bluuebunny/crossref_metadata_2025 huggingface dataset:
Pan-Cancer Characterization of Intratumoral Autonomic Innervation in 32 Cancer Types in the Cancer Genome Atlas
Authors: Zhang Jeff F. , Sheng Haiyang , Chen Jianhong , Mohammadpour Hemn , Ma Sung Jun , Farrugia Mark K. , Gandhi Shipra , Bouchard Elizabeth G. , Singh Anurag K. , Repasky Elizabeth A. , Khoury Thaer , Ambrosone Christine B. , Yao Song
Published: May 2022

Over the past two decades, multiple studies have demonstrated the important role that the autonomic nervous system (ANS) plays in tumorigenesis and cancer progression. However, the mechanisms by which this process occurs have only recently begun to be elucidated. Further, the extent of autonomic innervation in various cancer types and its effects on tumor molecular, immunological, and histopathological features, as well as on patient outcomes, are not yet fully characterized. In this study, we analyzed intratumoral ANS gene expression signatures, including overall intratumoral neuron growth and sympathetic and parasympathetic markers, across 32 cancer types using tumor transcriptomic and clinical annotation data available from The Cancer Genome Atlas (TCGA). Our analysis revealed wide variations in intratumoral ANS expression both within and across cancer types. The association of ANS signatures with tumor histopathological characteristics and survival outcomes also varied by cancer type. We found intratumoral ANS expression to be commonly correlated with angiogenesis, TGF-β signaling, and immunosuppression in the tumor microenvironment of many cancer types, which provide mechanistic insights into the involvement of intratumoral innervation in cancer development and progression. Our findings suggest that the potential benefits of cancer therapies targeting β-adrenergic receptor-mediated stress signaling pathways are likely dependent on cancer type.
Gene Expression Monotonicity across Bladder Cancer Stages Informs on the Molecular Pathogenesis and Identifies a Prognostic Eight-Gene Signature
Authors: Stroggilos Rafael , Frantzi Maria , Zoidakis Jerome , Mokou Marika , Moulavasilis Napoleon , Mavrogeorgis Emmanouil , Melidi Anna , Makridakis Manousos , Stravodimos Konstantinos , Roubelakis Maria G. , Mischak Harald , Vlahou Antonia
Published: May 2022

Despite advancements in molecular classification, tumor stage and grade still remain the most relevant prognosticators used by clinicians to decide on patient management. Here, we leverage publicly available data to characterize bladder cancer (BLCA)’s stage biology based on increased sample sizes, identify potential therapeutic targets, and extract putative biomarkers. A total of 1135 primary BLCA transcriptomes from 12 microarray studies were compiled in a meta-cohort and analyzed for monotonal alterations in pathway activities, gene expression, and co-expression patterns with increasing stage (Ta–T1–T2–T3–T4), starting from the non-malignant tumor-adjacent urothelium. The TCGA-2017 and IMvigor-210 RNA-Seq data were used to validate our findings. Wnt, MTORC1 signaling, and MYC activity were monotonically increased with increasing stage, while an opposite trend was detected for the catabolism of fatty acids, circadian clock genes, and the metabolism of heme. Co-expression network analysis highlighted stage- and cell-type-specific genes of potentially synergistic therapeutic value. An eight-gene signature, consisting of the genes AKAP7, ANLN, CBX7, CDC14B, ENO1, GTPBP4, MED19, and ZFP2, had independent prognostic value in both the discovery and validation sets. This novel eight-gene signature may increase the granularity of current risk-to-progression estimators.
Prognostic Neurotransmitter Receptors Genes Are Associated with Immune Response, Inflammation and Cancer Hallmarks in Brain Tumors
Authors: Belotti Yuri , Tolomeo Serenella , Yu Rongjun , Lim Wan-Teck , Lim Chwee Teck
Published: May 2022

Glioblastoma multiforme (GBM) is one of the most aggressive forms of cancer. Neurotransmitters (NTs) have recently been linked with the uncontrolled proliferation of cancer cells, but the role of NTs in the progression of human gliomas is still largely unexplored. Here, we investigate the genes encoding for neurotransmitter receptors (NTRs) by analyzing public transcriptomic data from GBM and LGG (low-grade glioma) samples. Our results showed that 50 out of the 98 tested NTR genes were dysregulated in brain cancer tissue. Next, we identified and validated NTR-associated prognostic gene signatures for both LGG and GBM. A subset of 10 NTR genes (DRD1, HTR1E, HTR3B, GABRA1, GABRA4, GABRB2, GABRG2, GRIN1, GRM7, and ADRA1B) predicted a positive prognosis in LGG and a negative prognosis in GBM. These genes were progressively downregulated across glioma grades and exhibited a strong negative correlation with genes associated with immune response, inflammasomes, and established cancer hallmarks genes in lower grade gliomas, suggesting a putative role in inhibiting cancer progression. This study might have implications for the development of novel therapeutics and preventive strategies that target regulatory networks associated with the link between the autonomic nervous system, cancer cells, and the tumor microenvironment.
Life Quality of Children Affected by Cleft Lip Palate and Alveolus (CLPA)
Authors: Pasini Marco , Cagidiaco Irene , Fambrini Eleonora , Miceli Marco , Carli Elisabetta
Published: May 2022

The aim of this study was to investigate the quality of life of children and adolescents affected by cleft lip, palate and alveolus (CLPA) in the Italian population after a tailored treatment dental program. A prospective study was conducted with subjects of both genders at the University Hospital of Pisa, Italy. This study included 32 patients (11 females and 21 males, mean age: 9.8 ± 2.1 years old) affected by CLPA (test group); a tailored oral hygiene instruction protocol was adopted in the test group since early age (6.1 ± 0.9 years old) after corrective surgery and regular dental hygiene appointments were scheduled. Moreover, a control group of 32 patients (11 females and 21 males, mean age: 10.1 ± 2.2 years old) without CLPA was included; control subjects were first-visit patients, matched for age and sex, who had not received a specific dental hygiene program before. The OHIP-14 (Oral Health Impact Profile) questionnaire was applied for the evaluation of the quality of life of patients of both groups and the questions were presented directly to the patients. Moreover, the DMFT (Decayed, Missed and Filled Teeth) index was measured. A statistical analysis was performed and the level of significance was set at: p < 0.05. The OHIP-14 scores presented significant differences between the two groups (p < 0.05); the test group exhibited a lower mean OHIP-14 score in comparison to the control group. The DMFT score was significantly lower in the test group in comparison to controls (p: 0.001, p < 0.05). The quality of life and DMFT score of children and adolescents affected by CLPA, after a tailored treatment dental program, were better than that of the subjects of the control group.
The UDP-Glycosyltransferase Gene Family in Achelura yunnanensis (Lepidoptera: Zygaenidae): Identification, Phylogeny, and Diverse Expression Patterns
Authors: Xiao Hai-Yan , Chen Dan-Lu , Lu Ting-Ting , Yao Yu-Juan , Liu Nai-Yong
Published: May 2022

The caterpillars of the Lepidoptera are important herbivores as most of them belong to serious agricultural and forestry pests. To adapt to their habitats and feeding host plants, the larvae utilize uridine diphosphate (UDP)-glycosyltransferases (UGTs) to metabolize plant defensive compounds and insecticides. However, information on the UGT gene family in Achelura yunnanensis remains scarce. Here, we characterized the UGT genes through gene identification, phylogenic analyses, and comprehensive expression profiles regarding sexes, tissues, and stages. Transcriptome analyses led to the yields of 50 transcripts encoding UGTs in A. yunnanensis, representing a comparable gene number compared to those in other lepidopteran species. Sequence and phylogenetic analyses revealed a low amino acid identity of 28.23% among 31 full-length AyunUGTs, but some members shared relatively high conservation (>50% identities) with a phylogenetically clustered distribution. In addition, the majority of AyunUGTs possessed conserved residues involved in the catalysis and sugar-donor binding. Combining RNA sequencing and PCR approaches, a number of AyunUGTs were found to have the expression in chemosensory or detoxification tissues, possibly associated with the sensing of odorant molecules and the metabolism of toxic chemicals. More importantly, at least 27 AyunUGTs displayed detectable expression in reproductive tissues of both sexes. This study identifies candidate A. yunnanensis UGTs responsible for detoxification, olfaction, and reproduction, allowing us to address putative roles of UGTs in the adaptation of larvae to the habitats and feeding hosts.
Lipomatous Tumors: A Comparison of MRI-Reported Diagnosis with Histological Diagnosis
Authors: Ballhause Tobias M. , Korthaus Alexander , Jahnke Martin , Frosch Karl-Heinz , Yamamura Jin , Dust Tobias , Schlickewei Carsten W. , Priemel Matthias H.
Published: May 2022

Lipomatous tumors are among the most common soft tissue tumors (STTs). Magnetic resonance imaging (MRI) is a state-of-the-art diagnostic tool used to differentiate and characterize STTs. Radiological misjudgment can lead to incorrect treatment. This was a single-center retrospective study. Two hundred and forty lipomatous tumors were included. MRI diagnoses were categorized as benign, intermediate, or malignant and were compared with histological diagnoses. Tumor volumes were measured by MRI and from surgical specimens. The tumor was correctly categorized 73.3% of the time. A total of 21.7% of tumors were categorized as more malignant in MRI reports than they were by histology, and vice versa for 5.0% of tumors. Volume measured by MRI was not different from actual tumor size in pathology. Atypical lipomatous tumors (ALTs) and liposarcomas (LPSs) were larger when compared with lipomata and occurred in older patients. Based on the MRI-suspected tumor entity, surgical treatment can be planned. Large lipomatous tumors in elderly patients are more likely to be ALTs. However, a safe threshold size or volume for ALTs cannot be determined.
Isolated Sphenoid Sinusitis: Anatomical Features for Choosing a Method of Treatment, a Case-Control Study
Authors: Karpishchenko Sergei , Vereshchagina Olga , Stancheva Olga , Nagornykh Tatiana , Krasichkov Alexander , Serdiukova Irina , Sinitca Aleksandr , Kaplun Dmitry
Published: May 2022

Isolated sphenoid sinusitis (ISS) is a group of pathologies characterized by inflammation in one or both sphenoid sinuses. The gold standard for analyzing and diagnosing ISS is computer tomography. Many researchers have discussed the treatment of patients with ISS variants such as fully opacified sinus, mostly with surgery. A retrospective analysis of clinical data of 59 patients (21 male (35%), 38 female (65%)) with ISS, who were treated in the Otorhinolaryngological Department of Pavlov First Saint Petersburg State Medical University between January 2017 and January 2020, was conducted. All patients were in the first stage of the same medical therapy. In cases where there was no recovery, these patients were referred to surgery. For the control group, we analyzed patients without any disorders according to CT-scan examination. After analyzing the obtained clinical and radiological data, we found indicators that were common in patients who did not recover after medical therapy. According to the reverse regression method statistical model, in male patients with a diffuse headache and nasal discharge it was shown that medical therapy was highly effective (more than 78%). The presence of nasal septum deviation and adenoids in male and female patients leads to the highest risk of surgical treatment (83% probability of the logistic model). The detailed analysis of CT-scans and the complaints of patients with ISS can be the key to determining the preferred therapy choice. Not all cases need to have an endoscopic opening of the sphenoid sinus, according to our research.
Graph-Embedded Online Learning for Cell Detection and Tumour Proportion Score Estimation
Authors: Chen Jinhao , Zhu Yuang , Chen Zhao
Published: May 2022

Cell detection in microscopy images can provide useful clinical information. Most methods based on deep learning for cell detection are fully supervised. Without enough labelled samples, the accuracy of these methods would drop rapidly. To handle limited annotations and massive unlabelled data, semi-supervised learning methods have been developed. However, many of these are trained off-line, and are unable to process new incoming data to meet the needs of clinical diagnosis. Therefore, we propose a novel graph-embedded online learning network (GeoNet) for cell detection. It can locate and classify cells with dot annotations, saving considerable manpower. Trained by both historical data and reliable new samples, the online network can predict nuclear locations for upcoming new images while being optimized. To be more easily adapted to open data, it engages dynamic graph regularization and learns the inherent nonlinear structures of cells. Moreover, GeoNet can be applied to downstream tasks such as quantitative estimation of tumour proportion score (TPS), which is a useful indicator for lung squamous cell carcinoma treatment and prognostics. Experimental results for five large datasets with great variability in cell type and morphology validate the effectiveness and generalizability of the proposed method. For the lung squamous cell carcinoma (LUSC) dataset, the detection F1-scores of GeoNet for negative and positive tumour cells are 0.734 and 0.769, respectively, and the relative error of GeoNet for TPS estimation is 11.1%.
Pole Feature Extraction of HF Radar Targets for the Large Complex Ship Based on SPSO and ARMA Model Algorithm
Authors: Zhou Sang , Gao Huotao , Ren Fangyu
Published: May 2022

Radar target characteristics need to be accurately extracted to enhance the role of high-frequency (HF) radar target recognition technology in modern radar, sea and air monitoring, and other applications. The pole characteristics of radar targets have become a mainstream research focus because of their inherent advantages for target recognition. However, existing pole extraction methods for complex targets generally have problems in early- and late-time responses aliasing and target information loss. To avoid this problem, this study proposes a new method to extract radar target poles based on the special particle swarm optimization algorithm (SPSO) and an autoregressive moving average (ARMA) model. This method, which does not involve the distinction between early-and late-time responses, is used to estimate an approximation of the entire scattering echo of the target. Then the parameters of the model are precisely optimized with the help of a particle swarm optimization algorithm combined with opposition-based learning and inertia weight decreasing. Strategy. Owing to the characteristics of the azimuth consistency of the target poles, a sliding window is used to calibrate the positions of multi-azimuth poles in the complex plane. The method was demonstrated to be feasible with good performance when it was applied to extract the pole features of ships at different azimuths in the high-frequency band.
High-Speed Control of AC Servo Motor Using High-Performance RBF Neural Network Terminal Sliding Mode Observer and Single Current Reconstructed Technique
Authors: Chen Huaizhi , Cai Changxin
Published: May 2022

This paper proposes a phase current reconstruction strategy based on a dc bus using a single current sensor for a surface permanent magnet synchronous motor (SPMSM). The method of a single current sensor reduces the number of mechanical hall sensors and shunt resistors by using a modified current reconstruction algorithm. The information of rotor position is estimated by the sliding mode observer for its rapid response and strong anti-interference ability, and the observer needs to detect voltage and current components from α − β coordinate system. In order to reduce the buffeting problem of sliding mode observers, an adaptive neural network is introduced, by the way of extracting angle speed estimated values from sliding mode observers, and these values are trained to obtain the compensate angular velocity and minus index value to suppress speed value. The performance of this sensorless speed regulation strategy in the high-speed region using a single current sensor with an optimized adaptive neural network is verified and evaluated by PSIM simulation and experiments.
Gaze-Based Interaction Intention Recognition in Virtual Reality
Authors: Chen Xiao-Lin , Hou Wen-Jun
Published: May 2022

With the increasing need for eye tracking in head-mounted virtual reality displays, the gaze-based modality has the potential to predict user intention and unlock intuitive new interaction schemes. In the present work, we explore whether gaze-based data and hand-eye coordination data can predict a user’s interaction intention with the digital world, which could be used to develop predictive interfaces. We validate it on the eye-tracking data collected from 10 participants in item selection and teleporting tasks in virtual reality. We demonstrate successful prediction of the onset of item selection and teleporting with an 0.943 F1-Score using a Gradient Boosting Decision Tree, which is the best among the four classifiers compared, while the model size of the Support Vector Machine is the smallest. It is also proven that hand-eye-coordination-related features can improve interaction intention recognition in virtual reality environments.
System-Based Testing of Protection for Center-Tapped Shunt Capacitor Banks
Authors: Mquqwana Manduleli Alfred , Krishnamurthy Senthil
Published: May 2022

In power systems, capacitor banks play a significant role in improving voltage profiles, reducing losses, and adjusting power factors. Security measures must be implemented quickly and reliably to protect them from a wide range of threats. As a consequence of capacitor bank failures, finding and fixing the damaged units/elements is more difficult, which may lead to voltage control difficulties or the loss of any of these benefits. The paper shows the application of system-based testing methods for protection systems using RelaySimTest software, which works with OMICRON injection test sets. System-based testing methods are applied to test voltage differential protection for center-tapped shunt capacitor banks. The use of system-based testing methods has many advantages over conventional testing methods, which include distributed testing, transient state conditions testing, etc., which in turn result in cost savings during the commissioning and testing phase. The impact of external faults on bank installation has been tested successfully.
A New Simple Function for Combustion and Cyclic Variation Modeling in Supercharged Spark Ignition Engines
Authors: Beccari Stefano , Pipitone Emiliano
Published: May 2022

Research in the field of Internal Combustion (IC) engines focuses on the drastic reduction of both pollutant and greenhouse gas emissions. A promising alternative to gasoline and diesel fuel is represented by the use of gaseous fuels, above all green hydrogen but also Natural Gas (NG). In previous works, the authors investigated the performance, efficiency, and emissions of a supercharged Spark Ignition (SI) engine fueled with mixtures of gasoline and natural gas; a detailed research involving the combustion process of this kind of fuel mixture has been previously performed and a lot of experimental data have been collected. Combustion modeling is a fundamental tool in the design and optimization process of an IC engine. A simple way to simulate the combustion evolution is to implement a mathematical function that reproduces the mass fraction burned (MFB) profile; the most used for this purpose is the Wiebe function. In a previous work, the authors proposed an innovative mathematical model, the Hill function, that allowed a better interpolation of experimental MFB profiles when compared to the Wiebe function. In the research work presented here, both the traditional Wiebe and the innovative Hill function have been calibrated using experimental MFB profiles obtained from a supercharged SI engine fueled with mixtures of gasoline and natural gas in different proportions; the two calibrated functions have been implemented in a zero-dimensional (0-D) SI engine model and compared in terms of both Indicated Mean Effective Pressure (IMEP) and cyclic pressure variation prediction reliability. It was found that the Hill function allows a better IMEP prediction for all the operating conditions tested (several engine speeds, supercharging pressures, and fuel mixtures), with a maximum prediction error of 2.7% compared to 4.3% of the Wiebe function. A further analysis was also performed regarding the cyclic pressure variation that affects all the IC engines during combustion and may lead to irregular engine operation; in this case, the Hill function proved to better predict the cyclic pressure variation with respect to the Wiebe function.
Dust Control Technology in Dry Directional Drilling in Soft and Broken Coal Seams
Authors: Wu Dongmei , Gao Jie , Lu Ke
Published: May 2022

High rate of dust generation and serious dust diffusion in dry directional drilling in soft and broken coal seams (SBCS) have long been critical problems in the mining process. To solve these problems, in this study, a dust hood was designed and applied to realize non-contact dust control in drilling holes. The optimal performance of the dust hood was achieved when different technical parameters, including the gap width between the dust hood and the drill pipe, the air-slot width of the sealing device, the slag discharge pressure, and the air curtain pressure were controlled at 2 mm, 0.2 mm, 0.3 MPa, and 0.5 MPa, respectively. As a result, the dust concentration was reduced from 540 mg/m3 to 15 mg/m3, with dust control efficiency reaching 97.2%. The in situ test results confirmed good dust control effects, as the dust control efficiency reached 98.3% after using the dust hood.
The Market Evolution of Medicinal and Aromatic Plants: A Global Supply Chain Analysis and an Application of the Delphi Method in the Mediterranean Area
Authors: Taghouti Ibtissem , Cristobal Roser , Brenko Anton , Stara Kalliopi , Markos Nikos , Chapelet Benjamin , Hamrouni Lamia , Buršić Dino , Bonet José-Antonio
Published: May 2022

There is an increasing evidence for the significant value and potential of Medicinal and Aromatic Plants (MAPs) worldwide. Among other non-wood forest products, MAPs are considered a key element of sustainable forest management and economic development. As part of Mediterranean cultural heritage, these plants are a major driver of rural tourism, in many areas representing an important raw material for various bio-based industrial sectors. Besides their economic value, MAPs enhance social integration and maintain gender balance as harvesting and processing MAPs is clearly a female dominated task. Despite the prominent contribution of MAPs to local development, conservation of biodiversity and the development of the traditional Mediterranean food system, many challenges and knowledge gaps could potentially place the sector’s development at risk. The aim of this work is to examine the present situation of the MAPs sector in the most productive countries around the Mediterranean and to identify future challenges and priority actions to develop the MAPs sector in the region. To do so, a supply chain analysis was performed to identify the main stakeholders involved. Various experts from Croatia, France, Greece, Spain, and Tunisia participated in the SWOT analysis and the Delphi approach employed in this study. The results highlight the main challenges facing the sector in Mediterranean countries. Five groups of challenges are identified, related mainly to certification and labelling, life quality and wellbeing, market development, research development, and transforming and processing. To overcome these challenges, a set of actions is validated by the interviewed experts with the aim of improving marketing strategies and including various innovations related to political, legal, organisational, and institutional frameworks.
Climate Risks and Opportunities of the Marine Fishery Industry: A Case Study in Taiwan
Authors: Ho Ching-Hsien
Published: May 2022

As climate change and extreme weather intensify, forecasting natural environmental changes involves high uncertainty and variation. Planned policy changes and the ability of fisheries to withstand these changes and impacts are major challenges in regard to addressing future climate hazards in Taiwan. Taiwan’s geographic location is favourable for the marine fishery industry, which is an important primary industry and a source of animal protein for residents of Taiwan. Recently, both long-term climate change and extreme climate hazards have led to shocks in the marine fishery industry. The resulting instability of the industry directly affects the market supply of and demand for seafood. We conduct a case study of a marine fishery industry in Taiwan that incorporates social concern assessments of risk perception and judgements of risk acceptance through risk management processes. Furthermore, we incorporate stakeholder participatory processes to reduce the gap in awareness of adaptation and to increase the opportunity to reach consensus and develop an integrated risk management model that enables decision-makers to better meet the needs of society. These measures will enhance all parties’ willingness to adapt and help achieve the goal of public–private collaboration in facing climate change challenges.
Impact of Modelling Surface Roughness in an Arterial Stenosis
Authors: Yi Jie , Tian Fang-Bao , Simmons Anne , Barber Tracie
Published: May 2022

Arterial stenosis is a problem of immediate significance, as cardiovascular disease is the number one leading cause of death worldwide. Generally, the study of stenotic flow assumes a smooth, curved stenosis and artery. However, the real situation is unlikely to present an infinitely smooth-surfaced arterial stenosis. Here, the impact of surface roughness on the flow in an arterial stenosis was studied via a computational fluid dynamics analysis. A patient-specific geometry with a smooth surface was reconstructed, and a partially rough model was built by artificially adding random roughness only on the stenotic region of the smooth model. It was found that the flow was oscillatory downstream of the stenosis in the models. A slightly lower velocity near the wall and more oscillatory flows were observed due to the presence of the roughness in the stenotic region. However, the pressure distributions did not vary significantly between the smooth and rough models. The differences in the wall shear metrics were slight in the stenotic region and became larger in the downstream region of the models.
Three-Phase-Lag Bio-Heat Transfer Model of Cardiac Ablation
Authors: Singh Sundeep , Saccomandi Paola , Melnik Roderick
Published: May 2022

Significant research efforts have been devoted in the past decades to accurately modelling the complex heat transfer phenomena within biological tissues. These modeling efforts and analysis have assisted in a better understanding of the intricacies of associated biological phenomena and factors that affect the treatment outcomes of hyperthermic therapeutic procedures. In this contribution, we report a three-dimensional non-Fourier bio-heat transfer model of cardiac ablation that accounts for the three-phase-lags (TPL) in the heat propagation, viz., lags due to heat flux, temperature gradient, and thermal displacement gradient. Finite element-based COMSOL Multiphysics software has been utilized to predict the temperature distributions and ablation volumes. A comparative analysis has been conducted to report the variation in the treatment outcomes of cardiac ablation considering different bio-heat transfer models. The effect of variations in the magnitude of different phase lags has been systematically investigated. The fidelity and integrity of the developed model have been evaluated by comparing the results of the developed model with the analytical results of the recent studies available in the literature. This study demonstrates the importance of considering non-Fourier lags within biological tissue for predicting more accurately the characteristics important for the efficient application of thermal therapies.
Studies on Flavor Compounds and Free Amino Acid Dynamic Characteristics of Fermented Pork Loin Ham with a Complex Starter
Authors: Tian Zhiqing , Zhu Qiujin , Chen Yuanshan , Zhou Ying , Hu Ke , Li Hongying , Lu Kuan , Zhou Jie , Liu Yuan , Chen Xi
Published: May 2022

Staphylococcus simulans and Lactobacillus plantarum screened from Guizhou specialty food were used to prepare fermented pork loin ham. The sensory qualities and flavor profiles of fermented pork loin hams from 0 to 42 days were investigated in order to reveal the dynamics of fermented pork loin ham. The results show that total free amino acids (TFAA) content reached the highest value on the 35th day, and the umami amino acids, including aspartic acid (ASP), glutamic acid (GLU), glycine (GLY), and alanine (ALA), were the main amino acids in all periods. Notably, the RV coefficient (0.875) indicates that free amino acids (FAA) are highly correlated with the sensory score of the E-tongue. In terms of the volatile compounds identified, the esters content gradually increased between 7 and 42 days, and ethyl octanoate was the most abundant compound during all periods. These esters imparted a characteristic aroma component to the fermented pork loin ham. The most important finding was that the increase in the content of esters represented by octanoic acid-ethyl ester might be related to the increase in the content of FAA with the increase in fermentation time. Both the E-nose and E-tongue showed good discrimination ability for fermented tenderloin ham with different fermentation times, which was crucial in cases with large clusters. In addition, the multiple factor analysis (MFA) indicated that the E-nose aroma value might be the key factor in distinguishing fermented pork loin ham with different fermentation times.
Identification of the CKM Gene as a Potential Muscle-Specific Safe Harbor Locus in Pig Genome
Authors: Xiong Youcai , Zhuang Rongzhi , Zhao Guangxing , Liu Yanwen , Su Yinyu , Wang Wei , Xi Xiaoning , Yang Yanyu , Han Xiaosong , Xie Shengsong , Wang Heng , Li Xinyun , Zuo Bo , Zhao Shuhong , Feng Zheng , Ruan Jinxue
Published: May 2022

Genetically modified pigs have shown considerable application potential in the fields of life science research and livestock breeding. Nevertheless, a barrier impedes the production of genetically modified pigs. There are too few safe harbor loci for the insertion of foreign genes into the pig genome. Only a few loci (pRosa26, pH11 and Pifs501) have been successfully identified to achieve the ectopic expression of foreign genes and produce gene-edited pigs. Here, we use CRISPR/Cas9-mediated homologous directed repair (HDR) to accurately knock the exogenous gene-of-interest fragments into an endogenous CKM gene in the porcine satellite cells. After porcine satellite cells are induced to differentiate, the CKM gene promoter simultaneously initiates the expression of the CKM gene and the exogenous gene. We infer preliminarily that the CKM gene can be identified as a potential muscle-specific safe harbor locus in pigs for the integration of exogenous gene-of-interest fragments.
The Effectiveness and Quality of Life Outcomes by Transoral Endoscopic Vestibular Thyroidectomy Using Intraoperative Indocyanin Green Fluorescence Imaging and Neuromonitoring—A Cohort Study
Authors: Alnehlaoui Fadi , Alsarraj Mohammad Nazih , Malaki Zuheir , Guraya Salman Yousuf
Published: May 2022

Background: Transoral endoscopic vestibular thyroidectomy (TOEVT), a variant of natural orifice transluminal endoscopic surgery, offers a scar-less thyroid to young females. However, few studies have compared the effectiveness and quality of life (QoL) outcomes of the TOEVT with open thyroidectomy (OT). This is the first study in the Middle East and North Africa region that compares the effectiveness, safety profile and QoL outcomes between TOEVT with OT. Methods: We reviewed the medical records of consecutive patients with TOETV and OT at Zulekha Hospital Sharjah and Dubai United Arab Emirates, between 1 January 2019 and 1 April 2021. The data for demographics, type of surgery, operative time, blood loss, post-operative nodule size, hospital stay and post-operative complications were analyzed. We used an SF-36 questionnaire pre- and postoperatively for the assessment of QoL in both groups. Findings: Out of a total of 41 OT and 32 TOEVT procedures, 59 patients (31 TOEVT and 28 OT) fulfilled the inclusion criteria. There were 45 women and 14 men with an average age of 41 years. The mean operating time was 126 min in TOEVT and 96 min in OT (p = 0.000). The mean thyroid size was 5.55 cm in TOEVT and 8.76 cm in OT (p = 0.000). Lastly, the mean intraoperative blood loss was 39 cc and 95.7 cc in TOEVT and OT, respectively (p = 0.001). There was one temporary hypocalcemia and seroma in TOEVT, four cases of temporary hypocalcemia and one with minor bleeding in OT. The post-operative QoL significantly improved in all patients. However, the QoL improved more significantly in the TOEVT group for bodily pain, vitality, role emotions and cosmetic concerns (p = 0.000). Conclusion: The safety profile and effectiveness of the TOEVT is comparable to the OT procedure. However, TOEVT has an additional advantage of being scarless and offers a better QoL.
Rhamnogalacturonan Endolyase Family 4 Enzymes: An Update on Their Importance in the Fruit Ripening Process
Authors: Morales-Quintana Luis , Ramos Patricio , Méndez-Yáñez Angela
Published: May 2022

Fruit ripening is a process that produces fruit with top sensory qualities that are ideal for consumption. For the plant, the final objective is seed dispersal. One of the fruit characteristics observed by consumers is texture, which is related to the ripening and softening of the fruit. Controlled and orchestrated events occur to regulate the expression of genes involved in disassembling and solubilizing the cell wall. Studies have shown that changes in pectins are closely related to the loss of firmness and fruit softening. For this reason, studying the mechanisms and enzymes that act on pectins could help to elucidate the molecular events that occur in the fruit. This paper provides a review of the enzyme rhamnogalacturonan endolyase (RGL; EC 4.2.2.23), which is responsible for cleavage of the pectin rhamnogalacturonan I (RGL-I) between rhamnose (Rha) and galacturonic acid (GalA) through the mechanism of β-elimination during fruit ripening. RGL promotes the loosening and weakening of the cell wall and exposes the backbone of the polysaccharide to the action of other enzymes. Investigations into RGL and its relationship with fruit ripening have reliably demonstrated that this enzyme has an important role in this process.
Factors Influencing the Levels of Awareness on Malaysian Healthy Plate Concept among Rural Adults in Malaysia
Authors: Che Abdul Rahim Norsyamlina , Ahmad Mohamad Hasnan , Siew Man Cheong , Zainuddin Ahmad Ali , Rodzlan Hasani Wan Shakira , Ganapathy Shubash Shander , Ahmad Noor Ani
Published: May 2022

Malaysian Healthy Plate was launched in 2017 as a vital component of the Malaysian Ministry of Health’s “Quarter-Quarter-Half” program. It is predicted that this concept will bring positive change to the citizen’s dietary habits; however, the residents in rural areas may experience less exposure to this campaign, or lack of understanding to the concept of Malaysian Healthy Plate. Hence, this study aims to assess factors affecting the campaign’s awareness among the rural population in Malaysia. The National Health and Morbidity Survey (NHMS) 2019 focused on Non-Communicable Diseases (NCDs). Data collection was carried out from July to September 2019. Questionnaires that pertained to awareness, knowledge, and practice were included in this nationwide survey. Data collected from adults in rural areas aged 18 years old and above were used as respondents for the statistical analysis. Complex sample multiple logistic regression analysis was conducted to determine the association between the independent variables and awareness of the Malaysian Healthy Plate concept. About four fifths (83.2%) of rural adults in Malaysia were unaware of the Malaysian Healthy Plate concept after three years of implementation. The unawareness was significantly higher in males (91.3%), adults aged above 60 years old (91.8%), adults of others ethnicity (88.5%), those without formal education (95.2%), widows/widowers/divorcees (88.1%), retirees/adults who were not working (88.4%), and household income at the bottom 40% (B40) (85.0%). Unawareness of this concept was significantly associated with male gender (aOR = 4.12; 95% CI: 3.06–5.56); age, 40–59 years (aOR = 1.46; 95% CI:1.08–1.97); without formal education (aOR = 3.47; 95% CI:1.34–9.01); working in private sector (aOR = 2.75; 95% CI: 1.59–4.77); self-employed (aOR = 2.78; 95% CI: 1.58–4.87); retirees (aOR = 2.32; 95% CI: 1.23–4.36); and unpaid workers (aOR = 2.61; 95% CI: 1.51–4.51). Awareness of the Malaysian Healthy Plate concept is associated with rural adults being males, with older age, with lower socio-economic status, without partner, and without job. This study suggests that a more effective strategy is needed to increase the awareness of the Malaysian Healthy Plate concept among rural adults.
Centering Indigenous Knowledges and Worldviews: Applying the Indigenist Ecological Systems Model to Youth Mental Health and Wellness Research and Programs
Authors: O’Keefe Victoria M. , Fish Jillian , Maudrie Tara L. , Hunter Amanda M. , Tai Rakena Hariata G. , Ullrich Jessica Saniġaq , Clifford Carrie , Crawford Allison , Brockie Teresa , Walls Melissa , Haroz Emily E. , Cwik Mary , Whitesell Nancy Rumbaugh , Barlow Allison
Published: May 2022

Globally, Indigenous communities, leaders, mental health providers, and scholars have called for strengths-based approaches to mental health that align with Indigenous and holistic concepts of health and wellness. We applied the Indigenist Ecological Systems Model to strengths-based case examples of Indigenous youth mental health and wellness work occurring in CANZUS (Canada, Australia, New Zealand, and United States). The case examples include research, community-led programs, and national advocacy. Indigenous youth development and well-being occur through strengths-based relationships across interconnected environmental levels. This approach promotes Indigenous youth and communities considering complete ecologies of Indigenous youth to foster their whole health, including mental health. Future research and programming will benefit from understanding and identifying common, strengths-based solutions beyond narrow intervention targets. This approach not only promotes Indigenous youth health and mental health, but ripples out across the entire ecosystem to promote community well-being.
Frailty as a Predictor of Poor Rehabilitation Outcomes among Older Patients Attending a Geriatric Day Hospital Program: An Observational Study
Authors: Andres Daniel , Imhoof Caroline , Bürge Markus , Jakob Gabi , Limacher Andreas , Stuck Anna K.
Published: May 2022

Background: The Geriatric Day Hospital (GDH) is an important outpatient geriatric service, but there are few data on the role of frailty as a potential predictor of poor outcomes in this setting. Methods: Data were analyzed from 499 patients aged ≥ 60 years attending a 12-week GDH program between 2018 and 2021. Frailty status was defined as non-frail (68, 13.6%), mild/moderate frailty (351, 70.3%), and severe frailty (80, 16.0%) based on the Clinical Frailty Scale (CFS). Outcomes were defined as (1) poor outcome (hospital readmission, death, or medical deterioration) during the program and (2) admission to permanent nursing home care upon completion of the program. Multivariate logistic models were used for predictive analyses. Results: The mean age was 80.3 (standard deviation 7.0); 58.3% were women. Overall, 77 patients (15.4%) had a poor outcome, and 48 (9.6%) were admitted to permanent nursing home care. Poor outcome was experienced by none of the non-frail patients (0%), by 49 (14.0%) patients with mild/moderate frailty, and 22 (27.5%) patients with severe frailty (adjusted OR, 2.0; 95% CI 1.3, 3.2; p < 0.01). Admission to a permanent nursing home care was experienced by none of the non-frail patients (0%), 20 (5.7%) of those with mild/moderate frailty, and 28 (35.0%) with severe frailty (adjusted OR, 2.9; 95% CI 1.3, 6.3; p < 0.01). Conclusions: The CFS is a promising risk predictor of poor outcome and admission to permanent nursing home discharge among older patients attending a GDH program.
Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development
Authors: Hwang Sung-Min , Jo Youn-Yi , Cohen Cinder Faith , Kim Yong-Ho , Berta Temugin , Park Chul-Kyu
Published: May 2022

The transient receptor potential vanilloid 1 (TRPV1) ion channel plays an important role in the peripheral nociceptive pathway. TRPV1 is a polymodal receptor that can be activated by multiple types of ligands and painful stimuli, such as noxious heat and protons, and contributes to various acute and chronic pain conditions. Therefore, TRPV1 is emerging as a novel therapeutic target for the treatment of various pain conditions. Notably, various peptides isolated from venomous animals potently and selectively control the activation and inhibition of TRPV1 by binding to its outer pore region. This review will focus on the mechanisms by which venom-derived peptides interact with this portion of TRPV1 to control receptor functions and how these mechanisms can drive the development of new types of analgesics.
4-Pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR)—A Novel Oncometabolite Modulating Cancer-Endothelial Interactions in Breast Cancer Metastasis
Authors: Koszalka Patrycja , Kutryb-Zajac Barbara , Mierzejewska Paulina , Tomczyk Marta , Wietrzyk Joanna , Serafin Pawel K. , Smolenski Ryszard T. , Slominska Ewa M.
Published: May 2022

The accumulation of specific metabolic intermediates is known to promote cancer progression. We analyzed the role of 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR), a nucleotide metabolite that accumulates in the blood of cancer patients, using the 4T1 murine in vivo breast cancer model, and cultured cancer (4T1) and endothelial cells (ECs) for in vitro studies. In vivo studies demonstrated that 4PYR facilitated lung metastasis without affecting primary tumor growth. In vitro studies demonstrated that 4PYR affected extracellular adenine nucleotide metabolism and the intracellular energy status in ECs, shifting catabolite patterns toward the accumulation of extracellular inosine, and leading to the increased permeability of lung ECs. These changes prevailed over the direct effect of 4PYR on 4T1 cells that reduced their invasive potential through 4PYR-induced modulation of the CD73-adenosine axis. We conclude that 4PYR is an oncometabolite that affects later stages of the metastatic cascade by acting specifically through the regulation of EC permeability and metabolic controls of inflammation.
Whole Aspect of Runx2 Functions in Skeletal Development
Authors: Komori Toshihisa
Published: May 2022

Runt-related transcription factor 2 (Runx2) is a fundamental transcription factor for bone development. In endochondral ossification, Runx2 induces chondrocyte maturation, enhances chondrocyte proliferation through Indian hedgehog (Ihh) induction, and induces the expression of vascular endothelial growth factor A (Vegfa), secreted phosphoprotein 1 (Spp1), integrin-binding sialoprotein (Ibsp), and matrix metallopeptidase 13 (Mmp13) in the terminal hypertrophic chondrocytes. Runx2 inhibits the apoptosis of the terminal hypertrophic chondrocytes and induces their transdifferentiation into osteoblasts and osteoblast progenitors. The transdifferentiation is required for trabecular bone formation during embryonic and newborn stages but is dispensable for acquiring normal bone mass in young and adult mice. Runx2 enhances the proliferation of osteoblast progenitors and induces their commitment to osteoblast lineage cells through the direct regulation of the expressions of a hedgehog, fibroblast growth factor (Fgf), Wnt, and parathyroid hormone-like hormone (Pthlh) signaling pathway genes and distal-less homeobox 5 (Dlx5), which all regulate Runx2 expression and/or protein activity. Runx2, Sp7, and Wnt signaling further induce osteoblast differentiation. In immature osteoblasts, Runx2 regulates the expression of bone matrix protein genes, including Col1a1, Col1a2, Spp1, Ibsp, and bone gamma carboxyglutamate protein (Bglap)/Bglap2, and induces osteoblast maturation. Osteocalcin (Bglap/Bglap2) is required for the alignment of apatite crystals parallel to the collagen fibers; however, it does not physiologically work as a hormone that regulates glucose metabolism, testosterone synthesis, or muscle mass. Thus, Runx2 exerts multiple functions essential for skeletal development.
Towards 3D Bioprinted Spinal Cord Organoids
Authors: Han Yilin , King Marianne , Tikhomirov Evgenii , Barasa Povilas , Souza Cleide Dos Santos , Lindh Jonas , Baltriukiene Daiva , Ferraiuolo Laura , Azzouz Mimoun , Gullo Maurizio R. , Kozlova Elena N.
Published: May 2022

Three-dimensional (3D) cultures, so-called organoids, have emerged as an attractive tool for disease modeling and therapeutic innovations. Here, we aim to determine if boundary cap neural crest stem cells (BC) can survive and differentiate in gelatin-based 3D bioprinted bioink scaffolds in order to establish an enabling technology for the fabrication of spinal cord organoids on a chip. BC previously demonstrated the ability to support survival and differentiation of co-implanted or co-cultured cells and supported motor neuron survival in excitotoxically challenged spinal cord slice cultures. We tested different combinations of bioink and cross-linked material, analyzed the survival of BC on the surface and inside the scaffolds, and then tested if human iPSC-derived neural cells (motor neuron precursors and astrocytes) can be printed with the same protocol, which was developed for BC. We showed that this protocol is applicable for human cells. Neural differentiation was more prominent in the peripheral compared to central parts of the printed construct, presumably because of easier access to differentiation-promoting factors in the medium. These findings show that the gelatin-based and enzymatically cross-linked hydrogel is a suitable bioink for building a multicellular, bioprinted spinal cord organoid, but that further measures are still required to achieve uniform neural differentiation.