Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Distribution, host range and toxicity assessment of different insecticides on Bactrocera diversa Coquillett, 1904 (Diptera: Tephritidae).

The present study was conducted to investigate the array of hosts, distribution and to evaluate the toxicity of four insecticides: imidacloprid, fipronil, cypermethrin and chlorpyrifos alone and in combination against 3rd instar maggot and adult stage of fruit fly Bactrocera diversa Coquillett, 1904 (Diptera: Tephritidae) during 2021. B. diversa maggots were found vigorously feeding inside the cucurbit hosts (pumpkin, cucumber, bitter gourd, watermelon, round melon, bottle gourd) collected from different localities of Poonch division of Azad Jammu & Kashmir, Pakistan, and this species is reported for the first time as new record to this region. Susceptibilities of B. diversa to insecticides were evaluated using topical method. Mortality was checked after 3, 6, 8 and 24h of exposure. Cypermethrin was most effective to kill 50% of both larval and adult stage with least LC50 [7.2(1.040±0.214), 17.4(0.748±0.193)], respectively followed by imidacloprid. Imidacloprid most effectively killed 90% of both larval and adult population with least LC90 value [73.2 (3.013±0.708) 16.9 (1.886±0.437)] respectively after 24 hours. Cypermethrin with chlorpyrifos most effectively killed 50 and 90 percent of both larval and adult stage of B. diversa with least LC50 value [11.3 (1.085±0.245), 2.5 (0.759±0.252)] and least LC90 value [171.3 (1.085±0.245), 121.9 (0.759±0.252)], respectively after 24h of exposure. Toxicity of each insecticide increased with exposure for longer time and increased dose. Cypermethrin is suggested as most effective against both larval and adult stages of B. diversa in combination with chlorpyrifos followed by imidacloprid.

Introduction of Rezum system technology to Ireland for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a pilot study on early outcomes and procedure cost analysis.

OBJECTIVE: Rezum technology uses heat from radiofrequency-generated water vapour to ablate prostate tissue. We evaluate the introduction of this thermal therapy to an Irish teaching hospital for the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. METHODS: A pilot study of men with moderate to severe lower urinary tract symptoms who underwent Rezum treatment to the prostate was performed. Perioperative efficacy was evaluated using international prostate symptom score (IPSS), quality of life score (IPSS-QOL), uroflowmetry and post-void residual (PVR) volumes. Costs were evaluated and compared against matched patients undergoing the standard of care, transurethral resection of the prostate (TURP). RESULT: Ten patients with a mean age of 70 ± 9 years who met the inclusion criteria underwent Rezum treatment. Mean PSA was 4.73 ± 4 ng/mL and mean prostate volume 72 ± 30 cc. Rezum therapy significantly improved both IPSS by 74% from mean baseline score of 20.8 ± 4 to 5.3 ± 1.49 (p < 0.001) and IPSS-QOL score by 84% from mean baseline score of 4.4 ± 0.7 to 0.6 ± 0.7 (p < 0.001) at 3 months. Maximum flow rate increase by 44% from 9.26 ± 2.5 to 13.34 ± 2.3 mL/s (p < 0.001). When compared to ten matched patients undergoing TURP in the same period, there was a significant cost saving of €1986.52 per patient for Rezum, overall up-front cost saving of €22,819 with an additional 19 bed days and 5 theatre hours spared. CONCLUSION: Rezum, a minimally invasive thermal therapy, provides significantly improved symptom relief and quality of life with a significant cost saving to the institution.

Audit of availability and distribution of paediatric cardiology services and facilities in Nigeria.

BACKGROUND: Paediatric cardiac services in Nigeria have been perceived to be inadequate but no formal documentation of availability and distribution of facilities and services has been done. OBJECTIVE: To evaluate and document the currently available paediatric cardiac services in Nigeria. METHODS: In this questionnaire-based, cross-sectional descriptive study, an audit was undertaken from January 2010 to December 2014, of the personnel and infrastructure, with their distributions according to geopolitical zones of Nigeria. RESULTS: Forty-eight centres participated in the study, with 33 paediatric cardiologists and 31 cardiac surgeons. Echocardiography, electrocardiography and pulse oximetry were available in 45 (93.8%) centres while paediatric intensive care units were in 23 (47.9%). Open-heart surgery was performed in six (12.5%) centres. South-West zone had the majority of centres (20; 41.7%). CONCLUSIONS: Available paediatric cardiac services in Nigeria are grossly inadequate and poorly distributed. Efforts should be intensified to upgrade existing facilities, establish new and functional centres, and train personnel.

Dual indices for prioritizing investment in decentralized HIV services at Nigerian primary health care facilities.

Decentralizing health services, including those for HIV prevention and treatment, is one strategy for maximizing the use of limited resources and expanding treatment options; yet few methods exist for systematically identifying where investments for service expansion might be most effective, in terms of meeting needs and rapid availability of improved services. The Nigerian Government, the United States Government under the President's Emergency Plan for AIDS Relief (PEPFAR) program and other donors are expanding services for prevention of mother-to-child transmission (PMTCT) of HIV to primary health care facilities in Nigeria. Nigerian primary care facilities vary greatly in their readiness to deliver HIV/AIDS services. In 2012, MEASURE Evaluation assessed 268 PEPFAR-supported primary health care facilities in Nigeria and developed a systematic method for prioritizing these facilities for expansion of PMTCT services. Each assessed facility was scored based on two indices with multiple, weighted variables: one measured facility readiness to provide PMTCT services, the other measured local need for the services and feasibility of expansion. These two scores were compiled and the summary score used as the basis for prioritizing facilities for PMTCT service expansion. The rationale was that using need and readiness to identify where to expand PMTCT services would result in more efficient allocation of resources. A review of the results showed that the indices achieved the desired effect-that is prioritizing facilities with high need even when readiness was problematic and also prioritizing facilities where rapid scale-up was feasible. This article describes the development of the two-part index and discusses advantages of using this approach when planning service expansion. The authors' objective is to contribute to development of methodologies for prioritizing investments in HIV, as well as other public health arenas, that should improve cost-effectiveness and strengthen services and systems in resource-limited countries.

Whole left ventricular functional assessment from two minutes free breathing multi-slice CINE acquisition.

Two major challenges in cardiovascular MRI are long scan times due to slow MR acquisition and motion artefacts due to respiratory motion. Recently, a Motion Corrected-Compressed Sensing (MC-CS) technique has been proposed for free breathing 2D dynamic cardiac MRI that addresses these challenges by simultaneously accelerating MR acquisition and correcting for any arbitrary motion in a compressed sensing reconstruction. In this work, the MC-CS framework is combined with parallel imaging for further acceleration, and is termed Motion Corrected Sparse SENSE (MC-SS). Validation of the MC-SS framework is demonstrated in eight volunteers and three patients for left ventricular functional assessment and results are compared with the breath-hold acquisitions as reference. A non-significant difference (P > 0.05) was observed in the volumetric functional measurements (end diastolic volume, end systolic volume, ejection fraction) and myocardial border sharpness values obtained with the proposed and gold standard methods. The proposed method achieves whole heart multi-slice coverage in 2 min under free breathing acquisition eliminating the time needed between breath-holds for instructions and recovery. This results in two-fold speed up of the total acquisition time in comparison to the breath-hold acquisition.

A rapid assessment of the availability and use of obstetric care in Nigerian healthcare facilities.

BACKGROUND: As part of efforts to reduce maternal deaths in Nigeria, pregnant women are being encouraged to give birth in healthcare facilities. However, little is known about whether or not available healthcare facilities can cope with an increasing demand for obstetric care. We thus carried out this survey as a rapid and tactical assessment of facility quality. We visited 121 healthcare facilities, and used the opportunity to interview over 700 women seeking care at these facilities. FINDINGS: Most of the primary healthcare facilities we visited were unable to provide all basic Emergency Obstetric Care (bEmOC) services. In general, they lack clinical staff needed to dispense maternal and neonatal care services, ambulances and uninterrupted electricity supply whenever there were obstetric emergencies. Secondary healthcare facilities fared better, but, like their primary counterparts, lack neonatal care infrastructure. Among patients, most lived within 30 minutes of the visited facilities and still reported some difficulty getting there. Of those who had had two or more childbirths, the conditional probability of a delivery occurring in a healthcare facility was 0.91 if the previous delivery occurred in a healthcare facility, and 0.24 if it occurred at home. The crude risk of an adverse neonatal outcome did not significantly vary by delivery site or birth attendant, and the occurrence of such an outcome during an in-facility delivery may influence the mother to have her next delivery outside. Such an outcome during a home delivery may not prompt a subsequent in-facility delivery. CONCLUSIONS: In conclusion, reducing maternal deaths in Nigeria will require attention to both increasing the number of facilities with high-quality EmOC capability and also assuring Nigerian women have access to these facilities regardless of where they live.

k-t Group sparse: a method for accelerating dynamic MRI.

Compressed sensing (CS) is a data-reduction technique that has been applied to speed up the acquisition in MRI. However, the use of this technique in dynamic MR applications has been limited in terms of the maximum achievable reduction factor. In general, noise-like artefacts and bad temporal fidelity are visible in standard CS MRI reconstructions when high reduction factors are used. To increase the maximum achievable reduction factor, additional or prior information can be incorporated in the CS reconstruction. Here, a novel CS reconstruction method is proposed that exploits the structure within the sparse representation of a signal by enforcing the support components to be in the form of groups. These groups act like a constraint in the reconstruction. The information about the support region can be easily obtained from training data in dynamic MRI acquisitions. The proposed approach was tested in two-dimensional cardiac cine MRI with both downsampled and undersampled data. Results show that higher acceleration factors (up to 9-fold), with improved spatial and temporal quality, can be obtained with the proposed approach in comparison to the standard CS reconstructions.

Age- and site-specific variation in the dermoscopic patterns of congenital melanocytic nevi: an aid to accurate classification and assessment of melanocytic nevi.

OBJECTIVES: To describe the dermoscopic features of congenital melanocytic nevi (CMN) and assess whether predominant dermoscopic patterns present in CMN are related to an individual's age (<12 years vs >or=12 years), sex, or lesional site (head, neck, and trunk vs extremities). DESIGN: Nonrandomized observational study. PATIENTS: A total of 77 consecutive patients, each with 1 CMN (n = 77 lesions), from an outpatient dermatology clinic. A diagnosis of CMN was established by (1) documentation of a melanocytic nevus during the first year of life or (2) by clinical examination and either clinical history or biopsy findings. MAIN OUTCOME MEASURES: Images of CMN were evaluated for specific dermoscopic structures and patterns. The distribution of patterns was assessed by age, sex, and lesional site. RESULTS: Most of the 77 lesions exhibited 1 of the following predominant dermoscopic patterns: reticular (18 lesions [23%]), globular (14 [18%]), or reticuloglobular (12 [16%]). Globular CMN were present in 5 of the 19 individuals who were younger than 12 years (26%) but in only 9 of the 58 individuals 12 years or older (16%). Reticular CMN were seen exclusively in the individuals who were 12 years or older. Congenital melanocytic nevi exhibiting no predominant pattern were more commonly present in the individuals younger than 12 years. Globular CMN were present in 11 head, neck, and trunk lesions (30%) compared with 3 extremity lesions (8%). Conversely, reticular CMN were present in 16 extremity lesions (40%) compared with 2 head, neck, and trunk lesions (5%). The predominant dermoscopic pattern did not vary based on sex. The most commonly observed dermoscopic structures were globules (in 64 lesions [83%]), hypertrichosis (in 61 [79%]), and reticular networks (in 55 [71%]). CONCLUSIONS: Our results suggest that the predominant dermoscopic patterns of CMN vary according to age and lesional site. These differences may inform future studies on the pathogenesis of CMN.