bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Reality-Based Interventions to Improve Balance in Patients with Traumatic Brain Injury: A Scoping Review
Authors: Hernan Gabriel , Ingale Neha , Somayaji Sujith , Veerubhotla Akhila
Published: April 2024

Introduction: Virtual reality (VR)-based interventions to improve balance and mobility are gaining increasing traction across patient populations. VR-based interventions are believed to be more enjoyable and engaging for patients with traumatic brain injury. This scoping review aims to summarize existing studies from the literature that used VR to improve balance and mobility and determine the gap in VR-based balance literature specific to individuals with traumatic brain injury. Methods: Two authors independently searched the literature using the search terms “Virtual Reality Traumatic Brain Injury Lower Limb”, “Virtual Reality Traumatic Brain Injury Balance”, and “Virtual Reality Traumatic Brain Injury Gait”. Results: A total of seventeen studies, specifically, three randomized controlled trials, one one-arm experimental study, two retrospective studies, two case studies, one feasibility/usability study, one cohort study, and seven diagnostic (validation) studies, met the inclusion criteria for this review. The methodological quality of the studies evaluated using the PEDro scale was fair. Discussion: Future studies should focus on large-scale clinical trials using validated technology to determine its effectiveness and dose–response characteristics. Additionally, standard assessment tools need to be selected and utilized across interventional studies aimed at improving balance and mobility to help compare results between studies.
Abstinence and Fear Experienced during This Period Produce Distinct Cortical and Hippocampal Adaptations in Alcohol-Dependent Rats
Authors: Steiner Noah L. , Purohit Dvijen C. , Tiefenthaler Casey M. , Mandyam Chitra D.
Published: April 2024

Previous studies demonstrate that ethanol dependence induced by repeating cycles of chronic intermittent ethanol vapor exposure (CIE) followed by protracted abstinence produces significant gray matter damage via myelin dysfunction in the rodent medial prefrontal cortex (mPFC) and alterations in neuronal excitability in the mPFC and the dentate gyrus (DG) of the hippocampus. Specifically, abstinence-induced neuroadaptations have been associated with persistent elevated relapse to drinking. The current study evaluated the effects of forced abstinence for 1 day (d), 7 d, 21 d, and 42 d following seven weeks of CIE on synaptic plasticity proteins in the mPFC and DG. Immunoblotting revealed reduced expression of CaMKII in the mPFC and enhanced expression of GABAA and CaMKII in the DG at the 21 d time point, and the expression of the ratio of GluN2A/2B subunits did not change at any of the time points studied. Furthermore, cognitive performance via Pavlovian trace fear conditioning (TFC) was evaluated in 3 d abstinent rats, as this time point is associated with negative affect. In addition, the expression of the ratio of GluN2A/2B subunits and a 3D structural analysis of neurons in the mPFC and DG were evaluated in 3 d abstinent rats. Behavioral analysis revealed faster acquisition of fear responses and reduced retrieval of fear memories in CIE rats compared to controls. TFC produced hyperplasticity of pyramidal neurons in the mPFC under control conditions and this effect was not evident or blunted in abstinent rats. Neurons in the DG were unaltered. TFC enhanced the GluN2A/2B ratio in the mPFC and reduced the ratio in the DG and was not altered by abstinence. These findings indicate that forced abstinence from CIE produces distinct and divergent alterations in plasticity proteins in the mPFC and DG. Fear learning-induced changes in structural plasticity and proteins contributing to it were more profound in the mPFC during forced abstinence.
The Relationship between Addictive Use of Short-Video Platforms and Marital Satisfaction in Older Chinese Couples: An Asymmetrical Dyadic Process
Authors: Deng Jinsong , Wang Menmen , Mu Weiqi , Li Siying , Zhu Ninghao , Luo Xiong , Yi Lan , Wu Yahan , Wang Kexin , Zhou Mingjie
Published: April 2024

Increasing evidence indicates that the addictive use of social media can have a detrimental effect on marital satisfaction, due mainly to the decrease in time and focus given to one’s spouse. However, the impact of social media use among older couples remains under-investigated, and the research that does exist relies on individual-level data that do not allow the exploration of the dynamics between the dyadic partners. Therefore, the present study focused on older adults’ use of short-video platforms, as these have been shown to be particularly addictive for older adults. A sample of 264 older couples was gathered (meanage = 68.02, SD = 8.68), and both spouses completed surveys reporting addictive use of short-video platforms, negative emotions, and marital satisfaction. Using an actor–partner interdependence model, we found an asymmetrical dyadic process in that the addictive use of short-video platforms by the wives was not only related to their own negative emotions, but also those of their spouse, as well as to decreased marital satisfaction. Meanwhile, addictive use by the husbands seemed to relate only to their own increased negative emotions, as well as to decreased marital satisfaction. Together, the findings from this study reveal dyadic dynamics with delineated pathways through which the addictive use of short-video platforms can damage older couples’ interactive processes and marital satisfaction.
Feasibility of Microbially Induced Carbonate Precipitation to Enhance the Internal Stability of Loess under Zn-Contaminated Seepage Conditions
Authors: He Pengli , Guo Jinjun , Zhang Shixu
Published: April 2024

Loess is widely distributed in Northwestern China and serves as the preferred engineering construction material for anti-fouling barriers. Heavy metal contamination in soil presents significant challenges to the engineering safety of vulnerable loess structures. Hence, there is an urgent need to investigate the impact of heavy metal ions on their percolation performance. In order to investigate the effectiveness of microbially induced carbonate precipitation (MICP) using Sporosarcina pasturii (CGMCC1.3687) bacteria in reducing internal seepage erosion, a saturated permeability test was conducted on reshaped loess under constant water head saturation conditions. The response of loess to deionized water (DW) and ZnCl2 solution seepages was analyzed by monitoring changes in cation concentration over time, measuring Zeta potential, and using scanning electron microscopy (SEM). The results indicate that the hydrolysis of Zn2+ creates an acidic environment, leading to the dissolution of carbonate minerals in the loess, which enhances its permeability. The adsorption of Zn2+ ions and the resulting diffusion double-layer (DDL) effect reduce the thickness of the diffusion layer and increase the number of free water channels. Additionally, the permeability of loess exposed to ZnCl2 solution seepage significantly increased by 554.5% compared to loess exposed to deionized water (DW) seepage. Following the seepage of ZnCl2 solutions, changes in micropore area ratio were observed, decreasing by 48.80%, while mesopore areas increased by 23.9%. MICP treatment helps reduce erosion and volume shrinkage in contaminated loess. Carbonate precipitation enhances the erosion resistance of contaminated loess by absorbing or coating fine particles and creating bridging connections with coarse particles. These research results offer new perspectives on enhancing the seepage properties of saturated loess in the presence of heavy metal erosion and the geochemical mechanisms involved.
Lessons Learned from Information Sources on Building Defect Studies
Authors: Berg Oppedal Line , Kvande Tore
Published: April 2024

Building defects are very prevalent and contribute significantly to a building’s economic value. There are numerous information sources on building defects that have significant potential for learning more about building defects. This study aimed to identify the information sources used in previous building defect studies and to identify the motivation for carrying out such studies. To fulfil this aim, a scoping study was carried out. The information sources identified included insurance companies, private databases, questionnaire surveys, lawsuits, building surveys, client complaint forms, and maintenance reports. This study found that insurance company and client complaint forms include the largest collection of real building defect cases, but such databases may lack detailed descriptions of the causes of the defects. The main purposes of the building defects studies identified here included design challenges, identification of defects, building maintenance management, quality management, systematization in data collection, providing an overview of typical defects, and classifying defects. Identification was found to be the most common purpose, indicating that the industry wants to learn more. This study identified research gaps in the climate perspective in relation to building defects. Most of the studies focused on the economical perspective, and none focused on the carbon footprint perspective. This study provides an overview of information sources, which can motivate stakeholders to collaborate in learning about the physical causes of building defects as well as about other key aspects such as fault, finances consequences, and procedural causes.
Comparison of Performance Analysis Results with Developed Site-Specific Response Spectra and Turkish Seismic Design Code: A Case Study from the SW Türkiye Region
Authors: Alpyürür Mehmet , Ulutaş Hakan
Published: April 2024

On 6 February 2023, the Kahramanmaraş earthquakes clearly showed that the elastic spectrum curves in TBEC-2018 are insufficient to represent earthquake behavior. In this study, the effect of using a site-specific spectrum curve instead of the elastic spectrum given in TBEC-2018 on the earthquake safety of a building is investigated. For this purpose, the provinces in southwest Anatolia, Türkiye, which is one of the most tectonically complex regions with frequent seismic events, were selected. In the first stage of the study, spectrum curves were obtained for earthquakes with return periods of 2475, 475, and 72 years for each of the provinces in this region. These spectrum curves were obtained using probabilistic seismic hazard studies that take into account the active faults of the provinces and earthquake activity in both historical and instrumental periods. In the second stage of the study, analytical models of a selected model RC building were created according to each province, and static pushover analyses of these building models were performed both according to the elastic spectrum given in TBEC-2018 and according to the spectrum curve created specifically for the province. The results of the analyses show that the change in the spectrum changes the target displacement level of the buildings, and as a result, the cross-sectional damage zone of the structural elements under the earthquake effect is changed. So much so that using the site-specific instead of the elastic spectrum given in TBEC-2018 changed the damage zone of 43% of the beams and 26.4% of the columns in the İzmir model. The change in the section damage zones changed the performance level of some floors of the models and the performance level of the building. The study revealed the importance of using the most realistic elastic spectrum curves in order to determine the earthquake performance of buildings that is as close as possible to their behavior in a possible earthquake.
Influences of the Decomposition Atmosphere and Heating Rate on the Pyrolysis Behaviors of Resin Sand
Authors: Xu Qingwei , Zhu Yaping , Xu Kaili , Li Bingjun , Su Nan
Published: April 2024

The pouring of sand casting is accompanied by severe heat conduction, and there is an urgent need to investigate the pyrolysis properties of foundry sand. The main purpose of this study was to investigate the pyrolysis behaviors of resin sand, including precoated sand (PCS), hot box sand (HBS), and warm box sand (WBS), at heating rates of 20 °C/min, 30 °C/min, and 40 °C/min in nitrogen and air atmospheres. The mass loss of the resin sand was monitored continuously with a simultaneous thermal analyzer, and the kinetic parameters of the resin sand were calculated based on the Coats–Redfern method and thermal data. The average mass loss of the resin sand during pyrolysis was 3.03%, which was much smaller than that of the other sands. The volatile release characteristic index of resin sand could not be calculated based on this concept. To solve this issue, the term Tstv/mloss was established, and its value was determined. With increasing heating rates from 20 °C/min to 30 °C/min and from 30 °C/min to 40 °C/min, the mass losses of the resin sand increased by 0.79% and 0.64%, respectively, and the volatile release characteristic indices of the resin sand increased by 3.8 × 10−10 and 1.06 × 10−9, respectively. In addition, the mass losses and volatile release characteristic indices of resin sand in an air atmosphere were greater than those in a nitrogen atmosphere. With increasing heating rate, the activation energy of the resin sand decreased in a nitrogen atmosphere. The findings concerning the thermal decomposition behaviors of resin sand provided a theoretical basis for the pouring step of the sand casting process.
Ground Deformation of Shield Tunneling through Composite Strata in Coastal Areas
Authors: Wu Xiong , Xu Jiangbo , Wang Shaowei , Sha Peng , Han Zemin , Chen Xinyu , Shu Sheng , Qiao Wei , Zeng Xianglong
Published: April 2024

In order to mitigate ground deformation during shield construction in both upper soft and lower hard strata of coastal areas, a numerical simulation was executed. This simulation assessed surface deformation under varying stratum ratios, grouting pressures, and earth bin pressures. The evaluation was primarily based on the amount of ground deformation, which revealed that hard rock strata offer superior settlement control compared to soft rock strata. The excavation of the right tunnel line increased disturbance to the left line at higher stratum ratios. Surface deformation demonstrated a linear correlation with earth pressure, with 130 kPa identified as the optimal point. Higher pressures resulted in extrusion deformation and ground uplift. Grouting pressure had a minimal impact on stratum deformation over time. The stratum ratio exerted the most significant influence on settlement, followed by earth pressure, with grouting pressure having the least impact. In the context of coastal tunnel construction, hard rock excavation is favored. Earth pressure must be balanced to prevent subsidence or uplift, while excessive grouting pressure does not significantly reduce subsidence. Grouting pressure should ensure the complete filling of voids.
Multilevel Social Determinants of Patient-Reported Outcomes in Young Survivors of Childhood Cancer
Authors: Sim Jin-ah , Horan Madeline R. , Choi Jaesung , Srivastava Deo Kumar , Armstrong Gregory T. , Ness Kirsten K. , Hudson Melissa M. , Huang I-Chan
Published: April 2024

In this study, the social determinants of patient-reported outcomes (PROs) in young survivors of childhood cancer aged <18 years are researched. This cross-sectional study investigated social determinants associated with poor PROs among young childhood cancer survivors. We included 293 dyads of survivors receiving treatment at St. Jude Children’s Research Hospital who were <18 years of age during follow-up from 2017 to 2018 and their primary caregivers. Social determinants included family factors (caregiver-reported PROs, family dynamics) and county-level deprivation (socioeconomic status, physical environment via the County Health Rankings & Roadmaps). PROMIS measures assessed survivors’ and caregivers’ PROs. General linear regression tested associations of social determinants with survivors’ PROs. We found that caregivers’ higher anxiety was significantly associated with survivors’ poorer depression, stress, fatigue, sleep issues, and reduced positive affect (p < 0.05); caregivers’ sleep disturbances were significantly associated with lower mobility in survivors (p < 0.05). Family conflicts were associated with survivors’ sleep problems (p < 0.05). Residing in socioeconomically deprived areas was significantly associated with survivors’ poorer sleep quality (p < 0.05), while higher physical environment deprivation was associated with survivors’ higher psychological stress and fatigue and lower positive affect and mobility (p < 0.05). Parental, family, and neighborhood factors are critical influences on young survivors’ quality of life and well-being and represent new intervention targets.
The Causes and Consequences of DNA Damage and Chromosomal Instability Induced by Human Papillomavirus
Authors: Jones Kathryn M. , Bryan Ava , McCunn Emily , Lantz Pate E. , Blalock Hunter , Ojeda Isabel C. , Mehta Kavi , Cosper Pippa F.
Published: April 2024

High-risk human papillomaviruses (HPVs) are the main cause of cervical, oropharyngeal, and anogenital cancers, which are all treated with definitive chemoradiation therapy when locally advanced. HPV proteins are known to exploit the host DNA damage response to enable viral replication and the epithelial differentiation protocol. This has far-reaching consequences for the host genome, as the DNA damage response is critical for the maintenance of genomic stability. HPV+ cells therefore have increased DNA damage, leading to widespread genomic instability, a hallmark of cancer, which can contribute to tumorigenesis. Following transformation, high-risk HPV oncoproteins induce chromosomal instability, or chromosome missegregation during mitosis, which is associated with a further increase in DNA damage, particularly due to micronuclei and double-strand break formation. Thus, HPV induces significant DNA damage and activation of the DNA damage response in multiple contexts, which likely affects radiation sensitivity and efficacy. Here, we review how HPV activates the DNA damage response, how it induces chromosome missegregation and micronuclei formation, and discuss how these factors may affect radiation response. Understanding how HPV affects the DNA damage response in the context of radiation therapy may help determine potential mechanisms to improve therapeutic response.
Outcomes and Adverse Events in Patients with Cancer after Diagnosis of Immunotherapy-Associated Diabetes Mellitus: A Retrospective Cohort Study
Authors: Duvalyan Eva , Brondfield Sam , Rushakoff Robert J. , Anderson Mark S. , Quandt Zoe
Published: April 2024

Immune checkpoint inhibitor (CPI)-induced diabetes mellitus (CPI-DM) is a rare immune-related adverse event (irAE). Patients and providers fear that continuing CPIs puts patients at risk for additional irAEs and thus may discontinue therapy. Currently, there are little data to inform this decision. Therefore, this study aims to elucidate whether discontinuing CPIs after diagnosis of CPI-DM impacts the development of future irAEs and cancer outcomes such as progression and death. Patients who developed CPI-DM during cancer treatment at UCSF from 1 July 2015 to 5 July 2023 were analyzed for cancer outcomes and irAE development. Fisher’s exact tests, Student t-tests, Kaplan–Meier methods, and Cox regression were used as appropriate. Of the 43 patients with CPI-DM, 20 (47%) resumed CPIs within 90 days of the irAE, 4 (9%) patients restarted after 90 days, and 19 (44%) patients never restarted. Subsequent irAEs were diagnosed in 9 of 24 (38%) who resumed CPIs and 3 of 19 (16%) who discontinued CPIs (p = 0.17). There was no significant difference in death (p = 0.74) or cancer progression (p = 0.55) between these two groups. While our single-institution study did not show worse cancer outcomes after discontinuing CPIs, many variables can impact outcomes, which our study was not adequately powered to evaluate. A nuanced approach is needed to decide whether to continue CPI treatment after a severe irAE like CPI-DM.
L-Glyceraldehyde Inhibits Neuroblastoma Cell Growth via a Multi-Modal Mechanism on Metabolism and Signaling
Authors: Forbes Martin , Kempa Richard , Mastrobuoni Guido , Rayman Liam , Pietzke Matthias , Bayram Safak , Arlt Birte , Spruessel Annika , Deubzer Hedwig E. , Kempa Stefan
Published: April 2024

Glyceraldehyde (GA) is a three-carbon monosaccharide that can be present in cells as a by-product of fructose metabolism. Bruno Mendel and Otto Warburg showed that the application of GA to cancer cells inhibits glycolysis and their growth. However, the molecular mechanism by which this occurred was not clarified. We describe a novel multi-modal mechanism by which the L-isomer of GA (L-GA) inhibits neuroblastoma cell growth. L-GA induces significant changes in the metabolic profile, promotes oxidative stress and hinders nucleotide biosynthesis. GC-MS and 13C-labeling was employed to measure the flow of carbon through glycolytic intermediates under L-GA treatment. It was found that L-GA is a potent inhibitor of glycolysis due to its proposed targeting of NAD(H)-dependent reactions. This results in growth inhibition, apoptosis and a redox crisis in neuroblastoma cells. It was confirmed that the redox mechanisms were modulated via L-GA by proteomic analysis. Analysis of nucleotide pools in L-GA-treated cells depicted a previously unreported observation, in which nucleotide biosynthesis is significantly inhibited. The inhibitory action of L-GA was partially relieved with the co-application of the antioxidant N-acetyl-cysteine. We present novel evidence for a simple sugar that inhibits cancer cell proliferation via dysregulating its fragile homeostatic environment.
Germline Genetic Mutations in Adult Patients with Sarcoma: Insight into the Middle East Genetic Landscape
Authors: Abu-Hijlih Ramiz , Sharaf Baha , Salah Samer , Bani Hani Hira , Alqaisieh Mohammad , Alzibdeh Abdulla , Ababneh Layan , Mahafdah Suleiman , Abdel-Razeq Hikmat
Published: April 2024

Data on germline mutations in soft tissue and bone sarcomas are scarce. We sought to identify the prevalence of germline mutations in adult sarcoma patients treated at a tertiary cancer center. Newly diagnosed patients were offered germline genetic testing via an 84-gene panel. The prevalence of pathogenic germline variants (PGVs) and their association with disease-, and patient- related factors are reported. A total of 87 patients were enrolled, the median age was 48 (19–78) years, and 47 (54%) were females. Gastrointestinal stromal tumors (n = 12, 13.8%), liposarcoma (n = 10, 11.5%), and Ewing sarcoma (n = 10, 11.5%) were the main subtypes. A total of 20 PGVs were detected in 18 (20.7%) patients. Variants of uncertain significance, in the absence of PGVs, were detected in 40 (45.9%) patients. Young age (p = 0.031), presence of a second primary cancer (p = 0.019), and female gender (p = 0.042) were correlated with the presence of PGVs. All identified PGVs have potential clinical actionability and cascade testing, and eight (44.44%) suggested eligibility for a targeted therapy. Almost one in five adult patients with soft tissue and bone sarcomas harbor pathogenic or likely pathogenic variants. Many of these variants are potentially actionable, and almost all have implications on cancer screening and family counselling. In this cohort from the Middle East, younger age, presence of a second primary tumor, and female gender were significantly associated with higher PGVs rates. Larger studies able to correlate treatment outcomes with genetic variants are highly needed.
Quantitative Optical Redox Imaging of Melanoma Xenografts with Different Metastatic Potentials
Authors: Peng April , Xu He N. , Moon Lily , Zhang Paul , Li Lin Z.
Published: April 2024

To develop imaging biomarkers for tumors aggressiveness, our previous optical redox imaging (ORI) studies of the reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp, containing flavin adenine dinucleotide, i.e., FAD) in tumor xenografts of human melanoma associated the high optical redox ratio (ORR = Fp/(Fp + NADH)) and its heterogeneity to the high invasive/metastatic potential, without having reported quantitative results for NADH and Fp. Here, we implemented a calibration procedure to facilitate imaging the nominal concentrations of tissue NADH and Fp in the mouse xenografts of two human melanoma lines, an indolent less metastatic A375P and a more metastatic C8161. Images of the redox indices (NADH, Fp, ORR) revealed the existence of more oxidized areas (OAs) and more reduced areas (RAs) within individual tumors. ORR was found to be higher and NADH lower in C8161 compared to that of A375P xenografts, both globally for the whole tumors and locally in OAs. The ORR in the OA can differentiate xenografts with a higher statistical significance than the global averaged ORR. H&E staining of the tumors indicated that the redox differences we identified were more likely due to intrinsically different cell metabolism, rather than variations in cell density.
Joint-Sparing Resection around the Knee for Osteosarcoma: Long-Term Outcomes of Biologic Reconstruction with Vascularized Fibula Graft Combined with Massive Allograft
Authors: Scanferla Roberto , Scolari Federico , Muratori Francesco , Tamburini Angela , Delcroix Luca , Scoccianti Guido , Beltrami Giovanni , Innocenti Marco , Campanacci Domenico Andrea
Published: April 2024

(1) Background: We aim to address the following questions. What was the complication rate of vascularized fibula graft (VFG) combined with massive allograft in patients treated with joint-sparing resection around the knee for a high-grade osteosarcoma? What was the long-term survivorship of VFG free from revision and graft removal? What were the functional results as assessed by the Musculoskeletal Tumor Society (MSTS) score? (2) Methods: 39 patients treated in our unit for osteosarcoma around the knee with intercalary resection and reconstruction with VFG combined with massive allograft were included; 26 patients underwent intercalary tibial resection, while 13 underwent intercalary femoral resection. (3) Results: Mean Follow-Up was 205 months (28 to 424). Complications that required surgery were assessed in requiring surgical revision in 19 patients (49%) after a mean of 31 months (0 to 107), while VFG removal was necessary in three patients (8%). The revision-free survival of the reconstructions was 59% at 5 years and 50% at 10 to 30 years. The overall survival of the reconstructions was 95% at 5 to 15 years and 89% at 20 to 30 years. The mean MSTS score was 29.3 (23 to 30). (4) Conclusions: VFG represents an effective reconstructive option after joint-sparing intercalary resection around the knee for osteosarcoma.
Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project)
Authors: Serradilla-Martín Mario , Villodre Celia , Falgueras-Verdaguer Laia , Zambudio-Carroll Natalia , Castell-Gómez José T. , Blas-Laina Juan L. , Borrego-Estella Vicente , Domingo-del-Pozo Carlos , García-Plaza Gabriel , González-Rodríguez Francisco J. , Montalvá-Orón Eva M. , Moya-Herraiz Ángel , Paterna-López Sandra , Suárez-Muñoz Miguel A. , Alkorta-Zuloaga Maialen , Blanco-Fernández Gerardo , Dabán-Collado Enrique , Gómez-Bravo Miguel A. , Miota-de-Llamas José I. , Rotellar Fernando , Sánchez-Pérez Belinda , Sánchez-Cabús Santiago , Pacheco-Sánchez David , Rodríguez-Sanjuan Juan C. , Varona-Bosque María A. , Carrión-Álvarez Lucía , de la Serna-Esteban Sofía , Dopazo Cristina , Martín-Pérez Elena , Martínez-Cecilia David , Castro-Santiago María J. , Dorcaratto Dimitri , Gutiérrez-Díaz Marta L. , Asencio-Pascual José M. , Burdío-Pinilla Fernando , Carracedo-Iglesias Roberto , Escartín-Arias Alfredo , Ielpo Benedetto , Rodríguez-Laiz Gonzalo , Valdivieso-López Andrés , De-Vicente-López Emilio , Alonso-Orduña Vicente , Ramia José M.
Published: April 2024

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.
Internet Access and Use by Patients with Gynecologic Malignancies: A Cross-Sectional Study
Authors: Bach Frederik , Engelhardt David , Mallmann Christoph A. , Tamir Sina , Schröder Lars , Domröse Christian M. , Mallmann Michael R.
Published: April 2024

The influence of digitalization on information-seeking, decision-making properties of patients, therapy monitoring, and patient–physician interactions has and will change the global health sector tremendously. With this study, we add knowledge on the degree of digitalization, digital device availability, the use and availability of home and mobile internet access, and the willingness to use novel forms of patient–physician interactions in a group of gynecologic cancer patients. From July 2017 to March 2022, 150 women with a diagnosis of gynecologic malignancy at the University Hospital of Cologne participated in this questionnaire-based cohort study. Any one of three potential internet access devices (stationary computer, smartphone, or tablet) is owned by 94% of patients and the only patient intrinsic factor that is significantly associated with the property of any one of these internet access devices is age. The Internet is used daily or several times per week to assess information on their disease by 92.8%, 90.1% use the Internet for communicational purposes and 71.9% and 93.6% are willing to communicate with their treating physicians via E-Mail or even novel forms of communication, respectively. In conclusion, the predominant majority of gynecologic cancer patients can be reached by modern internet-based E-Health technologies.
Advances in Molecular Understanding of Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis: Towards Precision Medicine
Authors: Tashkandi Hammad , Younes Ismail Elbaz
Published: April 2024

Myeloproliferative neoplasms (MPNs), including Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF), are characterized by the clonal proliferation of hematopoietic stem cells leading to an overproduction of hematopoietic cells. The last two decades have seen significant advances in our understanding of the molecular pathogenesis of these diseases, with the discovery of key mutations in the JAK2, CALR, and MPL genes being pivotal. This review provides a comprehensive update on the molecular landscape of PV, ET, and PMF, highlighting the diagnostic, prognostic, and therapeutic implications of these genetic findings. We delve into the challenges of diagnosing and treating patients with prognostic mutations, clonal evolution, and the impact of emerging technologies like next-generation sequencing and single-cell genomics on the field. The future of MPN management lies in leveraging these molecular insights to develop personalized treatment strategies, aiming for precision medicine that optimizes outcomes for patients. This article synthesizes current knowledge on molecular diagnostics in MPNs, underscoring the critical role of genetic profiling in enhancing patient care and pointing towards future research directions that promise to further refine our approach to these complex disorders.
Retreatment with Immune Checkpoint Inhibitors in the New Scenario of Immunotherapy in Non-Small Cell Lung Cancer
Authors: Rossi Sabrina , Masini Silvia , Finocchiaro Giovanna , Lorenzi Elena , Toschi Luca , Santoro Armando
Published: April 2024

The advent of immunotherapy has transformed the treatment paradigm for metastatic non-small cell lung cancer (NSCLC). In the past few years, several studies have investigated the potential role of immune checkpoint inhibitors (ICIs) in resectable and unresectable locally advanced disease, achieving remarkable results that led to their approval in clinical practice. However, there is limited evidence on immunotherapy rechallenge after recurrence, with the majority of available knowledge coming from retrospective studies which involve heavily pretreated patients with advanced NSCLC. The recent introduction in the curative setting and the potential regulatory restrictions raise questions about the optimal choice of first-line and subsequent therapies for patients with systemic relapse. The role of immunotherapy readministration in this new scenario needs to be clarified, as well as the identification of patients for whom it is more appropriate, including clinical characteristics, duration of response, switching to other ICIs, reasons for discontinuation and immune-related toxicity. Here, we review literature on rechallenge with immunotherapy, including efficacy, safety profile and potential predictive factors of response.
Assessing the Predictive Accuracy of EORTC, CUETO and EAU Risk Stratification Models for High-Grade Recurrence and Progression after Bacillus Calmette–Guérin Therapy in Non-Muscle-Invasive Bladder Cancer
Authors: Ślusarczyk Aleksander , Garbas Karolina , Pustuła Patryk , Zapała Łukasz , Radziszewski Piotr
Published: April 2024

The currently available EORTC, CUETO and EAU2021 risk stratifications were originally developed to predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). However, they have not been validated to differentiate between high-grade (HG) and low-grade (LG) recurrence-free survival (RFS), which are distinct events with specific implications. We aimed to evaluate the accuracy of available risk models and identify additional risk factors for HG RFS and PFS among NMIBC patients treated with Bacillus Calmette–Guérin (BCG). We retrospectively included 171 patients who underwent transurethral resection of the bladder tumor (TURBT), of whom 73 patients (42.7%) experienced recurrence and 29 (17%) developed progression. Initially, there were 21 low-grade and 52 high-grade recurrences. EORTC2006, EORTC2016 and CUETO recurrence scoring systems lacked accuracy in the prediction of HG RFS (C-index 0.63/0.55/0.59, respectively). EAU2021 risk stratification, EORTC2006, EORTC2016, and CUETO progression scoring systems demonstrated low to moderate accuracy (C-index 0.59/0.68/0.65/0.65) in the prediction of PFS. In the multivariable analysis, T1HG at repeat TURBT (HR = 3.17 p < 0.01), tumor multiplicity (HR = 2.07 p < 0.05), previous history of HG NMIBC (HR = 2.37 p = 0.06) and EORTC2006 progression risk score (HR = 1.1 p < 0.01) were independent predictors for HG RFS. To conclude, available risk models lack accuracy in predicting HG RFS and PFS in -NMIBC patients treated with BCG.
Digital Pathology for Better Clinical Practice
Authors: Hijazi Assia , Bifulco Carlo , Baldin Pamela , Galon Jérôme
Published: April 2024

(1) Background: Digital pathology (DP) is transforming the landscape of clinical practice, offering a revolutionary approach to traditional pathology analysis and diagnosis. (2) Methods: This innovative technology involves the digitization of traditional glass slides which enables pathologists to access, analyze, and share high-resolution whole-slide images (WSI) of tissue specimens in a digital format. By integrating cutting-edge imaging technology with advanced software, DP promises to enhance clinical practice in numerous ways. DP not only improves quality assurance and standardization but also allows remote collaboration among experts for a more accurate diagnosis. Artificial intelligence (AI) in pathology significantly improves cancer diagnosis, classification, and prognosis by automating various tasks. It also enhances the spatial analysis of tumor microenvironment (TME) and enables the discovery of new biomarkers, advancing their translation for therapeutic applications. (3) Results: The AI-driven immune assays, Immunoscore (IS) and Immunoscore-Immune Checkpoint (IS-IC), have emerged as powerful tools for improving cancer diagnosis, prognosis, and treatment selection by assessing the tumor immune contexture in cancer patients. Digital IS quantitative assessment performed on hematoxylin–eosin (H&E) and CD3+/CD8+ stained slides from colon cancer patients has proven to be more reproducible, concordant, and reliable than expert pathologists’ evaluation of immune response. Outperforming traditional staging systems, IS demonstrated robust potential to enhance treatment efficiency in clinical practice, ultimately advancing cancer patient care. Certainly, addressing the challenges DP has encountered is essential to ensure its successful integration into clinical guidelines and its implementation into clinical use. (4) Conclusion: The ongoing progress in DP holds the potential to revolutionize pathology practices, emphasizing the need to incorporate powerful AI technologies, including IS, into clinical settings to enhance personalized cancer therapy.
Association of miR-146a-5p and miR-21-5p with Prognostic Features in Melanomas
Authors: Naddeo Maria , Broseghini Elisabetta , Venturi Federico , Vaccari Sabina , Corti Barbara , Lambertini Martina , Ricci Costantino , Fontana Beatrice , Durante Giorgio , Pariali Milena , Scotti Biagio , Milani Giulia , Campione Elena , Ferracin Manuela , Dika Emi
Published: April 2024

Background: Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers. Methods: We quantified the expression of miR-146a-5p and miR-21-5p in 170 formalin-fixed paraffin embedded (FFPE) samples of CM, namely 116 superficial spreading melanoma (SSM), 26 nodular melanoma (NM), and 28 lentigo maligna melanoma (LMM). We correlated miRNA expression with specific histopathologic features including Breslow thickness (BT), histological subtype, ulceration and regression status, and mitotic index. Results: miR-146a-5p and miR-21-5p were significantly higher in NM compared to SSM and LMM. The positive correlation between miR-146a-5p and miR-21-5p expression and BT was confirmed for both miRNAs in SSM. Considering the ulceration status, we assessed that individual miR-21-5p expression was significantly higher in ulcerated CMs. The increased combined expression of the two miRNAs was strongly associated with ulceration (p = 0.0093) and higher mitotic rate (≥1/mm2) (p = 0.0005). We demonstrated that the combination of two-miRNA expression and prognostic features (BT and ulceration) can better differentiate cutaneous melanoma prognostic groups, considering overall survival and time-to-relapse clinical outcomes. Specifically, miRNA expression can further stratify prognostic groups among patients with BT ≥ 0.8 mm but without ulceration. Our findings provide further insights into the characterization of CM with specific prognostic features. The graphical abstract was created with BioRender.com.
A Simple Frailty Score Predicts Survival and Early Mortality in Systemic AL Amyloidosis
Authors: Ríos-Tamayo Rafael , Lecumberri Ramón , Cibeira María Teresa , González-Calle Verónica , Alonso Rafael , Domingo-González Amalia , Landete Elena , Encinas Cristina , Iñigo Belén , Blanchard María-Jesús , Alejo Elena , Krsnik Isabel , Gómez-Bueno Manuel , Garcia-Pavia Pablo , Segovia-Cubero Javier , Rosiñol Laura , Lahuerta Juan-José , Martínez-López Joaquín , Bladé Joan
Published: April 2024

Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality based on three frailty-associated variables: age, ECOG performance status (<2 vs. ≥2) and NT-proBNP (<8500 vs. ≥8500 ng/L). Four-hundred and sixteen consecutive newly diagnosed patients diagnosed at ten sites from the Spanish Myeloma Group were eligible for the study. The score was developed in a derivation cohort from a referral center, and it was externally validated in a multicenter cohort. Multivariate analysis showed that the three variables were independent predictors of survival. The score was able to discriminate four groups of patients in terms of overall survival and early mortality in both cohorts. Comorbidity was also analyzed with the Charlson comorbidity index, but it did not reach statistical significance in the model. A nomogram was created to easily estimate the mortality risk of each patient at each time point. This score is a simple, robust, and efficient approach to dynamically assess frailty-dependent mortality both at diagnosis and throughout follow-up. The optimal treatment for frail AL amyloidosis patients remains to be determined but we suggest that the estimation of frailty-associated risk could complement current staging systems, adding value in clinical decision-making in this complex scenario.
Update in the Treatment of Pleural Tumors: Robotic Surgery Combined with Hyperthermic Intrathoracic Chemotherapy
Authors: Romano Gaetano , Zirafa Carmelina Cristina , Ceccarelli Ilaria , Elia Gianmarco , Davini Federico , Melfi Franca
Published: April 2024

(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains part of the complex mosaic that is the multimodal approach for advanced stage thymoma and pleural malignancies. However, robotic pleurectomy/removal of pleural lesions in combination with intrathoracic chemotherapy is not currently being investigated. The aim of this study is to evaluate the safety of robotic pleurectomy/removal of relapses and HITHOC in patients with pleural recurrence of thymoma or MPM. (2) Methods: The data of nine consecutive patients affected by thymoma relapses or MPM who underwent robotic surgery in combination with HITHOC from February 2017 to November 2022 were collected and analyzed. Surgery performed prior to intrathoracic infusion of high-temperature chemotherapy consisted of removal of recurrences (three patients) or pleurectomy (six patients). All surgeries were performed with a four-port, fully robotic technique. (3) Results: No intraoperative complications occurred. No renal complications related to infusion were recorded. One patient, who underwent pleurectomy for MPM, had a grade II Clavien–Dindo postoperative complication. Oncological follow-up showed results in line with the literature. (4) Conclusions: With the limitation of the small number of patients, robotic surgery in combination with HITHOC seems to be safe in patients with pleural relapses of thymoma and early-stage MPM.
The Association between Blood Test Trends and Undiagnosed Cancer: A Systematic Review and Critical Appraisal
Authors: Virdee Pradeep S. , Collins Kiana K. , Friedemann Smith Claire , Yang Xin , Zhu Sufen , Roberts Sophie E. , Roberts Nia , Oke Jason L. , Bankhead Clare , Perera Rafael , Hobbs FD Richard , Nicholson Brian D.
Published: April 2024

Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient’s individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence.
Genomic Characterization of Partial Tandem Duplication Involving the KMT2A Gene in Adult Acute Myeloid Leukemia
Authors: Seto Andrew , Downs Gregory , King Olivia , Salehi-Rad Shabnam , Baptista Ana , Chin Kayu , Grenier Sylvie , Nwachukwu Bevoline , Tierens Anne , Minden Mark D. , Smith Adam C. , Capo-Chichi José-Mario
Published: April 2024

Background: Gene rearrangements affecting KMT2A are frequent in acute myeloid leukemia (AML) and are often associated with a poor prognosis. KMT2A gene fusions are often detected by chromosome banding analysis and confirmed by fluorescence in situ hybridization. However, small intragenic insertions, termed KMT2A partial tandem duplication (KMT2A-PTD), are particularly challenging to detect using standard molecular and cytogenetic approaches. Methods: We have validated the use of a custom hybrid-capture-based next-generation sequencing (NGS) panel for comprehensive profiling of AML patients seen at our institution. This NGS panel targets the entire consensus coding DNA sequence of KMT2A. To deduce the presence of a KMT2A-PTD, we used the relative ratio of KMT2A exons coverage. We sought to corroborate the KMT2A-PTD NGS results using (1) multiplex-ligation probe amplification (MLPA) and (2) optical genome mapping (OGM). Results: We analyzed 932 AML cases and identified 41 individuals harboring a KMT2A-PTD. MLPA, NGS, and OGM confirmed the presence of a KMT2A-PTD in 22 of the cases analyzed where orthogonal testing was possible. The two false-positive KMT2A-PTD calls by NGS could be explained by the presence of cryptic structural variants impacting KMT2A and interfering with KMT2A-PTD analysis. OGM revealed the nature of these previously undetected gene rearrangements in KMT2A, while MLPA yielded inconclusive results. MLPA analysis for KMT2A-PTD is limited to exon 4, whereas NGS and OGM resolved KMT2A-PTD sizes and copy number levels. Conclusions: KMT2A-PTDs are complex gene rearrangements that cannot be fully ascertained using a single genomic platform. MLPA, NGS panels, and OGM are complementary technologies applied in standard-of-care testing for AML patients. MLPA and NGS panels are designed for targeted copy number analysis; however, our results showed that integration of concurrent genomic alterations is needed for accurate KMT2A-PTD identification. Unbalanced chromosomal rearrangements overlapping with KMT2A can interfere with the diagnostic sensitivity and specificity of copy-number-based KMT2A-PTD detection methodologies.