bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment Outcomes in a Partial Hospital Program for Patients with Social Anxiety Disorder: The Effects of Comorbid Major Depression
Authors: Graham Allison , Terrill Douglas , Boyd Simone , Benjamin Isabel , Ward Madeline , Zimmerman Mark
Published: April 2021

Although previous studies have examined the impact of comorbid major depressive disorder (MDD) on social anxiety disorder (SAD), the results have been somewhat mixed. Furthermore, most studies have been conducted in inpatient or outpatient settings. Given the large body of literature that suggests that this particular comorbidity can have negative effects on treatment efficacy and outcomes, it is important to continue to explore its impact. The present study aims to clarify contradictions in the literature and expands on previous studies by examining patients in a partial hospitalization setting. Patients at Rhode Island Hospital with a diagnosis of SAD were compared to those with comorbid SAD and MDD on pre-treatment and post-treatment measures of anxiety and depression. The results indicated that while the comorbid group showed significantly less improvement post-treatment on anxiety symptoms and constructs related to remission from depression, they did not show significantly less improvement on depression symptoms. The implications of these results for clinical practice are discussed. KEYWORDS: Social Anxiety Disorder; Major Depressive Disorder; Comorbid Anxiety Disorders; Comorbid Mood Disorders; Treatment Outcomes; Partial Hospitalization Program
Long Memory in Earthquake Time Series: The Case Study of the Geysers Geothermal Field
Authors: Barani S. , Cristofaro L. , Taroni M. , Gil-Alaña L. A. , Ferretti G.
Published: April 2021

The present study aims at proving the existence of long memory (or long-range dependence) in the earthquake process through the analysis of time series of induced seismicity. Specifically, we apply alternative statistical techniques borrowed from econometrics to the seismic catalog of The Geysers geothermal field (California), the world’s largest geothermal field. The choice of the study area is essentially guided by the completeness of the seismic catalog at smaller magnitudes (a drawback of conventional catalogs of natural seismicity). Contrary to previous studies, where the long-memory property was examined by using non-parametric approaches (e.g., rescaled range analysis), we assume a fractional integration model for which the degree of memory is defined by a real parameterd, which is related to the best known Hurst exponent. In particular, long-memory behavior is observed ford> 0. We estimate and test the value ofd(i.e., the hypothesis of long memory) by applying parametric, semi-parametric, and non-parametric approaches to time series describing the daily number of earthquakes and the logarithm of the (total) seismic moment released per day. Attention is also paid to examining the sensitivity of the results to the uncertainty in the completeness magnitude of the catalog, and to investigating to what extent temporal fluctuations in seismic activity induced by injection operations affect the value ofd. Temporal variations in the values ofdare analyzed together with those of theb-value of the Gutenberg and Richter law. Our results indicate strong evidence of long memory, withdmostly constrained between 0 and 0.5. We observe that the value ofdtends to decrease with increasing the magnitude completeness threshold, and therefore appears to be influenced by the number of information in the chain of intervening related events. Moreover, we find a moderate but significant negative correlation betweendand theb-value. A negative, albeit weaker correlation is found betweendand the fluid injection, as well as betweendand the annual number of earthquakes.
Testicular Growth and Pubertal Onset in GH-Deficient Children Treated With Growth Hormone: A Retrospective Study
Authors: Cannarella Rossella , Caruso Manuela , Crafa Andrea , Timpanaro Tiziana Antonia , Lo Bianco Manuela , Presti Santiago , Condorelli Rosita A. , La Vignera Sandro , Calogero Aldo E.
Published: April 2021

The prevalence of idiopathic oligozoospermia has been esteemed as high as 75%. An Italian survey has reported bilateral testicular hypotrophy in 14% of final-year high school students. The search for determinants of testicular growth in childhood is important for the primary prevention of spermatogenic failure. Therefore, this retrospective study aimed to evaluate the testicular growth and pubertal onset in deficient children treated recombinant human growth hormone (rhGH). To accomplish this, the clinical charts of 93 patients with GH deficiency (GHD) were carefully reviewed. Their mean age at the time of diagnosis was 11.2 ± 2.4 years. rhGH was administered for 44.0 ± 22.4 months, and the onset of puberty was recorded after a mean of 25.8 ± 22.4 months from the first rhGH administration. As expected, serum insulin-like growth factor 1 (IGF1) levels increased significantly after treatment. Before rhGH therapy, the Tanner stage was I in 59 out of 70 boys (84.3%), II in 8/70 (11.4%), III in 3/70 (4.3%). No one was on stage IV or V. The mean Tanner stage was 1.19 ± 0.51. At the last visit, the Tanner stage was I in 8/72 boys (11.1%), II in 6/72 (8.3%), III in 6/72 (8.3%), IV in 16/72 (22.2%), and V in 36/72 (50.0%). After a mean of 44.0 ± 22.4 months of rhGH treatment, the mean Tanner stage was 4.05 ± 1.30. Patients treated with rhGH showed a significant testicular volume (TV) growth over time, whereas no growth was observed in age-matched but not yet treated patients, even when the age was compatible with a spontaneous start of puberty. The multivariate regression analysis showed that the duration of treatment and the mean rhGH dose significantly predicted the percentage of TV increase. In contrast, age, serum FSH, and IGF1 levels, and final rhGH dose did not impact TV growth over time. In conclusion, these findings suggest that GH may play a role in testicular growth and pubertal onset, despite the descriptive nature of this study. Further properly designed studies are needed to confirm these findings. This knowledge may be useful to implement the diagnostic-therapeutic algorithm in case of a lack of testicular growth in childhood.
A Novel Diagnostic Model for Primary Adrenal Lymphoma
Authors: Yu Kai , Xue Qingping , Zhou Fangli , Tian Haoming , Xiang Qiao , Chen Tao , Ren Yan
Published: April 2021

Objective

Primary adrenal lymphoma (PAL) is easily misdiagnosed as other adrenal masses, such as adrenocortical carcinoma and pheochromocytoma, but patients with PAL benefit little from surgery. The diagnostic method for PAL thus far is limited to adrenal biopsy. In our study, we aimed to develop a quick and efficient diagnostic method for PAL.

Methods and Results

At the same institution, 505 patients (between 2009 and 2019) and 171 patients (between 2019 and 2020) were separately included in the primary and validation studies. Univariate and multivariate analyses were conducted to evaluate clinical manifestations, laboratory findings, and radiological characteristics. Four determinants (age, bilateral masses, high-density lipoprotein cholesterol, and lactate dehydrogenase) were selected and further incorporated into a regression model to screen PAL. Accordingly, the nomogram was developed for clinical practice. In the primary study, the nomogram showed good discrimination, with an area under the receiver operating characteristic (ROC) curve (AUC) of 95.4% (95% CI, 90.6%–100.0%). Further validation study verified the efficacy of the nomogram, with an AUC of 99.0% (95% CI, 96.9%–100.00%) and 100.0% in all patients and patients with bilateral masses, respectively, and a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 66.67%/99.40%/66.67%/99.40%, 66.67%/100%/100%/92.86%, 50%/99.20%/50%/99.20%, and 100%/100%/100%/100%, in all patients, patients with bilateral adrenal masses, patients with nonfunctional adrenal masses, and patients with positive catecholamine results, respectively. The validation study also revealed a diagnostic specificity of 99.35% and 100% for patients with a unilateral adrenal mass and functional PCC, respectively.

Conclusions

The presented nomogram is the first user-friendly diagnostic model for PAL that simplifies the complex diagnostic process into personalized numeric estimates. We deem that patients who score below 50 are less likely to have PAL. We suggest that clinicians should arrange adrenal biopsy and surgery for patients with nonfunctional tumors and overt catecholamine-secreting tumors, respectively, who receive a score of 50 points or higher to confirm the diagnosis as soon as possible.
The Arachidonic Acid Metabolism Mechanism Based on UPLC-MS/MS Metabolomics in Recurrent Spontaneous Abortion Rats
Authors: Li Meihe , Haixia Yang , Kang Minchao , An Peng , Wu Xili , Dang Huimin , Xu Xin
Published: April 2021

Recurrent spontaneous abortion (RSA) remains a critical and challenging problem in reproduction. To discover novel biomarkers for RSA, ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) metabolomics approach was applied to detect RSA serum metabolic profiles and explore its possible pathogenesis and mechanism. The abortion rat model was established, and a metabolomics analysis was performed to evaluate the differentially expressed metabolites between the control and model groups. Immunohistochemistry (IHC), qRT-PCR, and Western blot further examined the expression of Arachidonic acid metabolism-related genes in uterus tissues. To identify arachidonic acid metabolism-related changes in RSA, ELISA’s potential mechanisms were further confirmed in serum. Ninety-one metabolites were significantly different between the two groups, as indicated by a VIP ≥1, fold change ≥1. The metabolic pathways involving arachidonic acid metabolism pathway (P= 0.00044) are related to RSA. Verification by experimental showed that compared with the control rats, the expression of the COX-1, COX-2, PTGFR, and TBXA2R genes associated with the arachidonic acid metabolism pathway has significantly increased the uterus and serum of RSA rats (P< 0.05). Regulation of the arachidonic acid metabolism pathway might serve as a promising therapeutic strategy for relieving RSA women’s symptoms.
T Cell Receptor Repertoires Acquired via Routine Pap Testing May Help Refine Cervical Cancer and Precancer Risk Estimates
Authors: Christley Scott , Ostmeyer Jared , Quirk Lisa , Zhang Wei , Sirak Bradley , Giuliano Anna R. , Zhang Song , Monson Nancy , Tiro Jasmin , Lucas Elena , Cowell Lindsay G.
Published: April 2021

Cervical cancer is the fourth most common cancer and fourth leading cause of cancer death among women worldwide. In low Human Development Index settings, it ranks second. Screening and surveillance involve the cytology-based Papanicolaou (Pap) test and testing for high-risk human papillomavirus (hrHPV). The Pap test has low sensitivity to detect precursor lesions, while a single hrHPV test cannot distinguish a persistent infection from one that the immune system will naturally clear. Furthermore, among women who are hrHPV-positive and progress to high-grade cervical lesions, testing cannot identify the ~20% who would progress to cancer if not treated. Thus, reliable detection and treatment of cancers and precancers requires routine screening followed by frequent surveillance among those with past abnormal or positive results. The consequence is overtreatment, with its associated risks and complications, in screened populations and an increased risk of cancer in under-screened populations. Methods to improve cervical cancer risk assessment, particularly assays to predict regression of precursor lesions or clearance of hrHPV infection, would benefit both populations. Here we show that women who have lower risk results on follow-up testing relative to index testing have evidence of enhanced T cell clonal expansion in the index cervical cytology sample compared to women who persist with higher risk results from index to follow-up. We further show that a machine learning classifier based on the index sample T cells predicts this transition to lower risk with 95% accuracy (19/20) by leave-one-out cross-validation. Using T cell receptor deep sequencing and machine learning, we identified a biophysicochemical motif in the complementarity-determining region 3 of T cell receptor β chains whose presence predicts this transition. While these results must still be tested on an independent cohort in a prospective study, they suggest that this approach could improve cervical cancer screening by helping distinguish women likely to spontaneously regress from those at elevated risk of progression to cancer. The advancement of such a strategy could reduce surveillance frequency and overtreatment in screened populations and improve the delivery of screening to under-screened populations.
Evaluation of the Immunogenic Response of a Novel Enterobactin Conjugate Vaccine in Chickens for the Production of Enterobactin-Specific Egg Yolk Antibodies
Authors: Zeng Ximin , Wang Huiwen , Huang Canghai , Logue Catherine M. , Barbieri Nicolle L. , Nolan Lisa K. , Lin Jun
Published: April 2021

Passive immunization with specific egg yolk antibodies (immunoglobulin Y, IgY) is emerging as a promising alternative to antibiotics to control bacterial infections. Recently, we developed a novel conjugate vaccine that could trigger a strong immune response in rabbits directed against enterobactin (Ent), a highly conserved siderophore molecule utilized by different Gram-negative pathogens. However, induction of Ent-specific antibodies appeared to be affected by the choice of animal host and vaccination regimen. It is still unknown if the Ent conjugate vaccine can trigger a specific immune response in layers for the purpose of production of anti-Ent egg yolk IgY. In this study, three chicken vaccination trials with different regimens were performed to determine conditions for efficient production of anti-Ent egg yolk IgY. Purified Ent was conjugated to three carrier proteins, keyhole limpet hemocyanin (KLH), bovine serum albumin (BSA) and CmeC (a subunit vaccine candidate), respectively. Intramuscular immunization of Barred Rock layers with KLH-Ent conjugate four times induced strong immune response against whole conjugate vaccine but the titer of Ent-specific IgY did not change in yolk with only a 4 fold increase detected in serum. In the second trial, three different Ent conjugate vaccines were evaluated in Rhode Island Red pullets with four subcutaneous injections. The KLH-Ent or CmeC-Ent conjugate consistently induced high level of Ent-specific IgY in both serum (up to 2,048 fold) and yolk (up to 1,024 fold) in each individual chicken. However, the Ent-specific immune response was only temporarily and moderately induced using a BSA-Ent vaccination. In the third trial, ten White Leghorn layers were subcutaneously immunized three times with KLH-Ent, leading to consistent and strong immune response against both whole conjugate and the Ent molecule in each chicken; the mean titer of Ent-specific IgY increased approximately 32 and 256 fold in serum and yolk, respectively. Consistent with its potent binding to various Ent derivatives, the Ent-specific egg yolk IgY also inhibited in vitro growth of a representative Escherichia coli strain. Together, this study demonstrated that the novel Ent conjugate vaccine could induce strong, specific, and robust immune response in chickens. The Ent-specific hyperimmune egg yolk IgY has potential for passive immune intervention against Gram-negative infections.
Integrative Transcriptomic, Proteomic and Functional Analysis Reveals ATP1B3 as a Diagnostic and Potential Therapeutic Target in Hepatocellular Carcinoma
Authors: Lu Shanshan , Cai Shenglan , Peng Xiaozhen , Cheng Ruochan , Zhang Yiya
Published: April 2021

The Na+/K+-ATPase (NKA), has been proposed as a signal transducer involving various pathobiological processes, including tumorigenesis. However, the clinical relevance of NKA in hepatocellular carcinoma (HCC) has not been well studied. This study revealed the upregulation of mRNA of ATP1A1, ATP1B1, and ATP1B3 in HCC using TCGA, ICGC, and GEO database. Subsequently, ATP1B3 was demonstrated as an independent prognostic factor of overall survival (OS) of HCC. To investigate the potential mechanisms of ATP1B3 in HCC, we analyzed the co-expression network using LinkedOmics and found that ATP1B3 co-expressed genes were associated with immune-related biological processes. Furthermore, we found that ATP1B3 was correlated immune cell infiltration and immune-related cytokines expression in HCC. The protein level of ATP1B3 was also validated as a prognostic significance and was correlated with immune infiltration in HCC using two proteomics datasets. Finally, functional analysis revealed that ATP1B3 was increased in HCC cells and tissues, silenced ATP1B3 repressed HCC cell proliferation, migration, and promoted HCC cell apoptosis and epithelial to mesenchymal transition (EMT). In conclusion, these findings proved that ATP1B3 could be an oncogene and it was demonstrated as an independent prognostic factor and correlated with immune infiltration in HCC, revealing new insights into the prognostic role and potential immune regulation of ATP1B3 in HCC progression and provide a novel possible therapeutic strategy for HCC.
Fit-For-All iPSC-Derived Cell Therapies and Their Evaluation in Humanized Mice With NK Cell Immunity
Authors: Flahou Charlotte , Morishima Tatsuya , Takizawa Hitoshi , Sugimoto Naoshi
Published: April 2021

Human induced pluripotent stem cells (iPSCs) can be limitlessly expanded and differentiated into almost all cell types. Moreover, they are amenable to gene manipulation and, because they are established from somatic cells, can be established from essentially any person. Based on these characteristics, iPSCs have been extensively studied as cell sources for tissue grafts, blood transfusions and cancer immunotherapies, and related clinical trials have started. From an immune-matching perspective, autologous iPSCs are perfectly compatible in principle, but also require a prolonged time for reaching the final products, have high cost, and person-to-person variation hindering their common use. Therefore, certified iPSCs with reduced immunogenicity are expected to become off-the-shelf sources, such as those made from human leukocyte antigen (HLA)-homozygous individuals or genetically modified for HLA depletion. Preclinical tests using immunodeficient mice reconstituted with a human immune system (HIS) serve as an important tool to assess the human alloresponse against iPSC-derived cells. Especially, HIS mice reconstituted with not only human T cells but also human natural killer (NK) cells are considered crucial. NK cells attack so-called “missing self” cells that do not express self HLA class I, which include HLA-homozygous cells that express only one allele type and HLA-depleted cells. However, conventional HIS mice lack enough reconstituted human NK cells for these tests. Several measures have been developed to overcome this issue including the administration of cytokines that enhance NK cell expansion, such as IL-2 and IL-15, the administration of vectors that express those cytokines, and genetic manipulation to express the cytokines or to enhance the reconstitution of human myeloid cells that express IL15R-alpha. Using such HIS mice with enhanced human NK cell reconstitution, alloresponses against HLA-homozygous and HLA-depleted cells have been studied. However, most studies used HLA-downregulated tumor cells as the target cells and testedin vitroafter purifying human cells from HIS mice. In this review, we give an overview of the current state of iPSCs in cell therapies, strategies to lessen their immunogenic potential, and then expound on the development of HIS mice with reconstituted NK cells, followed by their utilization in evaluating future universal HLA-engineered iPSC-derived cells.
Advances in Research on the Cardiovascular Complications of Acromegaly
Authors: Yang Han , Tan Huiwen , Huang He , Li Jianwei
Published: April 2021

Cardiovascular-related complications are one of the most common complications in patients with acromegaly, and can lead to an increased risk of death. Hypertension and cardiomyopathy are the main cardiovascular complications. The characteristics of acromegalic cardiomyopathy are concentric biventricular hypertrophy and diastolic dysfunction. In addition, arrhythmia and heart valve disease are common cardiac complications in acromegaly. Although the underlying pathophysiology has not been fully elucidated, the spontaneous overproduction of GH and IGF-1, increasing age, prolonged duration of disease and the coexistence of other cardiovascular risk factors are crucial to cardiac complications in patients with acromegaly. Early diagnosis and appropriate treatment of acromegaly might be beneficial for the prevention of cardiomyopathy and premature death.
Study on the Atomization Characteristics of Flat Fan Nozzles for Pesticide Application at Low Pressures
Authors: Li Shougen , Chen Chongchong , Wang Yaxiong , Kang Feng , Li Wenbin
Published: April 2021

Spraying is the most widely used means of pesticide application for pest control in agriculture and forestry. The atomization characteristics of the nozzles are directly related to the spray drift, rebound, and deposition. Previous research studies have mainly focused on the change pattern of atomization characteristics. Mathematical descriptions of the atomization characteristics of flat fan nozzles are rare, and pesticide application theories are also insufficient. Atomization characteristics mainly include droplet size and velocity. This study analyzes the influence of the spray parameters (spray angle, pressure, and equivalent orifice diameter of nozzles) and the spatial position in the flow field. To obtain the atomization characteristics of flat fan nozzles, the phase Doppler particle analyzer (PDPA) was selected for the accurate measurement of the droplet sizes and velocities at distances 0.30–0.60 m, using low spray pressures (0.15–0.35 MPa). The droplet size and velocity models were then established and validated. The results revealed that the average absolute error of the droplet size model was 23.74 µm and the average relative error was 8.23%. The average absolute and relative errors of the droplet velocity model were 0.37 m/s and 7.86%, respectively. At a constant spray pressure and angle, there was a positive correlation between the droplet size and the equivalent orifice diameter of the nozzles. The test also verified that the spray angle and distance had a negative correlation with the droplet velocity at a given pressure. The spray distance had no effect on the spray axial droplet size at constant spray pressure. In addition, the spray angle greatly affected the droplet velocity along the X-axis; similarly, the spray parameters, especially spray angle, greatly affected the droplet size.
Biofertilizer-Based Zinc Application Enhances Maize Growth, Gas Exchange Attributes, and Yield in Zinc-Deficient Soil
Authors: Saboor Abdul , Ali Muhammad Arif , Ahmed Niaz , Skalicky Milan , Danish Subhan , Fahad Shah , Hassan Fahmy , Hassan Mohamed M. , Brestic Marian , EL Sabagh Ayman , Datta Rahul
Published: April 2021

Zinc (Zn) concentration in soil varies from deficient to toxic. Its deficiency, as well as toxicity, through imbalanced application and cropping in industrial sites can reduce maize growth and yield. Therefore, balanced Zn application is necessary to save resources and achieve optimum growth and yield in maize. Arbuscular mycorrhizal fungi (AMF) can provide tolerance to the host plant against Zn-induced stress. Inoculation with AMF helps in regulating the uptake of Zn and enhances the growth and yield of crops. Different application rates of Zn (0, 20, 40, 60, 80, 100, and 120 mg Zn kg−1) were applied with inoculation with AMF (AM) and without AMF (NM). Results showed that root colonization was 45% higher in AMF-inoculated plants than non-inoculated plants. A significant increase in plant height (15%), number of leaves (35.4%), cob weight (4.39%), 1000-grain weight (10.5%), and biological yield (42.2%) signified the efficacious functioning of Zn20 + AM over sole inoculation with AM. We also observed that AMF inoculation with Zn20 helped to improve photosynthesis, transpiration, and stomatal conductance. Furthermore, both Zn20 + AM and Zn20 + AM significantly increased total soluble protein compared with AM. Higher application rates of zinc, i.e., Zn80 and Zn120, induced Zn toxicity with (AM) and without (NM) AMF. In conclusion, Zn20 + AM is an effective treatment to achieve better growth and maize yield without Zn deficiency or toxicity.
A Review on the Erosion Mechanism in Cavitating Jets and Their Industrial Applications
Authors: El Hassan Mouhammad , Bukharin Nikolay , Al-Kouz Wael , Zhang Jing-Wei , Li Wei-Feng
Published: April 2021

Cavitating jets have been widely studied for over a century, but despite the extensive literature on this subject, the implementation of cavitating jets in many industries is still very limited due to technical challenges. The main purpose of the present paper is to provide recommendations on using the cavitating jets based on a comprehensive literature review on the erosion mechanism in these jets. Self-resonating jets are extensively discussed in the present paper due to their importance in amplifying the erosion effect of cavitating jets. The influence of different jet nozzle geometric parameters and the operating conditions of the cavitating jet flow on the erosion mechanism is also discussed. Finally, well drilling in addition to multiple other industrial applications of cavitating jets are examined.
Security Vulnerabilities in LPWANs—An Attack Vector Analysis for the IoT Ecosystem
Authors: Torres Nuno , Pinto Pedro , Lopes Sérgio Ivan
Published: April 2021

Due to its pervasive nature, the Internet of Things (IoT) is demanding for Low Power Wide Area Networks (LPWAN) since wirelessly connected devices need battery-efficient and long-range communications. Due to its low-cost and high availability (regional/city level scale), this type of network has been widely used in several IoT applications, such as Smart Metering, Smart Grids, Smart Buildings, Intelligent Transportation Systems (ITS), SCADA Systems. By using LPWAN technologies, the IoT devices are less dependent on common and existing infrastructure, can operate using small, inexpensive, and long-lasting batteries (up to 10 years), and can be easily deployed within wide areas, typically above 2 km in urban zones. The starting point of this work was an overview of the security vulnerabilities that exist in LPWANs, followed by a literature review with the main goal of substantiating an attack vector analysis specifically designed for the IoT ecosystem. This methodological approach resulted in three main contributions: (i) a systematic review regarding cybersecurity in LPWANs with a focus on vulnerabilities, threats, and typical defense strategies; (ii) a state-of-the-art review on the most prominent results that have been found in the systematic review, with focus on the last three years; (iii) a security analysis on the recent attack vectors regarding IoT applications using LPWANs. Results have shown that LPWANs communication technologies contain security vulnerabilities that can lead to irreversible harm in critical and non-critical IoT application domains. Also, the conception and implementation of up-to-date defenses are relevant to protect systems, networks, and data.
Eye-Tracker Analysis of the Contrast Sensitivity of Anomalous and Normal Trichromats: A Loglinear Examination with Landolt-C Figures
Authors: Sipos László , Gere Attila , Kókai Zoltán , Nyitrai Ákos , Kovács Sándor , Urbin Ágnes , Samu Krisztián , Wenzel Klára
Published: April 2021

The contrast sensitivity of normal and anomalous trichromats were examined with Landolt-C figures by eye-tracking system. For the measurements, two series of test images (achromatic and colored) were designed. The difficulty levels of the tests were gradually increased after each right answer. In the case of the observation of the ring of the Landolt-C figures, the variables related to fixation duration, fixation count, visit duration and count significantly affected this subject, success or image parameters, and their interactions. The main questions of this study were as follows: Which statistical method is suitable to model the differences between anomalous and normal trichromats? Which eye-movement variables have a significant effect on the investigated parameters and on their interactions? Is there any significant difference between eye-movement variables of normal and anomalous trichromats? How does the survival time of anomalous and normal trichromats change in the case of achromatic and colored figures? The results showed that the right answers of anomalous and normal trichromats can be described with multiple or cross-classified contingency tables evaluated effectively by loglinear regression. The survival analysis showed that normal trichromats are more successful in interpreting colored images, while anomalous trichromats seemed to be more efficient in perceiving achromatic images.
Induction of Apoptosis of Cancer Cells Using the Cisplatin Delivery Based Electrospray (CDES) System
Authors: Lee Myung Chul , Pandey Shambhavi , Lim Jae Woon , Park Sangbae , Kim Jae Eun , Son Hyunmok , Han Jinsub , Seonwoo Hoon , Garg Pankaj , Chung Jong Hoon
Published: April 2021

Cisplatin, a representative anticancer drug used to treat cancer, has many adverse effects. In particular, it causes significant damage to the kidneys. Thus, many researchers have studied the delivery of drugs, such as cisplatin, to cancer areas using targeted drug-delivery systems. Here, we propose a new way to treat cancer by delivering anticancer drugs directly to the tumor site using the electrospray (ES) technique. We determined the optimal conditions for ES to promote the introduction of cisplatin into cancer cells. In our results, the group with cisplatin delivery-based electrospray (CDES) at 6 kV had an apoptosis of cancer cells approximately two times more than the group treated with cisplatin alone. We also confirmed that ES alone did not affect the survival of cells up to a voltage of 6 kV, but increased the permeability of the cell plasma membrane instantaneously, facilitating the influx of the drug.
A Duplicated Copy of the Meiotic Gene ZIP4 Preserves up to 50% Pollen Viability and Grain Number in Polyploid Wheat
Authors: Alabdullah Abdul Kader , Moore Graham , Martín Azahara C.
Published: April 2021

Although most flowering plants are polyploid, little is known of how the meiotic process evolves after polyploidisation to stabilise and preserve fertility. On wheat polyploidisation, the major meiotic gene ZIP4 on chromosome 3B duplicated onto 5B and diverged (TaZIP4-B2). TaZIP4-B2 was recently shown to promote homologous pairing, synapsis and crossover, and suppress homoeologous crossover. We therefore suspected that these meiotic stabilising effects could be important for preserving wheat fertility. A CRISPR Tazip4-B2 mutant was exploited to assess the contribution of the 5B duplicated ZIP4 copy in maintaining pollen viability and grain setting. Analysis demonstrated abnormalities in 56% of meiocytes in the Tazip4-B2 mutant, with micronuclei in 50% of tetrads, reduced size in 48% of pollen grains and a near 50% reduction in grain number. Further studies showed that most of the reduced grain number occurred when Tazip4-B2 mutant plants were pollinated with the less viable Tazip4-B2 mutant pollen rather than with wild type pollen, suggesting that the stabilising effect of TaZIP4-B2 on meiosis has a greater consequence in subsequent male, rather than female gametogenesis. These studies reveal the extraordinary value of the wheat chromosome 5B TaZIP4-B2 duplication to agriculture and human nutrition. Future studies should further investigate the role of TaZIP4-B2 on female fertility and assess whether different TaZIP4-B2 alleles exhibit variable effects on meiotic stabilisation and/or resistance to temperature change.
Neutrophil-to-Lymphocyte Ratio as a Cardiovascular Risk Marker May Be Less Efficient in Women Than in Men
Authors: Trtica Majnarić Ljiljana , Guljaš Silva , Bosnić Zvonimir , Šerić Vatroslav , Wittlinger Thomas
Published: April 2021

Cardiovascular disease (CVD) is the leading cause of death in women, although traditionally, it has been considered as a male dominated disease. Chronic inflammation plays a crucial role in the development of insulin resistance, diabetes type 2 and CVD. Since studies on women were scarce, in order to improve diagnosis and treatment of CVD, there is a need to improve understanding of the role of inflammation in the development of CVD in women. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive and widely available marker of inflammation, and has been studied in cardio-metabolic disorders. There is a paucity of data on sex specific differences in the lifetime course of NLR. Men and women differ to each other in sex hormones and characteristics of immune reaction and the expression of CVD. These factors can determine NLR values and their variations along the life course. In particular, menopause in women is a period associated with profound physiological and hormonal changes, and is coincidental with aging. An emergence of CV risk factors with aging, and age-related changes in the immune system, are factors that are associated with an increase in prevalence of CVD in both sexes. The aim of this review is to comprehend the available evidence on this issue, and to discuss sex specific differences in the lifetime course of NLR in the light of immune and inflammation mechanisms.
The Role of Nuclear Insulin and IGF1 Receptors in Metabolism and Cancer
Authors: Werner Haim , Sarfstein Rive , Laron Zvi
Published: April 2021

Insulin (InsR) and insulin-like growth factor-1 (IGF1R) receptors mediate the metabolic and growth-promoting actions of insulin and IGF1/IGF2, respectively. Evidence accumulated in recent years indicates that, in addition to their typical cell-surface localization pattern and ligand-activated mechanism of action, InsR and IGF1R are present in the cell nucleus of both normal and transformed cells. Nuclear translocation seems to involve interaction with a small, ubiquitin-like modifier protein (SUMO-1), although this modification is not always a prerequisite. Nuclear InsR and IGF1R exhibit a number of biological activities that classically fit within the definition of transcription factors. These nuclear activities include, among others, sequence-specific DNA binding and transcriptional control. Of particular interest, nuclear IGF1R was capable of binding and stimulating its cognate gene promoter. The physiological relevance of this autoregulatory mechanism needs to be further investigated. In addition to its nuclear localization, studies have identified IGF1R in the Golgi apparatus, and this particular distribution correlated with a migratory phenotype. In summary, the newly described roles of InsR and IGF1R as gene regulators, in concert with their atypical pattern of subcellular distribution, add a further layer of complexity to traditional models of cell signaling. Furthermore, and in view of the emerging role of IGF1R as a potential therapeutic target, a better understanding of the mechanisms responsible for nuclear IGF1R transport and identification of IGF1R interactors might help optimize target directed therapies in oncology.
Human Cadaveric Donor Cornea Derived Extra Cellular Matrix Microparticles for Minimally Invasive Healing/Regeneration of Corneal Wounds
Authors: Chandru Arun , Agrawal Parinita , Ojha Sanjay Kumar , Selvakumar Kamalnath , Shiva Vaishnavi K. , Gharat Tanmay , Selvam Shivaram , Thomas Midhun Ben , Damala Mukesh , Prasad Deeksha , Basu Sayan , Bhowmick Tuhin , Sangwan Virender Singh , Singh Vivek
Published: April 2021

Biological materials derived from extracellular matrix (ECM) proteins have garnered interest as their composition is very similar to that of native tissue. Herein, we report the use of human cornea derived decellularized ECM (dECM) microparticles dispersed in human fibrin sealant as an accessible therapeutic alternative for corneal anterior stromal reconstruction. dECM microparticles had good particle size distribution (≤10 µm) and retained the majority of corneal ECM components found in native tissue. Fibrin–dECM hydrogels exhibited compressive modulus of 70.83 ± 9.17 kPa matching that of native tissue, maximum burst pressure of 34.3 ± 3.7 kPa, and demonstrated a short crosslinking time of ~17 min. The fibrin–dECM hydrogels were found to be biodegradable, cytocompatible, non-mutagenic, non-sensitive, non-irritant, and supported the growth and maintained the phenotype of encapsulated human corneal stem cells (hCSCs) in vitro. In a rabbit model of anterior lamellar keratectomy, fibrin–dECM bio-adhesives promoted corneal re-epithelialization within 14 days, induced stromal tissue repair, and displayed integration with corneal tissues in vivo. Overall, our results suggest that the incorporation of cornea tissue-derived ECM microparticles in fibrin hydrogels is non-toxic, safe, and shows tremendous promise as a minimally invasive therapeutic approach for the treatment of superficial corneal epithelial wounds and anterior stromal injuries.
Recent Advances of Field-Effect Transistor Technology for Infectious Diseases
Authors: Panahi Abbas , Sadighbayan Deniz , Forouhi Saghi , Ghafar-Zadeh Ebrahim
Published: April 2021

Field-effect transistor (FET) biosensors have been intensively researched toward label-free biomolecule sensing for different disease screening applications. High sensitivity, incredible miniaturization capability, promising extremely low minimum limit of detection (LoD) at the molecular level, integration with complementary metal oxide semiconductor (CMOS) technology and last but not least label-free operation were amongst the predominant motives for highlighting these sensors in the biosensor community. Although there are various diseases targeted by FET sensors for detection, infectious diseases are still the most demanding sector that needs higher precision in detection and integration for the realization of the diagnosis at the point of care (PoC). The COVID-19 pandemic, nevertheless, was an example of the escalated situation in terms of worldwide desperate need for fast, specific and reliable home test PoC devices for the timely screening of huge numbers of people to restrict the disease from further spread. This need spawned a wave of innovative approaches for early detection of COVID-19 antibodies in human swab or blood amongst which the FET biosensing gained much more attention due to their extraordinary LoD down to femtomolar (fM) with the comparatively faster response time. As the FET sensors are promising novel PoC devices with application in early diagnosis of various diseases and especially infectious diseases, in this research, we have reviewed the recent progress on developing FET sensors for infectious diseases diagnosis accompanied with a thorough discussion on the structure of Chem/BioFET sensors and the readout circuitry for output signal processing. This approach would help engineers and biologists to gain enough knowledge to initiate their design for accelerated innovations in response to the need for more efficient management of infectious diseases like COVID-19.
Application of Virtual Environments for Biophilic Design: A Critical Review
Authors: Mollazadeh Maryam , Zhu Yimin
Published: April 2021

Biophilic design as a new design approach promotes the integration of natural elements into the built environment, leading to a significant impact on human health, well-being, and productivity. On the other hand, scholars have explored Virtual Environment (VE) to create virtual nature and provide a complex experience of exposure to natural elements virtually. However, there is a lack of understanding about such studies in general, which use VE as a reliable tool to support biophilic design. Thus, the authors conducted a literature review on the applications, capabilities, and limitations of VE for biophilic design. The literature review shows that VE is capable of supporting critical features of biophilic design studies such as representing combinations of biophilic patterns, providing multimodal sensory inputs, simulating stress induction tasks, supporting required exposure time to observe biophilic patterns, and measuring human’s biological responses to natural environment. However, factors affecting user’s experience of a virtual biophilic environment exist, such as VE experience dimensions, user-related factors, cybersickness, navigational issues, and possible limitations of VE sensory input. Overall, biophilic design studies in VEs are still limited. Nevertheless, there are many opportunities for further research in this field.
Stakeholder-Associated Factors Influencing Construction and Demolition Waste Management: A Systematic Review
Authors: Zhao Xianbo
Published: April 2021

Construction and demolition (C&D) activities generate a large amount of waste and have significant impacts on the environment. Thus, it is necessary to implement C&D waste management (WM), which requires the involvement of stakeholders and is influenced by a variety of factors. This study aims to undertake a systematic review of the stakeholder-associated factors influencing C&D WM. The Scopus search engine was used in a literature search, and two rounds of screening were performed. Only journal articles or reviews that were published in English after 2000 were used in this study. A total of 106 journal articles were reviewed. The review identified 35 stakeholder-associated factors influencing C&D WM and categorized them into six groups: regulatory environment, government and public supervision, advances in technologies, recycling market, knowledge, awareness, attitude, and behaviour of stakeholders, and project-specific factors. All the 35 factors are discussed in detail with considerations into relevant stakeholders. Although there have been studies focused on the factors influencing C&D WM, few have attempted to take stakeholders’ perspectives into consideration. This study expands the C&D WM literature by mapping the influential factors with relevant stakeholders and enables the practitioners to clearly understand their roles and responsibilities and make better informed decisions in the C&D WM process.
Prognostic and Predictive Biomarkers in Non-Small Cell Lung Cancer Patients on Immunotherapy—The Role of Liquid Biopsy in Unraveling the Puzzle
Authors: Augustus Elien , Zwaenepoel Karen , Siozopoulou Vasiliki , Raskin Jo , Jordaens Stephanie , Baggerman Geert , Sorber Laure , Roeyen Geert , Peeters Marc , Pauwels Patrick
Published: April 2021

In the last decade, immunotherapy has been one of the most important advances in the non-small cell lung cancer (NSCLC) treatment landscape. Nevertheless, only a subset of NSCLC patients benefits from it. Currently, the only Food and Drug Administration (FDA) approved diagnostic test for first-line immunotherapy in metastatic NSCLC patients uses tissue biopsies to determine the programmed death ligand 1 (PD-L1) status. However, obtaining tumor tissue is not always feasible and puts the patient at risk. Liquid biopsy, which refers to the tumor-derived material present in body fluids, offers an alternative approach. This less invasive technique gives real-time information on the tumor characteristics. This review addresses different promising liquid biopsy based biomarkers in NSCLC patients that enable the selection of patients who benefit from immunotherapy and the monitoring of patients during this therapy. The challenges and the opportunities of blood-based biomarkers such as cell-free DNA (cfDNA), circulating tumor cells (CTCs), exosomes, epigenetic signatures, microRNAs (miRNAs) and the T cell repertoire will be addressed. This review also focuses on the less-studied feces-based and breath-based biomarkers.
Successive Osteosarcoma Relapses after the First Line O2006/Sarcome-09 Trial: What Can We Learn for Further Phase-II Trials?
Authors: Thebault Eric , Piperno-Neumann Sophie , Tran Diep , Pacquement Hélène , Marec-Berard Perrine , Lervat Cyril , Castex Marie-Pierre , Cleirec Morgane , Bompas Emmanuelle , Vannier Jean-Pierre , Plantaz Dominique , Saumet Laure , Verite Cecile , Collard Olivier , Pluchart Claire , Briandet Claire , Monard Laure , Brugieres Laurence , Le Deley Marie-Cécile , Gaspar Nathalie
Published: April 2021

The purpose was to describe first and subsequent relapses in patients from the OS2006/Sarcome-09 trial, to help future trial design. We prospectively collected and analysed relapse data of all French patients included in the OS2006/Sarcome-09 trial, who had achieved a first complete remission. 157 patients experienced a first relapse. The median interval from diagnosis to relapse was 1.7 year (range 0.5–7.6). The first relapse was metastatic in 83% of patients, and disease was not measurable according to RECIST 1.1 criteria in 23%. Treatment consisted in systemic therapy (74%) and surgical resection (68%). A quarter of the patients were accrued in a phase-II clinical trial. A second complete remission was obtained for 79 patients. Most of them had undergone surgery (76/79). The 3-year progression-free and overall survival rates were 21% and 37%, respectively. In patients who achieved CR2, the 3y-PFS and OS rates were 39% and 62% respectively. Individual correlation between subsequent PFS durations was poor. For osteosarcoma relapses, we recommend randomised phase-II trials, open to patients from all age categories (children, adolescents, adults), not limited to patients with measurable disease (but stratified according to disease status), with PFS as primary endpoint, response rate and surgical CR as secondary endpoints.
RTK Inhibitors in Melanoma: From Bench to Bedside
Authors: Sabbah Malak , Najem Ahmad , Krayem Mohammad , Awada Ahmad , Journe Fabrice , Ghanem Ghanem E.
Published: April 2021

MAPK (mitogen activated protein kinase) and PI3K/AKT (Phosphatidylinositol-3-Kinase and Protein Kinase B) pathways play a key role in melanoma progression and metastasis that are regulated by receptor tyrosine kinases (RTKs). Although RTKs are mutated in a small percentage of melanomas, several receptors were found up regulated/altered in various stages of melanoma initiation, progression, or metastasis. Targeting RTKs remains a significant challenge in melanoma, due to their variable expression across different melanoma stages of progression and among melanoma subtypes that consequently affect response to treatment and disease progression. In this review, we discuss in details the activation mechanism of several key RTKs: type III: c-KIT (mast/stem cell growth factor receptor); type I: EGFR (Epidermal growth factor receptor); type VIII: HGFR (hepatocyte growth factor receptor); type V: VEGFR (Vascular endothelial growth factor), structure variants, the function of their structural domains, and their alteration and its association with melanoma initiation and progression. Furthermore, several RTK inhibitors targeting the same receptor were tested alone or in combination with other therapies, yielding variable responses among different melanoma groups. Here, we classified RTK inhibitors by families and summarized all tested drugs in melanoma indicating the rationale behind the use of these drugs in each melanoma subgroups from preclinical studies to clinical trials with a specific focus on their purpose of treatment, resulted effect, and outcomes.