bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial Dysfunction in Advanced Maternal Aged Cumulus Cells: A Possible Link to ATP Synthase Impairment?
Authors: Almeida-Reis Sandra , Carvalho Alexandra , Dias Conceição , Brito Raquel , Silva Rita , Almeida-Santos Teresa , Ramalho-Santos João , Sousa Ana Paula
Published: February 2024

Age-related changes in the mitochondrial status of human cumulus cells (hCCs) impact oocyte quality; however, the relationship between hCC mitochondrial (dys)function and reproductive aging remains poorly understood. This study aimed to establish the interplay between hCC mitochondrial dysfunction and women’s reproductive potential. In this investigation, 266 women were enrolled and categorized into two groups based on their age: a young group (<35 years old) and an advanced maternal age (AMA) group (≥35 years old). Comprehensive analysis of reproductive outcomes was conducted in our population. Various mitochondrial-related parameters were analyzed across distinct subsets. Specifically, mitochondrial membrane potential (∆Ψm) and mitochondrial mass were examined in 53 samples, mtDNA content in 25 samples, protein levels in 23 samples, bioenergetic profiles using an XF24 Extracellular Flux Analyzer in 6 samples, and levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in 39 and 43 samples, respectively. In our study, the reproductive potential of AMA women sharply decreased, as expected. Additionally, an impairment in the mitochondrial function of hCCs in older women was observed; however, no differences were found in terms of mitochondrial content. Regarding oxidative phosphorylation, metabolic profiling of hCCs from AMA women indicated a decrease in respiratory capacity, which was correlated with an age-dependent decrease in the ATP synthase (ATP5A1) protein level. However, intracellular ROS and ATP levels did not differ between groups. In conclusion, our study indicates that age-related dysfunction in hCCs is associated with impaired mitochondrial function, and, although further studies are required, ATP synthase could be relevant in this impairment.
Increased Risk for Non-Union in First Metatarsophalangeal Joint Arthrodesis following High-Velocity Reaming: A Retrospective Study
Authors: Albagli Assaf , Kadar Assaf , Gurel Ron , Luger Elchanan , Warschawski Yaniv , Factor Shai
Published: February 2024

Objective: Arthrodesis of the first metatarsophalangeal joint (MTPJ) is a reliable procedure for treating various pathologies related to this joint. However, non-union is a common and debilitating complication of the procedure. The purpose of this study was to assess whether the use of a mechanical reamer to prepare the joint surface increases the risk of non-union compared to traditional manual osteotomy. Methods: A retrospective study of all patients who underwent their first MTPJ arthrodesis surgery in our medical center between 2010 and 2015. The articular surface preparation of the MTPJ was either manually performed (Group 1) or mechanically conducted with reamers (Group 2). Data regarding demographic characteristics, indications for surgery, osteosynthesis methods, and post-operative complications, including non-union, infection, and revision rates, were collected for all patients. Results: A total of 83 patients with 92 primary first MTPJ arthrodesis (44 cases in Group 1 and 48 cases in Group 2) were included with a mean follow-up time of 45.3 months (SD 16.8). The two groups were comparable in terms of age, gender, comorbidities, indication for surgery, and follow-up time. The non-union rate was 15.9% in Group 1 and 25% in Group 2 (p = 0.28). Group 2 showed a significantly higher rate of revision surgery compared to Group 1 (43.7% vs. 22.7%, p = 0.03). Conclusions: The mechanical reamer group had a higher non-union rate and a significantly higher rate of revision surgery compared to low-energy manual joint preparation. In light of these findings, the use of mechanical reamers for joint preparation in the first MTPJ arthrodesis was discontinued at our medical center.
Endothelin-1 and Its Role in Cancer and Potential Therapeutic Opportunities
Authors: Harrison Madeline , Zinovkin Dmitry , Pranjol Md Zahidul Islam
Published: February 2024

Endothelin-1 (ET-1) plays a physiological role as a potent vasoconstrictor. It is implicated in an array of diseases, and its signalling is often found to be overactivated within cancers. ET-1 has been found to potentiate hallmarks of cancer progression such as cell proliferation, invasion and metastasis, as well as angiogenesis. ET-1 has also been implicated in inducing the epithelial–mesenchymal transition (EMT) and promoting resistance to anticancer drugs. Many preclinical efforts have been made to target ET-1 expression within cancer, such as by using ET-1 receptor antagonists, many of which have been approved for treating pulmonary hypertension. Targeting ET-1 has been shown to improve the response to various other cancer therapeutics, highlighting the potential benefits targeting this peptide may exert. Drug repurposing is an attractive strategy, and exploration of this avenue may be promising for targeting ET-1 in cancer. There are many clinical trials which have been completed and are currently undergoing involving the repurposing of ET-1 receptor antagonists for cancer treatment. In this review, the pathways through which ET-1 potentiates cancer will be discussed, as well as where the opportunity for therapeutic intervention lies in relation to cancer.
Evaluating the Connection between MicroRNAs and Long Non-Coding RNAs for the Establishment of the Major Depressive Disorder Diagnosis
Authors: Prodan-Bărbulescu Cătălin , Şeclăman Edward Paul , Enătescu Virgil , Faur Ionuţ Flaviu , Ghenciu Laura Andreea , Tuţac Paul , Paşca Paul , Grigoriţă Laura Octavia
Published: February 2024

The most prevalent mental illness worldwide and the main contributor to suicide and disability is major depressive disorder. Major depressive disorder is now diagnosed and treated based on the patient’s statement of symptoms, mental status tests, and clinical behavioral observations. The central element of this review is the increased need for an accurate diagnostic method. In this context, the present research aims to investigate the potential role of two non-coding RNA species (microRNA and long non-coding RNA) in peripheral blood samples and brain tissue biopsy from patients with major depressive disorder. This study reviewed the literature on microRNA and long non-coding RNA expression in blood and brain tissue samples in human and animal depression models by retrieving relevant papers using the PubMed database. The results reveal significant variations in microRNA and long non-coding RNA levels in depressed patients, making it a crucial diagnostic tool that predicts treatment outcomes. It can help track severe cases and adjust therapy dosages based on treatment responses. In conclusion, microRNAs and long non-coding RNAs are pertinent biomarkers that can be added to the diagnostic test panel for major depressive disorder. Both microRNAs and non-coding RNAs can also be used as a tool to track patient progress during therapy and to assist the attending physician in tracking the molecular development of the disease.
Device for Measuring Contact Reaction Forces during Animal Adhesion Landing/Takeoff from Leaf-like Compliant Substrates
Authors: Wang Zhouyi , Feng Yiping , Wang Bingcheng , Yuan Jiwei , Zhang Baowen , Song Yi , Wu Xuan , Li Lei , Li Weipeng , Dai Zhendong
Published: February 2024

A precise measurement of animal behavior and reaction forces from their surroundings can help elucidate the fundamental principle of animal locomotion, such as landing and takeoff. Compared with stiff substrates, compliant substrates, like leaves, readily yield to loads, presenting grand challenges in measuring the reaction forces on the substrates involving compliance. To gain insight into the kinematic mechanisms and structural–functional evolution associated with arboreal animal locomotion, this study introduces an innovative device that facilitates the quantification of the reaction forces on compliant substrates, like leaves. By utilizing the stiffness–damping characteristics of servomotors and the adjustable length of a cantilever structure, the substrate compliance of the device can be accurately controlled. The substrate was further connected to a force sensor and an acceleration sensor. With the cooperation of these sensors, the measured interaction force between the animal and the compliant substrate prevented the effects of inertial force coupling. The device was calibrated under preset conditions, and its force measurement accuracy was validated, with the error between the actual measured and theoretical values being no greater than 10%. Force curves were measured, and frictional adhesion coefficients were calculated from comparative experiments on the landing/takeoff of adherent animals (tree frogs and geckos) on this device. Analysis revealed that the adhesion force limits were significantly lower than previously reported values (0.2~0.4 times those estimated in previous research). This apparatus provides mechanical evidence for elucidating structural–functional relationships exhibited by animals during locomotion and can serve as an experimental platform for optimizing the locomotion of bioinspired robots on compliant substrates.
TriTrap: A Robotic Gripper Inspired by Insect Tarsal Chains
Authors: Winand Julian , Büscher Thies H. , Gorb Stanislav N.
Published: February 2024

Gripping, holding, and moving objects are among the main functional purposes of robots. Ever since automation first took hold in society, optimizing these functions has been of high priority, and a multitude of approaches has been taken to enable cheaper, more reliable, and more versatile gripping. Attempts are ongoing to reduce grippers’ weight, energy consumption, and production and maintenance costs while simultaneously improving their reliability, the range of eligible objects, working loads, and environmental independence. While the upper bounds of precision and flexibility have been pushed to an impressive level, the corresponding solutions are often dependent on support systems (e.g., sophisticated sensors and complex actuation machinery), advanced control paradigms (e.g., artificial intelligence and machine learning), and typically require more maintenance owed to their complexity, also increasing their cost. These factors make them unsuited for more modest applications, where moderate to semi-high performance is desired, but simplicity is required. In this paper, we attempt to highlight the potential of the tarsal chain principle on the example of a prototype biomimetic gripping device called the TriTrap gripper, inspired by the eponymous tarsal chain of insects. Insects possess a rigid exoskeleton that receives mobility due to several joints and internally attaching muscles. The tarsus (foot) itself does not contain any major intrinsic muscles but is moved by an extrinsically pulled tendon. Just like its biological counterpart, the TriTrap gripping device utilizes strongly underactuated digits that perform their function using morphological encoding and passive conformation, resulting in a gripper that is versatile, robust, and low cost. Its gripping performance was tested on a variety of everyday objects, each of which represented different size, weight, and shape categories. The TriTrap gripper was able to securely hold most of the tested objects in place while they were lifted, rotated, and transported without further optimization. These results show that the insect tarsus selected approach is viable and warrants further development, particularly in the direction of interface optimization. As such, the main goal of the TriTrap gripper, which was to showcase the tarsal chain principle as a viable approach to gripping in general, was achieved.
Stereotactic Electroencephalogram Recordings in Temporal Lobectomy Patients Demonstrates the Predictive Value of Interictal Cross-Frequency Correlations: A Retrospective Study
Authors: Sathe Anish Vinay , Alizadeh Mahdi , Johannan Emily , Raimondo Christian , Sperling Michael , Sharan Ashwini , Kogan Michael
Published: February 2024

Background: Positive correlations between low- and high-frequency spectra from stereotactic electroencephalogram (SEEG) recordings have been implicated in pathological brain activity interictally and have been used for ictal detection in both focal and network models. Objective: We evaluated SEEG signals in patients who ultimately underwent temporal lobectomy to evaluate their utility in seizure localization and prediction of seizure freedom post-resection. Methods: We retrospectively analyzed cross-frequency correlations between beta and high gamma (HG) interictal SEEG signals from 22 patients. We compared signals based on temporal versus extra-temporal locations, seizure-free (SF) versus non-seizure-free (NSF) outcomes, and mesial (M) versus mesial temporal-plus (M+) onset. Results: Positive cross-correlations were increased in temporal areas. NSF patients showed a higher proportion of positive electrodes in temporal areas. SF patients had a greater proportion of significant channels in mesial versus lateral temporal areas. HG/Beta correlations in mesial versus lateral temporal areas predicted seizure freedom better than ictal SEEG seizure onset localization to M or M+ locations. Conclusions: We present preliminary data that local HG/Beta correlations may predict epilepsy focus and surgical outcome and may have utility as adjunct methods to conventional SEEG analysis. Further studies are needed to determine strategies for prospective studies and clinical use.
Preventive Effect of a 7-Week App-Based Passive Psychoeducational Stress Management Program on Students
Authors: Weiss Elisabeth M. , Staggl Siegmund , Holzner Bernhard , Rumpold Gerhard , Dresen Verena , Canazei Markus
Published: February 2024

Passive psychoeducation is an easily accessible and cost-effective self-guided intervention that does not use elements of active psychotherapies or require homework. The present study aimed to investigate the acceptability and efficacy of a 7-week app-based passive psychoeducation stress management program to promote adaptive emotion regulation and coping skills in university students (i.e., 80% psychology students). Participants were tested via Lime-Survey® at pre- and post-test with the Depression Anxiety Stress Scale-21 (DASS-21), the Response Styles Questionnaire (RSQ), and the Emotion Regulation Questionnaire (ERQ). A stratified permutation block randomization by age, gender, and the DASS-21 stress subscale was performed. Each week, the psychoeducation group (n = 123) received different psychoeducation modules. At the end of each module, participants answered questions about their satisfaction with each module and adherence to psychoeducation. The control group (n = 130) received no intervention. The psychoeducation program led to a significant improvement in the adaptive emotion regulation strategy: “reappraisal” (p = 0.004) and a significant reduction in the dysfunctional coping style: “symptom-related rumination” (p = 0.01) but not to a significant reduction in depression, anxiety, and stress scores compared to the control group. Thus, the present study might demonstrate a preventive effect of an app-based passive psychoeducation program in students with low clinically relevant psychopathological symptoms.
Grit and Second Language Learning Engagement: The Mediating Role of Affect Balance
Authors: Wu Chenggang , Tian Xiaoyong , Jin Hui
Published: February 2024

The study of the relationship between key psychological attributes of learners and their engagement in second language (L2) learning helps to understand the critical personality mechanisms influencing language learning. The present study examined the L2 learning engagement from the perspectives of grit (i.e., consistent efforts and interests devoted to a long-term goal) and affect balance (a notion that takes into account both positive and negative emotions concurrently, assessing and evaluating which side holds more significance or influence). A cohort of English L2 learners (N = 394) participated in an online survey aimed at gauging their levels of grit, affect balance, and engagement in L2 learning. The results indicated that grit and affect balance were significantly correlated with behavioral engagement and affective engagement in L2 learning. However, among the two components of grit, namely consistency of interest, showed no significant relationship with L2 learning engagement, while perseverance of effort was significantly positively correlated with L2 learning engagement. Affect balance played a partially mediating and full mediating role between perseverance of effort and behavioral engagement as well as affective engagement respectively. These findings confirm the crucial role of perseverance of effort in second language learning and reveal the unique role of affect balance in their relationship.
Kano Model for Apartment-Unit Specialized Planning Guidelines to Prevent Infectious Diseases
Authors: Han Seung-Ju , Kim Eun-Jeong , Kim Mi-Kyung
Published: February 2024

Owing to the continued occurrence of infectious diseases, proactive prevention and management plans are required. This study aimed to develop design guidelines to effectively respond to infectious diseases based on the needs of apartment residents, which focused on a South Korean setting. The research method included a literature review to identify apartment planning concepts for preventing and managing infectious diseases, a survey of 300 participants using the Kano model, and an analysis of the quality attributes (QAs) of the survey results to prioritize design guidelines. After reviewing 20 studies, 65 items related to apartment-unit planning for infectious disease prevention, including 108 keywords, were identified. Using thematic analysis, the keywords converged into three planning concepts: hygiene, convenience, and comfort. Based on the literature review, 27 survey questions were derived, and a Kano model QA analysis was performed. As a result, 17 attractive QAs, two one-dimensional QAs, seven indifferent QAs, and one reverse QA were identified. Among these, 13 items that had a significant impact on residents’ satisfaction were classified as essential requirements, and the remaining 14 items were classified as recommended design guidelines. The results of this study provide insights into an evidence-based framework for complex building design guidelines to prevent the spread of infectious diseases.
Sustainable Structural Lightweight Concrete with Recycled Polyethylene Terephthalate Waste Aggregate
Authors: Resende Douglas Mol , de Carvalho José Maria Franco , Paiva Bárbara Oliveira , Gonçalves Gustavo dos Reis , Costa Lais Cristina Barbosa , Peixoto Ricardo André Fiorotti
Published: February 2024

Plastic is a widely consumed material with a high decomposition time, occupying significant space in landfills and dumps. Thus, strategies to reuse plastic waste are imperative for environmental benefit. Plastic waste is a promising eco-friendly building material for cement-based composites due to its reduced specific gravity and thermal conductivity. However, this waste reduces the composites’ mechanical strength. This work aims to produce and evaluate lightweight concretes made with only lightweight aggregates and mostly recycled plastic aggregates. Initially, an optimized dosage approach for lightweight concrete is presented. The mixture proportion of the lightweight concrete was based on the performance of mortars with the complete replacement of natural aggregate by recycled polyethylene terephthalate (PET) aggregates. The PET aggregates showed irregular shapes, impairing workability and providing lightweight concretes with around 18% water absorption and 21% void index. However, the concretes presented significantly low-unit weight, approximately 1200 kg/m3. This work presented a structural lightweight concrete (ACI 213-R) using only lightweight aggregates and mostly plastic waste aggregate, with a compressive strength of up to 17.6 MPa, a unit weight of 1282 kg/m3, and an efficiency factor of 12.3 MPa·cm3/g. The study shows that with an optimum dosage, reusing plastic waste in concrete is a viable alternative contributing to environmental sustainability.
From Design to Management: Exploring BIM’s Role across Project Lifecycles, Dimensions, Data, and Uses, with Emphasis on Facility Management
Authors: Altwassi Esraa J. , Aysu Emre , Ercoskun Kerem , Abu Raed Abeer
Published: February 2024

The importance of Building Information Modelling (BIM) in construction and facility operation is unquestionable, but there is a clear discrepancy between the data included in as-built BIM models and the expected use specified by customers. This disparity presents significant obstacles in properly using BIM for facility management and operational operations. The main goal of this research is to suggest inventive and pragmatic approaches that successfully address the discrepancy between the actual BIM model data, with a specific emphasis on COBie dataset, and the intended BIM applications outlined by stakeholders in the Employer’s Information Requirement (EIR) for facility management and operation. The study methodology is based on a comprehensive examination of current literature, demo case studies, as well as standards pertaining to BIM data, COBie.Type, and EIR requirements. The results of this study consist of a collection of standards, procedures, and suggested practices specifically designed to improve the utilization of as-built BIM model data for facility management and operation. These will closely correlate with the BIM applications stated by the client. Furthermore, the project seeks to enhance industry norms and practices, promoting enhanced cooperation and information sharing among stakeholders. This research has also investigated the efficiency of Solibri Model Checker (SMC) to validate the COBie type and component information provided by COBie.
CPX-351 Pharmacokinetics and Safety in Adults with Hematologic Malignancies and Renal Function Impairment: Phase 1 Trial
Authors: Solomon Scott R. , Powell Bayard L. , Koprivnikar Jamie , Lai Catherine , Male Heather , Michaelis Laura C. , Newell Laura F. , Sanford David , Jenkins Jack , Zelaya Amy , Coppola Sheryl , Faderl Stefan , Walter Roland B.
Published: February 2024

This open-label phase 1 study (clinicaltrials.gov, NCT03555955) assessed CPX-351 pharmacokinetics (PK) and safety in patients with hematologic malignancies with normal or impaired renal function. Patients were enrolled into three cohorts based on their creatinine clearance (CrCl): ≥90 mL/min (Cohort 1, normal renal function, n = 7), 30 to <59 mL/min (Cohort 2, moderate renal impairment, n = 8), or <30 mL/min (Cohort 3, severe renal impairment, n = 6). Patients received intravenous CPX-351 for initial induction; blood and urine samples were collected for PK analysis. The primary objective was to assess the PK parameters for cytarabine, daunorubicin, and their respective metabolites, arabinosyluracil (Ara-U) and daunorubicinol. Renal impairment did not significantly impact the cytarabine, daunorubicin, or daunorubicinol exposure, but it caused a slight increase in the Ara-U exposure. The CPX-351 side effect profile was similar in patients with impaired renal function compared to those with normal renal function. All the patients reported ≥1 treatment-emergent adverse event (TEAE), most commonly febrile neutropenia and nausea (57% each) and hyperglycemia (43%); no patients discontinued treatment due to TEAEs. These data suggest that CPX-351 dose adjustment is not required for patients with hematologic malignancies with moderate or severe renal impairment.
Super-Enhancer Dysregulation in Rhabdoid Tumor Cells Is Regulated by the SWI/SNF ATPase BRG1
Authors: Jones Cheyenne A. , Wang Jing , Evans James R. , Sisk Hannah R. , Womack Carl B. , Liu Qi , Tansey William P. , Weissmiller April M.
Published: February 2024

Mutations in the SWI/SNF chromatin remodeling complex occur in ~20% of cancers. In rhabdoid tumors defined by loss of the SWI/SNF subunit SMARCB1, dysregulation of enhancer-mediated gene expression is pivotal in driving oncogenesis. Enhancer dysregulation in this setting is tied to retention of the SWI/SNF ATPase BRG1—which becomes essential in the absence of SMARCB1—but precisely how BRG1 contributes to this process remains unknown. To characterize how BRG1 participates in chromatin remodeling and gene expression in SMARCB1-deficient cells, we performed a genome-wide characterization of the impact of BRG1 depletion in multiple rhabdoid tumor cell lines. We find that although BRG1-regulated open chromatin sites are distinct at the locus level, the biological characteristics of the loci are very similar, converging on a set of thematically related genes and pointing to the involvement of the AP-1 transcription factor. The open chromatin sites regulated by BRG1 colocalize with histone-marked enhancers and intriguingly include almost all super-enhancers, revealing that BRG1 plays a critical role in maintaining super-enhancer function in this setting. These studies can explain the essentiality of BRG1 to rhabdoid tumor cell identity and survival and implicate the involvement of AP-1 as a critical downstream effector of rhabdoid tumor cell transcriptional programs.
Unfolding the Complexity of Exosome–Cellular Interactions on Tumour Immunity and Their Clinical Prospects in Nasopharyngeal Carcinoma
Authors: Chak Paak-Ting , Kam Ngar-Woon , Choi Tsz-Ho , Dai Wei , Kwong Dora Lai-Wan
Published: February 2024

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy situated in the posterolateral nasopharynx. NPC poses grave concerns in Southeast Asia due to its late diagnosis. Together with resistance to standard treatment combining chemo- and radiotherapy, NPC presents high metastatic rates and common recurrence. Despite advancements in immune-checkpoint inhibitors (ICIs) and cytotoxic-T-lymphocytes (CTLs)-based cellular therapy, the exhaustive T cell profile and other signs of immunosuppression within the NPC tumour microenvironment (TME) remain as concerns to immunotherapy response. Exosomes, extracellular vesicles of 30–150 nm in diameter, are increasingly studied and linked to tumourigenesis in oncology. These bilipid-membrane-bound vesicles are packaged with a variety of signalling molecules, mediating cell–cell communications. Within the TME, exosomes can originate from tumour, immune, or stromal cells. Although there are studies on tumour-derived exosomes (TEX) in NPC and their effects on tumour processes like angiogenesis, metastasis, therapeutic resistance, there is a lack of research on their involvement in immune evasion. In this review, we aim to enhance the comprehension of how NPC TEX contribute to cellular immunosuppression. Furthermore, considering the detectability of TEX in bodily fluids, we will also discuss the potential development of TEX-related biomarkers for liquid biopsy in NPC as this could facilitate early diagnosis and prognostication of the disease.
Predictive Value of Magnetic Resonance Imaging in Risk Stratification and Molecular Classification of Endometrial Cancer
Authors: Bae Hanna , Rha Sung Eun , Kim Hokun , Kang Jun , Shin Yu Ri
Published: February 2024

This study evaluated the magnetic resonance imaging (MRI) findings of endometrial cancer (EC) patients and identified differences based on risk group and molecular classification. The study involved a total of 175 EC patients. The MRI data were retrospectively reviewed and compared based on the risk of recurrence. Additionally, the associations between imaging phenotypes and genomic signatures were assessed. The low-risk and non-low-risk groups (intermediate, high-intermediate, high, metastatic) showed significant differences in tumor diameter (p < 0.001), signal intensity and heterogeneity on diffusion-weighted imaging (DWI) (p = 0.003), deep myometrial invasion (involvement of more than 50% of the myometrium), cervical invasion (p < 0.001), extrauterine extension (p = 0.002), and lymphadenopathy (p = 0.003). Greater diffusion restriction and more heterogeneity on DWI were exhibited in the non-low-risk group than in the low-risk group. Deep myometrial invasion, cervical invasion, extrauterine extension, lymphadenopathy, recurrence, and stage discrepancy were more common in the non-low-risk group (p < 0.001). A significant difference in microsatellite stability status was observed in the heterogeneity of the contrast-enhanced T1-weighted images (p = 0.027). However, no significant differences were found in MRI parameters related to TP53 mutation. MRI features can be valuable predictors for differentiating risk groups in patients with EC. However, further investigations are needed to explore the imaging markers based on molecular classification.
C-Reactive Protein-to-Albumin Ratio to Predict Tolerability of S-1 as an Adjuvant Chemotherapy in Pancreatic Cancer
Authors: Funamizu Naotake , Sakamoto Akimasa , Hikida Takahiro , Ito Chihiro , Shine Mikiya , Nishi Yusuke , Uraoka Mio , Nagaoka Tomoyuki , Honjo Masahiko , Tamura Kei , Sakamoto Katsunori , Ogawa Kohei , Takada Yasutsugu
Published: February 2024

Adjuvant chemotherapy (AC) with S-1 after radical surgery for resectable pancreatic cancer (PC) has shown a significant survival advantage over surgery alone. Consequently, ensuring that patients receive a consistent, uninterrupted S-1 regimen is of paramount importance. This study aimed to investigate whether the C-reactive protein-to-albumin ratio (CAR) could predict S-1 AC completion in PC patients without dropout due to adverse events (AEs). We retrospectively enrolled 95 patients who underwent radical pancreatectomy and S-1 AC for PC between January 2010 and December 2022. A statistical analysis was conducted to explore the correlation of predictive markers with S-1 completion, defined as continuous oral administration for 6 months. Among the 95 enrolled patients, 66 (69.5%) completed S-1, and 29 (30.5%) failed. Receiver operating characteristic curve analysis revealed 0.05 as the optimal CAR threshold to predict S-1 completion. Univariate and multivariate analyses further validated that a CAR ≥ 0.05 was independently correlated with S-1 completion (p < 0.001 and p = 0.006, respectively). Furthermore, a significant association was established between a higher CAR at initiation of oral administration and acceptable recurrence-free and overall survival (p = 0.003 and p < 0.001, respectively). CAR ≥ 0.05 serves as a predictive marker for difficulty in completing S-1 treatment as AC for PC due to AEs.
Physiotherapy Interventions in Lung Cancer Patients: A Systematic Review
Authors: Valdivia-Martínez Manuel , Fernández-Gualda Miguel Ángel , Gallegos-García Elena , Postigo-Martin Paula , Fernández-González María , Ortiz-Comino Lucía
Published: February 2024

Background: Lung cancer is a very common disease and leads to a series of sequelae such as reduced lung capacity or reduced functional capacity in patients, which are associated not only with the disease itself, but also with medical treatment. Thus, physiotherapeutic interventions are needed to improve quality of life and reduce these symptoms. Objectives: To find out the effects of physiotherapy on functional capacity, lung capacity, dyspnea, pain, and quality of life in lung cancer patients. Methods: A systematic review was carried out in five databases. Randomized clinical trials published between 2019–2023 were selected, in which the physiotherapeutic treatment was physical exercise and/or respiratory physiotherapy. Results: Nine articles were included, in which the total sample consisted of 635 lung cancer patients. When combined, respiratory physiotherapy and physical exercise improved functional capacity and lung capacity (p < 0.05). Dyspnea also improved, but less significance was shown in the included studies. Conclusions: Multimodal physiotherapy interventions may offer benefits for some lung cancer patients, but the extent and nature of these benefits may vary depending on the intervention applied. Therefore, it would be of great interest to carry out further scientific research to support this conclusion.
Establishment of Different Intraoperative Monitoring and Mapping Techniques and Their Impact on Survival, Extent of Resection, and Clinical Outcome in Patients with High-Grade Gliomas—A Series of 631 Patients in 14 Years
Authors: Staub-Bartelt Franziska , Suresh Babu Marian Preetham , Szelényi Andrea , Rapp Marion , Sabel Michael
Published: February 2024

BACKGROUND: The resection of brain tumors can be critical concerning localization, but is a key point in treating gliomas. Intraoperative neuromonitoring (IONM), awake craniotomy, and mapping procedures have been incorporated over the years. Using these intraoperative techniques, the resection of eloquent-area tumors without increasing postoperative morbidity became possible. This study aims to analyze short-term and particularly long-term outcomes in patients diagnosed with high-grade glioma, who underwent surgical resection under various technical intraoperative settings over 14 years. METHODS: A total of 1010 patients with high-grade glioma that underwent resection between 2004 and 2018 under different monitoring or mapping procedures were screened; 631 were considered eligible for further analyses. We analyzed the type of surgery (resection vs. biopsy) and type of IONM or mapping procedures that were performed. Furthermore, the impact on short-term (The National Institute of Health Stroke Scale, NIHSS; Karnofsky Performance Scale, KPS) and long-term (progression-free survival, PFS; overall survival, OS) outcomes was analyzed. Additionally, the localization, extent of resection (EOR), residual tumor volume (RTV), IDH status, and adjuvant therapy were approached. RESULTS: In 481 patients, surgery, and in 150, biopsies were performed. The number of biopsies decreased significantly with the incorporation of awake surgeries with bipolar stimulation, IONM, and/or monopolar mapping (p < 0.001). PFS and OS were not significantly influenced by any intraoperative technical setting. EOR and RTV achieved under different operative techniques showed no statistical significance (p = 0.404 EOR, p = 0.186 RTV). CONCLUSION: Based on the present analysis using data from 14 years and more than 600 patients, we observed that through the implementation of various monitoring and mapping techniques, a significant decrease in biopsies and an increase in the resection of eloquent tumors was achieved. With that, the operability of eloquent tumors without a negative influence on neurological outcomes is suggested by our data. However, a statistical effect of monitoring and mapping procedures on long-term outcomes such as PFS and OS could not be shown.
Sarcopenic Obesity in Cervical Carcinoma: A Strong and Independent Prognostic Factor beyond the Conventional Predictors (ESTHER Study—AFRAID Project)
Authors: Medici Federica , Ferioli Martina , Cammelli Silvia , Forlani Ludovica , Laghi Viola , Ma Johnny , Cilla Savino , Buwenge Milly , Macchia Gabriella , Deodato Francesco , Vadalà Maria , Malizia Claudio , Tagliaferri Luca , Perrone Anna Myriam , De Iaco Pierandrea , Strigari Lidia , Bazzocchi Alberto , Rizzo Stefania , Arcelli Alessandra , Morganti Alessio Giuseppe
Published: February 2024

Locally advanced cervical cancer represents a significant treatment challenge. Body composition parameters such as body mass index, sarcopenia, and sarcopenic obesity, defined by sarcopenia and BMI ≥ 30 kg/m2, have been identified as potential prognostic factors, yet their overall impact remains underexplored. This study assessed the relationship between these anthropometric parameters alongside clinical prognostic factors on the prognosis of 173 cervical cancer patients. Survival outcomes in terms of local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were analyzed using Kaplan regression methods—Meier and Cox. Older age, lower hemoglobin levels, higher FIGO (International Federation of Gynecology and Obstetrics) stages, and lower total radiation doses were significantly associated with worse outcomes. Univariate analysis showed a significant correlation between BMI and the outcomes examined, revealing that normal-weight patients show higher survival rates, which was not confirmed by the multivariate analysis. Sarcopenia was not correlated with any of the outcomes considered, while sarcopenic obesity was identified as an independent negative predictor of DFS (HR: 5.289, 95% CI: 1.298–21.546, p = 0.020) and OS (HR: 2.645, 95% CI: 1.275–5.488, p = 0.009). This study highlights the potential of sarcopenic obesity as an independent predictor of clinical outcomes. These results support their inclusion in prognostic assessments and treatment planning for patients with advanced cervical cancer.
Achieving Textbook Outcomes after Laparoscopic Resection in Posterosuperior Segments of the Liver: The Impact of the Learning Curve
Authors: D’Silva Mizelle , Cho Jai-Young , Han Ho-Seong , Yoon Yoo-Seok , Lee Hae-Won , Lee Bo-Ram , Kang Mee-Young , Park Ye-Shong , Kim Jin-Ju
Published: February 2024

Achieving textbook outcomes (TOs) improves the short-term and long-term performance of a hospital. Our objective was to assess TOs in the laparoscopic liver resection (LLR) of tumors in the PS (posterosuperior) section of the liver and identify the impact of the learning curve. We conducted a retrospective cohort study analyzing patients who underwent LLR for lesions located in the PS segments. Patients were divided into a TO and no-TO group. TOs were defined as negative margins, no transfusion, no readmission, no major complications, no 30-day mortality, and a length of stay ≤ 50th percentile. Patients’ outcomes were assessed in two study periods before and after 2015. TOs were achieved in 47.6% (n = 117). In multivariable analysis, obesity (p = 0.001), shorter operation time (p < 0.001), less blood loss (p < 0.001), normal albumin (p = 0.003), and minor resection (p = 0.046) were significantly associated with achieving TOs. Although the 5-year recurrence-free survival rate (p = 0.096) was not significantly different, the 5-year overall survival rate was significantly greater in the TO group (p = 0.001). Body mass index > 25 kg/m2 (p = 0.020), age > 65 years (p = 0.049), and achievement of TOs (p = 0.024) were independently associated with survival. The proportion of patients who achieved a TO was higher after 2015 than before 2015 (52.3% vs. 36.1%; p = 0.022). TOs are important markers not only for assessing hospital and surgeon performance but also as predictors of overall survival. As the number of surgeons who achieve the learning curve increases, the number of patients with TOs will gradually increase with a subsequent improvement in overall survival.
Comparing Performances of Predictive Models of Toxicity after Radiotherapy for Breast Cancer Using Different Machine Learning Approaches
Authors: Ubeira-Gabellini Maria Giulia , Mori Martina , Palazzo Gabriele , Cicchetti Alessandro , Mangili Paola , Pavarini Maddalena , Rancati Tiziana , Fodor Andrei , del Vecchio Antonella , Di Muzio Nadia Gisella , Fiorino Claudio
Published: February 2024

Purpose. Different ML models were compared to predict toxicity in RT on a large cohort (n = 1314). Methods. The endpoint was RTOG G2/G3 acute toxicity, resulting in 204/1314 patients with the event. The dataset, including 25 clinical, anatomical, and dosimetric features, was split into 984 for training and 330 for internal tests. The dataset was standardized; features with a high p-value at univariate LR and with Spearman ρ>0.8 were excluded; synthesized data of the minority were generated to compensate for class imbalance. Twelve ML methods were considered. Model optimization and sequential backward selection were run to choose the best models with a parsimonious feature number. Finally, feature importance was derived for every model. Results. The model’s performance was compared on a training–test dataset over different metrics: the best performance model was LightGBM. Logistic regression with three variables (LR3) selected via bootstrapping showed performances similar to the best-performing models. The AUC of test data is slightly above 0.65 for the best models (highest value: 0.662 with LightGBM). Conclusions. No model performed the best for all metrics: more complex ML models had better performances; however, models with just three features showed performances comparable to the best models using many (n = 13–19) features.
Clinical Benefit from Docetaxel +/− Ramucirumab Is Not Associated with Mutation Status in Metastatic Non-Small-Cell Lung Cancer Patients Who Progressed on Platinum Doublets and Immunotherapy
Authors: Qin Kang , Wang Kaiwen , Li Shenduo , Hong Lingzhi , Padmakumar Priyadharshini , Waree Rinsurongkawong , Hubert Shawna M. , Le Xiuning , Vokes Natalie , Rai Kunal , Vaporciyan Ara , Gibbons Don L. , Heymach John V. , Lee J. Jack , Woodman Scott E. , Chung Caroline , Jaffray David A. , Altan Mehmet , Lou Yanyan , Zhang Jianjun
Published: February 2024

Docetaxel +/− ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/− ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/− ramucirumab n=381; platinum/taxane-based regimens n=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/− ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/− ramucirumab, the top mutated cancer genes included TP53 (n=167), KRAS (n=127), EGFR (n=65), STK11 (n=32), ERBB2 (HER2) (n=26), etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20–14.80 m versus 8.40 m, 95% Cl: 7.12–9.68 m, LogRank P=0.019) than docetaxel +/− ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/− ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/− ramucirumab in this patient population.
The Current Landscape of Prostate-Specific Membrane Antigen (PSMA) Imaging Biomarkers for Aggressive Prostate Cancer
Authors: Al Saffar Haidar , Chen David C. , Delgado Carlos , Ingvar Jacob , Hofman Michael S. , Lawrentschuk Nathan , Perera Marlon , Murphy Declan G. , Eapen Renu
Published: February 2024

The review examines the vital role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis, staging, and treatment of prostate cancer (PCa). It focuses on the superior diagnostic abilities of PSMA PET/CT for identifying both nodal and distant PCa, and its potential as a prognostic indicator for biochemical recurrence and overall survival. Additionally, we focused on the variability of PSMA’s expression and its impact on personalised treatment, particularly the use of [177Lu] Lu-PSMA-617 radioligand therapy. This review emphasises the essential role of PSMA PET/CT in enhancing treatment approaches, improving patient outcomes, and reducing unnecessary interventions, positioning it as a key element in personalised PCa management.
Characteristics of Early Pancreatic Cancer: Comparison between Stage 1A and Stage 1B Pancreatic Cancer in Multicenter Clinical Data Warehouse Study
Authors: Kim Hyo Suk , Choi Young Hoon , Lee Jae Sin , Jo Ik Hyun , Ko Sung Woo , Paik Kyu Hyun , Choi Hyun Ho , Lee Han Hee , Lim Yeon Soo , Paik Chang Nyol , Lee In Seok , Chang Jae Hyuck
Published: February 2024

Background: Little is known about the characteristics of early pancreatic cancer. We aimed to identify the characteristics, clues for early detection, and prognostic factors for early pancreatic cancer by analyzing a large number of patients with stage 1 pancreatic cancer. Methods: A clinical data warehouse that includes databases of all the medical records of eight academic institutions was used to select and analyze patients with pancreatic cancer that had been diagnosed from January 2010 to May 2023. Results: In total, 257 stage 1 pancreatic cancer patients were included. There were 134 men (52%), and the average age was 67.2 ± 9.9 years. Compared to patients with stage 1B pancreatic cancer (2–4 cm), patients with stage 1A pancreatic cancer (≤2 cm) had more tumors in the body and tail than in the head (p = 0.028), more new-onset diabetes and less old diabetes (p = 0.010), less jaundice (p = 0.020), more follow-up of IPMN (intraductal papillary mucinous neoplasm, p = 0.029), and more histories of acute pancreatitis (p = 0.013). The pathological findings showed that stage 1A pancreatic cancer involved more IPMNs (p < 0.001) and lower pancreatic intraepithelial neoplasia (p = 0.004). IPMN was present in all 13 pancreatic tumors that were smaller than 1 cm. In multivariate analysis, positive resection margin (odds ratio [OR] 1.536, p = 0.040), venous invasion (OR 1.710, p = 0.010), and perineural invasion (OR 1.968, p = 0.002) were found to be risk factors affecting disease-free survival, while old diabetes (odds ratio [OS] 1.981, p = 0.003) and perineural invasion (OR 2.270, p = 0.003) were found to be risk factors affecting overall survival. Conclusions: IPMN is closely associated with early pancreatic cancer and may provide an opportunity for early detection. The presence of perineural invasion was a crucial prognostic factor for both overall and disease-free survival in patients with stage 1 pancreatic cancer.
A Retrospective Analysis from Western Romania Comparing the Treatment and Survivability of p16-Positive versus p16-Negative Oropharyngeal Cancer
Authors: Chioreanu Alexandru , Balica Nicolae , Mot Cristian , Bugari Radmila , Morar Raluca , Baderca Flavia , Marti Teodora , Boru Casiana , Avram Cecilia , Dema Sorin , Vulcanescu Dan , Horhat Delia
Published: February 2024

Background: Oropharyngeal cancer is a global health concern due to its multifaceted nature. Recent molecular studies have linked p16 overexpression, associated with the human papillomavirus, to oropharyngeal cancer and its prognostic implications. Materials and Methods: This retrospective study in Western Romania examined 60 patients, categorizing them based on p16 biomarker status: 28 were p16 positive, and 32 were p16 negative. Statistical tests, including Fisher’s exact and chi2, were used for analysis. Results: Patients with p16-positive oropharyngeal cancer exhibited a better prognosis (3-year survival, p = 0.0477; midtreatment, p = 0.0349) and reported lower alcohol (p = 0.0046) and tobacco (p < 0.0001) use. Conclusions: The study highlights the importance of p16 testing in oropharyngeal carcinoma diagnosis. It suggests modifying treatment approaches based on p16 status and underscores the differing prognoses associated with p16-positive and p16-negative cases.