SERS) dual-response nanoprobe was proposed for ROS sensing on the basis of Ag etching. In this study, as a kind of ROS, hydrogen peroxide (H 2 O 2 ) was detected by the prepared nanoprobe. The linear ranges of 0.5-100 μM with a limit of detection (LOD) of 0.343 μM for the colorimetric determination and 1-50 μM with LOD of 0.294 μM for SERS determination were achieved. The detection of cellular ROS concentration after stimulation by cisplatin, paclitaxel, doxorubicin, and 5-fluorouracil was validated by the nanoprobe. The nanoprobe could also be used to detect the signal pathway of ROS production by cisplatin stimulation. This study provided a simple and novel dual-response nanoplatform for detecting and monitoring ROS in cells, which holds great potential for elucidating the mechanism of occurrence and treatment of ROS-involved diseases., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Infections in patients with neutropenia following chemotherapy are mostly manifested as fever (febrile neutropenia, FN). Some of the most important determinants of the risk of FN are the type of chemotherapy, the dose intensity and patient-specific factors. When the risk of FN is 20% or more granulopoiesis is prophylactically stimulated with granulocyte colony stimulating factor (G-CSF) after the treatment. Anemia should always be clarified and if necessary be treated according to the cause when symptomatic. If an absolute or functional iron deficiency is present, intravenous iron substitution is mostly necessary. Erythropoiesis-stimulating agents can be used after chemotherapy with hemoglobin (Hb) levels less than 10 g/dl (6.2 mmol/l). In cases of chronic anemia and Hb levels less than 7-8 g/dl (<4.3-5.0 mmol/l) the indications for transfusion of erythrocyte concentrates should be assessed primarily based on the individual clinical symptoms., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Three dimensional (3D) "in vitro" models are progressively being applied to investigate tumor cell biology and the interaction of cancer cells with tumor microenvironment under conditions more similar and realistic to "in vivo" behavior than standard bidimensional (2D) cultures., Methods: In the last years, different methods have been developed to create spheroids and organoids and each technique has advantages and limitations also based on individual needs and cell types used. This review offers an overview of methodologies used for 3D systems: scaffold-free and scaffold-based methods up to bioreactors and organ-on-chip models., Results: The principal goal for researchers is to select the 3D system that best suits their needs and that reflects the tumor model they want to study. A large chapter is dedicated to the application of these models to lymphomas' study, a neoplasm still little explored in the 3D field., Conclusion: These innovative and advanced models may represent new tools for cancer research and pre-clinical studies of new therapies in the perspective of precision medicine., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Molecularly imprinted polymers MIPs were successfully assembled around quantum dots (QDs), for the detection of the protein biomarker CA19-9 associated to pancreatic cancer (PC). These imprinted materials MIP@QDs were incorporated within the cellulose hydrogel with retention of its conformational structure inside the binding cavities. The concept is to use MIPs which function as the biorecognition elements, conjugated to cadmium telluride QDs as the sensing system. The excitation wavelength was set to 477 nm and the fluorescence signal was measured at its maximum intensity, with an emission range between 530 and 780 nm. The fluorescence quenching of the imprinted cellulose hydrogels occurred with increasing concentrations of CA19-9, showing linearity in the range 2.76 × 10 -2 - 5.23 × 10 2 U/ml, in a 1000-fold diluted human serum. Replicates of the imprinted hydrogel show a linear response below the cut-off values for pancreatic cancer diagnosis (< 23 U/ml), a limit of detection of 1.58 × 10 -3 U/ml and an imprinting factor (IF) of 1.76. In addition to the fact that the imprinted cellulose hydrogel displays good stability and selectivity towards CA19-9 when compared with the non-imprinted controls, the conjugation of MIPs to QDs increases the sensitivity of the system for an optical detection method towards ranges within clinical significance. This fact shows potential for the imprinted hydrogel to be applied as a sensitive, low-cost format for point-of-care tests (PoCTs)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The role of the extracellular matrix (ECM) remodeling in tumorigenesis and metastasis is becoming increasingly clear. Cancer development requires that tumor cells recruit a tumor microenvironment permissive for further tumor growth. This is a dynamic process that takes place by a cross-talk between tumor cells and ECM. As a consequence, molecules derived from the ECM changes associated to cancer are released into the bloodstream, representing potential biomarkers of tumor development. This article highlights the importance of developing and improving bioanalytical methods for the detection of ECM remodeling-derived components, as a step forward to translate the basic knowledge about cancer progression into the clinical practice., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

A near-infrared (NIR) fluorescence nanoprobe named RhI-DOX@ZIF-90 has been synthesized by wrapping the guest molecule (RhI and DOX) into ZIF-90 framework. The nanoprobe itself is non-fluorescent and the drug (DOX) is inactive. Upon the addition of ATP, the structure of RhI-DOX@ZIF-90 is degraded. The fluorescence of RhI is recovered and DOX is released. The nanoprobe can detect ATP with high sensitivity and selectivity. There is good linear relationship between the nanoprobe and ATP concentration from 0.25 to 10 mM and the detection limit is 0.10 mM. The nanoprobe has the ability to monitor the change of ATP level in living cells and DOX is released inducing apoptosis of cancer cells. RhI-DOX@ZIF-90 is capable of targeting mitochondria, which provides a basis for improving the efficiency of drug delivery by mitochondrial administration. In particular, the nanoprobe is preferentially accumulated in the tumor sites and detect ATP in tumor mice by fluorescence imaging using near-infrared fluorescence. At the same time, DOX can be released accurately in tumor sites and have good anti-tumor efficiency. So, this nanoprobe is a reliable tool to realize early diagnosis of cancer and improve effect of anticancer drug., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: The aim of the study is to evaluate the results of apical surgery (AS) in patients receiving high-dose antiresorptive medication (HDAR)., Methods: Retrospective descriptive quality control study conducted in an Oral and Maxillofacial Department at a University Hospital. Fourteen patients on HDAR met the inclusion criteria. Only descriptive statistics were applied., Results: Fourteen patients had operation on seventeen teeth. Mean HDAR treatment period before apical surgery: 25 months (SD, ± 24.27; range, 1-78 months). Drug holiday during surgery and initial healing: mean, 8 months (SD, ± 5.96; range, 0.4-22 months). Sixteen out of seventeen teeth healed clinically and showed complete or ongoing radiographic healing. All patients except one became free of symptoms. Mean follow-up: 13 months (SD, ± 9.05; range, 2-31 months). Radiographic healing according to Molven and Rud: 7, complete; 6, uncertain; 1, unsatisfactory. Three patients died during follow-up and were considered drop-outs., Conclusions: The present case series suggest that apical surgery is a valid treatment option for apical periodontitis in patients on HDAR, where orthograde endodontic retreatment is not possible. None of the patients developed medication-related osteonecrosis of the jaw. Further studies in larger study groups and with longer follow-up periods are needed. The regional scientific ethical committee provided a document exemption, registration date 20 November 2013, and the local data protection agency approved handling of the recorded data (No. 2012-41-0045), registration date 11 January 2012.

Purpose: Cancer-associated cachexia is a common condition in patients with advanced cancer, and is associated with extreme and involuntary weight loss and irreversible muscle wasting. Despite its high morbidity and mortality, there is no known treatment to reverse its effects. Thus, there is increasing interest in whether diet and exercise can assist in the minimization of cancer-associated cachexia., Methods: We reviewed the literature on the impact of dietary patterns, dietary components, and exercise on the progress and severity of cancer cachexia., Results: Although most studies have produced inconclusive or controversial findings, some promising studies using animal models and early human clinical trials suggest that dietary and physical therapy interventions may alleviate cancer-associated cachexia. Moreover, many studies suggest that controlling diet and exercise nevertheless improved the quality of life (QoL) for cancer patients with cachexia., Conclusion: Ongoing studies will continue to examine whether different forms of multimodal therapy-combinations of cancer treatment, dietary regimens, anti-inflammatory therapy, and physical therapy-are effective methods to improve outcomes in advanced cancer patients with cachexia. Moreover, future studies should examine the effects of such interventions on long-term QoL and establish nutritional guidelines for the management of cancer-associated cachexia.

Noble metal nanostructures with designed hot spots have been widely investigated as surface-enhanced Raman spectroscopy (SERS)-active substrates, particularly for selective and sensitive detection of protein cancer markers. For specific target recognition and efficient signal amplification, SERS probe design requires a choice of SERS-active nanostructures as well as their controlled functionalization with Raman dyes and target recognition entities such as antibodies. However, the chemical conjugation of antibodies and Raman dyes to SERS substrates has rarely been discussed to date, despite their substantial roles in detection schemes. The interfacial interactions of metal nanostructures with functional ligands during conjugation are known to be strongly influenced by the various chemical and physical properties of the ligands, such as size, molecular weight, surface charge, 3-dimensional structures, and hydrophilicity/hydrophobicity. In this review, we discuss recent developments in the design of SERS probes over the last 4 years, focusing on their conjugation chemistry for functionalization. A strong preference for covalent bonding is observed with Raman dyes having simpler molecular structures, whereas more complicated ones are non-covalently adsorbed. Antibodies are both covalently and non-covalently bonded to nanostructures, depending on their activity in the SERS probes. Considering that ligand conjugation is highly important for chemical stability, biocompatibility, and functionality of SERS probes, this review is expected to expand the understanding of their interfacial design, leading to SERS as one of the most promising spectroscopic analytical tools for the early detection of protein cancer markers.

This review provides a summary of known molecular alterations in commonly used cancer models and strives to stipulate how they may affect ambient mass spectrometry profiles. Immortalized cell lines are known to accumulate mutations, and xenografts derived from cell lines are known to contain tumour microenvironment elements from the host animal. While the use of human specimens for mass spectrometry profiling studies is highly encouraged, patient-derived xenografts with low passage numbers could provide an alternative means of amplifying material for ambient MS research when needed. Similarly, genetic preservation of patient tissue seen in some organoid models, further verified by qualitative proteomic and transcriptomic analyses, may argue in favor of organoid suitability for certain ambient profiling studies. However, to choose the appropriate model, pre-evaluation of the model's molecular characteristics in the context of the research question(s) being asked will likely provide the most appropriate strategy to move research forward. This can be achieved by performing comparative ambient MS analysis of the disease model of choice against a small amount of patient tissue to verify concordance. Disease models, however, will continue to be useful tools to orthogonally validate metabolic states of patient tissues through controlled genetic alterations that are not possible with patient specimens.

Gas signaling molecules, including carbon monoxide (CO), nitric oxide (NO), and hydrogen sulfide (H 2 S), have been shown to have cancer therapeutic potential, pointing to a new direction for cancer treatment. In recent years, a series of studies have confirmed that hydrogen (H 2 ), a weakly reductive gas, also has therapeutic effects on various cancers and can mitigate oxidative stress caused by radiation and chemotherapy, reducing tissue damage and immunosuppression to improve prognosis. Meanwhile, H 2 also has immunomodulatory effects, inhibiting T cell exhaustion and enhancing T cell anti-tumor function. It is worth noting that human intestinal flora can produce large amounts of H 2 daily, which becomes a natural barrier to maintaining the body's resistance to diseases such as tumors. Although the potential anti-tumor mechanisms of H 2 are still to be investigated, previous studies have shown that H 2 can selectively scavenge highly toxic reactive oxygen species (ROS) and inhibit various ROS-dependent signaling pathways in cancer cells, thus inhibiting cancer cell proliferation and metastasis. The ROS scavenging ability of H 2 may also be the underlying mechanism of its immunomodulatory function. In this paper, we review the significance of H 2 produced by intestinal flora on the immune homeostasis of the body, the role of H 2 in cancer therapy and the underlying mechanisms, and the specific application of H 2 to provide new ideas for the comprehensive treatment of cancer patients., (© 2024. The Author(s).)

Background: Secondary achalasia or pseudoachalasia is a clinical presentation undistinguishable from achalasia in terms of symptoms, manometric, and radiographic findings, but associated with different and identifiable underlying causes., Methods: A literature review was conducted on the PubMed database restricting results to the English language. Key terms used were "achalasia-like" with 63 results, "secondary achalasia" with 69 results, and "pseudoachalasia" with 141 results. References of the retrieved papers were also manually reviewed., Results: Etiology, diagnosis, and treatment were reviewed., Conclusions: Pseudoachalasia is a rare disease. Most available evidence regarding this condition is based on case reports or small retrospective series. There are different causes but all culminating in outflow obstruction. Clinical presentation and image and functional tests overlap with primary achalasia or are inaccurate, thus the identification of secondary achalasia can be delayed. Inadequate diagnosis leads to futile therapies and could worsen prognosis, especially in neoplastic disease. Routine screening is not justifiable; good clinical judgment still remains the best tool. Therapy should be aimed at etiology. Even though Heller's myotomy brings the best results in non-malignant cases, good clinical judgment still remains the best tool as well., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This article summarizes natural products that target the MAPK-signaling pathway in cancer therapy. The classification, chemical structures, and anti-cancer mechanisms of these natural products are elucidated, and comprehensive information is provided on their potential use in cancer therapy., Methods: Using the PubMed database, we searched for keywords, including "tumor", "cancer", "natural product", "phytochemistry", "plant chemical components", and "MAPK-signaling pathway". We also screened for compounds with well-defined structures that targeting the MAPK-signaling pathway and have anti-cancer effects. We used Kingdraw software and Adobe Photoshop software to draw the chemical compound structural diagrams., Results: A total of 131 papers were searched, from which 85 compounds with well-defined structures were selected. These compounds have clear mechanisms for targeting cancer treatment and are mainly related to the MAPK-signaling pathway. Examples include eupatilin, carvacrol, oridonin, sophoridine, diosgenin, and juglone. These chemical components are classified as flavonoids, phenols, terpenoids, alkaloids, steroidal saponins, and quinones., Conclusions: Certain MAPK pathway inhibitors have been used for clinical treatment. However, the clinical feedback has not been promising because of genomic instability, drug resistance, and side effects. Natural products have few side effects, good medicinal efficacy, a wide range of sources, individual heterogeneity of biological activity, and are capable of treating disease from multiple targets. These characteristics make natural products promising drugs for cancer treatment., (© 2024. The Author(s).)

Introduction: In recent decades, many theories have been proposed about the cause of hereditary diseases such as cancer. However, most studies state genetic and environmental factors as the most important parameters. It has been shown that gene expression data are valuable information about hereditary diseases and their analysis can identify the relationships between these diseases., Objective: Identification of damaged genes from various diseases can be done through the discovery of cell-to-cell biological communications. Also, extraction of intercellular communications can identify relationships between different diseases. For example, gene disorders that cause damage to the same cells in both breast and blood cancers. Hence, the purpose is to discover cell-to-cell biological communications in gene expression data., Methodology: The identification of cell-to-cell biological communications for various cancer diseases has been widely performed by clustering algorithms. However, this field remains open due to the abundance of unprocessed gene expression data. Accordingly, this paper focuses on the development of a semi-supervised ensemble clustering algorithm that can discover relationships between different diseases through the extraction of cell-to-cell biological communications. The proposed clustering framework includes a stratified feature sampling mechanism and a novel similarity metric to deal with high-dimensional data and improve the diversity of primary partitions., Results: The performance of the proposed clustering algorithm is verified with several datasets from the UCI machine learning repository and then applied to the FANTOM5 dataset to extract cell-to-cell biological communications. The used version of this dataset contains 108 cells and 86,427 promoters from 702 samples. The strength of communication between two similar cells from different diseases indicates the relationship of those diseases. Here, the strength of communication is determined by promoter, so we found the highest cell-to-cell biological communication between "basophils" and "ciliary.epithelial.cells" with 62,809 promoters., Conclusion: The maximum cell-to-cell biological similarity in each cluster can be used to detect the relationship between different diseases such as cancer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A viscosity-sensitive, lysosome-targeted near-infrared fluorescent probe (PYATT) was reported in this paper. The fluorescent spectra of PYATT are strongly dependent on viscosity, resulting in a Stokes shift of about 190 nm. Given its photostability, low cytotoxicity, and high fluorescence quantum yield, PYATT is expected to be used in cell imaging. Due to the higher viscosity of tumor cells than normal cells, the fluorescence intensity of PYATT in tumor cells is higher than normal cells, which can realize the visualization of tumors. The near-infrared probe (PYATT) is viscosity-dependent in lysosomes, which is valuable in early diagnosis and treatment of tumor., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: Guidelines recommend a structured symptom screening (SC) for especially advanced cancer patients (CPs). The aim of this multicenter German prospective quality assurance project KeSBa (Kennzahl Symptom- und Belastungserfassung) was to gain knowledge on SC procedures in Oncology Centers (OCs) for advanced cancer patients and a first impression on the consequences of SC., Methods: The KeSBa project consisted of three phases: pilot, 3 months screening and feedback phase. Participating OCs decided to use either the Minimal Documentation System (MIDOS) or the Integrated Palliative care Outcome Scale (IPOS) and defined the cutoff values for positive screening results., Results: Out of 172 certified German OCs, 40 (23%) participated in the KeSBa pilot phase, 29 (16.8%) in the 3 months screening phase using MIDOS (n = 18, 58.6%) or IPOS (n = 11, 41.3%) and in the feedback round. 25/29 performed paper-based screening (86.2%). 2.963 CPs were screened. Results were documented for 1255 (42.2%, SC +) positive and 874 (29.5%, SC-) negative screenings depending on the center´s schedules: 452 SC + CPs (28.4%) and 42 SC- CPs (2.6%) had contact to specialized palliative care or other supportive specialist teams afterwards, 458 SC + CPs (28.8%) and 605 SC- CPs (38.1%) remained in standard oncology care. In the feedback round missing resources (personal and IT) and improved communication were mentioned most often., Conclusion: Routine SC is feasible in advanced CPs treated in OCs but associated with considerable workload. In 42.2% of CPs SC was classified as positive, indicating the need of further diagnostics or professional judgment. SC requires staff and IT resources., (© 2023. The Author(s).)

Background: Protocadherin 10 (PCDH 10), a member of the superfamily of protocadherins, is a Ca2 + -dependent homophilic cell-cell adhesion molecule expressed on the surface of cell membranes. Protocadherin 10 plays a critical role in the central nervous system including in cell adhesion, formation and maintenance of neural circuits and synapses, regulation of actin assembly, cognitive function and tumor suppression. Additionally, Pcdh10 can serve as a non-invasive diagnostic and prognostic indicator for various cancers., Methods: This paper collects and reviews relevant literature in Pubmed., Conclusion: This review describes the latest research understanding the role of Pcdh10 in neurological disease and human cancer, highlighting the importance of scrutinizing its properties for the development of targeted therapies and identifying a need for further research to explore Pcdh10 functions in other pathways, cell types and human pathologies., (© 2023. The Author(s).)

Purpose: The WHO 2016 re-classification of myeloproliferative neoplasms resulted in a separation of essential thrombocythemia (ET) from the pre-fibrotic and fibrotic (overt) phases of primary myelofibrosis (MF). This study reports on a chart review conducted to evaluate the real life approach regarding clinical characteristics, diagnostic assessment, risk stratification and treatment decisions for MPN patients classified as ET or MF after implementation of the WHO 2016 classification., Methods: In this retrospective chart review, 31 office-based hematologists/oncologists and primary care centers in Germany participated between April 2021 and May 2022. Physicians reported available data obtained from patient charts via paper-pencil based survey (secondary use of data). Patient features were evaluated using descriptive analysis, also including diagnostic assessment, therapeutic strategies and risk stratification., Results: Data of 960 MPN patients diagnosed with essential thrombocythemia (ET) (n = 495) or myelofibrosis (MF) (n = 465) after implementation of the revised 2016 WHO classification of myeloid neoplasms was collected from the patient charts. While they met at least one minor WHO-criteria for primary myelofibrosis, 39.8% of those diagnosed with ET did not have histological BM testing at diagnosis. 63.4% of patients who were classified as having MF, however, did not obtain an early prognostic risk assessment. More than 50% of MF patients showed characteristics consistent with the pre-fibrotic phase, which was emphasized by the frequent use of cytoreductive therapy. Hydroxyurea was the most frequently used cytoreductive medication in 84.7% of ET and 53.1% of MF patients. While both ET and MF cohorts showed cardiovascular risk factors in more than 2/3 of the cases, the use of platelet inhibitors or anticoagulants varied between 56.8% in ET and 38.1% in MF patients., Conclusions: Improved histopathologic diagnostics, dynamic risk stratification including genetic risk factors for cases of suspected ET and MF are recommended for precise risk assessment and therapeutic stratification according to WHO criteria., (© 2023. The Author(s).)

Background: Cancer patients constitute one of the highest-risk patient groups during the COVID-19 pandemic. In this study, it was aimed to perform a systematic review and meta-analysis to determine both the incidence and ICU (Intensive Care Unit) admission rates and mortality in SARS-CoV-2 infected cancer patients., Methods: The PRISMA guidelines were closely followed during the design, analysis, and reporting of this systematic review and meta-analysis. A comprehensive literature search was performed for the published papers in PubMed/Medline, Scopus, medRxiv, Embase, and Web of Science (WoS) databases. SARS-CoV-2 infection pooled incidence in the cancer populations and the risk ratio (RR) of ICU admission rates/mortality in cancer and non-cancer groups, with 95% confidence intervals (CIs), were calculated using the random-effects model., Results: A total of 58 studies, involving 709,908 participants and 31,732 cancer patients, were included in this study. The incidence in cancer patients was calculated as 8% (95% CI: 8-9%). Analysis results showed that mortality and ICU admission rate was significantly higher in patients with cancer (RR = 2.26, 95% CI: 1.94-2.62, P < 0.001; RR = 1.45, 95% CI: 1.28-1.64, p < 0.001, respectively)., Conclusion: As a result, cancer was an important comorbidity and risk factor for all SARS-CoV-2 infected patients. This infection could result in severe and even fatal events in cancer patients. Cancer is associated with a poor prognosis in the COVID-19 pandemic. Cancer patients should be assessed more sensitively in the COVID-19 outbreak., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Omics data are crucial for medical diagnosis as it contains intrinsic biomedical information. Multi-omics integrated analysis has become a new direction for scientists to explore life mechanisms. Nevertheless, the quality of complex omics data often varies greatly due to different samples or even different omics types, it is challenging to dynamically capture the uncertainty for different kinds of omics data., Methods: This paper proposes a uncertainty-aware dynamic integration framework for multi-omics classification. The framework consists of three modules: deep embedding, confidence prediction, and downstream tasks. The deep embedding module extract key information from multi-omics data to obtain a low-dimensional feature representation which is used to train downstream tasks. Combined with the deep embedding module, the confidence prediction module is used to dynamically capture the uncertainty of the data. We introduce "confidNet" to assign a confidence value for each type of omics data, which is used for dynamic integration between multi-omics., Results: Compared with other integration methods, the proposed method can contain more crucial biomedical information in the obtained low-dimensional representation. Our framework realizes reliable integration among multiple omics, and it can still achieve high accuracy on small sample data sets. We have verified the effectiveness of the model in a large number of experiments., Conclusion: Our framework can be widely applied to high-dimensional omics data and has great potential to facilitate medical decision-making and biological analysis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Somatic mutations often occur at high relapse sites in protein sequences, which indicates that the location clustering of somatic missense mutations can be used to identify driving genes. However, the traditional clustering algorithm has such problems as the background signal over-fitting, the clustering algorithm is not suitable for mutation data, and the performance of identifying low-frequency mutation genes needs to be improved. In this paper, we propose a linear clustering algorithm based on likelihood ratio test knowledge to identify driver genes. In this experiment, firstly, the polynucleotide mutation rate is calculated based on the prior knowledge of likelihood ratio test. Then, the simulation data set is obtained through the background mutation rate model. Finally, the unsupervised peak clustering algorithm is used to, respectively, evaluate the somatic mutation data and the simulation data to identify the driver genes. The experimental results show that our method achieves a better balance of precision and sensitivity. It can also identify the driver genes missed by other methods, making it an effective supplement to other methods. We also discover some potential linkages between genes and between genes and mutation sites, which is of great value to target drug therapy research. Method framework: Our proposed model framework is as follows. a. Counting mutation sites and the number of mutations in tumor gene elements. b. The nucleotide context mutation frequency is counted based on the likelihood ratio test knowledge, and the background mutation rate model is obtained. c. Based on Monte Carlo simulation method, data sets with the same number of mutations as gene elements are randomly sampled to obtain simulated mutation data, and the sampling frequency of each mutation site is related to the mutation rate of polynucleotide. d. The original mutation data and the simulated mutation data after random reconstruction are clustered by peak density, respectively, and the corresponding clustering scores are obtained. e. We can obtain the clustering information statistics in each gene segment and score of each gene segment from the original single nucleotide mutation data through step d. f. According to the observed score and the simulated clustering score, the p-value of the corresponding gene fragment is calculated. g. We can obtain the clustering information statistics in each gene segment and score of each gene segment from the simulated single nucleotide mutation data through step d., (© 2023. International Association of Scientists in the Interdisciplinary Areas.)

Endoplasmic reticulum (ER)-mitochondria regions are specialized subdomains called also mitochondria-associated membranes (MAMs). MAMs allow regulation of lipid synthesis and represent hubs for ion and metabolite signaling. As these two organelles can module both the amplitude and the spatiotemporal patterns of calcium (Ca 2+ ) signals, this particular interaction controls several Ca 2+ -dependent pathways well known for their contribution to tumorigenesis, such as metabolism, survival, sensitivity to cell death, and metastasis. Mitochondria-mediated apoptosis arises from mitochondrial Ca 2+ overload, permeabilization of the mitochondrial outer membrane, and the release of mitochondrial apoptotic factors into the cytosol. Decreases in Ca 2+ signaling at the ER-mitochondria interface are being studied in depth as failure of apoptotic-dependent cell death is one of the predominant characteristics of cancer cells. However, some recent papers that linked MAMs Ca 2+ crosstalk-related upregulation to tumor onset and progression have aroused the interest of the scientific community.In this review, we will describe how different MAMs-localized proteins modulate the effectiveness of Ca 2+ -dependent apoptotic stimuli by causing both increases and decreases in the ER-mitochondria interplay and, specifically, by modulating Ca 2+ signaling., (© 2020. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

One of the most popular measures in the analysis of protein sequence evolution is the ratio of nonsynonymous distance (d N ) to synonymous distance (d S ). Under the assumption that synonymous substitutions in the coding region are selectively neutral, the d N /d S ratio can be used to statistically detect the adaptive evolution (or purifying selection) if d N /d S  > 1 (or d N /d S  < 1) significantly. However, due to strong structural constraints and/or variable functional constraints imposed on amino acid sites, most encoding genes in most species have demonstrated d N /d S  < 1. Consequently, the statistical power for testing d N /d S  = 1 may be insufficient to distinguish between different selection modes. In this paper, we propose a more powerful test, called d N /d S -H, in which a new parameter H, a relative measure of rate variation among sites, was introduced. Given the condition of strong purifying selections at some sites, the d N /d S -H model predicts d N /d S  = 1-H for neutral evolution, d N /d S  < 1-H for nearly neutral selection, and d N /d S  > 1-H for adaptive evolution. The potential of this new method for resolving the neutral-adaptive debates is illustrated by the protein sequence evolution in vertebrates, Drosophila and yeasts, as well as somatic cancer evolution (specialized as the C N /C S -H test)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Concern over substances that may cause cancer has led to various classification schemes to recognize carcinogenic threats and provide a basis to manage those threats. The least useful schemes have a binary choice that declares a substance carcinogenic or not. This overly simplistic approach ignores the complexity of cancer causation by considering neither how the substance causes cancer, nor the potency of that mode of action. Consequently, substances are classified simply as "carcinogenic", compromising the opportunity to properly manage these kinds of substances. It will likely be very difficult, if not impossible, to incorporate New Approach Methodologies (NAMs) into binary schemes. In this paper we propose a new approach cancer classification scheme that segregates substances by both mode of action and potency into three categories and, as a consequence, provides useful guidance in the regulation and management of substances with carcinogenic potential. Examples are given, including aflatoxin (category A), trichlorethylene (category B), and titanium dioxide (category C), which demonstrate the clear differentiation among these substances that generate appropriate levels of concern and management options., (© 2022. The Author(s).)

Programed cell death ligand 1 (PD-L1) is a protein biomarker overexpressed on exosomes derived from tumor cells. It plays an important role in tumor diagnosis, screening, evaluation of therapeutic efficacy, and prognosis. In this study, a facile method is presented to detect PD-L1-overexpressing cancer exosomes with high specificity and sensitivity. First, gold nanospheres (GNSs) were attached to the bottom of an eight-well chambered slide by electrostatic adsorption, forming the detection substrate. Then, Cy5-labeled CD63 aptamers (i.e., the capture probes) were modified on the GNSs by Au-S bond. After adding samples containing target exosomes which were stained by membrane dyes DiI in advance, FAM-labeled PD-L1 aptamers (i.e., the immunoprobes) were added to recognize PD-L1 on the target exosomes. By triple-color fluorescence co-localization (TFC) of the Cy5, DiI, and FAM channels, highly sensitive and reliable detection of the PD-L1-overexpressing exosomes was achieved in the concentration range 7.78 × 10 1 to 7.78 × 10 4 particles/mL with a detection limit down to 6 particles/mL. The advantages of the proposed detection method include the following; first, the detection substrate is easy to prepare and convenient to clean. Second, the TFC strategy can completely exclude nonspecific reaction sites and thus significantly improves the accuracy. Such a facile and reliable detection method holds a great potential in exosome-based cancer theranostics. In this paper, we proposed a triple-color fluorescence co-localization (TFC) strategy to significantly improve the reliability of exosome detection and the detection substrate is easy to prepare and convenient to clean. In addition, the LOD is down to 6 particles/mL, which is quite low compared with other detection methods., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

In recent years, clustering analysis of cancer genomics data has gained widespread attention. However, limited by the dimensions of the matrix, the traditional methods cannot fully mine the underlying geometric structure information in the data. Besides, noise and outliers inevitably exist in the data. To solve the above two problems, we come up with a new method which uses tensor to represent cancer omics data and applies hypergraph to save the geometric structure information in original data. This model is called hypergraph regularized tensor robust principal component analysis (HTRPCA). The data processed by HTRPCA becomes two parts, one of which is a low-rank component that contains pure underlying structure information between samples, and the other is some sparse interference points. So we can use the low-rank component for clustering. This model can retain complex geometric information between more sample points due to the addition of the hypergraph regularization. Through clustering, we can demonstrate the effectiveness of HTRPCA, and the experimental results on TCGA datasets demonstrate that HTRPCA precedes other advanced methods. This paper proposes a new method of using tensors to represent cancer omics data and introduces hypergraph items to save the geometric structure information of the original data. At the same time, the model decomposes the original tensor into low-order tensors and sparse tensors. The low-rank tensor was used to cluster cancer samples to verify the effectiveness of the method., (© 2021. International Association of Scientists in the Interdisciplinary Areas.)

The nucleation and growth theory, described by the Avrami equation (also called Johnson-Mehl-Avrami-Kolmogorov equation), and usually used to describe crystallization and nucleation processes in condensed matter physics, was applied in the present paper to cancer physics. This can enhance the popular multi-hit model of carcinogenesis to volumetric processes of single cell's DNA neoplastic transformation. The presented approach assumes the transforming system as a DNA chain including many oncogenic mutations. Finally, the probability function of the cell's cancer transformation is directly related to the number of oncogenic mutations. This creates a universal sigmoidal probability function of cancer transformation of single cells, as observed in the kinetics of nucleation and growth, a special case of a phase transition process. The proposed model, which represents a different view on the multi-hit carcinogenesis approach, is tested on clinical data concerning gastric cancer. The results also show that cancer transformation follows DNA fractal geometry., (© 2021. The Author(s).)