bluuebunny/crossref_metadata_2025 huggingface dataset:
Customized Manual Muscle Testing for Post-Stroke Upper Extremity Assessment
Authors: Roman Nadinne Alexandra , Miclaus Roxana Steliana , Nicolau Cristina , Sechel Gabriela
Published: March 2022

In neuro-rehabilitation, the assessment of post-stroke patients’ motor function of damaged upper extremities (UEs) is essential. Clinicians need clear and concise assessment instruments to monitor progress recorded in intensive rehabilitation sessions. One such instrument is Manual Muscle Testing (MMT), which, in our view, requires a modified scoring model aimed at improving the assessment process of patients’ motor and functional UE status, and recording their step-by-step-progress, especially if patients undergo a short length of hospitalization (of about 10 therapy days). Hence, this paper presents a new scoring system developed by the authors. This systemresults in a more precise MMT grading scale, which has more grades and can provide a more specific muscular assessment, while offering more clarity in quantifying patients’ progress after physical therapy. A prospective study was made of 41 post-stroke patients with upper extremity (UE) impairments. To determine the validity of the assessment tool for hypothesizing, and the unidimensionality and internal consistency of the customized model, exploratory and confirmatory factor analysis (CFA) with a structural equation model (SEM), Cronbach’s Alpha, and Pearson correlation coefficients were used with Fugl–Meyer (FM) assessments, the Modified Ashworth Scale (MAS), AROM, and the Modified Rankin Scale (MRS). Considering the unidimensionality of the instrument used, we performed a linear regression to identify whether certain movements performed segmentally by the manually evaluated muscles influence the measured manual score of the whole UE. All indices suggested a good model fit, and a Cronbach’s Alpha of 0.920 suggested strong internal consistency. The Pearson correlation coefficient of the MMT-customized score with AROM was 0.857, p < 0.001; that with FMUE was 0.905, p < 0.001; that with MRS was −0.608, p = 0.010; and that with MAS was −0.677, p < 0.001. The linear regression results suggest that wrist extensors, shoulder abductors, and finger flexors can influence the manual assessment of the muscle strength of the whole UE, thereby improving post-stroke patient management. The results of our research suggest that, using the proposed scoring, MMT may be a useful tool for UE assessment in post-stroke patients.
The Brain Dynamics of Syllable Duration and Semantic Predictability in Spanish
Authors: Muñetón-Ayala Mercedes , De Vega Manuel , Ochoa-Gómez John Fredy , Beltrán David
Published: March 2022

This study examines the neural dynamics underlying the prosodic (duration) and the semantic dimensions in Spanish sentence perception. Specifically, we investigated whether adult listeners are aware of changes in the duration of a pretonic syllable of words that were either semantically predictable or unpredictable from the preceding sentential context. Participants listened to the sentences with instructions to make prosodic or semantic judgments, while their EEG was recorded. For both accuracy and RTs, the results revealed an interaction between duration and semantics. ERP analysis exposed an interactive effect between task, duration and semantic, showing that both processes share neural resources. There was an enhanced negativity on semantic process (N400) and an extended positivity associated with anomalous duration. Source estimation for the N400 component revealed activations in the frontal gyrus for the semantic contrast and in the parietal postcentral gyrus for duration contrast in the metric task, while activation in the sub-lobar insula was observed for the semantic task. The source of the late positive components was located on posterior cingulate. Hence, the ERP data support the idea that semantic and prosodic levels are processed by similar neural networks, and the two linguistic dimensions influence each other during the decision-making stage in the metric and semantic judgment tasks.
Anticipatory Mourning and Narrative Meaning-Making in the Younger Breast Cancer Experience: An Application of the Meaning of Loss Codebook
Authors: Martino Maria Luisa , Lemmo Daniela , Testoni Ines , Iacona Erika , Pizzolato Laura , Freda Maria Francesca , Neimeyer Robert A.
Published: March 2022

Breast cancer (BC) in women under 50 is a potentially traumatic experience that can upset a woman’s life during a crucial phase of her lifespan. Anticipatory mourning linked to the diagnosis of BC can produce a series of inevitable losses similar to those of the bereaved. Narration can be one tool to construct meaning, to grow through the experience, and reconfigure time perspectives during and after the illness. The aim of this study was to apply the Meaning of Loss Codebook (MLC) to the narrative context of young women with BC. An ad hoc narrative interview was administered to 17 women at four times during the first year of treatment. A thematic analysis was performed using the MLC, adopting a bottom-up and top-down methodology. The results highlight the MLC’s usefulness in capturing the experiences of the women, allowing for a greater appreciation of the nuances of the meanings embodied in their narratives. The thematic categories grounded in the MLC cover the whole experience of BC during the first year of treatment, attesting to the possibility of extending the use of the MLC to observe the longitudinal elaboration of the psychic experience of BC in addition to its established validity in the context of bereavement and loss.
Public Service Motivation and Determining Factors to Attract and Retain Health Professionals in the Public Sector: A Systematic Review
Authors: Fernandes Alexandre , Santinha Gonçalo , Forte Teresa
Published: March 2022

(1) Background: The motivational determinants of health professionals to choose and remain in the public sector have been increasingly addressed, including the customized approach of Public Service Motivation (PSM). However, to date, no systematic research overview has been performed in this domain, leaving the body of literature unstructured. This article fills this gap by assessing the motivational factors of choice for the public sector in the health field, and the conceptual and methodological trends of this research stream. (2) Methods: This study follows the PRISMA protocol to ascertain patterns in past research and inform researchers, practitioners, and policymakers. Eighty-nine documents published between 1998 and 2021 were retained after selecting them according to their theme and outlined goals. (3) Results: Common motivational determinants are remuneration, available resources, work conditions, and frequency of contact and interaction with patients. The PSM construct and scale are often employed as main frameworks, but there is also a concern in assessing motivation drawing on psychological constructs that reflect the challenging line of work and environment that is health care, such as presenteeism, stress, and perception of hindrances. (4) Conclusions: By focusing on health professionals’ motivation, this study contributes to a timely systematization in challenging times for health institutions and their human resources.
The Use of Horizontal Shading Devices to Alleviate Overheating in Residential Buildings in the Severe Cold Region and Cold Region of China
Authors: Xu Yitong , Bo Rui , Chang Wen-Shao , Guo Haibo , Shao Yu
Published: March 2022

Global warming is resulting in higher summer indoor temperatures in the severe cold region and cold region of China, and this is affecting thermal comfort. Local building design codes consider these regions as cool in summer, and do not consider the phenomenon of overheating or propose countermeasures. This paper studied the possibility of overheating in residential buildings in these areas. It suggested alleviating this phenomenon using external horizontal shading, and discussed how to integrate thermal comfort into the building design and save energy consumption. The IESVE software was used to simulate 18-storey residential buildings with natural ventilation in Yichun, Harbin, Shenyang, Dalian, and Beijing, and to calculate the change in indoor operative temperature. Horizontal shading was designed for case study building to attempt to alleviate the overheating phenomenon in summer. The results showed that the case study building in the five cities experienced different degrees of overheating. External horizontal shading was successful in reducing indoor overheating, especially in the severe cold B and C zones and the cold A and B zones. The relevant building codes should be modified to take this into account. Reasonable design of horizontal shading can effectively reduce energy consumption, particularly when compared with air-conditioned buildings.
Harnessing the Heterogeneity of Prostate Cancer for Target Discovery Using Patient-Derived Explants
Authors: Centenera Margaret M. , Vincent Andrew D. , Moldovan Max , Lin Hui-Ming , Lynn David J. , Horvath Lisa G. , Butler Lisa M.
Published: March 2022

Prostate cancer is a complex and heterogeneous disease, but a small number of cell lines have dominated basic prostate cancer research, representing a major obstacle in the field of drug and biomarker discovery. A growing lack of confidence in cell lines has seen a shift toward more sophisticated pre-clinical cancer models that incorporate patient-derived tumors as xenografts or explants, to more accurately reflect clinical disease. Not only do these models retain critical features of the original tumor, and account for the molecular diversity and cellular heterogeneity of prostate cancer, but they provide a unique opportunity to conduct research in matched tumor samples. The challenge that accompanies these complex tissue models is increased complexity of analysis. With over 10 years of experience working with patient-derived explants (PDEs) of prostate cancer, this study provides guidance on the PDE method, its limitations, and considerations for addressing the heterogeneity of prostate cancer PDEs that are based on statistical modeling. Using inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) as an example of a drug that induces robust proliferative response, we demonstrate how multi-omics analysis in prostate cancer PDEs is both feasible and essential for identification of key biological pathways, with significant potential for novel drug target and biomarker discovery.
Converged DNA Damage Response Renders Human Hepatocellular Carcinoma Sensitive to CDK7 Inhibition
Authors: Xie Guiqin , Zhu Ailin , Gu Xinbin
Published: March 2022

Hepatocellular carcinoma (HCC) is a lethal malignancy with high mortality. The inhibition of cyclin-dependent kinase 7 (CDK7) activity has shown therapeutic efficacy in HCC. However, the underlying molecular mechanisms remain elusive. Here, we show that three HCC lines, HepG2, Hep3B, and SK-Hep-1, were highly susceptible to the CDK7 inhibitor THZ1. In mouse models, THZ1 effectively reduced HepG2 tumor growth and tumor weight. THZ1 arrested cell cycle and triggered MYC-related apoptosis in HepG2. To evaluate how MYC protein levels affected THZ1-induced apoptotic cell death, we overexpressed MYC in HepG2 and found that exogenously overexpressed MYC promoted cell cycle progression and increased cells in the S phase. THZ1 drastically engendered the apoptosis of MYC-overexpressing HepG2 cells in the S and G2/M phases. Importantly, transcription-inhibition-induced apoptosis is associated with DNA damage, and exogenous MYC expression further enhanced the THZ1-induced DNA damage response in MYC-overexpressing HepG2 cells. Consistently, in the HepG2 xenografts, THZ1 treatment was associated with DNA-damage-induced cell death. Together, our data indicate that the converged effect of MYC-promoted cell cycle progression and CDK7 inhibition by THZ1 confers the hypersensitivity of HCC to DNA-damage-induced cell death. Our findings may suggest a new therapeutic strategy of THZ1 against HCC.
Quantification of Tissue Compression Identifies High-Grade Glioma Patients with Reduced Survival
Authors: Fuster-Garcia Elies , Thokle Hovden Ivar , Fløgstad Svensson Siri , Larsson Christopher , Vardal Jonas , Bjørnerud Atle , Emblem Kyrre E.
Published: March 2022

The compression of peritumoral healthy tissue in brain tumor patients is considered a major cause of the life-threatening neurologic symptoms. Although significant deformations caused by the tumor growth can be observed radiologically, the quantification of minor tissue deformations have not been widely investigated. In this study, we propose a method to quantify subtle peritumoral deformations. A total of 127 MRI longitudinal studies from 23 patients with high-grade glioma were included. We estimate longitudinal displacement fields based on a symmetric normalization algorithm and we propose four biomarkers. We assess the interpatient and intrapatient association between proposed biomarkers and the survival based on Cox analyses, and the potential of the biomarkers to stratify patients according to their survival based on Kaplan–Meier analysis. Biomarkers show a significant intrapatient association with survival (p < 0.05); however, only compression biomarkers show the ability to stratify patients between those with higher and lower overall survival (AUC = 0.83, HR = 6.30, p < 0.05 for CompCH). The compression biomarkers present three times higher Hazard Ratios than those representing only displacement. Our study provides a robust and automated method for quantifying and delineating compression in the peritumoral area. Based on the proposed methodology, we found an association between lower compression in the peritumoral area and good prognosis in high-grade glial tumors.
Clinical Applications of Liquid Biopsy in Prostate Cancer: From Screening to Predictive Biomarker
Authors: Ionescu Filip , Zhang Jingsong , Wang Liang
Published: March 2022

Prostate cancer (PC) remains the most common malignancy and the second most common cause of cancer death in men. As a result of highly variable biological behavior and development of resistance to available agents under therapeutic pressure, optimal management is often unclear. Traditional surgical biopsies, even when augmented by genomic studies, may fail to provide adequate guidance for clinical decisions as these can only provide a snapshot of a dynamic process. Additionally, surgical biopsies are cumbersome to perform repeatedly and often involve risk. Liquid biopsies (LB) are defined as the analysis of either corpuscular (circulating tumor cells, extracellular vesicles) or molecular (circulating DNA or RNA) tumor-derived material. LB could more precisely identify clinically relevant alterations that characterize the metastatic potential of tumors, predict response to specific treatments or actively monitor for the emergence of resistance. These tests can potentially be repeated as often as deemed necessary and can detect real-time response to treatment with minimal inconvenience to the patient. In the current review, we consider common clinical scenarios to describe available LB assays in PC as a platform to explore existing evidence for their use in guiding decision making and to discuss current limitations to their adoption in the clinic.
Cost-Effectiveness of Artificial Intelligence Support in Computed Tomography-Based Lung Cancer Screening
Authors: Ziegelmayer Sebastian , Graf Markus , Makowski Marcus , Gawlitza Joshua , Gassert Felix
Published: March 2022

Background: Lung cancer screening is already implemented in the USA and strongly recommended by European Radiological and Thoracic societies as well. Upon implementation, the total number of thoracic computed tomographies (CT) is likely to rise significantly. As shown in previous studies, modern artificial intelligence-based algorithms are on-par or even exceed radiologist’s performance in lung nodule detection and classification. Therefore, the aim of this study was to evaluate the cost-effectiveness of an AI-based system in the context of baseline lung cancer screening. Methods: In this retrospective study, a decision model based on Markov simulation was developed to estimate the quality-adjusted life-years (QALYs) and lifetime costs of the diagnostic modalities. Literature research was performed to determine model input parameters. Model uncertainty and possible costs of the AI-system were assessed using deterministic and probabilistic sensitivity analysis. Results: In the base case scenario CT + AI resulted in a negative incremental cost-effectiveness ratio (ICER) as compared to CT only, showing lower costs and higher effectiveness. Threshold analysis showed that the ICER remained negative up to a threshold of USD 68 for the AI support. The willingness-to-pay of USD 100,000 was crossed at a value of USD 1240. Deterministic and probabilistic sensitivity analysis showed model robustness for varying input parameters. Conclusion: Based on our results, the use of an AI-based system in the initial low-dose CT scan of lung cancer screening is a feasible diagnostic strategy from a cost-effectiveness perspective.
PARP-1 Expression and BRCA1 Mutations in Breast Cancer Patients’ CTCs
Authors: Sklias Thodoris , Vardas Vasileios , Pantazaka Evangelia , Christopoulou Athina , Georgoulias Vassilis , Kotsakis Athanasios , Vasilopoulos Yiannis , Kallergi Galatea
Published: March 2022

BRCA1 and PARP are involved in DNA damage repair pathways. BRCA1 mutations have been linked to higher likelihood of triple negative breast cancer (TNBC). The aim of the study was to determine PARP-1 expression and BRCA1 mutations in circulating tumor cells (CTCs) of BC patients. Fifty patients were enrolled: 23 luminal and 27 TNBC. PARP expression in CTCs was identified by immunofluorescence. Genotyping was performed by PCR-Sanger sequencing in the same samples. PARP-1 expression was higher in luminal (61%) and early BC (54%), compared to TNBC (41%) and metastatic (33%) patients. In addition, PARP-1 distribution was mostly cytoplasmic in luminal patients (p = 0.024), whereas it was mostly nuclear in TNBC patients. In cytokeratin (CK)-positive patients, those with the CK+PARP+ phenotype had longer overall survival (OS, log-rank p = 0.046). Overall, nine mutations were detected; M1 and M2 were completely new and M4, M7 and M8 were characterized as pathogenic. M7 and M8 were predominantly found in metastatic TNBC patients (p = 0.014 and p = 0.002). Thus, PARP-1 expression and increased mutagenic burden in TNBC patients’ CTCs, could be used as an indicator to stratify patients regarding therapeutic approaches.
Exosomes on Endometrial Cancer: A Biomarkers Treasure Trove?
Authors: Sykaras Alexandros G. , Christofidis Konstantinos , Politi Ekaterini , Theocharis Stamatios
Published: March 2022

Endometrial cancer (EC) is one of the main causes of cancer-related death among women. In the last decade, the incidence of EC is on the rise, and the relative 5-year survival remains unchanged. This creates a dire need for new diagnostic and therapeutic approaches that can only result from a deeper understanding of the pathogenesis of the disease. In this direction, exosomes are under heavy research, with two main aims: to identify the potential diagnostic and prognostic markers and to develop technologies based on their use as therapeutic vectors targeting EC cells. Exosomes are widely available in all bodily fluids and are sources of ideal biomarkers for liquid biopsies. They are extracellular vesicles containing DNA, RNA, lipids, and proteins, which they transfer between cells, serving multiple functions and being implicated in both the physiological processes and the pathogenesis of diseases. Of all the biomolecules contained in exosomes, microRNAs (miRNAs) seem to have the most clinical utility in the diagnosis and treatment of EC. Exosomal miRNAs mediate the communication between EC cells, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) and have a pivotal role in the tumor cells’ proliferation, epithelial to mesenchymal transition (EMT), and the formation of a tumor microenvironment. They participate in many processes that are tied to carcinogenesis and cancer progression, and they are therefore considered as attractive therapeutic targets. Here, we review the functions of exosomes in EC, focusing on potential biomarkers of diagnostic and prognostic significance or potential therapeutic use.
Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study
Authors: Shimizu Takuto , Miyake Makito , Nishimura Nobutaka , Inoue Kuniaki , Fujii Koyo , Iemura Yusuke , Ichikawa Kazuki , Omori Chihiro , Tomizawa Mitsuru , Maesaka Fumisato , Oda Yuki , Miyamoto Tatsuki , Sakamoto Keiichi , Kiba Keisuke , Tanaka Masahiro , Oyama Nobuo , Okajima Eijiro , Fujimoto Ken , Hori Shunta , Morizawa Yosuke , Gotoh Daisuke , Nakai Yasushi , Torimoto Kazumasa , Tanaka Nobumichi , Fujimoto Kiyohide
Published: March 2022

To investigate the organ-specific response and clinical outcomes of mixed responses (MRs) to immune checkpoint inhibitors (ICIs) for unresectable or metastatic urothelial carcinoma (ur/mUC), we retrospectively analyzed 136 patients who received pembrolizumab. The total objective response rate (ORR) and organ-specific ORR were determined for each lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 as follows: (i) complete response (CR), (ii) partial response (PR), (iii) stable disease (SD), and (iv) progressive disease (PD). Most of the organ-specific ORR was 30–40%, but bone metastasis was only 5%. There was a significant difference in overall survival (OS) between responders and non-responders with locally advanced lesions and lymph node, lung, or liver metastases (HR 9.02 (3.63–22.4) p < 0.0001; HR 3.63 (1.97–6.69), p < 0.0001; HR 2.75 (1.35–5.59), p = 0.0053; and HR 3.17 (1.00–10.0), p = 0.049, respectively). MR was defined as occurring when PD happened in one lesion plus either CR or PR occurred in another lesion simultaneously, and 12 cases were applicable. MR was significantly associated with a poorer prognosis than that of the responder group (CR or PR; HR 0.09 (0.02–0.35), p = 0.004). Patients with bone metastases benefitted less. Care may be needed to treat patients with MR as well as patients with pure PD. Further studies should be conducted in the future.
Krüppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet
Authors: Brown Adam R. , Alhallak Iad , Simmen Rosalia C. M. , Melnyk Stepan B. , Heard-Lipsmeyer Melissa E. , Montales Maria Theresa E. , Habenicht Daniel , Van Trang T. , Simmen Frank A.
Published: March 2022

Obesity, oxidative stress, and inflammation are risk factors for hepatocellular carcinoma (HCC). We examined, in mice, the effects of Krüppel-like factor 9 (KLF9) knockout on: adiposity, hepatic and systemic oxidative stress, and hepatic expression of pro-inflammatory and NOX/DUOX family genes, in a high-fat diet (HFD) context. Male and female Klf9+/+ (wild type, WT) and Klf9−/− (knockout, KO) mice were fed HFD (beginning at age 35 days) for 12 weeks, after which liver and adipose tissues were obtained, and serum adiponectin and leptin levels, liver fat content, and markers of oxidative stress evaluated. Klf9−/− mice of either sex did not exhibit significant alterations in weight gain, adipocyte size, adipokine levels, or liver fat content when compared to WT counterparts. However, Klf9−/− mice of both sexes had increased liver weight/size (hepatomegaly). This was accompanied by increased hepatic oxidative stress as indicated by decreased GSH/GSSG ratio and increased homocysteine, 3-nitrotyrosine, 3-chlorotyrosine, and 4HNE content. Decreased GSH to GSSG ratio and a trend toward increased homocysteine levels were observed in the corresponding Klf9−/− mouse serum. Gene expression analysis showed a heightened pro-inflammatory state in livers from Klf9−/− mice. KLF9 suppresses hepatic oxidative stress and inflammation, thus identifying potential mechanisms for KLF9 suppression of HCC and perhaps cancers of other tissues.
Investigation of Colonic Regeneration via Precise Damage Application Using Femtosecond Laser-Based Nanosurgery
Authors: Donath Sören , Angerstein Leon , Gentemann Lara , Müller Dominik , Seidler Anna E. , Jesinghaus Christian , Bleich André , Heisterkamp Alexander , Buettner Manuela , Kalies Stefan
Published: March 2022

Organoids represent the cellular composition of natural tissue. So called colonoids, organoids derived from colon tissue, are a good model for understanding regeneration. However, next to the cellular composition, the surrounding matrix, the cell–cell interactions, and environmental factors have to be considered. This requires new approaches for the manipulation of a colonoid. Of key interest is the precise application of localized damage and the following cellular reaction. We have established multiphoton imaging in combination with femtosecond laser-based cellular nanosurgery in colonoids to ablate single cells in the colonoids’ crypts, the proliferative zones, and the differentiated zones. We observed that half of the colonoids recovered within six hours after manipulation. An invagination of the damaged cell and closing of the structure was observed. In about a third of the cases of targeted crypt damage, it caused a stop in crypt proliferation. In the majority of colonoids ablated in the crypt, the damage led to an increase in Wnt signalling, indicated via a fluorescent lentiviral biosensor. qRT-PCR analysis showed increased expression of various proliferation and Wnt-associated genes in response to damage. Our new model of probing colonoid regeneration paves the way to better understand organoid dynamics on a single cell level.
Simvastatin Prevents Liver Microthrombosis and Sepsis Induced Coagulopathy in a Rat Model of Endotoxemia
Authors: La Mura Vincenzo , Gagliano Nicoletta , Arnaboldi Francesca , Sartori Patrizia , Procacci Patrizia , Denti Luca , Liguori Eleonora , Bitto Niccolò , Ristagno Giuseppe , Latini Roberto , Dondossola Daniele , Salerno Francesco , Tripodi Armando , Colombo Massimo , Peyvandi Flora
Published: March 2022

Background: Endotoxemia causes endothelial dysfunction and microthrombosis, which are pathogenic mechanisms of coagulopathy and organ failure during sepsis. Simvastatin has potential anti-thrombotic effects on liver endothelial cells. We investigated the hemostatic changes induced by lipopolysaccharide (LPS) and explored the protective effects of simvastatin against liver vascular microthrombosis. Methods and results: We compared male Wistar rats exposed to LPS (5 mg/kg one i.p. dose) or saline in two experimental protocols—placebo (vehicle) and simvastatin (25 mg/kg die, orally, for 3 days before LPS). Morphological studies were performed by light- and electron-microscopy analyses to show intravascular fibrin deposition, vascular endothelial structure and liver damage. Peripheral- and organ-hemostatic profiles were analyzed using whole blood viscoelastometry by ROTEM, liver biopsy and western-blot/immunohistochemistry of thrombomodulin (TM), as well as immunohistochemistry of the von Willebrand factor (VWF). LPS-induced fibrin deposition and liver vascular microthrombosis were combined with a loss of sinusoidal endothelial TM expression and VWF-release. These changes were associated with parenchymal eosinophilia and necrosis. ROTEM analyses displayed hypo-coagulability in the peripheral blood that correlated with the degree of intrahepatic fibrin deposition (p < 0.05). Simvastatin prevented LPS-induced fibrin deposition by preserving TM expression in sinusoidal cells and completely reverted the peripheral hypo-coagulability caused by endotoxemia. These changes were associated with a significant reduction of liver cell necrosis without any effect on eosinophilia. Conclusions: Simvastatin preserves the antithrombotic properties of sinusoidal endothelial cells disrupted by LPS, deserving pharmacological properties to contrast sepsis-associated coagulopathy and hepatic failure elicited by endotoxemia
Insights into Early-Pregnancy Mechanisms: Mast Cells and Chymase CMA1 Shape the Phenotype and Modulate the Functionality of Human Trophoblast Cells, Vascular Smooth-Muscle Cells and Endothelial Cells
Authors: Zhang Ningjuan , Schumacher Anne , Fink Beate , Bauer Mario , Zenclussen Ana Claudia , Meyer Nicole
Published: March 2022

Spiral-artery (SA) remodeling is a fundamental process during pregnancy that involves the action of cells of the initial vessel, such as vascular smooth-muscle cells (VSMCs) and endothelial cells, but also maternal immune cells and fetal extravillous trophoblast cells (EVTs). Mast cells (MCs), and specifically chymase-expressing cells, have been identified as key to a sufficient SA-remodeling process in vivo. However, the mechanisms are still unclear. The purpose of this study is to evaluate the effects of the MC line HMC-1 and recombinant human chymase (rhuCMA1) on human primary uterine vascular smooth-muscle cells (HUtSMCs), a human trophoblast cell line (HTR8/SV-neo), and human umbilical-vein endothelial cells (HUVEC) in vitro. Both HMC-1 and rhuCMA1 stimulated migration, proliferation, and changed protein expression in HUtSMCs. HMC-1 increased proliferation, migration, and changed gene expression of HTR8/SVneo cells, while rhuCMA treatment led to increased migration and decreased expression of tissue inhibitors of matrix metalloproteinases. Additionally, rhuCMA1 enhanced endothelial-cell-tube formation. Collectively, we identified possible mechanisms by which MCs/rhuCMA1 promote SA remodeling. Our findings are relevant to the understanding of this crucial step in pregnancy and thus of the dysregulated pathways that can lead to pregnancy complications such as fetal growth restriction and preeclampsia.
STING Agonists/Antagonists: Their Potential as Therapeutics and Future Developments
Authors: Guerini Danilo
Published: March 2022

The cGAS STING pathway has received much attention in recent years, and it has been recognized as an important component of the innate immune response. Since the discovery of STING and that of cGAS, many observations based on preclinical models suggest that the faulty regulation of this pathway is involved in many type I IFN autoinflammatory disorders. Evidence has been accumulating that cGAS/STING might play an important role in pathologies beyond classical immune diseases, as in, for example, cardiac failure. Human genetic mutations that result in the activation of STING or that affect the activity of cGAS have been demonstrated as the drivers of rare interferonopathies affecting young children and young adults. Nevertheless, no data is available in the clinics demonstrating the therapeutic benefit in modulating the cGAS/STING pathway. This is due to the lack of STING/cGAS-specific low molecular weight modulators that would be qualified for clinical exploration. The early hopes to learn from STING agonists, which have reached the clinics in recent years for selected oncology indications, have not yet materialized since the initial trials are progressing very slowly. In addition, transforming STING agonists into potent selective antagonists has turned out to be more challenging than expected. Nevertheless, there has been progress in identifying novel low molecular weight compounds, in some cases with unexpected mode of action, that might soon move to clinical trials. This study gives an overview of some of the potential indications that might profit from modulation of the cGAS/STING pathway and a short overview of the efforts in identifying STING modulators (agonists and antagonists) suitable for clinical research and describing their potential as a “drug”.
Grape Cultivar Identification and Classification by Machine Olfaction Analysis of Leaf Volatiles
Authors: Khorramifar Ali , Karami Hamed , Wilson Alphus Dan , Sayyah Amir Hosein Afkari , Shuba Anastasiia , Lozano Jesús
Published: March 2022

Development of electronic technologies for precise identification of fruit crop cultivars in agricultural production provides an effective means for assuring product quality and authentication. The capabilities of discriminating between grape (Vitis vinifera L.) cultivars is essential for assuring certification of varieties sold in world markets. Machine olfaction, based on electronic-nose (e-nose) technologies, is readily available for rapid identification of fruit and vegetative agricultural products. This technology relies on detection of and discrimination between volatile organic compound (VOC) emissions from plant parts. It may be used in all stages of agricultural production to facilitate crop maintenance, cultivation, and harvesting decisions prior to marketing. An experimental e-nose device was constructed and tested in combination with five chemometric methods, including PCA, LDA, QDA, SVM, and ANN, as rapid, non-destructive tools for identification and classification of grape cultivars. An e-nose instrument equipped with nine metal oxide semiconductor (MOS) sensors was utilized to identify and classify five grape cultivars based on leaf VOC emissions using supervised and non-supervised methods. Grape leaf samples were first identified as belonging to specific cultivar types using PCA analyses, which are non-supervised classification methods, with the first two principal components (PC-1 and PC-2) accounting for 89% of the total variance. Four supervised statistical methods were further tested, including DA, QDA, SVM, and ANN, and provided effective discrimination accuracies of 98%, 99%, 92%, and 99%, respectively. These findings confirmed the suitable applicability of an MOS e-nose sensor array with supervised methods for accurate identification of grape cultivars, which is useful for authentication of vine cultivar types for commercial markets.
Moderators of Food Insecurity and Diet Quality in Pairs of Mothers and Their Children
Authors: Aggeli Christine , Patelida Maria , Grammatikopoulou Maria G. , Matzaridou Ekaterini-Avrakomi , Berdalli Marina , Theodoridis Xenophon , Gkiouras Konstantinos , Persynaki Angeliki , Tsiroukidou Kyriaki , Dardavessis Theodore , Tzimos Christos , Goulis Dimitrios G. , Vassilakou Tonia
Published: March 2022

Research has suggested that maternal diet and characteristics may influence the diet of offspring during childhood. The present cross-sectional study aimed to assess the influence of distinct maternal characteristics and the diet quality of mothers on the prevalence of household food insecurity (FI) and the diet quality of children. A total of 179 mother–child pairs were recruited from two primary schools in the metropolitan area of Thessaloniki. The children were aged between 10 and 12 years old. Diet quality was assessed as the level of adherence to the Mediterranean diet (MD), with the use of the KIDMED for the children and the MedDietScore for the mothers. The household FI and the social and demographic characteristics of the mothers were also recorded, and anthropometric measures of both the mothers and their children were collected. Approximately ¼ (26.3%) of the pairs reported some degree of FI, with a greater prevalence (64.7%) within single-mother families. Moreover, FI affected the level of maternal MD adherence (p = 0.011). On the other hand, FI was decreased in households with a greater maternal educational level (OR: 0.25; 95% CI: 0.10–0.63) and conjugal family status (OR: 0.15; 95% CI: 0.87–0.52). Maternal adherence to the MD was inversely related to the respective adherence of their offspring (OR: 0.93; 95% CI: 0.86–0.997), suggesting that during periods of financial constraints, maternal diet quality is compromised at the expense of affording a better diet for the minors in the family.
OK-432 Treatment of Ranula Intruding into the Cervical Region
Authors: Ohta Nobuo , Shirane Shion , Fukase Shigeru , Kawata Rei , Sato Teruyuki , Satani Nozomi , Suzuki Takahiro
Published: March 2022

Objectives: Plunging ranula intruding into the cervical region is rare and a standard therapy has not yet been consolidated. This paper investigates the outcomes and side effects of OK-432 treatment in patients with a ranula extending into the cervical region. Methods: The study design and setting consisted of a planned data collection at Tohoku Medical and Pharmaceutical University and Fukase Clinic. Eight patients with ranula extending into the cervical region received OK-432 treatment between January 2016 and February 2019. OK-432 treatment was performed for patients with ranula extending into the cervical region. Results: In all patients, a total shrinkage and marked reduction in lesions were observed without local scars or deformations after OK-432 treatment. Complications were local swelling and mild fever (37.5–38.5 °C), which lasted a few days in half of the patients. Conclusions: OK-432 treatment is straightforward, secure, and efficacious and can be substituted for surgery in the treatment of ranula extending into the cervical region.
Preparation and Strengthening Mechanisms of Ultrasonic-Assisted Cr3C2 Particle-Reinforced Al Matrix Composite
Authors: Xue Yisong , Zhai Wenyan , Li Xiao , Sun Liang , Wang Yiran , Liu Yanming , Dong Hui
Published: March 2022

A novelty Al matrix composite reinforced with Cr3C2 particles was prepared by an ultrasound vibration treatment-assisted casting process. The Cr3C2 content on the microstructure and mechanical properties of Cr3C2p/Al composite were researched systematically. The results indicated that Cr3C2 particles were effectively distributed around the grain boundary and led to a great reduction in crystalline size. The density, porosity, and Vickers hardness of the composites rose simultaneously with the increase of Cr3C2 content. Meanwhile, the tensile strength and yield strength increased by 104.5% and 85.7%, respectively by adding 3.0 wt. % Cr3C2. The fracture morphologies showed that the fracture mechanism was plastic fracture for the pure Al and gradually transformed to brittle fracture as the content of Cr3C2 exceeded 3.0 wt. %. Moreover, the strengthening mechanism of the composite was also discussed.
Evaluation of Tribological and Mechanical Properties of Carbon Steel with Fluoroligomeric Film at Piezoelectric Actuator Contact
Authors: Padgurskas Juozas , Rukuiža Raimundas , Žunda Audrius
Published: March 2022

The tribological investigations of carbon steel surfaces modified with fluoroligomeric materials were performed. Compared with the uncoated steel, the fluoroligomeric coated surface showed higher plasticity of the modified surface in the scratch tests where the fluoroligomeric film was not destroyed by higher loading. This could be explained by the lower micro hardness of the steel after processing by fluoroligomer and the influence of the adsorbic Rebinder effect. This study includes original results of the loading influence on the efficiency of the piezoelectric actuator and the wear value of the frictional element, which is important explaining the greater longevity of the piezoelectric actuator. Fluoroligomer treatment of the surface considerably improved the performance of the piezoelectric actuator. Using the reference steel roller in the piezoelectric actuator under minimum loads was characterized by a decrease in rotor speed with increasing the pressing of the frictional element. When the rotor was coated by fluoroligomer, the speed remained stable when increasing the pressing force. Using the reference steel roller, the rotation after short-term overloads was not restored, and rollers with fluoroligomeric surface started to rotate soon as the short-term overload was removed. The higher efficiency of piezoelectric actuators with a fluoroligomeric layer on the roller is related to almost two times lower wear of a friction element operating with coated rollers as compared to reference rollers.
Concordance between Preoperative mpMRI and Pathological Stage and Its Influence on Nerve-Sparing Surgery in Patients with High-Risk Prostate Cancer
Authors: Humke Clara , Hoeh Benedikt , Preisser Felix , Wenzel Mike , Welte Maria N. , Theissen Lena , Bodelle Boris , Koellermann Jens , Steuber Thomas , Haese Alexander , Roos Frederik , Kluth Luis Alex , Becker Andreas , Chun Felix K. H. , Mandel Philipp
Published: March 2022

Background: We aimed to determine the concordance between the radiologic stage (rT), using multiparametric magnetic resonance imaging (mpMRI), and pathologic stage (pT) in patients with high-risk prostate cancer and its influence on nerve-sparing surgery compared to the use of the intraoperative frozen section technique (IFST). Methods: The concordance between rT and pT and the rates of nerve-sparing surgery and positive surgical margin were assessed for patients with high-risk prostate cancer who underwent radical prostatectomy. Results: The concordance between the rT and pT stages was shown in 66.4% (n = 77) of patients with clinical high-risk prostate cancer. The detection of patients with extraprostatic disease (≥pT3) by preoperative mpMRI showed a sensitivity, negative predictive value and accuracy of 65.1%, 51.7% and 67.5%. In addition to the suspicion of extraprostatic disease in mpMRI (≥rT3), 84.5% (n = 56) of patients with ≥rT3 underwent primary nerve-sparing surgery with IFST, resulting in 94.7% (n = 54) of men with at least unilateral nerve-sparing surgery after secondary resection with a positive surgical margin rate related to an IFST of 1.8% (n = 1). Conclusion: Patients with rT3 should not be immediately excluded from nerve-sparing surgery, as by using IFST some of these patients can safely undergo nerve-sparing surgery.
Diurnal and Seasonal Patterns of Calling Activity of Seven Cuculidae Species in a Forest of Eastern China
Authors: Mei Jinjuan , Puswal Sabah Mushtaq , Wang Mei , Liu Fanglin
Published: March 2022

There is very little information on the diurnal and seasonal patterns of Cuculidae species’ calling activity in subtropical areas. In this study, we used passive acoustic monitoring to investigate the diurnal and seasonal patterns of calling activity of seven Cuculidae species at three sites in eastern China’s forest over a year. Our results showed that these species exhibited significant diurnal variations except for Cuculus micropterus. Eudynamys scolopaceus and Cuculus saturatus increased their vocal activity at dawn and dusk, whereas the other four species peaked their calling activity in the morning. Five species showed significant seasonal variations with a peak in vocal activities earlier in the season (late May or early June) and a gradual decline after that, except for Clamator coromandus, which displayed two peaks in seasonal calling activity. As for Cuculus micropterus, its calling activity was not significantly related to the season. Our study has provided basic knowledge about the calling patterns of seven Cuculidae species, and based on seasonal changes in vocal activity we propose that the breeding season of these species in east China begins in late May and ends in July.
Real-Time Classification of Invasive Plant Seeds Based on Improved YOLOv5 with Attention Mechanism
Authors: Yang Lianghai , Yan Jing , Li Huiru , Cao Xinyue , Ge Binjie , Qi Zhechen , Yan Xiaoling
Published: March 2022

Seeds of exotic plants transported with imported goods pose a risk of alien species invasion in cross-border transportation and logistics. It is critical to develop stringent inspection and quarantine protocols with active management to control the import and export accompanied by exotic seeds. As a result, a method for promptly identifying exotic plant seeds is urgently needed. In this study, we built a database containing 3000 images of seeds of 12 invasive plants and proposed an improved YOLOv5 target detection algorithm that incorporates a channel attention mechanism. Given that certain seeds in the same family and genus are very similar in appearance and are thus difficult to differentiate, we improved the size model of the initial anchor box to converge better; moreover, we introduce three attention modules, SENet, CBAM, and ECA-Net, to enhance the extraction of globally important features while suppressing the weakening of irrelevant features, thereby effectively solving the problem of automated inspection of similar species. Experiments on an invasive alien plant seed data set reveal that the improved network model fused with ECA-Net requires only a small increase in parameters when compared to the original YOLOv5 network model and achieved greater classification and detection accuracy without affecting detection speed.
Diagnosis of Acute Leukemia by Multiparameter Flow Cytometry with the Assistance of Artificial Intelligence
Authors: Zhong Pengqiang , Hong Mengzhi , He Huanyu , Zhang Jiang , Chen Yaoming , Wang Zhigang , Chen Peisong , Ouyang Juan
Published: March 2022

We developed an artificial intelligence (AI) model that evaluates the feasibility of AI-assisted multiparameter flow cytometry (MFC) diagnosis of acute leukemia. Two hundred acute leukemia patients and 94 patients with cytopenia(s) or hematocytosis were selected to study the AI application in MFC diagnosis of acute leukemia. The kappa test analyzed the consistency of the diagnostic results and the immunophenotype of acute leukemia. Bland–Altman and Pearson analyses evaluated the consistency and correlation of the abnormal cell proportion between the AI and manual methods. The AI analysis time for each case (83.72 ± 23.90 s, mean ± SD) was significantly shorter than the average time for manual analysis (15.64 ± 7.16 min, mean ± SD). The total consistency of diagnostic results was 0.976 (kappa (κ) = 0.963). The Bland–Altman evaluation of the abnormal cell proportion between the AI analysis and manual analysis showed that the bias ± SD was 0.752 ± 6.646, and the 95% limit of agreement was from −12.775 to 13.779 (p = 0.1225). The total consistency of the AI immunophenotypic diagnosis and the manual results was 0.889 (kappa, 0.775). The consistency and speedup of the AI-assisted workflow indicate its promising clinical application.
Rapid and Reliable Detection of SARS-CoV-2 Using Direct RT-LAMP
Authors: El-Kafrawy Sherif A. , El-Daly Mai M. , Hassan Ahmed M. , Harakeh Steve M. , Alandijany Thamir A. , Azhar Esam I.
Published: March 2022

Background: The global pandemic coronavirus SARS-CoV-2 has a healthcare, social and economic burden. To limit the spread of the virus, the World Health Organization (WHO) urgently called for extensive screening of suspected individuals; thus, a quick, simple, and sensitive diagnostic assay is always in need. Methods: We applied reverse transcription-loop-mediated isothermal amplification (RT-LAMP) for the detection of SARS-CoV-2. The RT-LAMP method was optimized by evaluating two fluorescence amplification mixes and several reaction times, and results were compared to the standard real-time RT-PCR (rtRT-PCR). The assay was validated using 200 nasopharyngeal swabs collected in viral transport media (62 positive for SARS-CoV-2, and 138 negative for SARS-CoV-2 detected by the rtRT-PCR method). The samples were diluted 1:4 in diethylpyrocarbonate (DEPC)-treated water, utilized for RT-LAMP using different singleplex and multiplex sets of LAMP primers (N gene, S gene, and orf1ab gene), and incubated at 65 °C using real-time PCR 7500. Results: Our direct detection with the RT-LAMP protocol showed 100% concordance (sensitivity and specificity) with the standard protocol used for the detection of SARS-CoV-2 nucleic acid. Conclusions: In this study, we set up a rapid, simple, and sensitive RT-LAMP assay for the detection of SARS-CoV-2 in clinical samples. The assay is suitable for point of care detection in public hospitals, medical centers in rural areas, and in transportation hubs.