bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient generation of null-segregant parthenocarpic tomato by CRISPR/Cas9 editing
Authors: Hara Chihiro Abe , Ueta Risa , Hashimoto Ryosuke , Osakabe Yuriko , Osakabe Keishi
Published: January 2020

Background
Genome editing technique is a powerful tool in plant genetic engineering to accelerate the rapid breeding of crop plants. Currently, obtaining transgene-free mutant plants is an important issue. transgene-free mutant plants such as null-segregant, can be segregated out from selfing or back-crossed populations. However, such procedures are time consuming, and, therefore, the development of efficient systems to eliminate transgenes in mutant plants is required.
Results
CRISPR/Cas9 vectors targeting Sl IAA9 were introduced into the tomato cultivars, Ailsa Craig, Moneymaker, Super Roma and Rio Grande, via Agrobacterium transformation. Bi-allelic mutations were detected at ratios of 9–46% in CRISPR/Cas9-transgenic T0 shoots. Sequence analysis revealed that the bi-allelic mutations generated stop codons by frame-shift of SlIAA9 amino acid sequences, indicating that sliaa9 knockout mutants with parthenocarpic phenotypes were generated in the T0 generation with high efficiency in these cultivars. Subsequently, many null-segregant (transgene free) lines, as confirmed by PCR and Southern blot, were isolated rapidly in the T1 generation by self-pollination.
Conclusions
The method used in this study is effective in achieving rapid isolation of null-segregants with high efficiency, while adding important traits to various cultivars at the same time. Our developed system would further increase the advantages of using CRISPR/Cas9 for the production of novel crop varieties in the future.
The prediction and risk point score (RPS) of noise induced hearing loss (NIHL)
Authors: Sun Ruican , Shang Weiwei , Cao Yingqiong , Lan Yajia
Published: January 2020

Background Noise induced hearing loss (NIHL) is a significant occupational health concern in many countries. Based on the realistic demands, we aimed to build the prediction risk model of noise induced hearing loss (NIHL) and developed the related risk point score (RPS). The results of this study expect to provide technology support for interventions and management, in order to enhance the application-orientated research on NIHL. Methods A total of 40433 participants of noise exposed workers were enrolled. The datasets from The National Key Occupational Diseases Survey (NKODS) from 2014 to 2017 in Sichuan province of China. The socio-demographic and occupational characteristics used the standardized questionnaires, and the level of NIHL were collected by audiometric testing, which was defined as binaural high-frequency threshold average (BHFTA) over 40dB. The prediction model expressed by linear format of logistic regression and based on model calculated the risk point score (RPS) of NIHL. Results Of the 40433 participants in the study, there are 9.97%(n=4029) of workers have NIHL (BHFBA >40). Age (OR=1.08, 95%CI: 1.071-1.083), sex (OR=3.34, 95%CI:2.997-3.715), noise exposure time (OR=1.01, 95%CI: 1.008-1.017), manufacturing industry(OR=1.35, 95%CI:1.207-1.500), construction industry (OR=2.59, 95%CI: 1.941-3.458), mining industry (OR=2.42, 95%CI: 2.132-2.740), foreign enterprise(OR=1.14, 95%CI: 0.962-1.353), private enterprise(OR=1.48, 95%CI: 1.361-1.603) are predictors of NIHL( P <0.05). The risk prediction model has a better effectiveness of NIHL (AUC= 0.7150). According to the NIHL- RPS calculated the individual score was 75 that the risk probability of NIHL was 37.97%. Conclusion The study found that the prevalence of NIHL at a moderate level in Sichuan province. Sex, age, noise exposure time, manufacturing industry, construction industry, mining industry, foreign enterprise, private enterprise are predictors of NIHL, and to develop the NIHL-RPS is necessary for application-orientated research on NIHL.
Two mathematical frameworks for vesicle release from a ribbon synapse of a retinal bipolar cell
Authors: Bassereh Hassan , Rattay Frank
Published: January 2020

Background: Bipolar cells communicate with amacrine and ganglion cells of the retina via both transient and sustained neurotransmitter release in ribbon synapses. Reconstructing the published quantitative release data from electrical soma stimulation (voltage clamp experiments) of rat rod bipolar cells were used to develop two simple models to predict the number of released vesicles as time series. In the experiment, the currents coming to the AII amacrine cell originating from releasing vesicles from the rod bipolar cell were recorded using paired-recordings in whole-cell voltage-clamp method. One of the models is based directly on terminal transmembrane voltage, so-called ‘modelV’, whereas the temporally exacter modelCa includes changes of intracellular calcium concentrations at terminals. Results: The intracellular calcium concentration method replicates a 0.43-ms signal delay for the transient release to pulsatile stimulation as a consequence of calcium channel dynamics in the presynaptic membrane, while the modelV has no signal delay. Both models produce the quite similar results in low stimuli amplitudes. However, for large stimulation intensities that may be done during extracellular stimulations in retinal implants, the modelCa predicts that the reversal potential of calcium limits the number of transiently released vesicles. Adding sodium and potassium ion channels to the axon of the cell enable to study the impact of spikes on the transient release in BC ribbons. A spike elicited by somatic stimulation causes the rapid release of all vesicles that are available for transient release, while a non-spiking BC with a similar morphometry needs stronger stimuli for any transient vesicle release. During extracellular stimulation, there was almost no difference in transient release between the active and passive cells because in both cases the terminal membrane of the cell senses the same potentials originating from the microelectrode. An exception was found for long pulses when the spike has the possibility to generate a higher terminal voltage than the passive cell. Simulated periodic 5 Hz stimulation showed a reduced transient release of 3 vesicles per stimulus, which is a recovery effect. Conclusions: We presented two mathematical concepts for vesicle release in ribbon synapses and explained decreasing efficiency in retinal implants for suprathreshold stimulation.
Optical quality assessment in patients with unilateral congenital ptosis: a matched case-control study
Authors: Shen Jianqin , Cui Hongguang , Tang Xuyuan , Han Wei
Published: January 2020

Background: To evaluate the differences in the corneal higher order aberrations (HOAs) and optical quality of the ptosis eyes compared with the normal fellow eyes in the unilateral congenital ptosis patients. Methods: A matched case-control study was performed in 17 pairs of eyes in 17 unilateral congenital ptosis patients. The ptosis eye was enrolled in the ptosis group while the normal fellow eye was enrolled in the normal group. The HOAs obtained from Pentacam HR and the optical quality parameters obtained from optical quality assessment system (OQAS) were compared between the two groups. Results: There were significant difference in vertical coma and vertical trefoil on the anterior corneal surface between the ptosis group and the normal group (p＜0.05). The OQAS parameters in the ptosis group were significantly different from that in the normal group (p＜0.05). The vertical fissure height (VFH) showed significant correlation with the total HOAs, 3 rd HOAs and vertical coma on the anterior corneal surface (p＜0.05). Conclusions: Compared with the normal fellow eyes, the ptosis eyes showed significantly degraded optical quality. The eyelid position was important for the changes of corneal HOAs in the ptosis eyes. The reasons for the discrepancy of the OQAS parameters between the ptosis eyes and normal fellow eyes were multiple.
Correlation of the Electrophysiological and Optical Coherence Tomography Changes in patients with Thyroid-Associated Ophthalmopathy
Authors: El-Shazly Amany Abd El-Fattah , Elsamkary Mahmoud Ahmed , Badran Tamer Abdel Fattah , Abdelgawad Randa Hesham Ali
Published: January 2020

Purpose: to study the structural and functional changes of the optic nerve & macula in patients with thyroid-associated ophthalmopathy (TAO) patients. Methods: Cross-sectional clinical study including 40 cases with TAO and 40 age and sex-matched healthy participants as a control. Complete ophthalmological assessment, evaluation of the proptosis, spectral domain OCT, and electrophysiological investigations (pattern electroretinogram [PERG], multifocal ERG (mfERG) & visual evoked potentials (PVEP) were performed to all participants. Results: Retinal nerve fibre (RNFL), central foveal (CFT) thickness and mean inner macular ring thickness are thinner in cases with proptosis. MfERG showed lower Retinal Response Density1 (RRD1), Ring 1 P1 amplitude and lower five-rings N1 amplitude. Central foveal thickness showed significant positive correlation with VA, BCVA, P50 amplitude and R1 N1 amplitude (r = 0.64, 0.65, 0.40 and 0.51 with p < 0 .001, < 0 .001, < 0 .001 and < 0 .001 respectively), and negative correlation with duration of the disease, degree of proptosis, clinical activity score and R1 N1 latency (r = -0.59, -0.78, -0.41 & -0.90 with p <0.001, <0.001, <0.001 & <0.001 respectively). RNFL thickness showed negative correlation with duration of the disease, degree of proptosis and clinical activity score (-0.77, -0.71 & -0.85 with p < 0 .001, < 0 .001 & < 0 .001 respectively). Multiple regression analyses showed that the degree of proptosis and P50 amplitude were the most important determinants for CFT (p = 0.03 & 0.02); whereas the duration of the disease, and activity score were the most important determinants for average RNFL thickness (p =‎ 0.004, and < 0.001‎ respectively). Conclusion: In the absence of fundus changes, macular thinning together with functional changes detected by PERG and mfERG could be used as good predictors of subclinical retinopathy in the cases of TAO.
Comparison of outcomes between intravitreal ranibizumab and intravitreal aflibercept for diabetic macular edema with “Treat-and-Extend” regimen
Authors: Sugimoto Masahiko , Chujo Shinichiro , Sasaki Taku , Ichio Atsushi , Miyata Ryohei , Matsubara Hisashi , Kondo Mineo
Published: January 2020

Background To compare the effectiveness of intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) performed with the Treat-and-Extend (TAE) regimen on eyes with diabetic macular edema (DME).Patients and methods This was a retrospective study of 125 eyes of 125 treatment naïve DME patients who received anti-VEGF injections at 3 consecutive monthly intervals as the loading phase. Of these 125 eyes, 26 eyes completed the treatment with the TAE regimen for at least 24 months. Among the 26 eyes, 13 eyes of 13 patients (mean age, 70.9±6.0 years) received intravitreal injections of 0.5 mg ranibizumab and 13 eyes of 13 patients (65.9±8.6 years) received 2 mg aflibercept. The changes in the best-corrected visual acuity (BCVA), central retinal thickness (CRT), diabetic retinopathy severity (DRS), and total injection numbers were compared between the two anti-VEGF agents.Results No significant differences were detected in the baseline demographics. At 24 months, the BCVA was significantly improved in both groups; from 0.31±0.19 to 0.10±0.12 logMAR units for IVR and 0.41±0.19 to 0.16±0.28 logMAR units for IVA ( P=1.29x10 -9 ). The CRT was significantly reduced in both groups; 440.9±69.3 to 307.5±66.4 μm for IVR and 473.9±71.5 to 317.8±71.2 μm for IVA ( P=3.55x10 -9 ). No significant differences were detected in the improvements of the BCVA and the CRT in both groups, and the total injection numbers were significant fewer for the IVA group (11.0±1.2) than the IVR group (12.0±1.0). The DRS was significantly improved in both groups ( P =0.0004 for IVR and P =0.009 for IVA).Conclusion No significant differences were detected in the improvements of the BCVA or CRT and injection numbers between IVR and IVA groups treated with the TAE regimen. These results indicate that the results of the treatment with both agents with the TAE regimen were equally effective.
Long-term survival of femoral neck fracture patients age over ninety: Arthroplasty compare with conservative treatment
Authors: Liu Yang , Zhang Chong-wei , Zhao Xiao-dan
Published: January 2020

Background The aging of the China population is expected to lead to increasing of nonagenarian and centenarian.The mortality rates of nonagenarian hip fracture patients would return to an equivalent mortality risk to the normal population at five years after injury. It is imperative to evaluate the 5-year mortality for this small but very challenging subgroup patients in order to optimize patient management. The main purpose of the current retrospective study was to compare the five-year survival between arthroplasty treatment and conservative treatment of femoral neck fracture patients age over 90 years during the same 16 -year period.Methods From January 1998 to December 2014, all consecutive nonagenarian and centenarian patients with femoral neck fracture admitted to our hospital were included for evaluation. The primary outcome was defined as thirty-day mortality, 1-year, 3-year, and 5-year mortality after injury. Survival status analysis was performed by the Kaplan–Meier method for mortality. Using the log-rank test, the stratified analyses were performed to compare the difference of overall cumulative mortality and three-time points (1-year, 3-year, and 5-year) mortality after injury were performed to compare the difference of survival distributions.Results Over the 16-year study period, the arthroplasty group and the conservative treatment group included 33 and 53 patients, respectively. The long-term survival probability of the arthroplasty group is significantly higher than the conservative treatment group( p=0.002277). The survival time of the arthroplasty group is significantly higher than the conservative treatment group(Median(P75-P25)=53(59) versus Median(P75-P25)=22(52), p=0.001). The difference of five time points (1-year, 2-year, 3-year, 4-year, and 5-year) mortality between the conservative group and arthroplasty group is significant except for 30-day mortality.The stratified analyses of overall cumulative mortality and three-time points (1-year, 3-year, and 5-year) mortality after injury demonstrated that the arthroplasty group is significant higher than the conservative treatment group.Conclusions Our study demonstrate that, compared with conservative treatment, arthroplasty surgery is more likely to improve the long-term survival of femoral neck fracture patients over 90s. What can be expected is that nearly half of patients will survive more than five years after surgery.
Hematological alteration among visceral leishmaniasis patients attending in Western Tigrai, Ethiopia, 2018/2019: A cross-sectional study
Authors: Gebremichail Gebremedhin , Tesfanchal Brhane , Belay Getachew , Gebremariam Gebreslassie , Teklehaymanot Gebreyohans , Haileslasie Hagos , Gebrewahid Aderajew , Mardu Fitsum , Adhanom Gebre , Berhe Brhane , Teame Hirut , Tsegaye Aster
Published: January 2020

Background: Hematological abnormalities are common in visceral leishmaniasis patients, which is one of the main public health problems worldwide. The most common hematological abnormalities are anemia, leucopenia and thrombocytopenia. Therefore, this study aimed to assess the hematological alteration among visceral leishmaniasis patients attending Western Tigrai, Ethiopia, 2019. Method: Hospital based comparative cross sectional study was conducted from November 2018 to March 2019 in Western Tigrai, Ethiopia. A total of 100 Visceral Leishmaniasis patients and 100 control groups were included in this study. Blood was collected and analyzed by mindray BC-5800 hematology analyzer. Data was entered and analyzed using Statistical package for social science version 23. Student independent t-test was used for data analysis. P value <0.05 was considered as statistically significant at 95% confidence level. Result: From the total 100 visceral leishmaniasis patients the following abnormalities were reported: 96(96%) anemia, 95(95%) leucopenia, 92(92%) neutropenia, 73(73%) Lymphopenia, 45(45%) eosinopenia and 97(97%) had thrombocytopenia. Red blood cell, hemoglobin, hematocrit, red cell indices and platelet were significantly lower (p<0.05) in visceral leishmaniasis patients compared with the control groups. Similarly the total White blood cell, neutrophil, lymphocyte, eosinophil and basophil count were significantly lower (p<0.05) in visceral leishmaniasis patients compared with the control groups. Conclusion: The major changes in peripheral blood of patient with visceral leishmaniasis are reduced number of red blood cells, reduction in leukocytes and decreased platelet count. Visceral leishmaniasis patients presented with anemia, leucopenia and thrombocytopenia. So this finding indicates that visceral leishmaniasis causes alterations of hematological parameters. Key words: Amastigote, Anemia, Hematological Parameters, Promastigote, Visceral leishmaniasis, Ethiopia .
DMFT in Iranian 12-year-old students residing in the desert region and its association with their individual and family factors- 2016
Authors: Alami Ali , erfanpoor saeed , Ramezani Ali , Jafari Alireza
Published: January 2020

BackgroundOral health in students, as an important health-related subject, would be effective on their growth, self-confidence, socialization, learning ability, daily activities, and quality of life. The aim of this study was to evaluate the DMFT index of 12-year-old students in Gonabad and Bajistan and its relation with their personal and family factors.MethodsAn analytic-cross sectional study conducted among 1280 the students residing in the two desert districts of Iran in 2016. The required data including the subjects’ demographic and family factors as well as their oral health situation extracted from The National School Oral Health Program. The data entered in SPSS (20) and analyzed via Kruskal Wallis, Mann-Whitney, and logistic regression model.ResultsMean (SD) of the students’ DMFT was 1.47 (1.82). This index was calculated 0.98 (1.47) for boy students and 1.91 (1.98) for girl students (P<0.001). There were significant association between mean of the students’ DMFT and their residency location (P=0.015), birth rank (P=0.032), and level of education of their mothers (P=0.035).ConclusionAccording to the findings, attention to oral health in students, especially in girls, seems necessary. Increasing the knowledge and sensitivity of parents (especially mothers) concerning oral health of their children, especially their girls, the use of intermediate forces such healthcare providers in school and oral health technicians in health centers, and the implementation of preventive interventions such as fissure sealant, fluoride varnish Therapy, and use of sodium fluoride mouthwash by students would be effective for improving the oral health of students.
Mutation Profiling of BCR-ABL Kinase Domain in Chronic Myeloid Leukaemia Patients with Imatinib Resistance
Authors: Yusoff Yuslina Mat , Anoar Sharifah Zahra , Seman Zahidah Abu , Said Siti Shahrum Mohamed , Kamaluddin Nor Rizan , Abdullah Julia , Yaacob Aliza Mohd , Esa Ezalia , Zakaria Zubaidah
Published: January 2020

Objective: Emergence of mutation in the BCR-ABL kinase domain (KD) impairs imatinib mesylate (IM) binding capacity, thus contribute to IM resistance. Identification of these mutations is important for treatment decision and precision medicine in CML patients. Our study aims to determine the genomic landscape of BCR ABL KD mutations in CML patients with IM resistance. Result: BCR-ABL KD mutations were observed in 23 patients (26.7%). Fifteen different types of mutations have been identified; Y253H, E255K, T267A, K285I, A287T, M290R, F311I, T315I, F317L, F359V, F359I, F359C, K357T, A399T and E459K. We also discovered three novel mutations; M290R, K285I and K357T and two silent mutations at codon 389 and 401. Mutational analysis is recommended to identify patients at risk of disease progression. Therefore, early detection of such mutations may allow timely treatment intervention to prevent or overcome resistance. Keywords: Chronic Myeloid Leukaemia; BCR-ABL kinase domain; imatinib resistance mutation.
Characteristics and outcomes of Stanford type A aortic dissection patients with post-operation severe hyperbilirubinemia: a retrospective cohort study
Authors: Chen Xiaolan , Bai Ming , Zhao Lijuan , Li Yangping , Yu Yan , Zhang Wei , Ma Feng , Zhou Meilan , Li Li , He Juan , Wang Yan , Wei Lei , Sun Shiren , Chen Xiangmei
Published: January 2020

Objective Hyperbilirubinemia is one of the common complications after cardiac surgery and is associated with increased mortality. However, to the best of our knowledge, the report on clinical significance of postoperative severe hyperbilirubinemia in Stanford type A aortic dissection (AAD) patients is limited. Therefore, the purpose of our present study is to assess the characteristics and outcomes of AAD patients with post-operation severe hyperbilirubinemia.Methods Patients who underwent surgical treatment for AAD in our center between January 2015 and December 2018 were retrospectively screened. In-hospital mortality, long-term mortality, acute kidney injury (AKI), and the requirement of continuous renal replacement therapy (CRRT) were assessed as endpoints. Univariate and multivariate regression models were employed to identify the risk factors of these endpoints.Results Of the 2210 screened patients, 271 (12.3%) were included. Of the included patients, 222 (81.9%) experienced postoperative AKI, and 50 (18.5%) received CRRT. In-hospital mortality was 30.3%. The 1-year, 2-year, and 3-year cumulative mortality were 32.9%, 33.9%, and 35.3%, respectively. Multivariate Logistic regression analysis indicated that age ( P < 0.033), AKI stage 3 ( P < 0.001), the total amount of blood transfusion after surgery ( P = 0.019), mean arterial pressure (MAP) in the first postoperative day ( P = 0.012), the use of extracorporeal membrane oxygenation (ECMO) after surgery ( P = 0.02), and the peak total bilirubin (TB) concentration ( P = 0.023) were independent risk factors of in-hospital mortality. The optimal cut-off value of peak TB on predicting in-hospital mortality was 121.2 μmol/l. Older age, high preoperative serum creatinine (SCr) concentration, and prolonged cardiopulmonary bypass (CPB) time were identified as the independent risk factors of AKI. High preoperative SCr concentration was identified as the only independent risk factor of the requirement of CRRT.Conclusions Post-operation severe hyperbilirubinemia is a common clinical presentation in AAD surgery patients. Post-operation severe hyperbilirubinemia AAD patients with older age, lower MAP, increased blood transfusion, stage 3 AKI, the use of ECMO, and the increased peak TB had higher risk of in-hospital mortality.
Identification, Genome Sizes, and Ploidy of Deutzia
Authors: Hembree William G. , Ranney Thomas G. , Lynch Nathan P. , Jackson Brian E.
Published: January 2020

The genus Deutzia, in the Hydrangeaceae family, includes ≈60 species that range in ploidy from diploid (2x) to tetradecaploid (14x). There have been extensive breeding efforts for Deutzia, but this has been limited to a few parental species. Although there have been numerous studies of the cytogenetics of some species of Deutzia, the ploidy level of many species remains unknown, and there are few cytogenetic data available for Deutzia hybrids and cultivars. The purpose of this study was to validate the identification and determine the genome sizes and ploidy of a diverse collection of Deutzia species and hybrids using cytology and flow cytometry. Accessions were identified using the most current taxonomic key and voucher specimens were deposited for each at the North Carolina State University herbarium. Corrected and updated species names are provided for all cultivars and accessions studied. Traditional cytology was performed for roots of representative taxa to calibrate the genome size with the ploidy level. The genome size and estimated ploidy were determined for 43 accessions using flow cytometry. Ploidy levels were reported for the first time for three species of Deutzia including D. calycosa (2n = 4x = 52), D. paniculata (2n = 4x = 52), and D. glauca (2n = 12x = 156). The base and monoploid genome size (1Cx) were somewhat variable and ranged from 1.20 to 2.05 pg. No anisoploid hybrids were documented, suggesting the presence of an interploid block. The information produced from this study are beneficial to future curation, research, development, and improvement of this genus with corrected nomenclature and clone-specific data regarding cytogenetics.
Inventario sistemático revisado y actualizado de los moluscos marinos ocurrentes en el Estado de Santa Catarina, Brasil
Authors: Agudo-Padrón A. Ignacio
Published: January 2020

Producto de 19 años completos de investigaciones de campo, examen de especímenes depositados em colecciones de museos y estudios referenciales paralelos, el inventário malacológico sistemático marino del Estado de Santa Catarina, Región Subtropical Central Sur del Brasil, es finalmente presentado, comportando un total de 671 espécies e subespécies confirmadas (11 Polyplacophora, 400 Gastropoda, 10 Scaphopoda, 226 Bivalvia y 24 Cephalopoda), distribuídas en 365 gêneros e 152 famílias, correspondientes al 42% del total estimado para el Brasil en general. De estas apenas dos son contempladas por categorias oficiales de conservación, cuatro constituyen reconocidas formas exóticas invasoras, y al menos otras 10 encuentranse directamente envolvidas en actividades antrópicas de maricultura, pesca y extractivismo.
Pagamento por serviços ambientais: instrumento de incentivo à preservação ambiental
Authors: Reis Josimar Vieira dos
Published: January 2020

Os problemas ambientais têm sido a preocupação geral da humanidade com a conservação do meio ambiente é, hodiernamente, uma questão de sobrevivência, de garantir sobrevida às gerações presentes e de possibilitar vida às futuras gerações. O presente trabalho está fundamentada nos principais aspectos sobre o pagamento por serviços ambientais (PSA), que é considerado um mecanismo promissor para resolver alguns problemas relacionados com a degradação dos ecossistemas, principalmente aquelas causadas pela degradação do homem. O pagamento por serviços ambientais ocorre quando beneficiários de uma melhoria da sua qualidade ou quantidade pagam os provedores deste serviço. Estes provedores que adotam práticas conservacionistas ou preservem áreas florestadas. Neste trabalho veremos seus principais aspectos e definições como formas de pagamento, seus desafios e a sua implementação como instrumento econômico, eficácia e eficiência diante do mercado econômico, aspectos sociais e de valor para a proteção dos ecossistemas. A pesquisa é do tipo revisão sistemática de literatura, e buscou informações mais gerais sobre o tema objeto de estudo, para posteriormente envolver um estudo sobre os fundamentos e principais aspectos dos mecanismos sobre o pagamento por serviços ambientais. Conclui-se que se trata de um projeto promissor, com potencial para apresentar equidade, eficácia e eficiência. O que já representa um reconhecimento por sua importância, bem como um avanço para a conservação do meio ambiente. Da mesma forma como as lições depreendidas podem subsidiar a estruturação e a gestão para futuras políticas públicas e projetos de PSA.
A mandiocultura e a produção de farinha: um estudo sobre a farinha produzida em Vitória de Santo Antão-PE
Authors: Ferreira Leonardo Rodrigues
Published: January 2020

A mandioca é um dos principais alimentos para milhares de pessoas que vivem nos países em desenvolvimento. Este trabalho tem objetivo apresentar a produção de mandioca e a fabricação de farinha em Vitória de Santo Antão na Zona da Mata Pernambucana. A pesquisa foi realizada com os produtores rurais de mandioca e a fabricação de farinha no Assentamento Açude Grande, zona rural do Município de Vitória de Santo Antão, em Pernambuco. Em um universo de 24 famílias, foi analisada uma amostra aleatória de 15 produtores, participantes do Projeto Corredor da Farinha. Os resultados da pesquisa revelaram a baixa escolaridade dos agricultores, a ausência da utilização de tecnologias adequadas devido aos recursos limitados, a resistência a mudanças e a falta de estrutura humana e financeira para os treinamentos e as capacitações desses produtores. Durante a pesquisa constatamos que a participação da produção da farinha de mandioca e seus derivados são de grande importância na economia local. Verificamos a importância de se preservar o cultivo da mandioca na região, pois a produção da cultura, ainda é realizada de forma rudimentar, como a produção de farinha que é feita de maneira artesanal, com tradições culturais.
Rural communities' perception of and willingness to pay for wastewater and stormwater management infrastructure in Bihar, India
Authors: Rashid Mohammad , Pandit Debapratim
Published: January 2020

Management of wastewater and stormwater is required for achieving total sanitation and conservation of fresh water resources. The wastewater and stormwater management (WSM) infrastructure suitable to rural areas is usually determined based on technical, environmental, and economic considerations and local communities' perception of infrastructure is ignored. This study analyses the rural communities' choice and perception of WSM infrastructure and their willingness to pay (WTP) for their improvement and maintenance. The households' choice and perception of different aspects of rural WSM infrastructure are determined using the RIDIT (relative to an identified distribution and transformation) analysis, service quality gap analysis, through establishing the relationship between households' satisfaction with individual aspects and overall quality of WSM, and WTP for the service improvement and maintenance. The study finds that rural people like to dispose of wastewater offsite as a good network of drains is found in the villages. However, several aspects of WSM are perceived as poor and require the attention of the policymakers. The rural households want improvement in several attributes and are willing to pay for the maintenance of improved service. The service quality of individual attributes of WSM infrastructure and socioeconomic characteristics of the households are essential determinants of their WTP.
Polymer-Lipid Hybrid Nanoparticles: A Next-Generation Nanocarrier for Targeted Treatment of Solid Tumors
Authors: Rizwanullah Md. , Alam Meraj , Harshita  , Mir Showkat R. , Rizvi Mohd. M.A. , Amin Saima
Published: January 2020

:

At present, cancer is the most deadly disease and one of the most common causes of death worldwide
providing different obstacles to chemotherapy including non-specific biodistribution of chemotherapeutic drugs,
dose-related adverse effects, development of metastasis and chemoresistance. Nanoparticle-based targeted delivery
of chemotherapeutics gained enormous attention in the treatment of solid tumors as they provide many significant
advantages including prolonged drug release, enhanced systemic half-life, decreased toxicity and targeted
drug delivery. Polymer–lipid hybrid nanoparticles (PLHNPs) are the most effective nanoplatform that develop
from building blocks of polymers and lipids. PLHNPs combine the unique advantages of both lipid-based
nanoparticles as well as polymeric nanoparticles. PLHNPs integrate biocompatible polymers and biomimetic
lipids in their architecture, which imparts PLHNPs with wide versatility for delivering chemotherapeutic drugs of
different physicochemical characteristics to their target site of action. The hybrid architecture of PLHNPs provides
many exceptional advantages such as small particle size, encapsulation of more than one anticancer drugs,
high drug loading capacity and modified drug release profile. Furthermore, the surface decoration of PLHNPs
improves the therapeutic potential of the chemotherapeutic drug by selective targeting of tumor tissue and reduces
the side effects by decreasing non-specific biodistribution. This review highlights the challenges in the treatment
of solid tumors by using nanoparticles system, rationale and targeting strategies of PLHNPs in the targeted treatment
of solid tumors, and current progress of PLHNPs in the management of different types of solid tumors.
Recent Nano-based Therapeutic Intervention of Bioactive Sesquiterpenes: Prospects in Cancer Therapeutics
Authors: Ansari Mohammad A. , Badrealam Khan F. , Alam Asrar , Tufail Saba , Khalique Gulshan , Equbal Mohammad J. , Alzohairy Mohammad A. , Almatroudi Ahmad , Alomary Mohammad N. , Pottoo Faheem H.
Published: January 2020

:

In the recent scenario, nanotechnology-based therapeutics intervention has gained tremendous impetus
all across the globe. Nano-based pharmacological intervention of various bioactive compounds has been explored
on an increasing scale. Sesquiterpenes are major constituents of essential oils (EOs) present in various plant species
which possess intriguing therapeutic potentials. However, owing to their poor physicochemical properties;
they have pharmacological limitations. Recent advances in nano-based therapeutic interventions offer various
avenues to improve their therapeutic applicability. Reckoning with these, the present review collates various
nano-based therapeutic intervention of sesquiterpenes with prospective potential against various debilitating diseases
especially cancer. In our viewpoint, considering the burgeoning advancement in the field of nanomedicine;
in the near future, the clinical applicability of these nano-formulated sesquiterpenes can be foreseen with great
enthusiasm.
Carbazole Derivatives as Kinase-Targeting Inhibitors for Cancer Treatment
Authors: Ceramella Jessica , Iacopetta Domenico , Barbarossa Alexia , Caruso Anna , Grande Fedora , Bonomo Maria Grazia , Mariconda Annaluisa , Longo Pasquale , Carmela Saturnino , Sinicropi Maria Stefania
Published: January 2020

Protein Kinases (PKs) are a heterogeneous family of enzymes that modulate several biological pathways, including cell division, cytoskeletal rearrangement, differentiation and apoptosis. In particular, due to their crucial role during human tumorigenesis and cancer progression, PKs are ideal targets for the design and development of effective and low toxic chemotherapeutics and represent the second group of drug targets after G-protein-coupled receptors. Nowadays, several compounds have been claimed to be PKs inhibitors, and some of them, such as imatinib, erlotinib and gefitinib, have already been approved for clinical use, whereas more than 30 others are in various phases of clinical trials. Among them, some natural or synthetic carbazole-based molecules represent promising PKs inhibitors due to their capability to interfere with PK activity by different mechanisms of action including the ability to act as DNA intercalating agents, interfere with the activity of enzymes involved in DNA duplication, such as topoisomerases and telomerases, and inhibit other proteins such as cyclindependent kinases or antagonize estrogen receptors. Thus, carbazoles can be considered a promising this class of compounds to be adopted in targeted therapy of different types of cancer.
The Potential Targets and Mechanisms of a Carbazole and Pyrazole Containing Anticancer Compound
Authors: Xie Jingping , Gore John C.
Published: January 2020

Aims:

Characterization of a small anticancer compound.

Background:

The development of small molecules as new anti-cancer therapeutics is necessary to
improve anti-tumor efficacy and reduce toxicities, especially for the treatment of brain tumors,
where only small molecules can effectively cross the brain-blood barrier. Several novel hits were
previously selected by concurrently screening colon and glioma cancer cell lines with a sensorconjugated
reporter system. Here, we focused on one of them.

Objective:

Elucidating the potential target(s) of a novel anticancer compound.

Methods:

Computer-assisted structural and motif analysis (least absolute shrinkage and selection
operator or LASSO score) was used to assess compound’s targets, then direct kinase activity assays
were used for the confirmation; Western blot of phosphorylated kinases, as well as FACS and
caspase 3/7 activity assays, were used to decipher the action mechanisms. Finally, the expression
profiling of proteins involved in various G-protein pathways by real-time PCR was performed.

Result:

The small chemical, (4E)-4-[2-(9-ethyl-9H-carbazol-3-yl)hydrazin-1-ylidene]-3-methyl-
4,5-dihydro-1H-pyrazol-5-one, with a formula C18H17N5O and MW of 319.36, designated as
VUGX01, was predicted to be a ligand/inhibitor to receptor tyrosine kinases (RTKs) by computer
analysis (least absolute shrinkage and selection operator or LASSO score). However, direct analysis
with recombinant kinases showed that it is not an effective inhibitor to the popular receptor kinases
at 1μM concentration. This compound can activate caspases in some tumor cell lines but has minimal
effects on the cell cycle. Drug treatments lead to the changes in phosphorylation of AKT and c-
RAF, as well as the expression level of MAP2K, suggesting this compound may interact with Gprotein
coupled receptors (GPCRs). The expression profiling of 82 proteins involved in various Gprotein
pathways by real-time PCR showed that the treatment up-regulates the expression of several
proteins, including angiotensinogen, angiotensin II receptor, and IP3-kinase catalytic subunit
gamma.

Conclusion:

VUGX01 can effectively block proliferation and induce apoptosis of certain types of
cancer cells, even it is predicted by high LASSO score, but it is not an effective RTKs inhibitor, it
may inhibit cell growth through acting as a novel ligand to one or several GPCRs.
Targeting Proliferating Cell Nuclear Antigen (PCNA) as an Effective Strategy to Inhibit Tumor Cell Proliferation
Authors: Cardano Miriana , Tribioli Carla , Prosperi Ennio
Published: January 2020

Targeting highly proliferating cells is an important issue for many types of aggressive tumors. Proliferating Cell Nuclear Antigen (PCNA) is an essential protein that participates in a variety of processes of DNA metabolism, including DNA replication and repair, chromatin organization and transcription and sister chromatid cohesion. In addition, PCNA is involved in cell survival, and possibly in pathways of energy metabolism, such as glycolysis. Thus, the possibility of targeting this protein for chemotherapy against highly proliferating malignancies is under active investigation. Currently, approaches to treat cells with agents targeting PCNA rely on the use of small molecules or on peptides that either bind to PCNA, or act as a competitor of interacting partners. Here, we describe the status of the art in the development of agents targeting PCNA and discuss their application in different types of tumor cell lines and in animal model systems.
Abnormalities of Cortical Thickness in Pediatric Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis
Authors: Deng Kan , Zou Rushi , Huang Bingsheng , Zeng Ping , Liang Dong , Huang Lifei , Bin Guo , Zou Dongfang , Zeng Hongwu , Zhang Jian
Published: January 2020

Objective:

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is
the most common intractable seizure type of pediatric epilepsy, with alterations in the cortex
across the whole brain. The aim of this study is to investigate the abnormalities of cortical thickness
in pediatric MTLE-HS.

Methods:

Subjects were recruited from Shenzhen Children’s Hospital between September 2015
and December 2016. MTLE was confirmed by the experienced neurological physician based on
International League Against Epilepsy (ILAE) diagnosis criteria, and structural magnetic resonance
imaging (MRI) was performed at 3T for quantitative assessment of cortical thickness. A
general linear model with age and gender as covariates was used to examine the vertex-wise differences
in cortical thickness between 1) left MTLE-HS (LMTLE-HS) and healthy controls (HC),
and 2) right MTLE-HS (RMTLE-HS) and HC. The family-wise error corrected significance
threshold was set at P < 0.05. Through a combination of probability and cluster-size thresholding,
cluster-wise P values were obtained for the resulting clusters.

Results:

13 LMTLE-HS, 6 RMTLE-HS, and 20 age-matched HC were finally enrolled in the
study. No significant difference in the mean age (LMTLE-HS vs. HC, p=0.57; RMTLE-HS vs.
HC, p=0.39) and gender ratio (LMTLE-HS vs. HC, p=0.24; RMTLE-HS vs. HC, p=0.72) was
found between MTLE-HS and HC. In LMTLE-HS, cortical thickness was found significantly decreased
in the ipsilateral caudal middle frontal gyrus (p=0.012) and increased in the contralateral
inferior temporal gyrus (p=0.020). In RMTLE-HS, cortical thickness significantly decreased in the
ipsilateral posterior parietal lobe (superior, p<0.001 and inferior parietal gyrus, p=0.03), the anterior
parietal lobe (postcentral gyrus, p=0.006), the posterior frontal lobe (precentral gyrus, p=0.04
and the lateral occipital gyrus, p<0.001), and the contralateral lateral occipital gyrus, middle frontal
(p<0.0001) and superior frontal gyrus (p<0.001), and pericalcarine cortex (p=0.020).

Conclusion:

We detected significant cortical abnormalities in pediatric MTLE-HS patients compared
with HC. These cortical abnormalities could be explained by specific pathogenesis in
MTLE-HS, and may finally contribute to understanding the intrinsic mechanism of MTLE-HS.
A Comprehension into Target Binding and Spatial Fingerprints of Noscapinoid Analogues as Inhibitors of Tubulin
Authors: Mandavi Seema , Verma Sant Kumar , Banjare Laxmi , Dubey Amit , Bhatt Renu , Thareja Suresh , Jain Akhlesh Kumar
Published: January 2020

Background:

Owing to its potential to interfere in microtubule dynamics in the mitotic
phase of cell cycle and selectively induce apoptosis in cancer cells without affecting normal cells,
noscapine and its synthetic analogues have been investigated by other research groups in different
cell lines for their capability to be used as anti-cancer agents.

Objective:

The present study is focused on the investigation of the mode of binding of noscapinoids
with tubulin, prediction of target binding affinities and mapping of their spatial fingerprints
(shape and electrostatic).

Methods:

Molecular docking assisted alignment based 3D-QSAR was used on a dataset (43 molecules)
having an inhibitory activity (IC50 = 1.2-250 μM) against human lymphoblast (CEM) cell
line.

Results:

Key amino acid residues of target tubulin were mapped for the binding
of most potent noscapine analogue (Compound 11) and were compared with noscapine. Spatial
fingerprints of noscapinoids for favorable tubulin inhibitory activity were generated and are proposed
herewith for further pharmacophoric amendments of noscapine analogues to design and develop
novel potent noscapine based anti-cancer agents that may enter into drug development pipeline.
Lead Adsorption in Manganese Oxides as Powders and Coatings Supported on Silica Gel Beads and Tin Inverse Opal-Like Structures
Authors: Martínez Maria Guadalupe Almanza , de Jesús Pérez Bueno José , Reza Elizabeth Manríquez , López Maria Luisa Mendoza
Published: January 2020

Background:

Pollution in water is of concern because of its negative influence on human
health and impact on ecosystems. Three-dimensional (3D) structures in the form of inverse opals and
opals-like structures were constructed on a scale of millimeters for their use in the adsorption of
heavy metals adsorption on manganese oxide-covered surfaces.

Objective:

Manganese oxides both, as commercial powders and as synthesized coatings by the chemical
bath method, have a high capacity of lead ions adsorption. The inverse opals and opals-like
structures increase the contact area and regulate the flux.

Methods:

The chemical bath method was used to coating surfaces of inverse opals and opals-like
structures. The size of structures was proposed in millimeters to guarantee an easier flow of water.

Results:

The manganese oxide deposits were predominantly constituted by an amorphous phase. The
present crystalline forms were identified as γ − MnO2, ε − MnO2, Birnessite, and pyrolusite. The best
adsorption was obtained with Mn(II, III) and Mn(II), with 91.4% and 80.6%, respectively.

Conclusion:

Mn(II, III) and Mn(II) had approximately three times better performance than oxides of
Mn(III), Mn(IV), and chemical bath deposited MnO2 in powder form in the lead adsorption.
Medication Non-adherence in Patients with Osteoporosis: Implications for Clinical Pharmacists and Osteoporosis Care Providers
Authors: Jarab Anan S. , Mukattash Tareq L. , Hilan Hayat
Published: January 2020

Background:

Poor adherence to the prescribed therapy leads to low bone mineral density
and enhance the development of osteoporosis complications and unnecessary hospitalization.

Objective:

To explore factors associated with medication non-adherence in patients with osteoporosis.
Findings would help guide the development of future pharmaceutical care interventions aim at
improving health outcomes for patients with osteoporosis.

Methods:

The study was conducted at an outpatient osteoporosis clinic at the Royal Medical Services
Hospital. Variables including socio-demographics and medical factors were collected using
medical records and custom-designed questionnaire. Medication adherence was assessed using the
validated 4-item Morisky Medication Adherence Scale. Logistic regression was performed to develop
a model with variables that best predicted medication non-adherence in patients with osteoporosis
in Jordan.

Results:

A total of 296 patients participated in the study. Most of the study participants (72.3%)
were found non-adherent. Patients were found less likely to adhere to the prescribed medications
with each unit increase in the number of prescribed medications (OR = 2.503, CI = 1.103-5.680)
and if they did not have a trust in the efficacy of the medications (OR = 5.544, CI = 0.990-31.058).

Conclusion:

Medication adherence for patients with osteoporosis has considered scope for improvement
in Jordan. Simplifying dosage regimen in addition to taking patients’ preferences when
selecting the medications should be taken into account in future interventions designed to improve
health outcomes for patients with osteoporosis.
Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes
Authors: Wang Gaifang , Farzaneh Maryam
Published: January 2020

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility
that occurs in about 1% of women between 30-40 years of age. There are few effective methods for
the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most
highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human
pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell.
Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate
for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from
adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent
state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal,
and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited
and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro
culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few
studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation
into oocytes have not been fully investigated. Therefore, in this review, we focus on the
differentiation potential of hPSCs into human oocyte-like cells.