bluuebunny/crossref_metadata_2025 huggingface dataset:
Social behaviors as welfare indicators in teleost fish
Authors: Cavallino Luciano , Rincón Laura , Scaia María Florencia
Published: April 2023

Animal welfare is a key issue not only for aquaculture industry and food production, but also for daily husbandry practices in research topics related to physiology in wild and farmed animals. In this context, teleost fish constitute interesting models to assess alternative welfare indicators because of their wide diversity in reproductive and social structures. Any framework for assessing teleost fish welfare needs to account for the physiological mechanisms involved in each species as a first step. A comprehensive approach should also take into account how these physiological and behavioral parameters can be altered by environmental enrichment considering the specific requirements in each case and identifying intrinsic biological characteristics of individual species. This review will show how cortisol and sex steroids regulate social behavior in teleost fish, and how different aspects of social behavior can be employed as welfare indicators according to specific characteristics in each case. This article will consider evidence in teleost fish, including cichlids, characids and cyprinids with different reproductive strategies and social structures (e.g., territorial social hierarchies or shoaling behavior). Neotropical species will be particularly emphasized. The main laboratory-based animal welfare indicators are cortisol, a classical stress hormone, together with sex steroids. Considering that the endocrine landscape is intrinsically related to social behavior, reproductive and agonistic behavioral traits such as aggression, anxiety and courtship are key elements to assess welfare under housing and culture conditions. This review highlights the importance of assessing physiological mechanisms and identifying behavioral characteristics in teleost fish, especially in Neotropical species, as a baseline to understand which environmental enrichment can improve animal welfare in each individual species.
The characteristics of head and neck squamous cell cancer in young adults: A retrospective single-center study
Authors: Révész Mónika , Oberna Ferenc , Slezák András , Ferenczi Örs , Kenessey István , Takácsi-Nagy Zoltán
Published: April 2023

We aimed to characterize clinical and prognostical factors of primary head and neck squamous cell carcinoma (HNSCC) in 85 young patients (≤39 years, median age: 37 years; between 2000–2018) in comparison with 140 institutional general HNSCC patients (median age: 61.5 years). The patient’s medical records were collected from the institutional database. The prevalence of smoking and alcohol consumption (65.8% and 48.1%) in the young group exceeded the regional population average but was below the institutional (86.4% and 55%) general HNSCC patient population. Primary tumor sites in the group of young patients were as follows: oral cavity (56.4%), oropharynx (17.6%), hypopharynx (11.7%), and larynx (14.1%). Cumulative five-year overall survival was 44.2% in the young group, but significantly better with early T (T1-2 vs. T3-4: 52.6% vs. 26.7%; p = 0.0058) and N0 status (N0 vs. N+: 65.2% vs. 32.3%; p = 0.0013). Young age, abstinence, earlier stage and laryngeal tumor site might predict a better prognosis. The age distribution and the high prevalence of traditional risk factors among the young patients as well as the predominance of oral cavity tumor localization suggest that the early onset of tumor development could be originated from the premature failure of the intrinsic protective mechanisms.
A Prospective Cohort Study Investigating the Impact of Neutering Bitches Prepubertally or Post-Pubertally on Physical Development
Authors: Moxon Rachel , Freeman Sarah L. , Payne Richard , Godfrey-Hunt Jasmine , Corr Sandra , England Gary C. W.
Published: April 2023

No previous large prospective cohort studies have been identified that have investigated the impact of the surgical neutering of bitches before or after known puberty on their growth and physical development. This study was designed to examine the data on physical development, vulval size, and conformation for bitches neutered by ovariohysterectomy before puberty (PPN, n = 155) or after puberty (control, n = 151) using a prospective cohort study design. Data were gathered at six- and 17-months of age using bespoke physical assessment forms and digital images of the vulva. PPN bitches had greater changes in height measurements (mean difference = 2.039, SEM = 0.334, 91% CI = 1.471 to 2.608, p < 0.001) and smaller changes in the measurements of vulval length (mean difference = −0.377, SEM = 0.079, 91% CI = −0.511 to −0.243, p < 0.001) and width (mean difference = −0.221, SEM = 0.063, 91% CI = −0.328 to −0.113, p < 0.001) between six- and 17-months of age than for the control bitches. Although not significant, the PPN bitches were taller (mean 58.5 vs. 56.6 cm) and heavier (mean 28.3 vs. 27.3 kg) with smaller vulval size measurements (mean vulval length 2.8 vs. 3.2 cm, mean vulval width 1.7 vs. 2.1 cm) at 17-months of age. At 17-months of age, significantly more PPN bitches had vulvas that appeared juvenile (Yates’ Chi-square = 14.834, D.F. = 1, p < 0.001) and recessed (Yates’ Chi-square = 7.792, D.F. = 1, p = 0.005) at the physical assessment, and significantly more PPN bitches had vulvas that appeared ‘recessed/inverted’ on the examination of digital images (Chi-square = 9.902, D.F. = 1, p = 0.002). The results from this study suggest no contraindications to prepubertal ovariohysterectomy for large breed bitches. However, any longer-term health implications of these differences in physical development need to be investigated and better understood prior to recommendations being made.
Population Genetic Study on the European Flounder (Platichthys flesus) from the Southern Baltic Sea Using SNPs and Microsatellite Markers
Authors: Kuciński Marcin , Jakubowska-Lehrmann Magdalena , Góra Agnieszka , Mirny Zuzanna , Nadolna-Ałtyn Katarzyna , Szlinder-Richert Joanna , Ocalewicz Konrad
Published: April 2023

The European flounder (Platichthys flesus), which is closely related to the recently discovered Baltic flounder (Platichthys solemdali), is currently the third most commercially fished species in the Baltic Sea. According to the available data from the Polish Fisheries Monitoring Center and fishermen’s observations, the body condition indices of the species in the Baltic Sea have declined in recent years. The aim of the present study was to obtain information on the current patterns of genetic variability and the population structure of the European flounder and to verify whether the Baltic flounder is present in the southern Baltic Sea. Moreover, we aimed to verify whether the observed decline in the body condition indices of the species in the Baltic Sea might be associated with adaptive alterations in its gene pool due to increased fishing pressure. For this purpose, 190 fish were collected from four locations along the central coastline of Poland, i.e., Mechelinki, Władysławowo, the Vistula Lagoon in 2018, and the Słupsk Bank in 2020. The fish were morphologically analyzed and then genetically screened by the application of nineteen microsatellite DNA and two diagnostic SNP markers. The examined European flounder specimens displayed a high level of genetic diversity (PIC = 0.832–0.903, I = 2.579–2.768). A lack of significant genetic differentiation (Fst = 0.004, p > 0.05) was observed in all the examined fish, indicating that the European flounder in the sampled area constitutes a single genetic cluster. A significant deficiency in heterozygotes (Fis = 0.093, p < 0.05) and overall deviations from Hardy–Weinberg expectations (H-WE) were only detected in fish sampled from the Słupsk Bank. The estimated effective population size (Ne) among the sampled fish groups varied from 712 (Słupsk Bank) to 10,115 (Władysławowo and Mechelinki). However, the recorded values of the Garza–Williamson indicator (M = 0.574–0.600) and the lack of significant (p > 0.05) differences in Heq > He under the SMM model did not support the species’ population size changes in the past. The applied SNP markers did not detect the presence of the Baltic flounder among the fish sampled from the studied area. The analysis of an association between biological traits and patterns of genetic diversity did not detect any signs of directional selection or density-dependent adaptive changes in the gene pool of the examined fish that might be caused by increased fishing pressure.
Short-Term Stability of Serum and Liver Extracts for Untargeted Metabolomics and Lipidomics
Authors: Hricko Jiri , Rudl Kulhava Lucie , Paucova Michaela , Novakova Michaela , Kuda Ondrej , Fiehn Oliver , Cajka Tomas
Published: April 2023

Thermal reactions can significantly alter the metabolomic and lipidomic content of biofluids and tissues during storage. In this study, we investigated the stability of polar metabolites and complex lipids in dry human serum and mouse liver extracts over a three-day period under various temperature conditions. Specifically, we tested temperatures of −80 °C (freezer), −24 °C (freezer), −0.5 °C (polystyrene box with gel-based ice packs), +5 °C (refrigerator), +23 °C (laboratory, room temperature), and +30 °C (thermostat) to simulate the time between sample extraction and analysis, shipping dry extracts to different labs as an alternative to dry ice, and document the impact of higher temperatures on sample integrity. The extracts were analyzed using five fast liquid chromatography-mass spectrometry (LC-MS) methods to screen polar metabolites and complex lipids, and over 600 metabolites were annotated in serum and liver extracts. We found that storing dry extracts at −24 °C and partially at −0.5 °C provided comparable results to −80 °C (reference condition). However, increasing the storage temperatures led to significant changes in oxidized triacylglycerols, phospholipids, and fatty acids within three days. Polar metabolites were mainly affected at storage temperatures of +23 °C and +30 °C.
Construction of an Escherichia coli Strain Capable of Utilizing Steamed Rice as the Sole Carbon and Energy Source by Extracellular Expression of Amylase and Its Use for the Production of Putrescine
Authors: Suzuki Hideyuki , Iwamoto Nana , Nishimura Manami
Published: April 2023

The amyE gene encoding α-amylase from Bacillus subtilis 168 was fused to several genes, the products of which are membrane proteins to express AmyE extracellularly. Genes of CapA, a subunit of the capsular poly-γ-glutamate synthetase of Bacillus subtilis subsp. natto; YiaTR232, the first 232 residues of YiaT, an outer membrane protein of Escherichia coli K-12; and PgsA, cytidine 5′-diphosphate-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase of B. subtilis subsp. natto, were used. The Escherichia coli strain harboring the plasmid carrying the pgsA-amyE fusion expressed a very high level of amylase not only on the extracellular surface of the cells but also in the medium and the intracellular space and solubilized steamed rice in two days. The N-terminal amino acid sequence of the amylase purified from the culture medium (Ser-Ala-Glu-Thr-Ala) indicated that it was cleaved at the signal peptide cleavage site of AmyE. The strain SH2204, transformed with pKN11 carrying speA (arginine decarboxylase gene), speB (agmatinase gene) and argAATG Y19C (N-acetylglutamate synthase gene) and pMAN63 carrying pgsA-amyE produced 1.2 mM putrescine from 5 mM arginine by adding 0.5 mM IPTG in eight days. Discarding steamed rice is not only a food loss, but also a waste of renewable, biogenerated resources due to the burning of it with petroleum, increasing carbon dioxide in the atmosphere. The E. coli strain developed in this study can help solve this problem because it can produce an important chemical using steamed rice as the sole carbon and energy source.
Comparisons of Spatial and Temporal Variations in PM2.5-Bound Trace Elements in Urban and Rural Areas of South Korea, and Associated Potential Health Risks
Authors: Nirmalkar Jayant , Lee Kwangyul , Ahn Junyoung , Lee Jiyi , Song Mijung
Published: April 2023

PM2.5-bound trace elements were chosen for health risk assessment because they have been linked to an increased risk of respiratory and cardiovascular illness. Since the Korean national air quality standard for ambient particulate matter is based on PM2.5 mass concentration, there have only been a few measurements of PM2.5 particles together with trace elements that can be utilized to evaluate their effects on air quality and human health. Thus, this study describes the trace elements bound to PM2.5 in Seoul (urban area) and Seosan (rural area) using online nondestructive energy-dispersive X-ray fluorescence analysis from December 2020 to January 2021. At both the Seoul and Seosan sites, S, K, Si, Ca, and Fe constituted most of the PM2.5-bound trace elements (~95%); major components such as S, K, and soil (estimatedcalculatedcalculated based on oxides of Si, Fe, Ca, and Ti) were presumably from anthropogenic and crustal sources, as well as favorable meteorological conditions. During winter, synoptic meteorology favored the transport of particles from severely contaminated regions, such as the East Asian outflow and local emissions. The total dry deposition flux for crustal elements was 894.5 ± 320.8 µg m−2 d−1 in Seoul and 1088.8 ± 302.4 µg m−2 d−1 in Seosan. Moreover, potential health risks from the trace elements were estimated. Cancer risk values for carcinogenic trace elements (Cr, As, Ni, and Pb) were within the tolerable limit (1 × 10−6), suggesting that adults and children were not at risk of cancer throughout the study period in Seoul and Seosan. Furthermore, a potential risk assessment of human exposure to remaining carcinogens (Cr, As, Ni, and Pb) and non-carcinogens (Cu, Fe, Zn, V, Mn, and Se) indicated that these trace elements posed no health risks. Nevertheless, trace element monitoring, risk assessment, and mitigation must be strengthened throughout the study area to confirm that trace-element-related health effects remain harmless. Researchers and policymakers can use the database from this study on spatial and temporal variation to establish actions and plans in the future.
The Association between Vessel Departures and Air Pollution in Helsinki Port Area 2016–2021
Authors: Heikkilä Mikko , Jalkanen Jukka-Pekka
Published: April 2023

European ports are struggling to install enough shore power connections to follow the European Commission initiative, which insists ships that lie alongside to be plugged in and have their auxiliary engines off in EU ports by 2030. The port of Helsinki is one of the busiest passenger ports in the world handling on average more than 10 million international passengers per year. As passenger ships consume more fuel than other vessel types, the shore power regulation poses additional challenges for the port of Helsinki. Passenger ferry and cruise ship terminals are in the middle of the city meaning that their air emissions carry a public health burden in the urban areas. Using port arrivals and departures combined with the EU Monitoring, Reporting and Verifying (MRV), this study estimates that 75–80% of the fuel combusted by ship auxiliary engines falls under the upcoming regulation. However, using statistical methods to find the association and effects between vessel movements and port air quality measurements, ship departures were found to have noticeable increases in the hourly mean NO2 concentration measured at the port terminals. This is most likely caused by starting cold main engines for departure and will not be solved by connecting ships to shore power.
Experimental Investigation on the Reaction Characteristics between Ozone and Vehicle Cabin/Furniture Materials
Authors: Gao Ying , Zhang Meixia , Wang Haimei , Xiong Jianyin
Published: April 2023

Volatile organic compounds (VOCs) emitted from building and vehicle cabin materials seriously affect indoor and in-cabin air quality, as well as human health. Previous studies revealed that some VOCs from building materials could react with ozone to affect the concentration levels of the indoor environment, but seldom refers to vehicle cabin materials. In this study, we performed experimental investigation for two kinds of vehicle cabin materials (car carpet, sealing strip) and one furniture material (medium-density fiberboard) by conducting small-scale chamber tests under two different conditions, with ozone (about 110 μg/m3) and without ozone (about 10 μg/m3), to explore the effect of in-cabin chemistry on VOC emissions. We observed the VOC concentration changes in the two scenarios and found that ozone had a significant impact on the concentrations of aldehydes and ketones while having little impact on the concentrations of benzene series. We introduced a gain ratio to quantitatively reflect the concentration changes in the presence of ozone. The gain ratio for aldehydes and ketones is greater than one, while that for the benzene series is basically around one with a small fluctuation range. This study demonstrates that ozone can react with VOCs containing unsaturated carbon–carbon bonds or carbon–oxygen bonds emitted from varied materials to produce aldehydes and ketones, which will further reduce indoor and in-cabin air quality.
Data-Driven Air Quality and Environmental Evaluation for Cattle Farms
Authors: Hu Jennifer , Jagtap Rushikesh , Ravichandran Rishikumar , Sathya Moorthy Chitra Priyaa , Sobol Nataliya , Wu Jane , Gao Jerry
Published: April 2023

The expansion of agricultural practices and the raising of animals are key contributors to air pollution. Cattle farms contain hazardous gases, so we developed a cattle farm air pollution analyzer to count the number of cattle and provide comprehensive statistics on different air pollutant concentrations based on severity over various time periods. The modeling was performed in two parts: the first stage focused on object detection using satellite data of farm images to identify and count the number of cattle; the second stage predicted the next hour air pollutant concentration of the seven cattle farm air pollutants considered. The output from the second stage was then visualized based on severity, and analytics were performed on the historical data. The visualization illustrates the relationship between cattle count and air pollutants, an important factor for analyzing the pollutant concentration trend. We proposed the models Detectron2, YOLOv4, RetinaNet, and YOLOv5 for the first stage, and LSTM (single/multi lag), CNN-LSTM, and Bi-LSTM for the second stage. YOLOv5 performed best in stage one with an average precision of 0.916 and recall of 0.912, with the average precision and recall for all models being above 0.87. For stage two, CNN-LSTM performed well with an MAE of 3.511 and an MAPE of 0.016, while a stacked model had an MAE of 5.010 and an MAPE of 0.023.
Paleo-Atmospheric Precipitation Recharged to Groundwater in Middle-Latitude Deserts of Northern China
Authors: Zhu Bing-Qi
Published: April 2023

It is a difficult and hot issue in the hydrological studies of arid areas to choose suitable methods to evaluate the recharge of atmospheric precipitation to groundwater and its response to climate change in desert areas. This study reviews the theories and problems of vadose (unsaturated)-zone tracing methods selected by predecessors in hydrological studies and takes the deserts in middle latitudes of northern China as an example to extract decadal, centennial, and millennian information of atmospheric precipitation to groundwater recharge on a regional scale since the late Holocene. The fluctuations of atmospheric precipitation and chronological sequences of desert unsaturated zone were estimated by using the chlorine mass balance (CMB) theory. It indicates that the Badain Jaran Desert in the central Alashan Plateau and the surrounding Gobi deserts have experienced fluctuations of groundwater recharge on a centennial scale during the late Holocene period from about 700 to 2000 years ago. Multiple CMB profile records can identify four periods of relative wetness (1330–1430, 1500–1620, 1700–1780, and 1950–1990) and three periods of relative drought (1430–1500, 1620–1700, and 1900–1950) over the past millennium. These records are consistent with other paleoclimatic records in the northern margin of the Qinghai-Tibet Plateau, and relatively correspond to those in the eastern part of China. This indicates that groundwater recharge in the Alashan Plateau broadly reflects the degree of climatic variability in northwest China over the centennial scale and may be affected by the changes in the intensity of the East Asian summer monsoon. The estimated average recharge rate of precipitation in the Alashan Plateau in the last millennium is about 1.3~2.6 mm/a, which brings new geological evidence for understanding the source of groundwater recharge in the region but is quite different from other environmental records. It should be noted that there are uncertainties in the CMB records of the vadose zone profiles, mainly due to the assumption of atmospheric Cl input in the CMB estimation and the selection of the homogeneous vadose profile (piston flow). This study suggests that this uncertainty and its error should be extensively tested in the future by comparing deterministic data (such as regional reference stations) with large-scale random atmospheric Cl input backgrounds.
Theoretical Investigation of Electron–Ion Recombination Process of Mg-like Gold
Authors: Xie Luyou , He Wenliang , Niu Shengbo , Rui Jinglin , Ma Yulong , Dong Chenzhong
Published: April 2023

The L-shell dielectronic and trielectronic recombinations of highly charged Mg-like gold ions (Au67+) in the ground state 2s22p63s2 1S0 have been studied systematically. The recombination cross-sections and rate coefficients are carefully calculated for ∆n = 1 (2s/2p → 3l) transitions using a flexible atomic code based on the relativistic configuration interaction method and considering the Breit and QED corrections. Detailed resonance energies and resonance strengths are presented for the stronger resonances of the LMn (n = 3–12) series. It is found that the contributions of the trielectronic recombination to the total cross-section is about 13.75%, which cannot be neglected. For convenience of application, the plasma rate coefficients are also calculated and fitted to a semiempirical formula, and in the calculations, the contributions from the higher excited resonance groups n ≥ 13 are evaluated by an extrapolation method, which is about 2.93% of the total rate coefficient.
Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance
Authors: Sapozhnikov Daniel M. , Szyf Moshe
Published: April 2023

As advances in genome engineering inch the technology towards wider clinical use—slowed by technical and ethical hurdles—a newer offshoot, termed “epigenome engineering”, offers the ability to correct disease-causing changes in the DNA without changing its sequence and, thus, without some of the unfavorable correlates of doing so. In this review, we note some of the shortcomings of epigenetic editing technology—specifically the risks involved in the introduction of epigenetic enzymes—and highlight an alternative epigenetic editing strategy using physical occlusion to modify epigenetic marks at target sites without a requirement for any epigenetic enzyme. This may prove to be a safer alternative for more specific epigenetic editing.
Identification of Novel Biomarkers of Spinal Muscular Atrophy and Therapeutic Response by Proteomic and Metabolomic Profiling of Human Biological Fluid Samples
Authors: Meneri Megi , Abati Elena , Gagliardi Delia , Faravelli Irene , Parente Valeria , Ratti Antonia , Verde Federico , Ticozzi Nicola , Comi Giacomo P. , Ottoboni Linda , Corti Stefania
Published: April 2023

Spinal muscular atrophy (SMA) is a neuromuscular disease resulting from mutations or deletions in SMN1 that lead to progressive death of alpha motor neurons, ultimately leading to severe muscle weakness and atrophy, as well as premature death in the absence of treatment. Recent approval of SMN-increasing medications as SMA therapy has altered the natural course of the disease. Thus, accurate biomarkers are needed to predict SMA severity, prognosis, drug response, and overall treatment efficacy. This article reviews novel non-targeted omics strategies that could become useful clinical tools for patients with SMA. Proteomics and metabolomics can provide insights into molecular events underlying disease progression and treatment response. High-throughput omics data have shown that untreated SMA patients have different profiles than controls. In addition, patients who clinically improved after treatment have a different profile than those who did not. These results provide a glimpse on potential markers that could assist in identifying therapy responders, in tracing the course of the disease, and in predicting its outcome. These studies have been restricted by the limited number of patients, but the approaches are feasible and can unravel severity-specific neuro-proteomic and metabolic SMA signatures.
Pre- and Postoperative Exercise Effectiveness in Mobility, Hemostatic Balance, and Prognostic Biomarkers in Hip Fracture Patients: A Study Protocol for a Randomized Controlled Trial
Authors: Skouras Apostolos Z. , Antonakis-Karamintzas Dimitrios , Tsolakis Charilaos , Tsantes Argirios E. , Kourlaba Georgia , Zafeiris Ioannis , Soucacos Fotini , Papagiannis Georgios , Triantafyllou Athanasios , Houhoula Dimitra , Savvidou Olga , Koulouvaris Panagiotis
Published: April 2023

Hip fractures are a major health concern, particularly for older adults, as they can reduce life quality, mobility loss, and even death. Current evidence reveals that early intervention is recommended for endurance in patients with hip fractures. To our knowledge, preoperative exercise intervention in patients with hip fractures remains poorly researched, and no study has yet applied aerobic exercise preoperatively. This study aims to investigate the short-term benefits of a supervised preoperative aerobic moderate-intensity interval training (MIIT) program and the added effect of an 8-week postoperative MIIT aerobic exercise program with a portable upper extremity cycle ergometer. The work-to-recovery ratio will be 1-to-1, consisting of 120 s for each bout and four and eight rounds for the pre- and postoperative programs, respectively. The preoperative program will be delivered twice a day. A parallel group, single-blinded, randomized controlled trial (RCT) was planned to be conducted with 58 patients each in the intervention and control groups. This study has two primary purposes. First, to study the effect of a preoperative aerobic exercise program with a portable upper extremity cycle ergometer on immediate postoperative mobility. Second, to investigate the additional effect of an 8-week postoperative aerobic exercise program with a portable upper extremity cycle ergometer on the walking distance at eight weeks after surgery. This study also has several secondary objectives, such as ameliorating surgical and keeping hemostatic balance throughout exercise. This study may expand our knowledge of preoperative exercise effectiveness in hip fracture patients and enhance the current literature about early intervention benefits.
Optimization of SSVEP-BCI Virtual Reality Stereo Stimulation Parameters Based on Knowledge Graph
Authors: Zhu Shixuan , Yang Jingcheng , Ding Peng , Wang Fan , Gong Anmin , Fu Yunfa
Published: April 2023

The steady-state visually evoked potential (SSVEP) is an important type of BCI that has various potential applications, including in virtual environments using virtual reality (VR). However, compared to VR research, the majority of visual stimuli used in the SSVEP-BCI are plane stimulation targets (PSTs), with only a few studies using stereo stimulation targets (SSTs). To explore the parameter optimization of the SSVEP-BCI virtual SSTs, this paper presents a parameter knowledge graph. First, an online VR stereoscopic stimulation SSVEP-BCI system is built, and a parameter dictionary for VR stereoscopic stimulation parameters (shape, color, and frequency) is established. The online experimental results of 10 subjects under different parameter combinations were collected, and a knowledge graph was constructed to optimize the SST parameters. The best classification performances of the shape, color, and frequency parameters were sphere (91.85%), blue (94.26%), and 13Hz (95.93%). With various combinations of virtual reality stereo stimulation parameters, the performance of the SSVEP-BCI varies. Using the knowledge graph of the stimulus parameters can help intuitively and effectively select appropriate SST parameters. The knowledge graph of the stereo target stimulation parameters presented in this work is expected to offer a way to convert the application of the SSVEP-BCI and VR.
Interleukin-6: A New Marker of Advanced-Sarcopenic HCC Cirrhotic Patients
Authors: Dalbeni Andrea , Natola Leonardo Antonio , Garbin Marta , Zoncapè Mirko , Cattazzo Filippo , Mantovani Anna , Vella Antonio , Canè Stefania , Kassem Jasmin , Bevilacqua Michele , Conci Simone , Campagnaro Tommaso , Ruzzenente Andrea , Auriemma Alessandra , Drudi Alessandro , Zanoni Giovanna , Guglielmi Alfredo , Milella Michele , Sacerdoti David
Published: April 2023

Hepatocellular carcinoma (HCC) is the major cause of liver-related death worldwide. Interleukin 6 (IL-6) promotes the growth of the HCC microenvironment. The correlation between Child–Pugh (CP) and HCC stage and between HCC stage and sarcopenia is still not clear. Our aim was to investigate whether IL-6 is correlated with HCC stage and could represent a diagnostic marker for sarcopenia. Ninety-three HCC cirrhotic patients in different stages, according to BCLC-2022 (stages A, B, and C), were enrolled. Anthropometric and biochemical parameters, comprehensive of IL-6, were collected. The skeletal muscle index (SMI) was measured using dedicated software on computer tomography (CT) images. IL-6 level was higher in advanced (BCLC C) compared to the early-intermediate (BCLC A-B) stages (21.4 vs. 7.7 pg/mL, p < 0.005). On multivariate analysis, IL-6 levels were statistically dependent on the degree of liver disease severity (CP score) and HCC stages (p = 0.001 and p = 0.044, respectively). Sarcopenic patients presented lower BMI (24.7 ± 5.3 vs. 28.5 ± 7.0), higher PMN/lymphocyte ratio (2.9 ± 2.4 vs. 2.3 ± 1.2) and increased values of log (IL-6) (1.3 ± 0.6 vs. 1.1 ± 0.3). Univariate logistic regression between sarcopenia and log (IL-6) showed a significant odds ratio (OR 14.88, p = 0.044) with an AUC of 0.72. IL-6 appears to be an effective biomarker for the diagnosis of advanced cirrhotic HCC. In addition, IL-6 could be considered a marker of cirrhotic HCC-related sarcopenia, suggesting further investigation with BIA- or CT-dedicated software.
Long Axial Field-of-View PET/CT Could Answer Unmet Needs in Gynecological Cancers
Authors: Triumbari Elizabeth Katherine Anna , Rufini Vittoria , Mingels Clemens , Rominger Axel , Alavi Abass , Fanfani Francesco , Badawi Ramsey D. , Nardo Lorenzo
Published: April 2023

Gynecological malignancies currently affect about 3.5 million women all over the world. Imaging of uterine, cervical, vaginal, ovarian, and vulvar cancer still presents several unmet needs when using conventional modalities such as ultrasound, computed tomography (CT), magnetic resonance, and standard positron emission tomography (PET)/CT. Some of the current diagnostic limitations are represented by differential diagnosis between inflammatory and cancerous findings, detection of peritoneal carcinomatosis and metastases <1 cm, detection of cancer-associated vascular complications, effective assessment of post-therapy changes, as well as bone metabolism and osteoporosis assessment. As a result of recent advances in PET/CT instrumentation, new systems now offer a long-axial field-of-view (LAFOV) to image between 106 cm and 194 cm (i.e., total-body PET) of the patient’s body simultaneously and feature higher physical sensitivity and spatial resolution compared to standard PET/CT systems. LAFOV PET could overcome the forementioned limitations of conventional imaging and provide valuable global disease assessment, allowing for improved patient-tailored care. This article provides a comprehensive overview of these and other potential applications of LAFOV PET/CT imaging for patients with gynecological malignancies.
Artificial Intelligence in the Diagnosis and Treatment of Pancreatic Cystic Lesions and Adenocarcinoma
Authors: Jiang Joanna , Chao Wei-Lun , Culp Stacey , Krishna Somashekar G.
Published: April 2023

Pancreatic cancer is projected to become the second leading cause of cancer-related mortality in the United States by 2030. This is in part due to the paucity of reliable screening and diagnostic options for early detection. Amongst known pre-malignant pancreatic lesions, pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent. The current standard of care for the diagnosis and classification of pancreatic cystic lesions (PCLs) involves cross-sectional imaging studies and endoscopic ultrasound (EUS) and, when indicated, EUS-guided fine needle aspiration and cyst fluid analysis. However, this is suboptimal for the identification and risk stratification of PCLs, with accuracy of only 65–75% for detecting mucinous PCLs. Artificial intelligence (AI) is a promising tool that has been applied to improve accuracy in screening for solid tumors, including breast, lung, cervical, and colon cancer. More recently, it has shown promise in diagnosing pancreatic cancer by identifying high-risk populations, risk-stratifying premalignant lesions, and predicting the progression of IPMNs to adenocarcinoma. This review summarizes the available literature on artificial intelligence in the screening and prognostication of precancerous lesions in the pancreas, and streamlining the diagnosis of pancreatic cancer.
ERBB2 Amplification as a Predictive and Prognostic Biomarker in Upper Tract Urothelial Carcinoma
Authors: Zimpfer Annette , Kdimati Said , Mosig Melanie , Rudolf Henrik , Zettl Heike , Erbersdobler Andreas , Hakenberg Oliver W. , Maruschke Matthias , Schneider Björn
Published: April 2023

Upper tract urothelial carcinomas (UTUCs) occur in about 5–10% of all urothelial carcinomas and are frequently discovered in high-stage disease. We aimed to evaluate human epidermal growth factor receptor 2 (ERBB2) protein expression immunohistochemically and ERBB2 amplification in UTUCs by fluorescence in situ hybridization, applying a tissue microarray technique. ERBB2 overexpression and ERBB2 amplification were defined according to the recommendations of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) for breast cancer and gastric carcinoma (GC), revealing scores of 2+ and 3+ in 10.2% and 41.8% of UTUCs, respectively. The performance parameters showed obviously higher sensitivity of ERBB2 immunoscoring according to the ASCO/CAP criteria for GC. ERBB2 amplification was detected in 10.5% of UTUCs. ERBB2 overexpression was more likely to be found in high-grade tumors and was associated with tumor progression. Univariable Cox regression analysis revealed a significantly lower progression-free survival (PFS) in cases with ERBB2 immunoscores of 2+ or 3+ according to the ASCO/CAP guidelines for GC. UTUCs with ERBB2 amplification showed a significantly shorter PFS in the multivariable Cox regression analysis. Irrespective of their ERBB2 status, patients with UTUC treated with platin showed a significantly lower PFS than UTUC patients who had not received any platin-based therapy. In addition, UTUC patients with a normal ERBB2 gene status who had not received platin-based therapy showed significantly longer overall survival. The results suggest that ERBB2 is a biomarker for progression in UTUCs and may define a distinct subgroup of UTUCs. As previously shown, ERBB2 amplification is infrequent. However, the small number of patients diagnosed with ERBB2-amplified UTUC might benefit from ERBB2-targeted cancer therapy. In clinical–pathological routine diagnostics, the determination of ERBB2 amplification is an established method in some defined entities and also successful in small samples. Still, the simultaneous use of ERBB2 immunohistochemistry and ERBB2 in situ hybridization would be important in order to record the low rate of amplified UTUC cases as completely as possible.
Comparison of 1.1 GBq and 2.2 GBq Activities in Patients with Low-Risk Differentiated Thyroid Cancer Requiring Postoperative 131I Administration: A Real Life Study
Authors: Campennì Alfredo , Ruggeri Rosaria Maddalena , Garo Maria Luisa , Siracusa Massimiliano , Restuccia Giovanna , Rappazzo Andrea , Rosarno Helena , Nicocia Antonio , Cardile Davide , Ovčariček Petra Petranović , Baldari Sergio , Giovanella Luca
Published: April 2023

Objectives: To compare the efficacy of low and moderate 131I activities in low-risk differentiated thyroid carcinoma (DTC) patients requiring postoperative thyroid remnant ablation in a real-world clinical setting. Methods: We retrospectively reviewed the records of 299 low-risk DTC patients (pT1-T2, Nx(0) Mx) who had undergone (near)-total thyroidectomy followed by 131I therapy, using either low (1.1 GBq) or moderate (2.2 GBq) radioiodine activities. The response to initial treatments was evaluated after 8–12 months, and patient responses were classified according to the 2015 American Thyroid Association guidelines. Results: An excellent response was observed in 274/299 (91.6%) patients, specifically, in 119/139 (85.6%) and 155/160 (96.9%) patients treated with low and moderate 131I activities, respectively (p = 0.029). A biochemically indeterminate or incomplete response was observed in seventeen (22.2%) patients treated with low 131I activities and three (1.8%) patients treated with moderate 131I activities (p = 0.001). Finally, five patients showed an incomplete structural response, among which three and two received low and moderate 131I activities, respectively (p = 0.654). Conclusions: When 131I ablation is indicated, we encourage the use of moderate instead of low activities, in order to reach an excellent response in a significantly larger proportion of patients, including patients with the unexpected persistence of the disease.
Cell–Cell Communication and Extracellular Vesicles in Cancer
Authors: Lin Ling , Zhou Yandong , Hu Kebin
Published: April 2023

Cell–cell communication, either through direct contact or indirectly, is critical for multiple cellular processes, such as proliferation, survival, differentiation, and transdifferentiation, and it plays a fundamental role in maintaining the integrity of tissue structure and cellular environment [...]
Flap Reconstruction Outcome Following Surgical Resection of Soft Tissue and Bone Sarcoma in the Setting of (Neo)adjuvant Therapy: A Sarcoma Center Experience
Authors: Lese Ioana , Baesu Crinu , Hoyos Isabel Arenas , Pais Michael-Alexander , Klenke Frank , Kollar Attila , Ionescu Codruta , Constantinescu Mihai , Olariu Radu
Published: April 2023

Background: Soft tissue and bone sarcomas are heterogeneous groups of malignant tumors. The shift in their management, with an emphasis on limb salvage, has deemed the involvement of reconstructive surgeons an integral part of their multidisciplinary treatment. We present our experience with free and pedicled flaps in the reconstruction of sarcomas at a tertiary referral university hospital and major sarcoma center. Materials and Methods: All patients undergoing flap reconstruction after sarcoma resection over a 5-year period have been included in the study. Patient-related data and postoperative complications were collected retrospectively, ensuring a minimum follow-up of 3 years. Results: A total of 90 patients underwent treatment with 26 free flaps and 64 pedicled flaps. Postoperative complications occurred in 37.7% of patients, and the flap failure rate was 4.4%. Diabetes, alcohol consumption and male gender were associated with increased early necrosis of the flap. Preoperative chemotherapy significantly increased the occurrence of early infection and late dehiscence, while preoperative radiotherapy was associated with a higher incidence of lymphedema. Intraoperative radiotherapy was associated with late seromas and lymphedema. Conclusions: Reconstructive surgery with either pedicled or free flaps is reliable, but it can be demanding in the setting of sarcoma surgery. A higher complication rate is to be expected with neoadjuvant therapy and with certain comorbidities.
An Isoxazoloquinone Derivative Inhibits Tumor Growth by Targeting STAT3 and Triggering Its Ubiquitin-Dependent Degradation
Authors: Xie Yuanzhu , Zhu Shuaiwen , Chen Ling , Liu Hongdou , Peng Ting , Ming Zhengnan , Zou Zizheng , Hu Xiyuan , Luo Wensong , Peng Kunjian , Nie Yuan , Luo Tiao , Ma Dayou , Liu Suyou , Luo Zhiyong
Published: April 2023

Background: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with shorter five-year survival than other breast cancer subtypes, and lacks targeted and hormonal treatment strategies. The signal transducer and activator of transcription 3 (STAT3) signaling is up-regulated in various tumors, including TNBC, and plays a vital role in regulating the expression of multiple proliferation- and apoptosis-related genes. Results: By combining the unique structures of the natural compounds STA-21 and Aulosirazole with antitumor activities, we synthesized a class of novel isoxazoloquinone derivatives and showed that one of these compounds, ZSW, binds to the SH2 domain of STAT3, leading to decreased STAT3 expression and activation in TNBC cells. Furthermore, ZSW promotes STAT3 ubiquitination, inhibits the proliferation of TNBC cells in vitro, and attenuates tumor growth with manageable toxicities in vivo. ZSW also decreases the mammosphere formation of breast cancer stem cells (BCSCs) by inhibiting STAT3. Conclusions: We conclude that the novel isoxazoloquinone ZSW may be developed as a cancer therapeutic because it targets STAT3, thereby inhibiting the stemness of cancer cells.
High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1–AMPK–ACC Pathway
Authors: Zhang Mingjiong , Cui Jiahua , Chen Haoyan , Wang Yu , Kuai Xingwang , Sun Sibo , Tang Qi , Zong Feng , Chen Qiaoyu , Wu Jianqing , Wu Shuangshuang
Published: April 2023

Background: Nicotinamide mononucleotide (NMN) is the physiological circulating NAD precursor thought to elevate the cellular level of NAD+ and to ameliorate various age-related diseases. An inseparable link exists between aging and tumorigenesis, especially involving aberrant energetic metabolism and cell fate regulation in cancer cells. However, few studies have directly investigated the effects of NMN on another major ageing-related disease: tumors. Methods: We conducted a series of cell and mouse models to evaluate the anti-tumor effect of high-dose NMN. Transmission electron microscopy and a Mito-FerroGreen-labeled immunofluorescence assay (Fe2+) were utilized to demonstrate ferroptosis. The metabolites of NAM were detected via ELISA. The expression of the proteins involved in the SIRT1–AMPK–ACC signaling were detected using a Western blot assay. Results: The results showed that high-dose NMN inhibits lung adenocarcinoma growth in vitro and in vivo. Excess NAM is produced through the metabolism of high-dose NMN, whereas the overexpression of NAMPT significantly decreases intracellular NAM content, which, in turn, boosts cell proliferation. Mechanistically, high-dose NMN promotes ferroptosis through NAM-mediated SIRT1–AMPK–ACC signaling. Conclusions: This study highlights the tumor influence of NMN at high doses in the manipulation of cancer cell metabolism, providing a new perspective on clinical therapy in patients with lung adenocarcinoma.
Geographical Disparities and Patients’ Mobility: A Plea for Regionalization of Pancreatic Surgery in Italy
Authors: Balzano Gianpaolo , Guarneri Giovanni , Pecorelli Nicolò , Partelli Stefano , Crippa Stefano , Vico Augusto , Falconi Massimo , Baglio Giovanni
Published: April 2023

Patients requiring complex treatments, such as pancreatic surgery, may need to travel long distances and spend extended periods of time away from home, particularly when healthcare provision is geographically dispersed. This raises concerns about equal access to care. Italy is administratively divided into 21 separate territories, which are heterogeneous in terms of healthcare quality, with provision generally decreasing from north to south. This study aimed to evaluate the distribution of adequate facilities for pancreatic surgery, quantify the phenomenon of long-distance mobility for pancreatic resections, and measure its effect on operative mortality. Data refer to patients undergoing pancreatic resections (in the period 2014–2016). The assessment of adequate facilities for pancreatic surgery, based on volume and outcome, confirmed the inhomogeneous distribution throughout Italy. The migration rate from Southern and Central Italy was 40.3% and 14.6%, respectively, with patients mainly directed towards high-volume centers in Northern Italy. Adjusted mortality for non-migrating patients receiving surgery in Southern and Central Italy was significantly higher than that for migrating patients. Adjusted mortality varied greatly among regions, ranging from 3.2% to 16.4%. Overall, this study highlights the urgent need to address the geographical disparities in pancreatic surgery provision in Italy and ensure equal access to care for all patients.
Feasibility, Reliability, and Safety of Remote Five Times Sit to Stand Test in Patients with Gastrointestinal Cancer
Authors: Steffens Daniel , Pocovi Natasha C. , Bartyn Jenna , Delbaere Kim , Hancock Mark J. , Koh Cherry , Denehy Linda , van Schooten Kimberley S. , Solomon Michael ,   on behalf of the Priority Trial Collaboration
Published: April 2023

Background: To determine the feasibility, reliability, and safety of the remote five times sit to stand test (5STS) test in patients with gastrointestinal cancer. Methods: Consecutive adult patients undergoing surgical treatment for lower gastrointestinal cancer at a major referral hospital in Sydney between July and November 2022 were included. Participants completed the 5STS test both face-to-face and remotely, with the order randomised. Outcomes included measures of feasibility, reliability, and safety. Results: Of fifty-five patients identified, seventeen (30.9%) were not interested, one (1.8%) had no internet coverage, and thirty-seven (67.3%) consented and completed both 5STS tests. The mean (SD) time taken to complete the face-to-face and remote 5STS tests was 9.1 (2.4) and 9.5 (2.3) seconds, respectively. Remote collection by telehealth was feasible, with only two participants (5.4%) having connectivity issues at the start of the remote assessment, but not interfering with the tests. The remote 5STS test showed excellent reliability (ICC = 0.957), with limits of agreement within acceptable ranges and no significant systematic errors observed. No adverse events were observed within either test environment. Conclusions: Remote 5STS for the assessment of functional lower extremity strength in gastrointestinal cancer patients is feasible, reliable, and safe, and can be used in clinical and research settings.