bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch–Sox9 Axis Mediates Hepatocyte Dedifferentiation in KrasG12V-Induced Zebrafish Hepatocellular Carcinoma
Authors: Sun Junhui , Chen Qi , Ma Jianlong
Published: April 2022

Liver cancer is one of the most prevalent cancers in humans. Hepatocytes normally undergo dedifferentiation after the onset of hepatocellular carcinoma, which in turn facilitates the progression of cancer. Although the process of hepatocellular carcinoma dedifferentiation is of significant research and clinical value, the cellular and molecular mechanisms underlying it are still not fully characterized. We constructed a zebrafish liver cancer model based on overexpression of the oncogene krasG12V to investigate the hepatocyte dedifferentiation in hepatocellular carcinoma. We found that, after hepatocarcinogenesis, hepatocytes dedifferentiated and the Notch signaling pathway was upregulated in this progress. Furthermore, we found that inhibition of the Notch signaling pathway or deficiency of sox9b both prevented hepatocyte dedifferentiation following hepatocellular carcinoma induction, reducing cancer metastasis and improving survival. In conclusion, we found that hepatocytes undergo dedifferentiation after hepatocarcinogenesis, a process that requires Notch signaling and likewise the activation of Sox9.
Leptin Signaling in Obesity and Colorectal Cancer
Authors: Socol Claudia Terezia , Chira Alexandra , Martinez-Sanchez Maria Antonia , Nuñez-Sanchez Maria Angeles , Maerescu Cristina Maria , Mierlita Daniel , Rusu Alexandru Vasile , Ruiz-Alcaraz Antonio Jose , Trif Monica , Ramos-Molina Bruno
Published: April 2022

Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin’s relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.
Making Informed Decisions to Improve Restaurant Image Using a Hybrid MADM Approach: A Case of Fast-Food Restaurants in an Island of East Malaysia
Authors: Krishnan Anath Rau , Hamid Rizal , Lin Ronia Yeap Siew , Tanakinjal Geoffrey Harvey , Rathakrishnan Balan
Published: April 2022

Restaurant image refers to an immediate perception that pops up in a customer’s mind when the name of a restaurant is mentioned. Therefore, it is crucial for restaurants, including fast-food restaurants (FFRs), to evaluate and sustain a positive restaurant image. However, evaluating and improving a restaurant’s image is challenging, since it counts in multiple service attributes associated with various degrees of unknown priority. Even so, the existing literature is yet to outspread the usage of an appropriate multi-attribute decision-making (MADM)-based approach to specifically evaluate the image of FFRs. Therefore, this research aimed at employing such an approach to evaluate the image of four FFRs on an island in East Malaysia, using various people, processes, and physical evidence attributes. Firstly, an initial list of FFR image attributes was elicited from the available literature. This initial list was then further validated through a two-round Delphi survey involving a panel of ten experts. A questionnaire was then designed based on the finalized attributes, and data collected from a sample of 251 respondents were analyzed using the compromised-analytical hierarchy process (C-AHP) method. The C-AHP results suggest that the strategies to improve an FFR’s image should primarily incorporate the following six attributes: hospitality, employees’ problem-solving skills, employees’ knowledge, food taste, physical cleanliness, and service response time. The FFR at the top of the ranking has the highest performance scores over these same six attributes. Surprisingly, employees’ appearance and restaurant exterior were reported as the two least important image attributes. This research is the first to demonstrate the application of a hybrid MADM-based approach to uncover the weights of FFR image attributes and rank those FFRs by computing their aggregated image scores.
Leveraging Frozen Pretrained Written Language Models for Neural Sign Language Translation
Authors: De Coster Mathieu , Dambre Joni
Published: April 2022

We consider neural sign language translation: machine translation from signed to written languages using encoder–decoder neural networks. Translating sign language videos to written language text is especially complex because of the difference in modality between source and target language and, consequently, the required video processing. At the same time, sign languages are low-resource languages, their datasets dwarfed by those available for written languages. Recent advances in written language processing and success stories of transfer learning raise the question of how pretrained written language models can be leveraged to improve sign language translation. We apply the Frozen Pretrained Transformer (FPT) technique to initialize the encoder, decoder, or both, of a sign language translation model with parts of a pretrained written language model. We observe that the attention patterns transfer in zero-shot to the different modality and, in some experiments, we obtain higher scores (from 18.85 to 21.39 BLEU-4). Especially when gloss annotations are unavailable, FPTs can increase performance on unseen data. However, current models appear to be limited primarily by data quality and only then by data quantity, limiting potential gains with FPTs. Therefore, in further research, we will focus on improving the representations used as inputs to translation models.
The Carniolan Honeybee from Slovenia—A Complete and Annotated Mitochondrial Genome with Comparisons to Closely Related Apis mellifera Subspecies
Authors: Moškrič Ajda , Marinč Andraž , Ferk Polonca , Leskošek Brane , Mosbech Mai-Britt , Bunikis Ignas , Pettersson Olga , Soler Lucile , Prešern Janez
Published: April 2022

The complete mitochondrial genome of the Carniolan honeybee (Apis mellifera carnica) from Slovenia, a homeland of this subspecies, was acquired in two contigs from WGS data and annotated. The newly obtained mitochondrial genome is a circular closed loop of 16,447 bp. It comprises 37 genes (13 protein coding genes, 22 tRNA genes, and 2 rRNA genes) and an AT-rich control region. The order of the tRNA genes resembles the order characteristic of A. mellifera. The mitogenomic sequence of A. m. carnica from Slovenia contains 44 uniquely coded sites in comparison to the closely related subspecies A. m. ligustica and to A. m. carnica from Austria. Furthermore, 24 differences were recognised in comparison between A. m. carnica and A. m. ligustica subspecies. Among them, there are three SNPs that affect translation in the nd2, nd4, and cox2 genes, respectively. The phylogenetic placement of A. m. carnica from Slovenia within C lineage deviates from the expected position and changes the perspective on relationship between C and O lineages. The results of this study represent a valuable addition to the information available in the phylogenomic studies of A. mellifera—a pollinator species of worldwide importance. Such genomic information is essential for this local subspecies’ conservation and preservation as well as its breeding and selection.
Wing Phenotypic Variation among Stomoxys calcitrans (Diptera: Muscidae) Populations in Thailand
Authors: Chaiphongpachara Tanawat , Duvallet Gerard , Changbunjong Tanasak
Published: April 2022

Stomoxys calcitrans (Linnaeus, 1758) (Diptera: Muscidae) is a cosmopolitan hematophagous ectoparasite of veterinary and medical importance. It is an important mechanical vector of several animal pathogens and can cause significant economic losses. However, the morphological variation of this species remains unknown. This study aimed to investigate the phenotypic variation in the wing size and shape of S. calcitrans populations in Thailand based on a landmark-based geometric morphometric approach. Specimens were collected from five populations in five geographical regions in Thailand. A total of 490 left wings of S. calcitrans (245 female and 245 male individuals) were used for geometric morphometric analysis. Wing size differences were detected between some populations of S. calcitrans, whereas wing shape differences were found among populations. Therefore, the phenotypic variation in S. calcitrans populations indicated that these populations are adaptive responses to local environmental pressures, suggesting the presence of phenotypic plasticity in this species.
Comparison of Clinical and Pathological Factors Affecting Early and Late Recurrences in Patients with Operable Breast Cancer
Authors: Yekedüz Emre , Dizdar Ömer , Kertmen Neyran , Aksoy Sercan
Published: April 2022

In this study, we aimed to assess clinicopathological factors affecting early and late recurrences in patients with operable breast cancer. Patients with early (≤5 years) and late (>5 years) recurrences were assessed. Prognostic factors for disease-free survival (DFS) were also evaluated in patients with recurrence. A total of 854 patients were included. There were 432 and 205 patients in the early and late recurrence groups, respectively. In multivariate analyses, HER2+ disease, lymph node metastasis, lymphovascular invasion (LVI), and high tumor grade were associated with increased risk of early recurrence, while HER2+ disease and LVI were associated with decreased risk of late recurrence. In multivariate analyses, presence of HER2+ disease and triple-negative breast cancer (TNBC) were poor prognostic factors for DFS in patients with early recurrence. Presence of LVI and perineural invasion (PNI) were poor prognostic factors for DFS in patients with late recurrence. Molecular subtypes and LVI were effective on the early and late recurrences. However, lymph node positivity and grade were only associated with the early recurrence. After 5 years, LVI and PNI were the prognostic factors for DFS.
Lumbosacral Transitional Vertebra Contributed to Lumbar Spine Degeneration: An MR Study of Clinical Patients
Authors: Cheng Linxiang , Jiang Chao , Huang Jiawei , Jin Jiale , Guan Ming , Wang Yue
Published: April 2022

We aimed to comprehensively characterize degenerative findings associated with various types of lumbosacral transitional vertebra (LSTV) on magnetic resonance images. Three hundred and fifty patients with LSTV (52.3 ± 10.9 years), including 182 Castellvi type I, 107 type II, 43 type III, and 18 type IV, and 179 controls without LSTV (50.6 ± 13.1 years), were studied. Discs, endplates, and posterior vertebral structures were assessed and compared to those of controls for the most caudal three discs on MRIs. There were no differences in degenerative findings between patients with type I LSTV and controls. For types III and IV, the transitional discs had smaller sizes, lower Pfirrmann scores, and lower rates of disc bulging (2.3% and 5.6% vs. 39.1%), osteophytes (2.3% vs. 15.1%), disc herniation (2.3% and 5.6% vs. 31.8%), and Modic changes (2.3% and 5.6% vs. 16.8%) than controls. However, the cranial discs had more severe Pfirrmann scores, disc narrowing and spinal canal narrowing, and greater rates of disc herniation (41.9% and 50.0% vs. 25.7%), endplate defects (27.9% and 33.3% vs. 14.4%) and spondylolisthesis (18.6% vs. 7.3%) than controls. Type II LSTV was associated with degenerative findings in the cranial segments but to a lesser degree, as compared with type III/IV LSTV. Thus, Castellvi type III/IV LSTV predisposed the adjacent spinal components to degeneration and protected the transitional discs. Type II LSTV had significant effects in promoting transitional and adjacent disc degeneration. Type I LSTV was not related to spinal degeneration.
Genito Pelvic Pain/Penetration Disorder (GPPPD) in Spanish Women—Clinical Approach in Primary Health Care: Review and Meta-Analysis
Authors: Berenguer-Soler María , Navarro-Sánchez Antonio , Compañ-Rosique Antonio , Luri-Prieto Paloma , Navarro-Ortiz Ramón , Gómez-Pérez Luis , Pérez-Tomás Carla , Font-Juliá Elsa , Gil-Guillén Vicente F. , Cortés-Castell Ernesto , Navarro-Cremades Felipe , Montejo Angel L. , Arroyo-Sebastián María del Ángel , Pérez-Jover Virtudes
Published: April 2022

Sexuality is a component of great relevance in humans. Sexual disorders are a major public health problem representing a high prevalence in the general population. DSM-5 genito-pelvic pain/penetration disorder (GPPPD) includes dyspareunia and vaginismus (DSM-IV-TR). To assess the importance of research on these disorders in Spain, we evaluated the Spanish scientific publications of primary and community care. The objective was to quantify the magnitude of the publications of GPPPD in Spanish women in primary and community care. For this, we used the method of conducting a systematic review and meta-analysis of studies evaluating GPPPD. As main results, of the 551 items found, we selected 11 studies that met the inclusion criteria. In primary care in Spain, one in nine women has these disorders; the percentage of women with GPPPD in this study (raw data) was 11.23% (95% CI: 0–29%) (vaginismus 5%; penetration pain 8.33%; dyspareunia 16.45%). These percentages can differ of those from other countries, and they are at the top of the data of the European countries (9−11.9%). There is much variability in the studies found in the world with respect to the prevalence of these health problems.
Personalized Therapeutic Strategies in the Management of Osteoporosis in Patients with Autoantibody-Positive Rheumatoid Arthritis
Authors: D’Onofrio Bernardo , di Lernia Michele , De Stefano Ludovico , Bugatti Serena , Montecucco Carlomaurizio , Bogliolo Laura
Published: April 2022

Bone mineral density (BMD) reduction and fragility fractures still represent a major source of morbidity in rheumatoid arthritis (RA) patients, despite adequate control of the disease. An increasing number of clinical and experimental evidence supports the role of autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in causing localized and generalised bone loss in ways that are both dependent on and independent of inflammation and disease activity. The human receptor activator of nuclear factor kappa B and its ligand—the so-called RANK-RANKL pathway—is known to play a key role in promoting osteoclasts’ activation and bone depletion, and RANKL levels were shown to be higher in ACPA-positive early untreated RA patients. Thus, ACPA-positivity can be considered a specific risk factor for systemic and periarticular bone loss. Through the inhibition of the RANK-RANKL system, denosumab is the only antiresorptive drug currently available that exhibits both a systemic anti-osteoporotic activity and a disease-modifying effect when combined with conventional synthetic or biologic disease-modifying anti-rheumatic drugs (DMARDs). Thus, the combination of DMARD and anti-RANKL therapy could be beneficial in the prevention of fragility fractures and structural damage in the subset of RA patients at risk of radiographic progression, as in the presence of ACPAs.
Neuron-Specific Enolase and S100B: The Earliest Predictors of Poor Outcome in Cardiac Arrest
Authors: Ryczek Robert , Kwasiborski Przemysław J. , Rzeszotarska Agnieszka , Dymus Jolanta , Galas Agata , Kaźmierczak-Dziuk Anna , Karasek Anna M. , Mielniczuk Marta , Buksińska-Lisik Małgorzata , Korsak Jolanta , Krzesiński Paweł
Published: April 2022

Background: Proper prognostication is critical in clinical decision-making following out-of-hospital cardiac arrest (OHCA). However, only a few prognostic tools with reliable accuracy are available within the first 24 h after admission. Aim: To test the value of neuron-specific enolase (NSE) and S100B protein measurements at admission as early biomarkers of poor prognosis after OHCA. Methods: We enrolled 82 consecutive patients with OHCA who were unconscious when admitted. NSE and S100B levels were measured at admission, and routine blood tests were performed. Death and poor neurological status at discharge were considered as poor clinical outcomes. We evaluated the optimal cut-off levels for NSE and S100B using logistic regression and receiver operating characteristic (ROC) analyses. Results: High concentrations of both biomarkers at admission were significantly associated with an increased risk of poor clinical outcome (NSE: odds ratio [OR] 1.042 per 1 ng/dL, [1.007–1.079; p = 0.004]; S100B: OR 1.046 per 50 pg/mL [1.004–1.090; p < 0.001]). The dual-marker approach with cut-off values of ≥27.6 ng/mL and ≥696 ng/mL for NSE and S100B, respectively, identified patients with poor clinical outcomes with 100% specificity. Conclusions: The NSE and S100B-based dual-marker approach allowed for early discrimination of patients with poor clinical outcomes with 100% specificity. The proposed algorithm may shorten the time required to establish a poor prognosis and limit the volume of futile procedures performed.
Motherhood and Me (Mom-Me): The Development of an Acceptance-Based Group for Women with Postpartum Mood and Anxiety Symptoms
Authors: Grunberg Victoria A. , Geller Pamela A. , Durham Kelley , Bonacquisti Alexa , Barkin Jennifer L.
Published: April 2022

Untreated postpartum mood and anxiety disorders (PMADs) place women and their families at risk for negative biopsychosocial sequelae. Innovative and tailored treatments are needed to address potential disruptions in maternal functioning. Third-wave cognitive–behavioral approaches, including acceptance and commitment therapy (ACT) and dialectical behavioral therapy (DBT), hold promise for optimizing functioning given the focus on values-based living, rather than symptom reduction. Purpose: The purpose of this paper is to describe the development of an innovative psychotherapy group for women with symptoms of PMADs. Methods: This seven-session group, Motherhood and Me (Mom-Me), includes selected skills training from ACT, DBT, and Emotion-Centered Problem-Solving Therapy. Results: Mom-Me group sessions are described, and an outline of key information (session goals, content, and homework assignments) is provided to facilitate practical implementation. Conclusion: In line with third-wave approaches, this group was developed to enhance maternal functioning, which, in turn, may help women cope with psychological distress during the transition to motherhood.
Activation of Sigma-1 Receptor Alleviates ER-Associated Cell Death and Microglia Activation in Traumatically Injured Mice
Authors: Shi Mingming , Liu Liang , Min Xiaobin , Mi Liang , Chai Yan , Chen Fanglian , Wang Jianhao , Yue Shuyuan , Zhang Jianning , Deng Quanjun , Chen Xin
Published: April 2022

Background: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) is associated with neuroinflammation and subsequent cell death following traumatic brain injury (TBI). The sigma-1 receptor (Sig-1R) acts as a dynamic pluripotent modulator of fundamental cellular processes at the mitochondria-associated membranes (MAMs). The activation of Sig-1R is neuroprotective in a variety of central nervous system diseases, but its impact on ER stress induced by traumatic brain injury is not known. This study investigated the role of Sig-1R in regulating the ER stress-mediated microglial activation and programmed cell death (apoptosis and pyroptosis) induced by TBI. Methods: Ten human brain tissues were obtained from The Tianjin Medical University General Hospital. Four normal brain tissues were obtained from patients who underwent surgery for cerebral vascular malformation, through which peripheral brain tissues were isolated. Six severe TBI tissues were from patients with brain injury caused by accidents. None of the patients had any other known neurological disorders. Mice with Sig-1R deletion using CRISPR technology were subjected to controlled cortical impact-induced injury. In parallel, wild type C57BL/6J mice were analyzed for outcomes after they were exposed to TBI and received the Sig-1R agonist PRE-084 (10 mg/kg daily for three days) either alone or in combination with the Sig-1R antagonist BD-1047 (10 mg/kg). Results: The expression of Sig-1R and the 78 kDa glucose-regulated protein, a known UPR marker, were significantly elevated in the injured cerebral tissues from TBI patients and mice subjected to TBI. PRE-084 improved neurological function, restored the cerebral cortical perfusion, and ameliorated and brain edema in C57BL/6J mice subjected to TBI by reducing endoplasmic reticulum stress-mediated apoptosis, pyroptosis, and microglia activation. The effect of PRE-084 was abolished in mice receiving Sig-1R antagonist BD-1047. Conclusions: ER stress and UPR were upregulated in TBI patients and mice subjected to TBI. Sig-1R activation by the exogenous activator PRE-084 attenuated microglial cells activation, reduced ER stress-associated programmed cell death, and restored cerebrovascular and neurological function in TBI mice.
Vesicoamniotic Shunting before 17 + 0 Weeks in Fetuses with Lower Urinary Tract Obstruction (LUTO): Comparison of Somatex vs. Harrison Shunt Systems
Authors: Strizek Brigitte , Spicher Theresa , Gottschalk Ingo , Böckenhoff Paul , Simonini Corinna , Berg Christoph , Gembruch Ulrich , Geipel Annegret
Published: April 2022

(1) Background: The aim of this study was to compare perinatal outcomes and complication rates of vesicoamniotic shunting (VAS) before 17 + 0 weeks in isolated LUTO (lower urinary tract obstruction) with the Somatex® intrauterine shunt vs. the Harrison fetal bladder shunt. (2) Methods: This is a retrospective cohort study in two tertiary fetal medicine centers. From 2004–2014, the Harrison fetal bladder shunt was used, and from late 2014–2017, the Somatex shunt. Obstetrics and pediatric charts were reviewed for complications, course of pregnancy, perinatal outcome, and postnatal renal function. (3) Results: Twenty-four fetuses underwent VAS with a Harrison (H) shunt and 33 fetuses with a Somatex (S) shunt. Live birth rates and survival to last follow-up were significantly higher in the Somatex group, at 84.8% and 81.8%, respectively, vs. 50% and 33.3% in the Harrison group (p = 0.007 and p < 0.001). The dislocation rate in the Somatex group (36.4%) was significantly lower than in the Harrison group (87.5%) (p < 0.001). The median time to dislocation was significantly different, at 20.6 days (H) vs. 73.9 days (S) (p = 0.002), as was gestational age at dislocation (17 (H) vs. 25 (S) weeks, p < 0.001). Renal function was normal in early childhood in 51% (S) vs. 29% (H) (p = 0.11). (4) Conclusions: VAS before 17 + 0 weeks gestational age with a Somatex shunt improves perinatal survival significantly and might even have a positive effect on renal function, probably due to the lower dislocation rates. A normal amount of amniotic fluid in the third trimester was the best predictor of normal renal function in early childhood.
Editorial to: Advance in the Treatment of Pediatric Leukemia
Authors: Handgretinger Rupert
Published: April 2022

The history of leukemia goes back many years and John Bennet, a Scottish physician, described in 1845 a 28-year old patient with swelling of the spleen who then developed fever, bleeding and increasing swellings in his neck, groin and armpits [...]
The Association between Human Epididymis Secretory Protein 4 and Metabolic Syndrome
Authors: Li Peng-Fei , Lin Yu-Jen , Liang Yao-Jen , Chen Wei-Liang
Published: April 2022

Individuals with metabolic syndrome (MetS) are known to have an increased risk of carcinogenesis. Human epididymis protein 4 (HE4) is a tumor marker and prognostic factor for epithelial ovarian carcinoma (EOC) patients. However, no studies have evaluated the association between MetS and HE4 levels. This study aimed to evaluate the relationship between HE4 levels and MetS in the National Health and Nutrition Examination Survey (NHANES 2001–2002). This cross-sectional analysis assessed all five components of MetS and HE4 levels in 2104 females (age ≥20 years) from the NHANES dataset. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria. The analysis indicated MetS in 593 individuals, and the β coefficient of their HE4 levels was 0.097 (95% CIs, 0.028–0.166, p = 0.006). Specifically, the β coefficients of the HE4 levels of participants with 1, 2, 3, and ≥4 features of MetS were 0.072 (95% confidence interval (CI): −0.015–0.159), 0.125 (95% CI: 0.030–0.220), 0.161 (95% CI: 0.053–0.270), and 0.242 (95% CI: 0.117–0.368), respectively, and all p values were <0.001. The p-value for the trend was <0.001. There was a significant association between the presence of MetS and HE4 levels. There were positive relationships between HE4 levels and an increased number of MetS components (with 1, 2, 3, and ≥4 features of MetS, all p values <0.001). Among the MetS components, low high-density lipoprotein levels and high triglyceride levels were independently associated with HE4 levels.
Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Meta-Analysis
Authors: Lin Jonathan B. , Serghiou Stylianos , Miller Joan W. , Vavvas Demetrios G.
Published: April 2022

Although complement inhibition has emerged as a possible therapeutic strategy for age-related macular degeneration (AMD), there is not a clear consensus regarding what aspects of the complement pathway are dysregulated in AMD and when this occurs relative to disease stage. We recently published a systematic review describing systemic complement activation profiles in patients with early/intermediate AMD or geographic atrophy (GA) compared to non-AMD controls. Here, we sought to meta-analyze these results to estimate the magnitude of complement dysregulation in AMD using restricted maximum likelihood estimation. The seven meta-analyzed studies included 710 independent participants with 23 effect sizes. Compared with non-AMD controls, patients with early/intermediate nonexudative AMD (N = 246) had significantly higher systemic complement activation, as quantified by the levels of complement proteins generated by common final pathway activation, and significantly lower systemic complement inhibition. In contrast, there were no statistically significant differences in the systemic levels of complement common final pathway activation products or complement inhibition in patients with GA (N = 178) versus non-AMD controls. We provide evidence that systemic complement over-activation is a feature of early/intermediate nonexudative AMD; no such evidence was identified for patients with GA. These findings provide mechanistic insights and inform future clinical trials.
Risk Factor Analysis of Early-Onset Cataracts in Taiwan
Authors: Tsai Lung-Hui , Chen Ching-Chung , Lin Chien-Ju , Lin Sheng-Pei , Cheng Ching-Ying , Hsieh Hsi-Pao
Published: April 2022

Purpose: According to previous studies, the prevalence rate of cataracts has increased in recent years. This study aims to investigate and analyze the risk factors of early-onset cataracts in Taiwan. Methods: A total of 71 subjects aged between 20 and 55 were diagnosed with cataracts in a medical center. Participants were divided into three groups: control, early-onset cataract (EOC), and combined (EOC combined with dry eye) groups. Eye examinations including autorefraction, best-corrected visual acuity (BCVA), subjective refraction, axial length, fundus, slit lamp, and reactive oxygen species (ROS, including total antioxidative capacity, TAC; C-reactive protein, CRP; and glutathione peroxidase, GPx) were performed. In addition, a questionnaire on patient information, history, habits, family history, and Depression Anxiety Stress Scales (DASS) was completed before the examination. Results: 27 non-EOC (control group), 20 EOC, and 24 combined patients participated in the study. Compared with the control group, Body Mass Index (BMI), gender, educational level, hypertension, diabetes, hyperlipidemia, chronic pain, and body-related diseases were significantly different between the three groups. Family history was also significantly different: family heart disease, hypertension, asthma, allergies, stroke, and immune system were also significantly different. In addition, subjects who took hypertensive drugs, antihistamines, and other medications were also significantly different. Statistical analysis indicated that best corrective visual acuity and the spherical equivalent were significantly different between the three groups. Similar results were found in CRP blood analysis. Discussion and Conclusion: According to the results, EOC may result from systemic diseases. The risk corresponded to an increase in ROS blood analysis. Furthermore, eye drops and medicine intake significantly influenced EOC patients. To prevent or defer early-onset cataracts, monitoring physical health, CRP, and GPx analysis may be worth considering in the future.
Investigating the Effects of Ironing Parameters on the Dimensional Accuracy, Surface Roughness, and Hardness of FFF-Printed Thermoplastics
Authors: Butt Javaid , Bhaskar Raghunath , Mohaghegh Vahaj
Published: April 2022

Ironing is a useful feature for parts made by fused filament fabrication (FFF), as it can smooth out surfaces using heat and extruding a small amount of material. Like any other processing parameter for FFF, ironing also requires optimisation to ensure a smooth surface can be achieved with limited adverse effects on the other features of the printed part. Even with such a beneficial use case, ironing is still considered experimental and, therefore, this study aims to investigate its effects on dimensional accuracy, surface roughness, and the hardness of two commonly used amorphous thermoplastics, i.e., ABS (acrylonitrile butadiene styrene) and ASA (acrylonitrile styrene acrylate). An extensive comparative analysis has been provided where parts have been manufactured using a low-cost, desktop-based 3D printer, with the two materials at three different ironing line spacings (0.1 mm, 0.2 mm, 0.3 mm), three different ironing flows (10%, 20%, 30%), and three different ironing speeds (50 mm/s, 100 mm/s, 150 mm/s). The study focuses on evaluating the effects of these different ironing parameters and determining the optimal combination for bespoke product requirements. The results showed that ASA was more adversely affected by the changes in ironing parameters compared to ABS. However, the different ironing parameters were proven to improve the smoothness as well as hardness of the parts, compared to the un-ironed samples of ABS and ASA. This work provides a good comparison between two popular amorphous materials and offers ways to leverage ironing parameters to achieve dimensional accuracy, optimal surface finish, and better hardness values.
Blending for Achieving Theoretical Mechanical and Electrical Property Enhancement in Polyacrylonitrile/SWNT Materials
Authors: Li Heng , Doyle Conor M. , Minus Marilyn L.
Published: April 2022

Filtration based processing of nanotube and polymer-nanotube dispersions is used to create polymer and nano-filler hybrid materials. The composite morphology consists of two layers: (1) a region where polymer chains have direct matrix interaction with the nano-fillers and (2) a nano-filler rich region excluded from matrix interactions. The experimental work here demonstrates the processing of this hybrid material using polyacrylonitrile (PAN) and single-wall carbon nanotubes (SWNT) at various PAN/SWNT weight concentrations. Mechanical analyses were performed to evaluate effective contributions from the SWNT in each of the defined layers. The region of high matrix-filler interactions exhibits blending behavior with material properties following suit. As a result, mechanical performance is consistent and begins to exceed theoretical predictions derived from Halpin–Tsai calculations. Tensile strength and modulus reached values as high as 60 MPa and 7.7 GPa, respectively, surpassing the performance of neat nano-filler (36 MPa, 3.9 GPa) and neat polymer matrix (44 MPa, 2.0 GPa) films. Additionally, the measurement of electrical properties shows that the blended polymer-SWNT region exhibits conductivity comparable to the filler. The results of this work suggest that blending polymers and nano-fillers is possible and may facilitate the production of materials with comparatively high mechanical performance and electrical conductivities.
Weakly Supervised Polyp Segmentation in Colonoscopy Images Using Deep Neural Networks
Authors: Chen Siwei , Urban Gregor , Baldi Pierre
Published: April 2022

Colorectal cancer (CRC) is a leading cause of mortality worldwide, and preventive screening modalities such as colonoscopy have been shown to noticeably decrease CRC incidence and mortality. Improving colonoscopy quality remains a challenging task due to limiting factors including the training levels of colonoscopists and the variability in polyp sizes, morphologies, and locations. Deep learning methods have led to state-of-the-art systems for the identification of polyps in colonoscopy videos. In this study, we show that deep learning can also be applied to the segmentation of polyps in real time, and the underlying models can be trained using mostly weakly labeled data, in the form of bounding box annotations that do not contain precise contour information. A novel dataset, Polyp-Box-Seg of 4070 colonoscopy images with polyps from over 2000 patients, is collected, and a subset of 1300 images is manually annotated with segmentation masks. A series of models is trained to evaluate various strategies that utilize bounding box annotations for segmentation tasks. A model trained on the 1300 polyp images with segmentation masks achieves a dice coefficient of 81.52%, which improves significantly to 85.53% when using a weakly supervised strategy leveraging bounding box images. The Polyp-Box-Seg dataset, together with a real-time video demonstration of the segmentation system, are publicly available.
Differences in the Structure and Antimicrobial Activity of Hydrazones Derived from Methyl 4-Phenylpicolinimidate
Authors: Gobis Katarzyna , Szczesio Małgorzata , Olczak Andrzej , Korona-Głowniak Izabela , Augustynowicz-Kopeć Ewa , Mazernt-Politowicz Ida , Ziembicka Dagmara , Główka Marek L.
Published: April 2022

Four novel methyl 4-phenylpicolinoimidate derivatives of hydrazone have been synthesized and evaluated for their antimicrobial activity, including tuberculostatic activity. The compounds obtained are condensates of hydrazonamide or hydrazide with 5-nitro-2-furaldehyde or 5-nitro-2-thiophenecarboxaldehyde. The antimicrobial activity of the tested compounds varied. Compound 3b exhibited significant activity against the tested Gram-positive bacteria (7.8–250 µg/mL). The results of structural tests revealed that the compound is the only one obtained in the form of a Z isomer. Tuberculostatic activity tests showed higher activity of derivatives 3a and 4a containing nitrofuran systems (MICs 3.1–12.5 µg/mL). This research allowed us to identify hydrazone 3b as a starting point for further optimization in the search for antimicrobial drugs. Likewise, compound 4a appears to be a good guiding structure for use in future research on new anti-tuberculosis drugs.
A Review on Reductions in the Stress-Intensity Factor of Cracked Plates Using Bonded Composite Patches
Authors: Aabid Abdul , Hrairi Meftah , Ali Jaffar Syed Mohamed , Sebaey Tamer Ali
Published: April 2022

In aerospace engineering applications, lightweight material structures are considered to perform difficult service conditions and afford energy efficiency. Therefore, composite materials have gained popularity due to their light weights and high performances in structural design. Mechanical loads and environmental conditions primarily create damage to structural materials, thus numerous studies have considered the repair of the damaged structure. Bonded composite repairs are generally chosen, as they provide enhanced stress-transfer mechanisms and joint efficiencies with the increased use of advanced composite materials in primary and secondary aircraft structural components. Thus, it is essential to have reliable and repeatable bonded repair procedures to restore damaged structural components. However, composite bonded repairs, especially with primary structures, present several scientific challenges in the current existing repair technologies. In this review, a study has been done on the bonded composite repair of damaged structures with the stress-intensity factor (SIF) as the parameter for defining the extent of failure by composite repair and unrepaired material structures. In this work, various types of repair methods and the techniques used by researchers are critically reviewed, and future opportunities are explored. The present study was limited to the composite and aluminium materials that are common in aerospace applications.
The Effect of Roughness in Absorbing Materials on Solar Air Heater Performance
Authors: Karmveer  , Kumar Gupta Naveen , Siddiqui Md Irfanul Haque , Dobrotă Dan , Alam Tabish , Ali Masood Ashraf , Orfi Jamel
Published: April 2022

Artificial roughness on the absorber of the solar air heater (SAH) is considered to be the best passive technology for performance improvement. The roughened SAHs perform better in comparison to conventional SAHs under the same operational conditions, with some penalty of higher pumping power requirements. Thermo-hydraulic performance, based on effective efficiency, is much more appropriate to design roughened SAH, as it considers both the requirement of pumping power and useful heat gain. The shape, size, and arrangement of artificial roughness are the most important factors for the performance optimization of SAHs. The parameters of artificial roughness and operating parameters, such as the Reynolds number (Re), temperature rise parameter (ΔT/I) and insolation (I) show a combined effect on the performance of SAH. In this case study, various performance parameters of SAH have been evaluated to show the effect of distinct artificial roughness, investigated previously. Therefore, thermal efficiency, thermal efficiency improvement factor (TEIF) and the effective efficiency of various roughened absorbers of SAH have been predicted. As a result, thermal and effective efficiencies strongly depend on the roughness parameter, Re and ΔT/I. Staggered, broken arc hybrid-rib roughness shows a higher value of TEIF, thermal and effective efficiencies consistently among all other distinct roughness geometries for the ascending values of ΔT/I. This roughness shows the maximum value of effective efficiency equals 74.63% at a ΔT/I = 0.01 K·m2/W. The unique combination of parameters p/e = 10, e/Dh = 0.043 and α = 60° are observed for best performance at a ΔT/I higher than 0.00789 K·m2/W.
The Potential Role of Cyclopeptides from Pseudostellaria heterophylla, Linum usitatissimum and Drymaria diandra, and Peptides Derived from Heterophyllin B as Dipeptidyl Peptidase IV Inhibitors for the Treatment of Type 2 Diabetes: An In Silico Study
Authors: Liao Hui-Jun , Tzen Jason T. C.
Published: April 2022

Dipeptidyl peptidase 4 (DPP4) inhibitors can treat type 2 diabetes by slowing GLP-1 degradation to increase insulin secretion. Studies have reported that Pseudostellaria heterophylla, Linum usita-tissimum (flaxseed), and Drymaria diandra, plants rich in Caryophyllaceae-type cyclopeptides and commonly used as herbal or dietary supplements, are effective in controlling blood sugar. The active site of DPP4 is in a cavity large enough to accommodate their cyclopeptides. Molecular modeling by AutoDock Vina reveals that certain cyclopeptides in these plants have the potential for DPP4 inhibition. In particular, “Heterophyllin B” from P. heterophylla, “Cyclolinopeptide C” from flaxseed, and “Diandrine C” from D. diandra, with binding affinities of −10.4, −10.0, and −10.7 kcal/mol, are promising. Docking suggests that DPP4 inhibition may be one of the reasons why these three plants are beneficial for lowering blood sugar. Because many protein hydrolysates have shown the effect of DPP4 inhibition, a series of peptides derived from Heterophyllin B precursor “IFGGLPPP” were included in the study. It was observed that IFWPPP (−10.5 kcal/mol), IFGGWPPP (−11.4 kcal/mol), and IFGWPPP (−12.0 kcal/mol) showed good binding affinity and interaction for DPP4. Various IFGGLPPP derivatives have the potential to serve as scaffolds for the design of novel DPP4 inhibitors.
Rock Fragmentation Prediction Using an Artificial Neural Network and Support Vector Regression Hybrid Approach
Authors: Amoako Richard , Jha Ankit , Zhong Shuo
Published: April 2022

While empirical rock fragmentation models are easy to parameterize for blast design, they are usually prone to errors, resulting in less accurate fragment size prediction. Among other shortfalls, these models may be unable to accurately account for the nonlinear relationship that exists between fragmentation input and output parameters. Machine learning (ML) algorithms are potentially able to better account for the nonlinear relationship. To this end, we assess the potential of the multilayered artificial neural network (ANN) and support vector regression (SVR) ML techniques in rock fragmentation prediction. Using geometric, explosives, and rock parameters, we build ANN and SVR models to predict mean rock fragment size. Both models yield satisfactory results and show higher performance when compared with the conventional Kuznetsov model. We further demonstrate an automated means of analyzing a varied number of hidden layers for an ANN using Bayesian optimization in the Keras Python library.
Cooperative SWIPT MIMO-NOMA for Reliable THz 6G Communications
Authors: Oleiwi Haider W. , Saeed Nagham , Al-Raweshidy Hamed
Published: April 2022

In this paper, cooperative simultaneous wireless information and power transfer (SWIPT) terahertz (THz) multiple-input multiple-output (MIMO) nonorthogonal multiple access (NOMA) are considered. The aim is to improve wireless connectivity, resource management, scalability, and user fairness, as well as to enhance the overall performance of wireless communications and reliability. We optimized the current wireless communication systems by utilizing MIMO-NOMA technology and THz frequencies, exploring the performance and gains obtained. Hence, we developed a path-selection mechanism for the far user to enhance the system performance. The EH SWIPT approach used to improve THz communications performance was investigated. Moreover, we proposed a reliable transmission mechanism with a non-LoS (NLoS) line of THz communications for open areas or any location where the intelligent reflecting surface (IRS) cannot be deployed, in addition to using the cheap decode-forward (DF) relaying instead of IRS. The performance and scalability of the upgradeable system were examined, using adjustable parameters and the simplest modulation scheme. The system presents a noticeable improvement in energy efficiency (EE) and spectral efficiency (SE), in addition to reliability. Accordingly, the outcome showed an improvement in the overall reliability, SE, EE, and outage probability as compared to the conventional cooperative networks of the recent related work (e.g., cooperative MIMO-NOMA with THz) by multiple times with a simpler design, whereas it outperformed our previous work, i.e., cooperative SWIPT SISO-NOMA with THz, by more than 50%, with a doubled individual user gain. This system reduces the transceiver hardware and improves reliability with increasing transmission rates.
Temporal Associations between Tri-Ponderal Mass Index and Blood Pressure in Chinese Children: A Cross-Lag Analysis
Authors: Cui Yixin , Zhang Fan , Wang Hao , Zhao Longzhu , Song Ruihan , Han Miaomiao , Shen Xiaoli
Published: April 2022

Background: No longitudinal studies have explored the relationship between tri-ponderal mass index (TMI) and blood pressure (BP) in children. This study is aimed to investigate the temporal associations between TMI and BP among children in China. Methods: A longitudinal study was carried out with Chinese children from 2014 to 2019. Data of the anthropometric examination and blood pressure were collected annually. TMI was calculated by dividing weight by the cube of height. BP was measured using a standard mercury sphygmomanometer. We investigated temporal associations between TMI and BP with a cross-lagged panel model using repeated measure data from 2014 (Wave 1), 2016 (Wave 2), and 2018 (Wave 3). Results: Results of the cross-lagged panel model showed that TMI was associated with subsequent BP. Participants with higher levels of TMI presented higher levels of BP (Wave 1: β = 0.737 for systolic blood pressure (SBP) and β = 0.308 for diastolic blood pressure (DBP), Wave 2: β = 0.422 for SBP and β = 0.165 for DBP, p < 0.01). In addition, children with higher BP could also present higher TMI (Wave 1: β = 0.004 for SBP and β = 0.006 for DBP, Wave 2: β = 0.003 for SBP and β = 0.005 for DBP, p < 0.01), but the cross-lag path coefficient indicated that the influence of TMI on BP was stronger than the influence of BP on TMI. Conclusions: There was a temporal association between TMI and BP in Chinese children. Higher TMI predicted higher subsequent BP rather than the reverse relationship.
Organoids, Assembloids and Embryoids: New Avenues for Developmental Biology, Disease Modeling, Drug Testing and Toxicity Assessment without Animal Experimentation
Authors: Ergün Süleyman , Wörsdörfer Philipp
Published: April 2022

The organs and tissues of our bodies consist of a specific set of cell types [...]
Development and Validation of Analytical Methods for Radiochemical Purity of 177Lu-PSMA-1
Authors: Orhon Pauline , Desruet Marie-Dominique , Piquemal Marie , De Leiris Nicolas , Djaileb Loïc , Vuillez Jean-Philippe , Bedouch Pierrick , Leenhardt Julien
Published: April 2022

Prostate Specific Membrane Antigen (PSMA) is a highly relevant target in nuclear medicine due to its overexpression in prostate cancer. The 68Ga/177Lu-PSMA-1 combination is a theranostic agent for the detection and treatment of tumors overexpressing the PSMA target. Specifically, 177Lu-PSMA-1 is used in the treatment of castration-resistant prostate cancer that is ineffective or intolerant to the latest generation of chemotherapy and/or hormone therapy. This radiopharmaceutical is manufactured in a radiopharmaceutical synthesizing unit and must pass a quality control where the radiochemical purity (RCP) is assessed prior to release of the batch. RCP evaluation is performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Since there is no monograph for 177Lu-PSMA-1 in the European Pharmacopoeia, we validate the analytical methods according to the EANM recommendations adapted from ICH Q2. Specificity, linearity, accuracy, precision, intermediate precision, limit of quantification (LOQ) and robustness were described for HPLC and TLC in this study. The results obtained demonstrated the robustness and reliability of the HPLC and TLC analytical methods for the evaluation of the RCP of 177Lu-PSMA-1.