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Land snails are a destructive agricultural pest in economic crops, but the populations for that pest are highly influenced by temperature and humidity, therefore climatic changes affected their behavior, distribution and population dynamics, for these reasons researchers should follow up on the changes in their behavior, distribution, and population dynamics. In this study, a survey study was conducted to define land snail species existing at Sharkia Governorate, Egypt, from January 2019 to March 2022 in horticultural, vegetable, and field crops and study the population dynamics for the dominant land snail species. Results showed that there are six species of land snails, these species were, Monacha cartusiana, Succinea putris, Eobania vermiculata, Theba pisana, Helicella vestalis, and Cochlicella acuta. The population dynamics of two prevalent land snail species (M. cartusiana and S. putris), were conducted during two successive growing seasons, the Egyptian clover harbored the highest number of M. cartusiana followed by wheat, while the onion was the lowest one during the study period. In the same trends, the land snail S. putris recorded the highest numbers during the growing season of the Egyptian clover crop. Finally, it is concluded that the land snail M. cartusiana considered the first grade of infestation existed everywhere at Sharkia Governorate, and the population density of the land snail is increase gradually after winter till reach the maximum density in spring.

Passive millimeter-wave imaging systems (PMWIS) are employed for detecting concealed objects by mapping millimeter waves emitted from materials or living tissues. The emitted waves are measured by a receiver or radiometers without employing external wave sources. In this paper, a new super-heterodyne receiver front-end of a PMWIS at 35 GHz with an even order band pass filter is simulated and implemented. The receiver has a suitable temperature resolution for the use of hidden object imaging, is integrated and lightweight assembled on one-layer board. It has a bandwidth of 1.5 GHz, a noise figure (NF) of 2.2, and a temperature resolution of 0.126 K. The even order filter is implemented based on the substrate-integrated waveguide (SIW) technology, with Chebyshev response. The filters are designed at the central frequency of 35 GHz with the bandwidth of 1.5 GHz and one of them has controllable transmission zeroes. The filters are made by printed circuit board technology, employing SIW as resonators, having a high-quality factor of 23.33. Additionally, a triple-stage radio frequency (RF) low noise amplifier has been implemented having the specification of: RF 34.25–35.75 GHz; bandwidth 1.5 GHz; gain >60 dB; NF

Purpose The goal of this study was to investigate the use of spectacles in everyday life after bilateral cataract surgery with a preoperative refractive target of emmetropia in both eyes. In addition, we analyzed the total cost of spectacles and the patientʼs visual satisfaction at least 6 months after surgery. Methods Patients after bilateral cataract surgery with implantation of an aspheric monofocal IOL (Tecnis 1, Johnson & Johnson) with a preoperative refractive target of emmetropia in both eyes and a documented refractive outcome were included in this prospective observational study. In a phone interview ≥ 6 months after surgery, the following items were assessed: type of spectacles purchased and overall cost, type of activity with and duration of spectacle wear, and satisfaction with the visual situation. Results Seventy patients were included in this study. Depending on their postoperative refraction, patients were divided into group A (n = 27) with perfect emmetropia in both eyes (i.e., spherical equivalent [SE] of ≥ − 0.25 D to ≤ + 0.25 D), group B (n = 21) with achieved emmetropia in one eye (i.e., SE of ≥ − 0.25 D to ≤ + 0.25 D) and a myopic refraction in the other eye ( Conclusions Most patients who achieve perfect bilateral emmetropia after implantation of monofocal aspheric lenses buy varifocal spectacles within 6 months, and more than half of all patients use their varifocal spectacles for more than 50% of their awakening time. The costs for such spectacles are high.

The 21-gene recurrence score assay has been validated as a predictive biomarker in early-stage HR+ and HER2-breast cancer. It is not indicated for use in HER2+ disease based on national guidelines. In this study, we assessed the value of 21-gene recurrence score (RS), or OncotypeDX (ODX), testing in HR+/HER2+ breast cancer. We used the National Cancer Database to identify patients with stages I-II, HR+/HER2+ breast cancer who received multi-gene testing with ODX. We then explored the prognostic and predictive value of this biomarker through various forms of survival modeling. ODX testing was performed in n = 5,280 patients. N = 2,678 patients (50.7%) had a RS 26, while n = 2,602 (49.3%) had a RS ≥26. In Kaplan-Meier survival modeling for patients with recurrence scores26, there was no significant difference in overall survival (p = 0.445) between patients receiving different systemic treatment regimens. However, when recurrence scores were ≥26, there was a statistically-significant difference in overall survival between systemic treatment regimens (p 0.001). 5-year overall survival was highest (97.4%) for patients receiving triple therapy (anti-HER2 with chemotherapy and endocrine therapy), followed by those receiving dual therapy with endocrine and anti-HER2 (96.7%), and endocrine with chemotherapy (94.9%). Patients receiving endocrine therapy alone exhibited the lowest 5-year overall survival (88.5%). RESULTS: Analysis from this large national cancer registry suggests that multigene testing may have predictive value in treatment selection for patients with early-stage, HR+/HER2+ breast cancer. Prospective trials are warranted to identify subgroups of patients with HR+/HER2+ breast cancer who can be spared anti-HER2 treatments and cytotoxic chemotherapy.

Objective: Being the second most common cancer in men, prostate cancer detection relies on laboratory tests, imaging, and surgical procedures, although biopsy remains the mainstay in diagnosis of prostate cancer. No clear cut-off of prostate specific antigen density (PSAD) for suspecting prostate cancer has been established in the Lebanese population. Our primary objective was to evaluate the diagnostic strength of the PSAD value versus total prostate specific antigen (tPSA) level in the Lebanese men in correlation with biopsy outcome to avoid unnecessary prostate biopsy. Methods: A retrospective study of 347 patients with history of prostate biopsy done for cancer suspicion included tPSA, prostate volume, and prostate density values and results of prostate biopsy. Data was collected from Bahman hospital and statistical analysis of the mean values of tPSA, prostate volume and PSAD in different age groups was done. Significance of the results was tested using. Results: On average, patients with negative biopsies were younger and they had lower tPSA levels, lower PSAD values and larger prostate volume compared to patients with positive biopsies. A PSAD cutoff of 0.185 ng/ml2 revealed the highest predictive strength for prostate cancer (6 times risk) compared with other parameters. These findings were mainly referred to patients with PSA > 10 ng/ml. Conclusions: A multifactorial approach must be conducted including all parameters in order to decide upon the need for prostate biopsy. PSAD proved to be a good marker in favor or against a prostate biopsy with a cut-off of 0.185 ng/ml2, especially in patients with tPSA level higher to 10 ng/ml. A multicenter study was recommended for better and more reliable results and more precise cut-offs.

In this research, an automatic algorithm of bread quality assessment using image processing techniques, is proposed. First, color images of bread with different qualities are photographed and a database of 1250 bread images is prepared. Then 2320 color and texture features are extracted from each bread images. Then, from this number of features, only 15 features containing sufficient information are selected. In addition, 54 appearance features are extracted from each bread image to determine its shape and size. Finally, bread images are classified using the multilevel Support Vector Machine classifier. The classification process is divided into five "one-against-all" classification problems. The proposed algorithm correctly identifies the bread appearance defects, including cuts, fractures, folds, non-uniformity, black and burnt areas in baking, deformity, color and size. The proposed algorithm, considering the extraction of only 15 features per an image, has a speed that guarantees its use in a machine vision system. The performance success of the proposed algorithm on the bread database, despite its very simple implementation, is 96.95%.

CRISPR/Cas9-based genome-editing therapies are poised to change the clinical outcome for many diseases with validated therapeutic targets awaiting an appropriate delivery system. Recent advances in lipid nanoparticle (LNP) technology make them an attractive platform for the delivery of various forms of CRISPR/Cas9, including the efficient and transient Cas9/gRNA ribonucleoprotein (RNP) complexes. In this study, we initially tested our novel LNP platform by delivering pre-complexed RNPs and template DNA to cultured mouse cortical neurons, and obtained successful ex vivo genome editing. We then directly injected LNP-packaged RNPs and DNA template into the mouse cornea to evaluate in vivo delivery. For the first time, we demonstrated wide-spread genome editing in the cornea using our LNP-RNPs. The ability of our LNPs to transfect the cornea highlights the potential of our novel delivery platform to be used in CRISPR/Cas9-based genome editing therapies of corneal diseases.

RESUMEN El sarcoma de Kaposi (SK) es el cáncer más frecuente en las personas que viven con VIH. Las investigaciones sobre esta condición son escasas en la región, por lo que, el objetivo de este artículo fue describir las características demográficas, clínicas y terapéuticas de los pacientes con VIH que desarrollaron SK en el Hospital Cayetano Heredia entre el 2000 y 2018. Se identificaron 129 casos de SK, con una mediana de edad de 33 años, con predominio en varones con el 92% (119/129), y en su mayoría hombres que tienen sexo con hombres (HSH). La mediana de tiempo desde el diagnóstico de VIH hasta el del SK fue de cinco meses, asociado con un recuento de linfocitos CD4 de 64 células/µL (RIC: 33-185) al momento del diagnóstico de SK. El compromiso cutáneo fue el más común; sin embargo, al menos la mitad de ellos también tuvo la forma visceral. ABSTRACT Kaposi’s sarcoma (KS) is the most frequent cancer in people living with HIV. Research on this condition is scarce in the region, therefore, this article aimed to describe the demographic, clinical and therapeutic characteristics of patients with HIV who developed KS at the Cayetano Heredia Hospital between 2000 and 2018. A total of 129 KS cases were identified, with a median age of 33 years, predominantly males with 92% (119/129), and mostly men who have sex with men (MSM). The median time from HIV diagnosis to KS diagnosis was five months, associated with a CD4 lymphocyte count of 64 cells/μL (IQR: 33-185) at KS diagnosis. Cutaneous involvement was the most common presentation; however, at least half also had the visceral form.

An Mw 7.8 earthquake occurred on the East Anatolian Fault (EAF) and the secondary Narlı Fault (NF) on Feb 6, 2023, closely followed by an Mw 7.5 event on the Sürgü Fault 9 hours later. We analyze the distant and local seismic data, high-rate GPS recordings, and radar satellite images by Slowness Enhanced Back-Projection and joint Finite Fault Inversion for the Mw 7.8 event to resolve its rupture process. The rupture first initiates and propagates on the NF. After reaching the junction with the EAF, it propagates bilaterally on the EAF, extending 120 km to the northeast at 3.05 km/s and 200 km to the southwest at 3.11 km/s. The southwest speed is further verified by local seismic recordings and the absence of Mach surface wave characteristics. Compared with the EAF, the NF features denser seismic activity in recent decades, suggesting that it was more favorable for rupture nucleation. The EAF segments where the largest coseismic slip occurred have been relatively quiescent since the late 1800s. But the coseismic slip is much larger than the slip deficit accumulated during this period, which could be attributed to an ~900-year supercycle. The EAF geometry is similar to other active fault systems, such as the San Andreas Fault (SAF) and San Jacinto Fault (SJF). Considering high slip rates, resemblant supercycle mode, and the lack of large earthquakes on the southern SAF and SJF since 1857, an M8 earthquake could potentially occur there if most moment accumulation is released at once.

Recent pharmacological studies demonstrate a role for zinc (Zn2+) in shaping intracellular calcium (Ca2+) dynamics and vice versa in excitable cells including neurons and cardiomyocytes. Herein, we sought to examine the dynamic of intracellular release of Ca2+ and Zn2+ upon modifying excitability of primary rat cortical neurons using electric field stimulation (EFS) in vitro. We show that exposure to EFS with an intensity of 7.69 V/cm induces transient membrane hyperpolarization together with transient elevations in the cytosolic levels of Ca2+ and Zn2+ ions. The EFS-induced hyperpolarization was inhibited by prior treatment of cells with the K+ channel opener diazoxide. Chemical hyperpolarization had no apparent effect on either Ca2+ or Zn2+. The source of EFS-induced rise in Ca2+ and Zn2+ seemed to be intracellular, and that the dynamic inferred of an interplay between Ca2+ and Zn2+ ions, whereby the removal of extracellular Ca2+ augmented the release of intracellular Ca2+ and Zn2+ and caused a stronger and more sustained hyperpolarization. We demonstrate that Zn2+ is released from intracellular vesicles located in the soma, with major co-localizations in the lysosomes and endoplasmic reticulum. These studies further support the use of EFS as a tool to interrogate the kinetics of intracellular ions in response to changing membrane potential in vitro.

Recently safety concerns have been raised in connection with high doses of recombinant adeno-associated viruses (rAAV). Therefore, we undertook a series of experiments to test viral capsid (rAAV9 and rAAV-PHP.B), dose, and route of administration (intrastromal, intravitreal, and intravenous) focused on aniridia, a congenital blindness that currently has no cure. The success of gene therapy for aniridia may depend on the presence of functional limbal stem cells (LSCs) in the damaged aniridic corneas and whether rAAV can transduce them. Both these concerns were unknown, and thus were also addressed by our studies. For the first time, we report ataxia and lethality after intravitreal or intrastromal rAAV-PHP.B virus injections. We demonstrated virus escape from the eye and transduction of non-ocular tissues by rAAV9 and rAAV-PHP.B capsids. We have also shown that intrastromal and intravitreal delivery of rAAV9 can transduce functional LSCs, as well as all four PAX6-expressing retinal cell types in aniridic eye, respectively. Overall, lack of adverse events and successful transduction of LSCs and retinal cells makes it clear that rAAV9 is the capsid of choice for future aniridia gene therapy. Our finding of rAAV lethality after intraocular injections will be impactful for other researchers developing rAAV-based gene therapies.

We explore the potential of the adjoint-state full waveform tsunami inversion method for tsunami warning and source imaging using S-net, an array of ocean bottom pressure gauges. Compared to finite-fault tsunami source inversions, the method we use does not require as densely gridded Green’s functions to obtain a high resolution result, thus reducing computation time. What is required is a dense instrument network with good azimuthal coverage. The S-net pressure gauges fulfill this requirement and reduce the data collection time, thus making it possible to invert the recordings for the tsunami source and issue a timely tsunami warning. We apply our method to synthetic waveforms of the 2011 Mw 9.0 Tohoku earthquake and tsunami as well as data from the 2016 Mw 6.9 Fukushima earthquake. The results of the synthetic tests show that using the first 5 minutes of the waveforms, the adjoint-state inversion method achieves good performance with an average accuracy score of 93%, with the error of predicted wave amplitudes ranging between -5.6 to 1.9 m. Our application to the 2016 Fukushima earthquake shows the required waveform duration to achieve accurate inversions for smaller events is longer than that of a larger event. However, using the first 25 minutes of the waveforms, the inversion yields a tsunami source that is sufficient for making accurate predictions of arrival times and amplitudes. Assuming a uniformly distributed fault slip, we estimated a stress drop for the latter event to be 4.6 MPa, which is in line with estimations from recent studies.

Fig. S1. Up-regulation of thyroid hormone synthesis-related genes in the BVE-Ctnnb1null thyroid tumors. Data are expressed as fold changes between BVE-Ctnnb1null and BVE tumors.

Fig. S2. Kdm4a expression in thyroid tumor samples and cell lines. Kdm4a expression was analyzed by RNA-Seq. in normal control thyroids, BVE-Ctnnb1wt (BVE) and BVE-Ctnnb1null thyroid tumors, and cell lines. * indicates statistically significant between normal and tumor samples or cell lines (p

BRAFV600E mutation is the most frequent genetic alteration in papillary thyroid cancer (PTC). β-Catenin (Ctnnb1) is a key downstream component of canonical Wnt signaling pathway and is frequently overexpressed in PTC. BRAFV600E-driven tumors have been speculated to rely on Wnt/β-catenin signaling to sustain its growth, although many details remain to be elucidated. In this study, we investigated the role of β-catenin in BrafV600E-driven thyroid cancer in a transgenic mouse model. In BrafV600E mice with wild-type (WT) Ctnnb1 (BVE-Ctnnb1WT or BVE), overexpression of β-catenin was observed in thyroid tumors. In BrafV600E mice with Ctnnb1 knockout (BVE-Ctnnb1null), thyroid tumor growth was slowed with significant reduction in papillary architecture. This was associated with increased expression of genes involved in thyroid hormone synthesis, elevated 124iodine uptake, and serum T4. The survival of BVE-Ctnnb1null mice was increased by more than 50% during 14-month observation. Mechanistically, downregulation of MAPK, PI3K/Akt, and TGFβ pathways and loss of epithelial–mesenchymal transition (EMT) were demonstrated in the BVE-Ctnnb1null tumors. Treatment with dual β-catenin/KDM4A inhibitor PKF118–310 dramatically improved the sensitivity of BVE-Ctnnb1WT tumor cells to BRAFV600E inhibitor PLX4720, resulting in significant growth arrest and apoptosis in vitro, and tumor regression and differentiation in vivo. These findings indicate that β-catenin signaling plays an important role in thyroid cancer growth and resistance to BRAFV600E inhibitors. Simultaneously targeting both Wnt/β-catenin and MAPK signaling pathways may achieve better therapeutic outcome in BRAFV600E inhibitor-resistant and/or radioiodine-refractory thyroid cancer.

Supplementary Table 2. Differentially expressed vitamin D responsive genes in BVECyp24a1-wt and BVECyp24a1-null cells

Supplementary Table 3. Top 100 differentially expressed genes in BVECyp24a1-null cells

Supplementary Table 1. Primer sequences for qPCR

CYP24A1, the primary inactivating enzyme for vitamin D, is often overexpressed in human cancers, potentially neutralizing the antitumor effects of calcitriol, the active form of vitamin D. However, it is unclear whether CYP24A1 expression serves as a functional contributor versus only a biomarker for tumor progression. In this study, we investigated the role of CYP24A1 on malignant progression of a murine model of BrafV600E-induced papillary thyroid cancer (PTC). Mice harboring wild-type Cyp24a1 (BVECyp24a1-wt) developed PTC at 5 weeks of age. Mice harboring a homozygous deletion of Cyp24a1 (BVECyp24a1-null) exhibited a 4-fold reduction in tumor growth. Notably, we found the tumorigenic potential of BVECyp24a1-null-derived tumor cells to be nearly abolished in immunocompromised nude mice. This phenotype was associated with downregulation of the MAPK, PI3K/Akt, and TGFβ signaling pathways and a loss of epithelial–mesenchymal transition (EMT) in BVECyp24a1-null cells, associated with downregulation of genes involved in EMT, tumor invasion, and metastasis. While calcitriol treatment did not decrease cell proliferation in BVECyp24a1-null cells, it strengthened antitumor responses to the BRAFV600E inhibitor PLX4720 in both BVECyp24a1-null and BVECyp24a1-wt cells. Our findings offer direct evidence that Cyp24a1 functions as an oncogene in PTC, where its overexpression activates multiple signaling cascades to promote malignant progression and resistance to PLX4720 treatment. Cancer Res; 77(8); 2161–72. ©2017 AACR.

Anaplastic thyroid carcinoma (ATC) is the rarest type of thyroid cancer but is the common cause of death from these tumors. The aggressive behavior of ATC makes it resistant to the conventional therapeutic approaches. Thus, the present study was designed to evaluate the anti-ATC efficacy of the curcumin analogue PAC. We have shown that PAC induces apoptosis in thyroid cancer cells in a time-dependent fashion through the mitochondrial pathway. Immunoblotting analysis revealed that PAC suppressed the epithelial-to-mesenchymal transition (EMT) process in ATC cells by increasing the epithelial marker E-cadherin and reducing the level of the mesenchymal markers N-cadherin, Snail, Slug and Twist1. This anti-EMT effect was confirmed by showing PAC-dependent inhibition of the proliferation and migration abilities of ATC cells. In addition, PAC downregulated ALDH1 and suppressed the formation of thyroid tumorespheres in vitro. Interestingly, PAC inhibited the AKT/mTOR pathway in ATC cells. Indeed, PAC downregulated mTOR and its downstream effectors p70S6K and 4E-BP1 more efficiently than the well-known mTOR inhibitor rapamycin. In addition to the promising in vitro anticancer efficacy, PAC significantly suppressed the growth of humanized thyroid tumor xenografts in mice. Together, these findings indicate that PAC could be considered as promising therapeutic agent for anaplastic thyroid carcinomas.

BRAFV600E mutation is the most frequent genetic alteration in papillary thyroid cancer (PTC). β-Catenin (Ctnnb1) is a key downstream component of canonical Wnt signaling pathway and is frequently overexpressed in PTC. BRAFV600E-driven tumors have been speculated to rely on Wnt/β-catenin signaling to sustain its growth, although many details remain to be elucidated. In this study, we investigated the role of β-catenin in BrafV600E-driven thyroid cancer in a transgenic mouse model. In BrafV600E mice with wild-type (WT) Ctnnb1 (BVE-Ctnnb1WT or BVE), overexpression of β-catenin was observed in thyroid tumors. In BrafV600E mice with Ctnnb1 knockout (BVE-Ctnnb1null), thyroid tumor growth was slowed with significant reduction in papillary architecture. This was associated with increased expression of genes involved in thyroid hormone synthesis, elevated 124iodine uptake, and serum T4. The survival of BVE-Ctnnb1null mice was increased by more than 50% during 14-month observation. Mechanistically, downregulation of MAPK, PI3K/Akt, and TGFβ pathways and loss of epithelial–mesenchymal transition (EMT) were demonstrated in the BVE-Ctnnb1null tumors. Treatment with dual β-catenin/KDM4A inhibitor PKF118–310 dramatically improved the sensitivity of BVE-Ctnnb1WT tumor cells to BRAFV600E inhibitor PLX4720, resulting in significant growth arrest and apoptosis in vitro, and tumor regression and differentiation in vivo. These findings indicate that β-catenin signaling plays an important role in thyroid cancer growth and resistance to BRAFV600E inhibitors. Simultaneously targeting both Wnt/β-catenin and MAPK signaling pathways may achieve better therapeutic outcome in BRAFV600E inhibitor-resistant and/or radioiodine-refractory thyroid cancer.