bluuebunny/crossref_metadata_2025 huggingface dataset:
Reference Values and Repeatability of Pulsed Wave Doppler Echocardiography Parameters in Normal Donkeys
Authors: Marzok Mohamed , Almubarak Adel I. , Al Mohamad Zakriya , Salem Mohamed , Farag Alshimaa M. , Ibrahim Hussam M. , El-Ashker Maged R. , El-khodery Sabry
Published: September 2022

In the present study, thirty clinically healthy donkeys were used to establish the reference values and repeatability for Pulsed Wave Doppler echocardiographic variables of the mitral valve, aortic valve and myocardial performance. 2-dimensional Color flow mapping and spectral Doppler modes were performed. For the mitral valve, the mean velocity, pressure gradient and duration of E-wave were 57.7 ± 12.5 cm/s, 1.4 ± 0.7 mmHg and 0.4 ± 0.13 s, respectively. The velocity, pressure gradient and duration of the A-wave were 32.3 ± 9.1 cm/s, 0.3 ± 0.04 mmHg and 0.3 ± 0.1 s, respectively. The mitral valve area, pressure half time, pulsatility index (PI), resistance index (RI) and velocity time integral (VTI) were 1.8 ± 0.5 cm2, 66 ± 17 ms, 2.8 ± 1.4, 0.9 ± 0.03 and 19.1 ± 5.7 cm, respectively. For the aortic valve, the mean velocity was 64.9 ± 10.4 cm/s, pressure gradient was 1.8 ± 0.4 mmHg, pulsatility index was 1.4 ± 0.3, resistance index was 0.9 ± 0.02, VTI was 25.02 ± 6.2 cm, systolic/diastolic was 19 ± 4.7 and heart rate was 95.7 ± 28.9 per minute. For Myocardial Performance Index (LV)–Tei Index, the mean ejection, isovolumic relaxation, isovolumic contraction time and myocardial performance index were 0.24 ± 0.01, 0.14 ± 0.01, 0.14 ± 0.02 and 1.2 ± 0.1 s, respectively. The results of the present study provide the reference values of PW echocardiographic parameter measurements in normal adult donkeys. Such reference values are helpful, especially when confronted with clinical cases with cardiovascular disorders.
Influence of Heat Stress on Poultry Growth Performance, Intestinal Inflammation, and Immune Function and Potential Mitigation by Probiotics
Authors: Ahmad Rafiq , Yu Yu-Hsiang , Hsiao Felix Shih-Hsiang , Su Chin-Hui , Liu Hsiu-Chou , Tobin Isabel , Zhang Guolong , Cheng Yeong-Hsiang
Published: September 2022

Heat stress has emerged as a serious threat to the global poultry industry due to climate change. Heat stress can negatively impact the growth, gut health, immune function, and production and reproductive performances of poultry. Different strategies have been explored to mitigate heat stress in poultry; however, only a few have shown potential. Probiotics are gaining the attention of poultry nutritionists, as they are capable of improving the physiology, gut health, and immune system of poultry under heat stress. Therefore, application of probiotics along with proper management are considered to potentially help negate some of the negative impacts of heat stress on poultry. This review presents scientific insight into the impact of heat stress on poultry health and growth performance as well as the application of probiotics as a promising approach to alleviate the negative effects of heat stress in poultry.
Comparative Analysis of In Situ Eukaryotic Food Sources in Three Tropical Sea Cucumber Species by Metabarcoding
Authors: Jia Chenghao , Zhang Yue , Xu Qiang , Sun Chunyang , Wang Yanan , Gao Fei
Published: September 2022

In this study, the eukaryotic composition of gut contents in three tropical sea cucumber species, Stichopus monotuberculatus, S. chloronotus and Holothuria atra were surveyed and compared by metabarcoding analysis based on 18S rRNA gene V4 region. The sequences were assigned to 21.80 ± 1.07, 22.60 ± 0.68 and 22.40 ± 0.25 different phyla from the gut contents of S. monotuberculatus, S. chloronotus and H. atra, respectively, and those in sediment samples were assigned to 21.00 ± 1.67 phyla. The results of α-diversity showed that surface sediments had a greater eukaryotic diversity than gut contents, yet the guts of sea cucumbers had an enrichment effect on some microorganisms, including Diatomea and Apicomplex. A comparison of the gut eukaryotic community among the three species suggested that the feeding preference was different: S. monotuberculatus fed mainly on Diatomea and Arthropoda, and the other two species had higher Apicomplexa concentrations, which may be due to differences in the morphology of the tentacles and habitat preferences. Moreover, obvious different eukaryotic community composition in the gut contents of the three sea cucumber species and the surrounding sediments also might result from the animals’ selective feeding for sediment patches. The current study filled in gaps about feeding mechanisms of tropical sea cucumbers and provided a basis for further exploring the mechanism about selective feeding and sea cucumber–sediment interaction in the future.
Designed Multifunctional Peptides for Intracellular Targets
Authors: Juretić Davor
Published: September 2022

Nature’s way for bioactive peptides is to provide them with several related functions and the ability to cooperate in performing their job. Natural cell-penetrating peptides (CPP), such as penetratins, inspired the design of multifunctional constructs with CPP ability. This review focuses on known and novel peptides that can easily reach intracellular targets with little or no toxicity to mammalian cells. All peptide candidates were evaluated and ranked according to the predictions of low toxicity to mammalian cells and broad-spectrum activity. The final set of the 20 best peptide candidates contains the peptides optimized for cell-penetrating, antimicrobial, anticancer, antiviral, antifungal, and anti-inflammatory activity. Their predicted features are intrinsic disorder and the ability to acquire an amphipathic structure upon contact with membranes or nucleic acids. In conclusion, the review argues for exploring wide-spectrum multifunctionality for novel nontoxic hybrids with cell-penetrating peptides.
Design of an IoT-Based Remote Learning System for Medical Skill Training in the Age of COVID-19: Focusing on CPR Skill Training
Authors: Kwon Yeram , Lee Hyeongmook , Kim Wonjoon
Published: September 2022

Medical skill education has been scaled down due to the COVID-19 pandemic. In particular, the decrease in CPR skill training has caused the quality of medical services to deteriorate. While new online education methods have emerged, few studies exist on online teaching and its effects. Since the online teaching of medical skills presents several challenges for instructors, it has not been as effective as face-to-face training. This study designed a new remote system focusing on medical skill education. The proposed video-based application prototype uses an IoT device to measure CPR performance metrics and provides real-time data to users. It was tested using the Kano model on a small group of subjects. The effects of skill training were analyzed quantitatively and qualitatively. A comparative analysis of the remote group and face-to-face group revealed similar average values for appropriate compression depth. In other categories, the remote group fared poorer than the face-to-face group. Considering the high scores given to system usability in the USE survey, remote education shows promise as an alternative to face-to-face education. The significance of this study lies in being the first to develop and test a remote education system for medical skill training in the age of COVID-19.
Adaptive Industrial Control System Attack Sample Expansion Algorithm Based on Generative Adversarial Network
Authors: Sha Yun , Chen Zhaoyu , Liu Xuejun , Yan Yong , Du Chenchen , Liu Jiayi , Han Ranran
Published: September 2022

The scarcity of attack samples is the bottleneck problem of anomaly detection of underlying business data in the industrial control system. Predecessors have done a lot of research on temporal data generation, but most of them are not suitable for industrial control attack sample generation. The change patterns of the characteristics of the underlying business data attack samples can be divided into three types: oscillation type, step type, and pulse type. This paper proposes an adaptive industrial control attack sample expansion algorithm based on GAN, which expands the three types of features in different ways. The basic network structure of data expansion adopts GAN. According to the characteristics of oscillation type changes, momentum is selected as the optimizer. Aiming at the characteristics of step type changes, the Adam optimization method is improved. For pulse type features, attack samples are generated according to the location and length of the pulse. Compared with previous time-series data generation methods, this method is more targeted for each feature and has higher similarities.
Major Contribution of Halogenated Greenhouse Gases to Global Surface Temperature Change
Authors: Lu Qing-Bin
Published: September 2022

This paper aims to better understand why there was a global warming pause in 2000–2015 and why the global mean surface temperature (GMST) has risen again in recent years. We present and statistically analyze substantial time-series observed datasets of global lower-stratospheric temperature (GLST), troposphere–stratosphere temperature climatology, global land surface air temperature, GMST, sea ice extent (SIE) and snow cover extent (SCE), combined with modeled calculations of GLSTs and GMSTs. The observed and analyzed results show that GLST/SCE has stabilized since the mid-1990s with no significant change over the past two and a half decades. Upper-stratospheric warming at high latitudes has been observed and GMST or global land surface air temperature has reached a plateau since the mid-2000s with the removal of natural effects. In marked contrast, continued drastic warmings at the coasts of polar regions (particularly Russia and Alaska) are observed and well explained by the sea-ice-loss warming amplification mechanism. The calculated GMSTs by the parameter-free quantum-physics warming model of halogenated greenhouse gases (GHGs) show excellent agreement with the observed GMSTs after the natural El Niño southern oscillation and volcanic effects are removed. These results have provided strong evidence for the dominant warming mechanism of anthropogenic halogenated GHGs. The results also call for closer scrutiny of the assumptions made in current climate models.
Association between Long-Term Exposure to Fine Particulate Matter and Asthma Incidence among School-Aged Children
Authors: Lim Hyun-Mook , Ryoo Seung-Woo , Hong Yun-Chul , Kim Soon-Tae , Lim Youn-Hee , Lee Dong-Wook
Published: September 2022

Studies on the correlation of long-term PM2.5 exposure with childhood-onset asthma are limited to western countries. We aimed to study the association between long-term PM2.5 exposure and childhood-onset asthma in South Korea, which has higher ambient PM2.5 levels than western countries. We constructed a retrospective cohort of children aged 6–14 years living in seven metropolitan cities using the National Health Insurance service in South Korea from 2011 to 2016. Children who made a hospital visit with asthma from 2008 to 2010 were excluded. A child was diagnosed with asthma incidence if he or she visited the hospital three times or more with a primary diagnostic code of asthma. A time-varying Cox regression model was constructed to investigate the association of long-term district-level PM2.5 exposure with asthma incidence. Of the 1,425,638 children evaluated, 52,133 showed asthma incidence, with an incidence rate of 6.9 cases/1000 person-years. A 10 µg/m3 increase in the 48-month moving average PM2.5 exposure was associated with an elevated risk of asthma incidence, with a hazard ratio of 1.075 (95% confidence interval: 1.024–1.126), and this association was robust for different PM2.5 exposure levels (12-, 36-, and 60-month moving average). In this study, long-term exposure to PM2.5 was associated with asthma incidence in school-aged children in South Korea. Policies to reduce environmental PM2.5 levels and protect children from PM2.5 are necessary to prevent childhood-onset asthma.
Tuning ANN Hyperparameters by CPSOCGSA, MPA, and SMA for Short-Term SPI Drought Forecasting
Authors: Alawsi Mustafa A. , Zubaidi Salah L. , Al-Ansari Nadhir , Al-Bugharbee Hussein , Ridha Hussein Mohammed
Published: September 2022

Modelling drought is vital to water resources management, particularly in arid areas, to reduce its effects. Drought severity and frequency are significantly influenced by climate change. In this study, a novel hybrid methodology was built, data preprocessing and artificial neural network (ANN) combined with the constriction coefficient-based particle swarm optimisation and chaotic gravitational search algorithm (CPSOCGSA), to forecast standard precipitation index (SPI) based on climatic factors. Additionally, the marine predators algorithm (MPA) and the slime mould algorithm (SMA) were used to validate the performance of the CPSOCGSA algorithm. Climatic factors data from 1990 to 2020 were employed to create and evaluate the SPI 1, SPI 3, and SPI 6 models for Al-Kut City, Iraq. The results indicated that data preprocessing methods improve data quality and find the best predictors scenario. The performance of CPSOCGSA-ANN is better than MPA-ANN and SMA-ANN algorithms based on various statistical criteria (i.e., R2, MAE, and RMSE). The proposed methodology yield R2 = 0.93, 0.93, and 0.88 for SPI 1, SPI 3, and SPI 6, respectively.
Gait Kinematics and Asymmetries Affecting Fall Risk in People with Chronic Stroke: A Retrospective Study
Authors: Wang Shuaijie , Bhatt Tanvi
Published: September 2022

Stroke survivors are at a relatively higher risk of falling than their healthy counterparts. To identify the key gait characteristics affecting fall risk in this population, this study analyzed the gait kinematics and gait asymmetries for 36 community-dwelling people with chronic stroke (PwCS). According to their fall history in the last 12 months, they were divided into a fall group (n = 21) and non-fall group (n = 15), and then the gait kinematics (step length, stride length, stance time, swing time, trunk angle, and segment angles for lower limbs) and their asymmetries (symmetry ratio and symmetry index) were compared between these two groups. To investigate the relationship between fall types and gait characteristics, these variables were also compared between 11 slip-fallers and non-fallers, as well as between 7 trip-fallers and non-fallers. Our results indicated that the fallers showed smaller trunk and thigh angle, larger shank angle, and higher gait asymmetries (trunk and foot). Such changes in gait pattern could also be found in the trip-fallers, except the trunk angle. Additionally, the trip-fallers also showed a shorter step length, shorter stride length, shorter swing time, larger foot angle on the paretic side, and higher asymmetries in shank angle and step length, while the slip-fallers only showed changes in trunk angle and thigh angle and higher asymmetries in step length and foot angle compared to the non-fall group. Our results indicated that improper or pathological gait patterns (i.e., smaller thigh angle or higher foot asymmetry) increases the risk of falling in PwCS, and different fall types are associated with different gait characteristics. Our findings would be helpful for the development of fall risk assessment methods that are based on kinematic gait measurements. Implementation of objective fall risk assessments in PwCS has the potential to reduce fall-related injuries, leading to a reduction in associated hospital costs.
Analysis of Differentially Expressed Genes, MMP3 and TESC, and Their Potential Value in Molecular Pathways in Colon Adenocarcinoma: A Bioinformatics Approach
Authors: Busuioc Constantin , Nutu Andreea , Braicu Cornelia , Zanoaga Oana , Trif Monica , Berindan-Neagoe Ioana
Published: September 2022

Despite the great progress in its early diagnosis and treatment, colon adenocarcinoma (COAD) is still poses important issues to clinical management. Therefore, the identification of novel biomarkers or therapeutic targets for this disease is important. Using UALCAN, the top 25 upregulated and downregulated genes in COAD were identified. Then, a Kaplan–Meier plotter was employed for these genes for survival analysis, revealing the correlation with overall survival rate only for MMP3 (Matrix Metallopeptidase 3) and TESC (Tescalcin). Despite this, the mRNA expression levels were not correlated with the tumor stages or nodal metastatic status. MMP3 and TESC are relevant targets in COAD that should be additionally validated as biomarkers for early diagnosis and prevention. Ingenuity Pathway Analysis revealed the top relevant network linked to Post-Translational Modification, Protein Degradation, and Protein Synthesis, where MMP3 was at the core of the network. Another important network was related to cell cycle regulation, TESC being a component of this. We should also not underestimate the complex regulatory mechanisms mediated by the interplay of the multiple other regulatory molecules, emphasizing the interconnection with molecules related to invasion and migration involved in COAD, that might serve as the basis for the development of new biomarkers and therapeutic targets.
Recent Advances in Silver Nanostructured Substrates for Plasmonic Sensors
Authors: Gahlaut Shashank K. , Pathak Anisha , Gupta Banshi D.
Published: September 2022

Noble metal nanostructures are known to confine photon energies to their dimensions with resonant oscillations of their conduction electrons, leading to the ultrahigh enhancement of electromagnetic fields in numerous spectroscopic methods. Of all the possible plasmonic nanomaterials, silver offers the most intriguing properties, such as best field enhancements and tunable resonances in visible-to-near infrared regions. This review highlights the recent developments in silver nanostructured substrates for plasmonic sensing with the main emphasis on surface plasmon resonance (SPR) and surface-enhanced Raman spectroscopy (SERS) over the past decade. The main focus is on the synthesis of silver nanostructured substrates via physical vapor deposition and chemical synthesis routes and their applications in each sensing regime. A comprehensive review of recent literature on various possible silver nanostructures prepared through these methodologies is discussed and critically reviewed for various planar and optical fiber-based substrates.
Caregiver Burden in Movement Disorders and Neurodegenerative Diseases: Editorial
Authors: Klietz Martin
Published: September 2022

Caregiver burden is still an unmet need in the treatment of many neurodegenerative diseases [...]
Overexpression of GDNF in Spinal Cord Attenuates Morphine Analgesic Tolerance in Rats with Bone Cancer Pain
Authors: Xu Wei , Ding Zhuofeng , Song Zongbin , Wang Jian , Zhang Jie , Zou Wangyuan
Published: September 2022

Bone cancer pain (BCP) is one of the typical and distressing symptoms in cancer patients. Morphine is a widely used analgesic drug for BCP; however, long-term morphine administration will lead to analgesic tolerance. Our previous study indicated that spinal glial cell line-derived neurotrophic factor (GDNF) exerts analgesic effects in rats with BCP. In this study, BCP was established by inoculated Walker 256 carcinoma cells into rat tibias, while morphine tolerance (MT) was induced by intrathecally injecting morphine twice daily from the 9th to 15th postoperative day (POD) in BCP rats. The BCP rats developed mechanical and thermal hyperalgesia on POD 5 and it lasted to POD 15. The analgesic effect of morphine was decreased after repeat administration. Western blots and immunochemistry tests showed that GDNF was gradually decreased in the spinal cord after the development of MT in rats with BCP, and GDNF was colocalized with the μ opioid receptor (MOR) in the superficial laminate of the spinal cords. The overexpression of GDNF by lentivirus significantly attenuated MT, and restored the expression of MOR in the spinal cord. In summary, our results suggest that the reduction of GDNF expression participated in the development of MT in rats with BCP and could be a promising therapeutic option for BCP.
EEG-Parameter-Guided Anesthesia for Prevention of Emergence Delirium in Children
Authors: Han Yaqian , Miao Mengrong , Li Pule , Yang Yitian , Zhang Hui , Zhang Beibei , Sun Mingyang , Zhang Jiaqiang
Published: September 2022

Background: Emergence delirium (ED) usually occurs in children after surgery with an incidence of 10−80%. Though ED is mostly self-limited, its potential injuries cannot be ignored. Whether electroencephalography (EEG)-parameter-guided anesthesia could reduce the incidence of ED in pediatric surgery has not been fully discussed to date. Methods: Fifty-four boys aged 2–12 years undergoing elective hypospadias surgery under sevoflurane anesthesia were selected. In the EEG-parameter-guided group (E group), sevoflurane was used for anesthesia induction and was maintained by titrating the spectral edge frequency (SEF) to 10–15 and combining the monitoring of density spectral array (DSA) power spectra and raw EEG. While in the control group (C group), anesthesiologists were blinded to the SedLine screen (including SEF, DSA, and raw EEG) and adjusted the intraoperative drug usage according to their experience. Patients with a Pediatric Anesthesia Emergence Delirium (PAED) score > 10 were diagnosed with ED, while patients with a PAED score > 2 were diagnosed with emergence agitation (EA). Results: Finally, a total of 37 patients were included in this trial. The incidence of ED in the E group was lower than in the C group (5.6% vs. 36.8%; p = 0.04), while the incidence of EA was similar in the two groups (61% vs. 78.9%; p = 0.48). Intraoperative parameters including remifentanil dosage and the decrease in mean arterial pressure (MAP) were not different between the two groups (p > 0.05), but the mean end-tidal sevoflurane concentration (EtSevo) was lower in the E group than in the C group (p > 0.05). Moreover, during PACU stay, the extubation time and discharge time of the groups were similar, while the PAED scores within 5 min from extubation and the Face, Legs, Activity, Cry, and Consolability (FLACC) scores within 30 min from extubation were lower in the E group than in the C group. Conclusion: EEG-parameter-guided anesthesia management reduced the incidence of ED in children. Studies with larger sample sizes are needed to obtain more convincing results.
The Therapeutic Role of Plastic and Reconstructive Surgery in the Interdisciplinary Treatment of Soft-Tissue Sarcomas in Germany—Cross-Sectional Results of a Prospective Nationwide Observational Study (PROSa)
Authors: Thomas Benjamin , Bigdeli Amir K. , Nolte Steffen , Gazyakan Emre , Harhaus Leila , Bischel Oliver , Lehner Burkhard , Egerer Gerlinde , Mechtersheimer Gunhild , Hohenberger Peter , Horch Raymund E. , Andreou Dimosthenis , Schmitt Jochen , Schuler Markus K. , Eichler Martin , Kneser Ulrich
Published: September 2022

Although the involvement of plastic surgery has been deemed important in the treatment of sarcoma patients to avoid oncological compromises and ameliorate patient outcomes, it is not ubiquitously available. The accessibility of defect reconstruction and its therapeutic impact on sarcoma care is the subject of this analysis. Cross-sectional data from 1309 sarcoma patients were collected electronically at 39 German study centers from 2017 to 2019. A total of 621 patients with surgical treatment for non-visceral soft-tissue sarcomas were included. The associated factors were analyzed exploratively using multifactorial logistic regression to identify independent predictors of successful defect reconstruction, as well Chi-squared and Cochran–Mantel–Haenszel tests to evaluate subgroups, including limb-salvage rates in extremity cases. A total of 76 patients received reconstructive surgery, including 52 local/pedicled versus 24 free flaps. Sarcomas with positive margins upon first resection (OR = 2.3, 95%CI = 1.2–4.4) that were excised at centers with lower degrees of specialization (OR = 2.2, 95%CI = 1.2–4.2) were independently associated with the need for post-oncological defect coverage. In this context, the inhouse availability of plastic surgery (OR = 3.0, 95%CI = 1.6–5.5) was the strongest independent predictor for successful flap-based reconstruction, which in turn was associated with significantly higher limb-salvage rates (OR = 1.4, 95%CI = 1.0–2.1) in cases of extremity sarcomas (n = 366, 59%). In conclusion, consistent referral to specialized interdisciplinary sarcoma centers significantly ameliorates patient outcomes by achieving higher rates of complete resections and offering unrestricted access to plastic surgery. The latter in particular proved indispensable for limb salvage through flap-based defect reconstruction after sarcoma resection. In fact, although there remains a scarcity of readily available reconstructive surgery services within the current sarcoma treatment system in Germany, plastic and reconstructive flap transfer was associated with significantly increased limb-salvage rates in our cohort.
Current Progress of CAR-NK Therapy in Cancer Treatment
Authors: Pang Zhaojun , Wang Zhongyi , Li Fengqi , Feng Chunjing , Mu Xin
Published: September 2022

CD8+ T cells and natural killer (NK) cells eliminate target cells through the release of lytic granules and Fas ligand (FasL)-induced target cell apoptosis. The introduction of chimeric antigen receptor (CAR) makes these two types of cells selective and effective in killing cancer cells. The success of CAR-T therapy in the treatment of acute lymphoblastic leukemia (ALL) and other types of blood cancers proved that the immunotherapy is an effective approach in fighting against cancers, yet adverse effects, such as graft versus host disease (GvHD) and cytokine release syndrome (CRS), cannot be ignored for the CAR-T therapy. CAR-NK therapy, then, has its advantage in lacking these adverse effects and works as effective as CAR-T in terms of killing. Despite these, NK cells are known to be hard to transduce, expand in vitro, and sustain shorter in vivo comparing to infiltrated T cells. Moreover, CAR-NK therapy faces challenges as CAR-T therapy does, e.g., the time, the cost, and the potential biohazard due to the use of animal-derived products. Thus, enormous efforts are needed to develop safe, effective, and large-scalable protocols for obtaining CAR-NK cells. Here, we reviewed current progress of CAR-NK therapy, including its biological properties, CAR compositions, preparation of CAR-NK cells, and clinical progresses. We also discussed safety issues raised from genetic engineering. We hope this review is instructive to the research community and a broad range of readers.
Clone Phylogenetics Reveals Metastatic Tumor Migrations, Maps, and Models
Authors: Chroni Antonia , Miura Sayaka , Hamilton Lauren , Vu Tracy , Gaffney Stephen G. , Aly Vivian , Karim Sajjad , Sanderford Maxwell , Townsend Jeffrey P. , Kumar Sudhir
Published: September 2022

Dispersal routes of metastatic cells are not medically detected or even visible. A molecular evolutionary analysis of tumor variation provides a way to retrospectively infer metastatic migration histories and answer questions such as whether the majority of metastases are seeded from clones within primary tumors or seeded from clones within pre-existing metastases, as well as whether the evolution of metastases is generally consistent with any proposed models. We seek answers to these fundamental questions through a systematic patient-centric retrospective analysis that maps the dynamic evolutionary history of tumor cell migrations in many cancers. We analyzed tumor genetic heterogeneity in 51 cancer patients and found that most metastatic migration histories were best described by a hybrid of models of metastatic tumor evolution. Synthesizing across metastatic migration histories, we found new tumor seedings arising from clones of pre-existing metastases as often as they arose from clones from primary tumors. There were also many clone exchanges between the source and recipient tumors. Therefore, a molecular phylogenetic analysis of tumor variation provides a retrospective glimpse into general patterns of metastatic migration histories in cancer patients.
Epidemiologic Trends of Cutaneous T-Cell Lymphoma in Arkansas Reveals Demographic Disparities
Authors: Kayishunge Delice , Ly Sophia , Su Joseph , Wong Henry K.
Published: September 2022

Accurate demographic data are critical for comprehending and treating cutaneous T-cell lymphoma (CTCL). Our research aimed to determine the demographics and incidence trends of CTCL patients in Arkansas compared to those of the national CTCL population to recognize the underlying disparities. We collected data from 143 CTCL patients at the University of Arkansas for Medical Sciences (UAMS) and national CTCL patient data from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis revealed that males are affected more than females across all ages and races. CTCL incidence and mortality data show that CTCL has a steady increase at the national level and in Arkansas while disproportionately affecting the young black male population. In Arkansas, more than one-third of black patients presented at an advanced stage (IIB+) compared to one-fifth in the white population, and the mean age of death was more than a decade younger for black (60 years) than for white patients (74.6 years). Nationally, black male patients had the greatest mortality rate (0.5) compared to 0.32 for white males. CTCL is 2.23 and 2.38 times more prevalent in urban versus rural areas in Arkansas and nationally, respectively. Most Arkansas patients reside near major interstates and chemical-emitting sites. In conclusion, our demographic analysis of Arkansas and national CTCL patients verifies recent trends toward more aggressive presentations in young black male patients, and our geographic findings suggest possible environmental risk factors.
PARP Inhibitors for Breast Cancer: Germline BRCA1/2 and Beyond
Authors: Menezes Maria , Raheem Farah , Mina Lida , Ernst Brenda , Batalini Felipe
Published: September 2022

Poly-adenosine diphosphate ribose polymerase (PARP) inhibitors (PARPi) are approved for BRCA1/2 carriers with HER2-negative breast cancer in the adjuvant setting with a high risk of recurrence as well as the metastatic setting. However, the indications for PARPi are broader for patients with other cancer types (e.g., prostate and ovarian cancer), involving additional biomarkers (e.g., ATM, PALB2, and CHEK) and genomic instability scores. Herein, we summarize the data on PARPi and breast cancer and discuss their use beyond BRCA carriers.
A Score to Predict the Malignancy of a Breast Lesion Based on Different Contrast Enhancement Patterns in Contrast-Enhanced Spectral Mammography
Authors: Nicosia Luca , Bozzini Anna Carla , Palma Simone , Montesano Marta , Pesapane Filippo , Ferrari Federica , Dominelli Valeria , Rotili Anna , Meneghetti Lorenza , Frassoni Samuele , Bagnardi Vincenzo , Sangalli Claudia , Cassano Enrico
Published: September 2022

Background: To create a predictive score of malignancy of a breast lesion based on the main contrast enhancement features ascertained by contrast-enhanced spectral mammography (CESM). Methods: In this single-centre prospective study, patients with suspicious breast lesions (BIRADS > 3) were enrolled between January 2013 and February 2022. All participants underwent CESM prior to breast biopsy, and eventually surgery. A radiologist with 20 years’ experience in breast imaging evaluated the presence or absence of enhancement and the following enhancement descriptors: intensity, pattern, margin, and ground glass. A score of 0 or 1 was given for each descriptor, depending on whether the enhancement characteristic was predictive of benignity or malignancy (both in situ and invasive). Then, an overall enhancement score ranging from 0 to 4 was obtained. The histological results were considered the gold standard in the evaluation of the relationship between enhancement patterns and malignancy. Results: A total of 321 women (median age: 51 years; range: 22–83) with 377 suspicious breast lesions were evaluated. Two hundred forty-nine lesions (66%) have malignant histological results (217 invasive and 32 in situ). Considering an overall enhancement score ≥ 2 as predictive of malignancy, we obtain an overall sensitivity of 92.4%; specificity of 89.8%; positive predictive value of 94.7%; and negative predictive value of 85.8%. Conclusions: Our proposed predictive score on the enhancement descriptors of CESM to predict the malignancy of a breast lesion shows excellent results and can help in early breast cancer diagnosis and in avoiding unnecessary biopsies.
Small Nucleolar RNAs in Pseudoexfoliation Glaucoma
Authors: Gasińska Karolina , Czop Marcin , Kosior-Jarecka Ewa , Wróbel-Dudzińska Dominika , Kocki Janusz , Żarnowski Tomasz
Published: September 2022

Small nucleolar RNAs (snoRNAs) are small non-coding regulatory RNAs that have been investigated extensively in recent years. However, the relationship between snoRNA and glaucoma is still unknown. This study aims to analyze the levels of snoRNA expression in the aqueous humor (AH) of patients with pseudoexfoliation glaucoma (PEXG) compared to a control group and identify hypothetical snoRNA-dependent mechanisms contributing to PEXG. The AH was obtained from eighteen Caucasian patients, comprising nine PEXG and nine age-matched control patients. RNA was isolated, and a microarray system was used to determine the snoRNA expression profiles. Functional and enrichment analyses were performed. We identified seven snoRNAs, SNORD73B, SNORD58A, SNORD56, SNORA77, SNORA72, SNORA64, and SNORA32, in the AH of the PEXG and control group patients. Five snoRNAs showed statistically significantly lower expression in the PEXG group, and two snoRNAs had statistically significantly higher expression in the PEXG group compared to the control group. In addition, we identified two factors—CACNB3 for SNORA64 and TMEM63C for SNORA32, similar to PEX-related genes (CACNA1A and TMEM136). The enrichment analysis for four genes targeted by snoRNAs revealed possible mechanisms associated with glaucoma and/or PEX, but the direct role of snoRNAs in these biological processes was not proven.
Comparative Analysis of Arsenic Transport and Tolerance Mechanisms: Evolution from Prokaryote to Higher Plants
Authors: Zhang Jie , Liu Jiayou , Zheng Fubin , Yu Min , Shabala Sergey , Song Won-Yong
Published: September 2022

Arsenic (As) is a toxic metalloid for all living organisms and can cause serious harm to humans. Arsenic is also toxic to plants. To alleviate As toxicity, all living organisms (from prokaryotes to higher plants) have evolved comprehensive mechanisms to reduce cytosolic As concentration through the set of As transporters localized at the plasma and tonoplast membranes, which operate either in arsenite As(III) extrusion out of cells (via ArsB, ACR3, and aquaporins) or by sequestering arsenic into vacuoles (by ABC transporters). In addition, a special arsenate resistance mechanism found in some bacterial systems has evolved in an As hyperaccumulating fern Pteris vittata, which involves transforming arsenate As(V) to an As(V) phosphoglycerate derivative by a glyceraldehyde 3-phosphate dehydrogenase and transporting this complex by an efflux transporter. In the present review, we summarize the evolution of these arsenic resistance mechanisms from prokaryotes to eukaryotes and discuss future approaches that could be utilized to better understand and improve As resistance mechanisms in plants.
Reduced miR-146a-5p Is a Biomarker of Infant Respiratory Diseases Contributing to Immune Dysregulation in Small Airway Epithelial Cells
Authors: Rodrigo-Muñoz José M. , Gil-Martínez Marta , Lorente-Sorolla Clara , Sastre Beatriz , García-García María Luz , Calvo Cristina , Casas Inmaculada , del Pozo Victoria
Published: September 2022

Respiratory diseases such as bronchiolitis, and those with wheezing episodes, are highly important during infancy due to their potential chronicity. Immune response dysregulation is critical in perpetuating lung damage. Epigenetic modifications including microRNA (miRNA) post-transcriptional regulation are among the factors involved in alleviating inflammation. We evaluated the expression of miR-146a-5p, a previously described negative regulator of immunity, in infants with respiratory diseases, in order to study epigenetic regulation of the immune response. Nasopharyngeal aspirate (NPA) was obtained from infants with bronchiolitis (ongoing and post-disease) or with wheezing episodes in addition to healthy controls. Virus presence was determined by nested PCR, while miRNA and gene expression were studied in cells from NPAs using qPCR. Healthy small airway epithelial cells (SAECs) were used as an in vitro model. We observe a reduction in miR-146a-5p expression in infants with either of the two diseases compared to controls, suggesting the potential of this miRNA as a disease biomarker. Post-bronchiolitis, miR-146a-5p expression increases, though without reaching levels of healthy controls. MiR-146a-5p expression correlates inversely with the immune-related gene PTGS2, while its expression correlates directly with TSLP. When heathy donor SAECs are stimulated by poly:IC, we observe an increase in miR-146a-5p, with wounds having a synergistic effect. In conclusion, infants with respiratory diseases present reduced miR-146a-5p expression, possibly affecting immune dysregulation.
Age and Sex-Related Changes in Retinal Function in the Vervet Monkey
Authors: Micaelo-Fernandes Catarina , Bouskila Joseph , Palmour Roberta M. , Bouchard Jean-François , Ptito Maurice
Published: September 2022

Among the deficits in visual processing that accompany healthy aging, the earliest originate in the retina. Moreover, sex-related differences in retinal function have been increasingly recognized. To better understand the dynamics of the retinal aging trajectory, we used the light-adapted flicker electroretinogram (ERG) to functionally assess the state of the neuroretina in a large cohort of age- and sex-matched vervet monkeys (N = 35), aged 9 to 28 years old, with no signs of obvious ocular pathology. We primarily isolated the cone–bipolar axis by stimulating the retina with a standard intensity light flash (2.57 cd/s/m2) at eight different frequencies, ranging from 5 to 40 Hz. Sex-specific changes in the voltage and temporal characteristics of the flicker waveform were found in older individuals (21–28 years-old, N = 16), when compared to younger monkeys (9–20 years-old, N = 19), across all stimulus frequencies tested. Specifically, significantly prolonged implicit times were observed in older monkeys (p < 0.05), but a significant reduction of the amplitude of the response was only found in old male monkeys (p < 0.05). These changes might reflect ongoing degenerative processes targeting the retinal circuitry and the cone subsystem in particular. Altogether, our findings corroborate the existing literature in humans and other species, where aging detrimentally affects photopic retinal responses, and draw attention to the potential contribution of different hormonal environments.
Inhibition of Mcl-1 Synergistically Enhances the Antileukemic Activity of Gilteritinib and MRX-2843 in Preclinical Models of FLT3-Mutated Acute Myeloid Leukemia
Authors: Wu Shuangshuang , Edwards Holly , Wang Deying , Liu Shuang , Qiao Xinan , Carter Jenna , Wang Yue , Taub Jeffrey W. , Wang Guan , Ge Yubin
Published: September 2022

FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (FLT3-ITD) mutations occur in about 25% of all acute myeloid leukemia (AML) patients and confer a poor prognosis. FLT3 inhibitors have been developed to treat patients with FLT3-mutated AML and have shown promise, though the acquisition of resistance occurs, highlighting the need for combination therapies to prolong the response to FLT3 inhibitors. In this study, we investigated the selective Mcl-1 inhibitor AZD5991 in combination with the FLT3 inhibitors gilteritinib and MRX-2843. The combinations synergistically induce apoptosis in AML cell lines and primary patient samples. The FLT3 inhibitors downregulate c-Myc transcripts through the suppression of the MEK/ERK and JAK2/STAT5 pathways, resulting in the decrease in c-Myc protein. This suppression of c-Myc plays an important role in the antileukemic activity of AZD5991. Interestingly, the suppression of c-Myc enhances AZD5991-inudced cytochrome c release and the subsequent induction of apoptosis. AZD5991 enhances the antileukemic activity of the FLT3 inhibitors gilteritinib and MRX-2843 against FLT3-mutated AML in vitro, warranting further development.
Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Promotes Forelimb Functional Recovery after Cervical Spinal Cord Injury
Authors: Zheng Yiyan , Gallegos Chrystine M. , Xue Haipeng , Li Shenglan , Kim Dong H. , Zhou Hongxia , Xia Xugang , Liu Ying , Cao Qilin
Published: September 2022

Locomotor function after spinal cord injury (SCI) is critical for assessing recovery. Currently, available means to improve locomotor function include surgery, physical therapy rehabilitation and exoskeleton. Stem cell therapy with neural progenitor cells (NPCs) transplantation is a promising reparative strategy. Along this line, patient-specific induced pluripotent stem cells (iPSCs) are a remarkable autologous cell source, which offer many advantages including: great potential to generate isografts avoiding immunosuppression; the availability of a variety of somatic cells without ethical controversy related to embryo use; and vast differentiation. In this current work, to realize the therapeutic potential of iPSC-NPCs for the treatment of SCI, we transplanted purified iPSCs-derived NPCs into a cervical contusion SCI rat model. Our results showed that the iPSC-NPCs were able to survive and differentiate into both neurons and astrocytes and, importantly, improve forelimb locomotor function as assessed by the grooming task and horizontal ladder test. Purified iPSC-NPCs represent a promising cell type that could be further tested and developed into a clinically useful cell source for targeted cell therapy for cervical SCI patients.
High Glucose Induces Late Differentiation and Death of Human Oral Keratinocytes
Authors: Shi Junhe , Han Chen , Chen Dandan , Trivedi Harsh M. , Bangash Hiba I. , Chen Lin
Published: September 2022

Keratinocytes are essential cells for wound repair. Impaired oral wound healing is common in diabetic patients with periodontal disease. High glucose, or hyperglycemia, impairs the cellular function of different cell types. However, it is unknown whether high glucose has a detrimental effect on the functions of oral keratinocytes. In the current study, a human gingival keratinocyte cell line, telomerase immortalized gingival keratinocytes (TIGK), was treated with high glucose (24 and 48 mM) for up to 120 h. Proliferation, migration, cell viability, and production of markers of differentiation, growth factors and enzymatic antioxidants were assessed after high glucose treatment. The results showed that high glucose significantly inhibited TIGK proliferation and migration. High glucose also induced significant cell death through apoptosis and necrosis as determined by flow cytometry, especially at 120 h after high glucose treatment. Necrosis was the dominant form of cell death induced. Real-time PCR showed that high glucose treatment upregulated mRNA expression of late keratinocyte differentiation makers, such as keratin 1, 10, 13 and loricrin, and downregulated enzymatic antioxidants, including superoxide dismutase 1, catalase, nuclear factor erythroid 2 -related factor 2, heme oxygenase 1. In conclusion, high glucose impairs the proliferation and migration of oral keratinocytes and likely induces cell death through the promotion of late cell differentiation and down-regulation of enzymatic antioxidants.
Investigation on Influencing Mechanism of Processing Parameters on Corrosion Resistance and Zinc Content of Anodic Coatings Developed on Magnesium Alloys in Near-Neutral Solutions
Authors: Zhang Wenxia , Zhu Yuanyuan , Zhao Rongfang , Zhang Shufang , Lai Xinying , Wang Yibo , Yan Zekun , Liu Wenjing , Zhang Rongfa
Published: September 2022

In near-neutral solutions, the effects of NH4HF2, H3PO4, phytic acid (IP6), and EDTA-ZnNa2 concentration on corrosion resistance and the Zn amount of micro-arc oxidation (MAO) coatings were revealed by an orthogonal experiment. The influencing order of four factors on coating corrosion resistance is EDTA-ZnNa2 > NH4HF2 > IP6 > H3PO4, while the sequence on the Zn amount is ranked as EDTA-ZnNa2 > NH4HF2 > H3PO4 > IP6. The fabricated Zn-containing coatings exhibit excellent corrosion resistance, and their icorr values are two orders of magnitude lower than that of the WE43 substrate, while the highest Zn amount achieves 4.12 wt.%. P and F compete to take part in coating formation, and Zn ions enter into anodic coatings by diffusion. Coating corrosion resistance is jointly determined by surface characteristics, which will provide the important theoretical foundation for fabricating Zn-containing coating with high corrosion resistance.
Influence of Moisture, Temperature and Bleaching on the Mechanical Properties of Coated Fiber-Based Substrates
Authors: Nienke Tobias , Kwade Arno , Eggerath Daniel
Published: September 2022

Substrates from fibrous materials are widely used in packaging applications and are produced in high quantities on roll-to-roll production lines. The anisotropic material behavior presents a demanding situation for the process control of the converting step. In this work, the influence of moisture and temperature on the mechanical properties of coated and uncoated fiber-based substrates and the influence of other material properties were investigated. The change of moisture content in relation to the surrounding temperature and relative humidity was investigated for different products. The hygroexpansion in dependence of the humidity is measured in machine and cross direction. The changes in the mechanical properties of the different materials due to changes in moisture content were investigated by tensile testing. The material behavior was highly responsive to the surrounding humidity and, thus, the material’s moisture content. A relative humidity between 60% and 70% showed the influence on the material properties most clearly. The presented work showed an influence of the coating on the moisture content for higher grammages. The effect of bleaching was also investigated. Bleaching decreases the potential for moisture absorption and, therefore, influences the moisture content and properties such as hygroexpansion. Coatings influence the hygroexpansion in an anisotropic manner. Coating and bleaching also influence the tensile properties of fiber-based materials. This article is an expanded version of a talk given at the 14th European Coating Symposium, 6–9 September 2021, Brussels, Belgium.